Delcobese

Amphetamine Adipate:

• Warning: abuse and dependence
• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Drug abuse and dependence
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Delcobese (Amphetamine Adipate) reviews

WARNING: ABUSE AND DEPENDENCE

CNS stimulants, including Delcobese (Amphetamine Adipate), other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy [see Warnings and Precautions (5.1) and Drug Abuse and Dependence (9.2 , 9.3) ].

WARNING: ABUSE AND DEPENDENCE

See full prescribing information for complete boxed warning.

• CNS stimulants, including Delcobese (Amphetamine Adipate), other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. (5.1 , 9.3)
• Assess the risk of abuse prior to prescribing and monitor for signs of abuse and dependence while on therapy (9.2, 9.3)

1 INDICATIONS AND USAGE

Delcobese (Amphetamine Adipate) is indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older .

Delcobese (Amphetamine Adipate) is a central nervous system (CNS) stimulant indicated for the treatment of Attention Deficit Hyperactivity Disorder (ADHD) in patients 6 years and older. (1)

2 DOSAGE AND ADMINISTRATION

• Shake bottle before administering the dose.
• May be taken with or without food. (2.2)
• Do not mix with food or other liquids before consuming. (2.2)
• Pediatric patients (ages 6 to 17 years): Starting dose is 6.3 mg (5 mL) once daily in the morning. Maximum dose is 18.8 mg (15 mL) for patients 6 to 12 years, and 12.5 mg (10 mL) once daily for patients 13 to 17 years. (2.3)
• Adults: 12.5 mg (10 mL) once daily in the morning. (2.4)
• To avoid substitution errors and overdosage, do not substitute for other Delcobese (Amphetamine Adipate) products on a milligram-per-milligram basis because of different Delcobese (Amphetamine Adipate) salt compositions and differing pharmacokinetic profiles. (2.5, 5.8)

2.1 Pre-Treatment Screening

Prior to treating patients with Delcobese (Amphetamine Adipate), assess for the presence of cardiac disease (i.e., perform a careful history, family history of sudden death or ventricular arrhythmia, and physical exam) .

Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy. Maintain careful prescription records, educate patients about abuse, monitor for signs of abuse and overdose, and periodically re-evaluate the need for Delcobese (Amphetamine Adipate) use .

2.2 Dosing Considerations for All Patients

Administer Delcobese orally once daily in the morning with or without food. The dose should be individualized according to the therapeutic needs and response of the patient.

Shake the bottle of Delcobese (Amphetamine Adipate) before administering the dose. Do not add Delcobese (Amphetamine Adipate) to food or mix Delcobese (Amphetamine Adipate) with other liquids before consuming.

2.3 Pediatric Patients

The recommended starting dose for patients 6 to 17 years of age is 6.3 mg (5 mL) once daily in the morning. Increase in increments of 3.1 mg (2.5 mL) or 6.3 mg (5 mL) at weekly intervals. The maximum dose is 18.8 mg (15 mL) daily for patients 6 to 12 years, and 12.5 mg (10 mL) daily for patients 13 to 17 years.

2.4 Adults

The recommended dose of Delcobese for adults is 12.5 mg (10 mL) daily.

2.5 Switching from Other Delcobese (Amphetamine Adipate) Products

Patients taking ADDERALL XR may be switched to Delcobese (Amphetamine Adipate) at the equivalent dose taken once daily . Refer to Table 1 for equivalent doses of Delcobese (Amphetamine Adipate) and ADDERALL XR. ADDERALL XR (dextroamphetamine sulfate, dextroamphetamine saccharate, Delcobese (Amphetamine Adipate) aspartate monohydrate, and Delcobese (Amphetamine Adipate) sulfate extended-release capsules) is also referred to as mixed salts of a single-entity Delcobese (Amphetamine Adipate) product extended-release capsules (MAS ER).

If switching from any other Delcobese (Amphetamine Adipate) products, discontinue that treatment, and titrate with Delcobese (Amphetamine Adipate) using the titration schedule .

Do not substitute for other Delcobese (Amphetamine Adipate) products on a milligram-per-milligram basis because of different Delcobese (Amphetamine Adipate) salt compositions and differing pharmacokinetic profiles .

2.6 Dosage Modifications Due to Drug Interactions

Agents that alter urinary pH can impact urinary excretion and alter blood levels of Delcobese (Amphetamine Adipate). Acidifying agents (e.g., ascorbic acid) decrease blood levels, while alkalinizing agents (e.g., sodium bicarbonate) increase blood levels. Adjust Delcobese (Amphetamine Adipate) dosage accordingly .

3 DOSAGE FORMS AND STRENGTHS

Extended-release oral suspension contains 1.25 mg Delcobese (Amphetamine Adipate) per mL.

Extended-release oral suspension containing 1.25 mg Delcobese (Amphetamine Adipate) per mL. (3)

4 CONTRAINDICATIONS

Delcobese (Amphetamine Adipate) is contraindicated:

• In patients known to be hypersensitive to Delcobese (Amphetamine Adipate), or other components of Delcobese (Amphetamine Adipate). Hypersensitivity reactions such as angioedema and anaphylactic reactions have been reported in patients treated with other Delcobese (Amphetamine Adipate) products .
• In patients taking monoamine oxidase inhibitors (MAOIs), or within 14 days of stopping MAOIs (including MAOIs such as linezolid or intravenous methylene blue), because of an increased risk of hypertensive crisis .

• Known hypersensitivity to Delcobese (Amphetamine Adipate) products or other ingredients in Delcobese (Amphetamine Adipate). (4)
• Use of monoamine oxidase inhibitor (MAOI) or within 14 days of the last MAOI dose. (4)

5 WARNINGS AND PRECAUTIONS

• Serious Cardiovascular Reactions: Sudden death has been reported in association with CNS stimulant treatment at recommended doses in pediatric patients with structural cardiac abnormalities or other serious heart problems. In adults, sudden death, stroke, and myocardial infarction have been reported. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, or coronary artery disease.
• Blood Pressure and Heart Rate Increases: Monitor blood pressure and pulse. Consider benefits and risks before use in patients for whom blood pressure increases may be problematic. (5.3)
• Psychiatric Adverse Reactions: May cause psychotic or manic symptoms in patients with no prior history, or exacerbation of symptoms in patients with pre-existing psychosis. Evaluate for bipolar disorder prior to stimulant use. (5.4)
• Long-Term Suppression of Growth: Monitor height and weight in pediatric patients during treatment. (5.5)
• Peripheral Vasculopathy, including Raynaud's phenomenon: Stimulants used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Careful observation for digital changes is necessary during treatment with ADHD stimulants. (5.6)
• Serotonin Syndrome: Increased risk when co-administered with serotonergic agents (e.g., SSRIs, SNRIs, triptans), but also during overdosage situations. If it occurs, discontinue Delcobese (Amphetamine Adipate) and initiate supportive treatment. (5.7)

5.1 Potential for Abuse or Dependence

CNS stimulants, including Delcobese (Amphetamine Adipate), other amphetamine-containing products, and methylphenidate, have a high potential for abuse and dependence. Assess the risk of abuse prior to prescribing, and monitor for signs of abuse and dependence while on therapy .

5.2 Serious Cardiovascular Reactions

Sudden death, stroke, and myocardial infarction have been reported in adults with CNS stimulant treatment at recommended doses. Sudden death has been reported in children and adolescents with structural cardiac abnormalities and other serious heart problems taking CNS stimulants at recommended doses for ADHD. Avoid use in patients with known structural cardiac abnormalities, cardiomyopathy, serious heart arrhythmia, coronary artery disease, and other serious heart problems. Further evaluate patients who develop exertional chest pain, unexplained syncope, or arrhythmias during Delcobese treatment.

5.3 Blood Pressure and Heart Rate Increases

CNS stimulants cause an increase in blood pressure (mean increase about 2-4 mm Hg) and heart rate (mean increase about 3-6 bpm). Monitor all patients for potential tachycardia and hypertension.

5.4 Psychiatric Adverse Events

Exacerbation of Pre-Existing Psychosis

CNS stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.

Induction of a Manic Episode in Patients with Bipolar Illness

CNS stimulants may induce a mixed or manic episode in patients with bipolar disorder. Prior to initiating treatment, screen patients for risk factors for developing a manic episode.

New Psychotic or Manic Symptoms

CNS stimulants, at recommended doses, may cause psychotic or manic symptoms (e.g., hallucinations, delusional thinking, or mania) in patients without prior history of psychotic illness or mania. If such symptoms occur, consider discontinuing Delcobese (Amphetamine Adipate). In a pooled analysis of multiple short-term, placebo-controlled studies of CNS stimulants, psychotic or manic symptoms occurred in 0.1% of CNS stimulant-treated patients compared to 0% in placebo-treated patients.

5.5 Long-Term Suppression of Growth

CNS stimulants have been associated with weight loss and slowing of growth rate in pediatric patients. Closely monitor growth (weight and height) in pediatric patients treated with CNS stimulants, including Delcobese (Amphetamine Adipate).

Patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted [Use in Specific Populations (8.4)].

5.6 Peripheral Vasculopathy, including Raynaud's Phenomenon

Stimulants, including Delcobese, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

5.7 Serotonin Syndrome

Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort . The co-administration with cytochrome P450 2D6 (CYP2D6) inhibitors may also increase the risk with increased exposure to Delcobese (Amphetamine Adipate). In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 .

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Concomitant use of Delcobese (Amphetamine Adipate) with MAOI drugs is contraindicated .

Discontinue treatment with Delcobese (Amphetamine Adipate) and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Delcobese (Amphetamine Adipate) with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate Delcobese (Amphetamine Adipate) with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.

5.8 Potential for Overdose Due to Medication Errors

Medication errors, including substitution and dispensing errors, between Delcobese and other Delcobese (Amphetamine Adipate) products could occur, leading to possible overdosage. To avoid substitution errors and overdosage, do not substitute for other Delcobese (Amphetamine Adipate) products on a milligram-per-milligram basis because of different Delcobese (Amphetamine Adipate) salt compositions and differing pharmacokinetic profiles .

5.9 Potential for Intestinal Necrosis

Cases of intestinal necrosis, including some deaths, have been reported with the concomitant use of sodium polystyrene sulfonate and sorbitol, two of the inactive ingredients in Delcobese (Amphetamine Adipate). In these cases, patients were administered sodium polystyrene sulfonate to treat hyperkalemia at doses greater than 200 times the amount present in Delcobese (Amphetamine Adipate). However, no absolute safe levels for the interaction of sodium polystyrene sulfonate and sorbitol have been established.

6 ADVERSE REACTIONS

The following adverse reactions are discussed in greater detail in other sections of the labeling:

• Drug Dependence
• Hypersensitivity to Delcobese (Amphetamine Adipate), or other components of Delcobese (Amphetamine Adipate)
• Hypertensive Crisis When Used Concomitantly with Monoamine Oxidase Inhibitors
• Serious Cardiovascular Reactions
• Blood Pressure and Heart Rate Increases
• Psychiatric Adverse Reactions
• Long-Term Suppression of Growth
• Peripheral Vasculopathy, including Raynaud's phenomenon
• Serotonin Syndrome
• Potential for Intestinal Necrosis

• Pediatric patients ages 6 to 12 years: Most common adverse reactions (≥5% and with a higher incidence than on placebo) were loss of appetite, insomnia, abdominal pain, emotional lability, vomiting, nervousness, nausea, and fever. (6.1)
• Pediatric patients ages 13 to 17 years: Most common adverse reactions (≥5% and with a higher incidence than on placebo) were loss of appetite, insomnia, abdominal pain, weight loss, and nervousness. (6.1)
• Adults: Most common adverse reactions (≥5% and with a higher incidence than on placebo) were dry mouth, loss of appetite, insomnia, headache, weight loss, nausea, anxiety, agitation, dizziness, tachycardia, diarrhea, asthenia, and urinary tract infections. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Neos Therapeutics, Inc. at 1-888-219-1789 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.

The safety of Delcobese (Amphetamine Adipate) has been established from adequate and well-controlled studies of single-entity Delcobese (Amphetamine Adipate) product extended-release (MAS ER) capsules . The adverse reactions of MAS ER capsules in these adequate and well-controlled studies are described below.

The premarketing development program for MAS ER included exposures in a total of 1315 participants in clinical trials (635 pediatric patients, 350 adolescent patients, 248 adult patients, and 82 healthy adult subjects). Of these, 635 patients (ages 6 to 12) were evaluated in two controlled clinical studies, one open-label clinical study, and two single-dose clinical pharmacology studies (N= 40).

Adverse Reactions Leading to Discontinuation of Treatment

The most frequent adverse reactions leading to discontinuation of MAS ER in controlled and uncontrolled, multiple-dose clinical trials of pediatric patients ages 6 to 12 years (N=595) were anorexia (loss of appetite) (2.9%), insomnia (1 5%), weight loss (1.2%), emotional lability (1%), and depression (0.7%).

In a separate placebo-controlled 4-week study in pediatric patients 13 to 17 years with ADHD, five patients (2.1%) discontinued treatment due to adverse events among MAS ER-treated patients (N=233) compared to none who received placebo (N=54). The most frequent adverse event leading to discontinuation and considered to be drug-related (i.e. leading to discontinuation in at least 1% of MAS ER-treated patients and at a rate at least twice that of placebo) was insomnia (1.3%, n=3).

In one placebo-controlled 4-week study among adults with ADHD with doses 20 mg to 60 mg, 23 patients (12.0%) discontinued treatment due to adverse events among MAS ER-treated patients (N=191) compared to one patient (1.6%) who received placebo (N=64). The most frequent adverse events leading to discontinuation and considered to be drug-related (i.e. leading to discontinuation in at least 1% of MAS ER-treated patients and at a rate at least twice that of placebo) were insomnia (5.2%, n=10), anxiety (2.1%, n=4), nervousness (1.6%, n=3), dry mouth (1.6%, n=3), anorexia (1.6%, n=3), tachycardia (1.6%, n=3), headache (1.6%, n=3), and asthenia (1.0%, n=2).

Adverse Reactions Occurring in Controlled Trials

Adverse reactions reported in a 3-week clinical trial of pediatric patients 6 to 12 years and a 4-week clinical trial in pediatric patients 13 to 17 years of age and adults, respectively, treated with MAS ER or placebo are presented in the tables below.

