TARCEVA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for TARCEVA (TARCEVA).
Erlotinib is a reversible tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR). It binds to the intracellular ATP-binding domain of EGFR, inhibiting autophosphorylation and downstream signaling pathways involved in cell proliferation, survival, and angiogenesis.
| Metabolism | Primarily metabolized by CYP3A4, with minor contributions from CYP1A2 and CYP1A1. Also metabolized by CYP3A5 and extrahepatic CYP1A1 in the lung. |
| Excretion | Primarily fecal (approximately 83% of dose) via hepatobiliary elimination; renal excretion accounts for less than 8% after oral administration. |
| Half-life | Terminal elimination half-life is about 36 hours in patients; steady-state is achieved within 7-10 days. |
| Protein binding | Approximately 93% bound to plasma albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Apparent Vd is about 268 L (3.8 L/kg for a 70 kg patient), indicating extensive extravascular distribution. |
| Bioavailability | Oral bioavailability is approximately 60%; food increases bioavailability (AUC by ~50%) with high-fat meals; take at least 1 hour before or 2 hours after food. |
| Onset of Action | Oral administration: clinical effect (improvement in progression-free survival) observed after 4-8 weeks of daily dosing. |
| Duration of Action | Continuous daily dosing: clinical benefit maintained until disease progression or unacceptable toxicity; drug accumulates over 7-10 days. |
| Action Class | Tyrosine kinase inhibitors |
| Brand Substitutes | Zyceva 150mg Tablet, Erleva 150mg Tablet, Erlotirel 150mg Tablet, Etbmed 150mg Tablet, Erlocip 150 Tablet, Birlotib 100 Tablet, Zyceva 100mg Tablet, Erlib 100mg Tablet, Erleva 100mg Tablet, Erlocip 100 Tablet |
150 mg orally once daily on an empty stomach (at least 1 hour before or 2 hours after food) for non-small cell lung cancer with EGFR exon 19 deletions or exon 21 (L858R) substitution mutations.
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or on dialysis; use with caution. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 75 mg once daily if not tolerated. Child-Pugh C: Not recommended (no data). |
| Pediatric use | Safety and effectiveness not established; no approved pediatric dosing. |
| Geriatric use | No specific dose adjustment; monitor for increased risk of adverse events (e.g., diarrhea, rash) due to age-related organ function decline. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for TARCEVA (TARCEVA).
| Breastfeeding | Erlotinib is excreted in human milk at low levels; the milk-to-plasma ratio is approximately 0.2. Based on limited data, the estimated infant dose is <10% of the maternal therapeutic dose. Due to the potential for serious adverse reactions in nursing infants (e.g., diarrhea, rash, growth retardation), breastfeeding is not recommended during erlotinib therapy and for at least 2 weeks after the final dose. |
| Teratogenic Risk | Tarceva (erlotinib) is an EGFR inhibitor classified as Pregnancy Category D. Based on its mechanism of action and animal studies, there is evidence of fetal harm. In pregnant rats and rabbits, erlotinib caused embryofetal lethality and malformations at maternal exposures less than the human dose. In humans, use during pregnancy should be avoided; if used, the patient should be apprised of potential hazards to the fetus. First trimester exposure carries the highest risk of major malformations; second and third trimester exposure may cause fetal growth restriction, oligohydramnios, and neonatal respiratory depression. Advise use of effective contraception during treatment and for at least 2 weeks after the last dose. |
■ FDA Black Box Warning
None
| Serious Effects |
["None"]
| Precautions | ["Pulmonary toxicity: Interstitial lung disease (ILD)-like events, including fatalities, have occurred; interrupt or discontinue if new or worsening pulmonary symptoms develop.","Hepatotoxicity: Liver function abnormalities, including hepatic failure and hepatorenal syndrome; monitor liver function tests periodically.","Gastrointestinal perforation: Cases of gastrointestinal perforation reported, some fatal; discontinue permanently.","Cutaneous reactions: Rash, dry skin, and other skin reactions; manage with topical or systemic therapies as needed.","Renal failure: Cases of hepatorenal syndrome and acute renal failure reported.","Ocular disorders: Keratitis, conjunctivitis, and other ocular toxicities; interrupt or discontinue if severe.","Myelosuppression: Monitor complete blood counts during therapy.","Drug interactions: Avoid concurrent use with potent CYP3A4 inhibitors or inducers; use caution with CYP3A4 substrates with narrow therapeutic index.","Pregnancy: Can cause fetal harm; advise effective contraception during treatment.","Anticoagulation: Monitor INR in patients taking warfarin."] |
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| Fetal Monitoring | If erlotinib is used during pregnancy, perform serial fetal ultrasound to monitor for growth restriction, oligohydramnios, and anatomical anomalies. Monitor maternal hepatic function (ALT, AST, bilirubin) and renal function monthly. Assess for signs of pulmonary toxicity (interstitial lung disease) and skin toxicity. In neonates exposed in utero, monitor for respiratory distress, diarrhea, and rash. Long-term follow-up is recommended. |
| Fertility Effects | Erlotinib may impair fertility in females based on animal studies showing ovarian dysfunction and reduced implantation. In male rats, erlotinib caused testicular degeneration and decreased sperm count. Human data are limited; however, the drug may affect spermatogenesis and ovarian reserve. Preclinical data suggest reversible impairment of fertility in both sexes after discontinuation. |