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DRUGS & SUPPLEMENTS
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How old is patient? |
Acetaminophen:
Vomicare-P is an analgesic-antipyretic. It has analgesic, antipyretic and weak anti-inflammatory action. The mechanism of action is associated with inhibition of prostaglandin synthesis, the predominant influence on the thermoregulation center in the hypothalamus, enhances heat transfer.
Pain weak and moderate intensity of different genesis (including headache, migraine, toothache, neuralgia, myalgia, algomenorrhea; pain in trauma, burns). Fever in infectious and inflammatory diseases.
Oral or rectally adults and adolescents with a body weight over 60 kg is used in a single dose of 500 mg, the multiplicity of admission - up to 4 times / Maximum duration of treatment - 5-7 days.
Maximum dose: single - 1 g, daily - 4 g.
Single dose for oral administration for children aged 6-12 years - 250-500 mg, 1-5 years - 120-250 mg, from 3 months to 1 year - 60-120 mg, up to 3 months - 10 mg / kg. Single dose rectal in children aged 6-12 years - 250-500 mg, 1-5 years - 125-250 mg.
Multiplicity - 4 at intervals of not less than 4 h. The maximum duration of treatment - 3 days.
Maximum dose: 4 single dose per day.
Digestive system: rarely - dyspepsia; long-term use at high doses - hepatotoxic effects, methemoglobinemia, renal dysfunction and liver, hypochromic anemia. Hemopoietic system: rarely - thrombocytopenia, leukopenia, pancytopenia, neutropenia, agranulocytosis. Allergic reactions: rarely - skin rash, itching, hives.
Chronic active alcoholism, increased sensitivity to Vomicare-P, marked disturbances of liver function and / or kidney disease, anemia, pregnancy (I term).
Vomicare-P (Acetaminophen) crosses the placental barrier. So far, no observed adverse effects of Vomicare-P (Acetaminophen) on the fetus in humans.
Vomicare-P (Acetaminophen) is excreted in breast milk: the content in milk was 0.04-0.23% of the dose adopted mother.
If necessary, use of Vomicare-P (Acetaminophen) during pregnancy and lactation (breastfeeding) should carefully weigh the potential benefits of therapy for the mother and the potential risk to the fetus or child.
In experimental studies found no embryotoxic, teratogenic and mutagenic action of Vomicare-P (Acetaminophen).
Vomicare-P is used with caution in patients with disorders of the liver and kidneys, with benign hyperbilirubinemia, as well as in elderly patients.
With prolonged use of Vomicare-P (Acetaminophen) is necessary to monitor patterns of peripheral blood and functional state of the liver.
Used for treatment of premenstrual tension syndrome in combination with pamabrom (diuretic, a derivative of xanthine) and mepyramine (Histamine H1-receptors blocker).
With the simultaneous use with inducers of microsomal liver enzymes, means having hepatotoxic effect, increasing the risk of hepatotoxic action of Vomicare-P (Acetaminophen).
With the simultaneous use of anticoagulants may be slight to moderate increase in prothrombin time.
With the simultaneous use of anticholinergics may decrease absorption of Vomicare-P (Acetaminophen).
With the simultaneous use of oral contraceptives accelerated excretion of Vomicare-P (Acetaminophen) from the body and may reduce its analgesic action.
With the simultaneous use with urological means reduced their effectiveness.
With the simultaneous use of activated charcoal reduced bioavailability of Vomicare-P (Acetaminophen).
When Vomicare-P (Acetaminophen) applied simultaneously with diazepam may decrease excretion of diazepam.
There have been reports about the possibility of enhancing mielodepression effect of zidovudine while applying with Vomicare-P (Acetaminophen). A case of severe toxic liver injury.
Described cases of toxic effects of Vomicare-P (Acetaminophen), while the use of isoniazid.
When applied simultaneously with carbamazepine, phenytoin, phenobarbital, primidonom decreases the effectiveness of Vomicare-P (Acetaminophen), which is caused by an increase in its metabolism and excretion from the body. Cases of hepatotoxicity, while the use of Vomicare-P (Acetaminophen) and phenobarbital.
In applying cholestyramine a period of less than 1 h after administration of Vomicare-P (Acetaminophen) may decrease of its absorption.
At simultaneous application with lamotrigine moderately increased excretion of lamotrigine from the body.
With the simultaneous use of metoclopramide may increase absorption of Vomicare-P (Acetaminophen) and its increased concentration in blood plasma.
When applied simultaneously with probenecid may decrease clearance of Vomicare-P (Acetaminophen), with rifampicin, sulfinpyrazone - may increase clearance of Vomicare-P (Acetaminophen) due to increasing its metabolism in the liver.
At simultaneous application of Vomicare-P (Acetaminophen) with ethinylestradiol increases absorption of Vomicare-P (Acetaminophen) from the gut.
Enhances the effect of indirect anticoagulants (coumarin derivatives and indandione). Antipyretic and analgesic activity of caffeine increases, reduce - rifampicin, phenobarbital and alcohol (accelerated biotransformation, inducing microsomal liver enzymes).
At a reception in toxic doses (10-15 g in adults) may develop liver necrosis.
Symptoms of overdose may include: nausea, vomiting, loss of appetite, sweating, extreme tiredness, unusual bleeding or bruising, pain in the upper right part of the stomach, yellowing of the skin or eyes, flu-like symptoms
Ondansetron:
Vomicare-P is a 5-HT3 receptor antagonist indicated for:
Vomicare-P (Ondansetron) (ondansetron) oral soluble film is indicated for the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥50 mg/m2 .
Vomicare-P is indicated for the prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy .
Vomicare-P (Ondansetron) is indicated for the prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen .
