Uses of Nibalap: - Breast cancer Breast cancer Hypersensitivity to lapatinib ditosylate

Cytotoxic Chemotherapy

Lapatinib is a 4-anilinoquinazoline tyrosine kinase inhibitor of both Epidermal Growth Factor Receptor (EGFR [ErbB1]) and Human Epidermal Receptor Type 2 (HER2 [ErbB2]) receptors. It blocks the phosphorylation and activation of downstream 2nd messengers (Erk1/2 and Akt) which regulate cellular proliferation and survival of ErbB- and ErbB2-expressing tumours.

How to use Lapatinib: Take this medicine in the dose and duration as advised by your doctor. Swallow it as a whole. Do not chew, crush or break it. Lapatinib is to be taken empty stomach. Administration: Should be taken on an empty stomach. Take at least 1 hr before or 1 hr after a meal. Do not eat/drink grapefruit products. Adult Dose: Oral Breast Cancer HER2-overexpressing metastatic breast cancer Indicated in combination with capecitabine for treatment of patients with advanced or metastatic breast cancer whose tumors overexpress HER2 and who have received prior therapy including an anthracycline, a taxane, and trastuzumab 1250 mg PO qDay on Days 1-21 continuously in combination with capecitabine (2000 mg/m²/day PO divided q12hr) on Days 1-14 in a repeating 21-day cycle Hormone-positive & HER2-positive advanced breast cancer Indicated in combination therapy with letrozole for treatment of postmenopausal women with hormone receptor-positive and HER2-positive breast cancer for whom hormonal therapy is indicated 1500 mg PO qDay administered continuously in combination with letrozole 2.5 mg PO qDay Hepatic Impairment Severe (Child-Pugh Class C) HER2 positive metastatic breast cancer: Reduce dose from 1250 mg/day to 750 mg/day Hormone receptor positive, HER2 positive breast cancer: Reduce dose from 1500 mg/day to 1000 mg/day Child Dose: Safety and efficacy not established

Increased conc w/ CYP3A4 inhibitors (eg ketoconazole, itraconazole or grapefruit juice), midazolam, irinotecan & digoxin. Decreased conc w/ CYP3A4 inducers (eg rifampin, carbamazepine, phenytoin) & proton-pump inhibitors (eg esomeprazole). Altered pharmacokinetics w/ P-glycoprotein, breast cancer resistance protein (BCRP) inhibitors & inducers, topotecan & rosuvastation. Increased incidence & severity of adverse events w/ paclitaxel & docetaxel. CYP3A4 or CYP2C8 substrates.

Hypersensitivity to lapatinib ditosylate

Common - Abdominal pain - Back pain - Breathing problems - Constipation - Cough - Diarrhea - Fatigue - Headache - Hot flashes - Increased bilirubin in the blood - Insomnia (difficulty in sleeping) - Joint pain - Liver damage - Loss of appetite - Mucosal inflammation - Nausea - Pain in extremity - Rash - Stomatitis (Inflammation of the mouth) - Vomiting - Weakness - Weight gain >10% (lapatinib+capecitabine) Diarrhea (65%),Anemia (56%),Hand-foot synd (53%),Increased LFTs (37-49%),Nausea (44%),Rash (28%),Vomiting (26%),Pain (23%),Neutropenia (22%),Thrombocytopenia (18%),Mucositis (15%),Stomatitis (14%),Dyspnea (12%),Dyspepsia (11%),Insomnia (10%) 1-10% Insomnia

Pregnancy category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Precaution: Evaluate left ventricular ejection fraction (LVEF) prior to treatment. Moderate or severe hepatic impairment. Patients who have or may develop QTc prolongation, including those w/ hypokalaemia or hypomagnesemia. Monitor liver function & pulmonary symptoms indicative of interstitial lung disease/pneumonitis. Pregnancy & lactation. Lactation: Do not nurse

There is no known antidote for overdoses of Lapatinib. The maximum oral doses of Lapatinib that have been administered in clinical trials are 1,800 mg once daily. More frequent ingestion of Lapatinib could result in serum concentrations exceeding those observed in clinical trials and could result in increased toxicity. Therefore, missed doses should not be replaced and dosing should resume with the next scheduled daily dose. Asymptomatic and symptomatic cases of overdose have been reported. The doses ranged from 2,500 to 9,000 mg daily and where reported, the duration varied between 1 and 17 days. Symptoms observed include Lapatinib-associated events and in some cases sore scalp, sinus tachycardia (with otherwise normal ECG), and/or mucosal inflammation. Because Lapatinib is not significantly renally excreted and is highly bound to plasma proteins, hemodialysis would not be expected to be an effective method to enhance the elimination of Lapatinib. Treatment of overdose with Lapatinib should consist of general supportive measures.

Store below 30°C in a dry place. Keep out of the reach of children.

Cytotoxic Chemotherapy

Kinase inhibitor, blocks EGF-receptor HER2 kinase; tyrosing kinase inhibition possibly blocks angiogenesis and cellular proliferation.

Based on findings in animal studies and its mechanism of action, Lapatinib can cause fetal harm when administered to a pregnant woman. There are no available human data to inform of the drug-associated risks. Advise pregnant women and females of reproductive potential of the potential risk to the fetus. There are no data on the presence of Lapatinib in human milk, or its effects on the breastfed child, or milk production. Because of the potential for serious adverse reactions in a breastfed child from Lapatinib, advise lactating women not to breastfeed during treatment with Lapatinib and for 1 week after the last dose.