Avomit - instructions for use, doses, side effects, contraindications

Excipients: sodium chloride 9.0 mg, citric acid monohydrate 2.0 mg, hydrochloric acid to pH 5.3 ± 0.3, sodium hydroxide to pH 5.3 ± 0.3, water for injection to 1.0 ml.

Description:

Transparent colorless liquid.

Pharmacotherapeutic group:Antiemetic means - serotonin receptor antagonist

ATX: & nbsp

A.04.A.A.02 Granizetron

Pharmacodynamics:

Granisetron is a selective antagonist of serotonin 5-HT₃-receptors located in the endings vagal nerve and trigger zone of the bottom of the IV ventricle of the brain (practically does not affect other receptors of serotonin), with pronounced antiemetic effect. Studies have shown that granisetron has low affinity for other receptor types, including other serotonin receptor subtypes and dopamine D₂-receptors. Eliminates the vomiting that occurs when the parasympathetic nervous system is excited, due to the release fromepotoneina with enterochromaffin cells.

Granisetron eliminates nausea and vomiting caused by cytotoxic chemotherapy, radiotherapy, as well as postoperative nausea and vomiting. Granisetron does not affect the concentration of prolactin and aldosterone in the blood plasma. Granisetron does not have a mutagenic effect in vivo and in vitro. When administered for life in high doses, it increases the risk of hepatocellular tumors in animals.

Pharmacokinetics:

Distribution

Granisetron is distributed to organs and tissues (including plasma and erythrocytes), the average volume of distribution is 3 l / kg. Linkage to 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 The research showed that ketoconazole inhibits granisetron metabolism, which involves the involvement of the CYP3A isoenzyme of the cytochrome P450 system. Other in vitro The research showed that granisetron does not affect the activity of the metabolic isozymes CYP3A4.

Excretion

Kidneys in unmodified form, on average, 12% and in the form of metabolites 47% of the dose. The remaining 41% of the dose is excreted by the intestines in the form of metabolites.

The half-life is 9 hours, with a wide individual variability. Concentrations of granisetron in the plasma are weakly correlated with its antiemetic effect. Therapeutic effect is observed even when granisetron is no longer found in plasma. The pharmacokinetics of granisetron remains linear in a dose range up to 2.5 and 4 times higher than recommended, respectively.

Pharmacokinetics in specific patient groups

Have elderly patients pharmacokinetic parameters after a single intravenous administration did not differ from those in patients of a young age.

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 plasma clearance is about half as compared with patients with normal liver function. Despite these changes, dose adjustment is not required.

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

Indications:

- Profilaktika and treatment of nausea and vomiting in the conduct of cytostatic chemotherapy in adults and children older than 2 years;

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

- treatment of postoperative nausea and vomiting in adults.

Contraindications:

- Hypersensitivity to the granisetron or any of the components of the drug in the anamnesis;

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

- the period of breastfeeding;

- dUp to 2 years of age (there is no data on efficiency and safety).

Carefully:

- Partial intestinal obstruction;

- pregnancy (for women during pregnancy) granisetron is assigned only if the intended benefit to the mother exceeds the potential risk to the fetus; granisetron does not have teratogenic effects on animals, studies in pregnant women have not been conducted);

- concomitant heart disease, cardiotoxic chemotherapy and / or associated electrolyte disturbances.

Dosing and Administration:

The drug Avomit® is administered intravenously.

Adults

Nausea and vomiting in cytotoxic and / or radiotherapy

With the preventive purpose:

Patients with a body weight of more than 50 kg: one vial (3 mg / 3 ml) is diluted in 20-50 ml of the infusion solution and administered intravenously drip for 5 minutes or undiluted intravenously in jet for 30 seconds before chemotherapy or radiation therapy begins.

Patients weighing less than 50 kg: the drug Avomit® is administered at a dose of 20-40 μg / kg.

In most cases, a single dose of Avomit® is sufficient to control nausea and vomiting within 24 hours.

With a curative purpose:

- if necessary in addition to the preventive administration of the drug Avomit ®, you can make 2 additional infusions (5 minutes each), each in a dose of not more than 3 mg,with an interval of at least 10 minutes for 24 hours. The maximum daily dose should not exceed 9 mg.

Therapy of postoperative nausea and vomiting

- once 1 mg intravenously (without dilution with a solution for infusions) slowly (at least 30 seconds). There is an experience of using granisetron preparations in a dose of up to 3 mg in patients who underwent elective surgery under anesthesia.

Children from 2 to 16 years old

Nausea and vomiting with cytotoxicth chemotherapy

With the preventive purpose:

-20 μg / kg in 10-30 ml of solution for infusions for 5 minutes intravenously

drip before the start of cytostatic therapy.

With a curative purpose:

if necessary, in addition to preventive administration of Avomit®, no more than 2 additional infusions (5 minutes each), each at a dose of 20 μg / kg, with an interval of at least 10 minutes, can be performed. The maximum daily dose should not exceed 60 mcg / kg.

Postoperative nausea and vomiting

There is not enough data to recommend granisetron for the prevention and treatment of postoperative nausea and vomiting in children.

Nausea and vomiting in radiation therapy

There is not enough data to recommend granisetron for the prevention and treatment of nausea and vomiting in radiation therapy in children.

Patients with renal or hepatic insufficiency, elderly patients

Correction of the dose is not required.

Preparation of a solution for intravenous infusion

The following infusion solutions are used to prepare the solution of Avomit® for intravenous drip injection: 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 prepared solution is stable for 24 hours at room temperature (15-25 ° C) under normal room lighting. In exceptional cases, the prepared solution can be stored for no more than 24 hours at a temperature of (5 ± 3) ° C if the dilution occurred in controlled and validated aseptic conditions. At the same time for the storage conditions (storage rules and duration) is the specialist who prepared the solution.