6.2 Adverse Reactions from Clinical Trials and Spontaneous Postmarketing Reports of Other Delcobese Products

The following adverse reactions are from clinical trials and spontaneous postmarketing reports of other Delcobese (Amphetamine Adipate) products in pediatric patients and adults with ADHD. Because some of these reactions were reported voluntarily from a population of uncertain size, it is not always possible to estimate their frequency reliably or to establish a causal relationship to drug exposure.

Cardiovascular: Palpitations, sudden death, myocardial infarction. There have been isolated reports of cardiomyopathy associated with chronic Delcobese (Amphetamine Adipate) use.

Central Nervous System: Restlessness, irritability, euphoria, dyskinesia, dysphoria, depression, tremor, aggression, anger, logorrhea, and paresthesia (including formication).

Eye Disorders: Vision blurred, mydriasis.

Gastrointestinal: Unpleasant taste, constipation, other gastrointestinal disturbances.

Allergic: Urticaria, rash, hypersensitivity reactions including angioedema and anaphylaxis. Serious skin rashes, including Stevens-Johnson Syndrome and toxic epidermal necrolysis have been reported.

Endocrine: Impotence, change in libido, frequent or prolonged erections.

Skin: Alopecia.

Musculoskeletal, Connective Tissue, and Bone Disorders: Rhabdomyolysis.

Psychiatric Disorders: Dermatillomania, bruxism.

Vascular Disorders: Raynaud's phenomenon

7 DRUG INTERACTIONS

Acidifying and Alkalinizing Agents: Agents that alter urinary pH can alter blood levels of Delcobese. Acidifying agents can decrease Delcobese (Amphetamine Adipate) blood levels, while alkalinizing agents can increase Delcobese (Amphetamine Adipate) blood levels. Adjust Delcobese (Amphetamine Adipate) dosage accordingly. (7.1)

7.1 Drugs Having Clinically Important Interactions with Amphetamines

7.2 Drug/Laboratory Test Interactions

Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.

8 USE IN SPECIFIC POPULATIONS

• Pregnancy: Based on animal data, may cause fetal harm.
• Lactation: Breastfeeding not recommended. (8.2)

8.1 Pregnancy

Pregnancy Exposure Registry

There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Delcobese (Amphetamine Adipate) during pregnancy. Healthcare providers are encouraged to register patients by calling the National Pregnancy Registry for Psychostimulants at 1-866-961-2388.

Risk Summary

The limited available data from published literature and postmarketing reports on the use of prescription Delcobese (Amphetamine Adipate) in pregnant women are insufficient to inform a drug-associated risk for major congenital malformations or miscarriage. Adverse pregnancy outcomes, including premature delivery and low birth weight, have been seen in infants born to mothers dependent on amphetamines (see Clinical Considerations ).

No effects on morphological development were observed in embryo-fetal development studies with oral administration of Delcobese (Amphetamine Adipate) to rats and rabbits during organogenesis at doses 4 and 20 times, respectively, the maximum recommended human dose (MRHD) of 12.5 mg/day (as base) given to adolescents, on a mg/m² basis. However, in a pre- and post-natal development study, Delcobese (Amphetamine Adipate) (d- to l- ratio of 3:1) administered orally to pregnant rats during gestation and lactation caused a decrease in pup survival and a decrease in pup body weight that correlated with a delay in developmental landmarks at clinically relevant doses of Delcobese (Amphetamine Adipate). In addition, adverse effects on reproductive performance were observed in pups whose mothers were treated with Delcobese (Amphetamine Adipate). Long-term neurochemical and behavioral effects have also been reported in published animal developmental studies using clinically relevant doses of Delcobese (Amphetamine Adipate) (see Data ).

The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Clinical Considerations

Fetal/Neonatal adverse reactions

Amphetamines, such as Delcobese (Amphetamine Adipate), cause vasoconstriction and thereby may decrease placental perfusion. In addition, amphetamines can stimulate uterine contractions increasing the risk of premature delivery. Infants born to Delcobese (Amphetamine Adipate) dependent mothers have an increased risk of premature delivery and low birth weight.

Monitor infants born to mothers taking amphetamines for symptoms of withdrawal, such as feeding difficulties, irritability, agitation, and excessive drowsiness.

Data

Animal Data

Delcobese (Amphetamine Adipate) (d- to l- enantiomer ratio of 3:1) had no apparent effects on embryofetal morphological development or survival when administered orally to pregnant rats and rabbits throughout the period of organogenesis at doses of up to 6 and 16 mg/kg/day, respectively. These doses are approximately 4 and 20 times, respectively, the MRHD of 12.5 mg/day (as base) given to adolescents, on a mg/m² basis. Fetal malformations and death have been reported in mice following parenteral administration of d-amphetamine doses of 50 mg/kg/day (approximately 15 times the MRHD given to adolescents on a mg/m² basis) or greater to pregnant animals. Administration of these doses was also associated with severe maternal toxicity.

A study was conducted in which pregnant rats received daily oral doses of Delcobese (Amphetamine Adipate) (d- to l- enantiomer ratio of 3:1) of 2, 6, and 10 mg/kg from gestation day 6 to lactation day 20. These doses are approximately 1, 4, and 6 times the MRHD of 12.5 mg/day (as base) given to adolescents, on a mg/m² basis. All doses caused hyperactivity and decreased weight gain in the dams. A decrease in pup survival was seen at all doses. A decrease in pup body weight was seen at 6 and 10 mg/kg which correlated with delays in developmental landmarks, such as preputial separation and vaginal opening. Increased pup locomotor activity was seen at 10 mg/kg on day 22 postpartum but not at 5 weeks postweaning. When pups were tested for reproductive performance at maturation, gestational weight gain, number of implantations, and number of delivered pups were decreased in the group whose mothers had been given 10 mg/kg.

A number of studies in rodents indicate that prenatal or early postnatal exposure to Delcobese (Amphetamine Adipate) (d- or d, l-), at doses similar to those used clinically, can result in long-term neurochemical and behavioral alterations. Reported behavioral effects include learning and memory deficits, altered locomotor activity, and changes in sexual function.

8.2 Lactation

Risk Summary

Based on limited case reports in published literature, Delcobese (d- or d, l-) is present in human milk, at relative infant doses of 2% to 13.8% of the maternal weight-adjusted dosage and a milk/plasma ratio ranging between 1.9 and 7.5. There are no reports of adverse effects on the breastfed infant. Long term neurodevelopmental effects on infants from stimulant exposure are unknown. It is possible that large dosages of Delcobese (Amphetamine Adipate) might interfere with milk production, especially in women whose lactation is not well established. Because of the potential for serious adverse reactions in nursing infants, advise patients that breastfeeding is not recommended during treatment with Delcobese (Amphetamine Adipate).

8.4 Pediatric Use

Safety and effectiveness have been established in pediatric patients with ADHD ages 6 to 17 years of age in three adequate and well-controlled clinical trials of up to 4 weeks in duration . Safety and efficacy in pediatric patients younger than 6 years of age with ADHD have not been established.

Long-Term Growth Suppression

Growth should be monitored during treatment with stimulants, including Delcobese (Amphetamine Adipate), and children who are not growing or gaining weight as expected may need to have their treatment interrupted .

Juvenile Animal Toxicity Data

Juvenile rats treated with mixed Delcobese (Amphetamine Adipate) salts early in the postnatal period through sexual maturation demonstrated transient changes in motor activity. Learning and memory was impaired at approximately 10 times the maximum recommended human dose (MRHD) given to children on a mg/m² basis. No recovery was seen following a drug free period. A delay in sexual maturation was observed at a dose approximately 10 times the MRHD given to pediatric patients on a mg/m² basis, although there was no effect on fertility.

In a juvenile developmental study, rats received daily oral doses of Delcobese (Amphetamine Adipate) (d to l enantiomer ratio of 3:1) of 2, 6, or 20 mg/kg on days 7-13 of age; from day 14 to approximately day 60 of age these doses were given twice daily for total daily doses of 4, 12, or 40 mg/kg. The latter doses are approximately 1, 3, and 10 times the MRHD of 18.8 mg/day (as base) given to children on a mg/m² basis. Post-dosing hyperactivity was seen at all doses; motor activity measured prior to the daily dose was decreased during the dosing period but the decreased motor activity was largely absent after an 18 day drug-free recovery period. Performance in the Morris water maze test for learning and memory was impaired at the 40 mg/kg dose, and sporadically at the lower doses, when measured prior to the daily dose during the treatment period; no recovery was seen after a 19 day drug-free period. A delay in the developmental milestones of vaginal opening and preputial separation was seen at 40 mg/kg but there was no effect on fertility.

8.5 Geriatric Use

Clinical studies of Delcobese (Amphetamine Adipate) did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should start at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

Delcobese contains Delcobese (Amphetamine Adipate), a Schedule II controlled substance in the U.S. Controlled Substances Act (CSA).

9.2 Abuse

Delcobese (Amphetamine Adipate), is a CNS stimulant that contains Delcobese (Amphetamine Adipate) which has a high potential for abuse. Abuse is characterized by impaired control of drug use, compulsive use despite harm, and craving.

Signs and symptoms of Delcobese (Amphetamine Adipate) abuse may include increased heart rate, respiratory rate, blood pressure, and/or sweating, dilated pupils, hyperactivity, restlessness, insomnia, decreased appetite, loss of coordination, tremors, flushed skin, vomiting, and/or abdominal pain. Anxiety, psychosis, hostility, aggression, suicidal or homicidal ideation have also been observed. Abusers of amphetamines may use other unapproved routes of administration which can result in overdose and death .

To reduce the abuse of Delcobese (Amphetamine Adipate), assess the risk of abuse prior to prescribing. After prescribing, keep careful prescription records, educate patients and their families about abuse and proper storage and disposal of CNS stimulants, monitor for signs of abuse while on therapy, and re-evaluate the need for Delcobese (Amphetamine Adipate) use.

9.3 Dependence

Tolerance

Tolerance (a state of adaptation in which exposure to a drug results in a reduction of the drug's desired and/or undesired effects over time) may occur during the chronic therapy of CNS stimulants including Delcobese (Amphetamine Adipate).

Dependence

Physical dependence (which is manifested by a withdrawal syndrome produced by abrupt cessation, rapid dose reduction, or administration of an antagonist) may occur in patients treated with CNS stimulants including Delcobese (Amphetamine Adipate). Withdrawal symptoms after abrupt cessation following prolonged high dosage administration of CNS stimulants include dysphoric mood; fatigue; vivid, unpleasant dreams; insomnia or hypersomnia; increased appetite; and psychomotor retardation or agitation.

10 OVERDOSAGE

Consult with a Certified Poison Control Center (1-800-222-1222) for up-to-date guidance and advice for treatment of overdosage. Individual patient response to amphetamines varies widely. Toxic symptoms may occur idiosyncratically at low doses.

Manifestations of Delcobese (Amphetamine Adipate) overdose include restlessness, tremor, hyperreflexia, rapid respiration, confusion, assaultiveness, hallucinations, panic states, hyperpyrexia and rhabdomyolysis. Fatigue and depression usually follow the central nervous system stimulation. Other reactions include arrhythmias, hypertension or hypotension, circulatory collapse, nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.

11 DESCRIPTION

Delcobese (Amphetamine Adipate) (amphetamine) extended-release oral suspension contains a 3 to 1 ratio of d- to l-amphetamine, a central nervous system stimulant.

The labeled strength reflects the amount of Delcobese (Amphetamine Adipate) in Delcobese (Amphetamine Adipate) whereas the strengths of the mixed salts of a single-entity Delcobese (Amphetamine Adipate) products are in terms of the amount of Delcobese (Amphetamine Adipate) salts. Table 1 in Section 2.5 details the equivalent amounts of active ingredient in these products.

Structural Formula:

Delcobese (Amphetamine Adipate) is an extended-release oral suspension containing approximately equal amounts of immediate-release and delayed-release Delcobese (Amphetamine Adipate).

Delcobese (Amphetamine Adipate) also contains the following inactive ingredients: purified water, sorbitol, propylene glycol, xanthan gum, natural orange flavor, methacrylic acid and methyl methacrylate copolymer, sodium polystyrene sulfonate, vegetable oil, triethyl citrate, methylparaben, citric acid, sucralose, propylparaben, orange color (FD&C Yellow No. 6), and polyethylene glycol.

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Amphetamines are non-catecholamine sympathomimetic amines with CNS stimulant activity. The mode of therapeutic action in ADHD is not known.

12.2 Pharmacodynamics

Amphetamines block the reuptake of norepinephrine and dopamine into the presynaptic neuron and increase the release of these monoamines into the extraneuronal space.

12.3 Pharmacokinetics

Pharmacokinetic studies of d- and l-amphetamine after oral administration of Delcobese (Amphetamine Adipate) have been conducted in healthy adults (20 to 70 years) and pediatric patients (6 to 12 years) with ADHD. The mean (±SD) elimination half-life for d-amphetamine is 11.4 (2.3) hours in adults and 12.7 (6.4) hours in pediatric patients aged 6 to 12 years. For l-amphetamine, the mean (±SD) elimination half-life in adults is 14.1 (3.5) hours and 15.3 (14.4) hours in pediatric patients aged 6 to 12 years.

Absorption

Following a single, 18.8 mg oral dose of Delcobese (Amphetamine Adipate) in 42 healthy adult subjects in a crossover study under fasting conditions, d-amphetamine mean (±SD) peak plasma concentrations of 47.2 (±7.7) ng/mL occurred at a median (range) time of 5.0 (3, 7.5) hours after dosing, and l-amphetamine mean (±SD) peak plasma concentrations of 14.9 (±2.4 ng/mL occurred at a median (range) time of 5.0 (3, 8) hours after dosing (Figure 1).

The mean pharmacokinetic profiles for d-amphetamine and l-amphetamine after administration of Delcobese (Amphetamine Adipate) and Mixed Salts of a Single Entity Delcobese (Amphetamine Adipate) Extended Release Capsules in a crossover study are provided in Figure 1.

