Generic
Lapatinib
6 brands available in the market
At a glance
Lapatinib is used in the treatment of breast cancer. It stops or slows down the growth of cancer cells. It is used for HER2-overexpressing metastatic breast cancer and hormone-positive, HER2-positive breast cancer.
Description
Lapatinib is a 4-anilinoquinazoline kinase inhibitor of the intracellular tyrosine kinase domains of both EGFR (ErbB1) and HER2 (ErbB2) receptors. It inhibits ErbB-driven tumor cell growth. Lapatinib is incompletely and variably absorbed from the GI tract; food increases exposure by 3-4 fold. It is primarily metabolized by CYP3A4 and excreted in feces and urine.
Indications
- HER2-overexpressing metastatic breast cancer (in combination with capecitabine) - patients who have received prior anthracycline, taxane, and trastuzumab therapy
- Hormone receptor-positive, HER2-positive breast cancer (in combination with letrozole) - postmenopausal women
Therapeutic class
Cytotoxic Chemotherapy
Pharmacological class
Tyrosine Kinase Inhibitor
Pharmacology
Lapatinib inhibits EGFR and HER2 tyrosine kinase domains, blocking ErbB-driven tumor cell growth. It inhibits angiogenesis and cellular proliferation.
Mechanism of action
Blocks EGF-receptor HER2 kinase, inhibiting cancer cell growth.
Dosage
HER2-Positive Metastatic Breast Cancer:
- 1,250 mg PO once daily on Days 1-21 + Capecitabine 2,000 mg/m²/day on Days 1-14 in a 21-day cycle
- Take at least 1 hour before or 1 hour after a meal
Hormone Receptor-Positive, HER2-Positive Breast Cancer:
- 1,500 mg PO once daily + Letrozole 2.5 mg once daily
- Take at least 1 hour before or 1 hour after a meal
Hepatic Impairment (Child-Pugh C): 1,250→750 mg/day (HER2+) or 1,500→1,000 mg/day (HR+/HER2+)
Administration
- Swallow tablet whole; do not chew, crush or break
- Take on an empty stomach (1 hour before or 1 hour after food)
- Take at the same time each day
- Once daily dose should be taken all at once; do not divide
Missed dose
If a dose is missed, wait until the next scheduled dose; do not double the next dose.
Side effects
Common Side Effects (with Capecitabine):
- Diarrhea
- Palmar-plantar erythrodysesthesia
- Nausea
- Rash
- Vomiting
- Fatigue
Other Side Effects:
- Abdominal pain, back pain, dyspnea, constipation, cough, headache, hot flashes, joint pain, hepatotoxicity, decreased appetite, stomatitis
Precautions & warnings
- Monitor for decreased LVEF (especially during first 12 weeks)
- Monitor liver function tests every 4-6 weeks for hepatotoxicity
- Monitor for diarrhea and treat with loperamide
- Monitor for interstitial lung disease/pneumonitis
- Monitor for QT prolongation
- Monitor for severe cutaneous reactions (Stevens-Johnson, toxic epidermal necrolysis)
- Can cause fetal harm during pregnancy
Contraindications
- Hypersensitivity to lapatinib ditosylate
Drug interactions
- CYP3A4 inhibitors (ketoconazole, itraconazole, grapefruit juice) increase concentration
- CYP3A4 inducers (rifampin, carbamazepine, phenytoin) decrease concentration
- Proton pump inhibitors (esomeprazole) decrease concentration
- Increased adverse events with paclitaxel and docetaxel
Food interactions
Safety with alcohol is not known; consult your doctor.
Use in pregnancy
Use in Pregnancy: Lapatinib is unsafe during pregnancy; definite evidence of risk to the fetus. Use only in life-threatening situations with doctor's advice.
Use in lactation
Use in Lactation: Lapatinib is unsafe during breastfeeding; may cause toxicity to the baby. Do not breastfeed during treatment and for 1 week after the last dose.
Pediatric use
Safety and efficacy not established in pediatric patients.
Geriatric use
Use with caution in elderly.
Renal / hepatic impairment
Renal Impairment: Use with caution in severe kidney disease; no dose adjustment in mild to moderate kidney disease.
Hepatic Impairment: Dose adjustment needed in severe liver disease (Child-Pugh C: 750-1,000 mg/day).
Overdose effects
No known antidote for overdose; doses of 2,500-9,000 mg/day have caused sore scalp, sinus tachycardia, mucosal inflammation. Hemodialysis is not effective.
Storage conditions
Store below 30°C in a dry place; keep out of reach of children.
Chemical structure
Lapatinib