osimertinib (Rx)

Brand and Other Names:Tagrisso
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Dosing & Uses

AdultPediatricGeriatric

Dosage Forms & Strengths

tablet

  • 40mg
  • 80mg

Non-Small Cell Lung Cancer

Indicated for the first-line 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 mutations, as detected by an FDA-approved test

Also indicated for metastatic EGFR T790M mutation positive NSCLC, as detected by an FDA approved test, in patients who have progressed on or after EGFR TKI therapy

80 mg PO qDay; continue until disease progression or unacceptable toxicity

Dosage Modifications

Renal impairment

  • Mild-to-moderate (CrCl 15-89 mL/min): No dose adjustment required
  • End-stage renal disease (ESRD): There is no recommended dose

Hepatic impairment

  • Mild (total bilirubin ≤upper limit of normal (ULN) and AST >ULN or total bilirubin between 1-1.5x ULN and any AST) or moderate (total bilirubin between 1-3x ULN and any AST): No dose adjustment required
  • Severe ((total bilirubin between 3-10x ULN and any AST): There is no recommended dose

Pulmonary adverse effects

  • Interstitial lung disease/pneumonitis: Permanently discontinue

Cardiac adverse effects

  • QTc interval >500 msec on at least 2 separate ECGs: Withhold until QTc interval <481 msec or recovery to baseline if baseline QTc is ≥481 msec, then resume at 40 mg dose
  • QTc interval prolongation with signs/symptoms of life-threatening arrhythmia: Permanently discontinue
  • Symptomatic CHF: Permanently discontinue

Other adverse effects

  • Adverse reaction≥Grade 3: Withhold for up to 3 weeks
  • If improvement to grade 0-2 within 3 weeks: Resume at 80 mg or 40 mg daily
  • If no improvement within 3 weeks: Permanently discontinue

Coadministration of CYP3A4 inducers

  • Strong CYP3A4 inducer: Avoid use; If coadministration is unavoidable, increase osimertinib dosage to 160 mg daily when coadministering with a strong CYP3A inducer; resume osimertinib at 80 mg 3 weeks after discontinuation of the strong CYP3A4 inducer
  • Moderate and/or weak CYP3A inducers: No dose adjustments required
  • Information on FDA-approved tests for the detection of EGFR mutations is available at http://www.fda.gov/companiondiagnostics

Dosing Considerations

First-line treatment of metastatic EGFR-positive NSCLC: Confirm the presence of EGFR exon 19 deletions or exon 21 L858R mutations in tumor or plasma specimens

Metastatic EGFR T790M mutation-positive NSCLC: Confirm the presence of T790M mutation in tumor specimens prior to initiating treatment

Safety and efficacy not established

No overall differences in effectiveness were observed based on age

Exploratory analysis suggests a higher incidence of Grade 3 and 4 adverse reactions (13.4% versus 9.3%) and more frequent dose modifications for adverse reactions (13.4% versus 7.6%) in patients ≥65 years as compared to those <65 year

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Interactions

Interaction Checker

and osimertinib

No Results

     activity indicator 
    No Interactions Found
    Interactions Found

    Contraindicated

      Serious - Use Alternative

        Significant - Monitor Closely

          Minor

            All Interactions Sort By:
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            Adverse Effects

            Adverse drug reactions listed are all grades of severity unless listed otherwise

            >10%

            Lymphopenia (63%)

            Thrombocytopenia (46%)

            Anemia (43%)

            Diarrhea (41%)

            Rash (34%)

            Neutropenia (27%)

            Hypermagnesemia (27%)

            Hyponatremia (26%)

            Dry skin (23%)

            Nail toxicity (22%)

            Fatigue (22%)

            Hypoglycemia (20%)

            Eye disorders (18%)

            Decreased appetite (18%)

            Cough (17%)

            Nausea (16%)

            Stomatitis (15%)

            Constipation (14%)

            Pruritus (14%)

            Vomiting (11%)

            1-10%

            Back pain (10%)

            Headache (10%)

            Hypokalemia (9%)

            Lymphopenia, Grade 3 or 4 (8.2%)

            Venous thromboembolism (7%)

            Pneumonia (4%)

            Interstitial lung disease/pneumonitis (3.3%)

            QTc increased from baseline >60 msec (2.7%)

            Neutropenia, Grade 3 or 4 (2.2%)

            Hyponatremia, Grade 3 or 4 (1.8%)

            Hypomagnesemia, Grade 3 or 4 (1.8%)

            Hypokalemia, Grade 3 or 4 (1.8%)

