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lapatinib (Rx)Brand and Other Names:Tykerb

 
 
 

Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 250mg
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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

Dosage modifications

  • Discontinue with decreased LVEF ≥Grade 2 or an LVEF that drops below the institution’s lower limit of normal; lapatinib may be restarted at 1000 mg/day after recovery
  • Other toxicities: Discontinue or interrupt dose should be considered when patients develop ≥Grade 2 NCI CTCAE toxicity; can be restarted at 1,250 mg/day when the toxicity improves to ≤Grade 1; if toxicity recurs, then lapatinib in combination with capecitabine should be restarted at a lower dose
  • Severe hepatic impairment: Reduce dose (see Hepatic Impairment)
  • Concomitant strong CYP3A4 inhibitors: Reduce dose to 500 mg/day
  • Concomitant strong CYP3A4 inducers: Gradually titrate from 1250 mg/day up to 4500 mg/day (HER2 positive metastatic breast cancer) or from 1500 mg/day up to 5500 mg/day (Hormone receptor positive, HER2 positive breast cancer)

Gastric Cancer (Orphan)

Treatment of ErbB2 positive gastric cancer

Orphan indication sponsor

  • GlaxoSmithKline; 1250 S. Collegeville Rd, P. O. Box 5089;Collegeville, PA 19426-0989

Esophageal Cancer (Orphan)

Treatment of ErbB2 positive esophageal cancer

Orphan indication sponsor

  • GlaxoSmithKline; 1250 S. Collegeville Rd, P. O. Box 5089;Collegeville, PA 19426-0989

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

Administration

Lapatinib should be taken at least 1 hour before or 1 hour after meals; however, capecitabine should be taken with food, or within 30 minutes after food

Modify dose for cardiac and other toxicities, severe hepatic impairment, and CYP3A4 interactions

Safety and efficacy not established

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Interactions

Interaction Checker

lapatinib and

No Results

     
     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10% (lapatinib+capecitabine vs capecitabine)

            Diarrhea (65% vs 40%)

            Anemia (56% vs 53%)

            Hand-foot synd (53% vs 51%)

            Increased LFTs (37-49% vs 30-43%)

            Nausea (44% vs 43%)

            Rash (28% vs 14%)

            Vomiting (26% vs 21%)

            Pain (23% vs 13%)

            Neutropenia (22% vs 31%)

            Thrombocytopenia (18% vs 17%)

            Mucositis (15% vs 12%)

            Stomatitis (14% vs 11%)

            Dyspnea (12% vs 8%)

            Dyspepsia (11% vs 3%)

            Insomnia (10% vs 6%)

            1-10%

            Insomnia

            LVEF decreased

            Postmarketing Reports

            Hypersensitivity reactions including anaphylaxis

            Nail disorders including paronychia

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            Warnings

            Black Box Warnings

            AST or ALT >3 times the upper limit of normal (ULN) or bilirubin >1.5 times ULN reported and may be a severe toxicity and/or fatal; onset may occur within days to several months after initiating therapy

            Contraindications

            Hypersensitivity to any component

            Cautions

            Severe hepatic impairment

            Concomitant QT-prolonging drugs; conditions that increase QT-prolongation risk

            Risk of severe diarrhea

            Substrate of & inhibits P-glycoprotein (ABCB1); caution if using concomitant ABCB1 substrates/inhibitors

            Severe cutaneous reactions reported; discontinue therapy if life-threatening reactions are suspected

            Decreases in left ventricular ejection fraction (LVEF) reported; confirm normal LVEF before initiating therapy and continue evaluations during treatment

            Hepatotoxicity reported with therapy; monitor liver function tests before initiation of treatment, every 4 to 6 weeks during treatment, and as clinically indicated; discontinue and do not restart therapy if patients experience severe changes in liver function tests

            Consider dose reduction in patients with severe hepatic impairment

            Linked to risk of interstitial lung disease & pneumonitis; monitor pulmonary symptoms

            Diarrhea

            • Diarrhea reported and may be severe; deaths reported
            • Generally occurs early during treatment with almost 50% first experiencing it within 6 days, and usually lasts 4-5 days
            • 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
            • Instruct patients to report any change in bowel patterns immediately
            • Prompt treatment of diarrhea with anti-diarrheal agents (eg, loperamide) after the first unformed stool is recommended
            • Severe cases may oral or IV electrolytes and fluids, antibiotics (eg, fluoroquinolones) if diarrhea persists beyond 24 hr, fever is present, or Grade 3-4 neutropenia
            • If severe, interrupt or discontinue lapatinib
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            Pregnancy & Lactation

            Pregnancy Category: D

            Lactation: Do not nurse

            Pregnancy Categories

            A:Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

            B:May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

            C:Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

            D:Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

            X:Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

            NA:Information not available.

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            Pharmacology

            Mechanism of Action

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

            Absorption

            Systemic absorption increased by food (AUC increase ~3-4 fold)

            Peak Plasma Time: 4 hr

            Peak Plasma Concentration: 2.43 mcg/mL (1.25 g dose)

            Distribution

            Protein Bound: 99%

            Metabolism

            Primarily metabolized by CYP3A4 and CYP3A5

            Enzymes inhibited: CYP3A4 and CYP2C8

            Eliminiation

            Half-Life: 24 hr

            Excretion: Feces

            Pharmacogenomics

            Mediates antibody-dependent cellular cytotoxicity against cells that overproduce HER2, and lacks effect on cells not overexpressing HER2

            HER2 testing should be performed

            Patients with breast cancers with intensive staining (3+) should definitely receive anti-HER2 therapy; the clinical relevance of 2+ staining is uncertain

            Genetic testing laboratories

            • The following companies currently offer IHC and/or FISH testing for HER2 overexpression
            • Dako (http://www.dakousa.com/)
            • Ventana Medical Systems (http://www.ventanamed.com/)
            • Vysis/Abbott Molecular (http://www.abbottmolecular.com/)
            • Invitrogen (http://www.invitrogen.com/)
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            Formulary

            FormularyPatient Discounts

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            The above information is provided for general informational and educational purposes only. Individual plans may vary and formulary information changes. Contact the applicable plan provider for the most current information.

            Tier Description
            1 This drug is available at the lowest co-pay. Most commonly, these are generic drugs.
            2 This drug is available at a middle level co-pay. Most commonly, these are "preferred" (on formulary) brand drugs.
            3 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs.
            4 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            5 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            6 This drug is available at a higher level co-pay. Most commonly, these are "non-preferred" brand drugs or specialty prescription products.
            NC NOT COVERED – Drugs that are not covered by the plan.
            Code Definition
            PA Prior Authorization
            Drugs that require prior authorization. This restriction requires that specific clinical criteria be met prior to the approval of the prescription.
            QL Quantity Limits
            Drugs that have quantity limits associated with each prescription. This restriction typically limits the quantity of the drug that will be covered.
            ST Step Therapy
            Drugs that have step therapy associated with each prescription. This restriction typically requires that certain criteria be met prior to approval for the prescription.
            OR Other Restrictions
            Drugs that have restrictions other than prior authorization, quantity limits, and step therapy associated with each prescription.
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