Lapatinib is an oral, small-molecule, dual tyrosine kinase inhibitor that targets both the epidermal growth factor receptor (EGFR/HER1) and the human epidermal growth factor receptor 2 (HER2/ErbB2). It is used in combination with other agents for the treatment of HER2-positive advanced or metastatic breast cancer. It works intracellularly to inhibit tumor cell proliferation and survival.
Adult: 1,250 mg (five 250 mg tablets) taken orally once daily on days 1-21 continuously when combined with capecitabine (2,000 mg/m²/day on days 1-14 in a 21-day cycle). For combination with letrozole: 1,500 mg (six 250 mg tablets) once daily continuously with letrozole 2.5 mg once daily.
Note: Take at least one hour before or one hour after food. Do not take with grapefruit or grapefruit juice. Swallow tablets whole with water; do not crush, split, or chew. If a dose is missed, do not double the next dose; take the next scheduled dose. Dosing should be continuous, not intermittent.
Lapatinib is a 4-anilinoquinazoline kinase inhibitor that reversibly binds to the intracellular ATP-binding site of the tyrosine kinase domains of both EGFR (HER1) and HER2 (ErbB2). This inhibition prevents autophosphorylation of the receptor tyrosine residues, blocking downstream signaling via the Ras/Raf/MAPK and PI3K/Akt/mTOR pathways, which are critical for cell proliferation, survival, angiogenesis, and metastasis.
Pregnancy: Category D: Based on animal studies and mechanism, lapatinib can cause fetal harm. Avoid in pregnancy. Women of childbearing potential must use effective contraception during and for at least 1 week after therapy.
Driving: Fatigue and dizziness have been reported. Patients should be cautioned about operating machinery or driving if they experience these effects.
| Strong CYP3A4 Inhibitors (e.g., Ketoconazole, Itraconazole, Clarithromycin, Ritonavir) | Significantly increases lapatinib plasma concentrations. Avoid concomitant use. If unavoidable, consider lapatinib dose reduction. | Major |
| Strong CYP3A4 Inducers (e.g., Rifampicin, Phenytoin, Carbamazepine, St. John's Wort) | Significantly decreases lapatinib plasma concentrations, reducing efficacy. Avoid concomitant use. | Major |
| P-gp Inhibitors (e.g., Verapamil, Quinidine) | May increase lapatinib concentrations. Monitor for adverse effects. | Moderate |
| Drugs that prolong QT interval (e.g., Class IA/III antiarrhythmics, Moxifloxacin) | Additive risk of QTc prolongation and cardiac arrhythmias. Use with extreme caution and monitor ECG. | Major |
| Antacids, H2 Blockers, PPIs (e.g., Omeprazole) | Reduced gastric acidity may decrease lapatinib solubility and absorption. Separate administration by at least 2 hours for H2 blockers and 4-6 hours for PPIs if possible. | Moderate |
| Warfarin | May increase INR and risk of bleeding. Monitor INR closely. | Moderate |