ERLOTINIB HYDROCHLORIDE
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ERLOTINIB HYDROCHLORIDE (ERLOTINIB HYDROCHLORIDE).
Erlotinib is a tyrosine kinase inhibitor that reversibly inhibits the epidermal growth factor receptor (EGFR) tyrosine kinase, thereby blocking downstream signaling pathways involved in cell proliferation and survival. It binds to the ATP-binding site of EGFR, preventing autophosphorylation and activation of downstream effectors such as PI3K/Akt and MAPK.
| Metabolism | Erlotinib is extensively metabolized primarily by CYP3A4, with minor contributions from CYP1A2 and CYP1A1. Hepatic metabolism to O-desmethyl erlotinib (active metabolite) and other inactive metabolites. |
| Excretion | Primarily hepatic metabolism (CYP3A4), with fecal excretion as metabolites (83%) and renal excretion (8% as parent and metabolites). |
| Half-life | Terminal half-life approximately 36 hours (range 24-48 hours) in clinical setting, supporting once-daily dosing. |
| Protein binding | Approximately 93% bound to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | Vd of 220-280 L (approx 3.5-4 L/kg for 70 kg adult), indicating extensive tissue distribution. |
| Bioavailability | Oral bioavailability about 60% (increased to ~100% when taken with food, but avoid food to reduce variability). |
| Onset of Action | Oral: Time to clinical effect (e.g., rash, diarrhea) typically within 7-10 days; antitumor effect assessed after 4-8 weeks. |
| Duration of Action | Duration of action corresponds to prolonged receptor inhibition (EGFR-TK) with once-daily dosing; clinical effects persist with continuous therapy; half-life supports sustained exposure. |
150 mg orally once daily on an empty stomach (at least 1 hour before or 2 hours after food).
| Dosage form | TABLET |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not recommended for patients with severe renal impairment (CrCl <15 mL/min) due to lack of data. |
| Liver impairment | For patients with severe hepatic impairment (Child-Pugh class C), consider dose reduction to 75 mg orally once daily. Mild to moderate impairment (Child-Pugh A or B) does not require adjustment. |
| Pediatric use | Not recommended for pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended; identical dosing to younger adults, but monitor renal and hepatic function due to age-related changes. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ERLOTINIB HYDROCHLORIDE (ERLOTINIB HYDROCHLORIDE).
| Breastfeeding | No data on presence in human milk, effects on breastfed infant, or milk production. M/P ratio unknown. Due to potential for serious adverse reactions in nursing infants, advise women not to breastfeed during treatment and for 2 weeks after last dose. |
| Teratogenic Risk | Risk Category D. Based on animal studies and mechanism of action, erlotinib can cause fetal harm. There are no adequate and well-controlled studies in pregnant women. In postmarketing reports, spontaneous abortions and congenital anomalies have been observed. Risks by trimester: First trimester: potential for teratogenicity (oligohydramnios, skeletal abnormalities). Second and third trimesters: risk of fetal growth restriction, oligohydramnios, and neonatal respiratory distress. |
■ FDA Black Box Warning
No FDA black box warnings.
| Serious Effects |
["Hypersensitivity to erlotinib or any component of the formulation"]
| Precautions | ["Interstitial lung disease (ILD)-like events, including fatalities","Hepatic impairment (increase toxicity, require dose adjustment)","Renal failure (monitor renal function)","Gastrointestinal perforation (rare but fatal)","Bullous and exfoliative skin disorders (Stevens-Johnson syndrome/toxic epidermal necrolysis)","Ocular toxicities (keratitis, corneal ulceration, perforation)","Hemorrhage (including epistaxis, gastrointestinal bleeding)","Embryofetal toxicity (cause fetal harm; advise contraception)","Drug interactions with strong CYP3A4 inducers/inhibitors and proton pump inhibitors"] |
| Food/Dietary | Take on an empty stomach: no food for at least 1 hour before or 2 hours after. Avoid grapefruit juice, grapefruit, and Seville oranges due to CYP3A4 inhibition increasing erlotinib exposure. Alcohol may increase risk of hepatotoxicity. |
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| Fetal Monitoring | Monitor pregnant women closely for signs of toxicity and fetal well-being. Serial fetal ultrasounds recommended to assess growth and amniotic fluid volume. Monitor maternal renal and hepatic function, and for gastrointestinal perforation, bullous skin disorders, and interstitial lung disease. |
| Fertility Effects | Based on animal studies, erlotinib may impair fertility in females of reproductive potential. In male rats, no effect on fertility observed, but testicular toxicity occurred. Human data limited; advise fertility preservation counseling. |
| Clinical Pearls | Administer on an empty stomach (at least 1 hour before or 2 hours after food) to ensure consistent absorption. Monitor for interstitial lung disease (ILD) symptoms (dyspnea, cough, fever) and consider drug discontinuation. Erlotinib is a potent CYP3A4 inhibitor; avoid concurrent use with CYP3A4 substrates with narrow therapeutic index (e.g., simvastatin). Smoking induces CYP1A2 and reduces erlotinib exposure; advise smoking cessation and consider dose adjustment in smokers. |
| Patient Advice | Take erlotinib at least 1 hour before or 2 hours after a meal with water. · Do not crush, chew, or split the tablet; swallow whole. · If you miss a dose, skip it and take the next dose as scheduled; do not double up. · Avoid grapefruit and Seville oranges (e.g., marmalade) as they may increase drug levels. · Contact your doctor immediately if you experience new or worsening shortness of breath, cough, or fever (signs of lung inflammation). · Use effective contraception during treatment and for at least 2 weeks after the last dose; erlotinib can harm a fetus. · Avoid smoking; it decreases drug effectiveness. Notify your doctor if you start or stop smoking. |