            Fatigue, Grade 3 or 4 (1.8%)

            Cardiomyopathy (1.4%)

            Diarrhea, Grade 3 or 4 (1.1%)

            Decreased appetite, Grade 3 or 4 (1.1%)

            <1%

            Keratitis

            Nausea

            Vomiting

            Rash

            Back pain

            Thrombocytopenia

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            Warnings

            Contraindications

            None

            Cautions

            Interstitial lung disease (ILD)/pneumonitis reported in 3.3% of patients during clinical trials; permanently discontinue if diagnosed with ILD/pneumonitis

            May prolong QTc interval; monitor ECG and electrolytes in patients with a history or predisposition for QTc prolongation or in those who are taking medications that are known to prolong the QTc interval; withhold then restart at a reduced dose or permanently discontinue

            Across clinical trials, cardiomyopathy (defined as cardiac failure, chronic cardiac failure, congestive heart failure, pulmonary edema or decreased ejection fraction) occurred in 2.6% of 1142 osimertinib-treated patients; 0.1% of cardiomyopathy cases were fatal; assess LVEF before treatment and then every 3 months thereafter

            Keratitis reported; promptly refer patients with signs and symptoms suggestive of keratitis (eg, eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain, red eye) to an ophthalmologist

            Can cause fetal harm; advise females of reproductive potential to use effect contraception during treatment and for 6 weeks after the final dose; males should use effective contraception for 4 months after the final dose

            Drug interaction overview

            • See Dosage Modifications
            • Coadministration with a strong CYP3A4 inducer decreased the exposure of osimertinib
            • Concurrent use with a BCRP substrate increased the exposure of the BCRP substrate compared to administering the BCRP substrate alone; monitor for adverse reactions of BCRP substrate
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            Pregnancy & Lactation

            Pregnancy

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

            There are no available data in humans

            Administration of osimertinib to pregnant rats was associated with embryo lethality and reduced fetal growth at plasma exposures 1.5 times the exposure at the recommended human dose

            Infertility

            • Based on animal studies, may impair fertility in females and males of reproductive potential

            Contraception

            • Females: Advise females of reproductive potential to use effective contraception during treatment with and for 6 weeks after the final dose
            • Males: Advise male patients with female partners of reproductive potential to use effective contraception during and for 4 months following the final dose

            Lactation

            Unknown if distributed in human breast milk

            Administration to rats during gestation and early lactation was associated with adverse effects, including reduced growth rates and neonatal death

            Because of the potential for serious adverse reactions in breastfed infants, advise a lactating woman not to breastfeed during treatment and for 2 weeks after the 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

            Kinase inhibitor of the epidermal growth factor receptor (EGFR), which binds irreversibly to certain mutant forms of EGFR (T790M, L858R, and exon 19 deletion) at ~9-fold lower concentrations than wild-type

            Absorption

            Peak plasma time: 6 hr

            Distribution

            Protein bound: 95%

            Vd, steady-state: 918 L

            Metabolism

            Main metabolic pathways of osimertinib were oxidation (predominantly CYP3A) and dealkylation in vitro

            Metabolites: Two pharmacologically-active metabolites (AZ7550 and AZ5104 circulating at approximately 10% of the parent) with similar inhibitory profiles to osimertinib have been identified

            Elimination

            Half-life: 48 hr

            Clearance: 14.3 L/hr

            Excretion: 68% (feces); 14% (urine); ~2% (unchanged osimertinib)

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            Administration

            Oral Administration

            Administer with or without food

            Missed dose: Do not make up the missed dose and take the next dose as scheduled

            Administration to patients with swallowing difficulty

            • Disperse tablet in 4 tablespoons of noncarbonated water only
            • Stir until tablet is completely dispersed and swallow or administer through nasogastric tube immediately
            • Do not crush, heat, or ultrasonicate during preparation
            • Rinse the container with 4-8 ounces of water and immediately drink

            Nasogastric tube administration

            • Disperse tablet as above in 15 mL of noncarbonated water, then use an additional 15 mL of water to transfer any residues to the syringe; administer resulting 30 mL liquid as per the nasogastric tube instructions with appropriate water flushes (~30 mL)

            Storage

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

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            Formulary

            FormularyPatient Discounts

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

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            • View the formulary and any restrictions for each plan.
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            • Compare formulary status to other drugs in the same class.
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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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            Medscape prescription drug monographs are based on FDA-approved labeling information, unless otherwise noted, combined with additional data derived from primary medical literature.