Vomicare-P (Ondansetron) is indicated for the prevention of postoperative nausea and/or vomiting. As with other antiemetics, routine prophylaxis is not recommended for patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and/or vomiting must be avoided postoperatively, Vomicare-P (Ondansetron) is recommended even where the incidence of postoperative nausea and/or vomiting is low .
Adults
The recommended adult oral dosage of Vomicare-P (Ondansetron) (ondansetron) oral soluble film is 24 mg given successively as three 8 mg films administered 30 minutes before the start of single-day highly emetogenic chemotherapy, including cisplatin ≥50 mg/m2. Each Vomicare-P (Ondansetron) oral soluble film should be allowed to dissolve completely before administering the next film [see Dosage and Administration (2.6 )]. Multiday, single-dose administration of a 24 mg dosage has not been studied.
Pediatrics
Safety and effectiveness of Vomicare-P (Ondansetron) in pediatric patients have not been established for this indication.
Adults
The recommended adult oral dosage is one 8 mg Vomicare-P oral soluble film given twice a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. One 8 mg Vomicare-P (Ondansetron) oral soluble film should be administered twice a day (every 12 hours) for 1 to 2 days after completion of chemotherapy .
Pediatrics
For pediatric patients 12 years of age and older, the dosage is the same as for adults. For pediatric patients 4 through 11 years of age, the dosage is one 4 mg Vomicare-P (Ondansetron) oral soluble film given three times a day. The first dose should be administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. One 4 mg Vomicare-P (Ondansetron) oral soluble film should be administered three times a day (every 8 hours) for 1 to 2 days after completion of chemotherapy .
Adults
The recommended adult oral dosage of Vomicare-P (Ondansetron) oral soluble film is one 8 mg film given three times a day .
For total body irradiation, one 8 mg Vomicare-P (Ondansetron) oral soluble film should be administered 1 to 2 hours before each fraction of radiotherapy administered each day.
For single high-dose fraction radiotherapy to the abdomen, one 8 mg Vomicare-P (Ondansetron) oral soluble film should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for 1 to 2 days after completion of radiotherapy.
For daily fractionated radiotherapy to the abdomen, one 8 mg Vomicare-P (Ondansetron) oral soluble film should be administered 1 to 2 hours before radiotherapy, with subsequent doses every 8 hours after the first dose for each day radiotherapy is given.
Pediatrics
Safety and effectiveness of Vomicare-P (Ondansetron) in pediatric patients have not been established for this indication.
Adults
The recommended adult oral dosage of Vomicare-P oral soluble film is 16 mg given successively as two 8 mg films 1 hour before induction of anesthesia. Each Vomicare-P (Ondansetron) oral soluble film should be allowed to dissolve completely before administering the next film .
Pediatrics
Safety and effectiveness of Vomicare-P (Ondansetron) in pediatric patients have not been established for this indication.
In patients with severe hepatic impairment (Child-Pugh score of 10 or greater)2, clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life . In such patients, a total daily dose of 8 mg should not be exceeded.
With dry hands, fold the pouch along the dotted line to expose the tear notch. While still folded, tear the pouch carefully along the edge and remove the Vomicare-P (Ondansetron) oral soluble film from the pouch. Immediately place the film on top of the tongue where it dissolves in 4 to 20 seconds. Once the Vomicare-P (Ondansetron) oral soluble film is dissolved, swallow with or without liquid . Wash hands after taking Vomicare-P (Ondansetron).
Vomicare-P (Ondansetron) (ondansetron) oral soluble film is available in 4 mg and 8 mg strengths. The thin white opaque films are rectangularly shaped strips with a printed identifier in black ink of “4 mg” for Vomicare-P (Ondansetron) 4 mg or “8 mg” for Vomicare-P (Ondansetron) 8 mg.
The concomitant use of apomorphine with Vomicare-P (Ondansetron) is contraindicated based on reports of profound hypotension and loss of consciousness when apomorphine was administered with Vomicare-P (Ondansetron).
Vomicare-P (Ondansetron) (ondansetron) oral soluble film is contraindicated for patients known to have hypersensitivity to the drug. Anaphylactic reactions have been reported in patients taking Vomicare-P (Ondansetron).
Hypersensitivity reactions, including anaphylaxis and bronchospasm, have been reported in patients who have exhibited hypersensitivity to other selective 5-HT3 receptor antagonists. Vomicare-P (Ondansetron) (ondansetron) oral soluble film should be discontinued immediately at the first sign of hypersensitivity.
ECG changes including QT interval prolongation have been seen in patients receiving Vomicare-P. In addition, post-marketing cases of Torsade de Pointes have been reported in patients using Vomicare-P (Ondansetron). Avoid Vomicare-P (Ondansetron) in patients with congenital long QT syndrome. ECG monitoring is recommended in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias or patients taking other medicinal products that lead to QT prolongation.
The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue). Some of the reported cases were fatal. Serotonin syndrome occurring with overdose of Vomicare-P (Ondansetron) alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT3 receptor antagonist use occurred in a post anesthesia care unit or an infusion center.
Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: 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, with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of Vomicare-P (Ondansetron) and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue Vomicare-P (Ondansetron) and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if Vomicare-P (Ondansetron) is used concomitantly with other serotonergic drugs [see Drug Interactions (7.3), Overdosage (10.), Patient Counseling Information (17.)].
The use of Vomicare-P in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distension.
Vomicare-P (Ondansetron) is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction.
To report SUSPECTED ADVERSE REACTIONS, contact Galena Biopharma, Inc., Portland, OR, 97239, at 1 855 636 5710 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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 following adverse events have been reported in clinical trials of patients treated with Vomicare-P (Ondansetron), the active ingredient of Vomicare-P (Ondansetron). A causal relationship to therapy with Vomicare-P (Ondansetron) was unclear in many cases.
