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 |
| Molecular Weight | 446.9 |
| 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 | Avoid use; animal studies show teratogenicity and embryotoxicity; human data limited. |
| 2nd trimester | Avoid use; may cause fetal harm; consider maternal benefit vs. risk. |
| 3rd trimester | Avoid use; risk of oligohydramnios and neonatal respiratory depression with close proximity to delivery. |
Clinical note
Comprehensive clinical and safety monograph for IRESSA (IRESSA).
| Placental transfer | Crosses placenta; documented in human studies with measurable fetal concentrations. |
| Breastfeeding | Excreted in human milk; potential for serious adverse reactions in nursing infants; discontinue breastfeeding or drug. |
| Lactation Rating |
■ FDA Black Box Warning
None
| Serious Effects |
Hypersensitivity to gefitinib or any excipientSevere hepatic impairment (Child-Pugh C)
| 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 |
| Food/Dietary | Avoid grapefruit and grapefruit juice as they may increase gefitinib exposure. No other specific food restrictions; take with or without food. Maintain adequate hydration and nutrition. |
| Clinical Pearls |
Loading safety data…
| L4 (Hazardous) |
| 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. |
| 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. |
| IRESSA (gefitinib) is an EGFR tyrosine kinase inhibitor indicated for first-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations. Monitor for interstitial lung disease (ILD) and severe hepatotoxicity. Dose adjustment for severe hepatic impairment. CYP3A4 inducer/inhibitor interactions are significant. |
| Patient Advice | Take exactly as prescribed, with or without food at the same time each day. · Do not crush or chew tablets; swallow whole with water. · Report any new or worsening respiratory symptoms (cough, dyspnea, fever) immediately. · Avoid grapefruit and grapefruit juice during treatment. · Use effective contraception during and for 2 weeks after stopping treatment. · Notify your doctor if you experience severe diarrhea, skin rash, or yellowing of eyes/skin. · Do not take St. John's wort or certain other medications without consulting your doctor. |