Active ingredient: Granisetron - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

• Antiemetics
• Serotonin Antagonists

Dosage Forms

• Liquid
• Tablet

Brands / Synonyms

Granisetron base; Granisetron HCl; Granisetron hydrochloride; Granisetron hydrochloride and intermediates; Granisetron [USAN:BAN:INN]; Granisetronum [INN-Latin]; Kytril; Kytril ; Kytril Injection

Indications

For the prevention of: nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin.

Pharmacology

Not Available

Mechanism of Action

Granisetron is a potent, selective antagonist of 5-hydroxytryptamine (serotonin) subtype 3 (5-HT 3) receptors. 5-HT 3 receptors are present peripherally on vagal nerve terminals and centrally in the area postrema of the brain. Cytotoxic drugs and radiation damage gastrointestinal mucosa, causing the release of serotonin from the enterochromaffin cells of the gastrointestinal tract. Stimulation of 5-HT 3 receptors causes transmission of sensory signals to the vomiting center via vagal afferent fibers to induce vomiting. By binding to 5-HT 3 receptors, granisetron blocks vomiting mediated by serotonin release. 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).

Absorption

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

Toxicity

LD₅₀>2000 mg/kg (rat, oral)

Biotrnasformation / Drug 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.

Contraindications

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

Drug Interactions

Not Available