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Pronunciation
(gra NI se tron)
Generic Available (U.S.)
Yes: Injection, tablet
Index Terms
U.S. Brand Names
Canadian Brand Names
Pharmacologic Category
Pharmacologic Category Synonyms
Use: Labeled Indications
Prophylaxis of nausea and vomiting associated with emetogenic chemotherapy and radiation therapy; prophylaxis and treatment of postoperative nausea and vomiting (PONV)
Use: Unlabeled/Investigational
Breakthrough treatment of nausea and vomiting associated with chemotherapy
Pregnancy Risk Factor
B
Pregnancy Considerations
There are no adequate or well-controlled studies in pregnant women. Teratogenic effects were not observed in animal studies. Injection (1 mg/mL strength) contains benzyl alcohol which may cross the placenta. Use only if benefit exceeds the risk.
Lactation
Excretion in breast milk unknown/use caution
Contraindications
Hypersensitivity to granisetron or any component of the formulation
Warnings/Precautions
Concerns related to adverse effects:
• Allergic reactions: Use with caution in patients allergic to other 5-HT3 receptor antagonists; cross-reactivity has been reported.
• ECG effects: Selective 5-HT3 antagonists, including granisetron, have been associated with a number of dose-dependent increases in ECG intervals (eg, PR, QRS duration, QT/QTc, JT), usually occurring 1-2 hours after I.V. administration. In general, these changes are not clinically relevant, however, when used in conjunction with other agents that prolong these intervals, arrhythmia may occur. When used with agents that prolong the QT interval (eg, Class I and III antiarrhythmics), clinically relevant QT interval prolongation may occur resulting in torsade de pointes. A number of trials have shown that 5-HT3 antagonists produce QT interval prolongation to variable degrees. Use with caution in patients at risk of QT prolongation and/or ventricular arrhythmia. Reduction in heart rate may also occur with the 5-HT3 antagonists. I.V. formulations of 5-HT3 antagonists have more association with ECG interval changes, compared to oral formulations.
Disease-related concerns:
• Long QT syndrome: Use with caution in patients with congenital long QT syndrome or other risk factors for QT prolongation (eg, medications known to prolong QT interval, electrolyte abnormalities [hypokalemia or hypomagnesemia], and cumulative high-dose anthracycline therapy).
Dosage form specific issues:
• Benzyl alcohol: Injection contains benzyl alcohol (1 mg/mL) which has been associated with "gasping syndrome" in neonates.
• Transdermal patch: Application site reactions, generally mild, have occurred with use; if skin reaction is severe or generalized, remove patch. Cover patch application site with clothing to protect from natural or artificial sunlight exposure while patch is applied and for 10 days following removal; granisetron may potentially be affected by natural or artificial sunlight. Do not apply to red, irritated or damaged skin.
Other warnings/precautions:
• Chemotherapy-related emesis: For chemotherapy, should be used on a scheduled basis, not on an “as needed” (PRN) basis, since data support the use of this drug only in the prevention of nausea and vomiting (due to antineoplastic therapy) and not in the rescue of nausea and vomiting. Should only be used in the first 24-48 hours of chemotherapy. Data does not support any increased efficacy in delayed nausea and vomiting.
• Ileus or gastric distention: Does not stimulate gastric or intestinal peristalsis; may mask progressive ileus and/or gastric distension.
• Postoperative nausea/vomiting use: Routine prophylaxis for PONV is not recommended in patients where there is little expectation of nausea and vomiting postoperatively. In patients where nausea and vomiting must be avoided postoperatively, administer to all patients even when expected incidence of nausea and vomiting is low.