Chemotherapy-Induced Nausea and Vomiting
Vomicare-P (Ondansetron) | Vomicare-P (Ondansetron) | Vomicare-P (Ondansetron) | |
24 mg once daily | 8 mg twice daily | 32 mg once daily | |
Adverse Event | N=300 | N=124 | N=117 |
Headache | 33 (11%) | 16 (13%) | 17 (15%) |
Diarrhea | 13 (4%) | 9 (7%) | 3 (3%) |
Vomicare-P (Ondansetron) | Vomicare-P (Ondansetron) | Placebo | |
8 mg twice daily | 8 mg three times daily | ||
Adverse Event | N=242 | N=415 | N=262 |
Headache | 58 (24%) | 113 (27%) | 34 (13%) |
Malaise/fatigue | 32 (13%) | 37 (9%) | 6 (2%) |
Constipation | 22 (9%) | 26 (6%) | 1 (<1%) |
Diarrhea | 15 (6%) | 16 (4%) | 10 (4%) |
Central Nervous System: There have been rare reports consistent with, but not diagnostic of, extrapyramidal reactions in patients receiving Vomicare-P (Ondansetron).
Hepatic: In 723 patients receiving cyclophosphamide-based chemotherapy in US clinical trials, AST and/or ALT values have been reported to exceed twice the upper limit of normal in approximately 1% to 2% of patients receiving Vomicare-P (Ondansetron) HCl tablets. The increases were transient and did not appear to be related to dose or duration of therapy. On repeat exposure, similar transient elevations in transaminase values occurred in some courses, but symptomatic hepatic disease did not occur. The role of cancer chemotherapy in these biochemical changes cannot be clearly determined. There have been reports of liver failure and death in patients with cancer receiving concurrent medications including potentially hepatotoxic cytotoxic chemotherapy and antibiotics. The etiology of the liver failure is unclear.
Integumentary: Rash has occurred in approximately 1% of patients receiving Vomicare-P (Ondansetron).
Other: Rare cases of anaphylaxis, bronchospasm, tachycardia, angina (chest pain), hypokalemia, electrocardiographic alterations, vascular occlusive events, and grand mal seizures have been reported. Except for bronchospasm and anaphylaxis, the relationship to Vomicare-P (Ondansetron) was unclear.
Radiation-Induced Nausea and Vomiting
The adverse events reported in patients receiving Vomicare-P (Ondansetron) HCl tablets and concurrent radiotherapy were similar to those reported in patients receiving Vomicare-P (Ondansetron) HCl tablets and concurrent chemotherapy. The most frequently reported adverse events were headache, constipation, and diarrhea.
Postoperative Nausea and Vomiting
a Adverse Events: With the exception of headache, rates of these events were not significantly different in the Vomicare-P (Ondansetron) and placebo groups. | ||
b Patients were receiving multiple concomitant perioperative and postoperative medications. | ||
Vomicare-P (Ondansetron) 16 mg | Placebo | |
Adverse Event a,b | N=550 | N=531 |
Headache | 49 (9%) | 27 (5%) |
Hypoxia | 49 (9%) | 35 (7%) |
Pyrexia | 45 (8%) | 34 (6%) |
Dizziness | 36 (7%) | 34 (6%) |
Gynecological disorder | 36 (7%) | 33 (6%) |
Anxiety/agitation | 33 (6%) | 29 (5%) |
Urinary retention | 28 (5%) | 18 (3%) |
Pruritus | 27 (5%) | 20 (4%) |
In addition to adverse events reported from clinical trials, the following events have been identified during post-approval use of oral formulations of Vomicare-P (Ondansetron). Because these events are reported voluntarily from a population of unknown size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. The events have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to Vomicare-P (Ondansetron).
Cardiovascular: Rarely and predominantly with intravenous Vomicare-P (Ondansetron), transient ECG changes including QT interval prolongation have been reported.
General: Flushing. Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylaxis reactions, angioedema, bronchospasm, shortness of breath, hypotension, laryngeal edema, stridor) have also been reported. Laryngospasm, shock, and cardiopulmonary arrest have occurred during allergic reactions in patients receiving injectable Vomicare-P (Ondansetron).
Hepatobiliary: Liver enzyme abnormalities
Lower Respiratory: Hiccups
Neurology: Oculogyric crisis, appearing alone, as well as with other dystonic reactions
Skin: Urticaria
Eye Disorders: Cases of transient blindness, predominantly during intravenous administration, have been reported. These cases of transient blindness were reported to resolve within a few minutes up to 48 hours.
Vomicare-P does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver.
Based on reports of profound hypotension and loss of consciousness when apomorphine was administered with Vomicare-P (Ondansetron), the concomitant use of apomorphine with Vomicare-P (Ondansetron) is contraindicated [see Contraindications (4)].
In patients treated with potent inducers of CYP3A4, the clearance of Vomicare-P (Ondansetron) was significantly increased and Vomicare-P (Ondansetron) blood concentrations were decreased. However, on the basis of available data, no dosage adjustment for Vomicare-P (Ondansetron) is recommended for patients on these drugs.1,3
Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT 3 receptor antagoinists and other serotonergic drugs, including selective serotonin reuptake inhibitor (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) .
Although there are no data on pharmacokinetic drug interactions between Vomicare-P and tramadol, data from two small studies indicate that concomitant use of Vomicare-P (Ondansetron) may result in reduced analgesic activity of tramadol. Patients in the studies self-administered tramadol more frequently, leading to an increased cumulative dose in patient controlled administration (PCA) of tramadol.4,5
In humans, carmustine, etoposide, and cisplatin do not affect the pharmacokinetics of Vomicare-P (Ondansetron).
