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Horizant

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Horizant uses


1 INDICATIONS AND USAGE

Horizant is indicated for:

1.1 Treatment of Restless Legs Syndrome

Horizant® (gabapentin enacarbil) Extended-Release Tablets are indicated for the treatment of moderate-to-severe primary Restless Legs Syndrome (RLS) in adults.

Horizant is not recommended for patients who are required to sleep during the daytime and remain awake at night.

1.2 Management of Postherpetic Neuralgia

Horizant (gabapentin enacarbil) Extended-Release Tablets are indicated for the management of postherpetic neuralgia (PHN) in adults.

2 DOSAGE AND ADMINISTRATION

Tablets should be swallowed whole and should not be cut, crushed, or chewed.

Tablets should be taken with food.

Horizant is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles .

Instruct patients to swallow tablets whole and not to cut, crush, or chew tablets. Take with food. (2)

RLS: 600 mg once daily taken at about 5 PM. (2.1)


PHN: The starting dose is 600 mg in the morning for 3 days, then increase to 600 mg twice daily beginning on day 4. (2.2)


Patients with renal impairment: Doses of Horizant must be adjusted in accordance with renal function. (2.3)

2.1 Restless Legs Syndrome

The recommended dosage for Horizant is 600 mg once daily at about 5 PM. A daily dose of 1,200 mg provided no additional benefit compared with the 600-mg dose, but caused an increase in adverse reactions .

If the dose is not taken at the recommended time, the next dose should be taken the following day as prescribed.

2.2 Postherpetic Neuralgia

The recommended dosage of Horizant is 600 mg twice daily. Horizant should be initiated at a dose of 600 mg in the morning for 3 days of therapy, then increased to 600 mg twice daily on day four. In the 12-week principal efficacy study, additional benefit of using doses greater than 1,200 mg a day was not demonstrated, and these higher doses resulted in an increase in adverse reactions .

If the dose is not taken at the recommended time, skip this dose, and the next dose should be taken at the time of the next scheduled dose.

2.3 Renal Impairment

Dosing of Horizant is adjusted in accordance with renal function, as represented by creatinine clearance . Target dose regimens are listed in Table 1 and Table 2.

Creatinine Clearance (mL/min) Target Dose Regimen
≥60 600 mg per day
30 – 59 Start at 300 mg per day and increase to 600 mg as needed
15 – 29 300 mg per day
<15 300 mg every other day
<15 on hemodialysis Not recommended
Creatinine Clearance

(mL/min)

 Titration Maintenance Tapering
≥60 600 mg in AM for 3 days 600 mg twice daily 600 mg in AM for 1 week
30 – 59 300 mg in AM for 3 days 300 mg twice daily. Increase to 600 mg twice daily as neededBased on tolerability and efficacy Reduce current maintenance dose to once daily in AM for 1 week
15 – 29 300 mg in AM on Day 1 and Day 3 300 mg in AM. Increase to 300 mg twice daily if needed If taking 300 mg twice daily, reduce to 300 mg once daily in AM for 1 week. If taking 300 mg once daily, no taper needed.
<15 None 300 mg every other day in AM. Increase to 300 mg once daily in AM if needed None
<15 on hemodialysis None 300 mg following every dialysis. Increase to 600 mg following every dialysis if needed None

In patients with stable renal function, CrCl can be estimated using the equation of Cockcroft and Gault:


where age is in years, weight is in kilograms, and SCr is serum creatinine in mg/dL.

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3 DOSAGE FORMS AND STRENGTHS

Horizant Extended-Release Tablets, 300 mg, are white to off-white, oval-shaped tablets debossed with "GS TF7" and 600 mg, are white to off-white, oval-shaped tablets debossed with "GS LFG". Both the 300 mg and 600 mg tablets may contain occasional black/grey spots.

Extended-Release Tablets: 300 mg and 600 mg. (3)

4 CONTRAINDICATIONS

None.

None. (4)

5 WARNINGS AND PRECAUTIONS

5.1 Effects on Driving

Horizant may cause significant driving impairment . The duration of driving impairment after starting therapy with Horizant is unknown. Patients taking Horizant should not drive until they have gained sufficient experience to assess whether Horizant impairs their ability to drive. However, prescribers and patients should be aware that patients' ability to assess their own driving competence, as well as their ability to assess the degree of somnolence caused by Horizant, can be imperfect. Whether the impairment is related to somnolence or other effects of Horizant is unknown.

5.2 Somnolence/Sedation and Dizziness

Horizant causes somnolence/sedation and dizziness. Patients should be advised not to drive a car or operate other complex machinery until they have gained sufficient experience on Horizant to assess whether Horizant impairs their ability to perform these tasks.

During the controlled trials in patients with RLS, somnolence/sedation was reported in 20% of patients treated with 600 mg of Horizant per day compared with 6% of patients receiving placebo. In those patients treated with Horizant who reported somnolence, the somnolence persisted during treatment in about 30%. In the remaining patients, symptoms resolved within 3 to 4 weeks. Dizziness was reported in 13% of patients receiving 600 mg of Horizant per day compared with 4% of patients receiving placebo. In those patients treated with Horizant who reported dizziness, symptoms persisted during treatment in about 20%. Somnolence/sedation led to withdrawal in 2% of patients receiving 600 mg of Horizant per day. Dizziness led to withdrawal in 1% of patients receiving 600 mg of Horizant per day. The incidence of these adverse reactions was greater in the patients receiving 1,200 mg per day.

During the 12-week, controlled study in patients with PHN, somnolence was reported in 10% of patients treated with 1,200 mg of Horizant per day compared with 8% of patients receiving placebo. Fatigue/asthenia was reported in 6% of patients treated with 1,200 mg of Horizant per day compared with 1% of patients receiving placebo. In those patients treated with 1,200 mg of Horizant per day who reported somnolence (10%), the somnolence persisted during treatment in about 27%. In the remaining patients, symptoms resolved within 4 to 5 weeks. Dizziness was reported in 17% of patients receiving 1,200 mg of Horizant per day compared with 15% of patients receiving placebo. In those patients treated with 1,200 mg of Horizant per day who reported dizziness, symptoms persisted during treatment in about 6%. Somnolence led to withdrawal in <1% of patients receiving 1,200 mg of Horizant per day compared with 2% of patients receiving placebo. Dizziness led to withdrawal in 2% of patients receiving 1,200 mg of Horizant per day compared with 3% of patients receiving placebo.

