No

Selective 5-HT₃ Receptor Antagonist

Prophylaxis and treatment of chemotherapy-related emesis; may be prescribed for patients who are refractory to or have severe adverse reactions to standard antiemetic therapy. Granisetron may be prescribed for young patients (ie, <45 years of age who are more likely to develop extrapyramidal reactions to high-dose metoclopramide) who are to receive highly emetogenic chemotherapeutic agents as listed:

Amifostine

Azacitidine

Carmustine greater than or equal to 200 mg/m²

Cisplatin greater than or equal to 50 mg/m²

Cyclophosphamide greater than or equal to 1 g/m²

Cytarabine greater than or equal to 1500 mg/m²

Dacarbazine greater than or equal to 500 mg/m²

Dactinomycin

Doxorubicin greater than or equal to 60 mg/m²

Lomustine greater than or equal to 60 mg/m²

Mechlorethamine

Melphalan greater than or equal to 100 mg/m²

Streptozocin

Thiotepa greater than or equal to 100 mg/m²

or two agents classified as having high or moderately high emetogenic potential as listed:

Agents with moderately high emetogenic potential (60% to 90%) (dose/m²):

Carboplatin 200-400 mg/m²

Carmustine <200 mg/m²

Cisplatin <50 mg/m²

Cyclophosphamide 600-999 mg/m²

Dacarbazine <500 mg/m²

Doxorubicin 21-59 mg/m²

Hexamethyl melamine

Ifosfamide greater than or equal to 5000 mg/m²

Lomustine <60 mg/m²

Methotrexate greater than or equal to 250 mg/m²

Pentostatin

Procarbazine

Granisetron should not be prescribed for chemotherapeutic agents with a low emetogenic potential (eg, bleomycin, busulfan, cyclophosphamide <1000 mg, etoposide, 5-fluorouracil, vinblastine, vincristine)

B

Previous hypersensitivity to granisetron

Use with caution in patients with liver disease or in pregnant patients

>10%: Central nervous system: Headache

1% to 10%:

Cardiovascular: Hyper/hypotension

Central nervous system: Dizziness, insomnia, anxiety

Gastrointestinal: Constipation, abdominal pain, diarrhea

Neuromuscular & skeletal: Weakness

<1%: Arrhythmias, somnolence, agitation, hot flashes, liver enzyme elevations

CYP3A3/4 enzyme substrate

I.V.: Stable when mixed in NS or D₅W for 24 hours at room temperature; protect from light; do not freeze vials

Selective 5-HT₃-receptor antagonist, blocking serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone

Onset of action: Commonly controls emesis within 1-3 minutes of administration

Duration: Effects generally last no more than 24 hours maximum

Distribution: V_d: 2-3 L/kg; widely distributed throughout the body

Half-life: Cancer patients: 10-12 hours; Healthy volunteers: 3-4 hours

Elimination: Primarily nonrenal, 8% to 15% of a dose is excreted unchanged in urine

I.V.: Children and Adults: 10 mcg/kg for 1-3 doses. Doses should be administered as a single IVPB over 5 minutes to 1 hour or by undiluted IV push over 30 seconds, given just prior to chemotherapy (15-60 minutes before); as intervention therapy for breakthrough nausea and vomiting, during the first 24 hours following chemotherapy, 2 or 3 repeat infusions (same dose) have been administered, separated by at least 10 minutes

Oral: Adults: 1 mg twice daily; the first 1 mg dose should be given up to 1 hour before chemotherapy, and the second tablet, 12 hours after the first; alternatively may give a single dose of 2 mg, up to 1 hour before chemotherapy

Note: Granisetron should only be given on the day(s) of chemotherapy

Dosing interval in renal impairment: Creatinine clearance values have no relationship to granisetron clearance

Dosing interval in hepatic impairment: Kinetic studies in patients with hepatic impairment showed that total clearance was approximately halved, however, standard doses were very well tolerated

May cause anxiety or insomnia

None reported

No information available to require special precautions

No effects or complications reported

This drug will be administered on days when you receive chemotherapy to reduce nausea and vomiting. If outpatient chemotherapy, you may be given oral medication to take after return home; take as directed. You may experience drowsiness; use caution when driving. For persistent acute headache request analgesic from prescriber. Frequent mouth care, chewing gum, or sucking on lozenges may relieve persistent nausea. Report unrelieved headache, fever, diarrhea, or constipation. Breast-feeding precautions: Consult prescriber if breast-feeding.