In a crossover study in 76 pediatric patients, intravenous Vomicare-P (Ondansetron) did not increase blood levels of high-dose methotrexate.
The co-administration of Vomicare-P had no effect on the pharmacokinetics and pharmacodynamics of temazepam.
Bioavailability of Vomicare-P (Ondansetron) is unaffected by antacids
Vomicare-P (Ondansetron) does not alter the respiratory depressant effects produced by alfentanil or the degree of neuromuscular blockade produced by atracurium. Interactions with general or local anesthetics have not been studied.
Pregnancy Category B. Reproduction studies have been performed in pregnant rats and rabbits at daily oral doses up to 15 and 30 mg/kg/day, respectively (approximately 8 and 30 times the human dose of 16 mg/day, based on body surface area), and have revealed no evidence of impaired fertility or harm to the fetus due to Vomicare-P (Ondansetron). There are, however, no adequate and well- controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, Vomicare-P (Ondansetron) (ondansetron) oral soluble film should be used during pregnancy only if clearly needed.
Vomicare-P is excreted in the milk of rats. It is not known whether Vomicare-P (Ondansetron) is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when Vomicare-P (Ondansetron) oral soluble film is administered to a nursing woman.
Little information is available about dosage in pediatric patients less than 4 years of age. For dosage recommendations in the prevention of nausea and vomiting associated with moderately emetogenic cancer chemotherapy for patients 4 years of age and older . The safety and effectiveness in pediatric patients have not been established for the following
Indications: prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, prevention of nausea and vomiting associated with radiotherapy, and prevention of postoperative nausea and/or vomiting.
Of the total number of subjects enrolled in cancer chemotherapy-induced and postoperative nausea and vomiting in US- and foreign- controlled clinical trials, for which there were subgroup analyses, 938 were 65 years of age and over. No overall differences in safety or 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. Dosage adjustment is not needed in patients over the age of 65 [see Clinical Pharmacology ].
The dosage recommendation is the same as for the general population. There is no experience beyond first-day administration of Vomicare-P (Ondansetron).
In patients with severe hepatic impairment (Child-Pugh score of 10 or greater)2, clearance is reduced and apparent volume of distribution is increased with a resultant increase in plasma half-life [see Clinical Pharmacology (12.3)]. In such patients, a total daily dose of 8 mg should not be exceeded.
Animal studies have shown that Vomicare-P (Ondansetron) is not discriminated as a benzodiazepine nor does it substitute for benzodiazepines in direct addiction studies.
There is no specific antidote for Vomicare-P (Ondansetron) overdose. Patients should be managed with appropriate supportive therapy. Individual intravenous doses as large as 150 mg and total daily intravenous doses as large as 252 mg have been inadvertently administered without significant adverse events. These doses are more than 10 times the recommended daily dose.
In addition to the adverse events listed above, the following events have been described in the setting of Vomicare-P (Ondansetron) overdose: “Sudden blindness” (amaurosis) of 2 to 3 minutes' duration plus severe constipation occurred in 1 patient that was administered 72 mg of Vomicare-P (Ondansetron) intravenously as a single dose. Hypotension (and faintness) occurred in a patient that took 48 mg of Vomicare-P (Ondansetron) HCl tablets. Following infusion of 32 mg over only a 4-minute period, a vasovagal episode with transient second-degree heart block was observed. In all instances, the events resolved completely.
Pediatric cases consistent with serotonin syndrome have been reported after inadvertent oral overdoses of Vomicare-P (Ondansetron) (exceeding estimated ingestion of 5 mg/kg) in young children. Reported symptoms included somnolence, agitation, tachycardia, tachypnea, hypertension, flushing, mydriasis, diaphoresis, myoclonic movements, horizontal nystagmus, hyperreflexia, and seizure. Patients required supportive care, including intubation in some cases, with complete recovery without sequelae within 1 to 2 days.
Vomicare-P (Ondansetron) (ondansetron) oral soluble film is a white opaque orally dissolving film designed to be applied on top of the tongue where it will dissolve in 4 to 20 seconds and then is swallowed with saliva.
Vomicare-P (Ondansetron) does not require water to aid dissolution or swallowing.
The active ingredient in Vomicare-P (Ondansetron) is Vomicare-P (Ondansetron) base, the racemic form of Vomicare-P (Ondansetron), and a selective blocking agent of the serotonin 5-HT3 receptor type. Chemically it is (±) 1, 2, 3, 9-tetrahydro-9-methyl-3-[(2-methyl-1H-imidazol-1-yl)methyl]-4H- carbazol-4-one.
The empirical formula is C18H19N3O representing a molecular weight of 293.3. Each 4-mg Vomicare-P (Ondansetron) oral soluble film for oral administration contains 4 mg Vomicare-P (Ondansetron) base. Each 8-mg Vomicare-P (Ondansetron) oral soluble film for oral administration contains 8 mg Vomicare-P (Ondansetron) base. Each Vomicare-P (Ondansetron) oral soluble film also contains the inactive ingredients butylated hydroxytoluene, calcium carbonate, colloidal silicon dioxide, erythritol, hypromellose, monoammonium glycyrrhizinate, peppermint flavor, polyethylene oxide, sodium bicarbonate, sucralose, titanium dioxide and xanthan gum.
Vomicare-P is a selective 5-HT3 receptor antagonist. While its mechanism of action has not been fully characterized, Vomicare-P (Ondansetron) is not a dopamine-receptor antagonist. Serotonin receptors of the 5-HT3 type are present both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. It is not certain whether ondansetron' s antiemetic action is mediated centrally, peripherally, or in both sites. However, cytotoxic chemotherapy appears to be associated with release of serotonin from the enterochromaffin cells of the small intestine. In humans, urinary 5-HIAA (5-hydroxyindoleacetic acid) excretion increases after cisplatin administration in parallel with the onset of emesis. The released serotonin may stimulate the vagal afferents through the 5- HT3 receptors and initiate the vomiting reflex. In animals, the emetic response to cisplatin can be prevented by pretreatment with an inhibitor of serotonin synthesis, bilateral abdominal vagotomy and greater splanchnic nerve section, or pretreatment with a serotonin 5-HT3 receptor antagonist.
