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Pharmacological properties Pharmacotherapeutic group: Antiemetics and antinauseants, serotonin (5-HT3) antagonists 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.  Interaction with neurotropic and other active substances through its activity on P 450-cytochrome has been reported.In vitro studies have shown that the cytochrome  P450 sub-family 3A4 (involved in the metabolism of some of the main narcotic agents) is not modified by granisetron. Although ketoconazole was shown to inhibit the ring oxidation of granisetron in vitro, this action is not considered clinically relevant. Although QT-prolongation has been observed with 5-HT3 receptors antagonists, this effect is of such occurrence and magnitude that it does not bear clinical significance in normal subjects. Nonetheless it is advisable to monitor both ECG and clinical abnormalities when treating patients concurrently with drugs known to prolong the QT. Pharmacokinetic properties Pharmacokinetics of the oral administration is linear up to 2.5-fold of the recommended dose in adults. It is clear from the extensive dose-finding programme that the antiemetic efficacy is not unequivocally correlated with either administered doses or plasma concentrations of granisetron. A fourfold increase in the initial prophylactic dose of granisetron made no difference in terms of either the proportion of patient responding to treatment or in the duration of symptoms control. Distribution: Granisetron is extensively distributed, with a mean volume of distribution of approximately 3 l/kg. Plasma protein binding is approximately 65%. Biotransformation: Granisetron is metabolized primarily in the liver by oxidation followed by conjugation. The major compounds are 7-OH-granisetron and its sulphate and glycuronide conjugates. Although antiemetic properties have been observed for 7-OH-granisetron and indazoline N-desmethyl granisetron, it is unlikely that these contribute significantly to the pharmacological activity of granisetron in man. In vitro liver microsomal studies show that granisetron’s major route of metabolism is inhibited by ketoconazole, suggestive of metabolism mediated by the cytochrome P-4503A subfamily. Elimination: Clearance is predominantly by hepatic metabolism. Urinary excretion of unchanged granisetron averages 12% of dose while that of metabolites amounts to about 47% of dose. The remainder is excreted in faeces as metabolites. Mean plasma half-life in patients by the oral and intravenous route is approximately 9 hours, with a wide inter-subject variability.

Each 3 ml ampoule contains 3 mg granisetron as granisetron hydrochloride in a 3 ml sterile concentrate for solution  The other ingredients are sodium chloride, citric acid monohydrate, sodium hydroxide and water for injections

Grani-Denk 1 mg/ml is used to prevent or treat nausea and vomiting (feeling and being sick) caused by other medical treatments, such as chemotherapy or radiotherapy for cancer, and by surgery

Do not use Grani-Denk 1 mg/ml  if you are allergic to granisetron or any of the other ingredients of this medicine (listed in section 6)  If you are not sure, talk to your doctor, pharmacist or nurse before having the injection.

If you notice the following problem you must see a doctor straight away: allergic reactions (anaphylaxis). The signs may include swelling of the throat, face, lips and mouth, difficulty in breathing or swallowing. Other side effects that may be experienced while using this medicine are: Very common (affects more than 1 user in 10) headache constipation. Your doctor will monitor your condition. Common (affects 1 to 10 users in 100) problems sleeping (insomnia) changes in how your liver is working shown by blood tests diarrhoea Uncommon (affects 1 to 10 users in 1,000) skin rashes or an allergic skin reaction or “nettle-rash” or “hives” (urticaria). The signs may include red, raised itchy bumps. changes in the heartbeat (rhythm) and changes seen on ECG readings (electrical recordings of the heart) abnormal involuntary movements, such as shaking, muscle rigidity and muscle contractions Serotonin Syndrome. The signs may include diarrhoea, nausea, vomiting, high temperature and blood pressure, excessive sweating and rapid heartbeat, agitation, confusion, hallucination, shivering, muscles shakes, jerks or stiffness, loss of coordination and restlessness.

Tell your doctor, pharmacist or nurse if you are taking, have recently taken or might take any other medicines, including medicines obtained without a prescription. This is because Grani-Denk 1 mg/ml can affect the way some medicines work. Also some other medicines can affect the way Grani-Denk 1 mg/ml works. In particular, tell your doctor, nurse or pharmacist if you are taking the following medicines:  medicines used to treat an irregular heartbeat  other ‘5-HT3 receptor antagonist’ medicines such as dolasetron or ondansetron (see “Warnings and precautions” above) phenobarbital, a medicine used to treat epilepsy • ketoconazole, a medicine used in the treatment of fungal infections  the antibiotic erythromycin used to treat bacterial infections  SSRIs (selective serotonin reuptake inhibitors) used to treat depression and/or anxiety. Examples are fluoxetine, paroxetine, sertraline, fluvoxamine, citalopram, escitalopram.  SNRIs (serotonin noradrenaline reuptake inhibitors) used to treat depression and/or anxiety. Examples are venlafaxine, duloxetine

Because the injection or infusion will be given to you by a doctor or nurse, it is unlikely that you will be given too much. However, if you are worried talk to your doctor or nurse.  Symptoms of overdose include mild headaches. You will be treated depending on your symptoms.

The injection will be given to you by a doctor or nurse. The dose of Grani-Denk 1 mg/ml varies from one patient to another. It depends on your age, weight, and whether you are being given the medicine to prevent, or treat nausea and vomiting.  The doctor will work out how much to give you. Grani-Denk 1 mg/ml can be given as an injection into the veins (intravenous). Prevention of feeling or being sick following radio- or chemotherapy  You will be given the injection before your radio- or chemotherapy starts. The injection into your veins will take between 30 seconds and 5 minutes and the dose will usually be between 1 mg and 3 mg. The medicine may be diluted before it is injected.  Treatment of feeling or being sick following radio- or chemotherapy  The injection will take between 30 seconds and 5 minutes and the dose will usually be between 1 mg and 3 mg. The medicine may be diluted before it is injected into your veins. You may be given more injections to stop your sickness after the first dose. There will be at least 10 minutes between each injection. The most granisetron you will be given is 9 mg a day

Store below 25 °C.  Do not freeze.