5.3 Lack of Interchangeability With Gabapentin

Horizant is not interchangeable with other gabapentin products because of differing pharmacokinetic profiles. The same dose of Horizant results in different plasma concentrations of gabapentin relative to other gabapentin products.

The safety and effectiveness of Horizant in patients with epilepsy have not been studied.

5.4 Suicidal Behavior and Ideation

Horizant is a prodrug of gabapentin, an antiepileptic drug (AED). AEDs increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Because Horizant is a prodrug of gabapentin, Horizant also increases this risk. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.

Pooled analyses of 199 placebo-controlled clinical trials (monotherapy and adjunctive therapy) of 11 different AEDs showed that patients randomized to 1 of the AEDs had approximately twice the risk [adjusted relative risk 1.8, 95% confidence interval (CI): 1.2, 2.7] of suicidal thinking or behavior compared with patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared with 0.24% among 16,029 placebo-treated patients, representing an increase of approximately 1 case of suicidal thinking or behavior for every 530 patients treated. There were 4 suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.

The increased risk of suicidal thoughts or behavior with AEDs was observed as early as 1 week after starting drug treatment with AEDs and persisted for the duration of treatment assessed.

Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.

The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5 to 100 years) in the clinical trials analyzed. Table 3 shows absolute and relative risk by indication for all evaluated AEDs.

Indication Placebo Patients With Events Per 1,000 Patients Drug Patients With Events Per 1,000 Patients Relative Risk: Incidence of Events in Drug Patients/Incidence in Placebo Patients Risk Difference: Additional Drug Patients With Events Per 1,000 Patients
Epilepsy 1.0 3.4 3.5 2.4
Psychiatric 5.7 8.5 1.5 2.9
Other 1.0 1.8 1.9 0.9
Total 2.4 4.3 1.8 1.9

The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.

Anyone considering prescribing Horizant must balance the risk of suicidal thoughts or behavior with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.

Patients, their caregivers, and families should be informed that Horizant increases the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.

Behaviors of concern should be reported immediately to healthcare providers.

5.5 Drug Reaction With Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan hypersensitivity, has been reported in patients taking antiepileptic drugs, including gabapentin. Horizant is a prodrug of gabapentin. Some of these events have been fatal or life-threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis, hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection. Eosinophilia is often present. Because this disorder is variable in its expression, other organ systems not noted here may be involved.

It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Horizant should be discontinued if an alternative etiology for the signs or symptoms cannot be established.

5.6 Discontinuation of Horizant

When discontinuing Horizant, patients with RLS receiving 600 mg or less once daily can discontinue the drug without tapering. If the recommended dose is exceeded, the dose should be reduced to 600 mg daily for 1 week prior to discontinuation to minimize the potential of withdrawal seizure.

In patients with PHN receiving Horizant twice daily, the dose should be reduced to once daily for 1 week prior to discontinuation to minimize the potential of withdrawal seizure, see Table 2 .

5.7 Tumorigenic Potential

In an oral carcinogenicity study, Horizant increased the incidence of pancreatic acinar cell adenoma and carcinoma in male and female rats . The clinical significance of this finding is unknown.

In clinical studies of gabapentin as adjunctive therapy in epilepsy comprising 2,085 patient-years of exposure in patients >12 years of age, new tumors were reported in 10 patients (2 breast, 3 brain, 2 lung, 1 adrenal, 1 non-Hodgkin's lymphoma, 1 endometrial carcinoma in situ), and preexisting tumors worsened in 11 patients (9 brain, 1 breast, 1 prostate) during or up to 2 years following discontinuation of gabapentin. Without knowledge of the background incidence and recurrence in a similar population not treated with gabapentin, it is impossible to know whether the incidence reported in this cohort is or is not affected by treatment.

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6 ADVERSE REACTIONS

The following adverse reactions are described in more detail in the Warnings and Precautions section of the label:


To report SUSPECTED ADVERSE REACTIONS, contact Arbor Pharmaceuticals, LLC at 1-866-516-4950 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 with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

In all controlled and uncontrolled trials across various patient populations, more than 2,300 patients have received Horizant orally in daily doses ranging from 600 to 3,600 mg.

Restless Legs Syndrome: The exposure to Horizant in 1,201 patients with RLS included 613 exposed for at least 6 months and 371 exposed for at least 1 year. Horizant in the treatment of RLS was studied primarily in placebo-controlled trials (n = 642), and in long- term follow-up studies. The population with RLS ranged from 18 to 82 years of age, with 60% being female and 95% being Caucasian.

The safety of Horizant in doses ranging from 600 to 2,400 mg has been evaluated in 515 patients with RLS in 3 double-blind, placebo-controlled, 12-week clinical trials. The 600-mg dose was studied in 2 of the 3 studies. Eleven out of 163 (7%) patients treated with 600 mg of Horizant discontinued treatment due to adverse reactions compared with 10 of the 245 (4%) patients who received placebo.

The most commonly observed adverse reactions (≥5% and at least 2 times the rate of placebo) in these trials for the 600-mg dose of Horizant were somnolence/sedation and dizziness. Table 4 lists treatment-emergent adverse reactions that occurred in ≥2% of patients with RLS treated with Horizant and numerically greater than placebo.

Body System/Adverse Reaction PlaceboPlacebo was a treatment arm in each of the 3 double-blind, placebo-controlled, 12-week clinical trials.

(N = 245)

%

 Horizant

600 mg/dayThe 600-mg dose of Horizant was a treatment arm in 2 of the 3 double-blind, placebo-controlled, 12-week clinical trials.

(N = 163)

%

 Horizant

1,200 mg/dayThe 1,200-mg dose of Horizant was a treatment arm in each of the 3 double-blind, placebo-controlled, 12-week clinical trials.

