Granisetron Information
Granisetron (Granisetron hydrochloride)
Granisetron (Granisetron hydrochloride) Description
Granisetron (Granisetron hydrochloride) Hydrochloride Injection is an antinauseant and antiemetic agent. Chemically it is -N-(9-methyl-9-azabicyclo [3.3.1] non-3-yl)-1-methyl-1H-indazole-3-carboxamide hydrochloride. Its chemical structure is:
Granisetron (Granisetron hydrochloride) hydrochloride
Granisetron (Granisetron hydrochloride) hydrochloride is a white to off-white solid that is readily soluble in water and normal saline at 20°C. Granisetron (Granisetron hydrochloride) hydrochloride injection is a clear, colorless, sterile, nonpyrogenic, aqueous solution for intravenous administration.
Granisetron (Granisetron hydrochloride) hydrochloride injection 0.1 mg/1 mL is available in a 1 mL single-use vial. Granisetron (Granisetron hydrochloride) hydrochloride injection 1 mg/1mL is available in 1 mL single-use and 4 mL multi-use vials.
0.1 mg/1 mL (preservative-free): Each 1 mL contains 0.112 mg Granisetron (Granisetron hydrochloride) hydrochloride equivalent to Granisetron (Granisetron hydrochloride) , 0.1 mg; sodium chloride, 9 mg; citric acid, monohydrate 0.67 mg (equivalent to 0.61 mg citric acid); sodium citrate dihydrate, 2.12 mg (equivalent to 1.86 mg sodium citrate) and Water for Injection, USP, q.s. The solution’s pH ranges from 4.0 to 6.0.
1 mg/1 mL (preservative-free): Each 1 mL contains 1.12 mg Granisetron (Granisetron hydrochloride) hydrochloride equivalent to Granisetron (Granisetron hydrochloride) , 1 mg; sodium chloride, 9 mg; citric acid, monohydrate 0.67 mg (equivalent to 0.61 mg citric acid); sodium citrate dihydrate, 2.12 mg (equivalent to 1.86 mg sodium citrate); and Water for Injection, USP, q.s. The solution’s pH ranges from 4.0 to 6.0.
1 mg/1mL (preserved): Each mL contains 1.12 mg Granisetron (Granisetron hydrochloride) hydrochloride equivalent to Granisetron (Granisetron hydrochloride) , 1 mg; sodium chloride, 9 mg; citric acid, monohydrate 0.67 mg (equivalent to 0.61 mg citric acid); sodium citrate dihydrate, 2.12 mg (equivalent to 1.86 mg sodium citrate); phenol, 5 mg, as a preservative, and Water for Injection, USP q.s. The solution pH ranges from 4.0 to 6.0.
Granisetron (Granisetron hydrochloride) Clinical Pharmacology
Granisetron (Granisetron hydrochloride) is a selective 5-hydroxytryptamine (5-HT) receptor antagonist with little or no affinity for other serotonin receptors, including 5-HT; 5-HT; 5-HT; 5-HT; for alpha, alpha or beta-adrenoreceptors; for dopamine-D; or for histamine-H; benzodiazepine; picrotoxin or opioid receptors.
Serotonin receptors of the 5-HT type are located peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. During chemotherapy-induced vomiting, mucosal enterochromaffin cells release serotonin, which stimulates 5-HTreceptors. This evokes vagal afferent discharge and may induce vomiting. Animal studies demonstrate that, in binding to 5-HT receptors, Granisetron (Granisetron hydrochloride) blocks serotonin stimulation and subsequent vomiting after emetogenic stimuli such as cisplatin. In the ferret animal model, a single Granisetron (Granisetron hydrochloride) injection prevented vomiting due to high-dose cisplatin or arrested vomiting within 5 to 30 seconds.
In most human studies, Granisetron (Granisetron hydrochloride) has had little effect on blood pressure, heart rate or ECG. No evidence of an effect on plasma prolactin or aldosterone concentrations has been found in other studies.
Granisetron (Granisetron hydrochloride) hydrochloride injection exhibited no effect on oro-cecal transit time in normal volunteers given a single intravenous infusion of 50 mcg/kg or 200 mcg/kg. Single and multiple oral doses slowed colonic transit in normal volunteers.
Granisetron (Granisetron hydrochloride) Indications And Usage
Granisetron (Granisetron hydrochloride) hydrochloride injection is indicated for:
• The prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin.
Granisetron (Granisetron hydrochloride) Contraindications
Granisetron (Granisetron hydrochloride) hydrochloride injection is contraindicated in patients with known hypersensitivity to the drug or to any of its components.
Granisetron (Granisetron hydrochloride) Warnings
Hypersensitivity reactions may occur in patients who have exhibited hypersensitivity to other selective 5-HTreceptor antagonists.
Granisetron (Granisetron hydrochloride) Precautions
Granisetron (Granisetron hydrochloride) hydrochloride is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction. The use of Granisetron (Granisetron hydrochloride) hydrochloride in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distention.
Granisetron (Granisetron hydrochloride) does not induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system . There have been no definitive drug-drug interaction studies to examine pharmacokinetic or pharmacodynamic interaction with other drugs; but in humans, Granisetron (Granisetron hydrochloride) hydrochloride injection has been safely administered with drugs representing benzodiazepines, neuroleptics and anti-ulcer medications commonly prescribed with antiemetic treatments. Granisetron (Granisetron hydrochloride) hydrochloride injection also does not appear to interact with emetogenic cancer chemotherapies. Because Granisetron (Granisetron hydrochloride) is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes, inducers or inhibitors of these enzymes may change the clearance and, hence, the half-life of Granisetron (Granisetron hydrochloride) . No specific interaction studies have been conducted in anesthetized patients. In addition, the activity of the cytochrome P-450 subfamily 3A4 (involved in the metabolism of some of the main narcotic analgesic agents) is not modified by Granisetron (Granisetron hydrochloride) hydrochloride .
