Granisetron Hydrochloride

Pronunciation: gra-NIS-e-tron HYE-droe-KLOR-ide
Class: 5-HT 3 receptor antagonist

Trade Names

Granisetron
- Injection, solution 0.1 mg/mL
- Injection, solution 1 mg/mL
- Tablets, oral 1 mg

Granisol
- Solution, oral 1 mg per 5 mL

Sancuso
- Patch, transdermal 3.1 mg per 24 h (34.3 mg per 52 cm 2 )

Pharmacology

Serotonin receptors of the 5-HT 3 type are located peripherally on vagal nerve terminals, enteric neurons in the GI tract, and centrally in the chemoreceptor trigger zone. During chemotherapy, mucosal enterochromaffin cells from the small intestine release serotonin, which stimulates the 5-HT 3 receptors. This evokes vagal afferent discharge, inducing vomiting.

Slideshow: The Ferocity of Chemotherapy - Does The End Justify The Means?

Pharmacokinetics

Absorption

Mean C max is 64 ng/mL (injection). When tablet is administered with food, AUC decreases 5% and C max increases 30%.

Transdermal

T max is 48 h. C max is 5 ng/mL. Mean AUC 0-168h is 527 ng•h/mL.

Distribution

Vd is about 3 L/kg. Protein binding is 65%.

Metabolism

Involves N-demethylation and aromatic ring oxidation followed by conjugation.

Elimination

Mean half-life is 5 h. Mean Cl is 0.79 L/h/kg. Cl is predominately by hepatic metabolism.

IV

Approximately 12% is excreted unchanged in the urine; the rest is excreted as metabolites (49% in the urine and 34% in the feces).

PO

Approximately 11% is eliminated unchanged in the urine; remainder is excreted as metabolites (48% in the urine and 38% in the feces).

Peak

5 to 30 sec (injection).

Special Populations

Renal Function Impairment

Cl not affected in patients with severe renal failure.

Hepatic Function Impairment

Total Cl decreased by about 50%.

Elderly

Mean values were lower for Cl and longer for half-life.

Gender

Men had a higher C max , but there was no difference in AUC.

Indications and Usage

Injection / PO

Prevention of chemotherapy-induced nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin; prevention of nausea and vomiting associated with radiation, including total body irradiation and fractionated abdominal radiation (oral only).

Transdermal

Prevention of nausea and vomiting in patients receiving moderately and/or highly emetogenic chemotherapy regimens of up to 5 consecutive days' duration.

Unlabeled Uses

Cancer-related pruritus; postanesthetic shivering; uremic pruritus.

Contraindications

Hypersensitivity to any component of the product.

Dosage and Administration

Chemotherapy-Induced Nausea and Vomiting
Adults

IV 10 mcg/kg given up to 30 min before starting chemotherapy. Give only on day(s) of chemotherapy.

PO 1 mg twice daily. Give the first oral dose up to 1 h before chemotherapy and the second dose 12 h later. Give granisetron only on day(s) of chemotherapy. Alternately, a single 2 mg dose may be given up to 1 h before chemotherapy.

Transdermal 1 patch to the upper outer arm a minimum of 24 h before chemotherapy; may be applied up to a max of 48 h before chemotherapy, as appropriate. Remove the patch a minimum of 24 h after completion of chemotherapy. The patch can be worn for up to 7 days, depending on the duration of the chemotherapy regimen.

Children (2 to 16 y of age)

IV 10 mcg/kg given up to 30 min before starting chemotherapy. Give only on day(s) of chemotherapy.

Radiation-Induced Nausea and Vomiting
Adults

PO 2 mg once daily. Give the dose up to 1 h before radiation therapy.

General Advice

  • Injection may be administered IV undiluted over 30 sec, or diluted with sodium chloride 0.9% or dextrose 5% and infused IV over 5 min.
  • Do not mix injection in a solution with other drugs.

Storage/Stability

Store tablets at 68° to 77°F. Store injection, oral solution, and transdermal patch at 59° to 86°F. Diluted solution for infusion may be stored at room temperature for up to 24 h. Multi-use vials should be used within 30 days of penetration. Protect from light.

Drug Interactions

Apomorphine

The risk of profound hypotension and loss of consciousness may be increased. Coadministration is contraindicated.

