Aksitinib (Axitinibum)

Pharmacodynamics Pharmacokinetics Indications Carefully Contraindications Dosing and Administration Side effects
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Clinical and pharmacological group: & nbsp

Antineoplastic agents - inhibitors of protein kinases

Included in the formulation
  • Inlita®
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    Pfizer Inc.     USA
  • Inlita®
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    Pfizer Manufakchuring Deutschland GmbH     Germany
    • АТХ:

    L.01.X.E.17   Aksitinib

    Pharmacodynamics:Aksitinib refers to second-generation drugs targeted (specific, targeted) cancer therapy. Selective tyrosine kinase inhibitor of receptors of vascular endothelial growth factor VFGFR-1, VEGFR-2 and VEGFR-3. These receptors are involved in pathological tumor growth, tumor metastasis and oncological angiogenesis. After binding the drug to these receptors, an important pathway called VEGF-mediated proliferation is blocked, which promotes the growth of blood vessels inside the tumor, thus inhibiting its development and metastatic process.

    In 2010, the drug was much more effective in patients with metastatic renal cell carcinoma compared with sorafenib.

    Pharmacokinetics:The half-life of axitinib from the blood plasma varies from 2.5 to 6.1 hours. When taking axitinib twice a dose of 5 mg, its cumulation is two times greater than with a single intake of 10 mg per day.

    The maximum plasma concentration of 27.8 ng / ml is noted 4 hours after administration. Aksitinib can be taken regardless of the food intake: the exposure is reduced only by 10% when taken with fatty foods, by 19% with high-calorie food.

    The mean values ​​of the maximum concentration and area under the concentration-time curve (AUC) increase in proportion to the increase in the dose of axitinib in the dose range from 5 mg to 10 mg. The binding of axitinib to plasma proteins in vitro about 99%, mainly with albumin.

    The rate of filtration of axitinib is 38 l / h. The volume of distribution is 160 liters. Aksitinib mainly metabolized in the liver with the participation of isoenzymes CYP3A4 and CYP3A5. 30-60% of the administered dose of axitinib is excreted through the intestine, 23% in the urine. 12% of the dose of axitinib is excreted unchanged only with feces: with its urine output its metabolites: sulfoxide and N-glucuronide. These metabolites have, respectively, 400 and 8000 times less activity than unchanged axitinib.

    Indications:Common renal cell carcinoma.
    ICD-10

    II.C64-C68.C64   Malignant neoplasm of kidney, except for renal pelvis

    Contraindications:- hypersensitivity to the drug;

    - severe impairment of liver function (Child-Pugh class C);

    - arterial thromboembolism in the last 12 months;

    - venous thromboembolism in the last 6 months;

    - Stomach ulcer, duodenal ulcer with episodes of gastrointestinal hemorrhage in the anamnesis;

    - Pregnancy and the period of breastfeeding (FDA - D action category for the fetus);

    - Children under 18 years of age (safety and efficacy not investigated).

    Carefully:Arterial hypertension.

    Patients with an increased risk of thromboembolic complications. There are 2 cases of fatal thromboembolism on the background of taking axitinib. No studies have been conducted in the group of patients with advanced thromboembolism.

    Impaired renal function, creatinine clearance less than 15 ml / min.

    Dysfunction of the liver: apply with a choice of dose in patients of Class A and B on the Child-Pugh scale.

    In addition, care should be taken when prescribing axitinib to patients with lactose intolerance or intolerance or glucose-galactose malabsorption.

    Patients with peptic ulcer of the stomach and duodenum in the anamnesis: the perforation of the ulcer is possible, therefore periodic monitoring of the symptoms is necessary.

    Pregnancy and lactation:The action category for the fetus by FDA - D. Well-controlled studies of the effects of axitinib on the fetus were not conducted. When used in pregnant women, harm to the fetus is possible (teratogenic, fetotoxic effect in experiments on mice).Women of childbearing age who receive axitinib, it is recommended to abstain from pregnancy.

    Lactation: There is no evidence of the ability of the drug to enter breast milk. Due to potential side effects, it is recommended to stop breastfeeding for the period of taking the drug.

    Dosing and Administration:The recommended starting dose is 5 mg orally 2 times a day, regardless of food intake.

    If there are no significant side effects within 2 weeks, and normal blood pressure is preserved without taking antihypertensive drugs, the dose is increased to 7 mg twice a day.

    Further increase in the dose is possible up to 10 mg 2 times a day.

    In case of adverse reactions, the dose is reduced to 3 mg, then to 2 mg twice a day.

    The maximum daily dose is 20 mg. The maximum single dose is 10 mg.

    Application in elderly patients

    Insufficiently studied. In clinical studies, 34% of patients were over 65 years of age. There were no significant differences in the safety and efficacy of axitinib in young and elderly patients. The dose adjustment is carried out on a general basis.

    Side effects:From the cardiovascular system: hypertension (40%), deep vein thrombosis, transient ischemic attack (1%).

    From the side of the central nervous system: dizziness, malaise, headache.

    Dermatological: rash, hair loss.

    From the sense organs: dysphonia, dysgeusia.

    From the digestive tract: diarrhea, nausea, vomiting, constipation, stomatitis, abdominal pain, hemorrhoidal hemorrhages (2%).

    From the genitourinary system: proteinuria (11%), hematuria (2%).

    From the respiratory system: cough, shortness of breath, hemoptysis.

    From the musculoskeletal system: arthralgia, myalgia.

    Other side effects: syndrome of palmar-plantar dysesthesia (erythematous rashes on the palms and soles).

    Overdose:Dizziness, nausea, hypertensive crisis, hemoptysis.

    Treatment: temporary withdrawal of the drug, maintenance and symptomatic therapy.

    Interaction:The drug practically does not interact with food.

    Inhibitors of isoenzymes CYP3A4 / 5, (ketoconazole, itraconazole, clarithromycin) cause approximately a twofold increase in the plasma concentration of axitinib. If you can not cancel them, you need to reduce the dose twice.

    Inductors CYP3A4 / 5 (rifampicin, dexamethasone, phenytoin, carbamazepine, phenobarbital) significantly reduce the plasma concentration of axitinib. Avoid co-administration of these drugs with axitinib.

    Special instructions:Patients with hepatic insufficiency (classes A and B on the Child-Pugh scale) need a two-fold reduction in the dose of the drug.

    Constant monitoring of blood pressure is mandatory, especially in the first weeks of taking the drug. The hypertensive crisis develops in approximately 1% of patients.

    The drug is canceled 24 hours before the planned surgical intervention.

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