Oral HER2-overexpressing hormone receptor positive metastatic breast cancer
Adult: In combination with letrozole in postmenopausal women for whom hormonal therapy is indicated: 1,500 mg once daily. Dose reduction, dosing interruption, or discontinuation may be required based on the type and severity of adverse effects or toxicity. Treatment recommendations may vary between countries (refer to detailed product guidelines).
Oral HER2-overexpressing advanced or metastatic breast cancer
Adult: In combination with capecitabine in patients who have received prior treatment which includes an anthracycline, a taxane, and trastuzumab: 1,250 mg once daily on days 1-21 of a 21-day cycle. Continue treatment until disease progression or unacceptable toxicity occurs. Dose reduction, dosing interruption, or discontinuation may be required based on the type and severity of adverse effects or toxicity (refer to detailed product guidelines).
What are the brands available for Lapatinib in Hong Kong?
Concomitant use with strong CYP3A4 inhibitors (e.g. ketoconazole, clarithromycin, ritonavir):
Avoid concomitant use with strong CYP3A4 inhibitors. If concomitant use cannot be avoided, dose reduction of lapatinib to 500 mg daily may be considered. If the strong inhibitor is stopped, a washout period of approx 1 week must be allowed before increasing the lapatinib dose to the usual recommended dose. Recommendations on dose adjustment may vary between countries (refer to country-specific product guidelines).
Concomitant use with strong CYP3A4 inducers (e.g. carbamazepine, rifampicin, phenytoin): HER2-overexpressing advanced or metastatic breast cancer:
Avoid concomitant use with strong CYP3A4 inducers. If concomitant use cannot be avoided, gradually titrate the lapatinib dose from 1,250 mg daily up to 4,500 mg daily based on tolerability. If the strong inducer is stopped, reduce the lapatinib dose to the usual recommended dose. Recommendations on dose adjustment may vary between countries (refer to country-specific product guidelines).
HER2-overexpressing hormone receptor positive metastatic breast cancer:
Avoid concomitant use with strong CYP3A4 inducers. If concomitant use cannot be avoided, gradually titrate the lapatinib dose from 1,500 mg daily up to 5,500 mg daily based on tolerability. If the strong inducer is stopped, reduce the lapatinib dose to the usual recommended dose. Recommendations on dose adjustment may vary between countries (refer to country-specific product guidelines).
Pharmacogenomics:
Based on studies, the human leucocyte antigen (HLA) alleles DRB1*07:01 and DQA1*02:01 have been associated with hepatotoxicity during lapatinib therapy. Patients carrying the HLA-DRB1*07:01 or HLA-DQA1*02:01 alleles have a higher incidence of severe liver injury compared to non-carriers. The prevalence of these alleles is approx 15-25% in Asian, African, Caucasian and Hispanic populations and only 1% in Japanese populations. Liver function monitoring is recommended in all patients treated with lapatinib regardless of genotype.
Hepatic Impairment
HER2-overexpressing advanced or metastatic breast cancer:
Severe: Dose reduction to 750 mg once daily may be considered. Recommendations on dosage adjustment in this population may vary between countries (refer to country-specific product guidelines).
HER2-overexpressing hormone receptor positive metastatic breast cancer:
Severe: Dose reduction to 1,000 mg once daily may be considered. Recommendations on dosage adjustment in this population may vary between countries (refer to country-specific product guidelines).
Administration
Lapatinib Should be taken on an empty stomach. Do not eat/drink grapefruit products.
Special Precautions
Patient with condition that can impair the left ventricular function or history of or predisposition to left ventricular dysfunction; risk factors for QT prolongation (e.g. hypokalaemia, hypomagnesaemia, congenital long QT syndrome, concomitant use with antiarrhythmics or drugs that are known to prolong QT interval, cumulative high-dose anthracycline treatment). Patients carrying HLA-DRB1*07:01 or HLA-DQA1*02:01 alleles. Concomitant administration with strong CYP3A4 inhibitors or inducers. Severe hepatic impairment. Pregnancy. Discontinue breastfeeding during therapy and for 1 week after the last dose.
Adverse Reactions
Significant: Decreased LVEF; QT interval prolongation (concentration-dependent); diarrhoea, ILD and pneumonitis. Gastrointestinal disorders: Nausea, vomiting, dyspepsia, constipation, abdominal pain, stomatitis. General disorders and administration site conditions: Fatigue, mucosal inflammation, asthenia. Immune system disorders: Hypersensitivity reactions (including anaphylaxis). Investigations: Decreased Hb, neutrophils, and platelet count. Metabolism and nutrition disorders: Anorexia. Musculoskeletal and connective tissue disorders: Pain in extremity, back pain, arthralgia. Nervous system disorders: Headache. Psychiatric disorders: Insomnia. Respiratory, thoracic and mediastinal disorders: Cough, dyspnoea, epistaxis. Skin and subcutaneous tissue disorders: Alopecia, rash, dry skin, pruritus, palmar-plantar erythrodysaesthesia, nail disorders (including paronychia), skin fissures. Vascular disorders: Hot flush. Potentially Fatal: Hepatotoxicity (including elevations of ALT or AST >3 times the ULN and total bilirubin >2 times the ULN); severe diarrhoea; severe cutaneous reactions (e.g. Stevens-Johnson syndrome, toxic epidermal necrolysis, erythema multiforme).
