Granisetron
Granisetron: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. Drug interactions
- 12. Analogs
- 13. Terms and conditions of storage
- 14. Terms of dispensing from pharmacies
- 15. Reviews
- 16. Price in pharmacies
Latin name: Granisetrone
ATX code: A04AA02
Active ingredient: Granisetron (Granisetronum)
Manufacturer: Ozone, LLC (Russia); R-Pharm, JSC (Russia)
Description and photo updated: 2019-18-03
Granisetron is a centrally acting antiemetic drug.
Release form and composition
Dosage forms:
- concentrate for preparation of solution for infusion: clear liquid without color (1 or 3 ml each in colorless glass vials, in a cardboard box of 5 or 10 vials);
- film-coated tablets: round biconvex, the core is almost white, the shell is white or almost white (10, 20, 30, 40, 50 or 100 pieces each in PET / polypropylene cans, sealed with PP / polyethylene screw caps with first opening control / “push-turn” system or stretch lids made of polyethylene with first opening control, in a cardboard box 1 can; 10, 30 or 50 pieces in blisters, in a cardboard box 1–5 or 10 packs).
Each pack also contains instructions for the use of Granisetron.
Composition of 1 ml of concentrate:
- active substance: granisetron - 1 mg (in the form of granisetron hydrochloride - 1.42 mg);
- auxiliary components: sodium chloride - 9 mg; citric acid monohydrate - 2 mg; hydrochloric acid - in the required amount; sodium hydroxide - in the required amount; water for injection - up to 1 ml.
Composition of 1 tablet:
- active substance: granisetron - 1 mg (in the form of granisetron hydrochloride - 1.12 mg);
- auxiliary components: lactose monohydrate - 75.38 mg; microcrystalline cellulose - 20 mg; sodium carboxymethyl starch - 2 mg; hypromellose - 1 mg; magnesium stearate - 0.5 mg;
- shell: macrogol-4000 - 0.42 mg; hypromellose - 1.74 mg; titanium dioxide - 0.84 mg.
Pharmacological properties
Pharmacodynamics
Granisetron is a selective antagonist of serotonin (5-hydroxytryptamine) 5-HT 3 -receptors, which are located in the trigger zone of the fundus of the IV ventricle of the brain and at the ends of the vagus nerve (practically does not affect other serotonin receptors). Has pronounced antiemetic properties. Studies have shown that granisetron has low affinity for other types of receptors, including other types of serotonin receptors and D 2 -dopamine receptors.
Granisetron helps to eliminate vomiting, which occurs when the parasympathetic nervous system is excited due to the release of serotonin by enterochromaffin cells. The substance is also effective for nausea and vomiting caused by radiation therapy, cytotoxic chemotherapy, and postoperative nausea and vomiting.
It has no effect on the plasma concentration of aldosterone and prolactin.
Due to the action on myocardial repolarization, hERG is blocked - the gene of specific potassium channels of the heart. On the ECG (electrocardiogram) indicators, this manifests itself in the form of changes in PR, QRS and especially in the lengthening of the QT interval.
Granisetron has a mutagenic effect. With lifelong administration in high doses in animals, there is an increase in the likelihood of developing hepatocellular tumors.
Pharmacokinetics
After oral administration of the tablets, granisetron is absorbed quickly and completely, however, due to the effect of the first pass through the liver, the absolute bioavailability decreases to 60%. Food intake has no effect on this indicator.
The substance is distributed to tissues and organs (including erythrocytes and plasma), the average V d (volume of distribution) is 3 l / kg. Binds to plasma proteins - at about 65%.
The average value of the clearance of the substance is approximately 27 l / h. With intravenous administration, C max (maximum concentration) of the substance in the blood serum is 63.8 ng / ml. The plasma concentration of granisetron with the severity of the antiemetic effect does not have a clear correlation. The development of a clinical effect can be observed even in cases where granisetron is not detected in the blood plasma.
Biological transformation occurs predominantly in the liver by N-demethylation and oxidation of the aromatic ring, and then by conjugation. The main metabolites are 7-OH-granisetron sulfate, 7-OH-granisetron, and glucuronic conjugates. Some of them, for example, indazoline N-desmethyl granisetron and 7-OH-granisetron, have antiemetic properties, while the likelihood of a significant manifestation of their effect on the human body is low. According to the studies, ketoconazole inhibits the metabolism of granisetron, which suggests the involvement of isoenzymes of the CYP3A subfamily. Based on other studies, granisetron does not affect the activity of the isoenzyme CYP3A4.
On average, 12% of the dose is excreted unchanged by the kidneys, and 47% in the form of metabolites. The remaining 41% of the substance is excreted as metabolites by the intestines.
T 1/2 (half-life) has a wide individual variability and with oral and intravenous administration is 9 hours.
With oral administration, the linear nature of the pharmacokinetics of granisetron remains in the range of doses that are up to 2.5 times higher than the recommended ones.
