LAPATINIB DITOSYLATE

LAPATINIB DITOSYLATE
(la-pa'ti-nib di-toe'si-late)
Tykerb
Classifications: antineoplastic agent; tyrosine kinase inhibitor; epidermal growth factor receptor inhibitor; signal transduction inhibitor;
Therapeutic: antineoplastic agent

Prototype: Gefitinib
Pregnancy Category: D

Availability

250 mg tablets

Action

An inhibitor of epidermal growth factor receptors [EGFR (ErbB1) and HER2 (ErbB2)] required for cell proliferation of certain breast cancers.

Therapeutic Effect

Inhibits ErbB-driven tumor cell growth in those who are positive for the HER2 receptor.

Uses

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.

Contraindications

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.

Cautious Use

Moderate to severe hepatic impairment; coronary artery disease; angina, cardiac arrhythmias, congenital QTc prolongation syndrome.

Route & Dosage

Breast Cancer
Adult: PO 1250 mg q.d. on days 1– 21 with capecitabine 2000 mg/m2/d q12h on days 1–14; repeat in 21-d cycle.

Hepatic Impairment
750 mg/d with severe hepatic function impairment (Child-Pugh class C).

Administration

Oral
  • 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. CV: 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.

Interactions

Drug: 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.

Pharmacokinetics

Peak: 4 h. Distribution: 9% Plasma protein bound. Metabolism: Extensive hepatic metabolism. Elimination: Fecal (major) and renal (minor). Half-Life: 24 h.

Nursing Implications

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.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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