Lapatinib

Registered South African indications:

• Breast cancer
  - In combination with capecitabine, for the treatment of advanced or metastatic breast cancer whose tumours overexpress HER2+/neu (ErbB2+) and who have received prior therapy including trastuzumab

Contraindications

• Hypersensitivity to the active ingredient or any of its excipients

Cautions

• Pregnancy
• Breastfeeding
• Severe renal impairment
• Moderate to severe hepatic impairment
• Porphyria
• Conditions that could impair left ventricular function
• Symptomatic cardiac failure
• QT prolongation or risk factors thereof
  - Hypokalemia
  - Hypomagnesemia
  - Congenital long QT syndrome
  - Conditions that increase exposure to lapatinib

Forms avail. in SA and covered in this monograph: tab

Used for the treatment of

• Breast cancer where tumours overexpress HER2 (ErbB2) (additional agent required) 
  - In combination with capecitabine for patients with advanced or metastatic disease following prior therapy, which must have included anthracyclines and taxanes and therapy with trastuzumab in the metastatic setting
  - In combination with trastuzumab for patients with hormone receptor-negative metastatic disease that has progressed on prior trastuzumab therapy(ies) in combination with chemotherapy
  - In combination with an aromatase inhibitor for postmenopausal women with hormone receptor positive metastatic disease, not currently intended for chemotherapy

Consult specialist for dosages and regimens

Not established for use in children

Pregnancy

• Caution
• There is no adequate data from the use of lapatinib in pregnant women. Animal studies have shown reproductive toxicity. The potential risk for humans is not known
• Lapatinib should not be used during pregnancy unless clearly necessary. Women of childbearing potential should be advised to use adequate contraception and avoid becoming pregnant while receiving treatment with lapatinib and for at least 5 days after the last dose

Breastfeeding

• Caution; not recommended
• The safe use of lapatinib during breastfeeding has not been established. It is not known whether lapatinib is excreted in human milk
• In rats, growth retardation was observed in pups which were exposed to lapatinib via breast milk
• Breastfeeding must be discontinued in women who are receiving therapy with lapatinib and for at least 5 days after the last dose

Fertility

• There is no adequate data from the use of lapatinib in women of childbearing potential

Renal Impairment

• Mild to moderate: No dose adjustment recommended
• Severe: Caution; no information available
  No experience of lapatinib in severe renal impairment

Hepatic Impairment

• Mild: No dose adjustment recommended
• Moderate to severe: Caution; no dose adjustment recommended
  Increased exposure to lapatinib may occur in moderate to severe hepatic impairment. Insufficient data is available to provide a dose adjustment recommendation. Lapatinib should be discontinued if changes in liver function are severe and patients should not be retreated with lapatinib

Elderly            

• No dose adjustment recommended

Porphyria Information

• Possibly porphyrinogenic (PSP)

Drugs in Sport

• Permitted - No warnings

Central Nervous System Disorders

• Insomnia
• Headache
• Fatigue

Cardiovascular Disorders

• Decreased left ventricular ejection fraction
• Ventricular arrhythmias
• Torsades de Pointes
• QT prolongation on electrocardiogram
• Hot flush

Respiratory Disorders

• Epistaxis
• Cough
• Dyspnoea
• Interstitial lung disease
• Pneumonitis
• Pulmonary arterial hypertension

Gastrointestinal Disorders

• Diarrhoea (may lead to dehydration)
• Nausea and vomiting
• Dyspepsia
• Stomatitis
• Constipation
• Abdominal pain

Hepatobiliary Disorders

• Hyperbilirubinaemia
• Hepatotoxicity

Endocrine and Metabolic Disorders

• Anorexia

Musculoskeletal Disorders

• Pain in extremity
• Back pain
• Arthralgia

Skin and Subcutaneous Tissue Disorders

• Rash
• Acneiform dermatitis
• Dry skin
• Palmar-plantar erythrodysaesthesia
• Alopecia
• Pruritus
• Nail disorders
• Paronychia
• Serious cutaneous reactions
• Stevens-Johnson syndrome
• Toxic epidermal necrolysis
• Mucosal inflammation

Immune, Blood and Lymphatic System Disorders

• Hypersensitivity reactions
• Anaphylaxis

• CYP3A4 inducers
• Rifampicin
• Rifabutin
• Carbamazepine
• Phenytoin
• CYP3A4 inhibitors
• Ritonavir
• Saquinavir
• Telithromycin
• Ketoconazole
• Itraconazole
• Voriconazole
• Posaconazole
• Nefazodone
• CYP3A4 substrates
• Cisapride
• Pimozide
• Midazolam (oral)
• CYP2C8 substrates
• Repaglinide
• Agents that increase gastric pH
• Esomeprazole
• P-glycoprotein inhibitors
• P-glycoprotein inducers
• Breast Cancer Resistance Protein inhibitors
• Breast Cancer Resistance Protein inducers
• Breast Cancer Resistance Protein substrates
• Topotecan
• Quinidine
• Verapamil
• Cyclosporine
• Erythromycin
• Paclitaxel 
• Docetaxel 
• Irinotecan 
• Digoxin 
• OATP1B1 substrates
• Rosuvastatin
• St John's wort (Hypericum perforatum)
• Grapefruit juice
• Food

• Left ventricular ejection fraction
• Full blood count with differential
• Hepatic function
• Electrolytes

None routine. Specific cases may require

• ECG
• Pregnancy test

Lapatinib, a 4-anilinoquinazoline, is an inhibitor of the intracellular tyrosine kinase domains of both EGFR (ErbB1) and of HER2 (ErbB2) receptors. Lapatinib inhibits ErbB-driven tumour cell growth in vitro and in various animal models.

Tablet 250mg

• Tykerb fct (Novartis) originator