(N = 269)

%
Nervous system disorders
Somnolence/sedation 6 20 27
Dizziness 4 13 22
Headache 11 12 15
Gastrointestinal disorders
Nausea 5 6 7
Dry mouth 2 3 4
Flatulence <1 3 2
General disorders and administration site conditions
Fatigue 4 6 7
Irritability 1 4 4
Feeling drunk 0 1 3
Feeling abnormal <1 <1 3
Peripheral edema 1 <1 3
Metabolism and nutritional disorders
Weight increased 2 2 3
Increased appetite <1 2 2
Ear and labyrinth disorders
Vertigo 0 1 3
Psychiatric disorders
Depression <1 <1 3
Libido decreased <1 <1 2

Adverse reactions reported in these three 12-week studies in <2% of patients treated with 600 mg of Horizant and numerically greater than placebo were balance disorder, blurred vision, disorientation, feeling drunk, lethargy, and vertigo.

The following adverse reactions were dose-related: somnolence/sedation, dizziness, feeling drunk, libido decreased, depression, headache, peripheral edema, and vertigo.

Postherpetic Neuralgia: The exposure to Horizant in 417 patients with PHN included 207 patients exposed for at least 3 months. Overall, the mean age of patients in the PHN studies ranged from 61 to 64 years of age across dose groups; the majority of patients were male (45% to 61%) and Caucasian (80% to 98%).

The safety of Horizant in doses ranging from 1,200 to 3,600 mg has been evaluated in 417 patients with PHN in 3 clinical studies. The principal efficacy study evaluating the efficacy and safety of Horizant in the management of PHN was a 12-week, double-blind, multicenter study comparing 1,200 mg/day, 2,400 mg/day and 3,600 mg/day to placebo. Six out of 107 (6%) patients treated with 1,200 mg of Horizant discontinued treatment due to adverse events compared with 12 of the 95 (13%) patients who received placebo.

The most commonly observed adverse reactions (≥10% and greater than placebo) in this trial for the 1,200 mg dose of Horizant were dizziness, somnolence, and headache. Table 5 lists treatment-emergent adverse reactions that occurred in ≥2% of patients with PHN treated with Horizant 1,200 mg/day and numerically greater than placebo.

Body System/Adverse Reaction Placebo

(N = 95)

%

 Horizant

1,200 mg/day

(N = 107)

%

 Horizant

2,400 mg/day

(N = 82)

%

 Horizant

3,600 mg/day

(N = 87)

%
Nervous System
Dizziness 15 17 26 30
Somnolence 8 10 11 14
Headache 9 10 10 7
Gastrointestinal disorders
Nausea 5 8 4 9
General disorders and administration site conditions
Fatigue/Asthenia 1 6 4 10
Peripheral edema 0 6 7 6
Psychiatric disorders
Insomnia 2 3 5 7
Metabolism and nutritional disorders
Weight increased 1 3 5 5
Eye disorders
Blurred vision 0 2 5 2

The following adverse reactions were also reported as ≥2% at 2,400 mg/day and/or 3,600 mg/day and appeared to be dose-related but were <2% at 1,200 mg/day: balance disorder, confusional state, depression, dry mouth, flatulence, increased appetite, irritability, and vertigo. Dizziness, somnolence, fatigue, and insomnia appeared to show a dose relationship.

6.2 Adverse Events Associated With Gabapentin

The following adverse events have been reported in patients receiving gabapentin, either in clinical trials or postmarketing: breast enlargement, gynecomastia, and elevated creatine kinase.

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7 DRUG INTERACTIONS

Horizant is released faster from Horizant Extended-Release tablets in the presence of alcohol. Consumption of alcohol is not recommended when taking Horizant .

Morphine: Horizant taken in conjunction with morphine causes increased somnolence/sedation, dizziness, and nausea when compared with either drug alone.

8 USE IN SPECIFIC POPULATIONS

Pregnancy: Based on animal data, may cause fetal harm.

8.1 Pregnancy

Pregnancy Category C. There are no adequate and well-controlled studies with Horizant in pregnant women. In nonclinical studies in rats and rabbits, administration of Horizant was developmentally toxic when administered to pregnant animals at doses and gabapentin exposures greater than those used clinically. Horizant should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

When pregnant rats were administered Horizant (oral doses of 200, 1,000, or 5,000 mg/kg/day) throughout the period of organogenesis, embryo-fetal mortality was increased at the 2 highest doses and fetal body weights were decreased at the high dose. The no-effect dose for embryo-fetal developmental toxicity in rats (200 mg/kg/day) represents approximately 2 times the gabapentin exposure associated with the maximum recommended human dose (MRHD) of 1,200 mg/day Horizant on an area under the curve (AUC) basis.

When pregnant rabbits were administered Horizant (oral doses of 200, 500, or 2,500 mg/kg/day) throughout the period of organogenesis, embryo-fetal mortality was increased and fetal body weights were decreased at the high dose. The no-effect dose for embryo-fetal developmental toxicity in rabbits (500 mg/kg/day) represents approximately 9 times the gabapentin exposure associated with the MRHD of 1,200 mg/day Horizant on an AUC basis.

When female rats were administered Horizant (oral doses of 200, 1,000, or 5,000 mg/kg/day) throughout the pregnancy and lactation periods, offspring growth and survival were decreased at the two highest doses. The no-effect dose for pre- and post-natal developmental toxicity in rats is approximately 2 times the MRHD on an AUC basis.

In reproductive and developmental studies of gabapentin, developmental toxicity was observed at all doses tested. Increased incidences of hydroureter and/or hydronephrosis were observed in rat offspring following treatment of pregnant animals in studies of fertility and general reproductive performance, embryo-fetal development, and peri- and post-natal development. Overall, a no-effect dose was not established. In mice, treatment of pregnant animals with gabapentin during the period of organogenesis resulted in delayed fetal skeletal ossification at all but the lowest dose tested. When pregnant rabbits were treated with gabapentin during the period of organogenesis, an increase in embryo-fetal mortality was observed at all doses of gabapentin tested.

