Locally advanced or metastatic non-small cell lung carcinoma, Locally advanced, unresectable or metastatic pancreatic cancer.
Erlotinib, a kinase inhibitor, is a quinazolinamine with the chemical name N-(3-ethynylphenyl)-6,7-bis(2-methoxyethoxy)4-quinazolinamine. Erlotinib reversibly inhibits the kinase activity of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor and thereby inhibiting further downstream signaling. Erlotinib binding affinity for EGFR exon 19 deletion or exon 21 (L858R) mutations is higher than its affinity for the wild-type receptor. Erlotinib inhibition of other tyrosine kinase receptors has not been fully characterized.
Oral (Adult)- Locally advanced or metastatic non-small cell lung carcinoma: 150 mg once daily until disease progression or unacceptable toxicity. Reduce dose in decrements of 50 mg when necessary. Locally advanced, unresectable or metastatic pancreatic cancer: As 1st-line treatment with gemcitabine: 100 mg once daily, reduce dose in decrements of 50 mg when necessary. Patient on CYP3A4 or CYP1A2 inhibitor: Reduce dose in decrements of 50 mg when necessary. Smokers or patient on CYP3A4 inducer: Increase dose as tolerated in increments of 50 mg at 2-wk intervals.
Anticoagulants: Interaction with coumarin-derived anticoagulants, including warfarin, leading to increased International Normalized Ratio (INR) and bleeding adverse reactions.
CYP3A4 inhibitors: Erlotinib is metabolized predominantly by CYP3A4. Co-treatment with the potent CYP3A4 inhibitor ketoconazole increased Erlotinib AUC by 67%. When Erlotinib was co-administered with Ciprofloxacin, an inhibitor of both CYP3A4 and CYP1A2, the Erlotinib exposure [AUC] and maximum concentration [Cmax] increased by 39% and 17%, respectively.
CYP3A4 inducers: Pre-treatment with the CYP3A4 inducer Rifampicin for 7-11 days prior to Erlotinib decreased Erlotinib AUC by 58% to 80%. Dose modifications are recommended.
Drugs affecting gastric pH: Co-administration of Erlotinib with omeprazole decreased Erlotinib AUC by 46% and co-administration of Erlotinib with Ranitidine 300 mg decreased Erlotinib AUC by 33%.
Contraindicated in pregnancy, hypersensitivity. Hepatic and renal impairment. Interrupt or discontinue therapy if patient develops unexplained pulmonary symptoms (e.g. dyspnoea, cough, fever), GI perforation, severe bullous, skin or ocular disorders, if dehydration occurs (esp in at-risk patients). Pregnancy and lactation. LFT (e.g. serum transaminase, bilirubin, alkaline phosphatase) should be periodically monitored. Renal function and electrolytes should be monitored periodically in patients at risk of dehydration.
Rash manifests as a mild or moderate erythematous and papulopustular rash. Bullous, blistering, and exfoliative skin conditions, diarrhoea, nausea, vomiting, stomatitis, GI bleeding, abdominal pain, anorexia, alopecia, pruritus, dry skin, paronychia, conjunctivitis, epistaxis, fatigue, alterations in LFT, abnormal eyelash growth, bilateral eardrum perforation, keratoconjunctivitis sicca or keratitis.
Category D: There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).
Single oral doses of Erlotinib up to 1,000 mg in healthy subjects and weekly doses up to 1,600 mg in cancer patients have been tolerated. Repeated twice-daily doses of 200 mg single-agent Erlotinib in healthy subjects were poorly tolerated after only a few days of dosing. Based on the data from these studies, an unacceptable incidence of severe adverse reactions, such as diarrhea, rash, and liver transaminase elevation, may occur above the recommended dose. In case of suspected overdose, Erlotinib should be withheld and symptomatic treatment instituted.
Store at a temperature not exceeding 30°C in a dry place. Protect from light and moisture.
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