Granisetron (Monograph)

Brand name: Kytril
Drug class: 5-HT3 Receptor Antagonists
Chemical name: endo-1-Methyl-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-1H-indazole-3-carboxamide monohydrochloride
Molecular formula: C₁₈H₂₄N₄O•ClH
CAS number: 107007-99-8

Medically reviewed by Drugs.com on Nov 27, 2023. Written by ASHP.

Introduction

Antiemetic; selective inhibitor of type 3 serotonergic (5-HT₃) receptors.

Uses for Granisetron

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic cancer chemotherapy, including high-dose cisplatin.

For prevention of nausea and vomiting associated with highly emetogenic chemotherapy regimens (including an anthracycline plus cyclophosphamide), ASCO recommends a 3-drug antiemetic regimen consisting of an NK₁ receptor antagonist (e.g., either oral aprepitant or IV fosaprepitant), a 5-HT₃ receptor antagonist (e.g., dolasetron, granisetron, ondansetron, palonosetron), and dexamethasone. ASCO states that fixed-combination netupitant and palonosetron plus dexamethasone is an additional treatment option.

For moderately emetogenic chemotherapy regimens, ASCO recommends a 2-drug antiemetic regimen preferably consisting of palonosetron and dexamethasone. If palonosetron is not available, a first-generation 5-HT₃ receptor antagonist (preferably granisetron or ondansetron) may be substituted. Limited evidence suggests that aprepitant may be added to this regimen; in such cases, use of any 5-HT₃ receptor antagonist is appropriate.

For chemotherapy regimens with a low emetogenic risk, ASCO recommends administration of a single dose of dexamethasone prior to chemotherapy.

For chemotherapy regimens with minimal emetogenic risk, ASCO states that routine antiemetic administration is not necessary.

Postoperative Nausea and Vomiting

Prevention and treatment of postoperative nausea and vomiting.

Routine prophylaxis not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively.

Recommended for patients who, in the clinician’s judgment, must avoid nausea and/or vomiting postoperatively, even when anticipated incidence is low.

Radiation-induced Nausea and Vomiting

Prevention of nausea and vomiting associated with radiation, including total body irradiation and daily fractionated abdominal radiation.

Granisetron Dosage and Administration

Administration

Administer orally, by IV infusion, or by direct IV injection.

Oral Administration

May use oral solution and tablets interchangeably.

For prevention of nausea and vomiting associated with chemotherapy, administer once or twice daily. Administer only on days when emetogenic chemotherapy is administered.

For prevention of radiation-induced nausea and vomiting, administer within 1 hour of radiation.

IV Administration

For solution and drug compatibility information, see Compatibility under Stability.

For prevention of nausea and vomiting associated with chemotherapy, administer approximately 30 minutes before administration of emetogenic drug, only on days when emetogenic chemotherapy is administered.

For prevention of postoperative nausea and vomiting, administer before induction of or immediately before reversal of anesthesia.

Dilution

IV infusion: Dilute in 5% dextrose or 0.9% sodium chloride injection to a total volume of 20–50 mL.

Rate of Administration

Direct IV injection: Administer undiluted over 30 seconds.

IV infusion: Infuse over 5 minutes.

Dosage

Available as granisetron hydrochloride; dosage expressed in terms of granisetron.

Pediatric Patients

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention

IV

Children 2–16 years of age: 10 mcg/kg by IV infusion or direct IV injection within 30 minutes before administration of chemotherapy.

Adults

Cancer Chemotherapy-induced Nausea and Vomiting

Prevention

Oral

2 mg once daily up to 1 hour before administration of chemotherapy.

Alternatively, 1 mg twice daily (first dose up to 1 hour before chemotherapy and second dose 12 hours after first dose).

IV

10 mcg/kg by IV infusion or direct IV injection within 30 minutes before administration of chemotherapy.

Postoperative Nausea and Vomiting

Prevention

IV

1 mg as a single dose by direct IV injection before induction of or immediately before reversal of anesthesia.

Treatment

IV

1 mg as a single dose by direct IV injection.

