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

Metastatic Non-Small Cell Lung Cancer

  • Indicated for first-line treatment in metastatic non-small cell lung cancer (NSCLC) whose tumors have nonresistant epidermal growth factor receptor (EGFR) mutations as detected by an FDA-approved test
  • 40 mg PO qDay until disease progression or no longer tolerated by the patient
  • See also Administration and Dosing Considerations

Metastatic Squamous Non-Small Cell Lung Cancer

  • Indicated for metastatic squamous NSCLC progressing after platinum-based chemotherapy
  • 40 mg PO qDay until disease progression or no longer tolerated by the patient
  • See also Administration

Dosage Modifications

Withhold dose for any drug-related adverse reactions

  • National Cancer Institute Common Terminology Criteria for Adverse Events (NCI CTCAE) Grade ≥3
  • Diarrhea Grade ≥2 persisting for 2 or more consecutive days while taking anti-diarrhea medication
  • Cutaneous reactions Grade 2 that are prolonged (>7 days) or intolerable
  • Renal impairment Grade ≥2
  • Resume treatment when the adverse reaction fully resolves, returns to baseline, or improves to Grade 1
  • Reinstitute afatinib at a reduced dose (eg, 10 mg/day less than the dose at which the adverse reaction occurred)

Permanently discontinue

  • Life-threatening bullous, blistering, or exfoliative skin lesions
  • Confirmed interstitial lung disease (ILD)
  • 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 2-3 days after P-gp inducer is discontinued

Renal impairment

  • Mild-to-moderate (CrCl 30-89 mL/min/1.73 m²): No dosage adjustment necessary
  • Severe (CrCl 15-29 mL/min/1.73 m²): 30 mg PO qDay
  • Severe (CrCl<15 mL/min/1.73 m²): Not studied

Hepatic impairment

  • Mild-to-moderate (Child Pugh A or B): No dosage adjustment necessary
  • Severe (Child Pugh C): Closely monitor and adjust dose if not tolerated

Dosing Considerations

EGFR mutation-positive metastatic NSCLC

  • Limitation of use: Safety and efficacy have not been established in patients whose tumors have resistant EGFR mutations
  • 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

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     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 (70-90%)

            Stomatitis (30-71%)

            Paronychia (11-58%)

            Increased ALT (10-54%)

            Decreased creatinine clearance (49%)

            Increase alkaline phosphate (34-51%)

            Increased AST (7-46%)

            Decreased lymphocytes (38%)

            Dry skin (31%)

            Decreased potassium (11-30%)

            Decreased appetite (25%)

            Pruritus (21%)

            Nausea (21%)

            Epistaxis (17%)

            Decreased weight (17%)

            Rash/dermatitis acneiform, Grade 3 or 4 (7-16%)

            Increased bilirubin (3-16%)

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

            Vomiting (13%)

            Cystitis (13%)

            Decreased WBC (12%)

            Cheilitis (12%)

            Rhinorrhea (11%)

            Paronychia, Grade 3 or 4 (1-11%)

            1-10%

            Stomatitis, Grade 3 or 4 (9%)

            Decreased lymphocytes, Grade 3 or 4 (9%)

            Decreased potassium, Grade 3 or 4 (1-8%)

            Stomatitis, Grade 3 or 4 (4%)

            Decreased appetite, Grade 3 or 4 (3%)

            Increased AST, Grade 3 or 4 (1-3%)

            Increase alkaline phosphate, Grade 3 or 4 (2-3%)

            Decreased creatinine clearance (2%)

            Nausea, Grade 3 or 4 (2%)

            Increased ALT, Grade 3 or 4 (1-2%)

            Decreased WBC, Grade 3 or 4 (1%)

            Vomiting, Grade 3 or 4 (1%)

            Cystitis, Grade 3 or 4 (1%)

            Decreased weight, Grade 3 or 4 (1%)

            Increased bilirubin, Grade 3 or 4 (1%)

            <1%

            Keratitis (0.8%)

            Postmarketing Reports

            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 (see Dosage Modifications)

            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 (see Dosage Modifications)

            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 (see Dosage Modifications)

            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 (see Pregnancy)

            Drug interactions overview

            • See also Dosage Modifications
            • Coadministration of P-gp inhibitors (eg, ritonavir, cyclosporine A, ketoconazole, itraconazole, erythromycin, verapamil, quinidine, tacrolimus, nelfinavir, saquinavir, and amiodarone) with afatinib can increase exposure to afatinib
            • Coadministration of P-gp inducers (eg, rifampicin, carbamazepine, phenytoin, phenobarbital, and St. John’s wort) with afatinib can decrease exposure to afatinib
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            Pregnancy & Lactation

            Pregnancy

            Based on findings from animal studies and mechanism of action, therapy can cause fetal harm when administered to a pregnant woman; there are no available data on use in pregnant women; administration to pregnant rabbits during organogenesis at exposures approximately 0.2 times exposure in humans at recommended dose of 40 mg daily resulted in embryotoxicity and, in rabbits showing maternal toxicity, increased abortions at late gestational stages; advise pregnant women of potential risk to a fetus

            Contraception

            • Advise females of reproductive potential to use effective contraception during treatment and for at least 2 weeks after the last dose of afatinib
            • Based on results from an animal fertility study, afatinib may reduce fertility in females and males of reproductive potential
            • Unknown if the effects on fertility are reversible

            Lactation

            There are no data on presence of afatinib in human milk or effects on breastfed infant or on milk production; presence shown in milk of lactating rats; because of potential for serious adverse reactions in nursing infants, advise a lactating woman not to breastfeed during treatment and for 2 weeks after final dose

            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

            Afatinib is a P-gp substrate and an inhibitor; BCRP substrate and an inhibitor

            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

            Missed dose: Do not take a missed dose within 12 hr of the next dose

            Storage

            Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°F)

            Dispense in the original container to protect from exposure to high humidity and light

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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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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.