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 |
| Molecular Weight | 446.9 |
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 | Avoid due to potential teratogenicity; case reports of fetal malformations. |
| 2nd trimester | Avoid; risk of oligohydramnios and fetal renal impairment. |
| 3rd trimester | Avoid; risk of neonatal respiratory distress and renal failure. |
Clinical note
Strong CYP3A4 inducers may decrease efficacy Can cause interstitial lung disease and diarrhea.
| Placental transfer | Crosses placenta; human data suggest significant transfer (maternal plasma to cord blood ratio ~0.6–0.8). |
| Breastfeeding | Excreted in human milk at low concentrations; potential for serious adverse effects in infant, including diarrhea and skin reactions. Manufacturer advises discontinue nursing or drug. |
| Lactation Rating |
■ FDA Black Box Warning
None.
| Common Effects | Diarrhea |
| Serious Effects |
Hypersensitivity to gefitinib or any excipients
| 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 |
| Food/Dietary | Avoid grapefruit and grapefruit juice, Seville oranges, and other foods that strongly inhibit CYP3A4. Coadministration with a high-fat meal may slightly reduce absorption but is clinically insignificant; take consistently with or without food. |
Loading safety data…
| L4 (Contraindicated) |
| 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. |
| 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. |
| Clinical Pearls | Gefitinib is an EGFR tyrosine kinase inhibitor indicated for first-line treatment of metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations. Monitor for interstitial lung disease (ILD) which can be fatal; discontinue if ILD is confirmed. Severe hepatotoxicity can occur; monitor LFTs monthly. Diarrhea is common; manage with loperamide and hydration. Administer without regard to food, but avoid grapefruit and Seville oranges due to CYP3A4 interaction. Dosage adjustment needed with strong CYP3A4 inhibitors or inducers. |
| Patient Advice | Take gefitinib exactly as prescribed, usually once daily with or without food. · Avoid grapefruit, grapefruit juice, and Seville oranges while on this medication. · If you miss a dose, take it as soon as you remember unless it is within 12 hours of the next dose; do not double dose. · Contact your doctor immediately if you experience new or worsening shortness of breath, cough, or fever (possible lung problems). · Report signs of liver injury: yellowing of skin or eyes, dark urine, severe nausea/vomiting, or pain in the upper right belly. · Diarrhea is common; use over-the-counter loperamide and drink plenty of fluids. Notify your doctor if diarrhea persists or is severe. · Use effective contraception during treatment and for at least 2 weeks after the last dose; do not breastfeed. · Tell your doctor about all medications you take, including prescription, over-the-counter, and herbal supplements. · Avoid direct sunlight; use sunscreen and protective clothing as gefitinib may increase sun sensitivity. · Do not stop or change your dose without consulting your healthcare provider. |