Granisetron 2 Mg Film-Coated Tablets
Out of date information, search anotherSUMMARY OF PRODUCT CHARACTERISTICS
1 NAME OF THE MEDICINAL PRODUCT
Granisetron 2 mg Film-coated Tablets
2 QUALITATIVE AND QUANTITATIVE COMPOSITION
Each film-coated tablet contains 2 mg granisetron (as hydrochloride). Excipients include lactose monohydrate (see section 4.3).
For a full list of excipients, see section 6.1.
3 PHARMACEUTICAL FORM
Film-coated Tablet.
White to off white, barrel shaped, film coated, biconvex tablet with ‘G2’ debossed on one side and plain on the other.
4 CLINICAL PARTICULARS
4.1 Therapeutic indications
Granisetron tablets are indicated for the prevention of nausea and vomiting induced by cytostatic therapy.
4.2 Posology and method of administration
Adults and children over 12 years
The dose of Granisetron is 1 mg twice a day or 2 mg once a day during cytostatic therapy.
The first dose of Granisetron should be administered within one hour before the start of cytostatic therapy.
Concomitant use of dexamethasone: The efficacy of Granisetron may be enhanced by the addition of dexamethasone.
Maximum Dose and Duration of Treatment
The maximum dose of Granisetron administered orally over 24 hours should not exceed 9 mg.
Children
There is insufficient evidence on which to base appropriate dosage regimens for children under 12 years old. Granisetron Tablets are therefore not recommended in this age group.
Elderly As for adults.
Renally Impaired As for adults.
Hepatically Impaired As for adults.
4.3 Contraindications
Hypersensitivity to granisetron, related substances such as other 5-HT3 receptor antagonists, or the excipients (see section 6.1).
Owing to the presence of lactose, patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.
4.4 Special warnings and precautions for use
As Granisetron may reduce lower bowel motility, patients with signs of subacute intestinal obstruction should be monitored following administration of Granisetron.
4.5 Interaction with other medicinal products and other forms of interaction
In studies in healthy subjects, no evidence of any interaction has been indicated between Granisetron and cimetidine or lorazepam. No evidence of drug interactions has been observed in clinical studies.
4.6 Fertility, Pregnancy and lactation
Whilst animal studies have shown no teratogenic effects, there is no experience of Granisetron in human pregnancy. Therefore Granisetron should not be administered to women who are pregnant unless there are compelling clinical reasons. There are no data on the excretion of Granisetron in breast milk. Breast feeding should therefore be discontinued during therapy.
4.7 Effects on ability to drive and use machines
There has been no evidence from human studies that Granisetron has any adverse effect on alertness.
4.8 Undesirable effects
|
Frequency Organ System |
Very Common (>1/10) |
Common (>1/100 to <1/10) |
Uncommon (>1/1,000 to <1/100) |
Rare (>1/10,000 to <1/1,000) |
Very rare (<1/10,000), not known (cannot be estimated from the available data) |
|
Psychiatric disorders |
Anorexia | ||||
|
Nervous system disorders |
Headache |
Coma; Extrapyramidal disorder | |||
|
Gastro intestinal disorders |
Nausea; Constipation |
Reduced appetite; Diarrhoea; Vomiting; Abdominal pain | |||
|
Skin and subcutaneous tissue disorders |
Rash | ||||
|
General disorders |
Asthenia; pain; fever |
Anaphylaxis; Fainting fits; |
|
Dizziness; Insomnia; Agitation | |||||
|
Cardiac disorders |
Arrhythmia; Chest pain | ||||
|
Hepatobiliary disorders |
Abnormal hepatic function; Raised transaminase levels |
4.9 Overdose
There is no specific antidote for Granisetron. In the case of overdosage, symptomatic treatment should be given. One patient has received 30mg of Granisetron intravenously. The patient reported a slight headache but no other sequelae were observed.
5 PHARMACOLOGICAL PROPERTIES
5.1 Pharmacodynamic properties
Pharmacotherapeutic group: Serotonin 5-HT3 receptor antagonist
ATC Code: A04AA02
Granisetron is a potent anti-emetic 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.
Granisetron is effective orally prophylactically in abolishing the retching and vomiting evoked by cytostatic therapy.
5.2 Pharmacokinetic properties
General Characteristics Absorption
Absorption of Granisetron is rapid and complete, though oral bioavailability is reduced to about 60% as a result of first pass metabolism. Oral bioavailability
is generally not influenced by food.
Distribution
Granisetron is extensively distributed, with a mean volume of distribution of approximately 3 l/kg; plasma protein binding is approximately 65%.
Biotransformation
Biotransformation pathways involve N-demethylation and aromatic ring oxidation followed by conjugation.
Elimination
Clearance is predominantly by hepatic metabolism. Urinary excretion of unchanged Granisetron averages 12% of dose whilst that of metabolites amounts to about 47% of dose. The remainder is excreted in faeces as metabolites. Mean plasma half-life in patients is approximately nine hours, with a wide inter-subject variability.
The pharmacokinetics of Granisetron demonstrate no marked deviations from linear pharmacokinetics at oral doses up to 2.5-fold of the recommended clinical dose.
Characteristics in Patients
The plasma concentration of Granisetron is not clearly correlated with antiemetic efficacy. Clinical benefit may be conferred even when Granisetron is not detectable in plasma.
In elderly subjects after single intravenous doses, pharmacokinetic parameters were within the range found for non-elderly subjects. In patients with severe renal failure, data indicate that pharmacokinetic parameters after a single intravenous dose are generally similar to those in normal subjects. In patients with hepatic impairment due to neoplastic liver involvement, total plasma clearance of an intravenous dose was approximately halved compared to patients without hepatic involvement. Despite these changes, no dosage adjustment is necessary.
5.3 Preclinical safety data
Data from two-year carcinogenicity studies have shown an increase in hepatocellular carcinoma and/or adenoma in rats and mice of both sexes given 50mg/kg (rat dosage reduced to 25mg/kg/day at week 59). Increases in hepatocellular neoplasia were also detected at 5mg/kg in male rats. In both species, drug-induced effects (hepatocellular neoplasia) were not observed in the low-dose group (1mg/kg).
In several in vitro and in vivo assays, Granisetron was shown to be non-genotoxic in mammalian cells.
6.1 List of excipients
Tablet core:
Microcrystalline Cellulose Lactose monohydrate Sodium Starch Glycollate Maize starch Magnesium Stearate
Film coat:
Hypromellose 15cP Titanium dioxide (E171) Macrogol 6000
6.2 Incompatibilities
Not applicable.
6.3 Shelf life
3 years.
6.4 Special precautions for storage
Store in the original package.
6.5 Nature and contents of container
Clear PVC/aluminium foil blister packs packed in cartons containing 5 tablets.
6.6
Special precautions for disposal
No special requirements.
7 MARKETING AUTHORISATION HOLDER
Cipla (EU) Limited,
Hillbrow House,
Hillbrow Road,
Esher,
Surrey,
KT10 9NW
8 MARKETING AUTHORISATION NUMBER(S)
PL 36390/0088
9 DATE OF FIRST AUTHORISATION/RENEWAL OF THE AUTHORISATION
12/10/2009
10 DATE OF REVISION OF THE TEXT
03/12/2012