PO: Z (Increased intrauterine growth restriction was reported in a study. Not recommended during pregnancy.)
Patient Counseling Information
Women of childbearing potential and men with female partners of reproductive potential must use proven birth control methods during therapy and for 1 week after the last dose.
Monitoring Parameters
Evaluate pregnancy status in women of childbearing potential prior to treatment initiation. Correct hypokalaemia or hypomagnesaemia before treatment. Monitor LVEF (at baseline and periodically during treatment); LFT, including bilirubin, alkaline phosphatase and transaminases (at baseline, every 4-6 weeks during treatment and as clinically appropriate); electrolytes, including K and Mg. Conduct ECG monitoring in patients at risk for prolongation of QT interval. Assess for signs and symptoms of interstitial lung disease or pneumonitis, fluid retention, diarrhoea, and dermatologic toxicity.
Overdosage
Symptoms: Known lapatinib-associated adverse events, sore scalp, and sinus tachycardia. Management: Supportive treatment.
Drug Interactions
Increased systemic lapatinib exposure with strong CYP3A4 inhibitors (e.g. ketoconazole, itraconazole, voriconazole, clarithromycin, ritonavir, saquinavir, nefazodone). Decreased systemic lapatinib exposure with strong CYP3A4 inducers (e.g. carbamazepine, rifampicin, rifabutin, phenytoin, phenobarbital). Potential reduction in absorption and solubility with agents that affect gastric acidity. May increase the risk of QT prolongation with cumulative high-dose anthracycline therapy, antiarrhythmic agents or other drugs known to prolong QT interval. May increase the serum concentrations of digoxin, paclitaxel, active metabolite of irinotecan, and midazolam. Inducers and inhibitors of P-gp and BCRP transport proteins may alter lapatinib distribution and/or exposure.
Food Interaction
May increase plasma concentration with food and grapefruit juice. May decrease systemic exposure with St. John's wort.
Action
Description: Mechanism of Action: Lapatinib, a 4-anilinoquinazoline antineoplastic agent, is an inhibitor of intracellular tyrosine kinase domains of both epidermal growth factor receptor (EGFR/ErbB1) and human epidermal growth factor receptor type 2 (HER2/ErbB2). It blocks the phosphorylation and activation of downstream 2nd messengers (Erk1/2 and Akt), which regulate cellular proliferation and survival in tumours expressing ErbB. Pharmacokinetics: Absorption: Variably and incompletely absorbed. Food increases systemic exposure. Time to peak plasma concentration: Approx 4 hours. Distribution: Plasma protein binding: >99%, mainly to albumin and α1-acid glycoprotein. Metabolism: Extensively metabolised in the liver primarily by CYP3A4 and CYP3A5 isoenzymes, and to a lesser extent by CYP2C19 and CYP2C8 isoenzymes forming oxidated metabolites. Excretion: Via faeces (approx 27% as unchanged drug, 14% as metabolites); urine (<2%). Elimination half-life: Approx 24 hours.
Chemical Structure
Lapatinib Source: National Center for Biotechnology Information. PubChem Compound Summary for CID 208908, Lapatinib. https://pubchem.ncbi.nlm.nih.gov/compound/Lapatinib. Accessed Nov. 25, 2024.
L01EH01 - lapatinib ; Belongs to the class of human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors. Used in the treatment of cancer.
References
Annotation of EMA Label for Lapatinib and HLA-DQA1, HLA-DRB1. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 05/11/2024.Annotation of FDA Label for Lapatinib and HLA-DQA1, HLA-DRB1. Pharmacogenomics Knowledgebase (PharmGKB). https://www.pharmgkb.org. Accessed 05/11/2024.Anon. Lapatinib. AHFS Clinical Drug Information [online]. Bethesda, MD. American Society of Health-System Pharmacists, Inc. https://www.ahfscdi.com. Accessed 22/11/2024.Brayfield A, Cadart C (eds). Lapatinib Tosilate. Martindale: The Complete Drug Reference [online]. London. Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/11/2024.HLA-DQA1 - Lapatinib. UpToDate Lexidrug, Pharmacogenomics Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 05/11/2024.HLA-DRB1 - Lapatinib. UpToDate Lexidrug, Pharmacogenomics Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 05/11/2024.Joint Formulary Committee. Lapatinib. British National Formulary [online]. London. BMJ Group and Pharmaceutical Press. https://www.medicinescomplete.com. Accessed 05/11/2024.Lapatinib. UpToDate Lexidrug, Lexi-Drugs Multinational Online. Waltham, MA. UpToDate, Inc. https://online.lexi.com. Accessed 05/11/2024.Novartis New Zealand Limited. Tykerb 250 mg Tablet data sheet 23 August 2021. Medsafe. http://www.medsafe.govt.nz. Accessed 22/11/2024.Tykerb Film-coated Tablets 250 mg (Novartis Corporation [Malaysia] Sdn. Bhd.). National Pharmaceutical Regulatory Agency - Ministry of Health Malaysia. https://www.npra.gov.my. Accessed 05/11/2024.Tykerb Tablet (Novartis Pharmaceuticals Corporation). DailyMed. Source: U.S. National Library of Medicine. https://dailymed.nlm.nih.gov/dailymed. Accessed 05/11/2024.Tyverb 250 mg Film-coated Tablets (Novartis Pharmaceuticals UK Limited). MHRA. https://products.mhra.gov.uk. Accessed 05/11/2024.
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