Radiation-induced Nausea and Vomiting

Prevention

Oral

2 mg once daily within 1 hour of radiation.

Special Populations

Hepatic Impairment

No dosage adjustment required.

Geriatric Patients

No dosage adjustment required.

Cautions for Granisetron

Contraindications

• Known hypersensitivity to granisetron or any ingredient in the formulation.

Warnings/Precautions

Sensitivity Reactions

Hypersensitivity reactions, including anaphylactic reaction, shortness of breath, hypotension, and urticaria, reported rarely.

Possible hypersensitivity reactions in patients who have exhibited hypersensitivity to other selective 5-HT₃ receptor antagonists.

General Precautions

GI Precautions

Does not stimulate gastric or intestinal peristalsis; do not use as a substitute for nasogastric suction.

May mask progressive ileus and/or gastric distention when used in patients undergoing abdominal surgery or in those with chemotherapy-induced nausea and vomiting.

Specific Populations

Pregnancy

Category B.

Lactation

Not known whether granisetron is distributed into milk. Caution advised if used in nursing women.

Pediatric Use

Safety and efficacy of IV granisetron for chemotherapy-induced nausea and vomiting not established in children <2 years of age; safety and efficacy of IV granisetron for prevention and treatment of postoperative nausea and vomiting not established in children of any age.

Safety and efficacy of oral granisetron not established in children of any age.

Geriatric Use

No substantial differences in safety and efficacy for chemotherapy-induced nausea and vomiting in geriatric patients relative to younger adults.

Insufficient experience with IV granisetron for postoperative nausea and vomiting in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.

Common Adverse Effects

Headache, constipation, pain, diarrhea, fever, abdominal pain, increased hepatic enzymes, asthenia, dyspepsia.

Drug Interactions

Apparently metabolized by CYP3A; does not induce or inhibit CYP isoenzymes.

Drugs Affecting Hepatic Microsomal Enzymes

Potential pharmacokinetic interaction (altered granisetron clearance and half-life) with inhibitors or inducers of CYP isoenzymes.

Specific Drugs

Granisetron Pharmacokinetics

Absorption

Bioavailability

Dose of oral solution is bioequivalent to corresponding dose of oral tablets.

Food

Food has minimal effect on extent of absorption; may increase peak plasma concentration by 30%.

Distribution

Extent

Distributes freely between plasma and red blood cells. Not known whether granisetron distributed into milk.

Plasma Protein Binding

Approximately 65%.

Elimination

Metabolism

Metabolized via N-demethylation and aromatic ring oxidation followed by conjugation; metabolism appears to be mediated by CYP3A subfamily.

Elimination Route

Excreted in urine as unchanged drug (11–12%) and metabolites (48–49%) and in feces as metabolites (34–38%).

Half-life

IV administration: Terminal half-life is approximately 9 hours in adult cancer patients or adults undergoing surgery.

Oral administration: Terminal half-life is approximately 6.2 hours in healthy adults.

Special Populations

In pediatric cancer patients, pharmacokinetic profile is similar to that in adult cancer patients.

In geriatric patients, mean clearance may be decreased and half-life increased compared with younger adults.

In patients with hepatic impairment due to neoplastic liver involvement, total clearance following a single IV dose is reduced by approximately 50% compared with patients without hepatic impairment.

In patients with severe renal impairment, total clearance following a single 40-mcg/kg IV dose is not altered.

Stability

Storage

Oral

Tablets

Tight container at 15–30°C; protect from light.

Solution

Tight container at 25°C (may be exposed to 15–30°C). Store in upright position; protect from light.

Parenteral

Injection

25°C (may be exposed to 15–30°C). Do not freeze; protect from light. Once multiple-dose vial is penetrated, use contents within 30 days.

Following dilution with sodium chloride 0.9% or dextrose 5% injection, stable for at least 24 hours at room temperature under normal lighting conditions.

Compatibility

Parenteral

Solution Compatibility

Drug Compatibility

Actions

• Antiemetic activity appears to be mediated both centrally (in medullary chemoreceptor trigger zone) and peripherally (in GI tract) via inhibition of 5-HT₃ receptors.

Advice to Patients

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

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