What is the dosage for lapatinib (Tykerb)?
HER2-Positive Metastatic Breast Cancer: The recommended dose of Tykerb is 1,250 mg given orally once daily on Days 1-21 continuously in combination with capecitabine 2,000 mg/m2 /day (administered orally in 2 doses approximately 12 hours apart) on Days 1-14 in a repeating 21-day cycle. Tykerb should be taken at least one hour before or one hour after a meal. The dose of Tykerb should be once daily (5 tablets administered all at once); dividing the daily dose is not recommended. Capecitabine should be taken with food or within 30 minutes after food.
If a day’s dose is missed, the patient should not double the dose the next day. Treatment should be continued until disease progression or unacceptable toxicity occurs. Hormone Receptor-Positive, HER2-Positive Metastatic Breast Cancer: The recommended dose of Tykerb is 1,500 mg given orally once daily continuously in combination with letrozole. When coadministered with Tykerb, the recommended dose of letrozole is 2.5 mg once daily. Tykerb should be taken at least one hour before or one hour after a meal. The dose of Tykerb should be once daily (6 tablets administered all at once); dividing the daily dose is not recommended.
What drugs interact with lapatinib (Tykerb)?
Effects of Lapatinib on Drug-Metabolizing Enzymes and Drug Transport Systems Lapatinib inhibits CYP3A4, CYP2C8, and P-glycoprotein (P-gp, ABCB1) in vitro at clinically relevant concentrations and is a weak inhibitor of CYP3A4 in vivo.
Caution should be exercised and dose reduction of the concomitant substrate drug should be considered when dosing Tykerb concurrently with medications with narrow therapeutic windows that are substrates of CYP3A4, CYP2C8, or P-gp.
Lapatinib did not significantly inhibit the following enzymes in human liver microsomes: CYP1A2, CYP2C9, CYP2C19, and CYP2D6 or UGT enzymes in vitro, however, the clinical significance is unknown.
Midazolam: Following coadministration of Tykerb and midazolam (CYP3A4 substrate), 24-hour systemic exposure (AUC) of orally administered midazolam increased 45%, while 24-hour AUC of intravenously administered midazolam increased 22%. Paclitaxel: In cancer patients receiving Tykerb and paclitaxel (CYP2C8 and P-gp substrate), 24-hour systemic exposure (AUC) of paclitaxel was increased 23%. This increase in paclitaxel exposure may have been underestimated from the in vivo evaluation due to study design limitations.
Digoxin: Following coadministration of Tykerb and digoxin (P-gp substrate), systemic AUC of an oral digoxin dose increased approximately 2.8-fold. Serum digoxin concentrations should be monitored prior to initiation of Tykerb and throughout coadministration. If digoxin serum concentration is greater than 1.2 ng/mL, the digoxin dose should be reduced by half. 7.2 Drugs That Inhibit or Induce Cytochrome P450 3A4 Enzymes Lapatinib undergoes extensive metabolism by CYP3A4, and concomitant administration of strong inhibitors or inducers of CYP3A4 alter lapatinib concentrations significantly. Dose adjustment of lapatinib should be considered for patients who must receive concomitant strong inhibitors or concomitant strong inducers of CYP3A4 enzymes.
Ketoconazole: In healthy subjects receiving ketoconazole, a CYP3A4 inhibitor, at 200 mg twice daily for 7 days, systemic exposure (AUC) to lapatinib was increased to approximately 3.6-fold of control and half-life increased to 1.7-fold of control. Carbamazepine: In healthy subjects receiving the CYP3A4 inducer, carbamazepine, at 100 mg twice daily for 3 days and 200 mg twice daily for 17 days, systemic exposure (AUC) to lapatinib was decreased approximately 72%.
Drugs That Inhibit Drug Transport Systems
Lapatinib is a substrate of the efflux transporter P-glycoprotein (P-gp, ABCB1). If Tykerb is administered with drugs that inhibit P-gp, increased concentrations of lapatinib are likely, and caution should be exercised.
Acid-Reducing Agents
The aqueous solubility of lapatinib is pH dependent, with higher pH resulting in lower solubility. However, esomeprazole, a proton pump inhibitor, administered at a dose of 40 mg once daily for 7 days, did not result in a clinically meaningful reduction in lapatinib steady-state exposure.
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