IRESSA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for IRESSA (IRESSA).
Gefitinib is a selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase. It binds reversibly to the ATP-binding site of EGFR, blocking downstream signaling pathways involved in cell proliferation and survival.
| Metabolism | Primarily metabolized by CYP3A4 and CYP2D6; minor contribution from CYP1A1, CYP1A2, and CYP2C19. |
| Excretion | Fecal (86%), renal (<4% unchanged drug and <1% as metabolites) |
| Half-life | Approximately 41 hours (range 30-60 hours) in steady state, supporting once-daily dosing |
| Protein binding | Approximately 90% bound to serum albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 1400 L (approximately 20 L/kg), indicating extensive tissue distribution |
| Bioavailability | Oral: Approximately 59% (range 50-70%); absorption is dose-proportional up to 500 mg; food increases AUC by 1.6-fold |
| Onset of Action | Oral: 2-5 days for measurable plasma concentrations; clinical response (tumor shrinkage) typically assessed after 4-6 weeks |
| Duration of Action | Continuous once-daily dosing; clinical effect sustained with regular administration; half-life supports 24-hour dosing interval |
| Action Class | Tyrosine kinase inhibitors |
| Brand Substitutes | Geftistar 250mg Tablet, Chemogef 250mg Tablet, Unigef 250mg Tablet, Geftib Tablet, Geftinat 250mg Tablet |
250 mg orally once daily.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥30 mL/min. For GFR <30 mL/min, use with caution; no specific dose recommendations available. |
| Liver impairment | Child-Pugh A and B: no dose adjustment. Child-Pugh C: use with caution; no specific dose recommendations. |
| Pediatric use | Safety and effectiveness not established; no weight-based guidelines available. |
| Geriatric use | No specific dose adjustment recommended; monitor for increased toxicity in elderly patients. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for IRESSA (IRESSA).
| Breastfeeding | Excreted in human milk; M/P ratio unknown. Potential for serious adverse reactions in nursing infants; discontinue breastfeeding or discontinue drug, considering importance of drug to mother. |
| Teratogenic Risk | Pregnancy Category D. First trimester: Risk of fetal harm due to EGFR inhibition; associated with skeletal abnormalities and developmental delay in animal studies. Second and third trimesters: Continued risk of oligohydramnios, renal impairment, and potential fetal death. Avoid pregnancy during treatment. |
■ FDA Black Box Warning
None
| Serious Effects |
["None known"]
| Precautions | ["Interstitial lung disease (ILD) or pneumonitis","Hepatotoxicity","Gastrointestinal perforation","Severe or persistent diarrhea","Ocular disorders including keratitis","Hemorrhage","Fetal harm if used during pregnancy"] |
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| Fetal Monitoring |
| Monitor for fetal growth restriction, oligohydramnios via ultrasound; assess renal function in neonates if exposure occurred. |
| Fertility Effects | May impair fertility in females through effects on ovarian function; reversible upon discontinuation. No data on male fertility. |