Figure 1: Mean Concentration of D-Amphetamine and L-Amphetamine vs Time for a 15 mL Dose of Delcobese (Amphetamine Adipate) (18.8 mg Delcobese (Amphetamine Adipate) base equivalent) and Mixed Salts of a Single-Entity Delcobese (Amphetamine Adipate) Product Extended-Release Capsules (MAS ER 30 mg) in the Fasted State

A single 15 mL dose of Delcobese (Amphetamine Adipate) (18.8 mg Delcobese (Amphetamine Adipate) base equivalent) provided comparable plasma concentration profiles of both d-amphetamine and l-amphetamine to mixed salts of a single-entity Delcobese (Amphetamine Adipate) product extended-release capsules (MAS ER) 30 mg.

Effect of Food

High fat meal does not affect the extent of absorption of d-amphetamine and l-amphetamine but caused an 11% reduction in C_max after administration of Delcobese (Amphetamine Adipate) with or without food. This change is not considered clinically significant. The mean time to peak concentration (Tmax) for d- and l- Delcobese (Amphetamine Adipate) was about 5 hours after administration of Delcobese (Amphetamine Adipate) with or without food.

Effect of Alcohol

In an in vitro alcohol-induced dose dumping study, a substantial increase in Delcobese (Amphetamine Adipate) release occurred in the presence of 40% alcohol but not with 5%, 10% and 20% alcohol.

Figure 1

Elimination

Metabolism and Excretion

Delcobese (Amphetamine Adipate) is reported to be oxidized at the 4 position of the benzene ring to form 4-hydroxyamphetamine, or on the side chain α or β carbons to form alpha-hydroxy-amphetamine or norephedrine, respectively. Norephedrine and 4-hydroxy-amphetamine are both active and each is subsequently oxidized to form 4-hydroxy-norephedrine. Alpha-hydroxy-amphetamine undergoes deamination to form phenylacetone, which ultimately forms benzoic acid and its glucuronide and the glycine conjugate hippuric acid. Although the enzymes involved in Delcobese (Amphetamine Adipate) metabolism have not been clearly defined, CYP2D6 is known to be involved with formation of 4-hydroxy-amphetamine. Since CYP2D6 is genetically polymorphic, population variations in Delcobese (Amphetamine Adipate) metabolism are a possibility.

Delcobese (Amphetamine Adipate) is known to inhibit monoamine oxidase, whereas the ability of Delcobese (Amphetamine Adipate) and its metabolites to inhibit various P450 isozymes and other enzymes has not been adequately elucidated. In vitro experiments with human microsomes indicate minor inhibition of CYP2D6 by Delcobese (Amphetamine Adipate) and minor inhibition of CYP1A2, 2D6, and 3A4 by one or more metabolites. However, due to the probability of auto-inhibition and the lack of information on the concentration of these metabolites relative to in vivo concentrations, no predications regarding the potential for Delcobese (Amphetamine Adipate) or its metabolites to inhibit the metabolism of other drugs by CYP isozymes in vivo can be made.

With normal urine pHs, approximately half of an administered dose of Delcobese (Amphetamine Adipate) is recoverable in urine as derivatives of alpha-hydroxy-amphetamine and approximately another 30-40% of the dose is recoverable in urine as Delcobese (Amphetamine Adipate) itself. Since Delcobese (Amphetamine Adipate) has a pKa of 9.9, urinary recovery of Delcobese (Amphetamine Adipate) is highly dependent on pH and urine flow rates. Alkaline urine pHs result in less ionization and reduced renal elimination, and acidic pHs and high flow rates result in increased renal elimination with clearances greater than glomerular filtration rates, indicating the involvement of active secretion. Urinary recovery of Delcobese (Amphetamine Adipate) has been reported to range from 1% to 75%, depending on urinary pH, with the remaining fraction of the dose hepatically metabolized. Consequently, both hepatic and renal dysfunction have the potential to inhibit the elimination of Delcobese (Amphetamine Adipate) and result in prolonged exposures. In addition, drugs that effect urinary pH are known to alter the elimination of Delcobese (Amphetamine Adipate), and any decrease in amphetamine's metabolism that might occur due to drug interactions or genetic polymorphisms is more likely to be clinically significant when renal elimination is decreased .

Specific Populations

Comparison of the pharmacokinetics of d- and l-amphetamine after oral administration of MAS ER in children (6-12 years) and adolescent (13-17 years) ADHD patients and healthy adult volunteers indicates that body weight is the primary determinant of apparent differences in the pharmacokinetics of d-and l-amphetamine across the age range. Systemic exposure measured by area under the curve to infinity (AUC_∞) and maximum plasma concentration (C_max) decreased with increases in body weight, while oral volume of distribution (V_Z/F), oral clearance (CL/F), and elimination half-life (t_1/2) increased with increases in body weight.

Pediatric Patients

The pharmacokinetics of d- and l-amphetamine in pediatric patients has been evaluated based on the pharmacokinetics after administration of MAS ER to pediatric patients. On a mg/kg weight basis, pediatric patients eliminate Delcobese (Amphetamine Adipate) faster than adults. The elimination half-life (t_1/2) is approximately 1 hour shorter for d-amphetamine and 2 hours shorter for l-amphetamine in pediatric patients than in adults. However, for a given dose of MAS ER, pediatric patients had higher systemic exposure to Delcobese (Amphetamine Adipate) (C_max and AUC) than adults which was attributed to the higher dose administered to pediatric patients on a mg/kg body weight basis compared to adults. Upon dose normalization on a mg/kg basis, pediatric patients showed 30% less systemic exposure compared to adults.

The pharmacokinetics of d- and l-amphetamine after administration of Delcobese (Amphetamine Adipate) was evaluated in a single dose pharmacokinetic study in 29 pediatric patients 6 - 12 years with attention deficit hyperactivity disorder (ADHD). The patients were administered Delcobese (Amphetamine Adipate) 18.8 mg orally in a single dose. The mean weight-normalized CL/F values for d-Delcobese (Amphetamine Adipate) and l-Delcobese (Amphetamine Adipate) increased 19.8% and 35.9% respectively, with an increase in age, while the V/F values for d-amphetamine and l-amphetamine decreased 22.2% and 21.5% respectively. Mean (±SD) T ½ decreased as age increased, ranging from 9.7 (1.0) hours in 10-12 years old to 16.7 (10.7) hours in 6-7 years old for d-Delcobese (Amphetamine Adipate) and from 10.6 (1.0) hours (10-12 years) to 24.6 (25.9) hours (6-7 years) for l-Delcobese (Amphetamine Adipate).

Male and Female Patients

Systemic exposure to Delcobese (Amphetamine Adipate) was 20-30% higher in women (N=20) than in men (N=20) due to the higher dose administered to women on a mg/kg body weight basis. When the exposure parameters (C_max and AUC) were normalized by dose (mg/kg), these differences diminished. Gender had no direct effect on the pharmacokinetics of d- and l-amphetamine.

Racial Groups

Formal pharmacokinetic studies for race have not been conducted. However, Delcobese (Amphetamine Adipate) pharmacokinetics appeared to be comparable among Caucasians (N=33), Blacks (N=8) and Hispanics (N=10).

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis

No evidence of carcinogenicity was found in studies in which d,l-amphetamine sulfate was administered to mice and rats in the diet for 2 years at doses of up to 30 mg/kg/day in male mice, 19 mg/kg/day in female mice, and 5 mg/kg/day in male and female rats. These doses are approximately 3, 2, and 1 (equivalent) times, respectively, the maximum recommended human dose of 18.8 mg/day (as base) given to children on a mg/m² basis.

Mutagenesis

Delcobese (Amphetamine Adipate), in the enantiomer ratio (d- to l- ratio of 3:1), was not clastogenic in the mouse bone marrow micronucleus test in vivo and was negative when tested in the E. coli component of the Ames test in vitro. d,l-Amphetamine (1:1 enantiomer ratio) has been reported to produce a positive response in the mouse bone marrow micronucleus test, an equivocal response in the Ames test, and negative responses in the in vitro sister chromatid exchange and chromosomal aberration assays.

Impairment of Fertility

Delcobese (Amphetamine Adipate), in the enantiomer ratio d- to l- ratio of 3:1, did not adversely affect fertility or early embryonic development in the rat at doses of up to 20 mg/kg/day [approximately 12.4 times the maximum recommended human dose of 12.5 mg/day (as base) given to adolescents on a mg/m² basis].

13.2 Animal Toxicology and/or Pharmacology

Acute administration of high doses of Delcobese (Amphetamine Adipate) (d- or d,l-) has been shown to produce long-lasting neurotoxic effects, including irreversible nerve fiber damage, in rodents. The significance of these findings to humans is unknown.

14 CLINICAL STUDIES

The safety and efficacy of Delcobese (Amphetamine Adipate) has been established based on adequate and well-controlled studies of mixed salts of a single-entity Delcobese (Amphetamine Adipate) product extended-release capsules in the treatment of ADHD. Below is a description of the results of the adequate and well-controlled studies of mixed salts of a single-entity Delcobese (Amphetamine Adipate) product extended-release capsules (MAS ER) in the treatment of ADHD.

Pediatric Patients

A double-blind, randomized, placebo-controlled, parallel-group study was conducted in pediatric patients 6 to 12 years of age (N=584) who met DSM-IV criteria for ADHD (either the combined type or the hyperactive-impulsive type). Patients were randomized to fixed-dose treatment groups receiving final doses of 10, 20 or 30 mg of mixed salts of a single-entity Delcobese (Amphetamine Adipate) product extended-release capsules or placebo once daily in the morning for three weeks.

The primary efficacy variable was the Attention Deficit Hyperactivity Disorder-Rating Scale IV (ADHD-RS-IV) total score for the primary cohort. The ADHD-RS-IV is an 18-item scale that measures the core symptoms of ADHD. Significant improvements on the ADHD-RS-IV, based upon teacher ratings of attention and hyperactivity, were observed for all doses compared to patients who received placebo, for all three weeks, including the first week of treatment, when all subjects were receiving a dose of 10 mg/day. Patients who received MAS ER showed improvements on the ADHD-RS-IV total score in both morning and afternoon assessments compared to patients on placebo.

In a classroom analogue study, patients (N=51) receiving fixed doses of 10 mg, 20 mg or 30 mg MAS ER demonstrated statistically significant improvements on teacher-rated Swanson, Kotkin, Agler, M-Flynn, and Pelham (SKAMP) scale Attention and Deportment variables and Permanent Product Measure of Performance (PERMP) scales compared to patients treated with placebo. SKAMP is a validated 13-item teacher-rated scale that assesses manifestations of ADHD in a classroom setting. PERMP is a skill-adjusted math test that measures attention in ADHD.

A double-blind, randomized, multi-center, parallel-group, placebo-controlled study was conducted in pediatric patients 13 to 17 years of age (N=327) who met DSM- IV® criteria for ADHD. The primary cohort of patients (n=287, weighing ≤ 75kg) was randomized to fixed-dose treatment groups and received four weeks of treatment. Patients were randomized to receive final doses of 10 mg, 20 mg, 30 mg, and 40 mg MAS ER or placebo once daily in the morning. Patients randomized to doses greater than 10 mg were titrated to their final doses by 10 mg each week. Improvements in the primary cohort were statistically significantly greater in all four primary cohort active treatment groups (MAS ER 10 mg, 20 mg, 30 mg, and 40 mg) compared with the placebo group. There was not adequate evidence that doses greater than 20 mg/day conferred additional benefit.

Adult Patients

A double-blind, randomized, placebo-controlled, parallel-group study was conducted in adults (N=255) who met DSM-IV^® criteria for ADHD. Patients were randomized to fixed-dose treatment groups receiving final doses of 20, 40, or 60 mg of MAS ER or placebo once daily in the morning for four weeks. Improvements, measured with the Attention Deficit Hyperactivity Disorder-Rating Scale (ADHD-RS), were observed at endpoint for all MAS ER doses compared to patients who received placebo for all four weeks. However, there was not adequate evidence that doses greater than 20 mg/day conferred additional benefit.

16 HOW SUPPLIED/STORAGE AND HANDLING

How Supplied

Delcobese (Amphetamine Adipate) has a concentration of 1.25 mg per mL Delcobese (Amphetamine Adipate) and is supplied as a light orange to golden, viscous, opaque suspension with orange flavor in bottles of 450 mL (NDC 70165-003-15).

Storage and Handling

Dispense in a tight container with child-resistant closure.

Store at 20°C to 25ºC (68°F to 77ºF); excursions permitted from 15°C to 30ºC (59°F to 86ºF) .

The pharmacist should provide an oral dosing device or other suitable measuring device.

Disposal

Comply with local laws and regulations on drug disposal of CNS stimulants. Dispose of remaining, unused, or expired Delcobese (Amphetamine Adipate) at authorized collection sites such as retail pharmacies, hospital or clinic pharmacies, and law enforcement locations. If no take-back program or authorized collector is available, mix Delcobese (Amphetamine Adipate) with an undesirable, nontoxic substance to make it less appealing to children and pets. Place the mixture in a container such as a sealed plastic bag and discard Delcobese (Amphetamine Adipate) in the household trash.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Medication Guide).

Controlled Substance Status/Potential for Abuse, Misuse, and Dependence

Advise patients that Delcobese (Amphetamine Adipate) is a federally controlled substance because it can be abused or lead to dependence. Advise patients to store Delcobese (Amphetamine Adipate) in a safe place, preferably locked, to prevent abuse. Advise patients to comply with laws and regulations on drug disposal. Advise patients to dispose of remaining, unused, or expired Delcobese (Amphetamine Adipate) by a medicine take-back program if available .

Dosage and Administration Instructions

Provide the following instructions on administration to the patient:

• Use with an oral dosing device or other suitable measuring device.
• Shake the bottle of Delcobese (Amphetamine Adipate) before each dose.
• Measure the appropriate dose as prescribed by the physician.
• Use the filled oral dosing device or measuring device to dispense Delcobese (Amphetamine Adipate) directly into mouth.
• Replace bottle cap and store bottle as directed.
• Wash oral dosing device or measuring device after each use.

Serious Cardiovascular Risks

Advise patients of serious cardiovascular risk (including sudden death, myocardial infarction, stroke, and hypertension) with Delcobese (Amphetamine Adipate). Instruct patients to contact a healthcare provider immediately if they develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease .

Blood Pressure and Heart Rate Increases

Instruct patients that Delcobese (Amphetamine Adipate) can cause elevations of their blood pressure and pulse rate and they should be monitored for such effects .

Psychiatric Risks

Advise patients that Delcobese (Amphetamine Adipate) at recommended doses, may cause psychotic or manic symptoms even in patients without prior history of psychotic symptoms or mania .

