Product Description

Category: Antiemetic, Gastrointestinal drugs

 

Indications And Usage:Clinical particulars: Therapeutic indications: Em-Ex® (Granisetron ) is indicated in adults for the prevention and treatment of - acute nausea and vomiting associated with chemotherapy and radiotherapy. - post-operative nausea and vomiting. Granisetron is indicated for the prevention of delayed nausea and vomiting associated with chemotherapy and radiotherapy. Granisetron is indicated in children aged 2 years and above for the prevention and treatment of acute nausea and vomiting associated with chemotherapy.

 

Contraindications:Hypersensitivity to the active substance or to any of the excipients.

 

Adverse Reactions:Undesirable effects: The most frequently reported adverse reactions for granisetron are headache and constipation which may be transient.  

System organ class Frequency

Psychiatric disorders Common: Insomnia

Nervous system disorders Very Common: Headache.Uncommon: Extrapyramidal reactions

Gastrointestinal disorders Very common: Constipation. Common: Diarrhoea

Hepatobiliary disorders Common: Transaminases increased

 

Dosage & Administration:Posology and method of administration: Chemo- and radiotherapy-induced nausea and vomiting (CINV and RINV) Prevention (acute and delayed nausea and vomiting): A dose of 1 – 3 mg (10 – 40 µg/kg) of Em-Ex® (Granisetron ) should be administered as a slow intravenous injection 5 minutes prior to the start of chemotherapy or radiotherapy. Treatment (acute nausea and vomiting): A dose of 1 – 3 mg (10 – 40 µg/kg) of Em-Ex® (Granisetron ) should be administered as a slow intravenous injection and administered over 5 minutes. Further maintenance doses of Em-Ex® (Granisetron ) may be administered at least 10 minutes apart. The maximum dose to be administered over 24 hours should not exceed 9 mg. Combination with adrenocortical steroid: The efficacy of parenteral Em-Ex® (Granisetron ) may be enhanced by an additional intravenous dose of an adrenocortical steroid. Paediatric population: The safety and efficacy of Em-Ex® (Granisetron ) in children aged 2 years and above has been well established for the prevention and treatment (control) of acute nausea and vomiting associated with chemotherapy. A dose of 10 – 40 µg/kg body weight (up to 3 mg) should be administered over 5 minutes prior to the start of chemotherapy.Post-operative nausea and vomiting (PONV): A dose of 1 mg (10 µg/kg) of Em-Ex® (Granisetron ) should be administered by slow intravenous injection. The maximum dose of Em-Ex® (Granisetron ) to be administered over 24 hours should not exceed 3 mg. For the prevention of PONV, administration should be completed prior to induction of anaesthesia. Special populations:Elderly and renal impairment : There are no special precautions required for its use in either elderly patients or those patients with renal or hepatic impairment. Hepatic impairment: There is no evidence to date for an increased incidence of adverse events in patients with hepatic disorders. On the basis of its kinetics, whilst no dosage adjustment is necessary, granisetron should be used with a certain amount of caution in this patient group .

 

Drug Interactions:- Medicinal products known to prolong QT interval and/or which are arrhythmogenic, - Phenobarbital

 

How Supplied:Carton box containing amber ( type I ) glass ampoule each of 1 ml & 3 ml solution + insert leaflet.

 

Pharmacokinetics:Pharmacokinetic properties:

Pharmacokinetics of the oral administration is linear up to 2.5-fold of the recommended dose in adults. It is clear from the extensive dose-finding programme that the antiemetic efficacy is not unequivocally correlated with either administered doses or plasma concentrations of granisetron. A fourfold increase in the initial prophylactic dose of granisetron made no difference in terms of either the proportion of patient responding to treatment or in the duration of symptom control. Distribution: Granisetron is extensively distributed, with a mean volume of distribution of approximately 3 l/kg. Plasma protein binding is approximately 65%. Biotransformation: Granisetron is metabolized primarily in the liver by oxidation followed by conjugation. The major compounds are 7-OH-granisetron and its. sulphate and glycuronide conjugates. Although antiemetic properties have been observed for 7-OH-granisetron and indazoline N-desmethyl granisetron, it is unlikely that these contribute significantly to the pharmacological activity of granisetron in man. 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 subfamily. Elimination: Clearance is predominantly by hepatic metabolism. Urinary excretion of unchanged granisetron averages 12% of dose while that of metabolites amounts to about 47% of dose. The remainder is excreted in faeces as metabolites. Mean plasma half-life in patients by the oral and intravenous route is approximately 9 hours, with a wide inter-subject variability.

 

Precautions:Special warnings and precautions for use:

As granisetron may reduce lower bowel motility, patients with signs of sub-acute intestinal obstruction should be monitored following its administration. As for other 5-HT3 antagonists, ECG changes including QT interval prolongation have been reported with granisetron. In patients with pre-existing arrhythmias or cardiac conduction disorders this might lead to clinical consequences. Therefore caution should be exercised in patients with cardiac co-morbidities, on cardiotoxic chemotherapy and/or with concomitant electrolyte abnormalities. Cross-sensitivity between 5-HT3 antagonists (e.g. dolasetron, ondansetron) has been reported.

 

Storage:Storage Condition: Store at temperature not exceeding 25˚ C, Protect from light.

 

Pharmacological Properties:Pharmacological properties: Pharmacodynamic properties: Pharmacotherapeutic group: Antiemetics and antinauseants, Serotonin (5-HT3) antagonists. Mechanism of action: Granisetron is a potent antiemetic and highly selective antagonist of 5-hydroxytryptamine (5 HT3) receptors. Radioligand binding studies have demonstrated that granisetron has negligible affinity for other receptor types including 5-HT and dopamine D2 binding sites. Chemotherapy- and radiotherapy-induced nausea and vomiting. Granisetron administered intravenously has been shown to prevent nausea and vomiting associated with cancer chemotherapy in adults and children 2 - 16 years of age. Post-operative nausea and vomiting: Granisetron administered intravenously has been shown to be effective for prevention and treatment of post-operative nausea and vomiting in adults.

 

Pregnancy & Lactation:Pregnancy:

There is limited amount of data from the use of granisetron in pregnant women. Animal studies do not indicate direct or indirect harmful effects with respect to reproductive toxicity. As a precautionary measure, it is preferable to avoid the use of granisetron during pregnancy.

Breastfeeding: It is unknown whether granisetron or its metabolites are excreted in human milk. As a precautionary measure, breastfeeding should not be advised during treatment with Granisetron.