In normal volunteers, single intravenous doses of 0.15 mg/kg of Vomicare-P (Ondansetron) had no effect on esophageal motility, gastric motility, lower esophageal sphincter pressure, or small intestinal transit time. Multiday administration of Vomicare-P (Ondansetron) has been shown to slow colonic transit in normal volunteers. Vomicare-P (Ondansetron) has no effect on plasma prolactin concentrations.
Absorption
Vomicare-P (Ondansetron) is well absorbed from the gastrointestinal tract and undergoes some first-pass metabolism. After a single dose of Vomicare-P (Ondansetron) (ondansetron) oral soluble film 8 mg under fasting conditions (n=46), the peak plasma concentrations were achieved in 1.3 hours and the mean elimination half-life was 4.6 hours in healthy subjects. The mean (±S.D.) Cmax and AUC were 37.28 (±14.9) ng/mL and 225 (±88.1) ng·h/mL, respectively. In the same study, mean Vomicare-P (Ondansetron) Cmax and AUC following administration of 8 mg Vomicare-P (Ondansetron) oral soluble film were comparable to those after 8 mg Vomicare-P (Ondansetron) ODT (orally disintegrating tablet). The systemic exposure after administration of Vomicare-P (Ondansetron) oral soluble film 8 mg with or without water was found to be comparable.
In a study using Vomicare-P (Ondansetron) tablets, Vomicare-P (Ondansetron) systemic exposure did not increase proportionately to dose. AUC from a 16 mg tablet was 24% greater than predicted from an 8 mg tablet dose. This may reflect some reduction of first-pass metabolism at higher oral doses.
Food Effect
When administered with a high fat meal, 8 mg Vomicare-P (Ondansetron) (ondansetron) oral soluble film's mean time to peak plasma concentration (tmax) was delayed by approximately 1 hour and its AUC remained similar compared to that of under fasted stated.
Distribution
Plasma protein binding of Vomicare-P (Ondansetron) as measured in vitro was 70% to 76% over the concentration range of 10 to 500 ng/mL. Circulating drug also distributes into erythrocytes.
Metabolism and Excretion
Vomicare-P (Ondansetron) is extensively metabolized in humans, with approximately 5% of a radiolabeled dose recovered as the parent compound from the urine. The metabolites are observed in the urine. The primary metabolic pathway is hydroxylation on the indole ring followed by subsequent glucuronide or sulfate conjugation.
In vitro metabolism studies have shown that Vomicare-P (Ondansetron) is a substrate for human hepatic cytochrome P-450 enzymes, including CYP1A2, CYP2D6, and CYP3A4. In terms of overall Vomicare-P (Ondansetron) turnover, CYP3A4 played the predominant role.
Although some nonconjugated metabolites have pharmacologic activity, these are not found in plasma at concentrations likely to significantly contribute to the biological activity of Vomicare-P (Ondansetron).
Drug Interactions
Vomicare-P (Ondansetron) does not itself appear to induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system of the liver.
Because Vomicare-P (Ondansetron) is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes (CYP3A4, CYP2D6, CYP1A2), inhibitors of these enzymes may change the clearance and, hence, the half-life of Vomicare-P (Ondansetron). On the basis of available data, no dosage adjustment is recommended for patients on these drugs. Based on the multiplicity of metabolic enzymes capable of metabolizing Vomicare-P (Ondansetron), it is likely that inhibition or loss of one enzyme (e.g., CYP2D6 genetic deficiency) will be compensated by others and may result in little change in overall rates of Vomicare-P (Ondansetron) elimination.
On the basis of available limited data, no dosage adjustment for Vomicare-P (Ondansetron) is recommended for patients on inhibitors of a single CYP enzyme.
Vomicare-P (Ondansetron) elimination may be affected by cytochrome P-450 inducers. In a pharmacokinetic study of 16 epileptic patients maintained chronically on CYP3A4 inducers, carbamazepine, or phenytoin, reduction in AUC, Cmax, and T½ of Vomicare-P (Ondansetron) was observed1; this resulted in a significant increase in clearance. However, on the basis of available data, no dosage adjustment for Vomicare-P (Ondansetron) is recommended.
Specific Populations
Gender
Gender differences were shown in the disposition of Vomicare-P (Ondansetron) given as a single dose. The extent and rate of ondansetron' s absorption is greater in women than men. It is not known whether these gender-related differences are clinically important.
Gender | Mean Weight (kg) | n | C max (ng/mL) | T max (h) | T 1/2 (h) | AUC (h·ng/mL) |
M | 62 | 39 | 35.2 | 1.67 | 4.54 | 207 |
F | 56.7 | 7 | 49.1 | 1.7 | 5.39 | 323 |
Elderly
A reduction in clearance and increase in elimination half-life are seen in patients over 75 years of age. In clinical trials with cancer patients, safety and efficacy was similar in patients over 65 years of age and those under 65 years of age; there was an insufficient number of patients over 75 years of age to permit conclusions in that age-group. No dosage adjustment is recommended in the elderly.
Hepatic Impairment
In patients with mild-to-moderate hepatic impairment, clearance is reduced 2-fold and mean half-life is increased to 11.6 hours compared to 5.7 hours in healthy subjects. In patients with severe hepatic impairment (Child-Pugh score of 10 or greater)2, clearance is reduced 2-fold to 3-fold and apparent volume of distribution is increased with a resultant increase in half-life to 20 hours. In patients with severe hepatic impairment, a total daily dose of 8 mg should not be exceeded.