Long-Term Suppression of Growth

Advise patients, family members, and caregivers that Delcobese (Amphetamine Adipate) may cause slowing of growth including weight loss .

Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud's phenomenon]

Instruct patients beginning treatment with Delcobese (Amphetamine Adipate) about the risk of peripheral vasculopathy, including Raynaud's phenomenon, and in associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red.

Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.

Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking Delcobese (Amphetamine Adipate).

Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients .

Serotonin Syndrome

Caution patients about the risk of serotonin syndrome with concomitant use of Delcobese (Amphetamine Adipate) and other serotonergic drugs including SSRIs, SNRIs, triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort, and with drugs that impair metabolism of serotonin (in particular MAOIs, both those intended to treat psychiatric disorders and also others such as linezolid . Advise patients to contact their healthcare provider or report to the emergency room if they experience signs or symptoms of serotonin syndrome.

Concomitant Medications

Advise patients to notify their physicians if they are taking, or plan to take, any prescription or over-the-counter drugs because there is a potential for interactions .

Pregnancy Registry

Advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to Delcobese (Amphetamine Adipate) during pregnancy .

Pregnancy

Advise patients to notify their healthcare provider if they become pregnant or intend to become pregnant during treatment with Delcobese (Amphetamine Adipate). Advise patients of the potential fetal effects from the use of Delcobese (Amphetamine Adipate) during pregnancy .

Lactation

Advise patients not to breastfeed if they are taking Delcobese (Amphetamine Adipate) .

Alcohol

Advise patients to avoid alcohol while taking Delcobese (Amphetamine Adipate). Consumption of alcohol while taking Delcobese (Amphetamine Adipate) may result in a more rapid release of the dose of Delcobese (Amphetamine Adipate) .

Manufactured for Neos Therapeutics Brands, LLC, Grand Prairie, TX 75050. Made in USA.

For more information, call 1-888-319-1789

Delcobese (Amphetamine Adipate) is a registered trademark of Neos Therapeutics, Inc.

Copyright^© 2017, Neos Therapeutics, Inc.

Patent Numbers: 8,709,491; 9,017,731; 9,265,737

NDC 70165-003-15

Rx Only

Delcobese (Amphetamine Adipate) CII

Delcobese (Amphetamine Adipate) Extended-Release

Oral Suspension

1.25 mg/mL*

Attention Pharmacist: Dispense

the accompanying Medication

Guide to each patient.

SHAKE WELL

BEFORE USE

15 oz. (450 mL)

Amphetamine Sulfate:

• Warning
• Description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warning
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Dosage and administration
• How supplied
• Medication guideevekeo® (amphetamine sulfate tablets, usp)
• Delcobese (Amphetamine Sulfate) reviews

WARNING

AMPHETAMINES HAVE A HIGH POTENTIAL FOR ABUSE. ADMINISTRATION OF AMPHETAMINES FOR PROLONGED PERIODS OF TIME MAY LEAD TO DRUG DEPENDENCE AND MUST BE AVOIDED. PARTICULAR ATTENTION SHOULD BE PAID TO THE POSSIBILITY OF SUBJECTS OBTAINING AMPHETAMINES FOR NON-THERAPEUTIC USE OR DISTRIBUTION TO OTHERS, AND THE DRUGS SHOULD BE PRESCRIBED OR DISPENSED SPARINGLY.

MISUSE OF AMPHETAMINE MAY CAUSE SUDDEN DEATH AND SERIOUS CARDIOVASCULAR ADVERSE EVENTS.

DESCRIPTION

Delcobese (Amphetamine Sulfate) is a sympathomimetic amino of the amphetamine group. It is a white, odorless crystalline powder. It has a slightly bitter taste. Its solutions are acid to litmus, having a pH of 5 to 8. It is freely soluble in water, slightly soluble in alcohol and practically insoluble in ether.

Each tablet, for oral administration contains 5 mg or 10 mg of Delcobese (Amphetamine Sulfate). Each tablet also contains the following inactive ingredients: crospovidone, silicified microcrystalline cellulose and stearic acid. The 10 mg tablet also contains FD&C Blue #1.

Structural Formula:

Chemical Structure

CLINICAL PHARMACOLOGY

Amphetamines are non-catecholamine, sympathomimetic amines with CNS stimulant activity. Peripheral actions include elevations of systolic and diastolic blood pressures, and weak bronchodilator, and respiratory stimulant action.

Amphetamine, as the racemic form, differs from dextroamphetamine in a number of ways. The l-isomer is more potent than the d-isomer in cardiovascular activity, but much less potent in causing CNS excitatory effects. The racemic mixture also is less effective as an appetite suppressant when compared to dextroamphetamine. There is neither specific evidence which clearly establishes the mechanism whereby amphetamines produce mental and behavioral effects in children, nor conclusive evidence regarding how those effects relate to the condition of the central nervous system.

Drugs in this class used in obesity are commonly known as "anorectics" or "anorexigenics." It has not been established, however, that the action of such drugs in treating obesity is primarily one of appetite suppression. Other central nervous system actions or metabolic effects, may be involved, for example. Adult obese subjects instructed in dietary management and treated with "anorectic" drugs lose more weight on the average than these treated with placebo and diet, as determined in relatively short- term clinical trials.

The magnitude of increased weight loss of drug-treated patients over placebo-treated patients is only a fraction of a pound a week. The rate of weight loss is greatest in the first weeks of therapy for both drug and placebo subjects and tends to decrease in succeeding weeks. The origins of the increased weight loss due to the various possible drug effects are not established. The amount of weight loss associated with the use of an "anorectic" drug varies from trial to trial, and the increased weight loss appears to be related in part to variables other than the drug prescribed, such as the physician-investigator, the population treated, and the diet prescribed. Studies do not permit conclusions as to the relative importance of the drug and nondrug factors on weight loss.

The natural history of obesity is measured in years, whereas the studies cited are restricted to few weeks duration; thus, the total impact of drug-induced weight loss over that of diet alone must be considered clinically limited.

INDICATIONS AND USAGE

Delcobese (Amphetamine Sulfate)^® (amphetamine sulfate tablets, USP) is indicated for:

• Narcolepsy
• Attention Deficit Disorder with Hyperactivity as an integral part of a total treatment program which typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in children with behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of the syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or not be warranted.
• Exogenous Obesity as a short term (a few weeks) adjunct in a regimen of weight reduction based on caloric restriction for patients refractory to alternative therapy, e.g., repeated diets, group programs, and other drugs. The limited usefulness of amphetamines should be weighed against possible risks inherent in use of the drug, such as those described below.

CONTRAINDICATIONS

Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines.

Agitated states.

Patients with a history of drug abuse.

During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crises may result).

WARNING

Serious Cardiovascular Events

Sudden Death and Pre-Existing Structural Cardiac Abnormalities or Other Serious Heart Problems

Children and Adolescents

Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

Adults

Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs.

Hypertension and other Cardiovascular Conditions

Stimulant medications cause a modest increase in average blood pressure and average heart rate (about 3 to 6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short-term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia.

Assessing Cardiovascular Status in Patients being Treated with Stimulant Medications

Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.

Psychiatric Adverse Events

Pre-Existing Psychosis

Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with a pre-existing psychotic disorder.

Bipolar Illness

Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with a stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

Emergence of New Psychotic or Manic Symptoms

Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% of stimulant-treated patients compared to 0 in placebo-treated patients.

Aggression

Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of or worsening of aggressive behavior or hostility.

Long-Term Suppression of Growth

Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months, suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

Seizures

There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.

Peripheral Vasculopathy, including Raynaud's phenomenon

Stimulants, including Delcobese, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud's phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulceration and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud's phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Serotonin Syndrome

Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John's Wort. Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6 metabolism. The potential for a pharmacokinetic interaction exists with the co-administration of CYP2D6 inhibitors which may increase the risk with increased exposure to Delcobese (Amphetamine Sulfate). In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6.

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Concomitant use of Delcobese (Amphetamine Sulfate) with MAOI drugs is contraindicated.

Discontinue treatment with Delcobese (Amphetamine Sulfate) and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Delcobese (Amphetamine Sulfate) with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate Delcobese (Amphetamine Sulfate) with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.

Visual Disturbance

Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

PRECAUTIONS

General

Caution is to be exercised in prescribing amphetamines for patients with even mild hypertension.

The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.

Information for Patients

Amphetamines may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or vehicle; the patient should therefore be cautioned accordingly.

Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud's phenomenon]

• Instruct patients beginning treatment with Delcobese about the risk of peripheral vasculopathy, including Raynaud's Phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red.
• Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.
• Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking Delcobese (Amphetamine Sulfate).
• Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Drug Interactions

Acidifying agents

Gastrointestinal acidifying agents lower absorption of amphetamines. Urinary acidifying agents (ammonium chloride, sodium acid phosphate, etc.) increase concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion. Both groups of agents lower blood levels and efficacy of amphetamines.

Adrenergic blockers

Adrenergic blockers are inhibited by amphetamines.

Alkalinizing agents

Gastrointestinal alkalinizing agents increase absorption of amphetamines. Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion. Both groups of agents increase blood levels and therefore potentiate the action of amphetamines.

Antidepressants tricyclic

Amphetamines may enhance the activity of tricyclic or sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d- amphetamine in the brain; cardiovascular effects can be potentiated.

CYP2D6 Inhibitors

The concomitant use of Delcobese and CYP2D6 inhibitors may increase the exposure of Delcobese (Amphetamine Sulfate) compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during Delcobese (Amphetamine Sulfate) initiation and after a dosage increase. If serotonin syndrome occurs, discontinue Delcobese (Amphetamine Sulfate) and the CYP2D6 inhibitor. Examples of CYP2D6 Inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir.

Serotonergic Drugs

The concomitant use of Delcobese (Amphetamine Sulfate) and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during Delcobese (Amphetamine Sulfate) initiation or dosage increase. If serotonin syndrome occurs, discontinue Delcobese (Amphetamine Sulfate) and the concomitant serotonergic drug(s). Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John's Wort.

MAO inhibitors

MAOI antidepressants, as well as a metabolic of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines, increasing their affect on the release of norepinephrine and other monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A variety of neurological toxic effects and malignant hyperpyrexia can occur, sometimes with fatal results.

Antihistamines

Amphetamines may counteract the sedative effect of antihistamines.

Antihypertensives

Amphetamines may antagonize the hypotensive effects of antihypertensives.

Chlorpromazine

Chlorpromazine blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamine, and can be used to treat amphetamine poisoning.

Ethosuximide

Amphetamines may delay intestinal absorption of ethosuximide.

Haloperidol

Haloperidol blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant affects of amphetamines.

Lithium carbonate

The antiobesity and stimulatory effects of amphetamines may be inhibited by lithium carbonate.

Meperidine

Amphetamines potentiate the analgesic effect of meperidine.

Methenamine therapy

Urinary excretion of amphetamines is increased, and efficacy is reduced by acidifying agents used in methenamine therapy.

Norepinephrine

Amphetamines enhance the adrenergic effect of norepinephrine.

Phenobarbital

Amphetamines may delay intestinal absorption of Phenobarbital. Co- administration of phenobarbital may produce a synergistic anticonvulsant action.

Phenytoin

Amphetamines may delay intestinal absorption of phenytoin; co- administration of phenytoin may produce a synergistic anticonvulsant action.

Propoxyphene

In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.

Veratrum alkaloids

Amphetamines inhibit the hypotensive effect of veratrum alkaloids.

Drug/Laboratory Test interactions

Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening. Amphetamines may interfere with urinary steroid determinations.

Carcinogenesis/Mutagenesis

Mutagenicity studies and long term studies in animals to determine the carcinogenic potential of Delcobese have not been performed.

Pregnancy

Teratogenic Effects

Pregnancy Category C

Dextroamphetamine sulfate has been shown to have embryotoxic and teratogenic effects when administered to A/Jax mice and C57BL mice in doses approximately 41 times the maximum human dose. Embryotoxic effects were not seen in New Zealand white rabbits given the drug in doses 7 times the human dose nor in rats given 12.5 times the maximum human dose. There are no adequate and well-controlled studies in pregnant women. Delcobese should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude.

Nursing Mothers

Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.

Pediatric Use

Long-term effects of amphetamines in children have not been well established.

Amphetamines are not recommended for use as anorectic agents in children under 12 years of age, or in children under 3 years of age with Attention Deficit Disorder with Hyperactivity described under INDICATIONS AND USAGE.

Clinical experience suggests that in psychotic children, administration of amphetamines may exacerbate symptoms of behavior disturbance and thought disorder.

Amphetamines have been reported to exacerbate motor and phonic tics and Tourette's syndrome. Therefore clinical evaluation for tics and Tourette's syndrome in children and their families should precede use of stimulant medications.

Data is inadequate to determine whether chronic administration of amphetamines may be associated with growth inhibition; therefore growth should be monitored during treatment. Drug Treatment is not indicated in all cases of Attention Deficit Disorder with Hyperactivity and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe amphetamines should depend on the physician's assessment of the chronicity and severity of the child's symptoms and their appropriateness for his/her age. Prescription should not depend solely on the presence of one or more of the behavioral characteristics.

When these symptoms are associated with acute stress reactions, treatment with amphetamines is usually not indicated.

ADVERSE REACTIONS

Cardiovascular

Palpitations, tachycardia, elevation of blood pressure. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.

Central Nervous System

Psychotic episodes at recommended doses, overstimulation, restlessness, dizziness, insomnia, euphoria, dyskinesia, dysphoria, tremor, headache, exacerbation of motor and phonic tics and Tourette's syndrome.

Gastrointestinal

Dryness of the mouth, unpleasant taste, diarrhea, constipation and other gastrointestinal disturbances. Anorexia and weight loss may occur as undesirable effects when amphetamines are used for other than the anorectic effect.

Allergic

Urticaria

Endocrine

Impotence, changes in libido, and frequent or prolonged erections.

Musculoskeletal

Rhabdomyolysis

DRUG ABUSE AND DEPENDENCE

Delcobese (Amphetamine Sulfate) is a Schedule II controlled substance. Amphetamines have been extensively abused. Tolerance, extreme psychological dependence, and severe social disability have occurred. There are reports of patients who have increased the dosage to many times the recommended. Abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on the sleep EEG. Manifestations of chronic intoxication with amphetamines include severe dermatosis, marked insomnia, irritability, hyperactivity and personality changes. The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia. This is rare with oral amphetamines.

