Tagrisso

— THERAPEUTIC CATEGORIES —
  • Respiratory and thoracic cancers
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Tagrisso Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Osimertinib 40mg, 80mg; tabs.

    Pharmacological Class

    Kinase inhibitor.

    How Supplied

    Tabs—30

    Storage

    Store bottles at 25°C (77°F). Excursions permitted to 15°C-30°C (59°F-86°F).

    Manufacturer

    AstraZeneca Pharmaceuticals

    Generic Availability

    NO

    Mechanism of Action

    Osimertinib is a 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 approximately 9­fold lower concentrations than wild-type. In vitro, osimertinib also inhibited the activity of HER2, HER3, HER4, ACK1, and BLK at clinically relevant concentrations.

    Tagrisso Indications

    Indications

    Adjuvant treatment after tumor resection in adults with 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. First-line treatment of adults with metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. In combination with pemetrexed and platinum-based chemotherapy for first-line treatment of adults with locally advanced or metastatic NSCLC whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations, as detected by an FDA-approved test. Treatment of adults with metastatic EGFR T790M mutation-positive NSCLC, as detected by an FDA-approved test, who have progressed on or after EGFR tyrosine kinase inhibitor therapy. 

    Tagrisso Dosage and Administration

    Adult

    Confirm presence of exon 19 deletion or exon 21 L858R or T790M mutation prior to treatment initiation. 80mg once daily. Adjuvant: treat until disease recurrence, unacceptable toxicity, or for up to 3 years. Metastatic or locally advanced: treat until disease progression or unacceptable toxicity. If swallowing difficulty, may disperse tab in 2oz (60mL) of non-carbonated water only; stir and swallow immediately, then rinse container with 4–8oz water and drink immediately; or if administration via NG tube is required, disperse tab in 15mL of non-carbonated water and use an additional 15mL of water to transfer any residues to the syringe; give resulting 30mL via NG tube as instructed with appropriate water flushes (~30mL). Concomitant strong CYP3A4 inducers (if unavoidable): increase dose to 160mg daily; resume at 80mg 3 weeks after discontinuing CYP3A4 inducer. Dose modifications: see full labeling.

    Children

    Not established.

    Tagrisso Contraindications

    Not Applicable

    Tagrisso Boxed Warnings

    Not Applicable

    Tagrisso Warnings/Precautions

    Warnings/Precautions

    Permanently discontinue if interstitial lung disease (ILD)/pneumonitis is confirmed; QTc interval prolongation with signs/symptoms of life-threatening arrhythmia; symptomatic CHF; or if no improvement within 3 weeks. Withhold dose if worsening respiratory symptoms indicative of ILD occur; if QTc interval >500msec on ≥2 separate ECGs; or adverse reactions of Grade ≥3 severity. Monitor ECGs and electrolytes periodically in patients with congenital long QTc syndrome, CHF, electrolyte abnormalities, or those who are taking drugs known to prolong the QTc interval. Conduct cardiac monitoring (including LVEF at baseline and during treatment) in patients with cardiac risk factors (in monotherapy) and in all patients (in combination with pemetrexed and platinum-based chemotherapy). Assess LVEF if relevant cardiac signs/symptoms develop. Perform CBCs with differential before and periodically during treatment. Promptly refer to an ophthalmologist if signs/symptoms suggestive of keratitis occur. Withhold dose if aplastic anemia, erythema multiforme major, Stevens-Johnson Syndrome, or toxic epidermal necrolysis is suspected; permanently discontinue if confirmed. Withhold dose and evaluate if cutaneous vasculitis suspected; consider permanent discontinuation based on severity if no other etiology. Embryo-fetal toxicity. Advise to use effective contraception during and for 6 weeks (females) or 4 months (males w. female partners) after the last dose. Pregnancy: exclude status prior to initiation. Nursing mothers: not recommended (during and for 2 weeks after the last dose).

    Tagrisso Pharmacokinetics

    Absorption

    Median time to maximal plasma concentration (Cmax): 6 hours (range 3–24 hours). 

    Distribution

    Mean volume of distribution at steady-state (Vss/F): 918 L.

    Plasma protein bound: 95%.

    Metabolism

    Oxidation (primarily CYP3A), dealkylation in vitro.

    Elimination

    Fecal (68%), renal (14%).

    Half-life: 48 hours.

    Tagrisso Interactions

    Interactions

    Antagonized by strong CYP3A inducers (eg, rifampin); avoid; if use is unavoidable, increase Tagrisso dose (see Adults). Potentiates BCRP (eg, rosuvastatin) or P-gp (eg, fexofenadine) substrates; monitor closely for related toxicity. Avoid concomitant QT-prolonging drugs.

    Tagrisso Adverse Reactions

    Adverse Reactions

    Leukopenia, lymphopenia, thrombocytopenia, diarrhea, anemia, rash, musculoskeletal pain, nail toxicity, neutropenia, dry skin, stomatitis, fatigue, cough.

    Tagrisso Clinical Trials

    See Literature

    Tagrisso Note

    Not Applicable

    Tagrisso Patient Counseling

    See Literature

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