In a published study, gabapentin (400 mg/kg/day) was administered by intraperitoneal injection to neonatal mice during the first postnatal week, a period of synaptogenesis in rodents (corresponding to the last trimester of pregnancy in humans). Gabapentin caused a marked decrease in neuronal synapse formation in brains of intact mice and abnormal neuronal synapse formation in a mouse model of synaptic repair. Gabapentin has been shown in vitro to interfere with activity of the α2δ subunit of voltage-activated calcium channels, a receptor involved in neuronal synaptogenesis. The clinical significance of these findings is unknown.

8.2 Labor and Delivery

The effect of Horizant on labor and delivery is unknown.

8.3 Nursing Mothers

It is not known whether gabapentin derived from Horizant is secreted in human milk; however, gabapentin is secreted into human milk following oral administration of gabapentin products. Because of the potential for adverse reactions in nursing infants from Horizant, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

8.4 Pediatric Use

Safety and effectiveness of Horizant in pediatric patients have not been studied.

8.5 Geriatric Use

Of the 515 patients treated with Horizant in the 3 double-blind, placebo-controlled, 12-week clinical trials for RLS, 11% were 65 to 74 years of age and 1% were 75 years of age and older. Clinical trials of Horizant for the treatment of RLS did not include a sufficient number of patients 65 years and older to determine whether they respond differently from younger individuals.

In the 12-week, double-blind, placebo-controlled study of Horizant for the management of PHN, 37% were 65 to 74 years of age and 13% were 75 years of age and older. The overall incidence of adverse events was comparable between the patients aged ≥18 to <65 years and ≥65 to <74 years. No overall differences in the safety and effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Gabapentin is known to be almost exclusively excreted by the kidney, and the risk of adverse reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, the frequency of dosing may need to be adjusted based on calculated creatinine clearance in these patients .

8.6 Renal Impairment

The dose of Horizant should be adjusted in patients with renal impairment .

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9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

Horizant, a prodrug of gabapentin, is not a scheduled drug.

9.2 Abuse

Gabapentin does not exhibit affinity for benzodiazepine, opiate, or cannabinoid 1 receptor sites. A small number of postmarketing cases report gabapentin misuse and abuse. These individuals were taking higher than recommended doses of gabapentin for unapproved uses. Most of the individuals described in these reports had a history of poly-substance abuse or used gabapentin to relieve symptoms of withdrawal from other substances.

When prescribing products that deliver gabapentin, carefully evaluate patients for a history of drug abuse and observe them for signs and symptoms of gabapentin misuse or abuse (e.g., development of tolerance, self dose escalation, and drug-seeking behavior).

9.3 Dependence

There are rare postmarketing reports of individuals experiencing withdrawal symptoms shortly after discontinuing higher than recommended doses of gabapentin used to treat illnesses for which the drug is not approved. Such symptoms included agitation, disorientation, and confusion after suddenly discontinuing gabapentin that resolved after restarting gabapentin. Most of these individuals had a history of poly-substance abuse or used gabapentin to relieve symptoms of withdrawal from other substances. The dependence and abuse potential of gabapentin has not been evaluated in human studies.

10 OVERDOSAGE

10.1 Human Overdose Experience

There have been no reports describing individuals who have taken an overdose of Horizant. The highest single dose of Horizant administered to date is 6,000 mg in healthy subjects. At this supratherapeutic dose there were no serious adverse events. The incidence of central nervous system adverse reactions, particularly dizziness and somnolence/sedation, is increased with doses greater than 600 mg daily.

10.2 Overdosage Management

In the event of an overdose, the patient should be treated supportively with appropriate monitoring as necessary. Gabapentin derived from Horizant can be removed from plasma by hemodialysis. The mean percentage of gabapentin recovered following hemodialysis in patients with end-stage renal disease was 29% (expressed as a proportion of the gabapentin released from Horizant).

Further management should be as clinically indicated or as recommended by a poison control center.

11 DESCRIPTION

Horizant (gabapentin enacarbil) is a prodrug of gabapentin. Horizant is described as (1-{[({(1RS)-1-[(2-Methylpropanoyl)oxy]ethoxy}carbonyl)amino]methyl} cyclohexyl) acetic acid. It has a molecular formula of C16H27NO6 and a molecular weight of 329.39. It is a racemate and has the following structural formula:

Horizant is a white to off-white crystalline solid with a melting onset of approximately 64°C and a solubility of 0.5 mg/mL in water and 10.2 mg/mL in phosphate buffer (pH 6.3).

Horizant is administered orally. Each Horizant Extended-Release Tablet contains 300 mg or 600 mg of Horizant and the following inactive ingredients: colloidal silicon dioxide, dibasic calcium phosphate dihydrate, glyceryl behenate, magnesium stearate, sodium lauryl sulfate, and talc.

Chemical Structure

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Horizant is a prodrug of gabapentin and, accordingly, its therapeutic effects in RLS and PHN are attributable to gabapentin.

The precise mechanism by which gabapentin is efficacious in RLS and PHN is unknown.

The mechanism of action by which gabapentin is efficacious in PHN is unknown but in animal models of analgesia, gabapentin prevents allodynia and hyperalgesia (exaggerated response to painful stimuli). Gabapentin prevents pain-related responses in several models of neuropathic pain in rats and mice (e.g., spinal nerve ligation models, spinal cord injury model, acute herpes zoster infection model). Gabapentin also decreases pain-related responses after peripheral inflammation (carrageenan footpad test, late phase of formalin test), but does not alter immediate pain-related behaviors (rat tail flick test, formalin footpad acute phase). The relevance of these models to human pain is not known.

Gabapentin is structurally related to the neurotransmitter gamma-aminobutyric acid (GABA) but has no effect on GABA binding, uptake, or degradation. Horizant and gabapentin have been tested in radioligand binding assays, and neither exhibited affinity for a number of other common receptor, ion channel, or transporter proteins.

In vitro studies have shown that gabapentin binds with high affinity to the α2δ subunit of voltage-activated calcium channels; however, the relationship of this binding to the therapeutic effects of Horizant in RLS and PHN is unknown.

