Erlotinib is an antitumor drug of the new generation, a potent inhibitor of epidermal growth factor receptor tyrosine kinase that is responsible for the intracellular phosphorylation of epidermal growth factor, the expression of which is observed on the surface of both normal and tumor cells. Inhibition of epidermal factor receptor phosphotyrosine inhibits the growth of tumor cell lines and/or leads to their death. Erlonat is a generic (analog) of the original preparation of Tarceva.
Erlotinib is well absorbed after ingestion. C max in plasma is 1.995 mg/ml and is reached after 4 hours. Bioavailability of erlotinib is 59%, eating can increase its bioavailability.
C ss are achieved by 7-8 days. Before taking the next dose, the mean C min of erlotinib in plasma is 1.238 mg/ml. AUC in the inter-dose interval after reaching C ss – 41.3 mg × h / ml.
Apparent V d – 232 l with distribution in the tumor tissue. In tumor tissue samples (lung cancer, laryngeal cancer) on the 9th day of treatment, the average concentration of erlotinib is 1.185 ng /g, which is 63% of the C max in plasma in equilibrium. The concentration of the main active metabolites in the tumor tissue is 160 ng/g, which corresponds to 113% C max in the plasma in the equilibrium state.
Studies on the distribution in tissues of labeled 14 C erlotinib following oral administration in athymic mice with a nude gene mutation with HT5 tumor cell transplant (using common autoradiography) demonstrated rapid and intensive tissue distribution. C max in tissue is about 73% of erlotinib concentration. T max in the fabric – 1 h.
Erlotinib is metabolized in the liver with the participation of the CYP3A4 isoenzyme, to a lesser extent CYP1A2 and the pulmonary is form CYP1A1. The extrahepatic metabolism involving the CYP3A4 isoenzyme in the intestine, the CYP1A1 isoenzyme in the lungs, the CYP1B1 isoenzyme in the tumor tissue provides the metabolic clearance of erlotinib. In vitro, 80-95% of erlotinib is metabolized with the participation of CYP3A4. Metabolism occurs in three ways: 1) O-dimethylation of one of the side or both chains, followed by oxidation to carboxylic acids; 2) oxidation of the acetylene moiety of the molecule followed by hydrolysis to arylcarboxylic acid, and 3) aromatic hydroxylation of the phenyl-acetylene moiety of the molecule. The main metabolites are formed as a result of O-dimethylation of one of the side chains and have activity comparable to erlotinib. They are present in plasma in concentrations,
The average ground clearance is 4.47 l / h. There was no relationship between clearance and age, body weight, sex, race of the patient. The average T 1/2 is 36.2 hours.
Supportive therapy for locally advanced or metastatic non-small cell lung cancer in the absence of disease progression after 4 courses of the first line of chemotherapy based on platinum drugs.
Locally distributed or metastatic non-small cell lung cancer after failure of one or more chemotherapy regimens.
Locally-distributed inoperable or metastatic pancreatic cancer as first-line therapy in combination with gemcitabine.
The dose is set individually depending on the indications and concomitant therapy. Take inside at a dose of 100-150 mg 1 time/day. The duration of use depends on the effectiveness and tolerability of therapy. With the development of severe adverse reactions, consideration should be given to reducing the dose or interrupting therapy.
From the digestive system: very often – diarrhea, nausea, vomiting, stomatitis, abdominal pain, flatulence, indigestion; often – gastrointestinal bleeding (including isolated cases with a fatal outcome), some of which were associated with simultaneous use of warfarin or NSAIDs; infrequent – perforation of the gastrointestinal tract, in some cases with a fatal outcome.
From the nervous system: very often – headache, neuropathy.
From the side of the psyche: very often – depression.
Other: very often – fatigue, severe infections (with or without neutropenia, pneumonia, sepsis, phlegmon), fever, chills, weight loss.
Contraindications for use
Severe liver dysfunction (10 or more Child-Pugh score); severe renal dysfunction; pregnancy; lactation period (breastfeeding); children and adolescents under 18; increased sensitivity to erlotinib.
Application in pregnancy and lactation
The use of erlotinib is contraindicated in pregnancy and lactation. During treatment with erlotinib and at least 2 weeks after the end, reliable contraceptive methods should be used.
Application for violations of liver function
Contraindicated in severe violations of the liver (10 or more points on the scale Child-Pugh). Hepatitis, hepatic insufficiency, including fatal cases, rarely occurred during the administration of erlotinib. In patients with a concomitant liver disease or receiving hepatotoxic drugs, it is recommended to monitor liver function. With the development of severe liver damage, erlotinib should be discontinued.
Application for violations of kidney function
Contraindicated in severe renal dysfunction. In rare cases, it is possible to develop hypokalemia and renal insufficiency, incl. with a lethal outcome. Some cases of kidney failure were caused by severe dehydration due to diarrhea, vomiting and/or anorexia, others – concomitant chemotherapy. In the most severe or persistent cases of diarrhea or conditions leading to dehydration, especially in patients at risk (elderly age, concomitant therapy or diseases), erlotinib is temporarily withdrawn and parenteral rehydration is performed. Patients with a high risk of dehydration should monitor serum electrolytes, including potassium, and kidney function.
Use in children
Contraindicated in children and adolescents less than 18 years.