Venotoklaks - instructions for use, dose, side effects, contraindications

Clinical and pharmacological group: & nbsp

Other antineoplastic agents

Included in the formulation

Wenklekst

pills inwards

EbbVi Ltd. Russia

АТХ:

L.01.X Other antineoplastic agents

Pharmacodynamics:

Selectively inhibits protein BCL-2, which has anti-apoptotic effect, providing high survival of tumor cells, and increases resistance to chemotherapy. By binding to the BCL-2 protein venetoclase displaces proapoptotic proteins BIM, by activating caspases and destroying the mitochondrial membranes, thus exerts a cytotoxic effect on tumor cells expressing BCL-2.

Pharmacokinetics:

After oral administration, the empty stomach is absorbed in the gastrointestinal tract. The maximum concentration in blood plasma is reached after 5-8 hours. The connection with plasma proteins is more than 99%.

Metabolism in the liver of CYP3A4 / 5 major metabolite M27.

T ½ is 26 h. Elimination with feces (99.9%) and kidneys (0.1%).

Indications:

It is used to treat chronic lymphocytic leukemia.

ICD-10

II.C81-C96.C91.1 Chronic lymphocytic leukemia

Contraindications:

Simultaneous reception with inhibitors of the isoenzyme CYP3A, age to 18 years, pregnancy and lactation, individual intolerance.

Carefully:

Gout, hyperuricemia, renal failure, acute infection, hypersensitivity.

Pregnancy and lactation:

Recommendations for FDA - category is not defined. Contraindicated in pregnancy and lactation.

Dosing and Administration:

Inside, in an initial dose of 20 mg 1 time / day with a weekly increase: twice (50, 100, 200 mg), to a maximum of 400 mg 1 time / day from the 5th week.

The highest daily dose: 400 mg.

The highest single dose: 400 mg.

Side effects:

Central and peripheral nervous system: headache, fatigue, insomnia.

Respiratory system: cough, nasopharyngitis, shortness of breath.

Hemopoietic system: anemia, neutropenia, thrombocytopenia.

The cardiovascular system: peripheral edema.

Digestive system: decreased appetite, stomatitis, nausea, vomiting, diarrhea, constipation.

Musculoskeletal system: back pain.

Dermatological reactions: hemorrhagic rash.

Reproductive system: reduction of male fertility.

Allergic reactions.

Overdose:

Possible development of tumor lysis syndrome during dose build-up.

Treatment is symptomatic on the background of a reduced dose or complete discontinuation of the drug.

Interaction:

Simultaneous administration with inhibitors of CYP3A (ketokenazole, conivaptan, clarithromycin, indinavir, telaprevir, intraconazole, voriconazole, posaconazole) increases the concentration of venetoclax, increasing side effects, including the development of tumor lysis syndrome.

Simultaneous reception with inductors CYP3A (carbamazepine, fentionine, rifampicin, St. John's wort, bosentan, etravirine, nafcillin, efavirenz) reduces the concentration of venetoclase.

Increases the concentration of warfarin.

Inhibits substrates of P-gp in the intestine - it is recommended to take digoxin, everolimus, sirolimus 6 hours before venetoclax.

Special instructions:

During treatment and within 3 months after its end, it is recommended to use reliable methods of contraception.

In the treatment it is not recommended to vaccinate with live vaccines and within 6 months after the end of treatment.

It is not recommended to drink the drug with grapefruit juice.

When taking the drug is not recommended driving and working with moving machinery.

Instructions

Venetoklaks (Venetoclax)