Doses should be given at least 15 minutes prior to initiation of chemotherapy

Injection: 1 mg/mL

Tablet: 1 mg (2s), (20s)

A 0.2 mg/mL oral suspension may be prepared by crushing twelve (12) 1 mg tablets and mixing with 30 mL water and enough cherry syrup to provide a final volume of 60 mL; this preparation is stable for 14 days at room temperature or when refrigerated

Andrews PL, "The Pharmacologic Profile of Granisetron (Kytril®)," Semin Oncol, 1994, 21(3 Suppl 5):3-9.

Blower P, "A Pharmacologic Profile of Oral Granisetron (Kytril® Tablets)," Semin Oncol, 1995, 22(4 Suppl 10):3-5.

Chung KC, Chin A, and Gill MA, "Stability of Granisetron Hydrochloride in a Disposable Elastomeric Infusion Device," Am J Health Syst Pharm, 1995, 52(14):1541-3.

Hacking A, "Oral Granisetron-Simple and Effective: A Preliminary Report. The Granisetron Study Group," Eur J Cancer, 1992, 28A(Suppl 1):S28-32.

Hahlen K, Quintana E, Pinkerton CR, et al, "A Randomized Comparison of Intravenously Administered Granisetron Versus Chlorpromazine Plus Dexamethasone in the Prevention of Ifosfamide-Induced Emesis in Children," J Pediatr, 1995, 126(2):309-13.

Heron JF, Goedhals L, Jordaan JP, et al, "Oral Granisetron Alone and in Combination With Dexamethasone: A Double-blind Randomized Comparison Against High-dose Metoclopramide Plus Dexamethasone in Prevention of Cisplatin-induced Emesis. The Granisetron Study Group," Ann Oncol, 1994, 5(7):579-84.

Joss RA and Dott CS, "Clinical Studies With Granisetron, a New 5-HT3 Receptor Antagonist for the Treatment of Cancer Chemotherapy-Induced Emesis," Eur J Cancer, 1993, 29A(Suppl 1):S22-9.

Lemerle J, Amaral D, Southall DP, et al, "Efficacy and Safety of Granisetron in the Prevention of Chemotherapy-Induced Emesis in Paediatric Patients," Eur J Cancer, 1991, 27(9):1081-3.

Morrow GR, Hickok JT, and Rosenthal SN, "Progress in Reducing Nausea and Emesis. Comparisons of Ondansetron (Zofran®), Granisetron (Kytril®), and Tropisetron (Navoban®)," Cancer, 1995, 76(3):343-57.

Palmer R, "Efficacy and Safety of Granisetron (Kytril®) in Two Special Populations: Children and Adults With Impaired Hepatic Function," Semin Oncol, 1994, 21(3 Suppl 5):22-5.

Plosker GL and Goa KL, "Granisetron: A Review of Its Pharmacological Properties and Therapeutic Use as an Antiemetic," Drugs, 1991, 42(5):805-24.

Quercia RA, Zhang JH, Fan C, et al, "Stability of Granisetron (Kytril®) in an Extemporaneously Prepared Oral Liquid," International Pharmaceutical Abstracts, 1996, May 15, Vol 33.

Yarker YE and McTavish D, "Granisetron. An Update of Its Therapeutic Use in Nausea and Vomiting Induced by Antineoplastic Therapy," Drugs, 1994, 48(5):761-93.