Tykerb

Breast cancer in adults whose tumours overexpress HER2 (ErbB2): In combination w/ capecitabine for patients w/ advanced or metastatic disease w/ progression following prior therapy, which must have included anthracyclines & taxanes & therapy w/ trastuzumab in the metastatic setting; in combination w/ trastuzumab for patients w/ hormone receptor -ve metastatic disease that has progressed on prior trastuzumab therapy(ies) in combination w/ chemotherapy; in combination w/ an aromatase inhibitor for postmenopausal women w/ hormone receptor +ve metastatic disease, not currently intended for chemotherapy & not previously treated w/ trastuzumab or an aromatase inhibitor.

Tykerb/capecitabine combination Tykerb 1,250 mg (5 tab) once daily continuously. Capecitabine 2,000 mg/m²/day taken in 2 doses 12 hr apart on days 1-14 in a 21-day cycle & taken w/ food or w/in 30 min after food. Tykerb/trastuzumab combination Tykerb 1,000 mg (4 tab) once daily continuously. Trastuzumab 4 mg/kg IV loading dose, followed by 2 mg/kg IV wkly. Tykerb/aromatase inhibitor combination Tykerb 1,500 mg (6 tab) once daily continuously.

Should be taken on an empty stomach: Take at least 1 hr before or after food. Standardise administration in relation to food intake.

Hypersensitivity.

Risk of decreases in left ventricular ejection fraction (LVEF). Has not been evaluated in patients w/ symptomatic cardiac failure. Evaluate cardiac function, including LVEF determination, prior to & during treatment. Caution in patients w/ conditions that could result in QTc prolongation (including hypokalemia, hypomagnesemia, & congenital long QT syndrome), co-administration of other QT-prolonging medicinal products, or conditions that increase lapatinib exposure. Correct hypokalemia or hypomagnesemia prior to treatment. Perform ECG w/ QT measurement prior to & 1-2 wk after start of therapy. Discontinue treatment in case of symptoms associated w/ decreased LVEF that are National Cancer Institute Common Terminology Criteria for Adverse Events (NCI-CTCAE) grade ≥3 or if LVEF drops below LLN. Risk of pulmonary toxicity (including ILD & pneumonitis). Monitor patients for symptoms of pulmonary toxicity (dyspnoea, cough, fever). Discontinue treatment in case of pulmonary symptoms which are NCI-CTCAE grade ≥3. Risk of hepatotoxicity. Increased risk of Tykerb-associated hepatotoxicity in patients who carry the HLA alleles DQA1*02:01 & DRB1*07:01. Monitor liver function (transaminases, bilirubin, alkaline phosphatase) before treatment initiation & mthly thereafter, or as clinically indicated. Permanently discontinue treatment in case of severe changes in liver function. Risk of diarrhoea (including severe diarrhoea). Determine patient's bowel pattern & any other symptoms at the start of therapy to identify changes during treatment & identify patients at greater risk of diarrhoea. Interrupt treatment in case of diarrhoea which is NCI-CTCAE grade 1 or 2 w/ complicating features or grade 3, & permanently discontinue in case of diarrhoea which is NCI-CTCAE grade 4. Risk of serious cutaneous reactions. Discontinue treatment if erythema multiforme or life-threatening reactions (eg, SJS or TEN) are suspected. Consider treatment discontinuation or interruption in case of other toxicities (NCI-CTCAE grade ≥2). Avoid co-administration w/ CYP3A4 inducers; strong CYP3A4 inhibitors; grapefruit juice; orally administered CYP3A4 &/or CYP2C8 substrates w/ narrow therapeutic windows; substances that increase gastric pH. Caution in patients w/ severe renal impairment, & moderate to severe hepatic impairment. Women of childbearing potential should use adequate contraception & avoid becoming pregnant while receiving treatment & for at least 5 days after the last dose. Should not be used during pregnancy unless clearly necessary. Discontinue breast-feeding while receiving therapy & for at least 5 days after the last dose. Safety & efficacy in childn <18 yr have not yet been established. Limited data on the use of Tykerb/capecitabine & Tykerb/trastuzumab in elderly patients ≥65 yr.

Anorexia; insomnia; headache; hot flush; epistaxis, cough, dyspnoea; diarrhoea (may lead to dehydration), nausea, vomiting, dyspepsia, stomatitis, constipation, abdominal pain; rash (including dermatitis acneiform), dry skin, palmar-plantar erythrodysaesthesia, alopecia, pruritus; pain in extremity, back pain, arthralgia; fatigue, mucosal inflammation, asthenia. Decreased LVEF; constipation; hyperbilirubinaemia, hepatotoxicity; nail disorders (including paronychia), skin fissures.

Increased systemic exposure w/ strong CYP3A4 inhibitors (eg, ritonavir, saquinavir, telithromycin, ketoconazole, itraconazole, voriconazole, posaconazole, nefazodone). Decreased systemic exposure w/ CYP3A4 inducers (eg, rifampicin, rifabutin, carbamazepine, phenytoin, St. John's wort); PPIs (eg, esomeprazole). Altered exposure &/or distribution w/ P-gp or BCRP inhibitors (eg, ketoconazole, itraconazole, quinidine, verapamil, cyclosporine, erythromycin) & inducers (eg, rifampicin, St. John's wort). Decreased solubility & absorption w/ substances that increase gastric pH. Increased AUC of oral midazolam; SN-38 (active metabolite of irinotecan); oral digoxin. Increased exposure of IV paclitaxel. Increased occurrence of docetaxel-induced neutropenia when co-administered w/ IV docetaxel. May affect pharmacokinetics of BCRP (eg, topotecan) & OATP1B1 (eg, rosuvastatin) substrates. Increased bioavailability w/ fatty meals & grapefruit juice. Caution when co-administered w/ moderate CYP3A4 inhibitors; P-gp substrates w/ narrow therapeutic windows. Avoid co-administration w/ substrates of CYP3A4 (eg, cisapride, pimozide, quinidine) & CYP2C8 (eg, repaglinide) w/ narrow therapeutic windows.

Targeted Cancer Therapy

L01EH01 - lapatinib ; Belongs to the class of human epidermal growth factor receptor 2 (HER2) tyrosine kinase inhibitors. Used in the treatment of cancer.

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