Instruction for use: Kytril

Dosage form: Concentrate for solution for infusion; film coated tablets

Active substance: Granisetron*

ATX

A04AA02 Granisetron

Pharmacological groups:

Antiemetic, serotonin receptor antagonist [Antiemetic]

Antiemetic, serotonin receptor antagonist [Serotonergic drugs]

The nosological classification (ICD-10)

R11 Nausea and vomiting: Postoperative vomiting; Nausea; Vomiting; Vomiting in the postoperative period; Vomiting medication; Vomiting in the background of radiation therapy; Vomiting uncontrollable; Vomiting in radiation therapy; Persistent vomiting; Indomitable vomiting; Postoperative nausea; Vomiting with chemotherapy; Vomiting of the central genesis; Vomiting with cytotoxic chemotherapy; Persistent hiccups; Repeated vomiting

T66 Unspecified radiation effects: Radiation disease; Diarrhea radiation; Gastrointestinal syndrome with irradiation; Radiation sickness; Radiation disorders of mucous membranes; Irradiation chronic; Osteoradionecrosis; Acute radiation sickness; Acute and chronic radiation injuries; Acute radiation syndrome with radiation therapy; Subacute and chronic radiation sickness; Radiation Neuropathy; Radiation edema; Radiation damage to the nervous system; Radiation immunodeficiency; Radiation syndrome; Radio-epileleitis; Radiation acute syndrome; State after irradiation; Cytopenia due to previous radiation or chemotherapy; Cytopenia radiation; Cytopenia due to radiation therapy; Cytopenia due to chemotherapy

Y43.1 Adverse reactions in the therapeutic use of antitumor antimetabolites: Treatment with mercaptopurine

Y43.2 Adverse reactions in the therapeutic use of antineoplastic natural preparations

Y43.3 Adverse reactions in the therapeutic use of other antitumor drugs

Z100 * CLASS XXII Surgical practice: Abdominal surgery; adenomectomy; Amputation; Coronary angioplasty; Angioplasty of the carotid arteries; Antiseptic skin treatment for wounds; Antiseptic Hand; Appendectomy; atherectomy; Balloon coronary angioplasty; Vaginal hysterectomy; The coronary bypass; Interventions in the vagina and cervix; Interventions on the bladder; Intervention in the mouth; Restoration and reconstructive surgery; Hand hygiene of medical personnel; Gynecologic surgery; Gynecological intervention; Gynecological surgery; Hypovolemic shock during operations; Disinfection of purulent wounds; Disinfection of wounds edges; Diagnostic intervention; Diagnostic procedures; Cervical Diathermocoagulation; Long-surgery; Replacing the fistula catheters; Infection in orthopedic surgery; Artificial heart valve; cystectomy; Short-term outpatient surgery; Short-term operation; Short surgical procedures; Krikotireotomiya; Blood loss during surgery; Bleeding during surgery and in the postoperative period; Kuldotsentez; laser photocoagulation; laser coagulation; retinal laser coagulation; Laparoscopy; Laparoscopy in Gynecology; CSF fistula; Small gynecological operations; Small surgical procedures; Mastectomy and subsequent plastic; mediastinotomy; Microsurgical operations on the ear; Mukogingivalnye operation; suturing; Minor surgery; neurosurgical operation; Immobilization of the eyeball in ophthalmic surgery; testectomy; pancreatectomy; Perikardektomiya; The period of rehabilitation after surgery; The period of convalescence after surgery; Percutaneous transluminal coronary angioplasty; Pleural thoracentesis; Pneumonia postoperative and posttraumatic; Preparation for surgical procedures; Preparation for surgery; Preparation of the surgeon's hands before surgery; Preparation of the colon for surgical procedures; Postoperative aspiration pneumonia in neurosurgical and thoracic surgery; Postoperative nausea; Postoperative bleeding; postoperative granuloma; postoperative shock; The early postoperative period; myocardial revascularization; Radiectomy; gastric Resection; bowel resection; uterine Resection; liver Resection; enterectomy; Resection of part of the stomach; Reocclusion of the operated vessel; Bonding tissues during surgical procedures; Removal of sutures; Condition after eye surgery; Condition after surgery; Condition after surgery in the nasal cavity; Condition after gastrectomy; Status after resection of the small intestine; Condition after tonsillectomy; Condition after removal of the duodenum; Condition after phlebectomy; Vascular surgery; Splenectomy; Sterilization of surgical instruments; Sterilization of surgical instruments; sternotomy; Dental surgery; Dental intervention in periodontal tissues; strumectomy; Tonsillectomy; Thoracic surgery; Thoracic surgery; total gastrectomy; Transdermal intravascular coronary angioplasty; Transurethral resection; Turbinektomiya; Removal of a tooth; cataract surgery; Removal of cysts; tonsillectomy; Removal of fibroids; Removing the mobile primary teeth; Removing polyps; Removing broken tooth; Removal of the uterus body; Removal of sutures; Fistula likvoroprovodyaschih ways; Frontoetmoidogaymorotomiya; Surgical infection; Surgical treatment of chronic limb ulcers; Surgery; The surgery in the anal area; The surgery on the colon; Surgical practice; The surgical procedure; Surgical interventions; Surgery on the gastrointestinal tract; Surgical procedures on the urinary tract; Surgical procedures on the urinary system; Surgical intervention of the genitourinary system; Surgical procedures on the heart; Surgical manipulation; surgery; Surgery on the veins; Surgical intervention; Vascular surgery; Surgical treatment of thrombosis; Surgery; cholecystectomy; Partial gastric resection; hysterectomy; Percutaneous transluminal coronary angioplasty; Percutaneous transluminal angioplasty; Coronary artery bypass; tooth Extirpation; Extirpation of milk teeth; pulpectomy; pulsative cardiopulmonary bypass; tooth Extraction; teeth Extraction; cataract extraction; Electrocoagulation; endourological intervention; episiotomy; Etmoidotomiya; Complications after tooth extraction

