Lapatinib
TYKERB
What it isOral dual tyrosine kinase inhibitor of EGFR (HER1) and HER2.
Why this oneCombined with capecitabine or letrozole for HER2-positive advanced or metastatic breast cancer, including after trastuzumab.
What limits itCauses diarrhea, decreased LVEF and QT prolongation, and has major CYP3A4-based drug interactions.
FDA label
Read the full label on DailyMed ↗
| FDA dosing | Population | Start | Target | Max |
|---|---|---|---|---|
| HER2+ advanced/metastatic breast cancer (with capecitabine) | Adults | 1,250 mg QD on Days 1-21 of repeating 21-day cycle (continuous) | Continue until progression/unacceptable toxicity | 1,250 mg/day (reduce to 1,000 mg/day for toxicity) |
| Hormone receptor+, HER2+ metastatic breast cancer (with letrozole 2.5 mg QD) | Adults | 1,500 mg QD continuously | 1,500 mg QD | 1,500 mg/day (reduce to 1,250 mg/day for toxicity) |
Renal Not studied; unlikely to need adjustment (<2% eliminated renally); no experience in severe renal impairment
Hepatic Severe (Child-Pugh C): consider reduced dose — 750 mg/day (capecitabine regimen) or 1,000 mg/day (letrozole regimen); no clinical data with these adjustments
Daily dose must not be divided (single daily administration)
Instructions
- Take >=1 h before or >=1 h after a meal (capecitabine: with food or within 30 min after)
- Take full daily dose at once QD — do not divide
- Missed day: do not double the next day
- Confirm LVEF within normal limits before starting; re-evaluate during treatment
- LFTs before starting, every 4-6 weeks, and as indicated; discontinue permanently for severe hepatotoxicity
- Avoid strong CYP3A4 inhibitors and grapefruit; if unavoidable, reduce to 500 mg/day, and after inhibitor stops wait ~1 week before returning to indicated dose
- Avoid strong CYP3A4 inducers; if unavoidable, titrate gradually up to 4,500 mg/day (capecitabine regimen) or 5,500 mg/day (letrozole regimen), and return to indicated dose when inducer stops
- Cardiac events (LVEF Grade >=2 or below LLN): discontinue; may restart at reduced dose (1,000 or 1,250 mg/day) after >=2 weeks if LVEF normalizes and asymptomatic
- Diarrhea Grade 3 (or complicated Grade 1-2): interrupt; resume at reduced dose when <=Grade 1; permanently discontinue for Grade 4
Cautions
- Hepatotoxicity (boxed): may be severe/fatal, days to months after start; monitor LFTs; do not retreat after severe changes
- Decreased LVEF: confirm normal LVEF at baseline and monitor; most decreases within first 12 weeks
- Severe diarrhea: manage early with antidiarrheals, fluids/electrolytes
- Interstitial lung disease/pneumonitis: discontinue for severe pulmonary symptoms
- QT prolongation: consider ECG and electrolyte monitoring
- Severe cutaneous reactions: discontinue if life-threatening suspected
- Embryo-fetal toxicity
Adverse reactions
- With capecitabine (>20%): diarrhea, palmar-plantar erythrodysesthesia, nausea, rash, vomiting, fatigue
- With letrozole (>=20%): diarrhea, rash, nausea, fatigue
Pregnancy Can cause fetal harm (mechanism + animal data); verify pregnancy status; use effective contraception
Lactation Do not breastfeed during treatment and for 1 week after last dose
⚠ BOXED WARNING
- Hepatotoxicity
Principal riskBoxed warning: hepatotoxicity, including severe and potentially fatal liver injury.
Cost, est. cash$50–$10,000/month or cycle
Generic entry2020
Classes and tags
Clinical profile
Legacy pregnancy categoryD
Defining liabilityMyelosuppression and agent-specific hepatic, cardiac, pulmonary, neurologic or reproductive toxicity require oncology monitoring.
Mechanism of action: Lapatinib ballicule
