Iressa - Side Effects & Drug Interactions

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In the event of acute onset or worsening of pulmonary symptoms (dyspnea, cough, fever), IRESSA therapy should be interrupted and a prompt investigation of these symptoms should occur. If interstitial lung disease is confirmed, IRESSA should be discontinued and the patient treated appropriately (see WARNINGS-Pulmonary Toxicity, PRECAUTIONS-Information for Patients and DOSAGE AND ADMINIS-TRATION- Dosage Adjustment sections). In patients receiving IRESSA therapy, there were reports of eye pain and corneal erosion/ ulcer, sometimes in association with aberrant eyelash growth (see PRECAU-TIONS- Information for Patients section).

There were also rare reports of pancre-atitis and very rare reports of corneal membrane sloughing, ocular ischemia/ hemorrhage, toxic epidermal necrolysis, erythema multiforme, and allergic reactions, including angioedema and urticaria. International Normalized Ratio (INR) elevations and/ or bleeding events have been reported in some patients taking warfarin while on IRESSA therapy. Patients taking warfarin should be monitored regularly for changes in prothrombin time or INR (see CLINICAL PHARMACOLOGY-Drug-Drug Interactions and PRECAUTIONS-Drug Interactions sections). Data from non-clinical (in vitro and in vivo) studies indicate that gefitinib has the potential to inhibit the cardiac action potential repolarization process (eg, QT interval). The clinical relevance of these findings is unknown.

Drug-Drug Interactions

In human liver microsome studies, gefitinib had no inhibitory effect on CYP1A2, CYP2C9, and CYP3A4 activities at concentrations ranging from 2- 5000 ng/ mL. At the highest concentration studied (5000 ng/ mL), gefitinib inhibited CYP2C19 by 24% and CYP2D6 by 43%. Exposure to metoprolol, a substrate of CYP2D6, was increased by 30% when it was given in combination with gefitinib (500 mg daily for 28 days) in patients with solid tumors. Rifampicin, an inducer of CYP3A4, reduced mean AUC of gefitinib by 85% in healthy male volunteers (see PRECAUTIONS-Drug Interactions and DOSAGE AND ADMINISTRATION-Dosage Adjustment sections).