12.3 Pharmacokinetics

Horizant is an extended-release formulation of Horizant, a prodrug of gabapentin. Horizant provides approximately dose-proportional and extended exposure to gabapentin over the range 300 to 6,000 mg. Horizant and gabapentin are not interchangeable because the same daily dose of each results in different plasma concentrations of gabapentin.

For subjects with PHN taking Horizant 600 mg twice daily, the estimated steady state mean Cmax was 5.35 μg/mL, mean AUC24 was approximately 109 μg*hr/mL, mean Cmin was 3.63 μg/mL, and mean peak trough ratio was 1.5.

Absorption: The pathway for absorption of Horizant is believed to include active transport via a proton-linked monocarboxylate transporter, MCT-1. This transporter is expressed at high levels in the intestinal tract and is not saturated by administration of high doses of Horizant. Mean bioavailability of gabapentin (based on urinary recovery of gabapentin) for Horizant in the fed state is about 75%. Bioavailability under fasting conditions has been estimated by gabapentin urinary recovery to be 42% to 65%. In a food effect study, the exposure of gabapentin increased by 24%, 34%, and 44% with low, moderate, and high fat meals, respectively. The Tmax of gabapentin after administration of 600 mg of Horizant was 5.0 hours in fasted subjects and 7.3 hours in fed subjects. Steady state is reached in 2 days with daily administration.

Distribution: Plasma protein binding of gabapentin has been reported to be <3%. The apparent volume of distribution of gabapentin in subjects receiving Horizant is 76 L.

Metabolism: After oral administration, Horizant undergoes extensive first-pass hydrolysis by non-specific carboxylesterases primarily in enterocytes and to a lesser extent in the liver, to form gabapentin, carbon dioxide, acetaldehyde, and isobutyric acid. Levels of Horizant in blood are low and transient (≤2% of corresponding gabapentin plasma levels). Released gabapentin is not appreciably metabolized in humans. Neither Horizant nor gabapentin are substrates, inhibitors, or inducers of the major cytochrome P450 enzymes (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4). Horizant is neither a substrate nor an inhibitor of P-glycoprotein in vitro.

Elimination: Following hydrolysis of Horizant, the released gabapentin is excreted unchanged by the kidney. Gabapentin renal excretion is believed to involve a component of active secretion via an organic cation transporter (OCT2) present in the kidney. In a human pharmacokinetic study with immediate release 14C Horizant, mean recovery of total radioactivity in urine was 94%, with 5% of the radioactive dose recovered in feces.

Apparent oral clearance (CL/F) of gabapentin from plasma after dosing of Horizant with food ranged from 6.0 to 9.3 L/hr. Following oral dosing of Horizant, plasma clearance of gabapentin is approximately proportional to creatinine clearance. Renal clearance (CLr) of gabapentin ranged from 5 to 7 L/hr, regardless of food intake or food type. The elimination half-life (t½) of gabapentin ranges from 5.1 to 6.0 hours and is unaltered by dose or following multiple doses of Horizant.

Special Populations:

Race: In the population pharmacokinetic study, the majority (94%) of subjects in the clinical studies was Caucasian, and no single other race was greater than 4%; therefore, the effect of race could not be studied.

Gender: There are no clinically meaningful differences in pharmacokinetics of Horizant between male and female patients.

Geriatric Patients: There are no clinically significant differences in pharmacokinetics of Horizant between geriatric patients (≥65 years of age) and younger patients (18 to <65 years of age). However, the pharmacokinetics in geriatric patients may be affected by an age-related decline in renal function .

Renal Impairment: Gabapentin clearance after dosing with Horizant is approximately proportional to CrCl. Apparent oral clearance (CL/F) decreased in moderate (4.2 L/hr) and severe renal impairment patients (1.7 L/hr) compared with 6.0 to 9.3 L/hr in patients without renal impairment. Similarly, CLr was decreased to 3 and 1 L/hr in moderate and severe renal impairment patients, respectively, compared with 5 to 7 L/hr in non-renal impairment patients. Dosage reduction in patients with renal dysfunction not on dialysis is necessary.

Gabapentin is effectively removed from plasma by hemodialysis. The mean percentage of gabapentin recovered following hemodialysis in patients with end-stage renal disease was 29% (expressed as a proportion of the gabapentin released from Horizant). For patients with PHN on hemodialysis, dosage reduction is required . For patients with RLS on hemodialysis, treatment with Horizant is not recommended .

Drug Interactions: Neither Horizant nor gabapentin are substrates, inhibitors, or inducers of the major cytochrome P450 enzymes. Horizant is neither a substrate nor an inhibitor of P-glycoprotein in vitro.

Pharmacokinetic drug-drug interaction studies were conducted to examine the potential for an interaction of Horizant with cimetidine and naproxen. No significant pharmacokinetic interactions were observed. No clinically relevant pharmacokinetic interactions are expected between Horizant and other substrates of organic cation transporter type 2 (OCT2) and monocarboxylate transporter type 1 (MCT-1).

Ethanol: An in vitro dissolution study was conducted to evaluate the impact of ethanol (5, 10, 20, and 40%), on the extended-release characteristics of Horizant. The in vitro study showed that about 63% of the total Horizant dose was released at 1 hour at the highest alcohol level (40%), and about 43% of total drug was released at 1 hour with 5% alcohol. Ethanol causes a more rapid release of Horizant from the extended-release tablets that may increase the risk for adverse events associated with Horizant. Consumption of alcohol is not recommended when taking Horizant.

Cimetidine: Gabapentin released from Horizant is eliminated by renal clearance via OCT2. Cimetidine is a known substrate for this same elimination pathway. Coadministration of 1,200 mg of Horizant once daily with cimetidine 400 mg 4 times daily showed no effect on cimetidine exposure. There was an increase in AUC of gabapentin (24%) and a decrease in renal clearance of gabapentin (20%); these effects are not expected to be clinically relevant. No clinically relevant pharmacokinetic interactions are expected between Horizant and other substrates of OCT2.

Naproxen: The pathway for absorption of Horizant includes active transport via a proton-linked MCT-1. Coadministration of 1,200 mg of Horizant once daily with naproxen 500 mg twice daily, a known substrate of MCT-1, showed no effect on naproxen exposure or steady-state gabapentin Cmax and AUC. No clinically relevant pharmacokinetic interactions are expected between Horizant and other substrates of MCT-1.

