Granisetron-Teva - instructions for use, dose, side effects, contraindications

Granisetron is a selective antagonist of 5-hydroxytryptamine (5-HT₃) receptors located in the endings of the vagus nerve (n.vagus) and the trigger zone of the bottom of the IV ventricle of the brain (practically does not affect other receptors of serotonin), with pronounced antiemetic effect. Has little affinity for other types of receptors, including 5-HT₁, 5-HT₂, 5-HT₄ and dopamine (D₂) receptors.

Eliminates the vomiting that occurs when the parasympathetic nervous system is excited, due to the release of serotonin by enterochromaffine cells.

Pharmacokinetics:

Distribution. Apparent volume of distribution (V_d) is 3 l / kg. Binding to plasma proteins is approximately 65%. The average value of the clearance of granisetron is approximately 27 l / h. The maximum concentration in serum (C_mOh) with intravenous administration of 63.8 ng / ml. It is distributed in plasma and erythrocytes. The concentration of granisetron in plasma does not have a clear correlation with the severity of the antiemetic effect. Clinical effect can be observed, even if granisetron is not found in the blood plasma.

Metabolism. Metabolised in the liver by N-detylation, oxidation and conjugation with the participation of isoenzyme CYP3A4 cytochrome P450. The resulting metabolites have antiserotonin activity.

Excretion. The half-life (T_1/2) with intravenous (IV) administration is 9 hours with a wide individual variability. On average, 12% of the administered dose is unchanged in the kidneys and 47% in the form of metabolites, the remainder. the drug is excreted by the intestines in the form of metabolites.

Pharmacokinetics in specific patient categories

After a single intravenous (iv) administration of the recommended dose of granisetron, the pharmacokinetic parameters in elderly patients remain within the limits of the norm.

Renal insufficiency does not have a significant effect on the kinetics of granisetron.

In patients with hepatic insufficiency, which has arisen in connection with a neoplasm of the liver, the total clearance is reduced approximately 2-fold. V_d and the overall clearance in adults and children with malignant neoplasms does not differ.

Indications:

- Prevention and treatment of nausea and vomiting in cytostatic chemotherapy in adults and children over 2 years of age;

- prevention and treatment of nausea and vomiting during radiation therapy in adults;

- treatment of postoperative nausea and vomiting in adults.

Contraindications:

- Hypersensitivity to granisetron and other components of the drug;

- hypersensitivity reactions to other selective antagonists of serotonin 5-HT₃ receptors (including ondansetron) in the anamnesis;

- the period of breastfeeding.

Carefully:

Partial intestinal obstruction, arrhythmias and conduction disorder in the anamnesis, pregnancy.

Data on efficacy and safety in the use of granisetron in children younger than 2 years are absent.

Pregnancy and lactation:

Despite the fact that teratogenicity of granisetron has not been proven, the use of Granisetron-Teva during pregnancy is possible only if the intended benefit to the mother exceeds the potential risk to the fetus.

There are no data on the penetration of granisetron into breast milk. It is necessary to suspend breastfeeding while taking the drug.

Dosing and Administration:

In the form of intravenous (IV) infusion.

Adults

Prevention of nausea and vomiting during cytostatic chemotherapy

Infusion of Granisetron-Teva is carried out at least 30 minutes before the start of cytostatic chemotherapy.

- Patients with a body weight of more than 50 kg: Granisetron-Teva concentrate concentrate 3mg / 3ml (1 ampoule) is diluted with an infusion solution to a volume of 15 ml and administered as an IV bolus infusion for at least 30 seconds or diluted with an infusion solution to a volume of 20-50 ml and injected into form IV infusion for at least 5 minutes.

- Patients weighing less than 50 kg: Concentrate Granisetron-Teva in a dose of 20-40 mkg / kg is diluted with an infusion solution to a volume of 10-30 ml and is administered as an intravenous drip infusion for at least 5 minutes.

Prophylactic administration of Granisetron-Teva should be completed before the start of cytostatic chemotherapy.

Prevention of nausea and vomiting during radiotherapy

The dosage regimen is the same as in the prevention of nausea and vomiting in the conduct of cytostatic chemotherapy.

Treatment of nausea and vomiting during cytostatic chemotherapy and radiotherapy

The dosage regimen is the same as in the prevention of nausea and vomiting in the conduct of cytostatic chemotherapy. If necessary, you can spend 2 additional intravenous infusions with an interval of at least 10 minutes in a dose of not more than 3 mg. The maximum daily dose should not exceed 9 mg (within 24 hours not more than 3 times 3 mg).

Treatment of postoperative nausea and vomiting

Concentrate Granisetron-Teva 1 mg / 1 ml (1 ampoule) is diluted with an infusion solution to a volume of 5 ml and administered as an IV bolus in a slow bolus for at least 30 seconds once.

Children over 2 years old

Prevention of nausea and vomiting in the conduct of cytostatic chemotherapy

Infusion of Granisetron-Teva is carried out at least 30 minutes before the start of cytostatic chemotherapy.

Concentrate Granisetron-Teva in a dose of 20 mkg / kg is diluted with an infusion solution to a volume of 10-30 ml and is administered as an intravenous drip infusion for at least 5 minutes.

Prophylactic administration of Granisetron-Teva should be completed before the start of cytostatic chemotherapy.

Treatment of nausea and vomiting during cytostatic chemotherapy

The dosage regimen is the same as in the prevention of nausea and vomiting in the conduct of cytostatic chemotherapy. If necessary, 2 additional intravenous infusions may be performed at intervals of at least 10 minutes at a dose of 20 μg / kg.