Composition and release form

Concentrate for solution for infusion 1 ml

Granisetron (in the form of granisetron hydrochloride) 1 mg (1.12 mg)

Auxiliary substances: sodium chloride; Citric acid monohydrate; Sodium hydroxide; Hydrochloric acid; water for injections

In ampoules of 3 ml; In a pack of cardboard 5 ampoules.

Tablets, coated with a coating.

Granisetron (in the form of granisetron hydrochloride) 1 mg (1.12 mg)

Auxiliary substances: MCC; Hypromellose 3 mPas (hydroxypropyl methylcellulose); Lactose monohydrate; Magnesium stearate; Sodium starch glycolate

Composition of the film shell: opadrai YS-1-18027-A (hypromellose, titanium dioxide E171, macrogol 400, polysorbate 80)

In the blister 10 pcs .; In a pack of cardboard 1 blister.

Description of dosage form

Concentrate: clear, colorless liquid.

Tablets: triangular, biconvex, coated, white or almost white; On one side of the tablet the engraving "K1".

Pharmachologic effect

Mode of action - antiemetic.

Pharmacodynamics

Granisetron is a selective antagonist of 5-hydroxytryptamine (5-HT3) receptors located at the ends of the vagus nerve and the trigger zone of the bottom of the IV ventricle of the brain (practically no effect on other receptors of serotonin), with pronounced antiemetic effect. Studies have shown that Kytril has low affinity for other types of receptors, including 5-HT and binding sites for dopamine D2. Eliminates the vomiting that occurs when the parasympathetic nervous system is excited, due to the release of serotonin by enterochromaffine cells.

Kytril eliminates nausea and vomiting caused by cytotoxic chemotherapy, radiotherapy, as well as postoperative nausea and vomiting.

Kytril does not affect the concentration of prolactin and aldosterone in the blood plasma.

