Grantryl 1 mg/1 ml & 3 mg/3 ml Injection

GRANTRYL is indicated for the management of nausea and vomiting induced by chemotherapy and radiotherapy. GRANTRYL is also indicated for the prevention and treatment of post-operative nausea and vomiting.

Chemotherapy induced nausea and vomiting (CINV):

Posology

Adults

Prevention: A dose of 1-3 mg (10 u2013 40 u03bcg/kg) of GRANTRYL should either be administered either as a slow intravenous injection (over 30 seconds), or as an intravenous infusion diluted in 20 u2013 50 mu2113 infusion fluid (see Preparation of dosage form) and administered over 5 minutes, prior to the start of chemotherapy.

Treatment: A dose of 1-3 mg (10 u2013 40 u03bcg/kg) of GRANTRYL should be administered either as a slow intravenous injection (over 30 seconds), or as an intravenous infusion diluted in 20u2013 50 mu2113 infusion fluid (see Preparation of dosage form) and administered over 5 minutes. Further maintenance doses of GRANTRYL may be administered, if required, at least 10 minutes apart. The maximum dose of GRANTRYL to be administered over 24 hours should not exceed 9 mg.

Paediatrics

GRANTRYL is contra-indicated in children under 2 years of age (see CONTRA-INDICATIONS). 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 mu2113 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.

Radiotherapy induced nausea and vomiting (RINV):

Adults

Prevention: A dose of 1-3 mg (10 u2013 40 u03bcg/kg) of GRANTRYL should be administered either as a slow intravenous injection (over 30 seconds) or as an intravenous infusion diluted in 20- 50 mu2113 infusion fluid and administered over 5 minutes, prior to the start of radiotherapy.

Paediatrics

Due to lack of data, GRANTRYL is not recommended for prevention and treatment of RINV in children.

Post-operative nausea and vomiting (PONV):

Adults

Prevention: A dose of 1 mg (10 u03bcg/kg) of GRANTRYL 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 GRANTRYL should be administered as a slow intravenous injection (over 30 seconds). The maximum dose for patients undergoing anaesthesia for surgery is a total dose of 3 mg of GRANTRYL intravenous in one day.

Paediatrics

Due to lack of data, GRANTRYL is not recommended for prevention and treatment of PONV in children.

Special dosage instructions:

Elderly patients (65 years of age or older) No dosage adjustments required.

Renal impairment No dosage adjustment required

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, GRANTRYL should be used with a certain amount of caution in this patient group. See Pharmacokinetics.

Method of administration

Preparation of dosage form: Use immediately after reconstitution. Solutions should not be stored for longer than 24 hours at a temperature of 2 u2013 8 u00b0C unless prepared under controlled aseptic conditions.

Adults: GRANTRYL may be diluted with 20 to 50 ml of the following infusion fluids:

• 0,9 % m/v sodium chloride
• 0,18 % m/v sodium chloride and 4 % m/v glucose
• 5 % m/v glucose
• Hartmannu2019s solution
• Sodium lactate
• 10 % m/v mannitol

Children (>2 years): GRANTRYL may be diluted with 10 to 30 ml of the following infusion fluids:

• 0,9 % m/v sodium chloride
• 0,18 % m/v sodium chloride and 4 % m/v glucose
• 5 % m/v glucose
• Hartmannu2019s solution
• Sodium lactate
• 10 % m/v mannitol

Hypersensitivity to any of the ingredients contained in GRANTRYL.

Children under the age of 2 years.

Pregnancy and lactation (see PREGNANCY AND LACTATION).

Congenital long QT-syndrome.

As GRANTRYL may reduce lower bowel motility, patients with signs of sub-acute intestinal obstruction should be monitored following administration of GRANTRYL.

The maximum dose of GRANTRYL to be administered over 24 hours should not exceed 9 mg (120 u03bcg/kg).

GRANTRYL may be associated with dysrhythmias or ECG abnormalities. This may have clinical significance in patients with pre-existing dysrhythmias or cardiac conduction disorders and/or patients with concomitant electrolyte disturbances, or in patients who are being treated with antidysrhythmic medicines, beta-blockers and medicines that prolong the QT-interval.

Cases of myocardial ischemia have been reported in patients treated with granisetron. In some patients, especially in the case of intravenous administration, symptoms appeared immediately after administration of granisetron. Patients should be alerted to the signs and symptoms of myocardial ischaemia.

Hepatic enzyme induction with phenobarbital resulted in an increase in total plasma clearance of intravenous GRANTRYL of approximately one-quarter. GRANTRYL may be co-administered with benzodiazepines, neuroleptics and anti-ulcer medications commonly prescribed with anti-emetic treatments. No apparent interaction with emetogenic cancer chemotherapies has been shown. No specific interaction studies have been conducted in anaesthetised patients, but GRANTRYL may be administered with commonly used anaesthetic and analgesic agents. In addition, in vitro human microsomal studies have shown that the cytochrome P450 subfamily 3A4 (involved in the metabolism of some of the main narcotic analgesic agents) is not modified by granisetron.

The use of GRANTRYL during pregnancy and lactation is contra-indicated as safety and efficacy have not been established (see CONTRA-INDICATIONS).

GRANTRYL may cause somnolence and transient visual disturbances. Patients should be advised not to drive or handle machinery if these side effects occur.

The following side effects may occur with use of GRANTRYL:

Infections and infestations

Frequency not known : Infection, urinary tract infection

Blood and lymphatic system disorders

Frequency not known : Anaemia, leukocytosis

Immune system disorders

Less frequent : Hypersensitivity reactions, including skin rashes and anaphylaxis.

Psychiatric disorders

Less frequent : Anxiety, insomnia, somnolence.

Nervous system disorders

Less frequent : Headache, dizziness, seizures, oculogyric crisis.

Eye disorders

Frequency not known : Transient visual disturbances such as blurred vision.

Cardiac disorders

Less frequent : Angina pectoris, dysrhythmias, atrial fibrillation, chest pain, fainting, tachycardia, bradycardia, ECG abnormalities, QT-prolongation. Frequency unknown: myocardial ischemia (see section 4.4)

Vascular disorders

Less frequent : Hypertension, hypotension, flushes.

Gastrointestinal disorders

Frequent : Abdominal pain, constipation, diarrhoea, hiccups

Less frequent : Dyspepsia, unusual taste in mouth.

Musculoskeletal disorders

Frequency not known : Dystonia and dyskinesia

Hepato-biliary disorders

Less frequent : A rise in hepatic transaminases.

General disorders and administration site disorders

Frequent : Asthenia/fatigue

Less frequent : Fever, injection site reactions.

Headache may occur. There is no specific antidote for granisetron. In the case of over-dosage, symptomatic and supportive treatment should be given.