afatinib (Rx)

Brand and Other Names:Gilotrif
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 20mg
  • 30mg
  • 40mg
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Non-Small Cell Lung Cancer

40 mg PO qDay 1 hr ac or 2 hr pc

Administer until disease progression or inability to tolerate drug

Indications

  • First-line treatment of patients with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test
  • Metastatic squamous NSCLC which has progressed after platinum-based chemotherapy

Dosage Modifications

Withhold dose for any drug-related adverse reactions of:

  • NCI CTCAE Grade 3 or higher
  • Diarrhea Grade 2 or higher persisting for 2 or more consecutive days while taking anti-diarrhea medication
  • Cutaneous reactions Grade 2 that are prolonged (>7 days) or intolerable
  • Renal dysfunction Grade 2 or higher
  • Decrease dose (ie, 10 mg/day less than previous dose) and resume treatment when adverse reaction fully resolves, returns to baseline, or improves to Grade 1

Permanently discontinue for:

  • Life-threatening bullous, blistering, or exfoliative skin lesions
  • Confirmed interstitial lung disease
  • Severe drug-induced hepatic impairment
  • Persistent ulcerative keratitis
  • Symptomatic left ventricular dysfunction
  • Severe or intolerable adverse reaction occurring at a dose of 20 mg/day

Coadministration with P-gp inhibitors

  • For patients who require therapy with a P-gp inhibitor, reduce afatinib daily dose by 10 mg if not tolerated
  • Resume previous dose after P-gp inhibitor is discontinued as tolerated

Coadministration with P-gp inducers

  • For patients who require chronic therapy with a P-gp inducer, increase afatinib daily dose by 10 mg as tolerated
  • Resume the previous dose 2 to 3 days after P-gp inducer is discontinued

Renal impairment

  • Mild (CrCl 60-89 mL/min): Adjustment to starting dose not required
  • Moderate (CrCl 30-59 mL/min or severe (CrCl <30 mL/min): Closely monitor and adjust dose if not tolerated
  • Severe (CrCl 15-30 mL/min): 30 mg once daily
  • Severe (CrCl<15 mL/min/1.73 m²): Not studied

Hepatic impairment

  • Mild-to-moderate (Child Pugh A or B): Adjustment to starting dose not required
  • Severe (Child Pugh C): Closely monitor and adjust dose if not tolerated

Dosing Considerations

Safety and efficacy have not been established in tumors with other EGFR mutations than those listed in the approved indication

Afatinib was approved concurrently with the diagnostic companion test, therascreen EGFR RGQ PCR Kit

Information on FDA-approved tests for the detection of EGFR mutations in NSCLC is available at: http://www.fda.gov/CompanionDiagnostics

CNS Tumors (Orphan)

Orphan designation for treatment of malignant brain and CNS tumors

Sponsor

  • Boehringer Ingelheim Pharmaceuticals, Inc; 900 Ridgebury Road, PO Box 368; Ridgefield, CT 06877-0368

Safety and efficacy not established

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Interactions

Interaction Checker

and afatinib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            All grades included unless otherwise noted

            >10%

            Diarrhea (75-96%)

            Rash/dermatitis acneiform (90%)

            Stomatitis (71%)

            Paronychia (58%)

            Dry skin (31%)

            Decreased appetite (29%)

            Pruritus (21%)

            Epistaxis (17%)

            Weight decreased (17%)

            Diarrhea, grades 3 or 4 (11-15%)

            Cystitis (13%)

            Cheilitis (12%)

            Pyrexia (12%)

            Rhinorrhea (11%)

            Conjunctivitis (11%)

            Increased ALT (11%)

            Hypokalemia (11%)

            1-10%

            Increased AST (8%)

            Interstitial lung disease (1.5%)

            <1%

            Keratitis (0.8%)

            Postmarketing Reports

            Nausea/vomiting

            Pancreatitis

            Toxic epidermal necrolysis/Stevens Johnson syndrome

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            Warnings

            Contraindications

            None

            Cautions

            May cause diarrhea that results in dehydration with or without renal impairment; some reported cases were fatal; withhold therapy for severe and prolonged diarrhea not responsive to antidiarrheal agents

            Postmarketing cases consistent with toxic epidermal necrolysis (TEN), including bullous and exfoliative skin disorders, and Stevens Johnson syndrome (SJS) reported; discontinue if life-threatening bullous, blistering, or exfoliating lesions occur; withhold therapy for severe and prolonged cutaneous reactions

            May increase risk for sunburn/phototoxicity; may worsen rash or acne; caution patients to limit sun exposure and where sunscreen and protective clothing

            Interstitial lung disease (ILD) or ILD-like adverse reactions reported (eg, lung infiltration, pneumonitis, acute respiratory distress syndrome, alveolitis allergy) occurred in 1%, of these, 0.4% were fatal; discontinue therapy if ILD diagnosed

            Hepatotoxicity reported; monitor with periodic liver testing; withhold or discontinue therapy for severe or worsening liver tests

            Keratitis, characterized as acute or worsening eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, and/or red eye occurred in 0.8%; withhold or discontinue therapy for confirmed ulcerative keratitis

            Based on its mechanism of action, afatinib can cause fetal harm; advise pregnant women and females of reproductive potential of potential risk to fetus and to use effective contraception

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            Pregnancy & Lactation

            Pregnancy Category: D; Advise females of reproductive potential to use highly effective contraception during treatment, and for at least 2 weeks after the last dose

            Lactation: Unknown if distributed in human breast milk; a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

            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

            Covalently binds to the kinase domains of EGFR (ErbB1), HER2 (ErbB2), and HER4 (ErbB4) and irreversibly inhibits tyrosine kinase autophosphorylation, resulting in downregulation of ErbB signaling

            Demonstrates inhibition of autophosphorylation and in vitro proliferation of cell lines expressing wild-type EGFR or those expressing selected EGFR exon 19 deletion mutations or exon 21 L858R mutations, including some with a secondary T790M mutation

            In addition, afatinib inhibited in vitro proliferation of cell lines overexpressing HER2

            Absorption

            Bioavailability: 92%

            Peak plasma time: 2-5 hr

            High fat meal decreases Cmax by 50% and AUC by 39% relative to the fasted condition (take on empty stomach)

            Distribution

            Protein bound: 95%

            Metabolism

            Covalent adducts to proteins are the major circulating metabolites of afatinib and enzymatic metabolism of afatinib is minimal

            Elimination

            Half-life: 37 hr

            Excretion: 85% feces; 4% urine

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            Administration

            Oral Administration

            Take PO on empty stomach, at least 1 hr before or 2 hr after a meal

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            Formulary

            FormularyPatient Discounts

            Adding plans allows you to compare formulary status to other drugs in the same class.

            To view formulary information first create a list of plans. Your list will be saved and can be edited at any time.

            Adding plans allows you to:

            • View the formulary and any restrictions for each plan.
            • Manage and view all your plans together – even plans in different states.
            • Compare formulary status to other drugs in the same class.
            • Access your plan list on any device – mobile or desktop.

            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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