Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/46
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| dailymed-drugs:46 | rdf:type | http://www4.wiwiss.fu-berli... | lld:dailymed |
| dailymed-drugs:46 | rdf:type | dailymed-instance:drugs | lld:dailymed |
| dailymed-drugs:46 | rdfs:label | Granisetron Hydrochloride (Tablet, Film Coated) | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:dosage | Emetogenic Chemotherapy: The recommended adult dosage of oral granisetron hydrochloride tablets is 2 mg once daily or 1 mg twice daily. In the 2 mg once-daily regimen, two 1 mg tablets are given up to 1 hour before chemotherapy. In the 1 mg twice-daily regimen, the first 1 mg tablet is given up to 1 hour before chemotherapy, and the second tablet, 12 hours after the first. Either regimen is administered only on the day(s) chemotherapy is given. Continued treatment, while not on chemotherapy, has not been found to be useful.<br/>Use in the Elderly, Pediatric Patients, Renal Failure Patients or Hepatically Impaired Patients: No dosage adjustment is recommended (see CLINICAL PHARMACOLOGY, Pharmacokinetics).<br/>Radiation (Either Total Body Irradiation or Fractionated Abdominal Radiation): The recommended adult dosage of oral granisetron hydrochloride tablets is 2 mg once daily. Two 1 mg tablets are taken within 1 hour of radiation.<br/>Pediatric Use: There is no experience with oral granisetron hydrochloride tablets in the prevention of radiation-induced nausea and vomiting in pediatric patients.<br/>Use in the Elderly: No dosage adjustment is recommended. | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:descripti... | Granisetron hydrochloride tablets contain granisetron hydrochloride, an antinauseant and antiemetic agent. Chemically it is endo-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1-methyl-1H-indazole-3-carboxamide hydrochloride. CHNO���HCl M.W. 348.9 (312.4 free base) Granisetron hydrochloride is a white to off-white crystalline powder that is freely soluble in water and slightly soluble in methanol.<br/>Tablets for Oral Administration: Each white to off-white, film-coated, capsule-shaped, granisetron hydrochloride tablet contains 1.12 mg granisetron hydrochloride equivalent to granisetron, 1 mg. Inactive ingredients are: hypromellose, lactose monohydrate, macrogol, magnesium stearate, microcrystalline cellulose, polysorbate 80, sodium starch glycolate, and titanium dioxide. | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:clinicalP... | Granisetron 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-HTtype are located peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. During chemotherapy that induces vomiting, mucosal enterochromaffin cells release serotonin, which stimulates 5-HTreceptors. This evokes vagal afferent discharge, inducing vomiting. Animal studies demonstrate that, in binding to 5-HTreceptors, granisetron blocks serotonin stimulation and subsequent vomiting after emetogenic stimuli such as cisplatin. In the ferret animal model, a single granisetron injection prevented vomiting due to high-dose cisplatin or arrested vomiting within 5 to 30 seconds. In most human studies, granisetron 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. Following single and multiple oral doses, granisetron hydrochloride tablets slowed colonic transit in normal volunteers. However, granisetron hydrochloride had no effect on oro-cecal transit time in normal volunteers when given as a single intravenous (IV) infusion of 50 mcg/kg or 200 mcg/kg.<br/>Pharmacokinetics: In healthy volunteers and adult cancer patients undergoing chemotherapy, administration of granisetron hydrochloride tablets produced mean pharmacokinetic data shown in Table 1.<br/>Absorption: When granisetron tablets were administered with food, AUC was decreased by 5% and Cincreased by 30% in non-fasted healthy volunteers who received a single dose of 10 mg.<br/>Distribution: Plasma protein binding is approximately 65% and granisetron distributes freely between plasma and red blood cells.<br/>Metabolism: Granisetron metabolism involves N-demethylation and aromatic ring oxidation followed by conjugation. In vitro liver microsomal studies show that granisetron's major route of metabolism is inhibited by ketoconazole, suggestive of metabolism mediated by the cytochrome P-450 3A subfamily. Animal studies suggest that some of the metabolites may also have 5-HTreceptor antagonist activity.<br/>Elimination: Clearance is predominantly by hepatic metabolism. In normal volunteers, approximately 11% of the orally administered dose is eliminated unchanged in the urine in 48 hours. The remainder of the dose is excreted as metabolites, 48% in the urine and 38% in the feces.