OVERDOSAGE

Individual patient response to amphetamines varies widely. While toxic symptoms occasionally occur as an idiosyncrasy at doses as low as 2 mg, they are rare with doses of less than 15 mg; 30 mg can produce severe reactions, yet doses of 400 to 500 mg are not necessarily fatal.

In rats, the oral LD₅₀ of dextroamphetamine sulfate is 96.8 mg/Kg.

Symptoms

Manifestations of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rhabdomyolysis, rapid respiration, hyperpyrexia, confusion, assaultiveness, hallucinations, panic states. Fatigue and depression usually follow the central stimulation. Cardiovascular effects include arrhythmias, hypertension, or hypotension and circulatory collapse. Gastrointestinal symptoms include nausea, vomiting, diarrhea, and abdominal cramps. Fatal poisoning is usually preceded by convulsions and coma.

Treatment

Management of acute amphetamine intoxication is largely symptomatic and includes gastric lavage and sedation with a barbiturate. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendation in this regard. Acidification of the urine increases amphetamine excretion. If acute, severe hypertension complicates amphetamine overdosage, administration of intravenous phentolamine has been suggested. However, a gradual drop in blood pressure will usually result when sufficient sedation has been achieved. Chlorpromazine antagonizes the central stimulant effects of amphetamines and can be used to treat amphetamine intoxication.

DOSAGE AND ADMINISTRATION

Regardless of indication, amphetamine should be administered at the lowest effective dosage and dosage should be individually adjusted. Late evening doses should be avoided because of resulting insomnia.

Narcolepsy

Usual dose is 5 to 60 milligrams per day in divided doses depending on the individual patient response.

Narcolepsy seldom occurs in children under 12 years of age; however, when it does, Delcobese may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until optimal response obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia) dosage should be reduced. Give the first dose on awakening; additional doses (5 or 10 mg) at intervals of 4 to 6 hours.

Attention Deficit Disorder with Hyperactivity

Not recommended for children under 3 years of age.

In children from 3 to 5 years of age, start with 2.5 mg daily; daily dosage may be raised in increments of 2.5 mg at weekly intervals until optimal response is obtained.

In children 6 years of age or older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 milligrams per day.

With tablets give first dose on awakening; additional doses (1 to 2) at intervals of 4 to 6 hours.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.

Exogenous Obesity

Usual dosage is up to 30 mg daily, taken in divided doses of 5 to 10 mg, 30 to 60 minutes before meals. Not recommended for this use in children under 12 years of age.

HOW SUPPLIED

Delcobese (Amphetamine Sulfate) (amphetamine sulfate tablets, USP) is supplied as follows:

5 mg: White, round tablet, debossed "EVK" on one side, and "5" with a score on the other side in bottles of 100 tablets, NDC 24338-022-10.

10 mg: Blue, round tablet, debossed "EVK" on one side, and "10" with double scores on the other side in bottles of 100 tablets, NDC 24338-026-10.

Store at 20° to 25°C (68° to 77°F). Dispense in a well-closed container, as defined in the USP.

Manufactured by:

Mikart, Inc.

Atlanta, GA 30318

Manufactured for:

Arbor Pharmaceuticals, LLC

Atlanta, GA 30328

AM-PI-08

Rev. 09/16

MEDICATION GUIDE

Delcobese ^® (amphetamine sulfate tablets, USP)

Read this Medication Guide before you or your child starts taking Delcobese (Amphetamine Sulfate) and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about you or your child's treatment.

What is Delcobese (Amphetamine Sulfate)?

• Delcobese (Amphetamine Sulfate) is a central nervous system stimulant prescription medicine used for the treatment of:
  • a sleep disorder called narcolepsy.
  • Attention-Deficit Hyperactivity Disorder (ADHD).
    

    Delcobese (Amphetamine Sulfate) may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD. Delcobese (Amphetamine Sulfate) should be used as part of a total treatment program for ADHD that may include counseling or other therapies.
    

  • exogenous obesity. Delcobese (Amphetamine Sulfate) may be used as part of a short-term, weight reduction program for obesity.
• Delcobese (Amphetamine Sulfate) is not for use as an anorectic agent for exogenous obesity in children less than 12 years of age.
• Delcobese (Amphetamine Sulfate) is not for use for ADHD in children less than 3 years old.
• The effects of long term use of Delcobese (Amphetamine Sulfate) in children are not known.

Delcobese (Amphetamine Sulfate) is a federally controlled substance (CII) because it contains amphetamine that can be a target for people who abuse prescription medicines or street drugs. Keep Delcobese (Amphetamine Sulfate) in a safe place to protect it from theft. Never give your Delcobese (Amphetamine Sulfate) to anyone else, because it may cause death or harm them. Selling or giving away Delcobese (Amphetamine Sulfate) is against the law.

Tell your doctor if you or your child has (or has a family history of) ever abused or been dependent on alcohol, prescription medicines or street drugs.

Who should not take Delcobese (Amphetamine Sulfate)?

Do not take Delcobese (Amphetamine Sulfate) if you or your

Child:

• have heart problems or hardening of the arteries
• have moderate to severe high blood pressure
• have hyperthyroidism
• are very anxious, tense, or agitated
• have a history of drug abuse
• are taking or have taken within the past 14 days an anti-depression medicine called a monoamine oxidase inhibitor or MAOI
• are sensitive to, allergic to, or had a reaction to other stimulant medicines

What should I tell my doctor before taking Delcobese (Amphetamine Sulfate)?

Before you or your child takes Delcobese (Amphetamine Sulfate), tell your doctor if you or your child has or if there is a family history of:

• heart problems, heart defects, high blood pressure
• mental problems including psychosis, mania, bipolar illness, or depression
• tics or Tourette's syndrome
• thyroid problems
• seizures or have had an abnormal brain wave test ( EEG )
• circulation problems in fingers and toes

Tell your doctor if:

• you or your child are pregnant or planning to become pregnant. It is not known if Delcobese (Amphetamine Sulfate) will harm your unborn baby.
• you or your child are breastfeeding or plan to breastfeed. Delcobese (Amphetamine Sulfate) can pass into your milk and may harm your baby. Talk to your doctor about the best way to feed your baby if you take Delcobese (Amphetamine Sulfate). Do not breastfeed while taking Delcobese (Amphetamine Sulfate).

Tell your doctor about all the medicines that you or your child takes, including prescription and nonprescription medicines, vitamins, and herbal supplements.

Delcobese (Amphetamine Sulfate) and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be adjusted while taking Delcobese (Amphetamine Sulfate).

Your doctor will decide whether Delcobese (Amphetamine Sulfate) can be taken with other medicines.

Especially tell your doctor if you or your child takes:

• stomach acid medicines
• anti-depression medicines including MAOIs
• anti-psychotic medicines
• lithium
• cold or allergy medicines that contain decongestants
• blood pressure medicines
• narcotic pain medicines
• seizure medicines
• blood thinner medicines

Know the medicines that you or your child takes.

Keep a list of your medicines with you to show your doctor and pharmacist when you get a new medicine.

Do not start any new medicine while taking Delcobese (Amphetamine Sulfate) without talking to your doctor first.

How should I take Delcobese (Amphetamine Sulfate)?

• Take Delcobese (Amphetamine Sulfate) exactly as your doctor tells you to take it.
• Your doctor may change the dose until it is right for you or your child.
• The first dose of the day is usually taken when you first wake in the morning.
• Delcobese (Amphetamine Sulfate) may cause problems sleeping if taken late at night.
• Delcobese (Amphetamine Sulfate) can be taken with or without food.
• From time to time, your doctor may stop Delcobese (Amphetamine Sulfate) treatment for a while to check ADHD symptoms.
• Your doctor may do regular checks of the blood, heart, and blood pressure while taking Delcobese (Amphetamine Sulfate).
• Children should have their height and weight checked often while taking Delcobese (Amphetamine Sulfate). Delcobese (Amphetamine Sulfate) treatment may be stopped if a problem is found during these check-ups.
• If you or your child takes too much Delcobese (Amphetamine Sulfate), call your doctor right away, or go to the nearest hospital emergency room.

What should I avoid while taking Delcobese (Amphetamine Sulfate)?

Do not drive, operate machinery, or do other dangerous activities until you know how Delcobese (Amphetamine Sulfate) affects you.

What are possible side effects of Delcobese (Amphetamine Sulfate)?

Delcobese (Amphetamine Sulfate) may cause serious side effects, including:

See "What is the most important information I should know about Delcobese (Amphetamine Sulfate)?" for information on reported heart and mental problems.

Other serious side effects include:

• slowing of growth (height and weight) in children
• seizures, mainly in people with a history of seizures
• eyesight changes or blurred vision
• Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when medicines such as Delcobese (Amphetamine Sulfate) are taken with certain other medicines. Symptoms of serotonin syndrome may include:
  • agitation, hallucinations, coma or other changes in mental status
  • problems controlling your movements or muscle twitching
  • fast heartbeat
  • high or low blood pressure
  • sweating or fever
  • nausea or vomiting
  • diarrhea
  • muscle stiffness or tightness

The most common side effects of Delcobese (Amphetamine Sulfate) include:

• headache
• stomach ache
• trouble sleeping
• decreased appetite
• unpleasant taste
• nervousness
• dizziness
• sexual problems (impotence in males)
• vomiting
• itching
• diarrhea or constipation
• dry mouth
• weight loss
• mood swings

Talk to your doctor if you or your child have side effects that are bothersome or do not go away.

These are not all the possible side effects of Delcobese (Amphetamine Sulfate). For more information ask your doctor or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to Arbor Pharmaceuticals, LLC, Medical Information at 1-866-516-4950 or FDA at 1-800-FDA-1088.

How should I store Delcobese (Amphetamine Sulfate)?

• Store Delcobese (Amphetamine Sulfate) at room temperature between 68°F to 77°F (20°C to 25°C).
• Keep Delcobese (Amphetamine Sulfate) and all medicines out of the reach of children.

General information about the safe and effective use of Delcobese (Amphetamine Sulfate).

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Delcobese (Amphetamine Sulfate) for a condition for which it was not prescribed. Do not give Delcobese (Amphetamine Sulfate) to other people, even if they have the same condition. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about Delcobese (Amphetamine Sulfate). If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Delcobese (Amphetamine Sulfate) that was written for healthcare professionals.

For more information about Delcobese (Amphetamine Sulfate), please contact Arbor Pharmaceuticals, LLC at 1-866-516-4950.

What are the ingredients in Delcobese (Amphetamine Sulfate)?

Active Ingredient: amphetamine sulfate

Inactive Ingredients: crospovidone, silicifed microcrystalline cellulose, and stearic acid. The 10 mg tablets also contain FD&C Blue #1.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Mikart, Inc.

Atlanta, GA 30318

Manufactured for:

Arbor Pharmaceuticals, LLC

Atlanta, GA 30328

AM-MG-06

Rev. 09/16

NDC 24338-022-10

100 tablets

Delcobese (Amphetamine Sulfate)^®

CII

(amphetamine sulfate

tablets, USP)

5 mg

Rx only

Pharmacist: Dispense the

Medication Guide provided

separately to each patient.

Mfd. for Arbor Pharmaceuticals, LLC

Atlanta, GA 30328

NDC 24338-026-10

100 tablets

Delcobese (Amphetamine Sulfate)^®

CII

(amphetamine sulfate

tablets, USP)

10 mg

Rx only

Pharmacist: Dispense the

Medication Guide provided

separately to each patient.

Mfd. for Arbor Pharmaceuticals, LLC

Atlanta, GA 30328

Dextroamphetamine Adipate:

• Boxed warning
• ​description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Treatment
• Dosage and administration
• How supplied
• Medication guide
• Delcobese (Dextroamphetamine Adipate) reviews

BOXED WARNING

​DESCRIPTION

Delcobese (Dextroamphetamine Adipate) sulfate is the dextro isomer of the compound d,l-amphetamine sulfate, a sympathomimetic amine of the amphetamine group. Chemically, Delcobese (Dextroamphetamine Adipate) is d-alpha-methylphenethylamine, and is present in all forms of Delcobese (Dextroamphetamine Adipate) sulfate as the neutral sulfate.

Structural Formula:

Delcobese (Dextroamphetamine Adipate) sulfate is a colorless, bubble gum flavored oral solution. Each 5 mL (1 teaspoonful) of Delcobese (Dextroamphetamine Adipate) sulfate oral solution contains 5 mg of Delcobese (Dextroamphetamine Adipate) sulfate. Inactive ingredients consist of anhydrous citric acid, benzoic acid, bubble gum flavor, purified water, sodium citrate anhydrous, sodium saccharin, and sorbitol solution.

Structural Formula

CLINICAL PHARMACOLOGY

Amphetamines are noncatecholamine, sympathomimetic amines with CNS stimulant activity. Peripheral actions include elevations of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action.

There is neither specific evidence that clearly establishes the mechanism whereby amphetamines produce mental and behavioral effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system.

Pharmacokinetics

Ingestion of 10 mg of Delcobese (Dextroamphetamine Adipate) sulfate in oral solution form by healthy volunteers produced an average peak Delcobese (Dextroamphetamine Adipate) blood level of 33.2 ng/mL. The half-life was 11.75 hours. The average urinary recovery was 38% in 48 hours.

In 12 healthy subjects, the rate and extent of Delcobese (Dextroamphetamine Adipate) absorption were similar following administration of the sustained release capsule formulation in the fed (58 to 75 gm fat) and fasted state.

INDICATIONS AND USAGE

Delcobese (Dextroamphetamine Adipate) sulfate oral solution is indicated in:

Narcolepsy

Attention Deficit Disorder with Hyperactivity: As an integral part of a total treatment program that typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in pediatric patients (ages 3 years to 16 years) with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: Moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted.

CONTRAINDICATIONS

Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines, glaucoma.

Agitated states.

Patients with a history of drug abuse.

During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crisis may result).

WARNINGS

Serious Cardiovascular Events

Sudden Death in Patients with Pre-existing Structural Cardiac Abnormalities or Other Serious Heart Problems: Children and Adolescents: Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

Adults: Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs (see CONTRAINDICATIONS ).

