Gefitinib
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From MedlinePlus, U.S. National Library of Medicine
Kinase Inhibitor
Dosing in kidney impairment
Renal Impairment Less than four percent (<4%) of gefitinib and its metabolites are excreted via the kidney. No clinical studies were conducted with IRESSA in patients with severe renal impairment.
Dosing in liver impairment
Hepatic Impairment The systemic exposure of gefitinib was compared in patients with mild, moderate, or severe hepatic impairment due to cirrhosis (according to Child-Pugh classification) and healthy subjects with normal hepatic function (N=10/group). The mean systemic exposure (AUC 0-∞ ) was increased by 40% in patients with mild impairment, 263% in patients with moderate impairment, and 166% in patients with severe hepatic impairment.
Monitor adverse reactions when IRESSA is administered to patients with moderate and severe hepatic impairment. In a study comparing 13 patients with liver metastases and moderate hepatic impairment (addition of CTC grade of baseline AST/SGOT, ALP, and bilirubin equals 3 to 5) to 14 patients with liver metastases and normal hepatic function, the systemic exposure of gefitinib was similar [see Warnings and Precautions ] .
Preparation and administration
Administration to Patients Who Have Difficulty Swallowing Solids Immerse IRESSA tablets in 4 to 8 ounces of water by dropping the tablet in water, and stir for approximately 15 minutes. Immediately drink the liquid or administer through a naso-gastric tube. Rinse the container with 4 to 8 ounces of water and immediately drink or administer through the naso-gastric tube.
Drug interactions
Check gefitinib against a medication listLabel text (4 paragraphs)
7 DRUG INTERACTIONS • CYP3A4 Inducer: Increase IRESSA to 500 mg daily in patients receiving a strong CYP3A4 inducer. ( 2.4 , 7.1 ) • CYP3A4 Inhibitor: Monitor adverse reactions if concomitant use with IRESSA. ( 7.1 ) • Drugs Affecting Gastric pH: Avoid concomitant use of IRESSA with proton pump inhibitors, if possible. ( 7.1 ) • Hemorrhage in patients taking warfarin: Monitor changes in prothrombin time or INR. ( 7.2 )
7.1 Drugs Affecting Gefitinib Exposure CYP3A4 Inducer Drugs that are strong inducers of CYP3A4 increase the metabolism of gefitinib and decrease gefitinib plasma concentrations. Increase IRESSA to 500 mg daily in patients receiving a strong CYP3A4 inducer (e.g., rifampicin, phenytoin, or tricyclic antidepressant) and resume IRESSA at 250 mg 7 days after discontinuation of the strong inducer [see Dosage and Administration (2.4) , Clinical Pharmacology (12.3) ] . CYP3A4 Inhibitor Drugs that are strong inhibitors of CYP3A4 (e.g., ketoconazole and itraconazole) decrease gefitinib metabolism and increase gefitinib plasma concentrations.
Monitor adverse reactions when administering strong CYP3A4 inhibitors with IRESSA. Drugs Affecting Gastric pH Drugs that elevate gastric pH (e.g., proton pump inhibitors, histamine H 2 -receptor antagonists, and antacids) may reduce plasma concentrations of gefitinib. Avoid concomitant use of IRESSA with proton pump inhibitors, if possible. If treatment with a proton-pump inhibitor is required, take IRESSA 12 hours after the last dose or 12 hours before the next dose of the proton-pump inhibitor. Take IRESSA 6 hours after or 6 hours before an H 2 -receptor antagonist or an antacid [see Clinical Pharmacology (12.3) ] .
7.2 Hemorrhage in Patients taking Warfarin International Normalized Ratio (INR) elevations and/or hemorrhage 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.
Contraindications
None. None. (4)
Safety data
Reported adverse events (FAERS)
Liver injury (LiverTox)
BLikelihood score B: Likely cause of clinically apparent liver injury.
Gefitinib is a selective tyrosine kinase receptor inhibitor used in the therapy of non-small cell lung cancer. Gefitinib therapy is associated with transient elevations in serum aminotransferase levels and rare instances of clinically apparent acute liver injury.
ABCDEA: well known cause; E: unlikely cause. [HD]: high doses only.
Pregnancy and lactation
Pregnancy
8.1 Pregnancy Risk Summary Based on its mechanism of action and animal data, IRESSA can cause fetal harm when administered to a pregnant woman. In animal reproductive studies, oral administration of gefitinib from organogenesis through weaning resulted in fetotoxicity and neonatal death at doses below the recommended human dose ( see Animal Data ). Advise pregnant women of the potential hazard to a fetus or potential risk for loss of the pregnancy. The background risk of major birth defects and miscarriage for the indicated population is unknown; however, the background risk in the U.S.
general population of major birth defects is 2-4% and miscarriage is 15-20% of clinically recognized pregnancies. Data Animal Data A single dose study in rats showed that gefitinib crosses the placenta after an oral dose of 5 mg/kg (30 mg/m 2 , about 0.2 times the recommended human dose on a mg/m 2 basis). When pregnant rats were treated with 5 mg/kg from the beginning of organogenesis to the end of weaning there was a reduction in the number of offspring born alive. This effect was more severe at 20 mg/kg (approximate the human clinical dose on a mg/m 2 basis) and was accompanied by high neonatal mortality soon after parturition.
In rabbits, a dose of 20 mg/kg/day (240 mg/m 2 , about twice the recommended dose in humans on a mg/m 2 basis) caused reduced fetal weight.
Breastfeeding (LactMed)
No information is available on the clinical use of gefitinib during breastfeeding. Because gefitinib is 90% bound to plasma proteins, the amount in milk is likely to be low. However, its half-life is about 48 hours and it might accumulate in the infant. The manufacturer recommends that breastfeeding be discontinued during gefitinib therapy.
Supply and cost
Drug shortage status
Recalls (last 24 months)
Therapeutic equivalence (Orange Book)
Price ladder
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