INDICATIONS     CONTRA-INDICATIONS     DOSAGE     SIDE-EFFECTS     PREGNANCY     OVERDOSE     IDENTIFICATION     PATIENT INFORMATION

Logo KYTRIL ORAL (Tablets)
KYTRIL 3 mg (Ampoule)

SCHEDULING STATUS:
S4

PROPRIETARY NAMES
(and dosage form):

KYTRIL ORAL (Tablets)
KYTRIL 3 mg (Ampoule)

COMPOSITION:
Pharmaceutical Form
Oral: Each KYTRIL tablet contains
granisetron hydrochloride equivalent to 1,0 mg granisetron free base.
Intravenous: Each KYTRIL 3 mg ampoule contains a sterile, clear solution equivalent to 1 mg granisetron free base per 1 mL isotonic solution. The content allows withdrawal of 3 mL.

PHARMACOLOGICAL CLASSIFICATION:
A.5.7.2. Anti-emetics and anti-vertigo preparations.

PHARMACOLOGICAL ACTION:
KYTRIL
is a selective antagonist of 5-hydroxytryptamine (5-HT)3-receptors. Radioligand binding studies have demonstrated that KYTRIL has negligible affinity for other receptor types including 5-HT and dopamine D2 binding sites.

INDICATIONS:
KYTRIL
3 mg (ampoule) is indicated for the prevention or treatment of nausea and vomiting induced by cytostatic therapy.
KYTRIL ORAL (tablets) is indicated for the prevention of nausea and vomiting induced by moderately emetogenic cytostatic therapy.

CONTRA-INDICATIONS:
Sensitivity to any of the ingredients.

WARNINGS:
A dose related increase in background hepatocellular carcinoma and/or adenoma in rats and mice of both sexes receiving in excess of 25 times the intended dose for 2 years have been reported. None of these findings were present after one year at any of the doses. The clinical relevance of this finding is unclear.
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 µg/kg).

DOSAGE:
Adults:
Oral:
The dose of KYTRIL is 1 mg twice a day for up to one week following cytostatic therapy. The first dose of KYTRIL should be administered within one hour before the start of cytostatic therapy.

Intravenous: The dose of KYTRIL is 3 mg (corresponding to a dose of plus minus 40 µg/kg) which should be diluted as directed in 20 to 50 mL infusion fluid and administered over 5 minutes by slow intravenous injection or infusion.

Maximum Daily Dose:
Up to two additional 5-minute administrations of 3 mg KYTRIL may be administered within a 24 hour period.

Additional administration should be administered at least 10 minutes apart. The maximum dose of KYTRIL infusion to be administered over 24 hours should not exceed 9 mg (120 µg/kg).

The experience of the use of granisetron beyond 7 cycles of chemotherapy is limited.

Special Groups:
Although present experience indicates that no dosage adjustment is required, care should be exercised when administering KYTRIL to elderly patients and patients with renal or hepatic impairment.

Children:
Insufficient data is available at present to enable a dosage recommendation to be made in children.

DIRECTIONS FOR USE:
Preparing the Injection:
To prepare the dose of KYTRIL 3 mg the contents of one ampoule (3 mg) or 40 µg/kg is withdrawn from the ampoule and diluted with infusion fluid, to a total volume of 20 to 50 mL in any of the following solutions: 0,9% m/v sodium chloride, 0,18% m/v sodium chloride and 4% m/v dextrose, 5% m/v dextrose, Hartmann’s solution, sodium lactate and 10% m/v mannitol.

Stability:
Ideally intravenous injections of KYTRIL 3 mg should be prepared at the time of administration.

However, the recommended solutions of KYTRIL 3 mg have been shown to be stable for at least 24 hours in the following solutions when stored at room temperature: 0,9% m/v sodium chloride, 0,18% m/v sodium chloride and 4% m/v dextrose, 5% m/v dextrose, Hartmann’s solution, sodium lactate and 10% m/v mannitol.

Compatibility:
As a general precaution, KYTRIL 3 mg should not be mixed in solution with other medicines. Prophylactic administration of KYTRIL 3 mg should be completed prior to the start of cytostatic therapy. No interactions with KYTRIL 3 mg have been recorded with multiple chemotherapy regimes including cisplatin up to 120 mg/m2.

SIDE-EFFECTS AND SPECIAL PRECAUTIONS:
Side-effects:
Headache and constipation have been the most frequently noted adverse events. A rise in hepatic transaminases may occur. Minor skin rashes have been noted less frequently.

Interactions:
In humans, hepatic enzyme induction with phenobarbital resulted in an increase in total plasma clearance of intravenous KYTRIL of approximately one-quarter.

KYTRIL has been administered in humans with benzodiazepines, neuroleptics and antiulcer medications, commonly prescribed with anti-emetic treatments. Additionally, KYTRIL has shown no apparent drug interaction with emetogenic cancer chemotherapies.

Use in pregnancy and lactating mothers:
Safety in pregnancy and lactation has not been established.

Effects on ability to drive and use machines:
There have been reports of somnolence in clinical studies and this should be taken into account

KNOWN SYMPTOMS OF OVERDOSAGE AND PARTICULARS OF ITS TREATMENT:
Headache may occur. There is no specific antidote for KYTRIL 3 mg. In the case of overdosage, symptomatic treatment should be given.

IDENTIFICATION:
KYTRIL ORAL:
Each KYTRIL ORAL tablet is presented as white triangular film-coated tablets.

KYTRIL 3 mg: Each KYTRIL 3 mg ampoule contains a clear, colourless or slightly straw-coloured sterile solution.

PRESENTATION:
KYTRIL ORAL
is supplied in blister packs containing 5 tablets per blister strip.
KYTRIL 3 mg is supplied in cartons containing 5 or 10 ampoules.

STORAGE INSTRUCTIONS:
Store below 30°C.
Ampoules removed from the pack should be stored protected from direct sunlight.
Do not freeze.
KEEP OUT OF REACH OF CHILDREN.

REGISTRATION NUMBERS:
KYTRIL ORAL:
28/5.7.2/0162
KYTRIL 3 mg: Y/5.7.2/272

NAME AND BUSINESS ADDRESS OF THE APPLICANT:
SmithKline beecham Pharmaceuticals (Pty) Ltd.
6 Carey Street, Wynberg Ext. 6,
Johannesburg, 2090

DATE OF PUBLICATION OF THIS PACKAGE INSERT:
24.12.1993

KYTRIL and the SB logo are trademarks

P1276

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