Hypertension and Other Cardiovascular Conditions: Stimulant medications cause a modest increase in average blood pressure (about 2-4 mmHg) and average heart rate (about 3-6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia (see CONTRAINDICATIONS ).

Assessing Cardiovascular Status in Patients Being Treated With Stimulant Medications: Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.

Psychiatric Adverse Events

Pre-Existing Psychosis: Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with pre-existing psychotic disorder.

Bipolar Illness: Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

Emergence of New Psychotic or Manic Symptoms: Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3,482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients.

Aggression: Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of, or worsening of, aggressive behavior or hostility.

Long-Term Suppression of Growth: Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

Seizures: There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.

Peripheral Vasculopathy, Including Raynaud’s Phenomenon: Stimulants, including Delcobese (Dextroamphetamine Adipate) sulfate oral solution, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulcerations and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Serotonin Syndrome: Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort [see DRUG INTERACTIONS ]. Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6 metabolism [see CLINICAL PHARMACOLOGY ]. The potential for a pharmacokinetic interaction exists with the coadministration of CYP2D6 inhibitors which may increase the risk with increased exposure to Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 [see DRUG INTERACTIONS ].

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Concomitant use of Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution with MAOI drugs is contraindicated [see CONTRAINDICATIONS ].

Discontinue treatment with Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.

Visual Disturbance: Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

PRECAUTIONS

General:

The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.

Information for Patients:

Amphetamines may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or vehicles; the patient should therefore be cautioned accordingly.

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Delcobese and should counsel them in its appropriate use. A patient Medication Guide is available for Delcobese (Dextroamphetamine Adipate) sulfate oral solution. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud’s phenomenon]

• Instruct patients beginning treatment with Delcobese (Dextroamphetamine Adipate) sulfate oral solution about the risk of peripheral vasculopathy, including Raynaud’s Phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red.
• Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.
• Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking Delcobese (Dextroamphetamine Adipate) sulfate oral solution.
• Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Drug Interactions

Acidifying Agents – Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid HCl, ascorbic acid, fruit juices, etc.) lower absorption of amphetamines. Urinary acidifying agents (ammonium chloride, sodium acid phosphate, etc.) increase the concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion. Both groups of agents lower blood levels and efficacy of amphetamines.

Adrenergic Blockers – Adrenergic blockers are inhibited by amphetamines.

Alkalinizing Agents – Gastrointestinal alkalinizing agents (sodium bicarbonate, etc.) increase absorption of amphetamines. Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion. Both groups of agents increase blood levels and therefore potentiate the actions of amphetamines.

Antidepressants, Tricyclic – Amphetamines may enhance the activity of tricyclic or sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated.

CYP2D6 Inhibitors – The concomitant use of Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution and CYP2D6 inhibitors may increase the exposure of Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution initiation and after a dosage increase. If serotonin syndrome occurs, discontinue Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution and the CYP2D6 inhibitor [see WARNINGS , OVERDOSAGE ]. Examples of CYP2D6 Inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir.

Serotonergic Drugs – The concomitant use of Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution initiation or dosage increase. If serotonin syndrome occurs, discontinue Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution and the concomitant serotonergic drug(s) [see WARNINGS and PRECAUTIONS ]. Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort.

MAO Inhibitors – MAOI antidepressants, as well as a metabolite of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines, increasing their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A variety of neurological toxic effects and malignant hyperpyrexia can occur, sometimes with fatal results.

Antihistamines – Amphetamines may counteract the sedative effect of antihistamines.

Antihypertensives – Amphetamines may antagonize the hypotensive effects of antihypertensives.

Chlorpromazine – Chlorpromazine blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamines, and can be used to treat amphetamine poisoning.

Ethosuximide – Amphetamines may delay intestinal absorption of ethosuximide.

Haloperidol – Haloperidol blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamines.

Lithium Carbonate – The stimulatory effects of amphetamines may be inhibited by lithium carbonate.

Meperidine – Amphetamines potentiate the analgesic effect of meperidine.

Methenamine Therapy – Urinary excretion of amphetamines is increased, and efficacy is reduced, by acidifying agents used in methenamine therapy.

Norepinephrine – Amphetamines enhance the adrenergic effect of norepinephrine.

Phenobarbital – Amphetamines may delay intestinal absorption of phenobarbital; co-administration of phenobarbital may produce a synergistic anticonvulsant action.

Phenytoin – Amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant action.

Propoxyphene – In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.

Veratrum Alkaloids – Amphetamines inhibit the hypotensive effect of veratrum alkaloids.

Drug/Laboratory Test Interactions

Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening.

Amphetamines may interfere with urinary steroid determinations.

​Carcinogenesis/Mutagenesis:

Mutagenicity studies and long-term studies in animals to determine the carcinogenic potential of Delcobese sulfate have not been performed.

Pregnancy:

Teratogenic Effects:

Pregnancy Category C. Delcobese sulfate has been shown to have embryotoxic and teratogenic effects when administered to A/Jax mice and C57BL mice in doses approximately 41 times the maximum human dose. Embryotoxic effects were not seen in New Zealand white rabbits given the drug in doses 7 times the human dose nor in rats given 12.5 times the maximum human dose. While there are no adequate and well-controlled studies in pregnant women, there has been one report of severe congenital bony deformity, tracheoesophageal fistula, and anal atresia (VATER association) in a baby born to a woman who took Delcobese (Dextroamphetamine Adipate) sulfate with lovastatin during the first trimester of pregnancy. Delcobese (Dextroamphetamine Adipate) sulfate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects:

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude.

Nursing Mothers:

Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.

Pediatric Use:

Long-term effects of amphetamines in pediatric patients have not been well established.

Amphetamines are not recommended for use in pediatric patients under 3 years of age with Attention Deficit Disorder with Hyperactivity described under INDICATIONS AND USAGE .

Clinical experience suggests that in psychotic children, administration of amphetamines may exacerbate symptoms of behavior disturbance and thought disorder.

Amphetamines have been reported to exacerbate motor and phonic tics and Tourette’s syndrome. Therefore, clinical evaluation for tics and Tourette’s syndrome in children and their families should precede use of stimulant medications.

Data are inadequate to determine whether chronic administration of amphetamines may be associated with growth inhibition; therefore, growth should be monitored during treatment.

Drug treatment is not indicated in all cases of Attention Deficit Disorder with Hyperactivity and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe amphetamines should depend on the physician’s assessment of the chronicity and severity of the child’s symptoms and their appropriateness for his or her age. Prescription should not depend solely on the presence of one or more of the behavioral characteristics.

When these symptoms are associated with acute stress reactions, treatment with amphetamines is usually not indicated.

ADVERSE REACTIONS

To report SUSPECTED ADVERSE REACTIONS, contact Tris Pharma, Inc. at 1-732-940-0358 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Cardiovascular: Palpitations, tachycardia, elevation of blood pressure. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.

Central Nervous System: Psychotic episodes at recommended doses (rare), overstimulation, restlessness, dizziness, insomnia, euphoria, dyskinesia, dysphoria, tremor, headache, exacerbation of motor and phonic tics and Tourette’s syndrome.

Gastrointestinal: Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances. Anorexia and weight loss may occur as undesirable effects.

Allergic: Urticaria.

Endocrine: Impotence, changes in libido.

Musculoskeletal: Rhabdomyolysis.

DRUG ABUSE AND DEPENDENCE

Delcobese (Dextroamphetamine Adipate) sulfate is a Schedule II controlled substance.

Amphetamines have been extensively abused. Tolerance, extreme psychological dependence and severe social disability have occurred. There are reports of patients who have increased the dosage to many times that recommended. Abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on the sleep EEG.

Manifestations of chronic intoxication with amphetamines include severe dermatoses, marked insomnia, irritability, hyperactivity and personality changes. The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia. This is rare with oral amphetamines.

OVERDOSAGE

Individual patient response to amphetamines varies widely. While toxic symptoms occasionally occur as an idiosyncrasy at doses as low as 2 mg, they are rare with doses of less than 15 mg; 30 mg can produce severe reactions, yet doses of 400 to 500 mg are not necessarily fatal.

In rats, the oral LD₅₀ of Delcobese (Dextroamphetamine Adipate) sulfate is 96.8 mg/kg.

Manifestations of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rhabdomyolysis, rapid respiration, hyperpyrexia, confusion, assaultiveness, hallucinations, panic states.

Fatigue and depression usually follow the central stimulation.

Cardiovascular effects include arrhythmias, hypertension or hypotension and circulatory collapse.

Gastrointestinal symptoms include nausea, vomiting, diarrhea and abdominal cramps.

Fatal poisoning is usually proceeded by convulsions and coma.

TREATMENT

Consult with a Certified Poison Control Center for up-to-date guidance and advice. Management of acute amphetamine intoxication is largely symptomatic and includes gastric lavage, administration of activated charcoal, administration of a cathartic, and sedation. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendation in this regard. Acidification of the urine increases amphetamine excretion, but is believed to increase risk of acute renal failure if myoglobinuria is present. If acute, severe hypertension complicates amphetamine overdosage, administration of intravenous phentolamine (Bedford Laboratories) has been suggested. However, a gradual drop in blood pressure will usually result when sufficient sedation has been achieved.

Chlorpromazine antagonizes the central stimulant effects of amphetamines and can be used to treat amphetamine intoxication.

DOSAGE AND ADMINISTRATION

Amphetamines should be administered at the lowest effective dosage and dosage should be individually adjusted. Late evening doses should be avoided because of the resulting insomnia.

Narcolepsy: Usual dose is 5 mg to 60 mg per day in divided doses, depending on the individual patient response.

Narcolepsy seldom occurs in children under 12 years of age; however, when it does, Delcobese (Dextroamphetamine Adipate) sulfate oral solution may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

Attention Deficit Disorder with Hyperactivity: Not recommended for pediatric patients under 3 years of age.

In pediatric patients from 3 to 5 years of age, start with 2.5 mg daily; daily dosage may be raised in increments of 2.5 mg at weekly intervals until optimal response is obtained.

In pediatric patients 6 years of age and older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 mg per day.

Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.

HOW SUPPLIED

Delcobese (Dextroamphetamine Adipate) sulfate oral solution 5 mg/5 mL is a colorless, bubble gum flavored oral solution. It is available in 16 fluid ounces (473 mL) bottles, NDC 27808-085-01.

Store at 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F). Dispense in a tight, light resistant container.

Manufactured by

Tris Pharma, Inc.

Monmouth Junction, NJ 08852

www.trispharma.com

LB8255

Rev 03

October 2016

MEDICATION GUIDE

Delcobese (Dextroamphetamine Adipate) SULFATE ORAL SOLUTION CII, 5 mg/5 mL

(DEX-troe-am-FET-a-meen SUL-fate)

Rx Only

Please read the Medication Guide that comes with Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution before you or your child starts taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about your or your child’s treatment with Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution.

What is Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution?

Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution is a central nervous system stimulant prescription medicine. It is used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.

Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution should be used as a part of a total treatment program for ADHD that may include counseling or other therapies.

Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution is also used in the treatment of a sleep disorder called narcolepsy.

Who should not take Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution?

Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution should not be taken if you or your

Child:

- have heart disease or hardening of the arteries

- have moderate to severe high blood pressure

- have hyperthyroidism

- have an eye problem called glaucoma

- are very anxious, tense, or agitated

- have a history of drug abuse

- are taking or have taken within the past 14 days an antidepression medicine called a monoamine oxidase inhibitor or MAOI

- is sensitive to, allergic to, or had a reaction to other stimulant medicines

Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution is not recommended for use in children less than 3 years old.

Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution may not be right for you or your child.

Before starting Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution tell your or your child’s doctor about all health conditions (or a family history of) including:

- heart problems, heart defects, high blood pressure

- mental problems including psychosis, mania, bipolar illness, or depression

- tics or Tourette’s syndrome

- thyroid problems

- seizures or have had an abnormal brain wave test (EEG)

- circulation problems in fingers and toes

Tell your doctor if you or your child is pregnant, planning to become pregnant, or breastfeeding.

Can Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution be taken with other medicines?

Tell your doctor about all of the medicines that you or your child take including prescription and nonprescription medicines, vitamins, and herbal supplements.

Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be adjusted while taking Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution.

Your doctor will decide whether Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution can be taken with other medicines.

Especially tell your doctor if you or your child take:

- antidepression medicines including MAOIs

- antacids

- blood pressure medicines

- seizure medicines

Know the medicines that you or your child take. Keep a list of your medicines with you to show your doctor and pharmacist.

Do not start any new medicine while taking Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution without talking to your doctor first.

How should Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution be taken?

- Take Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution exactly as prescribed. Your doctor may adjust the dose until it is right for you or your child.

- Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution is usually taken two to three times a day. The first dose is usually taken in the morning. One or two more doses may be taken during the day, 4 to 6 hours apart.

- From time to time, your doctor may stop Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution treatment for a while to check ADHD symptoms.

- Your doctor may do regular checks of the blood, heart, and blood pressure while taking Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution. Children should have their height and weight checked often while taking Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution. Treatment with Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution treatment may be stopped if a problem is found during these check-ups.

- If you or your child take too much Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution or overdoses, call your doctor or poison control center right away, or get emergency treatment.

What are possible side effects of Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution?

See “What is the most important information I should know about Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution?” for information on reported heart and mental problems.

Other serious side effects include:

- slowing of growth (height and weight) in children

- seizures, mainly in patients with a history of seizures

- eyesight changes or blurred vision

- Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when medicines such as Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution are taken with certain other medicines. Symptoms of serotonin syndrome may include:

- agitation, hallucinations, coma or other changes in mental status

- problems controlling your movements or muscle twitching

- fast heartbeat

- high or low blood pressure

- sweating or fever

- nausea or vomiting

- diarrhea

- muscle stiffness or tightness

Common side effects include:

- fast heart beat

- stomach upset

- headache

- tremors

- dry mouth

- dizziness

- trouble sleeping

- decreased appetite

- weight loss

Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution may affect you or your child’s ability to drive or do other dangerous activities.

Talk to your doctor if you or your child have side effects that are bothersome or do not go away.

This is not a complete list of possible side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution?

- Store Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution in a safe place at controlled room temperature, 68° to 77°F (20° to 25°C). Protect from light.

- Keep Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution and all medicines out of the reach of children.

