Tykerb

• Metastatic HER2‑Positive Breast Cancer
• With capecitabine: for patients previously treated with an anthracycline, a taxane, and trastuzumab
• With letrozole: first‑line therapy in postmenopausal women with hormone‑receptor‑positive, HER2‑positive disease

Off‑Label (Clinically Accepted)

• Adjuvant treatment in early‑stage HER2‑positive breast cancer when trastuzumab is contraindicated
• Investigational use in other HER2‑expressing tumors (e.g., gastric carcinoma)

• Route: Oral, once daily on an empty stomach (no food ≥1 hour before or after)
• Formulation: 250 mg film‑coated tablets

Adults

• With capecitabine: 1,250 mg once daily
• With letrozole: 1,000 mg once daily
• Continue until disease progression or unacceptable toxicity

Elderly (≥65 years)

• No routine adjustment; monitor for diarrhea and liver toxicity

Hepatic Impairment

• Moderate (Child‑Pugh B): reduce to 750 mg once daily
• Severe (Child‑Pugh C): reduce to 250 mg once daily

Renal Impairment

• No adjustment required

Lapatinib reversibly inhibits the intracellular tyrosine kinase domains of HER2 and EGFR. By blocking ATP binding, it prevents receptor phosphorylation and downstream signals (RAS/RAF/MAPK and PI3K/AKT pathways), leading to reduced tumor cell proliferation and enhanced apoptosis in HER2‑overexpressing cancers.

• Absorption: Peak concentration ~4 hours postdose; bioavailability ~14%
• Distribution: Volume of distribution ~2,500 L; ~99% plasma‑protein bound
• Metabolism: Primarily by CYP3A4, with contribution from CYP3A5 and CYP2C19
• Elimination: ~91% fecal, ~1% renal
• Half‑Life: ~24 hours; steady state in 6–7 days

• Pregnancy (Category D): Positive evidence of fetal risk; use only if benefit outweighs risk
• Lactation: Unknown excretion in milk; advise against breastfeeding during therapy and for one week after discontinuation

• Class: Tyrosine Kinase Inhibitor
• Subclass: Dual EGFR/HER2 inhibitor

• Hypersensitivity to lapatinib or excipients
• Pregnancy unless no alternative exists

• Hepatotoxicity: Monitor LFTs at baseline and monthly for 6 months
• Diarrhea: Prophylactic loperamide at first occurrence; monitor hydration
• Cardiac Dysfunction: Assess LVEF at baseline and periodically; discontinue if symptomatic or significant decline
• QT Prolongation: Caution with other QT‑prolonging drugs; monitor ECG and electrolytes
• Skin Reactions: Rash and hand‑foot syndrome may require dose modification

• Very Common (≥10%): Diarrhea, rash, nausea, fatigue, elevated liver enzymes
• Common (1–10%): Decreased LVEF, hand‑foot syndrome, stomatitis, vomiting, headache
• Rare (<1%): Interstitial lung disease, severe hepatotoxicity, cardiac failure

• CYP3A4 inhibitors (e.g., ketoconazole): ↑ lapatinib levels → ↑ toxicity
• CYP3A4 inducers (e.g., rifampin): ↓ drug levels → ↓ efficacy
• Grapefruit juice: Avoid (↑ exposure)
• Acid‑reducing agents: May ↓ absorption; separate dosing by ≥4 hours

• ASCO–CCO 2024: Endorses lapatinib + letrozole as an alternative first‑line in HR+/HER2+ metastatic breast cancer for patients unsuitable for chemotherapy
• No new FDA label changes as of late 2024

• Temperature: 20 °C–25 °C (68 °F–77 °F); excursions 15 °C–30 °C permitted
• Humidity: Protect from moisture; keep in original blister pack
• Light: Store in a well‑closed container, away from direct sunlight
• Handling: Do not refrigerate; keep out of reach of children