Kitril

General characteristics. Structure:

Active agent: гранисетрон 1 mg (in the form of a granisetron of a hydrochloride of 1.12 mg);

Excipients: lactoses monohydrate - 69.4 mg, a gipromelloza (3 мПа.с) - 4.0 mg, sodium carboxymethylstarch - 5.0 mg, cellulose microcrystallic - 20.0 mg, magnesium stearate - 0.5 mg;

Cover: gipromelloza (6 мПа.с), titanium dioxide (E171), macrogoal 400, polysorbate of 80 - 3.0 mg; use of ready mix of Opadray (Opadry) YS-1-18027-A is allowed.

Pharmacological properties:

Pharmacodynamics. Granisetron is the selection antagonist of the 5-gidroksitriptaminovy (5-HT3) receptors located in the terminations of a vagal nerve and a trigger zone of a bottom of the IV cerebral cavity (practically does not influence other receptors of serotonin), with the expressed antiemetic effect. Researches showed that at the drug Kitril® low affinity to other types of receptors, including 5-HT and dopamine D2 receptors. Eliminates the vomiting arising at excitement of a parasympathetic nervous system owing to serotonin release by enterokhromaffinny cells.
Китрил® eliminates the nausea and vomiting caused by cytotoxic chemotherapy, radiation therapy and also postoperative nausea and vomiting.
Китрил® does not influence concentration of prolactin and Aldosteronum in a blood plasma.
Китрил® has no mutagen effect of in vivo and in vitro. At lifelong introduction in high doses increases risk of developing of hepatocellular tumors at animals.

Pharmacokinetics. Absorption. Absorption of a granisetron after oral administration - bystry and full, but absolute bioavailability decreases to 60% due to effect of "the first passing" through a liver. Meal does not influence bioavailability of a granisetron.

Distribution. Granisetron is distributed on bodies and fabrics (including plasma and erythrocytes), the average volume of distribution makes 3 l/kg. Communication with proteins of plasma makes about 65%.

Metabolism. Biotransformation happens generally in a liver by N-demethylation and oxidation of an aromatic ring to the subsequent conjugation. The researches in vitro showed what кетоконазол inhibits metabolism of a granisetron that assumes participation of isoenzymes of a subfamily of CYP3A. Other researches in vitro showed what гранисетрон does not influence activity of an isoenzyme of CYP3A4.

Removal. Kidneys in not changed look remove on average 12% and in the form of metabolites of 47% of a dose. The remained 41% are removed through intestines in the form of metabolites.
The elimination half-life at oral administration makes 9 hours, with wide individual variability.
Concentration of a granisetron in plasma indistinctly correlate with its antiemetic action. The therapeutic effect is observed even then when гранисетрон it is not found in plasma any more.
The pharmacokinetics of a granisetron at oral administration keeps linear character in the range of the doses, to 2.5 times exceeding recommended.

Indications to use:

Prevention of nausea and vomiting when carrying out cytostatic chemotherapy and radiation therapy at adults.

Route of administration and doses:

Standard mode of dosing
Cytostatic chemotherapy (prevention)
Inside on 1 mg 2 times a day or 2 mg of 1 times a day no more than 7 days after the beginning of cytostatic therapy. At the same time the first dose has to be accepted in 1 hour prior to cytostatic therapy.
Radiation therapy (prevention)
In 2 mg of 1 times a day; at the same time the first dose has to be accepted in 1 hour prior to radiation therapy.
Special mode of dosing
Children
Tablets of the drug Kitril® are not recommended for use for children up to 12 years as there are not enough data allowing to set the optimum mode of dosing at this age group. For prevention and treatment of nausea and vomiting when performing cytostatic therapy at children other dosage form of the drug Kitril® - a concentrate for preparation of solution for infusions is used (see the instruction on a medical use).

Features of use:

Patients with signs of partial obstruction of intestines after administration of the drug Kitril® have to be under observation of the doctor as Kitril® can reduce motility of intestines.
Китрил® it is safe for use at elderly and patients with a renal or liver failure.
At healthy volunteers of Kitril® at intravenous administration in a dose to 200 mkg/kg does not exert clinically significant impact on the electroencephalogram or results of psychometric tests.
As well as at use of other antagonists of serotoninovy 5-HT3-retseptorov, at therapy by the drug Kitril® it was reported about changes of the ECG parameters, including cases of increase in an interval of QT. These changes were insignificant and, as a rule, had no clinical value, in particular had no signs of proaritmogenny action. However at patients with already existing arrhythmias or diseases which are followed by disturbance of cordial conductivity observed changes of the ECG parameters at therapy by the drug Kitril® can lead to clinically significant effects. In this regard the patients with the accompanying heart diseases who are receiving cardiotoxic chemotherapy and/or having the accompanying electrolytic disturbances should show care at purpose of drug.