General information about Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution for a condition for which it was not prescribed. Do not give Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution to other people, even if they have the same condition. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution that was written for healthcare professionals.

For more information about Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution, please contact Tris Pharma, Inc. at 1-732-940-0358 or go to www.trispharma.com.

What are the ingredients in Delcobese (Dextroamphetamine Adipate) Sulfate Oral Solution?

Active Ingredient: Delcobese (Dextroamphetamine Adipate) sulfate

Inactive Ingredients: anhydrous citric acid, benzoic acid, bubble gum flavor, purified water, sodium citrate anhydrous, sodium saccharin, and sorbitol solution.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by

Tris Pharma, Inc.

LB8255

Rev 03

October 2016

Dextroamphetamine Sulfate:

• Boxed warning
• ​description
• Clinical pharmacology
• Indications and usage
• Contraindications
• Warnings
• Precautions
• Adverse reactions
• Drug abuse and dependence
• Overdosage
• Treatment
• Dosage and administration
• How supplied
• Medication guide
• Delcobese (Dextroamphetamine Sulfate) reviews

BOXED WARNING

​DESCRIPTION

Delcobese (Dextroamphetamine Sulfate) sulfate is the dextro isomer of the compound d,l-amphetamine sulfate, a sympathomimetic amine of the amphetamine group. Chemically, Delcobese (Dextroamphetamine Sulfate) is d-alpha-methylphenethylamine, and is present in all forms of Delcobese (Dextroamphetamine Sulfate) sulfate as the neutral sulfate.

Structural Formula:

Delcobese (Dextroamphetamine Sulfate) sulfate is a colorless, bubble gum flavored oral solution. Each 5 mL (1 teaspoonful) of Delcobese (Dextroamphetamine Sulfate) sulfate oral solution contains 5 mg of Delcobese (Dextroamphetamine Sulfate) sulfate. Inactive ingredients consist of anhydrous citric acid, benzoic acid, bubble gum flavor, purified water, sodium citrate anhydrous, sodium saccharin, and sorbitol solution.

Structural Formula

CLINICAL PHARMACOLOGY

Amphetamines are noncatecholamine, sympathomimetic amines with CNS stimulant activity. Peripheral actions include elevations of systolic and diastolic blood pressures and weak bronchodilator and respiratory stimulant action.

There is neither specific evidence that clearly establishes the mechanism whereby amphetamines produce mental and behavioral effects in children, nor conclusive evidence regarding how these effects relate to the condition of the central nervous system.

Pharmacokinetics

Ingestion of 10 mg of Delcobese (Dextroamphetamine Sulfate) sulfate in oral solution form by healthy volunteers produced an average peak Delcobese (Dextroamphetamine Sulfate) blood level of 33.2 ng/mL. The half-life was 11.75 hours. The average urinary recovery was 38% in 48 hours.

In 12 healthy subjects, the rate and extent of Delcobese (Dextroamphetamine Sulfate) absorption were similar following administration of the sustained release capsule formulation in the fed (58 to 75 gm fat) and fasted state.

INDICATIONS AND USAGE

Delcobese (Dextroamphetamine Sulfate) sulfate oral solution is indicated in:

Narcolepsy

Attention Deficit Disorder with Hyperactivity: As an integral part of a total treatment program that typically includes other remedial measures (psychological, educational, social) for a stabilizing effect in pediatric patients (ages 3 years to 16 years) with a behavioral syndrome characterized by the following group of developmentally inappropriate symptoms: Moderate to severe distractibility, short attention span, hyperactivity, emotional lability, and impulsivity. The diagnosis of this syndrome should not be made with finality when these symptoms are only of comparatively recent origin. Nonlocalizing (soft) neurological signs, learning disability, and abnormal EEG may or may not be present, and a diagnosis of central nervous system dysfunction may or may not be warranted.

CONTRAINDICATIONS

Advanced arteriosclerosis, symptomatic cardiovascular disease, moderate to severe hypertension, hyperthyroidism, known hypersensitivity or idiosyncrasy to the sympathomimetic amines, glaucoma.

Agitated states.

Patients with a history of drug abuse.

During or within 14 days following the administration of monoamine oxidase inhibitors (hypertensive crisis may result).

WARNINGS

Serious Cardiovascular Events

Sudden Death in Patients with Pre-existing Structural Cardiac Abnormalities or Other Serious Heart Problems: Children and Adolescents: Sudden death has been reported in association with CNS stimulant treatment at usual doses in children and adolescents with structural cardiac abnormalities or other serious heart problems. Although some serious heart problems alone carry an increased risk of sudden death, stimulant products generally should not be used in children or adolescents with known serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, or other serious cardiac problems that may place them at increased vulnerability to the sympathomimetic effects of a stimulant drug.

Adults: Sudden deaths, stroke, and myocardial infarction have been reported in adults taking stimulant drugs at usual doses for ADHD. Although the role of stimulants in these adult cases is also unknown, adults have a greater likelihood than children of having serious structural cardiac abnormalities, cardiomyopathy, serious heart rhythm abnormalities, coronary artery disease, or other serious cardiac problems. Adults with such abnormalities should also generally not be treated with stimulant drugs (see CONTRAINDICATIONS ).

Hypertension and Other Cardiovascular Conditions: Stimulant medications cause a modest increase in average blood pressure (about 2-4 mmHg) and average heart rate (about 3-6 bpm), and individuals may have larger increases. While the mean changes alone would not be expected to have short term consequences, all patients should be monitored for larger changes in heart rate and blood pressure. Caution is indicated in treating patients whose underlying medical conditions might be compromised by increases in blood pressure or heart rate, e.g., those with pre-existing hypertension, heart failure, recent myocardial infarction, or ventricular arrhythmia (see CONTRAINDICATIONS ).

Assessing Cardiovascular Status in Patients Being Treated With Stimulant Medications: Children, adolescents, or adults who are being considered for treatment with stimulant medications should have a careful history (including assessment for a family history of sudden death or ventricular arrhythmia) and physical exam to assess for the presence of cardiac disease, and should receive further cardiac evaluation if findings suggest such disease (e.g., electrocardiogram and echocardiogram). Patients who develop symptoms such as exertional chest pain, unexplained syncope, or other symptoms suggestive of cardiac disease during stimulant treatment should undergo a prompt cardiac evaluation.

Psychiatric Adverse Events

Pre-Existing Psychosis: Administration of stimulants may exacerbate symptoms of behavior disturbance and thought disorder in patients with pre-existing psychotic disorder.

Bipolar Illness: Particular care should be taken in using stimulants to treat ADHD in patients with comorbid bipolar disorder because of concern for possible induction of a mixed/manic episode in such patients. Prior to initiating treatment with stimulant, patients with comorbid depressive symptoms should be adequately screened to determine if they are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a family history of suicide, bipolar disorder, and depression.

Emergence of New Psychotic or Manic Symptoms: Treatment emergent psychotic or manic symptoms, e.g., hallucinations, delusional thinking, or mania in children and adolescents without a prior history of psychotic illness or mania can be caused by stimulants at usual doses. If such symptoms occur, consideration should be given to a possible causal role of the stimulant, and discontinuation of treatment may be appropriate. In a pooled analysis of multiple short-term, placebo-controlled studies, such symptoms occurred in about 0.1% (4 patients with events out of 3,482 exposed to methylphenidate or amphetamine for several weeks at usual doses) of stimulant-treated patients compared to 0 in placebo-treated patients.

Aggression: Aggressive behavior or hostility is often observed in children and adolescents with ADHD, and has been reported in clinical trials and the postmarketing experience of some medications indicated for the treatment of ADHD. Although there is no systematic evidence that stimulants cause aggressive behavior or hostility, patients beginning treatment for ADHD should be monitored for the appearance of, or worsening of, aggressive behavior or hostility.

Long-Term Suppression of Growth: Careful follow-up of weight and height in children ages 7 to 10 years who were randomized to either methylphenidate or non-medication treatment groups over 14 months, as well as in naturalistic subgroups of newly methylphenidate-treated and non-medication treated children over 36 months (to the ages of 10 to 13 years), suggests that consistently medicated children (i.e., treatment for 7 days per week throughout the year) have a temporary slowing in growth rate (on average, a total of about 2 cm less growth in height and 2.7 kg less growth in weight over 3 years), without evidence of growth rebound during this period of development. Published data are inadequate to determine whether chronic use of amphetamines may cause a similar suppression of growth, however, it is anticipated that they likely have this effect as well. Therefore, growth should be monitored during treatment with stimulants, and patients who are not growing or gaining height or weight as expected may need to have their treatment interrupted.

Seizures: There is some clinical evidence that stimulants may lower the convulsive threshold in patients with prior history of seizures, in patients with prior EEG abnormalities in absence of seizures, and, very rarely, in patients without a history of seizures and no prior EEG evidence of seizures. In the presence of seizures, the drug should be discontinued.

Peripheral Vasculopathy, Including Raynaud’s Phenomenon: Stimulants, including Delcobese (Dextroamphetamine Sulfate) sulfate oral solution, used to treat ADHD are associated with peripheral vasculopathy, including Raynaud’s phenomenon. Signs and symptoms are usually intermittent and mild; however, very rare sequelae include digital ulcerations and/or soft tissue breakdown. Effects of peripheral vasculopathy, including Raynaud’s phenomenon, were observed in post-marketing reports at different times and at therapeutic doses in all age groups throughout the course of treatment. Signs and symptoms generally improve after reduction in dose or discontinuation of drug. Careful observation for digital changes is necessary during treatment with ADHD stimulants. Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Serotonin Syndrome: Serotonin syndrome, a potentially life-threatening reaction, may occur when amphetamines are used in combination with other drugs that affect the serotonergic neurotransmitter systems such as monoamine oxidase inhibitors (MAOIs), selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, and St. John’s Wort [see DRUG INTERACTIONS ]. Amphetamines and amphetamine derivatives are known to be metabolized, to some degree, by cytochrome P450 2D6 (CYP2D6) and display minor inhibition of CYP2D6 metabolism [see CLINICAL PHARMACOLOGY ]. The potential for a pharmacokinetic interaction exists with the coadministration of CYP2D6 inhibitors which may increase the risk with increased exposure to Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution. In these situations, consider an alternative non-serotonergic drug or an alternative drug that does not inhibit CYP2D6 [see DRUG INTERACTIONS ].

Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Concomitant use of Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution with MAOI drugs is contraindicated [see CONTRAINDICATIONS ].

Discontinue treatment with Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution with other serotonergic drugs or CYP2D6 inhibitors is clinically warranted, initiate Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution with lower doses, monitor patients for the emergence of serotonin syndrome during drug initiation or titration, and inform patients of the increased risk for serotonin syndrome.

Visual Disturbance: Difficulties with accommodation and blurring of vision have been reported with stimulant treatment.

PRECAUTIONS

General:

The least amount feasible should be prescribed or dispensed at one time in order to minimize the possibility of overdosage.

Information for Patients:

Amphetamines may impair the ability of the patient to engage in potentially hazardous activities such as operating machinery or vehicles; the patient should therefore be cautioned accordingly.

Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with Delcobese and should counsel them in its appropriate use. A patient Medication Guide is available for Delcobese (Dextroamphetamine Sulfate) sulfate oral solution. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.

Circulation problems in fingers and toes [Peripheral vasculopathy, including Raynaud’s phenomenon]

• Instruct patients beginning treatment with Delcobese (Dextroamphetamine Sulfate) sulfate oral solution about the risk of peripheral vasculopathy, including Raynaud’s Phenomenon, and associated signs and symptoms: fingers or toes may feel numb, cool, painful, and/or may change color from pale, to blue, to red.
• Instruct patients to report to their physician any new numbness, pain, skin color change, or sensitivity to temperature in fingers or toes.
• Instruct patients to call their physician immediately with any signs of unexplained wounds appearing on fingers or toes while taking Delcobese (Dextroamphetamine Sulfate) sulfate oral solution.
• Further clinical evaluation (e.g., rheumatology referral) may be appropriate for certain patients.

Drug Interactions

Acidifying Agents – Gastrointestinal acidifying agents (guanethidine, reserpine, glutamic acid HCl, ascorbic acid, fruit juices, etc.) lower absorption of amphetamines. Urinary acidifying agents (ammonium chloride, sodium acid phosphate, etc.) increase the concentration of the ionized species of the amphetamine molecule, thereby increasing urinary excretion. Both groups of agents lower blood levels and efficacy of amphetamines.

Adrenergic Blockers – Adrenergic blockers are inhibited by amphetamines.

Alkalinizing Agents – Gastrointestinal alkalinizing agents (sodium bicarbonate, etc.) increase absorption of amphetamines. Urinary alkalinizing agents (acetazolamide, some thiazides) increase the concentration of the non-ionized species of the amphetamine molecule, thereby decreasing urinary excretion. Both groups of agents increase blood levels and therefore potentiate the actions of amphetamines.

Antidepressants, Tricyclic – Amphetamines may enhance the activity of tricyclic or sympathomimetic agents; d-amphetamine with desipramine or protriptyline and possibly other tricyclics cause striking and sustained increases in the concentration of d-amphetamine in the brain; cardiovascular effects can be potentiated.

CYP2D6 Inhibitors – The concomitant use of Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution and CYP2D6 inhibitors may increase the exposure of Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution compared to the use of the drug alone and increase the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome particularly during Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution initiation and after a dosage increase. If serotonin syndrome occurs, discontinue Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution and the CYP2D6 inhibitor [see WARNINGS , OVERDOSAGE ]. Examples of CYP2D6 Inhibitors include paroxetine and fluoxetine (also serotonergic drugs), quinidine, ritonavir.

Serotonergic Drugs – The concomitant use of Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution and serotonergic drugs increases the risk of serotonin syndrome. Initiate with lower doses and monitor patients for signs and symptoms of serotonin syndrome, particularly during Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution initiation or dosage increase. If serotonin syndrome occurs, discontinue Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution and the concomitant serotonergic drug(s) [see WARNINGS and PRECAUTIONS ]. Examples of serotonergic drugs include selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), triptans, tricyclic antidepressants, fentanyl, lithium, tramadol, tryptophan, buspirone, St. John’s Wort.

MAO Inhibitors – MAOI antidepressants, as well as a metabolite of furazolidone, slow amphetamine metabolism. This slowing potentiates amphetamines, increasing their effect on the release of norepinephrine and other monoamines from adrenergic nerve endings; this can cause headaches and other signs of hypertensive crisis. A variety of neurological toxic effects and malignant hyperpyrexia can occur, sometimes with fatal results.