Adverse Reactions
>10%:
Central nervous system: Headache (3% to 21%; transdermal patch: 1%)
Gastrointestinal: Constipation (3% to 18%)
Neuromuscular & skeletal: Weakness (5% to 18%)
1% to 10%:
Cardiovascular: QTc prolongation (1% to 3%), hypertension (1% to 2%)
Central nervous system: Pain (10%), fever (3% to 9%), dizziness (4% to 5%), insomnia (<2% to 5%), somnolence (1% to 4%), anxiety (2%), agitation (<2%), CNS stimulation (<2%)
Dermatologic: Rash (1%)
Gastrointestinal: Diarrhea (3% to 9%), abdominal pain (4% to 6%), dyspepsia (3% to 6%), taste perversion (2%)
Hepatic: Liver enzymes increased (5% to 6%)
Renal: Oliguria (2%)
Respiratory: Cough (2%)
Miscellaneous: Infection (3%)
<1%, postmarketing, and/or case reports: Agitation, allergic reactions; anaphylaxis (including hypotension, dyspnea, urticaria); angina, application site reactions (transdermal patch), arrhythmias, atrial fibrillation, extrapyramidal syndrome, hot flashes, hypotension, hypersensitivity, syncope
Metabolism/Transport Effects
Substrate of CYP3A4 (minor)
Drug Interactions
Apomorphine: Antiemetics (5HT3 Antagonists) may enhance the hypotensive effect of Apomorphine. Risk X: Avoid combination
Conivaptan: May increase the serum concentration of CYP3A4 Substrates. Management: Upon completion/discontinuation of conivaptan, allow at least 7 days before initiating therapy with drugs that are CYP3A4 substrates. Risk D: Consider therapy modification
Tocilizumab: May decrease the serum concentration of CYP3A4 Substrates. Risk C: Monitor therapy
Storage
I.V.: Store at 15°C to 30°C (59°F to 86°F). Protect from light. Do not freeze vials. Stable when mixed in NS or D5W for 7 days under refrigeration and for 3 days at room temperature.
Oral: Store tablet or oral solution at 15°C to 30°C (59°F to 86°F). Protect from light.
Transdermal patch: Store at 20°C to 25°C (68°F to 77°F). Keep patch in original packaging until immediately prior to use.
Compatibility
Stable in D51/2NS, D5NS, D5W, NS, bacteriostatic water.
Y-site administration: Compatible: Acyclovir, allopurinol, amifostine, amikacin, aminophylline, amphotericin B cholesteryl sulfate complex, ampicillin, ampicillin/sulbactam, amsacrine, aztreonam, bleomycin, bumetanide, buprenorphine, butorphanol, calcium gluconate, carboplatin, carmustine, cefazolin, cefepime, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftizoxime, ceftriaxone, cefuroxime, chlorpromazine, cimetidine, ciprofloxacin, cisplatin, cladribine, clindamycin, co-trimoxazole, cyclophosphamide, cytarabine, dacarbazine, dactinomycin, daunorubicin, dexamethasone sodium phosphate, dexmedetomidine, diphenhydramine, dobutamine, docetaxel, dopamine, doxorubicin, doxorubicin liposome, doxycycline, droperidol, enalaprilat, etoposide, etoposide phosphate, famotidine, fenoldopam mesylate, filgrastim, floxuridine, fluconazole, fludarabine, fluorouracil, furosemide, gallium nitrate, ganciclovir, gatifloxacin, gemcitabine, gentamicin, haloperidol, heparin, hetastarch in lactated electrolytes, hydrocortisone sodium succinate, hydromorphone, hydroxyzine, idarubicin, ifosfamide, imipenem/cilastatin, leucovorin calcium, levoleucovorin, linezolid, lorazepam, magnesium sulfate, mechlorethamine, melphalan, meperidine, mesna, methotrexate, methylprednisolone sodium succinate, metoclopramide, metronidazole, mitomycin, mitoxantrone, morphine, nalbuphine, netilmicin, ofloxacin, paclitaxel, pemetrexed, piperacillin, piperacillin/tazobactam, potassium chloride, prochlorperazine edisylate, promethazine, propofol, ranitidine, sargramostim, sodium bicarbonate, streptozocin, teniposide, thiotepa, ticarcillin, ticarcillin/clavulanate, tobramycin, topotecan, vancomycin, vinblastine, vincristine, vinorelbine, zidovudine. Incompatible: Amphotericin B.
Compatibility in syringe: Compatible: Dexamethasone sodium phosphate, methylprednisolone sodium succinate.
Compatibility when admixed: Compatible: Dexamethasone sodium phosphate, methylprednisolone sodium succinate.
