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

Clinical and pharmacological group: & nbsp

Antineoplastic antibiotics

Included in the formulation

Ikzempra®

lyophilizate d / infusion

Bristol-Myers Squibb Manufacturing Company Puerto Rico

Included in the list (Order of the Government of the Russian Federation No. 2782-r of 30.12.2014):

ONLS

АТХ:

L.01.D.C.04 Ixabepilone

Pharmacodynamics:

Stabilizes the dynamics of microtubules, which leads to blockade of mitosis of tumor cells and to their apoptosis and death. It has low sensitivity to tumor resistance factors: the protein of multiple drug resistance (MRP-1) and the P-glycoprotein (P-gp), which plays a role in the formation of resistance to the action of antitumour agents. Ixabepilone, binding to tubulin, inhibits the dynamics of microtubules of various forms of β-tubulin, including βIII-isoform tubulin, the excessive expression of which is associated with the development of resistance to taxanes. In addition, Ixabepilone has an anti-angiogenic effect.

Pharmacokinetics:

After intravenous administration, the maximum concentration in the blood plasma is reached 3 hours after the end of the infusion. The connection with plasma proteins is 67-77%.

Metabolism in the liver up to 30 metabolites.

The elimination half-life is 52 hours. Elimination by the kidneys.

Indications:

It is used to treat locally advanced or metastatic breast cancer.

ICD-10

II.C50.C50 Malignant neoplasm of breast

Contraindications:

Absolute number of neutrophils is less than 1500 cells / μl or platelets - less than 100,000 cells / μl, individual intolerance, age under 18 years.

Carefully:

Neuropathy, diabetes, cardiovascular dysfunction in history, hepatic insufficiency.

Pregnancy and lactation:

Recommendations for FDA - category D. Contraindicated in pregnancy and lactation.

Dosing and Administration:

40 mg / m² intravenously, as a three-hour infusion every 3 weeks.

The highest daily dose: 40 mg / m².

The highest single dose: 40 mg / m².

Side effects:

Central and peripheral nervous system: headache, peripheral sensory neuropathy, insomnia, cognitive impairment, fainting, rarely peripheral motor neuropathy, impaired coordination of movements, hemorrhagic stroke.

Respiratory system: shortness of breath, cough, rarely - pneumonitis, respiratory failure, dysphonia, pulmonary edema.

The system of hematopoiesis: anemia, neutropenia, thrombocytopenia, leukopenia, febrile neutropenia, rarely - lymphopenia, coagulopathy.

The cardiovascular system: "Tides" with heat, lower blood pressure, ventricular dysfunction, myocardial infarction, supraventricular arrhythmia, thrombosis, rarely - angina pectoris, myocardial ischemia, cardiomyopathy, atrial fibrillation, hypovolemic shock, pulmonary embolism, vasculitis, hemorrhage.

Digestive system: stomatitis / mucositis, abdominal pain, vomiting, diarrhea, constipation, nausea, gastroesophageal reflux disease, esophagitis, colitis, intestinal obstruction, impaired gastric emptying, rarely - dysphagia, gastrointestinal bleeding, gastritis.

Musculoskeletal system: myalgia, arthralgia, muscle weakness, rarely - muscle spasms, lockjaw.

Dermatological reactions: alopecia, skin rash, syndrome eritrodizestezii fingers and toes, hyperpigmentation of the skin, itching, peeling skin, nail infections, rarely - erythema multiforme.

Allergic reactions.

Overdose:

Increased side effects.

Treatment is symptomatic.

Interaction:

Inducers of CYP3A4 isoenzyme Ixabepilone slow metabolism and increase its concentration in plasma.

Preparations that induce the isoenzyme CYP3A4 (dexamethasone, carbamazepine, rifabutin, phenytoin, phenobarbital, rifampicin, preparations of St. John's wort perfumed), accelerate the metabolism of Ixabepilone and reduce its concentration in the blood plasma.

Special instructions:

To prevent hypersensitivity reactions, all patients approximately 1 hour before the infusion of Ixabepilone should undergo adequate premedication using: blocker H₁-gistaminovyh receptors (diphenhydramine 50 mg orally) and blocker H₂-gistaminovyh receptors (ranitidine 150-300 mg orally or 50 mg intravenously).

If there is a history of hypersensitivity to ixabepilone in addition to premedication with H blockers₁- and H₂-gistaminovyh receptors require premedication glucocorticosteroids (dexamethasone 20 mg intravenously 30 minutes before infusion or inside 12 and 6 hours before infusion).

Patients receiving Ixabepilone treatment are prohibited from driving and working with moving mechanisms.

Instructions

Ixabepilone (Ixabepilonum)