Influence on ability to driving of vehicles and work with cars and mechanisms
Data on influence of the drug Kitril® on ability to driving of the vehicle are absent. However it is necessary to be careful, meaning that in isolated cases at therapy by the drug Kitril® it was reported about drowsiness and dizziness.

Side effects:

In most cases side effects at use of the drug Kitril® were not heavy and were transferred by patients without therapy interruption.
Hard cases of manifestation of hypersensitivity are celebrated rare and sometimes (for example, an anaphylaxis).
- From a nervous system: headache, sleeplessness, drowsiness, weakness, alarm, concern, dizziness.
- From the alimentary system: an abdominal pain, a lock, diarrhea, a meteorism, increase in activity of "hepatic" transaminases (ALT, nuclear heating plant) usually within their normal values, dyspepsia, heartburn, change of flavoring feelings.
- From immune system: skin rash, hyperthermia, bronchospasm, small tortoiseshell, itch, hypersensitivity reactions.
- From cardiovascular system: arrhythmia, stethalgia, decrease or increase in arterial pressure.
As well as at use of other antagonists of serotoninovy 5-HT3-retseptorov, at therapy by the drug Kitril® it was reported about cases of changes of parameters of the electrocardiogram (ECG), including cases of increase in an interval of QT. These changes were insignificant and, as a rule, had no clinical value, in particular had no signs of proaritmogenny action.
- From skin and a hypodermic fatty tissue: skin rash, hypostasis/face edema.
- From an organism in general: a grippopodobny syndrome, including fever and a fever.

Interaction with other medicines:

Granisetron does not influence activity of an isoenzyme of CYP3A4 (which is responsible for metabolism of some narcotic analgetics). Efficiency of a granisetron can be increased by intravenous administration of dexamethasone (8-20 mg) prior to the beginning of chemotherapy.
The researches in vitro showed what кетоконазол inhibits metabolism of a granisetron that assumes participation of isoenzymes of a subfamily of CYP3A. Special researches on interaction with means for the general anesthesia were not conducted, but гранисетрон it is well transferred at simultaneous use with similar drugs and narcotic analgetics.
At induction of "hepatic" enzymes phenobarbital observed increase in clearance of a granisetron (at intravenous administration) approximately on a quarter.
Interaction at simultaneous use with benzodiazepines, tranquilizers, antiulcerous drugs from group of blockers H2 - histamine receptors and the cytostatic medicines causing vomiting is not revealed.
As well as at use of other antagonists of serotoninovy 5-HT3-retseptorov, at therapy granisetrony it was reported about cases of changes of the ECG parameters, including cases of increase in an interval of QT. These changes were insignificant and, as a rule, had no clinical value, in particular had no signs of proaritmogenny action. However at the patients receiving the accompanying therapy by drugs with the known ability to prolong an interval of QT and/or aritmogenny activity observed changes on an ECG at therapy granisetrony can lead to clinically significant effects.

Contraindications:

Hypersensitivity to a granisetron or any of drug components.
Reactions of hypersensitivity to other selection antagonists of serotoninovy 5-HT3-retseptorov in the anamnesis.
Feeding by a breast.
Children's age up to 12 years (there are not enough data allowing to set the optimum mode of dosing at this age group).

With care
Partial intestinal obstruction.
Pregnancy (to women during pregnancy of Kitril® it is appointed only in that case when the estimated advantage for mother exceeds potential risk for a fruit; Китрил® has no teratogenic effect on animals, researches at pregnant women were not conducted).
Deficit of lactase, lactose intolerance, glyukozo-galaktozny malabsorption.

Overdose:

At single intravenous administration of 38 mg of a granisetron development of serious undesirable effects, except a slight headache was not observed. The specific antidote for the drug Kitril® is not known. In case of overdose a symptomatic treatment.

Storage conditions:

At a temperature not above 30 °C.
To store in the place, unavailable to children.

Issue conditions:

According to the recipe

Packaging:

Tablets, film coated, 1 mg
On 10 tablets in the blister from PVC / aluminum foil.
On 1 blister together with the application instruction place in a cardboard pack.