The maximum daily dose should not exceed 60 mcg / kg.

In patients with renal or hepatic insufficiency, and elderly patients correction of the dose is not required.

Preparation of a solution for intravenous infusion

To obtain a solution of the Granisetron-Teva preparation for intravenous infusion, sterile infusion solutions are used: 0.9% sodium chloride solution, 0.18% sodium chloride solution and 4% dextrose solution, 5% dextrose solution, Hartman's solution, sodium lactate solution or 10% mannitol solution. Use of other infusion solutions is not allowed. A solution for intravenous infusion is prepared immediately before use. The finished solution is stable for 24 hours at room temperature, protected from direct sunlight.

Side effects:

The incidence of side effects is classified according to the recommendations of the World Health Organization: very often - not less than 10%; often - not less than 1%, but less than 10%; infrequently - not less than 0,1%, but less than 1%; rarely - not less than 0.01%, but less than 0.1%; very rarely - less than 0.01%, including isolated cases.

From the nervous system: very often - headache; often - insomnia, drowsiness, weakness; rarely - dystonia, dyskinesia; very rarely - anxiety, anxiety, anorexia, fainting, dizziness, coma.

From the digestive system: very often constipation; often - abdominal pain, diarrhea, vomiting, decreased appetite, flatulence; rarely - a violation of liver function; increased activity of "hepatic" enzymes (aspartate aminotransferase, alanine aminotransferase), heartburn, changes in taste.

From the cardiovascular system: rarely - arrhythmia, pain in the heart; very rarely - lowering blood pressure (BP), increasing blood pressure.

From the immune system: rarely - hypersensitivity reactions, anaphylaxis, dyspnea, bronchospasm, urticaria; very rarely - skin rash, itching, swelling / swelling of the face.

Other: often - asthenia, pain syndrome, fever, flu-like syndrome.

Overdose:

The use of granisetron in the form of a single injection at a dose of 30 mg was accompanied by an easy headache. Serious adverse reactions were not observed.

Treatment: the specific antidote is unknown. Conduct symptomatic therapy.

Interaction:

Pharmaceutically incompatible with other medicines.

Granisetron does not change the activity of cytochrome P450 isoenzymes. Inductors and inhibitors of cytochrome P450 isoenzymes can influence T_1/2and the clearance of granisetron.

With the intravenous administration of granisetron for the isoenzymes of the cytochrome P450 system, phenobarbital resulted in an increase in the total plasma clearance by approximately 25%. Research in vitro showed that ketoconazole can inhibit the metabolism of granisetron by affecting the isoenzyme CYP3A4 cytochrome P450. The clinical significance of this fact is unknown.

The effectiveness of granisetron can be enhanced by intravenous administration of glucocorticosteroids.

To date, there have been no signs of interactions between granisetron and drugs often prescribed for the purpose of antiemetic treatment (eg, benzodiazepines and antipsychotics), as well as drugs prescribed for digestive disorders. In addition, there were no any interactions between granisetron and vomiting cytostatic drugs.

Special instructions:

As granisetron can reduce intestinal motility, patients with signs of partial obstruction of the intestine after granisetron administration should be under the supervision of a doctor.

Elderly patients, as well as patients with impaired renal or hepatic function, do not need special precautions.Although to date no evidence of an increase in the incidence of adverse events in patients with impaired hepatic function has been identified, granisetron in this group of patients should be used with caution, given its pharmacokinetics.

The use of 5-HT antagonists₃-receptors, including granisetron, may be accompanied by the occurrence of arrhythmias or abnormalities of the ECG from the norm. This effect can be clinically significant in patients with previous heart rhythm disturbances and conduction, as well as in patients receiving antiarrhythmic drugs or beta-blockers.

With a high degree of emetogenic action or high-dose cytostatic chemotherapy, in order to increase the efficiency of granisetron, dexamethasone before cytostatic therapy or methylprednisolone before and after cytostatic therapy.

In 1 ml of Granisetron-Teva, 0.15 mmol (3.5 mg) of sodium is contained. This fact should be taken into account for patients who follow a diet with a restriction of sodium intake, if the daily dose of the drug exceeds 6.6 ml.

Effect on the ability to drive transp. cf. and fur:

Considering the possibility of developing dizziness, during the treatment with granisetron it is necessary to take care when driving vehicles and engage in potentially dangerous activities that require an increased concentration of attention and speed of psychomotor reactions.

Form release / dosage:

Concentrate for solution for infusion, 1 mg / ml.

Packaging:

For 1 or 3 ml in ampoules of colorless glass type I with a white break point.

5 ampoules in a plastic pallet are placed together with instructions for use in a cardboard box.

Storage conditions:

Store at a temperature of no higher than 25 ° C, in a place protected from light.

Do not freeze.

Keep out of the reach of children.

Shelf life:

3 years.

Do not use after the expiration date printed on the package.

Terms of leave from pharmacies:On prescription

Registration number:LP-001058

Date of registration:27.10.2011

Date of cancellation:2016-10-27

The owner of the registration certificate:Teva Pharmaceutical Enterprises Co., Ltd.Teva Pharmaceutical Enterprises Co., Ltd. Israel

Manufacturer: & nbsp

TEVA Pharmaceutical Works Private, Ltd. Co. Hungary

Representation: & nbspTeva Teva Israel

Information update date: & nbsp26.12.2015

Illustrated instructions

Instructions

Granisetron-Teva (Granisetrone-Teva)