Mechanism of Action
Selective 5-HT3-receptor antagonist, blocking serotonin, both peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone
Pharmacodynamics/Kinetics
Duration: Oral, I.V.: Generally up to 24 hours
Absorption: Oral: Tablets and oral solution are bioequivalent; Transdermal patch: ~66% over 7 days
Distribution: Vd: 2-4 L/kg; widely throughout body
Protein binding: 65%
Metabolism: Hepatic via N-demethylation, oxidation, and conjugation; some metabolites may have 5-HT3 antagonist activity
Half-life elimination: Oral: 6 hours; I.V.: 9 hours
Time to peak, plasma: Transdermal patch: Maximum systemic concentrations: ~48 hours after application (range: 24-168 hours)
Excretion: Urine (12% as unchanged drug, 48% to 49% as metabolites); feces (34% to 38% as metabolites)
Dosage
Oral: Adults:
Prophylaxis of chemotherapy-related emesis: 2 mg once daily up to 1 hour before chemotherapy or 1 mg twice daily; the first 1 mg dose should be given up to 1 hour before chemotherapy.
Prophylaxis of radiation therapy-associated emesis: 2 mg once daily given 1 hour before radiation therapy.
I.V.:
Children ≥2 years and Adults: Prophylaxis of chemotherapy-related emesis:
Within U.S.: 10 mcg/kg/dose (maximum: 1 mg/dose) given 30 minutes prior to chemotherapy; for some drugs (eg, carboplatin, cyclophosphamide) with a later onset of emetic action, 10 mcg/kg every 12 hours may be necessary
Outside U.S.: 40 mcg/kg/dose (or 3 mg/dose); maximum: 9 mg/24 hours
Breakthrough: Granisetron has not been shown to be effective in terminating nausea or vomiting once it occurs and should not be used for this purpose.
Adults: PONV:
Prevention: 1 mg given undiluted over 30 seconds; the manufacturer recommends administration before induction of anesthesia or immediately before reversal of anesthesia. Note: The Society for Ambulatory Anesthesia (SAMBA) Guidelines recommend a dosage range of 0.35-1.5 mg administered at the end of surgery (Gan, 2007). However, doses ≤1 mg are generally used since doses >1 mg are not more effective. Of note, 5 mcg/kg (~0.35 mg in a 70 kg adult) has been shown to be effective; doses >5 mcg/kg were not more effective (Mikawa, 1997).
Treatment: 1 mg given undiluted over 30 seconds
Transdermal patch: Adults: Prophylaxis of chemotherapy-related emesis: Apply 1 patch at least 24 hours prior to chemotherapy; do not apply ≥48 hours before chemotherapy. Remove patch a minimum of 24 hours after chemotherapy completion. Maximum duration: Patch may be worn up to 7 days, depending on chemotherapy regimen duration.
Dosing interval in renal impairment: No dosage adjustment required.
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, and dose adjustments are not necessary.
Administration: Oral
Doses should be given up to 1 hour prior to initiation of chemotherapy/radiation
Administration: I.V.
Administer I.V. push over 30 seconds or as a 5- to 10-minute infusion
Prevention of PONV: Administer before induction of anesthesia or immediately before reversal of anesthesia.
Treatment of PONV: Administer undiluted over 30 seconds.
Administration: Topical
Transdermal (Sancuso®): Apply patch to clean, dry, intact skin on upper outer arm. Do not use on red, irritated or damaged skin. Remove patch from pouch immediately before application. Do not cut patch.
Administration: I.V. Detail
pH: 4.7-7.3
Patient Education
This drug is given to prevent nausea and vomiting. If this medication is given by intravenous infusion you will be monitored during infusion. Report immediately any chest pain, respiratory difficulty, or pain or itching at infusion site. Remove patch from packaging pouch immediately before application; do not cut patch. Apply to clean, dry, intact skin on upper outer arm. You may experience headache, drowsiness, or dizziness. Report chest pain or palpitations, persistent headache, excessive drowsiness, fever, or changes in elimination patterns (constipation or diarrhea).
Geriatric Considerations
Clinical trials with patients older than 65 years of age are limited; however, the data indicates that safety and efficacy are similar to that observed in younger adults. No adjustment in dose necessary for elderly.
Anesthesia and Critical Care Concerns/Other Considerations
Clinical Pearls/Comments: For prevention of postoperative nausea and vomiting (PONV), granisetron has been shown effective in lower doses of 5 mcg/kg (~0.35 mg) (Mikawa, 1997).
Dental Health: Effects on Dental Treatment
No significant effects or complications reported
Dental Health: Vasoconstrictor/Local Anesthetic Precautions
No information available to require special precautions
Mental Health: Effects on Mental Status
May cause anxiety or insomnia
Mental Health: Effects on Psychiatric Treatment
None reported
Nursing: Physical Assessment/Monitoring
Assess allergy history (selective 5-HT3 receptor antagonists) prior to administering. Use with caution in presence of, or potential for, cardiac conduction abnormalities (eg, QT prolongation, medication known to prolong QT interval, electrolyte abnormalities). Oral, I.V., and transdermal formulations have different doses and schedules and should not be administered on a PRN basis.
Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Injection, solution: 0.1 mg/mL (1 mL [DSC]); 1 mg/mL (1 mL, 4 mL)
Kytril®: 1 mg/mL (4 mL [DSC]) [contains benzyl alcohol]
Injection, solution [preservative free]: 0.1 mg/mL (1 mL); 1 mg/mL (1 mL)
Patch, transdermal:
Sancuso®: 3.1 mg/24 hours (1s) [52 cm2, total granisetron 34.3 mg]
Solution, oral:
Granisol™: 2 mg/10 mL (30 mL) [contains sodium benzoate; orange flavor]
Tablet, oral: 1 mg
Kytril®: 1 mg
Pricing: U.S. (www.drugstore.com)
Tablets (Granisetron HCl)
1 mg (2): $45.99
Tablets (Kytril)
1 mg (2): $131.98
Extemporaneously Prepared
Note: Commercial oral solution is available (0.2 mg/mL)
A 0.2 mg/mL oral suspension may be made with tablets. Crush twelve 1 mg tablets in a mortar and reduce to a fine powder. Add 30 mL distilled water, mix well, and transfer to a bottle. Rinse the mortar with 10 mL cherry syrup and add to bottle. Add sufficient quantity of cherry syrup to make a final volume of 60 mL. Label “shake well”. Stable 14 days at room temperature or refrigerated (Quercia, 1997).
A 50 mcg/mL oral suspension may be made with tablets and one of three different vehicles (Ora-Sweet®, Ora-Plus®, or a mixture of methylcellulose 1% and Simple Syrup, N.F.). Crush one 1 mg tablet in a mortar and reduce to a fine powder. Add 20 mL of the chosen vehicle and mix to a uniform paste; transfer to a calibrated bottle. Label "shake well" and "refrigerate". Stable for 91 days refrigerated (Nahata, 1998).
Nahata MC, Morosco RS, and Hipple TF, "Stability of Granisetron Hydrochloride in Two Oral Suspensions," Am J Health Syst Pharm, 1998, 55(23):2511-3.
Quercia RA, Zhang J, Fan C, et al, "Stability of Granisetron Hydrochloride in an Extemporaneously Prepared Oral Liquid," Am J Health Syst Pharm, 1997, 54(12):1404-6.
References
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.
Gan TJ, Meyer TA, Apfel CC, et al, “Society for Ambulatory Anesthesia Guidelines for the Management of Postoperative Nausea and Vomiting,” Anesth Analg, 2007, 105(6):1615-28.
Gill D and Howell J, “Pharmacokinetics and Bioavailability of Transdermal Granisetron After a Six-Day Application of Three Patch Sizes, Compared to 2 mg Once-Daily Oral Dose of Granisetron for Five Days,” Support Care Cancer, 2008, 16(6):619-756 [abstract from 2008 International MASCC/ISOO Symposium].
Kris MG, Hesketh PJ, Somerfield MR, et al, “American Society of Clinical Oncology Guideline for Antiemetics in Oncology: Update 2006,” J Clin Oncol, 2006, 24(18):2932-47.
Mikawa K, Takao Y, Nishina K, et al, “Optimal Dose of Granisetron for Prophylaxis Against Postoperative Emesis After Gynecological Surgery,”Anesth Analg, 1997, 85(3):652-6.
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.
Multinational Association of Supportive Care in Cancer (MASCC), “Antiemetic Guidelines,” Updated April 2010. Available at http://data.memberclicks.com/site/mascc/MASCC_Guidelines_English_2010.pdf
National Comprehensive Cancer Network® (NCCN), “Clinical Practice Guidelines in Oncology™: Antiemesis,” Version 2.2010. Available at http://www.nccn.org/professionals/physician_gls/PDF/antiemesis.pdf
Navari RM and Koeller JM, “Electrocardiographic and Cardiovascular Effects of the 5-Hydroxytryptamine3 Receptor Antagonists,” Ann Pharmacother, 2003, 37(9):1276-86.
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.
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.
International Brand Names
Lexi-Comp.com
Last full review/revision May 2011
Content last modified May 2011
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