Clinical medicine profile
Granisetron
Therapeutic agent (verify pharmacological class)
- Route
- See product SmPC
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- Hypersensitivity to the active substance or excipients.
- Additional absolute contraindications are indication- and product-specific — consult SmPC.
Precautions
- WARNINGS Serotonin Syndrome The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists alone but particularly with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and intravenous methylene blue).
- Some of the reported cases were fatal.
- Serotonin syndrome occurring with overdose of another 5-HT3 receptor antagonist alone has also been reported.
- The majority of reports of serotonin syndrome related to 5-HT3 receptor antagonist use occurred in a post-anesthesia care unit or an infusion center.
- Symptoms associated with serotonin syndrome may include mental status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures, and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
- Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of granisetron and other serotonergic drugs.
- If symptoms of serotonin syndrome occur, discontinue granisetron and initiate supportive treatment.
- Patients should be informed of the increased risk of serotonin syndrome, especially if granisetron is used concomitantly with other serotonergic drugs [see Drug Interactions ].
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
DOSAGE AND ADMINISTRATION Emetogenic Chemotherapy The recommended adult dosage of oral granisetron hydrochloride is 2 mg once daily or 1 mg twice daily. In the 2 mg once-daily regimen, 10 mL of GRANISOL oral solution (2 teaspoonfuls, equivalent to 2 mg of granisetron) are given up to 1 hour before chemotherapy. In the 1 mg twice-daily regimen, the first teaspoonful (5 mL) of GRANISOL oral solution is given up to 1 hour before chemotherapy, and the second teaspoonful (5 mL) of GRANISOL oral solution, 12 hours after the first. Either regimen is administered only on the day(s) chemotherapy is given. Continued treatment, while not on chemotherapy, has not been found to be useful. Use in the Elderly, Renal Failure Patients or Hepatically Impaired Patients No dosage adjustment is recommended (see CLINICAL PHARMACOLOGY: Pharmacokinetics ). Pediatric Use Safety and effectiveness in pediatric patients have not been established. Radiation (Either Total Body Irradiation or Fractionated Abdominal Radiation) The recommended adult dosage of oral granisetron hydrochloride is 2 mg once daily. Ten milliliters of GRANISOL oral solution (2 teaspoonfuls, equivalent to 2 mg of granisetron) are taken within 1 hour of radiation. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Use in the Elderly No dosage adjustment is recommended.
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
- INDICATIONS AND USAGE Granisetron is indicated for the prevention of: Nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin.
- Nausea and vomiting associated with radiation, including total body irradiation and fractionated abdominal radiation.
Adverse effects
- ADVERSE REACTIONS QT prolongation has been reported with granisetron (see PRECAUTIONS and Drug Interactions ).
- Chemotherapy-Induced Nausea and Vomiting Over 3700 patients have received Kytril tablets in clinical trials with emetogenic cancer therapies consisting primarily of cyclophosphamide or cisplatin regimens.
- In patients receiving Kytril tablets 1 mg bid for 1, 7 or 14 days, or 2 mg daily for 1 day, adverse experiences reported in more than 5% of the patients with comparator and placebo incidences are listed in Table 4 .
- Table 4 Principal Adverse Events in Clinical Trials Percent of Patients With Event Kytril 1 Tablets 1 mg twice a day (n=978) Kytril 1 Tablets 2 mg once a day N=1450) Comparator 2 (n=599) Placebo (n=185) Headache 3 21% 20% 13% 12% Constipation 18% 14% 16% 8% Asthenia 14% 18% 10% 45 Diarrhea 8% 9% 10% 4% Abdominal Pain 6% 4% 6% 3% Dyspepsia 4% 6% 5% 4% 1 Adverse events were recorded for 7 days when Kytril tablets were given on a single day and for up to 28 days when Kytril tablets were administered for 7 or 14 days. 2 Metoclopramide/dexamethasone
- phenothiazines/dexamethasone
- dexamethasone alone
- prochlorperazine. 3 Usually mild to moderate in severity.
- Other adverse events reported in clinical trials were: Gastrointestinal : In single-day dosing studies in which adverse events were collected for 7 days, nausea (20%) and vomiting (12%) were recorded as adverse events after the 24-hour efficacy assessment period.
- Hepatic : In comparative trials, elevation of AST and ALT (> 2 times the upper limit of normal) following the administration of Kytril tablets occurred in 5% and 6% of patients, respectively.
- These frequencies were not significantly different from those seen with comparators (AST: 2%
- ALT: 9%).
- Cardiovascular : Hypertension (1%)
- hypotension, angina pectoris, atrial fibrillation, and syncope have been observed rarely.
- Central Nervous System : Dizziness (5%), insomnia (5%), anxiety (2%), somnolence (1%).
Drug interactions
Open multi-drug checker ↗- Professional use: confirm indication, dose, duration, monitoring and patient counselling points against current Kenya STG / EML and the product SmPC.
- Document allergy status and key interactions.
Mechanism & disposition
A specific serotonin [5HT3] antagonist.
Read complete mechanism
A specific serotonin [5HT3] antagonist. [Emetogenics like cyto- toxic drugs and radiation damage gastrointestinal mucosa. This leads to the release of serotonin from the enterochromaffin cells of the gastrointestinal tract. 5-HT3 recep- tors are stimulated causing transmission of sensory signals to the vomiting center via vagal afferent fibers to induce vomiting.
Product-specific
Product-specific
See product SmPC
When Kytril tablets were administered with food, AUC was decreased by 5% and C max increased by 30% in non-fasted healthy volunteers who received a single dose of 10 mg.
(L/kg) Total Clearance (L/h/kg) Cancer Patients 1 mg bid, 7 days (n=27) 5.99 [0.63 to 30.9] N.D. 1 N.D. 0.52 [0.09 to 7.37] Volunteers Single 1 mg dose (n=39) 3.63 [0.27 to 9.14] 6.23 [0.96 to 19.9] 3.94 [1.89 to 39.4] 0.41 [0.11 to 24.6] A 2 mg dose of GRANISOL oral solution is...
Granisetron metabolism involves N-demethylation and aromatic ring oxidation followed by conjugation. In vitro liver microsomal studies show that granisetron's major route of metabolism is inhibited by ketoconazole, suggestive of metabolism mediated by the cytochrome P-450 3A subf...
Clearance is predominantly by hepatic
was determined to be 8.95 hours. N.D. Not determined. Peak Plasma Concentration (ng/mL) Terminal Phase Half-Life (h) Volume of
Pregnancy, lactation & diet
Pregnancy Teratogenic Effects Pregnancy Category B Reproduction studies have been performed in pregnant rats at oral doses up to 125 mg/kg/day (750 mg/m 2 /day, 507 times the recommended human dose based on body surface area) and pregnant rabbits at oral doses up to 32 mg/kg/day (378 mg/m 2 /day, 255 times the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to granisetron. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers It is not known whether granisetron is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when granisetron is administered to a nursing woman.
Brands & loaded prices
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Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.