Geficent 250: Each tablet contains Gefitinib INN 250 mg.
Gefitinib reversibly inhibits the kinase activity of wild-type and certain activating mutations of EGFR, preventing autophosphorylation of tyrosine residues associated with the receptor, thereby inhibiting further downstream signalling and blocking EGFR-dependent proliferation.
Gefitinib binding affinity for EGFR exon 19 deletion or exon 21 point mutation L858R mutations is higher than its affinity for the wild-type EGFR. Gefitinib also inhibits IGF and PDGF-mediated signalling at clinically relevant concentrations; inhibition of other tyrosine kinase receptors has not been fully characterized.
Limitation of Use: Safety and efficacy of Gefitinib have not been established in patients whose tumors have EGFR mutations other than exon 19 deletions or exon 21 (L858R) substitution mutations.
Hepatotoxicity: Periodic liver function testing should be performed. Gefitinib should be withheld for Grade 2 or higher for ALT and/or AST elevations. It should be discontinued for severe hepatic impairment.
Gastrointestinal perforation: Gefitinib should be discontinued for gastrointestinal perforation.
Diarrhea: Gefitinib should be withheld for Grade 3 or higher diarrhea.
Ocular Disorders including Keratitis: Gefitinib should be withheld for signs and symptoms of severe or worsening ocular disorders including keratitis. It should be discontinued for persistent ulcerative keratitis.
Bullous and Exfoliative Skin Disorders: Gefitinib should be withheld for Grade 3 or higher skin reactions or exfoliative conditions.
Embryo-fetal Toxicity: Gefitinib can cause fetal harm. Potential risk of Gefitinib to a fetus should be advised and effective contraception should be used.
It is not known whether Gefitinib is excreted in human milk. Breast-feeding should be discontinued during treatment with Gefitinib.
The safety and effectiveness of Gefitinib in pediatric patients have not been established.
No overall differences in safety were observed between patients 65 years and older and those younger than 65 years. There is insufficient information to assess for differences in efficacy between older and younger patients.
Drugs that are strong inducers of CYP3A4 increase the metabolism of gefitinib and decrease gefitinib plasma concentrations. Increase Gefitinib to 500 mg daily in patients receiving a strong CYP3A4 inducer (e.g., rifampicin, phenytoin, or tricyclic antidepressant) and resume Gefitinib at 250 mg 7 days after discontinuation of the strong inducer.
Drugs that are strong inhibitors of CYP3A4 (e.g. Ketoconazole and Itraconazole) decrease Gefitinib metabolism and increase Gefitinib plasma concentrations. Adverse reactions should be monitored when administering strong CYP3A4 inhibitors with Gefitinib.
Drugs Affecting Gastric pH
Drugs that elevate gastric pH (e.g., proton pump inhibitors, histamine H2-receptor antagonists, and antacids) may reduce plasma concentrations of Gefitinib. Concomitant use of Gefitinib with proton pump inhibitors should be avoided, if possible. If treatment with a proton-pump inhibitor is required, Gefitinib should be taken 12 hours after the last dose or 12 hours before the next dose of the proton-pump inhibitor. Gefitinib should be taken 6 hours after or 6 hours before an H2-receptor antagonist or an antacid.
Hemorrhage in Patients taking Warfarin
International Normalized Ratio (INR) elevations and/or hemorrhage have been reported in some patients taking warfarin while on Gefitinib therapy. Patients taking warfarin should be monitored regularly for changes in prothrombin time or INR.