<br/>Subpopulations: | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:activeIng... | dailymed-ingredient:Granise... | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:contraind... | Granisetron hydrochloride tablets are contraindicated in patients with known hypersensitivity to the drug or any of its components. | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:supply | Granisetron hydrochloride tablets are available as: 1 mg, white to off-white, film-coated, capsule-shaped tablet, debossed with the number���93���on one side and���7485���on the other. They are available in blister cards of 2 (1 card of 2 unit dose tablets) and blister cards of 20 (4 cards of 5 unit dose tablets each). Store at 20��to 25��C (68��to 77��F) [See USP Controlled Room Temperature]. Keep container closed tightly. Protect from light. Manufactured In Israel By: TEVA PHARMACEUTICAL IND. LTD. Jerusalem, 91010, Israel Manufactured For: TEVA PHARMACEUTICALS USA Sellersville, PA 18960 Rev. A 10/2007 | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:activeMoi... | dailymed-ingredient:Granise... | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:inactiveI... | dailymed-ingredient:magnesi... | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:inactiveI... | dailymed-ingredient:microcr... | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:inactiveI... | dailymed-ingredient:hyprome... | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:inactiveI... | dailymed-ingredient:polysor... | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:inactiveI... | dailymed-ingredient:sodium_... | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:inactiveI... | dailymed-ingredient:titaniu... | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:inactiveI... | dailymed-ingredient:lactose... | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:inactiveI... | dailymed-ingredient:macrogo... | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:precautio... | Granisetron is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction. The use of granisetron in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distention.<br/>Drug Interactions: Granisetron does not induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system in vitro. There have been no definitive drug-drug interaction studies to examine pharmacokinetic or pharmacodynamic interaction with other drugs; however, in humans, granisetron hydrochloride injection has been safely administered with drugs representing benzodiazepines, neuroleptics, and anti-ulcer medications commonly prescribed with antiemetic treatments. Granisetron hydrochloride injection also does not appear to interact with emetogenic cancer chemotherapies. Because granisetron 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. 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 in vitro. In in vitro human microsomal studies, ketoconazole inhibited ring oxidation of granisetron. However, the clinical significance of in vivo 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. The clinical significance of this change is not known.<br/>Carcinogenesis, Mutagenesis, Impairment of Fertility: In a 24 month carcinogenicity study, rats were treated orally with granisetron 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 mbody surface area), these doses represent 4, 20, and 101 times the recommended clinical dose (1.48 mg/m, oral) 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, 20 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, 101 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, 4 times the recommended human dose based on body surface area) in males and 5 mg/kg/day (30 mg/m/day, 20 times the recommended human dose based on body surface area) in females. In a 12 month oral toxicity study, treatment with granisetron 100 mg/kg/day (600 mg/m/day, 405 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 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 hydrochloride should be prescribed only at the dose and for the indication recommended (see INDICATIONS AND USAGE and DOSAGE AND ADMINISTRATION). Granisetron was not mutagenic in in vitro Ames test and mouse lymphoma cell forward mutation assay, and in vivo mouse micronucleus test and in vitro and ex vivo rat hepatocyte UDS assays. It, however, produced a significant increase in UDS in HeLa cells in vitro and a significant increased incidence of cells with polyploidy in an in vitro human lymphocyte chromosomal aberration test. Granisetron at oral doses up to 100 mg/kg/day (600 mg/m/day, 405 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.