Classifications: antineoplastic agent; tyrosine kinase inhibitor; epidermal growth factor receptor inhibitor; signal transduction inhibitor; Therapeutic: antineoplastic agent
Pregnancy Category: D
250 mg tablets
An inhibitor of epidermal growth factor receptors [EGFR (ErbB1) and HER2 (ErbB2)] required for cell proliferation of certain
Inhibits ErbB-driven tumor cell growth in those who are positive for the HER2 receptor.
Treatment of advanced or metastatic breast cancer in patients whose tumor overexpresses the human epidermal receptor type
2 (HER2) protein and who have received prior therapy including an anthracycline, a taxane, and trastuzumab.
Hypersensitivity to lapatinib, capecitabine, doxifluridine, 5-FU; myelosuppression; dihydropyrimidine dehydrogenase (DPD)
deficiency; active infection; jaundice; severe renal failure or impairment; hypokalemia, hypomagnesemia; females of child-bearing
age; pregnancy (category D), lactation; children <18 y.
Moderate to severe hepatic impairment; coronary artery disease; angina, cardiac arrhythmias, congenital QTc prolongation
Route & Dosage
Adult: PO 1250 mg q.d. on days 1 21 with capecitabine 2000 mg/m2/d q12h on days 114; repeat in 21-d cycle.
750 mg/d with severe hepatic function impairment (Child-Pugh class C).
- Give lapatinib at least 1 h before/after a meal.
- Give capecitabine with food or within 30 min after food.
- Note that concurrent use with strong CYP3A4 inhibitors/inducers should be avoided (see Drug Interactions). If concurrent
use is necessary, dosage adjustments are required.
- Store at 15°30° C (59°86° F) in a tightly closed container.
Adverse Effects (≥1%)CNS: Insomnia
QT prolongation. GI: Diarrhea,
dyspepsia, mucosal inflammation, nausea,
stomatitis, vomiting. Hematologic:
Neutropenia, thrombocytopenia. Metabolic:
Elevated ALT and AST levels, hyperbilirubinemia. Musculoskeletal:
Back pain, pain in extremities. Respiratory:
Dyspnea, pneumonitis. Skin:
Dry skin, palmar-plantar erythrodysesthesia, rash.
InteractionsDrug: inhibitors of cyp3a4
(ketoconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole
) will increase lapatinib plasma level. inducers of cyp3a4
(dexamethasone, phenytoin, carbamazepine, rifampin, rifabutin, rifapentin, phenobarbital
) will decrease lapatinib plasma level. Lapatinib can increase plasma levels of theophylline
and warfarin. Food: Grapefruit juice
may increase the plasma level of lapatinib; co-administration with food increases lapatinib plasma levels. Herbal: St. John's wort
will decrease plasma levels of lapatinib.
4 h. Distribution:
9% Plasma protein bound. Metabolism:
Extensive hepatic metabolism. Elimination:
Fecal (major) and renal
Assessment & Drug Effects
- Prior to initiating therapy, hypokalemia and hypomagnesemia should be corrected.
- Monitor cardiac status (i.e., LV ejection fraction, ECG with QT measurement) throughout therapy.
- Monitor for and report severe diarrhea as it may cause dehydration and serious electrolyte imbalances.
- Lab tests: Baseline and periodic serum electrolytes; periodic CBC with differential and platelet count, Hgb, Hct, LFTs.
- Monitor for theophylline and warfarin toxicity with concurrent use.
Patient & Family Education
- Adhere to directions regarding medication and food.
- Report promptly any of the following: palpitations, shortness of breath, severe diarrhea.
- Do not eat grapefruit or drink grapefruit juice while taking lapatinib.
- Do not take St. John's wort or OTC medications for stomach ulcers while taking lapatinib unless approved by the physician.
- Women are advised to use effective means of contraception while taking lapatinib.