Gefitinib

Indications

Gefitinib is used for: Non-small Cell Lung Cancer

Adult Dose

Oral Locally advanced or metastatic non-small cell lung carcinoma Adult: 250 mg once daily until disease progression or unacceptable toxicity

Child Dose

Renal Dose

Administration

Film-coated tab: May be taken with or without food. May also be dispersed in ½ glass of plain, non-carbonated water. No other liqd should be used. Drop the tab in water & stir w/o crushing until it disperses (approx 10 min). Drink immediately. Rinse glass w/ another ½ glass of water & drink. Dispersed liqd may also be administered via NG tube.

Contra Indications

Hypersensitivity. Lactation.

Precautions

Patients w/ concurrent idiopathic pulmonary fibrosis, acute onset or worsening pulmonary or eye symptoms. Renal and hepatic impairment. Pregnancy. Monitoring Parameters Monitor liver function, prothrombin time or INR frequently. Lactation Unknown if distributed in human breast milk; not recommended

Pregnancy-Lactation

Pregnancy Based on its mechanism of action and animal data, gefitinib can cause fetal harm when administered to a pregnant woman Advise females of reproductive potential to use effective contraception during treatment with gefitinib and for at least 2 weeks following completion of therapy Advise pregnant women of the potential hazard to a fetus or potential risk for loss of the pregnancy Lactation Unknown if distributed in human breast milk; not recommended Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Interactions

Concomitant use w/ CYP3A4 inducers (e.g. rifampicin, phenytoin, carbamazepine, barbiturates) may reduce serum gefitinib levels. Plasma concentrations may be increased w/ potent CYP3A4 inhibitors (e.g. itraconazole, ketoconazole). Increased INR or bleeding events w/ warfarin. May increase plasma levels of metoprolol. May exacerbate vinorelbine-induced neutropenia. Decreased plasma levels and potential reduction in efficacy w/ drugs that affect gastric pH (e.g. PPIs, H2-receptor antagonists).

Adverse Effects

Side effects of Gefitinib : >10% Skin reactions, all grades (47%), Diarrhea, all grades (29%), Decreased appetite, all grades (17%), Vomiting, all grades (14%), Increased ALT, all grades (11.4%) 1-10% Increased AST, all grades (7.9%), Stomatitis, all grades (7%), Conjunctivitis, blepharitis, and dry eye (6.7%), Conjunctivitis/blepharitis/dry eye (6%), Increased ALT, grades 3-4 (5.1%), Nail disorders, all grades (5%), Diarrhea, grades 3-4 (3%), Increased AST, grades 3-4 (3%), Increased bilirubin, all grades (2.7%), Decreased appetite, grades 2-3 (2.3%), Skin reactions, grades 3-4 (2%), Interstitial lung disease, all grades (1.3%), Vomiting, grades 3-4 (1.2%) <1% Interstitial lung disease, grades 3-4 (0.7%), Increased bilirubin, grades 3-4 (0.7%), Stomatitis, all grades (0.3%), Corneal erosion and aberrant eyelash growth (0.2%), Nail disorders, grades 3-4 (0.1%), Gastrointestinal perforation (0.1%), Ocular keratitis (0.1%), Erythema multiforme and dermatitis bullous (0.08%), Fatal hepatoxicity (0.04%)

Mechanism of Action

Gefitinib is a synthetic anilinoquinazoline which inhibits the intracellular phosphorylation of numerous tyrosine kinases associated w/ transmembrane cell surface receptors found on both normal and cancer cells, including epidermal growth factor receptor (EGFR) tyrosine kinase. Tyrosine kinase activity appears to be essentially important to cell proliferation and survival.