Morphine: Administration of a single 600-mg dose of Horizant 2 hours after a single 60-mg dose of extended-release morphine sulfate in 18 subjects was associated with increased somnolence/sedation, dizziness, and nausea for the combination compared to Horizant or morphine alone as measured by the visual analog scale. No changes in Cmax and AUC of gabapentin, morphine or its active metabolite morphine-6-glucuronide were observed.

12.6 Cardiac Electrophysiology

At a dose of 6,000 mg, Horizant does not prolong QTc to a clinically relevant extent.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis: Oral (gavage) carcinogenicity studies were conducted in mice and rats. In mice, Horizant was tested at doses of 500, 2,000, or 5,000 mg/kg/day for up to 104 weeks. There was no evidence of drug-related carcinogenicity. The highest dose tested is 16 times the MRHD of 1,200 mg/day, on a plasma AUC basis.

In rats, Horizant was tested at doses of 500, 2,000, or 5,000 mg/kg/day for up to 97 weeks in mid-dose males, 90 weeks in high-dose males, and 104 weeks in females. The plasma exposures (AUC) for gabapentin at these doses are approximately 4, 17, and 37 times, respectively, that in humans at the MRHD. Increases in the incidence of pancreatic acinar adenoma and carcinoma were found in mid-dose males and high-dose males and females.

In 2-year dietary carcinogenicity studies of gabapentin, no evidence of drug-related carcinogenicity was observed in mice treated at doses up to 2,000 mg/kg/day. In rats, increases in the incidence of pancreatic acinar cell adenoma and carcinoma were found in male rats receiving the highest dose (2,000 mg/kg), but not at doses of 250 or 1,000 mg/kg/day. At 1,000 mg/kg/day, the plasma AUC for gabapentin is estimated to be approximately 13 times that in humans at the MRHD.

Studies designed to investigate the mechanism of gabapentin-induced pancreatic carcinogenesis in rats indicate that gabapentin stimulates DNA synthesis in rat pancreatic acinar cells in vitro and thus may be acting as a tumor promoter by enhancing mitogenic activity. It is not known whether gabapentin has the ability to increase cell proliferation in other cell types or in other species, including human.

Mutagenesis: Horizant was negative in in vitro bacterial reverse mutation (Ames) and in vivo rat micronucleus assays. In an in vitro human lymphocyte assay, there was an increase in the number of chromosomal aberrations with Horizant. This in vitro response was attributed to acetaldehyde released by hydrolysis of Horizant during the incubation period. Acetaldehyde is known to cause chromosome aberrations in vitro, but is readily metabolized in vivo. The small quantity of acetaldehyde formed from Horizant in vivo is rapidly cleared by normal metabolic activity.

Impairment of Fertility: Oral administration of Horizant (doses of 0, 200, 1,000, or 5,000 mg/kg/day) to male and female rats prior to and throughout mating and continuing in females up to day 7 of gestation resulted in no adverse effects on fertility. The highest dose tested is approximately 39 times the MRHD on an AUC basis.

14 CLINICAL STUDIES

14.1 Restless Legs Syndrome 12-Week Pivotal Studies

The effectiveness of Horizant in the treatment of moderate-to-severe primary RLS was demonstrated in two 12-week clinical studies in adults diagnosed with RLS using the International Restless Legs Syndrome Study Group diagnostic criteria. Key diagnostic criteria for RLS are: an urge to move the legs usually accompanied or caused by uncomfortable and unpleasant leg sensations, symptoms begin or worsen during periods of rest or inactivity such as lying or sitting, symptoms are partially or totally relieved by movement such as walking or stretching at least as long as the activity continues, and symptoms are worse or occur only in the evening or night. Patients were required to have a total score of ≥15 on the International Restless Legs Syndrome (IRLS) Rating Scale at baseline. Patients with RLS secondary to other conditions (e.g., pregnancy, renal failure, iron deficiency anemia) were excluded. In study 1, patients were randomized to receive 1,200 mg of Horizant (N = 112) or placebo (N = 108) taken once daily at about 5 PM with food. In study 2, patients were randomized to receive 600 mg of Horizant (N = 114), 1,200 mg of Horizant (N = 111), or placebo (N = 96) taken once daily at about 5 PM with food.

Efficacy was evaluated using the IRLS Rating Scale and Clinical Global Impression of Improvement (CGI-I) scores. The IRLS Rating Scale contains 10 items designed to assess the severity of sensory and motor symptoms, sleep disturbance, daytime somnolence/sedation, and impact on activities of daily living and mood associated with RLS. The range of scores is 0 to 40, with 0 being absence of RLS symptoms and 40 the most severe symptoms. The CGI-I Scale allows the investigator to rate the patient's overall change in RLS symptoms since baseline, whether or not in the opinion of the investigator the change is related to study drug treatment. The change from baseline in the IRLS Rating Scale at Week 12 and the proportion of responders on the CGI-I Scale defined as a rating of "much improved" or "very much improved" at Week 12 were co-primary outcomes in these studies.

In these 2 studies, the mean age of patients studied was 50 years (range: 18 to 81 years); 59% of the patients were female. The racial distribution for these studies was as follows: Caucasian, 95%; black, 2%; and other, 3%.

Statistically significant differences (P<0.05) between the treatment groups receiving 600 and 1,200 mg of Horizant and the group receiving placebo were observed at Week 12 for both the mean change from baseline in the IRLS Scale total score and the proportion of responders ("much improved" or "very much improved") on the CGI-I Scale as described in Table 6.

Week 12 Study 1 Study 2
Horizant 1,200 mg

(N = 112)

 Placebo

(N = 108)

 Horizant 600 mg

(N = 114)

 Horizant 1,200 mg

(N = 111)

 Placebo

(N = 96)
Mean Change in IRLS Score -13.2 -8.8 -13.8 -13.0 -9.8
Proportion of RespondersCGI-I Responders = "much improved" and "very much improved." on CGI-I 76% 39% 73% 77% 45%

Figure 1 presents the improvement in mean IRLS Rating Scale total score in patients treated with placebo or 600 or 1,200 mg of Horizant over the 12 weeks of treatment in study 2.

