Erlotinib

Indications

Erlotinib is used for: Small cell lung cancer, Pancreatic cancer

Adult Dose

Oral Locally advanced or metastatic non-small cell lung carcinoma Adult: 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 Adult: As 1st-line treatment with gemcitabine: 100 mg once daily, reduce dose in decrements of 50 mg when necessary.

Child Dose

Safety and efficacy not established

Renal Dose

Administration

Should be taken on an empty stomach. Take on an empty stomach at least 1 hr before or 2 hr after meals.

Contra Indications

Hypersensitivity.

Precautions

Pregnancy and lactation. Interrupt Erlotinib therapy if patient develops unexplained pulmonary symptoms e.g. dyspnoea, cough, fever; discontinue therapy if interstitial lung disease is diagnosed. Monitor liver functions periodically; extreme caution is needed if total bilirubin is 3x >ULN; close monitoring is required in patients with hepatic impairment. Interrupt/discontinue therapy if severe changes in liver functions (doubling of total bilirubin and/or tripling of transaminases) occur. Interrupt therapy in the event of dehydration especially in patients with predisposing factors to renal failure. Monitor renal function and serum electrolytes in patients at risk of dehydration. Interrupt or discontinue therapy if patient develops severe bullous and exfoliative skin disorders; eye pain or other acute/worsening ocular disorders. If patient develops GI perforation, discontinue therapy permanently. Patients with CV disorders. Monitor prothrombin time/INR in patients taking warfarin or other coumarin-derivative anticoagulants. Lactation: excretion in milk unknown/not recommended

Pregnancy-Lactation

Pregnancy Based on animal data and its mechanism of action, erlotinib can cause fetal harm when administered to a pregnant woman Advise females of reproductive potential to use effective contraception during treatment and for 1 month after the last dose Lactation No data exist on the presence of erlotinib in human milk, or the effects of erlotinib on the breastfed infant or on milk production Because of the potential for serious adverse reactions in breastfed infants, including interstitial lung disease, hepatotoxicity, bullous and exfoliative skin disorders, microangiopathic hemolytic anemia, with thrombocytopenia, ocular disorders, and diarrhea Advise a lactating woman not to breastfeed during treatment and for 2 weeks after the final dose

Interactions

Increased serum levels w/ potent CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, atazanavir). CYP3A4 inducers (e.g. rifampicin, carbamazepine, phenytoin, phenobarbital) may reduce exposure of erlotinib. Increased serum levels w/ potent inhibitors of CYP1A2 (e.g. ciprofloxacin) or capecitabine. Use w/ P-glycoprotein inhibitors (e.g. ciclosporin, verapamil) may cause altered distribution or elimination of erlotinib. Drugs that increase the pH of the GI tract (e.g. antacids, H2-receptor antagonists, or PPIs) may reduce the solubility of erlotinib thus lowering its bioavailability. Concomitant use w/ warfarin or other coumarin derivates may increase INR and bleeding events.

Adverse Effects

Side effects of Erlotinib : >10% Rash (75-76%), Anorexia (52-69%), Diarrhea (54-55%), Fatigue (52-79%), Nausea (33-40%), Infection (39%), Vomiting (23-25%), Dyspnea (24%), Stomatitis (17-19%), Cough (16%), Pruritus (13%), Conjunctivitis (12%), Dry skin (12%), Keratoconjunctivitis sicca (12%), Abdominal pain (11%) 1-10% Elevated LFT's (grade 2), Acne, Paronychia, Weight loss, Pneumonitis pulmonary infiltrate, Pulmonary fibrosis <1% Interstitial lung disease-like events

Mechanism of Action

Erlotinib is an epidermal growth factor receptor/human epidermal growth factor receptor type 1 (EGFR/HER1) tyrosine kinase inhibitor. It reversibly inhibits the kinase activity of EGFR, preventing autophosphorylation of tyrosine residues associated w/ the receptor, thereby inhibiting further downstream signaling and resulting in cell death.