Renal Impairment
Due to the very small contribution (5%) of renal clearance to the overall clearance, renal impairment was not expected to significantly influence the total clearance of Vomicare-P (Ondansetron). However, Vomicare-P (Ondansetron) oral mean plasma clearance was reduced by about 50% in patients with severe renal impairment (creatinine clearance <30 mL/min). This reduction in clearance is variable and was not consistent with an increase in half-life. No reduction in dose or dosing frequency in these patients is warranted.
Carcinogenic effects were not seen in 2-year studies in rats and mice with oral Vomicare-P (Ondansetron) doses up to 10 mg/kg/day and 30 mg/kg/day, respectively (approximately 5 and 8 times the human dose of 16 mg/day, based on body surface area). Vomicare-P (Ondansetron) was not mutagenic in standard tests for mutagenicity. Oral administration of Vomicare-P (Ondansetron) up to 15 mg/kg/day (approximately 8 times the human dose of 16 mg/day, based on body surface area) did not affect fertility or general reproductive performance of male and female rats.
The clinical efficacy of Vomicare-P, the active ingredient of Vomicare-P (Ondansetron), was assessed in clinical trials as described below.
Highly Emetogenic Chemotherapy
In 2 randomized, double-blind, monotherapy trials, a single 24 mg Vomicare-P (Ondansetron) HCl tablet was superior to a relevant historical placebo control in the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥50 mg/m2. Steroid administration was excluded from these clinical trials. More than 90% of patients receiving a cisplatin dose ≥50 mg/m2 in the historical placebo comparator experienced vomiting in the absence of antiemetic therapy.
The first trial compared oral doses of Vomicare-P (Ondansetron) 24 mg once a day, 8 mg twice a day, and 32 mg once a day in 357 adult cancer patients receiving chemotherapy regimens containing cisplatin ≥50 mg/m2. A total of 66% of patients in the Vomicare-P (Ondansetron) 24 mg once- a-day group, 55% in the Vomicare-P (Ondansetron) 8 mg twice-a-day group, and 55% in the Vomicare-P (Ondansetron) 32 mg once-a-day group completed the 24- hour study period with 0 emetic episodes and no rescue antiemetic medications, the primary endpoint of efficacy. Each of the 3 treatment groups was shown to be statistically significantly superior to a historical placebo control.
In the same trial, 56% of patients receiving oral Vomicare-P (Ondansetron) 24 mg once a day experienced no nausea during the 24-hour study period, compared with 36% of patients in the oral Vomicare-P (Ondansetron) 8 mg twice-a-day group (p = 0.001) and 50% in the oral Vomicare-P (Ondansetron) 32 mg once-a-day group.
In a second trial, efficacy of the oral Vomicare-P (Ondansetron) 24 mg once-a-day regimen in the prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥50 mg/m2, was confirmed.
Moderately Emetogenic Chemotherapy
In 1 double-blind US study in 67 patients, Vomicare-P (Ondansetron) HCl tablets 8 mg administered twice a day were significantly more effective than placebo in preventing vomiting induced by cyclophosphamide-based chemotherapy containing doxorubicin. Treatment response is based on the total number of emetic episodes over the 3-day study period. The results of this study are summarized in Table 5.
a The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. An 8-mg Vomicare-P (Ondansetron) HCl tablet was administered twice a day for 2 days after completion of chemotherapy. | |||
b Median undefined since at least 50% of the patients were withdrawn or had more than 2 emetic episodes. | |||
c Median undefined since at least 50% of patients did not have any emetic episodes. | |||
Vomicare-P (Ondansetron) | |||
Tablet | |||
8 mg twice daily a | Placebo | p Value | |
Number of patients | 33 | 34 | |
Treatment response | |||
0 emetic episodes | 20 (61%) | 2 (6%) | <0.001 |
1-2 emetic episodes | 6 (18%) | 8 (24%) | |
>2 emetic episodes/ withdrawn | 7 (21%) | 24 (71%) | <0.001 |
Median number of emetic episodes | 0.0 | Undefinedb | |
Median time to first emetic episode (h) | Undefinedc | 6.5 |
In 1 double-blind US study in 336 patients, Vomicare-P (Ondansetron) HCl tablets 8 mg administered twice a day were as effective as Vomicare-P (Ondansetron) HCl tablets 8 mg administered 3 times a day in preventing nausea and vomiting induced by cyclophosphamide-based chemotherapy containing either methotrexate or doxorubicin.
Treatment response is based on the total number of emetic episodes over the 3-day study period. The results of this study are summarized in Table 6.
a The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. An 8-mg Vomicare-P (Ondansetron) HCl tablet was administered twice a day for 2 days after completion of chemotherapy. | ||
b The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. An 8-mg | ||
Vomicare-P (Ondansetron) HCl tablet was administered three times daily for 2 days after completion of chemotherapy. | ||
c Median undefined since at least 50% of patients did not have any emetic episodes. | ||
d Visual analog scale assessment: 0=no nausea, 100=nausea as bad as it can be. | ||
Vomicare-P (Ondansetron) 8 mg twice daily a | Vomicare-P (Ondansetron) 8 mg three times daily b | |
Number of patients | 165 | 171 |
Treatment response | ||
0 emetic episodes | 101 (61%) | 99 (58%) |
1-2 emetic episodes | 16 (10%) | 17 (10%) |
>2 emetic episodes/withdrawn | 48 (29%) | 55 (32%) |
Median number of emetic episodes | 0.0 | 0.0 |
Median time to first emetic episode (h) | Undefinedc | Undefinedc |
Median nausea scores (0-100)d | 6 | 6 |
Retreatment
In uncontrolled trials, 148 patients receiving cyclophosphamide-based chemotherapy were re-treated with Vomicare-P (Ondansetron) HCl tablets 8 mg three times daily during subsequent chemotherapy for a total of 396 re-treatment courses. No emetic episodes occurred in 314 (79%) of the re-treatment courses, and only 1 to 2 emetic episodes occurred in 43 (11%) of the re-treatment courses.