In patients with hepatic insufficiency associated with neoplastic changes, the total plasma clearance is approximately 1/2 in comparison with this indicator in patients without liver dysfunction. Despite these changes, dose adjustment is not required.
With the introduction of granisetron at a dose of 0.02 mg / kg in children, clinically significant differences in pharmacokinetic parameters from those in adults were not observed.
Indications for use
- nausea and vomiting during cytostatic chemotherapy: therapy (infusion solution) and prevention;
- nausea and vomiting during radiation therapy: therapy and prevention;
- postoperative nausea and vomiting: therapy (infusion solution).
Contraindications
Absolute:
- burdened history of hypersensitivity reactions to other selective antagonists of serotonin 5-HT 3 receptors;
- breast-feeding;
- age up to 2 or 12 years (for infusion solution and tablets, respectively);
- individual intolerance to the components of the drug.
Relative (Granisetron is prescribed under medical supervision):
- partial intestinal obstruction;
- concomitant heart disease, especially with arrhythmia in the syndrome of long QT interval;
- cardiotoxic chemotherapy and / or the presence of concomitant electrolyte disturbances;
- hereditary galactose intolerance, lactase deficiency, glucose-galactose malabsorption (for tablets);
- pregnancy.
Granisetron, instructions for use: method and dosage
Film-coated tablets
Granisetron tablets should be taken orally, swallowed whole with water.
Recommended dosage regimen:
- cytostatic chemotherapy (use for prophylaxis): 2 times a day, 1 mg or once a day 2 mg, no longer than 7 days after the start of cytostatic therapy. The first dose should be taken 1 hour before the start of cytostatic therapy;
- radiation therapy (use for treatment and prevention): 1 time per day, 2 mg no longer than 7 days after the start of radiation therapy. The first dose should be taken 1 hour before the start of radiation therapy.
Concentrate for solution for infusion
A solution prepared from Granisetron concentrate is intended for intravenous administration.
To obtain a solution, you can use the following infusion solutions: Hartmann's solution; 0.9% sodium chloride solution; 5% dextrose solution; 0.18% sodium chloride solution and 4% dextrose solution; mannitol solution or sodium lactate solution. Other solutions cannot be used.
The concentrate for the preparation of the infusion solution must be used immediately after opening the bottle; further use of the drug remaining in the bottle is prohibited.
The solution must be applied immediately after preparation. The ready-made solution is stable for 24 hours under normal room lighting at a temperature of 15-25 ° C.
Intravenous administration of the drug is allowed without dilution.
Recommended adult dosing regimen for cytostatic chemotherapy (prophylaxis):
- patients weighing 50 kg or more: 1 bottle (3 mg / 3 ml) should be diluted in 20-50 ml of infusion solution, administration time - 5 minutes; the drug must be used before starting cytostatic chemotherapy; also 1 bottle (3 mg / 3 ml) can be administered as a bolus (over 30 seconds);
- patients weighing up to 50 kg: 0.02–0.04 mg / kg; the infusion must be completed before starting cytostatic therapy.
According to clinical data, most patients required only 1 dose of Granisetron for 24 hours to control vomiting and nausea.
The dosage regimen for radiation therapy (prophylactic use) is the same as for the prevention of vomiting and nausea during cytostatic chemotherapy.
In a small number of patients with cytostatic chemotherapy and radiation therapy during treatment with Granisetron, severe nausea and indomitable vomiting may occur. If necessary, 2 additional infusions (lasting 5 minutes) can be carried out, each in a dose of up to 3 mg, with an interval of at least 10 minutes for 24 hours. The maximum daily dose is 9 mg.
In case of postoperative nausea and vomiting, 1 mg of Granisetron is injected once slowly (at least 30 seconds) for therapy. There is experience of using the drug at a dose of up to 3 mg in patients who have undergone elective surgery under anesthesia.
After elimination of nausea and vomiting, pills may be prescribed for prophylactic purposes.
Recommended dosing regimen for pediatric patients with cytostatic chemotherapy:
- therapy: no more than 2 additional infusions (over 5 minutes), single dose - 0.02 mg / kg, with a break of at least 10 minutes. The maximum daily dose is 0.06 mg / kg;
- prevention: before the start of cytostatic therapy, a single infusion at a dose of 0.02 mg / kg in 10-30 ml of solution for infusion for 5 minutes.
There is no information on the use of the drug for the treatment of postoperative vomiting and nausea in children.
Side effects
Adverse events associated with the use of Granisetron are most often not severe and do not require discontinuation of the drug.
There is evidence of rare and sometimes severe cases of hypersensitivity manifestations (for example, in the form of anaphylaxis).