Pharmacokinetics

Suction

Absorption of granisetron after oral administration is rapid and complete, but absolute bioavailability is reduced to 60% due to the effect of "first passage" through the liver. Eating does not affect the bioavailability of the drug.

Distribution

Kytrile is distributed to organs and tissues, the average volume of distribution is 3 l / kg. It is distributed in plasma and in erythrocytes. The connection with plasma proteins is approximately 65%.

Metabolism

Biotransformation occurs mainly in the liver by N-demethylation and oxidation of the aromatic ring, followed by conjugation. In vitro studies have shown that ketoconazole inhibits the metabolism of Kitryl, which involves the participation of the isoenzyme 3A of the cytochrome P450 system.

Excretion

With urine, unchanged, on average, 12% and in the form of metabolites - 47% of the dose. The remaining 41% are excreted in the form of metabolites.

T1 / 2 for oral and intravenous administration is 9 hours, with a wide individual variability.

Concentrations of granisetron in plasma do not clearly correlate with its antiemetic effect. The therapeutic effect is observed even when granisetron is no longer detected in the plasma.

Pharmacokinetics in specific patient groups

In elderly patients, pharmacokinetic parameters after a single intravenous administration did not differ from those in young patients.

In patients with severe renal failure, pharmacokinetic parameters after a single intravenous administration did not differ from those in patients with normal renal function.

In patients with hepatic insufficiency caused by neoplastic changes, the total level of plasma clearance is approximately half that of patients with normal liver function. Despite these changes, dose adjustment is not required.

Pharmacokinetics in children: when granisetron was administered at a dose of 20 mcg / kg body weight, there was no clinically significant difference in pharmacokinetics in adults and children.

Indications the Kytril

Cytostatic chemotherapy

Prevention of nausea and vomiting when performing cytostatic chemotherapy in adults (coated tablets);

Prevention and therapy of nausea and vomiting in the conduct of cytostatic chemotherapy in adults and children over 2 years (concentrate for the preparation of a solution for infusions).

Radiation therapy

Prevention of nausea and vomiting during radiotherapy in adults (coated tablets);

Prevention and therapy of nausea and vomiting when performing radiation therapy in adults (concentrate for the preparation of a solution for infusions).

Postoperative nausea and vomiting

Therapy of postoperative nausea and vomiting in adults (concentrate for solution for infusion).

Contraindications

Hypersensitivity to granisetron or any of the components of the drug;

Hypersensitivity reactions to other selective antagonists of 5-HT3 receptors in the anamnesis;

lactation.

Carefully:

Partial intestinal obstruction;

pregnancy.

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

Application in pregnancy and breastfeeding

For women during pregnancy, Kytril is prescribed only if the intended benefit to the mother exceeds the potential risk to the fetus and the baby. Kytril does not have teratogenic effects on animals, studies in pregnant women have not been conducted.

Side effects

In most cases, side effects with Kytril were not severe and were tolerated by patients without discontinuing therapy.

Rare and sometimes severe cases of hypersensitivity (eg anaphylaxis) are noted.

On the part of the digestive system: abdominal pain, constipation, diarrhea, flatulence, increased activity of hepatic transaminases (ALT, AST) usually within their normal values, dyspepsia; Rarely - heartburn, a change in taste.

From the nervous system: headache, insomnia, drowsiness, weakness; Rarely - anxiety, restlessness, dizziness.

On the part of the immune system: skin rash, hyperthermia, bronchospasm, urticaria, itching; Rarely - hypersensitivity reactions.

From the cardiovascular system: arrhythmia, chest pain, decrease or increase in blood pressure.

From the skin and its appendages: very rarely - skin rash, swelling / swelling of the face.

On the part of the body as a whole: very rarely - the flu-like syndrome.

Interaction

Kytril does not affect the activity of the metabolizing enzymes of the 3A4 subfamily of the cytochrome P450 system, which are responsible for the metabolism of some narcotic analgesics. Efficacy of Kytril may be enhanced by IV administration of dexamethasone (8-20 mg) prior to chemotherapy.