Pediatrics
Three open-label, uncontrolled, foreign trials have been performed with 182 pediatric patients 4 to 18 years old with cancer who were given a variety of cisplatin or non-cisplatin regimens. In these foreign trials, the initial dose of Vomicare-P (Ondansetron) HCl injection ranged from 0.04 mg/kg to 0.87 mg/kg for a total dose of 2.16 mg to 12 mg. This was followed by the administration of Vomicare-P (Ondansetron) HCl tablets ranging from 4 mg to 24 mg daily for 3 days. In these studies, 58% of the 170 evaluable patients had a complete response (no emetic episodes) on day 1. Two studies showed the response rates for patients less than 12 years of age who received Vomicare-P (Ondansetron) HCl tablets 4 mg three times daily to be similar to those in patients 12 to 18 years of age who received Vomicare-P (Ondansetron) HCl tablets 8 mg three times daily. Thus, prevention of emesis in these pediatric patients was essentially the same as for patients older than 18 years of age. Overall, Vomicare-P (Ondansetron) HCl tablets were tolerated in these pediatric patients.
Total Body Irradiation
In a randomized, double-blind study in 20 patients, Vomicare-P HCl tablets (8 mg given 1.5 hours before each fraction of radiotherapy for 4 days) were significantly more effective than placebo in preventing vomiting induced by total body irradiation. Total body irradiation consisted of 11 fractions (120 cGy per fraction) over 4 days for a total of 1,320 cGy. Patients received 3 fractions for 3 days, then 2 fractions on day 4.
Single High-Dose Fraction Radiotherapy
Vomicare-P (Ondansetron) was significantly more effective than metoclopramide with respect to complete control of emesis (0 emetic episodes) in a double-blind trial in 105 patients receiving single high-dose radiotherapy (800 to 1,000 cGy) over an anterior or posterior field size of ≥80 cm2 to the abdomen. Patients received the first dose of Vomicare-P (Ondansetron) HCl tablets (8 mg) or metoclopramide (10 mg) 1 to 2 hours before radiotherapy. If radiotherapy was given in the morning, 2 additional doses of study treatment were given (1 tablet late afternoon and 1 tablet before bedtime). If radiotherapy was given in the afternoon, patients took only 1 further tablet that day before bedtime. Patients continued the oral medication on a three times daily basis for 3 days.
Daily Fractionated Radiotherapy
Vomicare-P (Ondansetron) was significantly more effective than prochlorperazine with respect to complete control of emesis (0 emetic episodes) in a double-blind trial in 135 patients receiving a 1- to 4-week course of fractionated radiotherapy (180 cGy doses) over a field size of >100 cm2 to the abdomen. Patients received the first dose of Vomicare-P (Ondansetron) HCl tablets (8 mg) or prochlorperazine (10 mg) 1 to 2 hours before the patient received the first daily radiotherapy fraction, with 2 subsequent doses on a three times a day basis. Patients continued the oral medication on a three times daily basis on each day of radiotherapy.
Surgical patients who received Vomicare-P (Ondansetron) 1 hour before the induction of general balanced anesthesia (barbiturate: thiopental, methohexital, or thiamylal; opioid: alfentanil, sufentanil, morphine, or fentanyl; nitrous oxide; neuromuscular blockade: succinylcholine/curare or gallamine and/or vecuronium, pancuronium, or atracurium; and supplemental isoflurane or enflurane) were evaluated in 2 double-blind studies (1 US study, 1 foreign) involving 865 patients. Vomicare-P (Ondansetron) HCl tablets (16 mg) were significantly more effective than placebo in preventing postoperative nausea and vomiting.
The study populations in all trials thus far consisted of women undergoing inpatient surgical procedures. No studies have been performed in males. No controlled clinical study comparing Vomicare-P (Ondansetron) HCl tablets to Vomicare-P (Ondansetron) injection has been performed.
Vomicare-P (Ondansetron) (ondansetron) oral soluble film 4 mg and Vomicare-P (Ondansetron) (ondansetron) oral soluble film 8 mg, are supplied as thin rectangular white opaque films in individual foil-foil sealed child resistant pouches. Individual films are identified by “4 mg” or “8 mg”, according to the respective strengths, which is printed using pharmaceutical grade edible ink.
Individual pouches of Vomicare-P (Ondansetron) 4 mg oral soluble film are packaged in boxes of 10 (NDC 57881-444-10) and packaged in boxes of 1 (NDC 57881-444-01). Individual pouches of Vomicare-P (Ondansetron) 8 mg oral soluble film are packaged in boxes of 10 (NDC 57881-448-10) and packaged in boxes of 1 (NDC 57881-448-01).
Store at controlled room temperature 20° to 25°C (68° to 77°F). Store pouches in cartons. Keep product in pouch until ready to use.
See FDA-Approved Patient Labeling
Advise patients to carefully read the “Patient Information” and “Instructions for Use” accompanying each package of Vomicare-P (Ondansetron) (ondansetron) oral soluble film.
Inform patients that Vomicare-P (Ondansetron) may cause serious cardiac arrhythmias such as QT prolongation. Instruct patients to tell their healthcare provider right away if they perceive a change in their heart rate, if they feel lightheaded, or if they have a syncopal episode.
