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U.S. Department of Health and Human Services

Safety

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Tykerb (lapatinib) Tablets

Detailed View: Safety Labeling Changes Approved By FDA Center for Drug Evaluation and Research (CDER)

 

June 2013

Summary View

 

WARNINGS AND PRECAUTIONS

Diarrhea
  • Diarrhea has been reported during treatment with Tykerb. The diarrhea may be severe, and deaths have been reported. Diarrhea generally occurs early during treatment with Tykerb, with almost half of those patients with diarrhea first experiencing it within 6 days. This usually lasts 4 to 5 days. Lapatinib-induced diarrhea is usually low-grade, with severe diarrhea of NCI CTCAE Grades 3 and 4 occurring in <10% and <1% of patients, respectively. Early identification and intervention is critical for the optimal management of diarrhea. Patients should be instructed to report any change in bowel patterns immediately. Prompt treatment of diarrhea with anti-diarrheal agents (such as loperamide) after the first unformed stool is recommended. Severe cases of diarrhea may require administration of oral or intravenous electrolytes and fluids, use of antibiotics such as fluoroquinolones (especially if diarrhea is persistent beyond 24 hours, there is fever, or Grade 3 or 4 neutropenia), and interruption or discontinuation of therapy with Tykerb.
 

PATIENT COUNSELING INFORMATION

Information for Patients
  • Tykerb often causes diarrhea which may be severe in some cases. Patients should be told how to manage and/or prevent diarrhea and to inform their physician immediately if there is any change in bowel patterns or severe diarrhea occurs during treatment with Tykerb.

PATIENT INFORMATION

What are the possible side effects of TYKERB?
  • Diarrhea:...Call your doctor immediately at the first sign of diarrhea, as it is important that this is treated right away.

 

February 2012

Summary View

 

DRUG INTERACTIONS

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.

 

August 2011

Summary View 

 

DRUG INTERACTIONS

Effects of Lapatinib on Drug Metabolizing Enzymes and Drug Transport Systems
  • 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%.
  • 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 >1.2 ng/mL, the digoxin dose should be reduced by half

 

The detailed view includes drug products with safety labeling changes to the BOXED WARNING, CONTRAINDICATIONS, WARNINGS, PRECAUTIONS, ADVERSE REACTIONS, or PATIENT PACKAGE INSERT/MEDICATION GUIDE sections. Deletions or editorial revisions made to these sections are not included in this summary.

 

July 2008

Summary View

 

Sections ModifiedSummary of Changes to Contraindications and Warnings

BOXED WARNING

  • WARNING: HEPATOTOXICITY

WARNINGS AND PRECAUTIONS

  • Hepatotoxicity
  • Patients with Severe Hepatic Impairment

ADVERSE REACTIONS

  • Clinical Trials Experience
    • Hepatotoxicity

USE IN SPECIFIC POPULATIONS

  • Hepatic Impairment

PATIENT PACKAGE INSERT

  • Before you start taking Tykerb, tell your doctor about all of your medical conditions, including if you...
    • have liver problems. You may need a lower dose of Tykerb.
  • What are the possible side effects of Tykerb?
    • Serious side effects include...
      • liver problems, which may cause itching, yellow eyes or skin, dark urine, or pain or discomfort in the right upper area of the belly.
      • Your doctor should do blood tests to check your liver before you start taking Tykerb and during treatment.

BOXED WARNING

WARNING: HEPATOTOXICITY

Hepatotoxicity has been observed in clinical trials and postmarketing experience. The hepatotoxicity may be severe and deaths have been reported. Causality of the deaths is uncertain. [See Warnings and Precautions (5.2).]

WARNINGS AND PRECAUTIONS

Hepatotoxicity

Hepatotoxicity (ALT or AST >3 times the upper limit of normal and total bilirubin >1.5 times the upper limit of normal) has been observed in clinical trials (<1% of patients) and postmarketing experience. The hepatotoxicity may be severe and deaths have been reported. Causality of the deaths is uncertain. The hepatotoxicity may occur days to several months after initiation of treatment. Liver function tests (transaminases, bilirubin, and alkaline phosphatase) should be monitored before initiation of treatment, every 4 to 6 weeks during treatment, and as clinically indicated. If changes in liver function are severe, therapy with Tykerb should be discontinued and patients should not be retreated with Tykerb [see Adverse Reactions (6.1)].

Patients with Severe Hepatic Impairment

...In patients who develop severe hepatotoxicity while on therapy, Tykerb should be discontinued and patients should not be retreated with Tykerb [see Warnings and Precautions (5.2)]