<br/>Pregnancy:<br/>Teratogenic Effects:<br/>Nursing Mothers: It is not known whether granisetron is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when granisetron hydrochloride is administered to a nursing woman.<br/>Pediatric Use: Safety and effectiveness in pediatric patients have not been established.<br/>Geriatric Use: During clinical trials, 325 patients 65 years of age or older received granisetron hydrochloride tablets; 298 were 65 to 74 years of age, and 27 were 75 years of age or older. Efficacy and safety were maintained with increasing age. | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:overdosag... | There is no specific treatment for granisetron hydrochloride overdosage. In case of overdosage, symptomatic treatment should be given. Overdosage of up to 38.5 mg of granisetron hydrochloride injection has been reported without symptoms or only the occurrence of a slight headache. | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:genericMe... | Granisetron Hydrochloride | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:fullName | Granisetron Hydrochloride (Tablet, Film Coated) | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:adverseRe... | Chemotherapy-Induced Nausea and Vomiting: Over 3700 patients have received granisetron hydrochloride tablets in clinical trials with emetogenic cancer therapies consisting primarily of cyclophosphamide or cisplatin regimens. In patients receiving granisetron hydrochloride tablets 1 mg bid for 1, 7 or 14 days, or 2 mg qd for 1 day, adverse experiences reported in more than 5% of the patients with comparator and placebo incidences are listed in Table 4. Other adverse events reported in clinical trials were: Gastrointestinal: In single-day dosing studies in which adverse events were collected for 7 days, nausea (20%) and vomiting (12%) were recorded as adverse events after the 24 hour efficacy assessment period. Hepatic: In comparative trials, elevation of AST and ALT (>2 times the upper limit of normal) following the administration of granisetron hydrochloride tablets occurred in 5% and 6% of patients, respectively. These frequencies were not significantly different from those seen with comparators (AST: 2%; ALT: 9%). Cardiovascular: Hypertension (1%); hypotension, angina pectoris, atrial fibrillation, and syncope have been observed rarely. Central Nervous System: Dizziness (5%), insomnia (5%), anxiety (2%), somnolence (1%). One case compatible with, but not diagnostic of, extrapyramidal symptoms has been reported in a patient treated with granisetron hydrochloride tablets. Hypersensitivity: Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylaxis, shortness of breath, hypotension, urticaria) have been reported. Other: Fever (5%). Events often associated with chemotherapy also have been reported: leukopenia (9%), decreased appetite (6%), anemia (4%), alopecia (3%), thrombocytopenia (2%). Over 5000 patients have received injectable granisetron hydrochloride in clinical trials. Table 5 gives the comparative frequencies of the five commonly reported adverse events (���3%) in patients receiving granisetron hydrochloride injection, 40 mcg/kg, in single-day chemotherapy trials. These patients received chemotherapy, primarily cisplatin, and intravenous fluids during the 24 hour period following granisetron hydrochloride injection administration. In the absence of a placebo group, there is uncertainty as to how many of these events should be attributed to granisetron hydrochloride, except for headache, which was clearly more frequent than in comparison groups.<br/>Radiation-Induced Nausea and Vomiting: In controlled clinical trials, the adverse events reported by patients receiving granisetron hydrochloride tablets and concurrent radiation were similar to those reported by patients receiving granisetron hydrochloride tablets prior to chemotherapy. The most frequently reported adverse events were diarrhea, asthenia and constipation. Headache, however, was less prevalent in this patient population. | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:indicatio... | Granisetron hydrochloride tablets are indicated for the prevention of: | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:represent... | http://www4.wiwiss.fu-berli... | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:routeOfAd... | http://www4.wiwiss.fu-berli... | lld:dailymed |
| dailymed-drugs:46 | dailymed-instance:name | Granisetron Hydrochloride | lld:dailymed |
| http://www4.wiwiss.fu-berli... | dailymed-instance:producesD... | dailymed-drugs:46 | lld:dailymed |