HER2/EGFR tyrosine-kinase inhibitor Pregnancy: Can cause fetal harm based on animal studies and mechanism of action; no human data. In animals, exposure during organogenesis and lactation led to offspring death within 4 days of birth at maternal exposures >=3.3 times the human clinical exposure at 1,250 mg with capecitabine, and lapatinib caused fetal anomalies (rats) or abortions (rabbits) at maternally toxic doses. Advise pregnant women and females of reproductive potential of the potential risk to the fetus and to use effective contraception.

Lapatinib (Specialist drug)

Brand names: Tyverb

Lapatinib is an oral dual tyrosine kinase inhibitor of HER2 and EGFR used as a specialist treatment for HER2-positive breast cancer, usually in combination with chemotherapy or endocrine therapy. It is taken once daily under oncology supervision.

Auto-extracted from the source labelling — not yet independently clinician-verified. These values were distilled from the UK SPC (or the US label where noted) but have not had a clinician sign-off. Confirm against the current SmPC before prescribing.

Adult dose

Dose: HER2-positive metastatic breast cancer: 1,250 mg (5 x 250 mg tablets) daily, in combination with capecitabine 2,000 mg/m2/day

Route: Oral - at least one hour before or one hour after a meal; take the whole daily dose all at once, do not divide it (capecitabine, by contrast, is taken with food or within 30 minutes after food)

Frequency: Once daily on Days 1 to 21 continuously, in a repeating 21-day cycle (capecitabine is given orally in 2 doses approximately 12 hours apart on Days 1 to 14 of the cycle). Continue until disease progression or unacceptable toxicity

Source: US FDA prescribing information for lapatinib tablets (AvKARE, label date 2025-03-12, https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=302a4314-e1d6-3ce6-e063-6394a90a75a1). NO UK eMC SPC WAS IN THE SOURCE BUNDLE - dose is taken from US labelling and must be verified against the UK SPC before publication. VERBATIM: 'The recommended dose of lapatinib tablets is 1,250 mg given orally once daily on Days 1 to 21 continuously in combination with capecitabine 2,000 mg/m2/day (administered orally in 2 doses approximately 12 hours apart) on Days 1 to 14 in a repeating 21-day cycle.' SECOND INDICATION - hormone receptor-positive, HER2-positive metastatic breast cancer: 1,500 mg (6 x 250 mg tablets) orally once daily continuously in combination with letrozole; when coadministered with lapatinib the recommended letrozole dose is 2.5 mg once daily. If a day's dose is missed, do not double the dose the next day. CARDIAC EVENTS: discontinue if left ventricular ejection fraction falls by NCI CTCAE grade 2 or greater, or below the institution's lower limit of normal; may be restarted after a minimum of 2 weeks if LVEF recovers to normal and the patient is asymptomatic - at a reduced dose of 1,000 mg/day with capecitabine, or 1,250 mg/day with letrozole. DIARRHOEA: interrupt for NCI CTCAE grade 3 diarrhoea, or grade 1-2 with complicating features (moderate to severe abdominal cramping, nausea or vomiting >= grade 2, decreased performance status, fever, sepsis, neutropenia, frank bleeding or dehydration); reintroduce at a lower dose (1,250 to 1,000 mg/day, or 1,500 to 1,250 mg/day) once diarrhoea resolves to grade 1 or less; discontinue permanently for grade 4 diarrhoea. SEVERE HEPATIC IMPAIRMENT (Child-Pugh Class C): a reduction from 1,250 mg/day to 750 mg/day, or from 1,500 mg/day to 1,000 mg/day, is predicted to normalise the AUC and should be considered (no clinical data with this adjustment). STRONG CYP3A4 INHIBITORS: avoid; if unavoidable, a reduction to 500 mg/day is predicted to normalise exposure and should be considered, and after stopping the inhibitor allow a washout of about 1 week before titrating back up. STRONG CYP3A4 INDUCERS: avoid; if unavoidable, titrate gradually from 1,250 mg/day up to 4,500 mg/day, or from 1,500 mg/day up to 5,500 mg/day, based on tolerability. PAEDIATRIC: safety and effectiveness in paediatric patients have not been established, so paedDose is null; verify any under-18 use against a children's formulary and local protocol. NOTE: source label sections were truncated at the fetch limit.

Dose auto-extracted from US FDA prescribing information (openFDA / DailyMed) — cross-check; US labelling may differ from UK — not yet clinician-verified. Always confirm against the product SmPC and your local formulary before prescribing.

Contraindications

Known severe hypersensitivity (e.g. anaphylaxis) to lapatinib or any of its components

Side effects

Diarrhoea (including severe diarrhoea) - the most common reaction with both combinations
Palmar-plantar erythrodysaesthesia (with capecitabine) and rash, including severe cutaneous reactions
Nausea and vomiting
Fatigue
Decreased left ventricular ejection fraction
Hepatotoxicity; interstitial lung disease and pneumonitis; QT interval prolongation

Interactions

Strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin, voriconazole) - avoid; if unavoidable consider reducing lapatinib to 500 mg/day
Grapefruit - may increase lapatinib plasma concentrations; avoid
Strong CYP3A4 inducers (e.g. dexamethasone, phenytoin, carbamazepine, rifampicin, rifabutin, rifapentine, phenobarbital, St John's Wort) - avoid; if unavoidable, titrate the lapatinib dose upwards gradually
Substrates of CYP3A4, CYP2C8 or P-glycoprotein (ABCB1) with narrow therapeutic windows - lapatinib inhibits these in vitro at clinically relevant concentrations and is a weak CYP3A4 inhibitor in vivo; use caution and consider reducing the dose of the concomitant substrate (e.g. oral midazolam AUC increased 45%)

Clinical monograph

How it works

It reversibly inhibits the intracellular tyrosine kinase domains of HER2 (ERBB2) and EGFR (ERBB1), blocking downstream growth and survival signalling in HER2-positive tumour cells.

Prescribing in practice

It can reduce left ventricular ejection fraction and cause QT prolongation, so cardiac function and electrolytes should be assessed and monitored.
Hepatotoxicity occurs and liver function must be monitored; severe diarrhoea is also common and needs early management.
It is metabolised by CYP3A4, so avoid strong inducers and inhibitors and take consistently in relation to food as directed.

Monitoring

Monitor left ventricular ejection fraction, liver function tests and for diarrhoea during treatment.

Counselling the patient

Report breathlessness, ankle swelling or palpitations, which may indicate a heart problem.
Manage diarrhoea early and contact the team if it is severe or persistent.
Avoid grapefruit and tell the team about all other medicines, as interactions are important.

Evidence & guidelines

Lapatinib combined with capecitabine improved outcomes in HER2-positive advanced breast cancer after trastuzumab in a pivotal trial.

Reference: NICE TA257; SmPC; Drug verified in RxNorm (NLM); confirm dosing against the manufacturer SPC (eMC). Verify against your local formulary and current prescribing references before prescribing. The structured dose values shown have been reviewed by a clinician. Monograph status: clinician-reviewed (2026-07-04).

Curated clinical cross-links plus same-class fallbacks.

Calculators

Pathways