Similar to gefitinib, erlotinib specifically targets the epidermal growth factor receptor (EGFR) tyrosine kinase. It binds in a reversible fashion to the adenosine triphosphate (ATP) binding site of the receptor. Erlotinib has recently been shown to be a potent inhibitor of JAK2V617F activity. JAK2V617F is a mutant of tyrosine kinase JAK2, is found in most patients with polycythemia vera (PV) and a substantial proportion of patients with idiopathic myelofibrosis or essential thrombocythemia. The study suggests that erlotinib may be used for treatment of JAK2V617F-positive PV and other myeloproliferative disorders.
Antineoplastic Agents Protein Kinase Inhibitors Antineoplastic and Immunomodulating Agents Cytochrome P-450 CYP1A2 Inhibitors Cytochrome P-450 CYP1A2 Inducers Cytochrome P-450 CYP2C8 Inhibitors Cytochrome P-450 CYP2C8 Inducers CYP2D6 Inducers CYP2D6 Inducers (strong) CYP3A4 Inhibitors
Erlotinib 150 MG
For the treatment of patients with locally advanced or metastatic non-small cell lung cancer after failure of at least one prior chemotherapy regimen. Also for use, in combination with gemcitabine, as the first-line treatment of patients with locally advanced, unresectable or metastatic pancreatic cancer.
The mechanism of clinical antitumor action of erlotinib is not fully characterized. Erlotinib inhibits the intracellular phosphorylation of tyrosine kinase associated with the epidermal growth factor receptor (EGFR). Specificity of inhibition with regard to other tyrosine kinase receptors has not been fully characterized. EGFR is expressed on the cell surface of normal cells and cancer cells.
Erlotinib is about 60% absorbed after oral administration and its bioavailability is substantially increased by food to almost 100%. Peak plasma levels occur 4 hours after dosing. The solubility of erlotinib is pH dependent. Solubility decreases pH increases. Smoking also decrease the exposure of erlotinib.
Apparent volume of distribution = 232 L
Metabolism occurs in the liver. In vitro assays of cytochrome P450 metabolism showed that erlotinib is metabolized primarily by CYP3A4 and to a lesser extent by CYP1A2, and the extrahepatic isoform CYP1A1.
Following a 100 mg oral dose, 91% of the dose was recovered in which 83% was in feces (1% of the dose as unchanged parent compound) and 8% in urine (0.3% of the dose as unchanged parent compound).
Median half-life of 36.2 hours.
Symptoms of overdose include diarrhea, rash, and liver transaminase elevation. The most common adverse reactions (>50%) in NSCLC are rash, diarrhea, anorexia and fatigue. The most common adverse reactions (>50%) in pancreatic cancer are fatigue, rash, nausea and anorexia.
Take at least 1 hour before or 2 hours after any food. Take with a glass of water.
Chance of getting an infection. Wash hands often. Stay away from people with infections, colds, or flu. Feeling dizzy. Rise slowly over a few minutes when sitting or lying down. Be careful climbing. Feeling tired or weak. Rash. Upset stomach or throwing up. Many small meals, good mouth care, sucking hard, sugar-free candy, or chewing sugar-free gum may help. Loose stools (diarrhea). Headache. Belly pain. Cough. Eye irritation. Skin irritation. Harm to the lungs may rarely happen.