Intravenous administration of the drug without dilution is permissible.

Side effects:

In most cases, side effects with granisetron were not severe and were tolerated by patients without discontinuing therapy. Rare and sometimes severe cases of hypersensitivity (for example, anaphylaxis).

The frequency of adverse reactions listed below, was determined according to the following criteria: very often (≥ 10%), often (≥ 1% and <10%), rare (≥ 0.1% and <1%), rare (≥ 0.01 % and <0.1%), very rarely (<0.01%), including individual reports.

Impaired nervous system: very often - headache; rarely - serotonin syndrome (including changes in mental state, autonomic dysfunction and disorders of the nervous and muscular systems); rarely - anxiety, restlessness, dizziness.

Disorders from the gastrointestinal tract: very often constipation; rarely - heartburn, a change in taste.

Disorders from the liver and bile ducts: often, an increase in the activity of "hepatic" transaminases (ALT, ACT) usually within their normal values.

Immune system disorders: infrequently - reactions of hypersensitivity, including anaphylaxis and urticaria.

Violations from the heart and blood vessels: infrequent - increasing the interval QT.

Disturbances from knives and subcutaneous tissues: infrequent skin rash; very rarely - edema / edema of the face.

General disorders and disorders at the place of administration: very rarely - the hippopotent syndrome (including fever and chills).

Postmarketing surveillance

Impaired nervous system: insomnia, drowsiness, weakness.

Disorders from the digestive system: abdominal pain, diarrhea, flatulence, indigestion.

Immune system disorders: hyperthermia, bronchospasm, pruritus.

Disorders from the cardiovascular system: arrhythmia, chest pain, decreased or increased blood pressure.

Overdose:

Specific antidotes for granisetron do not exist. In case of an overdose, treatment is symptomatic. The use of 38 mg of granisetron in the form of a single intravenous injection was not accompanied by the development of serious undesirable effects other than mild headache.

Interaction:

Granisetron does not affect activity isoenzyme CYP3A4 (responsible for the metabolism of some narcotic analgesics). Efficiency granisetron can be strengthened intravenous administration of dexamethasone (8-20 mg) before the start of chemotherapy.

In vitro The research showed that ketoconazole inhibits metabolism granisetron, which involves the participation of isoenzyme CYP3A4. Special research on the interaction with means for general anesthesia was not carried out, but granisetron it is well tolerated with simultaneous appointment 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 approximately a quarter.

He interaction at simultaneous appointment with benzodiazepines, tranquilizers, antiulcer drugs and cytotoxic drugs means that cause vomiting.

In patients receiving concomitant therapy with drugs with a known ability to prolong the interval QT and / or arrhythmogenic activity, the observed changes on the ECG during granisetron therapy can lead to clinically significant consequences.

As with other antagonists of serotonin 5-NT₃-receptors, when using granisetron in combination with other serotonergic drugs cases of development serotonin syndrome (including changes in the mental state, autonomic dysfunction and disorders of the nervous and muscular systems).

Special instructions:

Since Avomit® can inhibit intestinal motility, patients with signs of partial bowel obstruction after the administration of Avomit® should be under the supervision of a physician.

Granisetron is safe for use in the elderly and patients with renal or hepatic insufficiency.

Granisetron with intravenous administration at a dose of up to 200 μg / kg does not have a clinically significant effect on the electroencephalogram or the results of psychometric tests. As with other 5-NT₃ antagonists, with therapy with granisetron preparations reported changes in ECG parameters, including cases of increasing the interval QT. These changes were insignificant and, as a rule, did not have clinical significance, in particular, had no signs of pro-arrhythmogenic effect. However, in patients with pre-existing arrhythmias or diseases accompanied by cardiac conduction disorders, the observed changes in ECG parameters during granisetron therapy can lead to clinically significant consequences.In this regard, caution should be exercised in prescribing patients with concomitant heart disease who receive cardiotoxic chemotherapy and / or have associated electrolyte disturbances.

Cases of cross-sensitivity between antagonists of serotonin 5-HT₃receptors. It is necessary to observe the patient's condition in case of clinical necessity simultaneous application of granisetron with other serotonergic drugs.

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

Data on the effect of Avomit® on the ability to drive a vehicle are not available. However, one should remember about the possible occurrence of drowsiness and other undesirable phenomena from the nervous system in the treatment with Avomit®. When these undesirable phenomena appear, one should refrain from performing these activities.

Form release / dosage:Concentrate for solution for infusion, 1 mg / ml.

Packaging:

1 mg / 1 ml and 3 mg / 3 ml (1 mg / ml) in neutral glass vials hermetically sealed with rubber stoppers, with a run-off caps with aluminum.

For 1 or 5 vials (1 ml of concentrate) in a planar cell pack with instructions for use in a pack of cardboard.

For 1 bottle (3 ml of concentrate) with instructions for use in a pack of cardboard.

For 5 vials (3 ml of concentrate) in a contour acheive box with instructions for use in a pack of cardboard.

Storage conditions:

In dry, dark place at a temperature of no higher than 30 ° C. Do not freeze.

Keep out of the reach of children.

Shelf life:

2 years.

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

Terms of leave from pharmacies:On prescription

Registration number:LSR-002262/10

Date of registration:18.03.2010/26.08.2016

Expiration Date:Unlimited

The owner of the registration certificate:BIOCAD, CJSC BIOCAD, CJSC Russia

Manufacturer: & nbsp

BIOCAD, CJSC Russia

Representation: & nbspBIOCAD CJSC BIOCAD CJSC Russia

Information update date: & nbsp21.01.2017

Illustrated instructions

Instructions

Avomit® (Avomit®)