Anticancer drug. As a selective inhibitor of tyrosine kinase of epidermal growth factor receptors, the expression of which is observed in many solid tumors, inhibits tumor growth, metastasis, and angiogenesis, and accelerates tumor cell apoptosis.
Inhibits the growth of various lines of human tumor cells and increases antitumor activity of chemotherapy drugs, radiation and hormone therapy.
Gefitinib instructions for use
After oral absorption is relatively slow. Bioavailability is 59%. Eating does not affect the bioavailability of the drug. Vd — 1400 L. the plasma protein Binding (serum albumin and a,-glycoprotein) is 90%. Metabolized with the participation of isoenzyme CYP3A4.
The main metabolite has 14 times less activity compared to gefitinib in respect of cellular growth stimulated by an epidermal growth factor, which makes it unlikely to have a significant impact on the clinical activity of gefitinib. T1 / 2 — 41H. The drug is excreted mainly in feces. Less than 4% of the administered dose is excreted in the urine.
Locally advanced or metastatic non-small cell lung cancer refractory to chemotherapy regimes containing platinum derivatives and docetaxel.
The drug is prescribed orally 250 mg 1 p/day regardless of food intake. Before taking the tablet can be dissolved in 100 ml of drinking (non-carbonated) water. Other liquids cannot be used to dissolve the drug.
For the right dissolution, it is necessary to lower the tablet into the water without kneading, stirring until completely dissolved (about 10 minutes) and immediately drink the resulting solution. Pour another half a glass of water, washing the walls, and drink the resulting solution.
Is not required correction doses depending on the patient’s age, body mass, ethnicity, sex, renal function, as well as in moderate and severe hepatic insufficiency due to metastatic lesions of the liver.
With poorly bathing diarrhea during treatment or adverse reactions from the skin, a short break in treatment (up to 14 days) is possible, followed by the resumption of the drug at a dose of 250 mg/day.
From the coagulation system: hematuria and nosebleeds; hypercoagulation and/or increase in the frequency of bleeding while taking warfarin.
On PS: diarrhea (more than 20%, 8 cases — expressed), nausea, vomiting, anorexia, stomatitis, dehydration, asymptomatic increase in liver transaminases, pancreatitis.
From the organs of vision: conjunctivitis, blepharitis; reversible erosion of the cornea, impaired eyelash growth.
From the respiratory system: interstitial pneumonia (3-4 degrees of toxicity, up to death).
Dermatological reactions: rash (pustular), pruritus, dry skin on the background of erythema; nail changes, alopecia; toxic epidermal necrolysis and erythema multiforme.
AR: angioedema, urticaria.
Pregnancy; lactation; childhood and adolescence; increased sensitivity to gefitinib or other components of the drug.
With caution, the drug should be prescribed for idiopathic pulmonary fibrosis, interstitial pneumonia, pneumoconiosis, post-radiation pneumonia, drug pneumonia (marked by an increased mortality rate from these diseases in the treatment of Iressa); with an increase in the activity of hepatic transaminases.
increase in the frequency and severity of certain adverse reactions, mainly diarrhea, and skin rashes.
conduct symptomatic therapy. The antidote is not known.
Interaction with other drugs
The joint appointment of gefitinib and rifampicin (a potent inducer of CYP3A4) leads to a decrease in the mean AUC values for gefitinib by 83%. Co-administration of Itraconazole (inhibitor of CYP3A4) leads to an increase of 80% AUC of gefitinib that can be clinically significant, as adverse events are dose-dependent and concentration.
The simultaneous appointment of drugs that contribute to a significant and prolonged increase in pH of gastric contents, led to a decrease in AUC for gefitinib by 47%.
In a joint application, vinorelbine may increase neitropeniceskih action vinorelbine. Simultaneous administration of gefitinib with drugs, inducers of CYP3A4 isoenzymes, such as phenytoin, carbamazepine, rifampicin, barbiturates, St. John’s wort tincture, can reduce the effectiveness of gefitinib.