Possible adverse reactions [> 10% - very common; (> 1% and 0.1% and 0.01% and <0.1%) - rarely; <0.01% - very rare]:
- immune system: rarely - hypersensitivity reactions, including anaphylaxis and urticaria;
- digestive system: very often - constipation; often - an increase in the activity of hepatic transaminases (aspartate aminotransferase, alanine aminotransferase), usually without exceeding their normal values; rarely - a change in taste, heartburn;
- nervous system: very often - headache; infrequently - serotonin syndrome (including changes in mental state, autonomic dysfunction and disorders of the muscular and nervous systems); rarely - anxiety, anxiety, dizziness;
- cardiovascular system: infrequently - prolongation of the QT interval; As in the case of the use of other antagonists of serotonin 5-HT 3 -receptors, changes in ECG parameters were reported against the background of the use of Granisetron, including cases of prolongation of the QT interval (insignificant and, as a rule, had no clinical significance, in particular, without signs of proarrhythmogenic action);
- skin and subcutaneous tissue: infrequently - skin rash; very rarely - edema, including of the face;
- organism as a whole: very rarely - flu-like syndrome, including chills and fever.
Adverse reactions registered during the post-marketing use of Granisetron (with an unknown frequency):
- digestive system: abdominal pain, flatulence, diarrhea, dyspepsia;
- nervous system: drowsiness, insomnia, weakness;
- cardiovascular system: chest pain, arrhythmia, increase / decrease in blood pressure;
- immune system: bronchospasm, hyperthermia, itching.
The frequency and severity of adverse reactions may vary depending on the form of release of Granisetron.
Overdose
A single intravenous administration of 38 mg of Granisetron was not accompanied by the development of serious adverse reactions, with the exception of mild headache.
Therapy: symptomatic. The specific antidote is unknown.
special instructions
The condition of patients with signs of partial intestinal obstruction after the administration of Granisetron should be monitored by a doctor, since the drug can reduce the motility of the gastrointestinal tract.
Granisetron is safe for use in elderly patients and patients with hepatic / renal impairment.
In patients with pre-existing arrhythmias or diseases that are accompanied by impaired cardiac conduction, changes in ECG parameters that occur during the use of Granisetron can lead to clinically significant consequences. Therefore, caution should be exercised when prescribing the drug to patients with heart disease, concomitant electrolyte disturbances and / or receiving cardiotoxic chemotherapy.
There are reports of cases of cross-sensitivity between antagonists of serotonin 5-HT 3 receptors.
If there is a clinical need for the combined use of Granisetron with other serotonergic drugs, the patient's condition should be monitored.
Influence on the ability to drive vehicles and complex mechanisms
While driving with Granisetron, the likelihood of drowsiness, dizziness and asthenia should be taken into account when driving.
Application during pregnancy and lactation
- pregnancy: due to the fact that the safety of use in this group of patients has not been established, Granisetron can only be used in cases where the expected benefit is higher than the potential risk;
- lactation period: the use of the drug is contraindicated.
Pediatric use
Contraindication (due to insufficient information that allows you to establish the optimal dosage regimen in this age group of patients):
- infusion solution - up to 2 years;
- tablets - up to 12 years.
Drug interactions
Granisetron does not affect the activity of the CYP3A4 isoenzyme of the cytochrome P 450 system, which is responsible for the metabolic process of some narcotic analgesics. The efficacy of the drug with intravenous administration of dexamethasone (at a dose of 8–20 mg) before chemotherapy can be enhanced.
According to the research data, ketoconazole inhibits the metabolism of Granisetron by acting on the isoenzyme 3A of the cytochrome P 450 system.
With the induction of hepatic enzymes with phenobarbital, an increase in the clearance of Granisetron by approximately 25% is noted.
Special studies of the effect of Granisetron on patients who are under anesthesia have not been carried out, but the drug is well tolerated when used in combination with similar drugs and narcotic analgesics.
Interaction with simultaneous use with tranquilizers, neuroleptics, benzodiazepines, antiulcer drugs from the group of H 2 -histamine receptor blockers (for example, cimetidine) and vomiting cytostatic drugs have not been identified.
In patients who receive concomitant therapy with agents with a known ability to prolong the QT interval and / or arrhythmogenic activity, when treated with Granisetron, the observed changes in the ECG can cause clinically significant consequences.
When using Granisetron in combination with other serotonergic drugs, as in the treatment of other antagonists of serotonin 5-HT 3 receptors, there have been cases of serotonin syndrome, including changes in mental state, disorders of the muscular and nervous systems and autonomic dysfunction.
Analogs
Granisetron analogs are Granisetron Kabi, Avomit, Notyrol, Kitril, Granisetron-TL.
Terms and conditions of storage
Store in a place protected from light at temperatures up to 25 ° C. Keep out of the reach of children.
Shelf life: tablets - 3 years; concentrate - 2 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Granisetron
Reviews of Granisetron are few. Most often, patients indicate that the drug has the claimed therapeutic effect.
Price for Granisetron in pharmacies
The approximate price for Granisetron (10 tablets) is 2,870-5,050 rubles.
Anna Kozlova Medical journalist About the author
Education: Rostov State Medical University, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
