gefitinib (Rx)

Brand and Other Names:Iressa
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Dosing & Uses

AdultPediatric

Dosage Forms & Strengths

tablet

  • 250mg

Non-small Cell Lung Cancer

Indicated for the treatment of patients with metastatic non-small cell lung cancer (NSCLC) whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test

250 mg PO qDay until disease progression or unacceptable toxicity

Dosage Modifications

Withhold for up to 14 days following adverse effects

  • Acute onset or worsening pulmonary symptoms (dyspnea, cough, fever)
  • ≥Grade 2 ALT and/or AST elevations
  • ≥Grade 3 diarrhea
  • Signs and symptoms of severe or worsening ocular disorders including keratitis
  • ≥Grade 3 skin reactions
  • May resume gefitinib when adverse effect fully resolves or improves to Grade 1

Permanently discontinue for

  • Confirmed interstitial lung disease
  • Severe hepatic impairment
  • Gastrointestinal perforation
  • Persistent ulcerative keratitis

Coadministration with strong CYP3A4 inducers

  • Increase dose to 500 mg PO qDay in the absence of severe adverse drug reactions
  • Resume 250 mg qDay after discontinuation of the strong CYP3A4 inducer

Safety and efficacy not established

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Interactions

Interaction Checker

and gefitinib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

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            Adverse Effects

            >10%

            Skin reactions, all grades (47%)

            Diarrhea, all grades (29%)

            Decreased appetite, all grades (17%)

            Vomiting, all grades (14%)

            Increased ALT, all grades (11.4%)

            1-10%

            Increased AST, all grades (7.9%)

            Stomatitis, all grades (7%)

            Conjunctivitis, blepharitis, and dry eye (6.7%)

            Conjunctivitis/blepharitis/dry eye (6%)

            Increased ALT, grades 3-4 (5.1%)

            Nail disorders, all grades (5%)

            Diarrhea, grades 3-4 (3%)

            Increased AST, grades 3-4 (3%)

            Increased bilirubin, all grades (2.7%)

            Decreased appetite, grades 2-3 (2.3%)

            Skin reactions, grades 3-4 (2%)

            Interstitial lung disease, all grades (1.3%)

            Vomiting, grades 3-4 (1.2%)

            <1%

            Interstitial lung disease, grades 3-4 (0.7%)

            Increased bilirubin, grades 3-4 (0.7%)

            Stomatitis, all grades (0.3%)

            Corneal erosion and aberrant eyelash growth (0.2%)

            Nail disorders, grades 3-4 (0.1%)

            Gastrointestinal perforation (0.1%)

            Ocular keratitis (0.1%)

            Erythema multiforme and dermatitis bullous (0.08%)

            Fatal hepatoxicity (0.04%)

            Postmarketing Reports

            Renal and urinary disorders: Cystitis, hemorrhagic cystitis

            Skin and subcutaneous tissue disorders: Cutaneous vasculitis

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            Warnings

            Contraindications

            None

            Cautions

            Interstitial lung disease (ILD) or ILD-like adverse drug reactions reported (eg, lung infiltration, pneumonitis, acute respiratory distress syndrome, or pulmonary fibrosis); permanently discontinue if confirmed

            Increased ALT, AST, and bilirubin reported; obtain periodic liver function testing and withhold drug for worsening liver function or discontinue with severe hepatic impairment

            Gastrointestinal perforation reported; permanently discontinue

            Severe or persistent diarrhea may occur; withhold drug for up to 14 days

            Ocular disorders reported (eg, keratitis, corneal erosion, aberrant eyelash growth, conjunctivitis, blepharitis, dry eye); interrupt or discontinue for severe, or worsening ocular disorders

            Bullous conditions including toxic epidermal necrolysis, Stevens Johnson syndrome and erythema multiforme reported rarely; discontinue drug

            Based on its mechanism of action and data from animal reproduction studies, gefitinib can cause fetal harm when administered to a pregnant woman (see Pregnancy)

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            Pregnancy

            Pregnancy

            Based on its mechanism of action and animal data, gefitinib can cause fetal harm when administered to a pregnant woman

            Advise females of reproductive potential to use effective contraception during treatment with gefitinib and for at least 2 weeks following completion of therapy

            Advise pregnant women of the potential hazard to a fetus or potential risk for loss of the pregnancy

            Animal studies

            • In animal reproductive studies, oral administration of gefitinib from organogenesis through weaning resulted in fetotoxicity and neonatal death at doses below the recommended human dose

            Lactation

            Unknown if distributed in human breast milk; not recommended

            Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

            Animal studies

            • Animal studies indicate the gefitinib and its metabolites are present in rat milk at a concentration higher than those in maternal plasma
            • Because of the potential for serious adverse reactions in nursing infants, advise women to discontinue breastfeeding during treatment

            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

            Reversibly inhibits the kinase activity of wild-type and certain activating mutations of epidermal growth factor receptor (EGFR), preventing autophosphorylation of tyrosine residues associated with the receptor, thereby inhibiting further downstream signalling and blocking EGFR-dependent proliferation

            EGFR is expressed on the cell surface of both normal and cancer cells and plays a role in the processes of cell growth and proliferation

            Binding affinity for EGFR exon 19 deletion or exon 21 point mutation L858R mutations is higher than its affinity for the wild-type EGFR

            Absorption

            Oral bioavailability, mean: 60%

            Peak plasma concentration: 3-7 hr

            Steady-state achieved: 10 days

            Distribution

            Protein bound: 90%

            Vd: 1400 L

            Metabolism

            Extensive hepatic metabolism, predominantly by CYP3A4

            Major active metabolite component was O-desmethyl gefitinib produced by CYP2D6 metabolism and accounted for 14% of the dose

            Elimination

            Half-life: 48 hr

            Excretion: 86% feces; <4% urine

            Pharmacogenomics

            CYP2D6 poor metabolizers

            • CYP2D6 metabolizes gefitinib to O-desmethyl gefitinib in vitro
            • In healthy CYP2D6 poor metabolizers, O-desmethyl gefitinib concentration was not measurable and the mean exposure to gefitinib was 2-fold higher as compared to the extensive metabolizers
            • This increase in exposure may be clinically important because some adverse drug reactions are related to higher exposure of gefitinib
            • No dose adjustment is recommended in patients with a known CYP2D6 poor metabolizer genotype, but these patients should be closely monitored for adverse reactions
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            Administration

            Instructions

            May take with or without food

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

            Difficulty swallowing

            • Immerse tablet in 4-8 ounces of water and stir for approximately 15 minutes
            • Immediately drink the liquid or administer through a NG tube
            • Rinse the container with an additional 4-8 ounces of water and immediately drink or administer through the NG tube to assure complete dose
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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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