GRANI DENK

A serotonin receptor (5HT-3 selective) antagonist that has been used as an antiemetic and antinauseant for cancer chemotherapy patients.

For the prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy (including high dose cisplatin), postoperation, and radiation (including total body irradiation and daily fractionated abdominal radiation).

Granisetron is a selective inhibitor of type 3 serotonergic (5-HT 3 ) receptors.

Granisetron has little or no affinity for other serotonin receptors, including 5-HT 1, 5-HT 1A, 5-HT 1B/C, or 5-HT 2; for alpha 1 -, alpha 2 -, or beta-adrenoreceptors; for dopamine D 2 receptors; for histamine H 1 receptors; for benzodiazepine receptors; for picrotoxin receptors; or for opioid receptors.

In most human studies, granisetron has had little effect on blood pressure, heart rate, or electrocardiogram (ECG).

The drug is structurally and pharmacologically related to ondansetron, another selective inhibitor of 5-HT 3 receptors.

The serontonin 5-HT 3 receptors are located on the nerve terminals of the vagus in the periphery, and centrally in the chemoreceptor trigger zone of the area postrema.

The temporal relationship between the emetogenic action of emetogenic drugs and the release of serotonin, as well as the efficacy of antiemetic agents suggest that chemotherapeutic agents release serotonin from the enterochromaffin cells of the small intestine by causing degenerative changes in the GI tract.

The serotonin then stimulates the vagal and splanchnic nerve receptors that project to the medullary vomiting center, as well as the 5-HT3 receptors in the area postrema, thus initiating the vomiting reflex, causing nausea and vomiting.

5-hydroxytryptamine receptor 3A Antagonist.

of is rapid and complete, though oral bioavailability is reduced to about 60% as a result of first pass metabolism.

Primarily hepatic; undergoes N -demethylation and aromatic ring oxidation followed by conjugation.

Animal studies suggest that some of the metabolites may have 5-HT 3 receptor antagonist activity.

Hover over products below to view reaction partners Granisetron 9'-desmethylgranisetron 7-hydroxygranisetron.

The remainder of the dose is excreted as metabolites, 48% in the urine and 38% in the feces.

4-6 hours in healthy patients, 9-12 hours in cancer patients.

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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.

The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists alone but particularly 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 another 5-HT3 receptor antagonist 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 mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).

Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of granisetron and other serotonergic drugs.

If symptoms of serotonin syndrome occur, discontinue granisetron and initiate supportive treatment.

Patients should be informed of the increased risk of serotonin syndrome, especially if granisetron is used concomitantly with other serotonergic drugs.

Granisetron is contraindicated in patients with known hypersensitivity to the drug or any of its components.

The recommended adult dosage of oral granisetron hydrochloride is 2 mg once daily or 1 mg twice daily.

In the 2 mg once-daily regimen, 10 mL of GRANISOL oral solution (2 teaspoonfuls, equivalent to 2 mg of granisetron) are given up to 1 hour before chemotherapy.

In the 1 mg twice-daily regimen, the first teaspoonful (5 mL) of GRANISOL oral solution is given up to 1 hour before chemotherapy, and the second teaspoonful (5 mL) of GRANISOL oral solution, 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.

Use in the

Elderly, Renal Failure Patients or Hepatically Impaired Patients No dosage adjustment is recommended.

Safety and effectiveness in pediatric patients have not been established.

Radiation (Either Total Body Irradiation or Fractionated Abdominal Radiation) The recommended adult dosage of oral granisetron hydrochloride is 2 mg once daily.

Ten milliliters of

GRANISOL oral solution (2 teaspoonfuls, equivalent to 2 mg of granisetron) are taken within 1 hour of radiation.

No dosage adjustment is recommended.

Clear, orange-colored, orange-flavored, 2 mg/10 mL, in 30 mL amber glass bottles with child-resistant closures: NDC 80056-801-30 Storage Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). .

Keep bottle closed tightly and stored in an upright position.

Protect from light.

Vegas, NV 89113.

Reproduction studies have been performed in pregnant rats at oral doses up to 125 mg/kg/day (750 mg/m 2 /day, 507 times the recommended human dose based on body surface area) and pregnant rabbits at oral doses up to 32 mg/kg/day (378 mg/m 2 /day, 255 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.

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.

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 is administered to a nursing woman.

Safety and effectiveness in pediatric patients have not been established.

During clinical trials, 325 patients 65 years of age or older received Kytril tablets; 298 were to 74 years of age, and were 75 years of age or older.

Efficacy and safety were maintained with increasing age.