GEFITINIB
Clinical safety rating: avoid
Contraindicated (not allowed)
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor; inhibits EGFR autophosphorylation and downstream signaling, leading to cell cycle arrest and apoptosis in EGFR-overexpressing tumors.
| Metabolism | Hepatic, primarily via CYP3A4 and CYP2D6; also metabolized by CYP1A1, CYP1A2, CYP2C19, and CYP3A5. |
| Excretion | Primarily fecal (86% unchanged + metabolites), renal excretion <5% |
| Half-life | Terminal half-life 48 hours (range 24-85 hr); supports once-daily dosing, steady state achieved by day 7-10 |
| Protein binding | 90-92% bound to albumin and alpha-1-acid glycoprotein |
| Volume of Distribution | 1400 L (approx 20 L/kg), indicating extensive tissue distribution |
| Bioavailability | Oral: 60% (range 40-90%), food reduces AUC by 34% |
| Onset of Action | Oral: Clinical effect (tumor response) typically observed within 2-4 weeks |
| Duration of Action | Duration dependent on continued dosing; effect wanes over weeks after discontinuation due to receptor turnover |
250 mg orally once daily
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for GFR ≥20 mL/min; insufficient data for GFR <20 mL/min |
| Liver impairment | Child-Pugh A and B: no adjustment; Child-Pugh C: reduce to 250 mg every other day |
| Pediatric use | Not established; safety and efficacy not studied in pediatric patients |
| Geriatric use | No specific dose adjustments; monitor for adverse effects due to potential age-related renal or hepatic function decline |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Strong CYP3A4 inducers may decrease efficacy Can cause interstitial lung disease and diarrhea.
| Breastfeeding | It is not known whether gefitinib is excreted in human breast milk. However, due to the potential for serious adverse reactions in nursing infants from gefitinib, women should not breastfeed during treatment and for at least 2 weeks after the last dose. The M/P ratio has not been determined. |
| Teratogenic Risk | Gefitinib is an epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor. Based on its mechanism of action, it has the potential to cause fetal harm when administered to a pregnant woman. There are no adequate and well-controlled studies in pregnant women. In animal studies, gefitinib was embryotoxic and teratogenic at doses lower than the recommended human dose. First trimester exposure is associated with a risk of major congenital malformations. Second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and renal impairment. Women of childbearing potential should use effective contraception during treatment and for at least 2 weeks after the last dose. |
■ FDA Black Box Warning
None.
| Common Effects | Diarrhea |
| Serious Effects |
["None known"]
| Precautions | ["Interstitial lung disease (ILD) including fatalities: monitor for pulmonary symptoms; discontinue if ILD suspected","Hepatotoxicity: monitor liver function tests; discontinue if severe elevation","Gastrointestinal perforation: rare but serious","Severe diarrhea: manage with loperamide and hydration","Cutaneous reactions: monitor for severe skin reactions","QT prolongation: caution in patients with risk factors","Embryo-fetal toxicity: can cause fetal harm; advise reproductive potential of effective contraception"] |
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| Fetal Monitoring | Monitor maternal liver function tests (ALT, AST, bilirubin) monthly during treatment due to risk of hepatotoxicity. Monitor for interstitial lung disease (ILD) symptoms (dyspnea, cough, fever) and consider hold if suspected. Monitor renal function and electrolytes periodically. In pregnant patients, perform serial fetal ultrasound to assess growth, amniotic fluid volume, and renal development. Monitor for maternal hypertension and proteinuria. |
| Fertility Effects | Gefitinib may impair fertility in both males and females based on animal studies. In humans, there is limited data; however, the drug may cause ovarian failure or testicular damage due to its antiproliferative effects. |