Tykerb (lapatinib ditosylate)

Dosage of lapatinib ditosylate monohydrate is expressed in terms of lapatinib.

If adverse reactions occur during lapatinib therapy, temporary interruption of therapy, dosage reduction, and/or permanent discontinuance of the drug may be necessary. If dosage reduction is required, the dosage of lapatinib should be reduced as described in Table 1.

Table 1: Recommended Dosage Reduction for Lapatinib Toxicity

Adverse Reaction Recommended Dosage Recommended Dosage Reduction of Lapatinib Reduction of Lapatinib when Used in Combination when Used in Combination with Letrozole for with Capecitabine for Hormone HER2-positive, Advanced Receptor-positive, or Metastatic Breast HER2-positive Metastatic Cancer Breast Cancer Cardiac events 1.25 g once daily 1 g once daily Diarrhea 1.25 g once daily in 1.25 g once daily in patients previously patients previously receiving 1.5 g once receiving 1.5 g once daily 1 g once daily in daily 1 g once daily in patients previously patients previously receiving 1.25 g once receiving 1.25 g once daily daily Other toxicity 1.25 g once daily 1 g once daily

Table 2 indicates the recommended dosage modification (i.e., temporary interruption of therapy, dosage reduction, discontinuance of therapy) for adverse effects according to severity.

Table 2. Dosage Modification for Lapatinib Toxicity.

Adverse Reaction and Severity Modification Cardiac Events Grade >=2 decreased LVEF or LVEF Discontinue lapatinib; may restart that decreases below institution's at a reduced dosage (see Table 1) lower limit of normal (LLN) after >=2 weeks if LVEF returns to normal and the patient is asymptomatic Diarrhea Grade 3 or Grade 1-2 with Withhold therapy; may restart at a complicating features reduced dosage (see Table 1) once diarrhea resolves to <=grade 1 Grade 4 Permanently discontinue lapatinib Interstitial Lung Disease/Pneumonitis Grade >=3 Discontinue lapatinib Other Toxicity Grade >=2 Consider interruption or discontinuance of lapatinib May restart at the standard dosage of 1.25 or 1.5 g once daily once the toxicity improves to grade <=1; If the toxicity recurs, restart lapatinib at a reduced dosage (see Table 1)

Severity is defined by the National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE)

Complicating features include moderate to severe abdominal cramping, nausea or vomiting of grade >=2, decreased performance status, sepsis, fever, neutropenia, frank bleeding, or dehydration

Avoid concomitant use of lapatinib with potent inhibitors of cytochrome P-450 (CYP) isoenzyme 3A4. If concomitant therapy cannot be avoided, consider reduction of the lapatinib dosage to 500 mg daily. This recommendation is based on pharmacokinetic considerations; no clinical data on this dosage adjustment are available. If the potent CYP3A4 inhibitor is discontinued, a period of approximately 1 week should elapse before lapatinib dosage is increased to the usual recommended dosage.

Avoid concomitant use of lapatinib with potent CYP3A4 inducers. If concomitant therapy cannot be avoided, consider an increase in lapatinib dosage. Lapatinib dosage should be increased gradually as tolerated from a dosage of 1.5 g daily up to 5.5 g daily when given in combination with letrozole for the treatment of hormone receptor-positive, HER2-positive metastatic breast cancer and from a dosage of 1.25 g daily up to 4.5 g daily when given in combination with capecitabine for the treatment of HER2-positive, advanced or metastatic breast cancer. These recommendations are based on pharmacokinetic considerations; no clinical data on these dosage adjustments in these patient populations are available. If the potent CYP3A4 inducer is discontinued, reduce the lapatinib dosage to the usual recommended dosage.

Lapatinib is administered orally once daily. Administer the drug at least 1 hour before or 1 hour after meals. Do not divide the daily dosage because such administration may increase systemic exposure to the drug (by approximately twofold). Advise patients not to double the next dose if a dose is missed. Store lapatinib tablets at 20-25degreesC (excursions permitted between 15-30degreesC).

No dosing information is available for this tab.

No dosing information is available for this tab.

Lapatinib is metabolized by cytochrome P-450 (CYP) isoenzymes, principally by CYP3A4 and 3A5. Lapatinib inhibits CYP3A4 and CYP2C8, but does not substantially inhibit CYP isoenzymes 1A2, 2C9, 2C19, and 2D6 or uridine 5'-diphospho-glucuronosyltransferase (UGT) enzymes in vitro.

Lapatinib is a substrate and inhibitor of efflux transporter P-glycoprotein (P-gp).

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

*Known hypersensitivity (e.g., anaphylaxis) to the drug or any ingredient in the formulation.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects reported in >=20% of patients receiving lapatinib in combination with capecitabine include diarrhea, palmar-plantar erythrodysesthesia, nausea, vomiting, rash, and fatigue.

Adverse effects reported in >=20% of patients receiving lapatinib in combination with letrozole include diarrhea, rash, nausea, and fatigue.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Safety and efficacy have not been established in children.

Lapatinib can cause fetal harm if administered to pregnant women based on its mechanism of action and animal findings. (See Fetal/Neonatal Morbidity and Mortality under Cautions.) Inform pregnant women and females of reproductive potential of the potential hazard to the fetus. (See Females and Males of Reproductive Potential under Cautions.)

It is not known whether lapatinib is distributed into human milk. Because of the potential for serious adverse reactions to lapatinib in nursing infants, advise women to discontinue nursing while receiving lapatinib and for at least 1 week after the drug is discontinued. The effects of the drug on nursing infants or on the production of milk are unknown.

The manufacturer makes no specific dosage recommendations for geriatric patients.

No substantial differences in safety or efficacy have been observed in geriatric patients relative to younger adults, but increased sensitivity cannot be ruled out.