In human microsomal studies, ketoconazole inhibited ring oxidation of Granisetron (Granisetron hydrochloride) hydrochloride. However, the clinical significance of pharmacokinetic interactions with ketoconazole is not known. In a human pharmacokinetic study, hepatic enzyme induction with phenobarbital resulted in a 25% increase in total plasma clearance of intravenous Granisetron (Granisetron hydrochloride) hydrochloride. The clinical significance of this change is not known.
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In a 24-month carcinogenicity study, rats were treated orally with Granisetron (Granisetron hydrochloride) 1, 5 or 50 mg/kg/day (6, 30 or 300 mg/m/day). The 50 mg/kg/day dose was reduced to 25 mg/kg/day (150 mg/m/day) during week 59 due to toxicity. For a 50 kg person of average height (1.46 m body surface area), these doses represent 16, 81 and 405 times the recommended clinical dose (0.37 mg/m, IV) on a body surface area basis. There was a statistically significant increase in the incidence of hepatocellular carcinomas and adenomas in males treated with 5 mg/kg/day (30 mg/m/day, 81 times the recommended human dose based on body surface area) and above, and in females treated with 25 mg/kg/day (150 mg/m/day, 405 times the recommended human dose based on body surface area). No increase in liver tumors was observed at a dose of 1 mg/kg/day (6 mg/m/day, 16 times the recommended human dose based on body surface area) in males and 5 mg/kg/day (30 mg/m/day, 81 times the recommended human dose based on body surface area) in females. In a 12-month oral toxicity study, treatment with Granisetron (Granisetron hydrochloride) 100 mg/kg/day (600 mg/m/day, 1622 times the recommended human dose based on body surface area) produced hepatocellular adenomas in male and female rats while no such tumors were found in the control rats. A 24-month mouse carcinogenicity study of Granisetron (Granisetron hydrochloride) did not show a statistically significant increase in tumor incidence, but the study was not conclusive.
Because of the tumor findings in rat studies, Granisetron (Granisetron hydrochloride) hydrochloride injection should be prescribed only at the dose and for the indication recommended (see and ).
Granisetron (Granisetron hydrochloride) was not mutagenic in an Ames test and mouse lymphoma cell forward mutation assay, and mouse micronucleus test and and rat hepatocyte UDS assays. It, however, produced a significant increase in UDS in HeLa cells and a significant increased incidence of cells with polyploidy in an human lymphocyte chromosomal aberration test.
Granisetron (Granisetron hydrochloride) at subcutaneous doses up to 6 mg/kg/day (36 mg/m/day, 97 times the recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.
Reproduction studies have been performed in pregnant rats at intravenous doses up to 9 mg/kg/day (54 mg/m/day, 146 times the recommended human dose based on body surface area) and pregnant rabbits at intravenous doses up to 3 mg/kg/day (35.4 mg/m/day, 96 times the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to Granisetron (Granisetron hydrochloride) . There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Granisetron (Granisetron hydrochloride) Overdosage
There is no specific antidote for Granisetron (Granisetron hydrochloride) hydrochloride injection overdosage. In case of overdosage, symptomatic treatment should be given. Overdosage of up to 38.5 mg of Granisetron (Granisetron hydrochloride) hydrochloride injection has been reported without symptoms or only the occurrence of a slight headache.
Granisetron (Granisetron hydrochloride) Dosage And Administration
The recommended dosage for Granisetron (Granisetron hydrochloride) hydrochloride injection is 10 mcg/kg administered intravenously within 30 minutes before initiation of chemotherapy, and only on the day(s) chemotherapy is given.
Granisetron (Granisetron hydrochloride) hydrochloride injection may be administered intravenously either undiluted over 30 seconds, or diluted with 0.9% Sodium Chloride or 5% Dextrose and infused over 5 minutes.
Intravenous infusion of Granisetron (Granisetron hydrochloride) hydrochloride injection should be prepared at the time of administration. However, Granisetron (Granisetron hydrochloride) hydrochloride injection has been shown to be stable for at least 24 hours when diluted in 0.9% Sodium Chloride or 5% Dextrose and stored at room temperature under normal lighting conditions.
As a general precaution, Granisetron (Granisetron hydrochloride) hydrochloride injection should not be mixed in solution with other drugs. Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.
Granisetron (Granisetron hydrochloride) How Supplied
Granisetron (Granisetron hydrochloride) Hydrochloride Injection, 0.1 mg/mL (free base), is supplied in 1 mL single-use vials. CONTAINS NO PRESERVATIVE.
Granisetron (Granisetron hydrochloride) Hydrochloride Injection, 1 mg/mL (free base), is supplied in 1 mL single-use vials. CONTAINS NO PRESERVATIVE.
Granisetron (Granisetron hydrochloride) Hydrochloride Injection, 1 mg/mL (free base) is supplied in 4 mL multi-use vials. CONTAINS PRESERVATIVE.
Granisetron (Granisetron hydrochloride)
Granisetron (Granisetron hydrochloride)
