Granisetron

Granisetron is a highly selective 5-HT3 receptor antagonist with little or no affinity for other serotonin receptors. It blocks serotonin peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone.

Serotonin receptors of the 5-HT3 type are located peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. During chemotherapy that induces vomiting, mucosal enterochromaffin cells release serotonin, which stimulates 5-HT3 receptors. This evokes vagal afferent discharge, inducing vomiting. Animal studies demonstrate that, in binding to 5-HT3 receptors, granisetron blocks serotonin stimulation and subsequent vomiting after emetogenic stimuli such as cisplatin. In the ferret animal model, a single granisetron injection prevented vomiting due to high-dose cisplatin or arrested vomiting within 5 to 30 seconds.

In most human studies, granisetron has had little effect on blood pressure, heart rate or ECG. No evidence of an effect on plasma prolactin or aldosterone concentrations has been found in other studies.

Tablet-

Emetogenic Chemotherapy: The recommended adult dosage of oral Granisetron is 2 mg once daily or 1 mg twice daily. In the 2 mg once-daily regimen, two 1 mg tablets is given up to 1 hour before chemotherapy. In the 1 mg twice-daily regimen, the first 1 mg tablet is given up to 1 hour before chemotherapy, and the second tablet is given 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.

Injection-

Chemotherapy Induced Nausea and Vomiting:

• Adults: The recommended dosage for Granisetron Injection is 10 mcg/kg administered intravenously within 30 minutes before initiation of chemotherapy, and only on the day(s) chemotherapy is given. Granisetron Injection may be administered intravenously either undiluted over 30 seconds, or diluted with 0.9% Sodium Chloride or 5% Dextrose and infused over 5 minutes. As a general precaution, Granisetron Injection should not be mixed in solution with other drugs.
• Paediatric Patients: The recommended dose in paediatric patients 2 to 16 years o f age is 10 mcg/kg. Paediatric patients under 2 years o f age have not beenstudied.
• Geriatric Patients, Renal Failure Patients or Hepatically Impaired Patients: No dosage adjustment is required.

Treatment of Postoperative Nausea and Vomiting:

• Adults: The recommended dosage for prevention of postoperative nausea and vomiting is, a single dose of 1 mg of Granisetron should be diluted to 5 ml andadministered as a slow intravenous injection (over 30 seconds). Administration should be completed prior to induction of anesthesia. The recommended dosage for the treatment of nausea and vomiting after surgery is 1 mg of Granisetron undiluted, administered intravenously over 30 seconds.
• Paediatric Patients: Safety and effectiveness of Granisetron Injection have not been established in paediatric patients for the prevention or treatment of post operative nausea or vomiting.
• Geriatricpatients, Renal Failure Patients or Hepatically Impaired Patients: No dosage adjustment is required.

Induced metabolism with phenobarbital. Risk of serotonin syndrome with other serotonergic agents e.g. SSRIs, and serotonin and norepinephrine reuptake inhibitors (SNRIs). Altered clearance with CYP enzyme inducers or inhibitors. Concomitant use with drugs known to prolong QT interval may result in clinical consequences.

Granisetron is contraindicated in patients with known hypersensitivity to granisetron.

Headache, insomnia, constipation, diarrhoea, elevated hepatic transaminases; QT prolongation; bradycardia, palpitations, sick sinus syndrome, chest pain. Application site reactions (transdermal): Rash, pain, erythema, pruritus, irritation, burn, vesicles, urticaria, discolouration; patch non-adhesion.

Pregnancy Category B. No evidence of impaired fertility or harm to the animal fetus have been found. However, this drug may be used in pregnancy only if clearly needed. It is not known whether granisetron is excreted in human milk. So cautions hould be exercised when granisetron is administered to a nursing mother.

Patient with cardiac co-morbidities, on cardiotoxic chemotherapy and/or woth concomitant electrolyte abnormalities. May mask progressive ileus and/or gastric distention. Childn. Pregnancy and lactation.

Pediatric Uses: Safety and effectiveness of granisetron in paediatric patients under 2 years have not been established.

Geriatric use: Efficacy and safety were maintained with increasing age

Anti-emetic drugs, Supportive Care Therapy

Store between 15-30°C. Protect from light.