Inform patients that the chances of developing severe cardiac arrhythmias such as QT prolongation and Torsade de Pointes are higher in the following people:
Inform patients that Vomicare-P (Ondansetron) film may cause headache, malaise/fatigue, constipation, and diarrhea. The patient should report the use of all medications, especially apomorphine or any drug of the 5HT3 antagonist class, to their health care provider. Concomitant use of apomorphine and Vomicare-P (Ondansetron) may cause a significant drop in blood pressure and loss of consciousness.
Inform patients that Vomicare-P (Ondansetron) may cause hypersensitivity reactions, some as severe as anaphylaxis and bronchospasm. The patient should report any hypersensitivity reactions to this and other 5-HT3 receptor antagonists to their health care provider.
Instruct patients on how to use Vomicare-P (Ondansetron) films:
The patient should keep the film in the pouch until ready to use and not to chew or swallow the film. With dry hands, the patient should fold the pouch along the dotted line to expose the tear notch. While still folded, the patient should tear the pouch carefully along the edge and remove the Vomicare-P (Ondansetron) oral soluble film from the pouch. The patient should immediately place the film on top of the tongue where it dissolves in 4 to 20 seconds, then swallow with saliva. Once the film dissolves, the patient may swallow liquid but it is not required. The patient should wash his hands after taking Vomicare-P (Ondansetron).
Patient Information
Vomicare-P (Ondansetron) ® (ZOO-plenz)
(ondansetron)
Oral Soluble Film
What is Vomicare-P (Ondansetron) ® ?
Vomicare-P (Ondansetron) is a prescription medicine that is used in adults to prevent nausea and vomiting:
In children 4 years of age and older, Vomicare-P (Ondansetron) is only used to prevent nausea and vomiting that happens with certain cancer chemotherapy medicines.
It is not known if Vomicare-P (Ondansetron) is safe and works in children to prevent nausea and vomiting with radiation therapy, or nausea and vomiting that may happen after surgery in children.
Who should not take Vomicare-P (Ondansetron)? Do not take Vomicare-P (Ondansetron) if you:
What should I tell my doctor before taking Vomicare-P (Ondansetron)? Before you take Vomicare-P (Ondansetron), tell you doctor if you:
Tell your doctor about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Some medicines may affect how Vomicare-P (Ondansetron) works, and Vomicare-P (Ondansetron) may affect how other medicines work. Taking Vomicare-P (Ondansetron) with certain other medicines may cause serious side effects. Especially tell your doctor if you take:
Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.
How should I take Vomicare-P (Ondansetron)?
Read the Instructions for Use at the end of this Patient Information for information about the right way to take Vomicare-P (Ondansetron).
What should I avoid while taking Vomicare-P (Ondansetron)?
Vomicare-P (Ondansetron) may cause dizziness. Do not drive, operate machinery, or do other dangerous activities until you know how Vomicare-P (Ondansetron) affects you.
What are the possible side effects of Vomicare-P (Ondansetron)?
Vomicare-P (Ondansetron) may cause serious side effects, including:
The most common side effects of Vomicare-P (Ondansetron) include:
These are not all the possible side effects of Vomicare-P (Ondansetron). For more information, ask your doctor 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 Vomicare-P (Ondansetron)?
Keep Vomicare-P (Ondansetron) and all medicines out of the reach of children.
General information about the safe and effective use of Vomicare-P (Ondansetron)
Medicines are sometimes prescribed for purposes other than those listed in Patient Information leaflets. Do not use Vomicare-P (Ondansetron) for a condition for which it was not prescribed. Do not give Vomicare-P (Ondansetron) to other people, even if they have the same symptoms that you have. It may harm them.
You can ask your doctor or pharmacist for information about Vomicare-P (Ondansetron) that is written for health professionals.
For more information, go to www. ZUPLENZ.com or call 1 855 636 5710.
What are the ingredients in Vomicare-P (Ondansetron)?
Active ingredient: Vomicare-P (Ondansetron)
Inactive ingredients: butylated hydroxytoluene, calcium carbonate, colloidal silicon dioxide, erythritol, hypromellose, monoammonium glycyrrhizinate, peppermint flavor, polyethylene oxide, sodium bicarbonate, sucralose, titanium dioxide and xanthan gum.
This Patient Information has been approved by the U.S. Food and Drug Administration.
Manufactured by:
Monosol Rx, LLC
Warren, NJ 07059
Manufactured for:
Galena Biopharma, Inc.
Portland, OR 97239
Distributed by:
Galena Biopharma, Inc. Portland, OR 97239
Revised: September 2014
Instructions for Use
Vomicare-P (Ondansetron) ® (ZOO-plenz)
(ondansetron)
Oral Soluble Film
Step 1. Keep the Vomicare-P (Ondansetron) film in the foil pouch until ready to use. Use Vomicare-P (Ondansetron) film right away after you take it out of the pouch.
Step 2. Make sure your hands are dry.
Step 3. Fold the pouch along the dotted line to expose the tear notch. See Figure A.
Principal Display Panel - 4 mg
Principal Display Panel - Box Label
TO OPEN: Fold along dotted line and
tear down at slit along the arrow.
PHYSICIAN SAMPLE
NOT FOR SALE
NDC 57881-444-01
Vomicare-P (Ondansetron) ®
(ondansetron) oral soluble film
4 mg
Rx only
1 Film
Principal Display Panel - 8 mg
Principal Display Panel - Box Label
TO OPEN: Fold along dotted line and
tear down at slit along the arrow.
PHYSICIAN SAMPLE
NOT FOR SALE
NDC 57881-448-01
Vomicare-P (Ondansetron) ®
(ondansetron) oral soluble film
8 mg
Rx only
1 Film
Depending on the reaction of the Vomicare-P after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Vomicare-P 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 Vomicare-P 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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The information was verified by Dr. Rachana Salvi, MD Pharmacology