Granisetron 1 Mg/1 Ml/3 Ml Solution

GRANISETRON FRESENIUS is indicated for the prevention and treatment of nausea and vomiting induced by cytostatic therapy (chemotherapy and radiotherapy) and for the prevention and treatment of post-operative nausea and vomiting.

Posology
Chemotherapy induced nausea and vomiting (CINV)
Adults: Intravenous: Prevention: A dose of 1 u2013 3 mg (10 u2013 40 u03bcg/kg) of GRANISETRON FRESENIUS should be administered either as a slow intravenous injection (over 30 seconds) or as an intravenous infusion diluted in 20 to 50 mL infusion fluid and administered over 5 minutes, prior to the start of chemotherapy. Treatment: A dose of 1 u2013 3 mg (10 u2013 40 u03bcg/kg) of GRANISETRON FRESENIUS should be administered either as a slow intravenous injection (over 30 seconds) or as an intravenous infusion diluted in 20 to 50 mL infusion fluid and administered over 5 minutes. Further treatment doses of GRANISETRON FRESENIUS may be administered, if required, at least 10 minutes apart. The maximum dose of GRANISETRON FRESENIUS to be administered over 24 hours should not exceed 9 mg.
Intramuscular: Prevention and treatment: A dose of 3 mg of GRANISETRON FRESENIUS should be administered by the intramuscular route, 15 minutes prior to the start of chemotherapy. Two subsequent 3 mg doses of GRANISETRON FRESENIUS may be administered, if required, within a 24 hour period.
Paediatrics (children of 2 years and older): Intravenous: A dose of 10 u2013 40 u03bcg/kg body weight (up to 3 mg) should be administered as an intravenous infusion, diluted in 10 to 30 mL infusion fluid and administered over 5 minutes prior to the start of chemotherapy. One additional dose may be administered within a 24 hour period if required. This additional dose should not be administered until at least 10 minutes after the initial infusion. Intramuscular: Insufficient data are currently available to recommend the use of GRANISETRON FRESENIUS by the intramuscular route in children.
Radiotherapy induced nausea and vomiting (RINV)
Adults: Intravenous: Prevention: A dose of 1 u2013 3 mg (10 u2013 40 u03bcg/kg) of GRANISETRON FRESENIUS should be administered either as a slow intravenous injection (over 30 seconds) or as an intravenous infusion diluted in 20 to 50 mL infusion fluid and administered over 5 minutes, prior to the start of radiotherapy. Paediatrics: There is insufficient information to recommend the use of GRANISETRON FRESENIUS in the prevention and treatment of RINV in children.
Post operative nausea and vomiting (PONV)
Adults: Intravenous: Prevention: A dose of 1 mg (10 u03bcg/kg) of GRANISETRON FRESENIUS should be administered as a slow intravenous injection (over 30 seconds) prior to induction of anaesthesia. Treatment: A dose of 1 mg (10 u03bcg/kg) of GRANISETRON FRESENIUS should be administered by slow intravenous injection (over 30 seconds). The maximum dose for patients undergoing anaesthesia for surgery is a total dose of 3 mg GRANISETRON FRESENIUS intravenous in one day. Paediatrics: There is insufficient information to recommend the use of GRANISETRON FRESENIUS in the prevention and treatment of PONV in children.
Elderly: No dosage adjustment required.
Renal impairment: No dosage adjustment required.
Hepatic impairment: No dosage adjustment required.
Method of administration
Intravenous infusion, slow intravenous injection or intramuscular injection. Prophylactic administration of GRANISETRON FRESENIUS should be completed prior to the start of cytostatic therapy or induction of anaesthesia. For instructions on preparing the injection and for compatibility of GRANISETRON FRESENIUS with infusion fluids, see section 6.6.

• Hypersensitivity to granisetron or to any of the excipients of GRANISETRON FRESENIUS (see section 6.1).
• Children under the age of 2 years.
• Congenital long QT syndrome.