Drugs that prolong the QT interval (eg, antiarrhythmic agents [eg, amiodarone, bretylium, disopyramide, dofetilide, procainamide, quinidine, sotalol], arsenic trioxide, chlorpromazine, cisapride, dolasetron, droperidol, gatifloxacin, halofantrine, levomethadyl, mefloquine, mesoridazine, moxifloxacin, pentamidine, pimozide, probucol, sparfloxacin, thioridazine, vandetanib, ziprasidone)

The risk of life-threatening cardiac arrhythmias, including torsades de pointes, may be increased. Caution is advised when 2 drugs that are suspected to prolong the QT interval are given concurrently. If coadministration is not contraindicated in the respective product information, monitor patients for QT prolongation, especially when a new drug is added to a stable regimen of another QT-prolonging agent.

Phenobarbital

Hepatic enzyme induction with phenobarbital may increase granisetron total plasma Cl, which would be expected to decrease granisetron plasma concentrations. The clinical relevance of this change is not known.

Adverse Reactions

Cardiovascular

Hypertension (2%); angina pectoris, atrial fibrillation, AV block, ECG abnormalities, hypotension, sinus bradycardia, syncope, ventricular ectopy including nonsustained tachycardia; QT prolongation (postmarketing).

CNS

Headache (21%); asthenia (18%); dizziness, insomnia (5%); anxiety (2%); agitation, CNS stimulation (less than 2%); somnolence (1%).

Dermatologic

Alopecia (3%); rash (1%).

GI

Nausea (20%); constipation (18%); vomiting (12%); diarrhea (9%); abdominal pain, decreased appetite, dyspepsia, elevated ALT (6%); elevated AST (5%); taste disorder (2%).

Hematologic

Leukopenia (9%); anemia (4%); thrombocytopenia (2%).

Hypersensitivity

Hypersensitivity reactions, including anaphylaxis, hypotension, shortness of breath, urticaria (rare).

Miscellaneous

Fever (9%).

Precautions

Pregnancy

Category B .

Lactation

Undetermined.

Children

Safety and efficacy of the injection in children younger than 2 y not established. Safety and efficacy of the oral solution, tablet, and transdermal patch in children not established.

Hypersensitivity

May occur in patients who have exhibited sensitivity to other selective 5-HT 3 receptor antagonists.

Photosensitivity

May occur with the transdermal patch.

Benzyl alcohol

Some formulations of granisetron 1 mg/mL injection may contain benzyl alcohol, which has been associated with “gasping syndrome” in neonates.

Dermatologic effects

If severe reactions or a generalized skin reaction occurs (eg, allergic rash, including erythematous, macular, papular rash, pruritus), the patch should be removed.

GI

May mask a progressive ileus and/or gastric distention.

QT prolongation

Has been reported.

Overdosage

Symptoms

Headache.

Patient Information

  • Advise patient, family, or caregiver that IV medication will be prepared and administered by a health care provider in a medical facility.
  • Review dosing schedule with patients. Caution patients taking oral medication that tablets or solution must be taken no more than 1 h before chemotherapy administration or radiation therapy to provide greatest protection against nausea and vomiting.
  • Advise patients that medication will greatly reduce likelihood of nausea or vomiting, but that these events are still possible.
  • Instruct patients to inform their health care provider if medication does not prevent nausea or vomiting.
  • Advise patients to report any of the following to their health care provider: intolerable headache, persistent or intolerable constipation or diarrhea, persistent weakness.
  • Advise patients that if severe or generalized skin reactions occur when using the transdermal patch, to remove the patch.
  • Advise patients to cover the patch application site with clothing if there is a risk of exposure to sunlight during the period of wear and for 10 days following its removal.
  • Advise patients of the risk of allergic reactions if they have had a prior allergic reaction to a class of antiemetics known as 5-HT 3 receptor antagonists.
  • Advise patients that the use of granisetron may mask a progressive ileus and/or gastric distension caused by the underlying condition; instruct patients to tell their health care provider if they have pain or swelling in their abdomen.
  • Inform patients that ECG changes (QT prolongation) have been reported with the use of granisetron. Caution patients about the use of this drug if they have heart problems or take medications for heart problems.

Copyright © 2009 Wolters Kluwer Health.

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