Figure 1. Study 2, Mean (±SD) IRLS Rating Scale Total Score Over 12 Weeks

(Observed Case Data, Modified Intent-To-Treat Population)

Figure 1

14.2 Postherpetic Neuralgia 12-Week Study

The efficacy of Horizant for the management of postherpetic neuralgia was established in a multicenter, randomized, double-blind, parallel-group, placebo-controlled, 12- week study evaluating the efficacy, safety, and dose response of 3 maintenance doses of Horizant (1,200, 2,400, and 3,600 mg/day, with 107, 82, and 87 patients in each dosing group, respectively). Patients greater than 18 years of age with a documented medical diagnosis of PHN of at least three months duration were enrolled. To ensure that patients had significant pain, randomized patients were required to have a minimum baseline 24-hour average Pain Intensity Numerical Rating Scale (PI-NRS) intensity score of at least 4.0 on the 11-point numerical PI-NRS, ranging from 0 ("no pain") to 10 ("pain as bad as you can imagine").

In this study, a total of 276 patients received Horizant while 95 patients received placebo. Following a 1-week baseline period during which patients were screened for eligibility, patients began a 1-week up-titration period followed by a 12-week maintenance treatment period, and then a 1-week down-titration period.

Treatment with Horizant statistically significantly improved the mean pain score and increased the proportion of patients with at least a 50% reduction in pain score from baseline at all doses tested. A benefit over placebo was observed for all 3 doses of Horizant as early as Week 1 and maintained to the end of treatment. Additional benefit of using doses of greater than 1,200 mg a day was not demonstrated.

For various degrees of improvement in pain from baseline to end of maintenance treatment, Figure 2 shows the fraction of patients achieving that degree of improvement. The figure is cumulative, so that patients whose change from baseline is, for example, 50%, are also included at every level of improvement below 50%. Patients who did not complete the study were assigned 0% improvement.

Figure 2. Percent of Patients Achieving Various Levels of Improvement in Pain Intensity

Figure 2

14.3 Effects on Driving

Driving performance was assessed in a three way crossover study in healthy volunteers (mean age 36 years). Subjects were dosed at approximately 5 pm with Horizant 600 mg (for five days), diphenhydramine 50 mg (1 dose), and placebo (for five days). After the last dose, driving was evaluated on a computer-based simulation for 1 hour in the evening approximately 2 to 4 hours after dosing (7 to 9 pm), in the morning after dosing (7 to 9 am), and at midday the day after dosing (11 am to 1 pm). The primary endpoint of the study was lane position variability. There was no difference in change from baseline in lane position variability for Horizant compared to placebo at any of the simulated driving timepoints. Secondary measures included speed variability and the occurrence of simulated crashes. Subjects in this study experienced simulated crashes as described in Table 7. At the times that simulated crashes occurred, there was an increase in average speed variability in the HORIZANT- and diphenhydramine-treated groups that was most notable in patients who experienced simulated crashes, but no increases in lane position variability. Later time points post-dosing or the effects of driving after more than five days of dosing with Horizant were not evaluated.

Simulated Driving Timepoint and Hours Post Dose Baseline Placebo Horizant

600 mg

 Diphenhydramine

50 mg
N = 36 N = 36 N = 35 N = 36
n (%) n (%) n (%) n (%)
Day 5

Evening (7 to 9 pm)

2 to 4 hours post dose

 0 (0) 0 (0) 0 (0) 3 (9)
Day 6

Morning (7 to 9 am)

14 to 16 hours post dose

 2 (6) 1 (3) 1 (3) 0 (0)
Day 6

Midday (11 am to 1 pm)

18 to 20 hours post dose

 1 (3) 0 (0) 3 (9) 3 (8)

The results of a separate 2-week driving simulation study in patients (mean age 47 years) with moderate-to-severe primary RLS showed that once daily doses of 1,200 mg and 1,800 mg of Horizant significantly impaired simulated driving performance based on lane position variability. An increased number of simulated crashes were reported in patients tested near Tmax after receiving 1,200 mg or 1,800 mg of Horizant compared to patients treated with diphenhydramine 50 mg. In addition, patients receiving 1,200 mg of Horizant experienced an increased number of simulated crashes at 14 to 16 hours after dosing compared with placebo, diphenhydramine, and 1,800 mg of Horizant.

The design limitations of these two studies do not permit inference regarding dose response relationship or the duration of the effect Horizant has on driving in patients with RLS.

The results of a separate driving simulation study comparing untreated RLS patients and healthy subjects showed no difference in lane position variability but an increase in speed variability associated with a greater number of simulated crashes in RLS patients relative to healthy subjects, which may indicate impaired driving in RLS patients in the absence of medication.

16 HOW SUPPLIED/STORAGE AND HANDLING

Horizant Extended-Release Tablets containing 300 mg of Horizant are white to off-white, with occasional black/grey spots, oval-shaped tablets debossed with "GS TF7".

Horizant Extended-Release Tablets containing 600 mg of Horizant are white to off-white, with occasional black/grey spots, oval-shaped tablets debossed with "GS LFG". They are supplied as follows:


Store at 25°C (77°F); excursions permitted 15° to 30°C (59° to 86°F) . Protect from moisture. Do not remove desiccants.

17 PATIENT COUNSELING INFORMATION

See FDA-approved patient labeling.

Physicians should instruct their patients to read the Medication Guide before starting therapy with Horizant and to reread it upon prescription renewal for new information regarding the use of Horizant.

17.1 Effects on Driving

Patients should be told that Horizant may cause a significant driving impairment. Accordingly, they should be advised not to drive a car until they have gained sufficient experience on Horizant to assess whether Horizant impairs their ability to drive, although patients' ability to determine their level of impairment can be unreliable. Patients should be told that it is not known how long this effect lasts.

17.2 Somnolence/Sedation and Dizziness

Patients should be told that Horizant can cause significant somnolence and dizziness. This typically resolves within several weeks of initiating treatment. Accordingly, they should be told not to operate dangerous machinery until they have gained sufficient experience on Horizant to assess whether Horizant impairs their ability to operate dangerous machinery safely.

