Kytril 1 mg/2 mg/3 mg Tablets

KYTRIL is indicated for the prevention and treatment (control) of:

• a) acute and delayed nausea and vomiting associated with chemotherapy (CINV) and radiotherapy (RINV).
• b) post-operative nausea and vomiting (PONV).

Chemotherapy Induced Nausea and Vomiting (CINV)

Adults

Tablets: Prevention: 1 mg twice a day or 2 mg once a day for up to one week following chemotherapy. The first dose of KYTRIL should be administered within 1 hour before the start of therapy.

Intravenous: Prevention: A dose of 1 - 3 mg (10 - 40 u03bcg/kg) of KYTRIL should be administered either as a slow intravenous injection (over 30 seconds) or as an intravenous infusion diluted in 20 to 50 muf06c infusion fluid and administered over 5 minutes, prior to the start of chemotherapy.

Treatment: A dose of 1 - 3 mg (10 - 40 u03bcg/kg) KYTRIL should be administered either as a slow intravenous injection (over 30 seconds) or as an intravenous infusion diluted in 20 to 50 muf06c infusion fluid and administered over 5 minutes. Further treatment doses of KYTRIL may be administered, if required, at least 10 minutes apart. The maximum dose of KYTRIL to be administered over 24 hours should not exceed 9 mg.

Intramuscular: Prevention & Treatment: A dose of 3 mg of KYTRIL should be administered by the intramuscular route, 15 minutes prior to the start of chemotherapy.

Paediatrics

Intravenous: A dose of 10 - 40 u03bcg/kg body weight (up to 3 mg) should be administered as an intravenous infusion, diluted in 10 to 30 muf06c 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 KYTRIL by the intramuscular route in children.

Radiotherapy Induced Nausea and Vomiting (RINV)

Adults

Tablets: 2 mg once a day for up to one week following radiotherapy. The first dose of KYTRIL should be administered within 1 hour before the start of therapy.

Intravenous: Prevention: A dose of 1 - 3 mg (10 - 40 u03bcg/kg) of KYTRIL should be administered either as a slow intravenous injection (over 30 seconds) or as an intravenous infusion diluted in 20 to 50 muf06c infusion fluid and administered over 5 minutes, prior to the start of radiotherapy.

Paediatrics

There is insufficient information to recommend use of KYTRIL 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 KYTRIL 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 KYTRIL 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 of KYTRIL intravenous in one day.

Paediatrics

There is insufficient information to recommend use of KYTRIL in the prevention and treatment of postoperative nausea and vomiting in children.

Special Dosage Instructions

Geriatrics: No dosage adjustments required.

Renal impairment: No dosage adjustments required.

Hepatic Impairment: No dosage adjustments required.

KYTRIL is contraindicated in patients hypersensitive to granisetron or its excipients. Children under the age of 2 years.

As KYTRIL may reduce lower bowel motility, patients with signs of sub-acute intestinal obstruction should be monitored following administration of KYTRIL. The maximum dose of KYTRIL to be administered over 24 hours should not exceed 9 mg (120 u03bcg/kg).

In humans, hepatic enzyme induction with phenobarbital resulted in an increase in total plasma clearance of intravenous KYTRIL of approximately one-quarter. In vitro human microsomal studies, ketoconazole inhibited ring oxidation of KYTRIL. However given the absence of pK/pD relationship with granisetron, these changes are believed to have no clinical consequences. KYTRIL has been administered in humans with benzodiazepines, neuroleptics and anti-ulcer medications commonly prescribed with anti-emetic treatments. Additionally, KYTRIL has shown no apparent interaction with emetogenic cancer chemotherapies. No specific interaction studies have been conducted in anaesthetised patients, but KYTRIL has been safely 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 KYTRIL.

Safety in pregnancy and lactation has not been established. There are no studies in pregnant women and it is not known whether granisetron is excreted in human milk. Use of KYTRIL during pregnancy or lactation should be limited to situations where the potential benefit to the mother justifies the potential risk to the foetus or nursing infant.

There have been reports of somnolence in clinical studies and this should be taken into account.

All side effects were reported as very rare (< 1/10 000)

• Nervous system disorders: Headache
• Gastrointestinal disorders: Constipation
• Skin disorders: Skin rashes
• General disorders: Allergic reactions and anaphylaxis
• Liver and Biliary System Disorders: A rise in hepatic transaminases may occur.

Headache may occur. There is no specific antidote for KYTRIL. In the case of overdosage, symptomatic treatment should be given.