GRANISETRON FRESENIUS may reduce intestinal motility. Patients showing symptoms of sub-acute intestinal obstruction or ileus following administration of GRANISETRON FRESENIUS should be monitored carefully. 5-HT3 antagonists, such as GRANISETRON FRESENIUS, may be associated with dysrhythmias or ECG abnormalities including QT interval prolongation. This potentially may have clinical significance in patients with pre-existing dysrhythmias or cardiac conduction disorders or patients who are being treated with anti-dysrhythmic medicines or beta-blockers. Caution should be exercised in patients with cardiac co-morbidities, patients on cardiotoxic chemotherapy and/or with concomitant electrolyte abnormalities (see section 4.5). Cases of myocardial ischaemia have been reported in patients treated with serotonin receptor antagonists. In some patients, especially in the case of intravenous administration, symptoms appeared immediately after administration of a serotonin receptor antagonist (e.g. granisetron). Patients should be alerted to the signs and symptoms of myocardial ischaemia. Cross-sensitivity between 5-HT3 antagonists (e.g. dolasetron, ondansetron) has been reported. There have been reports of serotonin syndrome with the use of 5-HT3 antagonists either alone, but mostly in combination with other serotonergic medicines (including selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs)). Appropriate observation of patients for serotonin syndrome-like symptoms is advised. No special precautions are required for the elderly or renally and/or hepatically impaired patients. Owing to kinetics a degree of caution should be exercised in using GRANISETRON FRESENIUS with this category. Sodium content GRANISETRON FRESENIUS contains 3,57 mg sodium per mL, equivalent to 0,2 % of the WHO recommended maximum daily intake of 2 g sodium for an adult.

As for other 5-HT3 antagonists, cases of ECG modifications including QT prolongation have been reported with GRANISETRON FRESENIUS. In patients concurrently treated with medicines known to prolong the QT interval and/or which are dysrhythmogenic, this may lead to clinical consequences (see section 4.4). This may also have clinical significance in patients who are being treated with anti-dysrhythmic medicines or beta-blockers (see section 4.4). In vitro, it could be shown that metabolism of GRANISETRON FRESENIUS is inhibited by ketoconazole, a potent CYP3A inhibitor. Co-administration of GRANISETRON FRESENIUS with systemic ketoconazole may, therefore, increase the elimination half-life of GRANISETRON FRESENIUS. In humans, hepatic enzyme induction with phenobarbital resulted in an increase in total plasma clearance of GRANISETRON FRESENIUS of approximately 25 %. The clinical significance of this change is not known. No interaction was found between GRANISETRON FRESENIUS and benzodiazepines (lorazepam), neuroleptics (haloperidol) or anti-ulcer medicines (cimetidine). Additionally, GRANISETRON FRESENIUS has not shown any apparent medicine interaction with emetogenic cancer chemotherapies. No specific interaction studies have been conducted in anaesthetised patients. There have been reports of serotonin syndrome following concomitant use of 5-HT3 antagonists and other serotonergic medicines (including SSRIs and SNRIs) (see section 4.4).

Pregnancy
There is limited data on the use of GRANISETRON FRESENIUS 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 FRESENIUS during pregnancy.
Breastfeeding
There is no data on the excretion of GRANISETRON FRESENIUS in breast milk. As a precautionary measure, breastfeeding is not advisable during treatment with GRANISETRON FRESENIUS.
Fertility
In rats, GRANISETRON FRESENIUS had no harmful effects on reproductive performance or fertility.

Special care should be taken with patients performing tasks requiring concentration as somnolence may occur.

a) Summary of the safety profile
The most frequently reported adverse reactions for GRANISETRON FRESENIUS are headache and constipation which may be transient. ECG changes including QT prolongation have been reported with GRANISETRON FRESENIUS (see sections 4.4 and 4.5).
System organ class
Frequent
Less frequent
Immune system disorders
Hypersensitivity reactions
Anaphylaxis*
Shortness of breath*
Hypotension*
Urticaria*
Oedema
Facial oedema
Nervous system disorders
Headache
Somnolence
Agitation
Anxiety
Insomnia
Taste disorder
Extrapyramidal reactions
Dystonia
Dyskinesia
Serotonin syndrome
Eye disorders
Abnormal vision
Ear and labyrinth disorders
Dizziness
Cardiac disorders
Dysrhythmias
Sinus bradycardia
Atrial fibrillation
AV- block
Ventricular ectopy
Non-sustained tachycardia
ECG abnormalities
QT interval prolonged
Myocardial ischaemia (see section 4.4)
Vascular disorders
Hypertension
Hypotension
Gastrointestinal disorders
Constipation
Diarrhoea
Anorexia
Hepatobiliary disorders
Raised transaminase levels
Abnormal hepatic function
Skin and subcutaneous tissue disorders
Skin rash
Local irritation at administration site**
General disorders and administrative site conditions
Fever
Asthenia
b) Tabulated list of adverse reactions
* Hypersensitivity reactions.
** After repeated intravenous administration.
c) Description of selected adverse reactions
As for other 5-HT3 antagonists, ECG changes including QT prolongation have been reported with GRANISETRON FRESENIUS (see sections 4.4 and 4.5).

Overdosage of up to 38,5 mg of GRANISETRON FRESENIUS (more than 10 times the recommended dose) as a single injection has been reported without symptoms or only the occurrence of a slight headache. There is no specific antidote for GRANISETRON FRESENIUS overdosage. In case of overdosage, symptomatic treatment should be given.