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

It binds to epidermal growth factor receptors HER1 / EGFR and inhibits tyrosine kinase, an enzyme responsible for the intracellular phosphorylation process of HER1 / EGFR. HER1 / EGFR is expressed on the surface of both normal and cancer cells. Inhibition of phosphotyrosine EGFR inhibits the growth of tumor cell lines and / or causes their death.

Pharmacokinetics:

Well absorbed after ingestion. Bioavailability - 59%, food intake increases bioavailability. FROM_max in blood plasma is achieved after 4 hours. The connection with plasma proteins is 95%. FROM_ss in the blood is achieved after 7-8 days of admission. Biotransformation occurs in the liver with the participation of enzymes CYP3A4, to a lesser extent - CYP1A2 and the pulmonary isoform CYP1A1. The half-life is 36 hours. Metabolites and trace amounts of erlotinib are excreted through the intestine (more than 90%) and kidneys (less than 10%).

Indications:

Locally advanced, inoperable or metastatic pancreatic cancer as the first line of therapy (in combination with gemcitabine).

Locally advanced or metastatic non-small cell lung cancer after ineffective use of one or more chemotherapy regimens.

ICD-10

II.C15-C26.C25 Malignant neoplasm of pancreas

II.C30-C39.C34 Malignant neoplasm of bronchi and lungs

Contraindications:

Hypersensitivity, severe hepatic impairment, age to 18 years.

Carefully:

Violations of liver function of medium or severe degree.

Pregnancy and lactation:

Recommendations for FDA - category D.

The use of the drug is contraindicated in pregnancy and lactation.

Dosing and Administration:

Inside, 1 hour before or 2 hours after a meal, 150 mg once a day.

Side effects:

Most often: a rash (69-75%), usually after 8-10 days, and diarrhea (48-54%), usually after 12-15 days, mostly 1 and 2 degrees of severity.

Central and peripheral nervous system: very often - headache, neuropathy, depression.

Respiratory system: very often - cough, shortness of breath; often - epistaxis; infrequently - interstitial lung diseases.

Digestive system: very often - anorexia, diarrhea, vomiting, stomatitis, abdominal pain, indigestion; often - gastrointestinal bleeding, violations of the liver.

Musculoskeletal system: myalgia, ossalgia.

Skin: very often - a rash, alopecia, dry skin, itching.

Sense organs: very often - conjunctivitis.

Overdose:

Symptoms: increased side effects.

Treatment is symptomatic.

Interaction:

Inhibitors of CYP3A4 (eg, ketoconazole) reduce the metabolism of erlotinib and increase its concentration in the blood plasma. Care should be taken with this combination and in case of development of toxicity, a reduction in the dose of erlotinib is necessary.

Inductors CYP3A4 (for example, carbamazepine, rifampicin, phenytoin) increase the metabolism of erlotinib and significantly reduce its concentration in the blood plasma.

With the simultaneous use of warfarin and other coumarin derivatives, prothrombin time or an international normalized ratio should be monitored regularly.

Special instructions:

If severe or moderate diarrhea occurs, prescription of antidiarrhoeal agents (for example, loperamide) is possible.

Before treatment and then monthly monitored the activity of transaminases, alkaline phosphatase, and bilirubin. If necessary, the dose of erlotinib is corrected.

During treatment and for at least 2 weeks after its end, reliable contraceptive methods should be used.

Instructions

Erlotinib (Erlotinibum)