Antihistamines – Amphetamines may counteract the sedative effect of antihistamines.

Antihypertensives – Amphetamines may antagonize the hypotensive effects of antihypertensives.

Chlorpromazine – Chlorpromazine blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamines, and can be used to treat amphetamine poisoning.

Ethosuximide – Amphetamines may delay intestinal absorption of ethosuximide.

Haloperidol – Haloperidol blocks dopamine and norepinephrine reuptake, thus inhibiting the central stimulant effects of amphetamines.

Lithium Carbonate – The stimulatory effects of amphetamines may be inhibited by lithium carbonate.

Meperidine – Amphetamines potentiate the analgesic effect of meperidine.

Methenamine Therapy – Urinary excretion of amphetamines is increased, and efficacy is reduced, by acidifying agents used in methenamine therapy.

Norepinephrine – Amphetamines enhance the adrenergic effect of norepinephrine.

Phenobarbital – Amphetamines may delay intestinal absorption of phenobarbital; co-administration of phenobarbital may produce a synergistic anticonvulsant action.

Phenytoin – Amphetamines may delay intestinal absorption of phenytoin; co-administration of phenytoin may produce a synergistic anticonvulsant action.

Propoxyphene – In cases of propoxyphene overdosage, amphetamine CNS stimulation is potentiated and fatal convulsions can occur.

Veratrum Alkaloids – Amphetamines inhibit the hypotensive effect of veratrum alkaloids.

Drug/Laboratory Test Interactions

Amphetamines can cause a significant elevation in plasma corticosteroid levels. This increase is greatest in the evening.

Amphetamines may interfere with urinary steroid determinations.

​Carcinogenesis/Mutagenesis:

Mutagenicity studies and long-term studies in animals to determine the carcinogenic potential of Delcobese sulfate have not been performed.

Pregnancy:

Teratogenic Effects:

Pregnancy Category C. Delcobese sulfate has been shown to have embryotoxic and teratogenic effects when administered to A/Jax mice and C57BL mice in doses approximately 41 times the maximum human dose. Embryotoxic effects were not seen in New Zealand white rabbits given the drug in doses 7 times the human dose nor in rats given 12.5 times the maximum human dose. While there are no adequate and well-controlled studies in pregnant women, there has been one report of severe congenital bony deformity, tracheoesophageal fistula, and anal atresia (VATER association) in a baby born to a woman who took Delcobese (Dextroamphetamine Sulfate) sulfate with lovastatin during the first trimester of pregnancy. Delcobese (Dextroamphetamine Sulfate) sulfate should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Nonteratogenic Effects:

Infants born to mothers dependent on amphetamines have an increased risk of premature delivery and low birth weight. Also, these infants may experience symptoms of withdrawal as demonstrated by dysphoria, including agitation, and significant lassitude.

Nursing Mothers:

Amphetamines are excreted in human milk. Mothers taking amphetamines should be advised to refrain from nursing.

Pediatric Use:

Long-term effects of amphetamines in pediatric patients have not been well established.

Amphetamines are not recommended for use in pediatric patients under 3 years of age with Attention Deficit Disorder with Hyperactivity described under INDICATIONS AND USAGE .

Clinical experience suggests that in psychotic children, administration of amphetamines may exacerbate symptoms of behavior disturbance and thought disorder.

Amphetamines have been reported to exacerbate motor and phonic tics and Tourette’s syndrome. Therefore, clinical evaluation for tics and Tourette’s syndrome in children and their families should precede use of stimulant medications.

Data are inadequate to determine whether chronic administration of amphetamines may be associated with growth inhibition; therefore, growth should be monitored during treatment.

Drug treatment is not indicated in all cases of Attention Deficit Disorder with Hyperactivity and should be considered only in light of the complete history and evaluation of the child. The decision to prescribe amphetamines should depend on the physician’s assessment of the chronicity and severity of the child’s symptoms and their appropriateness for his or her age. Prescription should not depend solely on the presence of one or more of the behavioral characteristics.

When these symptoms are associated with acute stress reactions, treatment with amphetamines is usually not indicated.

ADVERSE REACTIONS

To report SUSPECTED ADVERSE REACTIONS, contact Tris Pharma, Inc. at 1-732-940-0358 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Cardiovascular: Palpitations, tachycardia, elevation of blood pressure. There have been isolated reports of cardiomyopathy associated with chronic amphetamine use.

Central Nervous System: Psychotic episodes at recommended doses (rare), overstimulation, restlessness, dizziness, insomnia, euphoria, dyskinesia, dysphoria, tremor, headache, exacerbation of motor and phonic tics and Tourette’s syndrome.

Gastrointestinal: Dryness of the mouth, unpleasant taste, diarrhea, constipation, other gastrointestinal disturbances. Anorexia and weight loss may occur as undesirable effects.

Allergic: Urticaria.

Endocrine: Impotence, changes in libido.

Musculoskeletal: Rhabdomyolysis.

DRUG ABUSE AND DEPENDENCE

Delcobese (Dextroamphetamine Sulfate) sulfate is a Schedule II controlled substance.

Amphetamines have been extensively abused. Tolerance, extreme psychological dependence and severe social disability have occurred. There are reports of patients who have increased the dosage to many times that recommended. Abrupt cessation following prolonged high dosage administration results in extreme fatigue and mental depression; changes are also noted on the sleep EEG.

Manifestations of chronic intoxication with amphetamines include severe dermatoses, marked insomnia, irritability, hyperactivity and personality changes. The most severe manifestation of chronic intoxication is psychosis, often clinically indistinguishable from schizophrenia. This is rare with oral amphetamines.

OVERDOSAGE

Individual patient response to amphetamines varies widely. While toxic symptoms occasionally occur as an idiosyncrasy at doses as low as 2 mg, they are rare with doses of less than 15 mg; 30 mg can produce severe reactions, yet doses of 400 to 500 mg are not necessarily fatal.

In rats, the oral LD₅₀ of Delcobese (Dextroamphetamine Sulfate) sulfate is 96.8 mg/kg.

Manifestations of acute overdosage with amphetamines include restlessness, tremor, hyperreflexia, rhabdomyolysis, rapid respiration, hyperpyrexia, confusion, assaultiveness, hallucinations, panic states.

Fatigue and depression usually follow the central stimulation.

Cardiovascular effects include arrhythmias, hypertension or hypotension and circulatory collapse.

Gastrointestinal symptoms include nausea, vomiting, diarrhea and abdominal cramps.

Fatal poisoning is usually proceeded by convulsions and coma.

TREATMENT

Consult with a Certified Poison Control Center for up-to-date guidance and advice. Management of acute amphetamine intoxication is largely symptomatic and includes gastric lavage, administration of activated charcoal, administration of a cathartic, and sedation. Experience with hemodialysis or peritoneal dialysis is inadequate to permit recommendation in this regard. Acidification of the urine increases amphetamine excretion, but is believed to increase risk of acute renal failure if myoglobinuria is present. If acute, severe hypertension complicates amphetamine overdosage, administration of intravenous phentolamine (Bedford Laboratories) has been suggested. However, a gradual drop in blood pressure will usually result when sufficient sedation has been achieved.

Chlorpromazine antagonizes the central stimulant effects of amphetamines and can be used to treat amphetamine intoxication.

DOSAGE AND ADMINISTRATION

Amphetamines should be administered at the lowest effective dosage and dosage should be individually adjusted. Late evening doses should be avoided because of the resulting insomnia.

Narcolepsy: Usual dose is 5 mg to 60 mg per day in divided doses, depending on the individual patient response.

Narcolepsy seldom occurs in children under 12 years of age; however, when it does, Delcobese (Dextroamphetamine Sulfate) sulfate oral solution may be used. The suggested initial dose for patients aged 6 to 12 is 5 mg daily; daily dose may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. In patients 12 years of age and older, start with 10 mg daily; daily dosage may be raised in increments of 10 mg at weekly intervals until optimal response is obtained. If bothersome adverse reactions appear (e.g., insomnia or anorexia), dosage should be reduced. Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

Attention Deficit Disorder with Hyperactivity: Not recommended for pediatric patients under 3 years of age.

In pediatric patients from 3 to 5 years of age, start with 2.5 mg daily; daily dosage may be raised in increments of 2.5 mg at weekly intervals until optimal response is obtained.

In pediatric patients 6 years of age and older, start with 5 mg once or twice daily; daily dosage may be raised in increments of 5 mg at weekly intervals until optimal response is obtained. Only in rare cases will it be necessary to exceed a total of 40 mg per day.

Give first dose on awakening; additional doses (1 or 2) at intervals of 4 to 6 hours.

Where possible, drug administration should be interrupted occasionally to determine if there is a recurrence of behavioral symptoms sufficient to require continued therapy.

HOW SUPPLIED

Delcobese (Dextroamphetamine Sulfate) sulfate oral solution 5 mg/5 mL is a colorless, bubble gum flavored oral solution. It is available in 16 fluid ounces (473 mL) bottles, NDC 27808-085-01.

Store at 20° to 25°C (68° to 77°F); excursions permitted from 15° to 30°C (59° to 86°F). Dispense in a tight, light resistant container.

Manufactured by

Tris Pharma, Inc.

Monmouth Junction, NJ 08852

www.trispharma.com

LB8255

Rev 03

October 2016

MEDICATION GUIDE

Delcobese (Dextroamphetamine Sulfate) SULFATE ORAL SOLUTION CII, 5 mg/5 mL

(DEX-troe-am-FET-a-meen SUL-fate)

Rx Only

Please read the Medication Guide that comes with Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution before you or your child starts taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your doctor about your or your child’s treatment with Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution.

What is Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution?

Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution is a central nervous system stimulant prescription medicine. It is used for the treatment of Attention-Deficit Hyperactivity Disorder (ADHD). Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution may help increase attention and decrease impulsiveness and hyperactivity in patients with ADHD.

Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution should be used as a part of a total treatment program for ADHD that may include counseling or other therapies.

Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution is also used in the treatment of a sleep disorder called narcolepsy.

Who should not take Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution?

Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution should not be taken if you or your

Child:

- have heart disease or hardening of the arteries

- have moderate to severe high blood pressure

- have hyperthyroidism

- have an eye problem called glaucoma

- are very anxious, tense, or agitated

- have a history of drug abuse

- are taking or have taken within the past 14 days an antidepression medicine called a monoamine oxidase inhibitor or MAOI

- is sensitive to, allergic to, or had a reaction to other stimulant medicines

Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution is not recommended for use in children less than 3 years old.

Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution may not be right for you or your child.

Before starting Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution tell your or your child’s doctor about all health conditions (or a family history of) including:

- heart problems, heart defects, high blood pressure

- mental problems including psychosis, mania, bipolar illness, or depression

- tics or Tourette’s syndrome

- thyroid problems

- seizures or have had an abnormal brain wave test (EEG)

- circulation problems in fingers and toes

Tell your doctor if you or your child is pregnant, planning to become pregnant, or breastfeeding.

Can Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution be taken with other medicines?

Tell your doctor about all of the medicines that you or your child take including prescription and nonprescription medicines, vitamins, and herbal supplements.

Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution and some medicines may interact with each other and cause serious side effects. Sometimes the doses of other medicines will need to be adjusted while taking Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution.

Your doctor will decide whether Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution can be taken with other medicines.

Especially tell your doctor if you or your child take:

- antidepression medicines including MAOIs

- antacids

- blood pressure medicines

- seizure medicines

Know the medicines that you or your child take. Keep a list of your medicines with you to show your doctor and pharmacist.

Do not start any new medicine while taking Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution without talking to your doctor first.

How should Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution be taken?

- Take Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution exactly as prescribed. Your doctor may adjust the dose until it is right for you or your child.

- Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution is usually taken two to three times a day. The first dose is usually taken in the morning. One or two more doses may be taken during the day, 4 to 6 hours apart.

- From time to time, your doctor may stop Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution treatment for a while to check ADHD symptoms.

- Your doctor may do regular checks of the blood, heart, and blood pressure while taking Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution. Children should have their height and weight checked often while taking Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution. Treatment with Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution treatment may be stopped if a problem is found during these check-ups.

- If you or your child take too much Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution or overdoses, call your doctor or poison control center right away, or get emergency treatment.

What are possible side effects of Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution?

See “What is the most important information I should know about Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution?” for information on reported heart and mental problems.

Other serious side effects include:

- slowing of growth (height and weight) in children

- seizures, mainly in patients with a history of seizures

- eyesight changes or blurred vision

- Serotonin syndrome. A potentially life-threatening problem called serotonin syndrome can happen when medicines such as Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution are taken with certain other medicines. Symptoms of serotonin syndrome may include:

- agitation, hallucinations, coma or other changes in mental status

- problems controlling your movements or muscle twitching

- fast heartbeat

- high or low blood pressure

- sweating or fever

- nausea or vomiting

- diarrhea

- muscle stiffness or tightness

Common side effects include:

- fast heart beat

- stomach upset

- headache

- tremors

- dry mouth

- dizziness

- trouble sleeping

- decreased appetite

- weight loss

Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution may affect you or your child’s ability to drive or do other dangerous activities.

Talk to your doctor if you or your child have side effects that are bothersome or do not go away.

This is not a complete list of possible side effects. Ask your doctor or pharmacist for more information.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution?

- Store Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution in a safe place at controlled room temperature, 68° to 77°F (20° to 25°C). Protect from light.

- Keep Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution and all medicines out of the reach of children.

General information about Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution for a condition for which it was not prescribed. Do not give Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution to other people, even if they have the same condition. It may harm them and it is against the law.

This Medication Guide summarizes the most important information about Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution that was written for healthcare professionals.

For more information about Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution, please contact Tris Pharma, Inc. at 1-732-940-0358 or go to www.trispharma.com.

What are the ingredients in Delcobese (Dextroamphetamine Sulfate) Sulfate Oral Solution?

Active Ingredient: Delcobese (Dextroamphetamine Sulfate) sulfate

Inactive Ingredients: anhydrous citric acid, benzoic acid, bubble gum flavor, purified water, sodium citrate anhydrous, sodium saccharin, and sorbitol solution.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by

Tris Pharma, Inc.

LB8255

Rev 03

October 2016