In vitro studies have shown that ketoconazole inhibits the metabolism of Kytril, which involves the participation of the isoenzyme 3A of the cytochrome P450 system. Special studies on the interaction with funds for general anesthesia have not been carried out, but Kytril is well tolerated with concomitant administration with similar drugs and narcotic analgesics.

When induction of hepatic enzymes with phenobarbital, an increase in the clearance of granisetron (with iv introduction) was observed by about a quarter.

There was no interaction with concomitant administration with benzodiazepines, tranquilizers, antiulcer drugs and cytotoxic drugs that cause vomiting.

Dosing and Administration

IV, inside.

Standard dosing regimen

Adults

Cytostatic chemotherapy (prevention)

Orally: inside 1 mg twice a day or 2 mg once a day for no more than 7 days after the start of cytostatic therapy. The first dose should be taken 1 hour before the start of cytostatic therapy.

IV:

- patients with a body weight of more than 50 kg: one ampoule (3 mg / 3 ml) is diluted in 20-50 ml infusion solution and injected intravenously for 5 min before the start of cytostatic chemotherapy; One ampoule (3 mg / 3 ml) can also be administered iv bolus (for 30 s);

- patients with a body weight of less than 50 kg: 20-40 μg / kg; The infusion should be completed before the start of cytostatic therapy.

Radiation therapy (prevention)

Oral: inside 2 mg once a day; With the first dose to be taken 1 hour before the start of radiotherapy.

IV: the dosing regimen is similar to that see "Cytostatic chemotherapy (prophylaxis)".

Cytostatic chemotherapy and radiotherapy (therapy)

IV: if necessary, you can make 2 additional infusions (5 minutes each), each dose of no more than 3 mg, with an interval of at least 10 minutes for 24 hours. The maximum daily dose should not exceed 9 mg.

Postoperative nausea and vomiting (therapy)

IV: once 1 mg iv slowly (at least 30 seconds).

Special dosing regimen

Children

Cytostatic chemotherapy (prevention)

IV: a single IV infusion at a dose of 20 mcg / kg in 10-30 ml of a solution for infusions for 5 min, before the start of cytostatic therapy.

Cytostatic chemotherapy (therapy)

IV: no more than 2 additional infusions (within 5 minutes), each dose of 20 μg / kg, with an interval of at least 10 minutes. The maximum daily dose should not exceed 60 mcg / kg.

Postoperative nausea and vomiting (therapy)

Data on the use of Kytril for the therapy of postoperative nausea and vomiting in children are absent.

Patients with renal or hepatic insufficiency, elderly patients. Correction of the dose is not required.

Preparation of solution for intravenous infusion

The following infusion solutions are used for the preparation of Kytril solution for IV administration: 0.9% sodium chloride solution, 0.18% sodium chloride solution and 4% dextrose solution, 5% dextrose solution, Hartman solution, sodium lactate solution or mannitol solution . Use of other solutions is not allowed. It is recommended to inject the infusion solution immediately after its preparation. The finished solution is stable for 24 hours at room temperature (15-25 ° C), under normal room lighting.

Allowed IV the introduction of the drug without dilution.

Overdose

Symptoms: The use of 38 mg granisetron in the form of a single intravenous injection was not accompanied by the development of serious adverse effects other than mild headache.

Treatment: a specific antidote for Kytril is not known. In case of an overdose, treatment is symptomatic.

Special instructions

Since Kytril can reduce intestinal motility, patients with signs of partial obstruction of the intestine after the administration of the drug should be under the supervision of a physician.

Influence on ability to drive vehicles and work with machines and mechanisms

Data on the impact of Kytril on the ability to drive a vehicle are missing. However, one should remember about the possible occurrence of drowsiness during therapy with Kytril.

Storage conditions of the drug Kytril

At a temperature not higher than 30 ° C.

Keep out of the reach of children.

Shelf life of the drug Kytril

Film-coated tablets 1 mg - 5 years.

Concentrate for solution for infusion 1 mg / ml - 3 years.

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