17.3 Suicidal Behavior and Ideation

Patients, their caregivers, and families should be counseled that Horizant may increase the risk of suicidal thoughts and behavior, and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm.

Behaviors of concern should be reported immediately to healthcare providers.

17.4 Drug Reaction With Eosinophilia and Systemic Symptoms /Multiorgan Hypersensitivity

Patients should be instructed that multiorgan hypersensitivity reactions may occur with Horizant. Patients should contact their physician immediately if they experience any signs or symptoms of these conditions .

17.5 Lack of Interchangeability With Gabapentin

Patients should be advised that doses of Horizant and other gabapentin products are not interchangeable.

17.6 Dosing Instructions

17.7 Alcohol


Horizant is a registered trademark of Arbor Pharmaceuticals, LLC.

Manufactured for:

Arbor Pharmaceuticals, LLC

Atlanta, GA 30328

©2016, Arbor Pharmaceuticals, LLC. All rights reserved.

HZT-PI-00

PHARMACIST-DETACH HERE AND GIVE TO PATIENT

MEDICATION GUIDE

Horizant® (ho-ri' zant)

(gabapentin enacarbil)

Extended-Release Tablets

Read this Medication Guide before you start taking Horizant and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.

What is the most important information I should know about Horizant?

Horizant can cause serious side effects:


What is Horizant?

Horizant is a prescription medicine used to treat adults with:


Horizant is not for people with RLS who need to sleep during the daytime and need to stay awake at night.

Horizant is not the same medicine as gabapentin (for example, NEURONTIN® or GRALISE®) and should not be used in its place.

It is not known if Horizant is safe and effective in children.

What should I tell my healthcare provider before taking Horizant?

Before taking Horizant, tell your healthcare provider if you:


Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist when you get a new medicine.

How should I take Horizant?


What should I avoid while taking Horizant?


What are the possible side effects of Horizant?


The most common side effects of Horizant include:


Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects of Horizant. For more information, ask your healthcare provider or pharmacist.

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 Horizant?


Keep Horizant and all medicines out of the reach of children.

General Information about the safe and effective use of Horizant

Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use Horizant for a condition for which it was not prescribed. Do not give Horizant to other people, even if they have the same symptoms that you have. It may harm them.

This Medication Guide summarizes the most important information about Horizant. If you would like more information, talk with your healthcare provider.

You can ask your healthcare provider or pharmacist for information about Horizant that was written for healthcare professionals.

For more information about Horizant, go to www. HORIZANT.com or call 1-866-516-4950.

What are the ingredients in Horizant?

Active ingredients: Horizant

Inactive ingredients: Both the 300 mg and 600 mg tablets contain colloidal silicon dioxide, dibasic calcium phosphate dihydrate, glyceryl behenate, magnesium stearate, sodium lauryl sulfate, and talc.

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

Manufactured for:

Arbor Pharmaceuticals, LLC

Atlanta, GA 30328

Revised: October 2016

Horizant is a registered trademark of Arbor Pharmaceuticals, LLC. The other brands listed are trademarks of their respective owners and are not trademarks of Arbor Pharmaceuticals, LLC. The makers of these brands are not affiliated with and do not endorse Arbor Pharmaceuticals, LLC or its products.

©2016, Arbor Pharmaceuticals, LLC. All rights reserved.

HZT-MG-00

30 Tablets

NDC 53451-0103-1

Horizant®

Horizant

extended-release tablets

300 mg

Dispense the accompanying

Medication Guide to each patient.

Rx only

arbor

PHARMACEUTICALS, LLC

30 Tablets

NDC 53451-0101-1

Horizant®

Horizant

extended-release tablets

600 mg

Dispense the accompanying

Medication Guide to each patient.

Rx only

arbor

PHARMACEUTICALS, LLC

Horizant pharmaceutical active ingredients containing related brand and generic drugs:


Horizant available forms, composition, doses:


Horizant destination | category:


Horizant Anatomical Therapeutic Chemical codes:


Horizant pharmaceutical companies:


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References

  1. Dailymed."HORIZANT (GABAPENTIN ENACARBIL) TABLET, EXTENDED RELEASE [ARBOR PHARMACEUTICALS]". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  2. Dailymed."GABAPENTIN ENACARBIL: DailyMed provides trustworthy information about marketed drugs in the United States. DailyMed is the official provider of FDA label information (package inserts).". https://dailymed.nlm.nih.gov/dailym... (accessed August 28, 2018).
  3. "Gabapentin enacarbil". https://pubchem.ncbi.nlm.nih.gov/co... (accessed August 28, 2018).

Frequently asked Questions

Can i drive or operate heavy machine after consuming Horizant?

Depending on the reaction of the Horizant after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Horizant not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.

Is Horizant addictive or habit forming?

Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.

Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.

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Review

sdrugs.com conducted a study on Horizant, and the result of the survey is set out below. It is noteworthy that the product of the survey is based on the perception and impressions of the visitors of the website as well as the views of Horizant consumers. We, as a result of this, advice that you do not base your therapeutic or medical decisions on this result, but rather consult your certified medical experts for their recommendations.

Visitor reports

Visitor reported useful

No survey data has been collected yet

Visitor reported side effects

No survey data has been collected yet

One visitor reported price estimates

What is your opinion about drug cost? Did you feel the cost is apt, or did you feel it is expensive?
The report given by the sdrugs.com website users shows the following figures about several people who felt the medicine Horizant is expensive, and the medicine is not expensive. The results are mixed. The perception of the cost of the medicine to be expensive or not depends on the brand name of the medicine, country, and place where it is sold, and the affordability of the patient. You can choose a generic drug in the place of the branded drug to save the cost. The efficiency of the medicine will not vary if it is generic or a branded one.
Visitors%
Expensive1
100.0%

Visitor reported frequency of use

No survey data has been collected yet

Visitor reported doses

No survey data has been collected yet

Visitor reported time for results

No survey data has been collected yet

Visitor reported administration

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Visitor reported age

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The information was verified by Dr. Rachana Salvi, MD Pharmacology


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