Treatment of metastatic epidermal growth factor receptor (EGFR) T790M mutation-positive non–small-cell lung cancer (NSCLC) in patients who have progressed on or after EGFR tyrosine kinase inhibitor therapy.
First-line treatment of metastatic NSCLC in patients whose tumors have EGFR exon 19 deletions or exon 21 L858R mutations.
Action
Irreversibly binds to select mutant forms of EGFR (including T790M), resulting in inactivation of kinases that regulate proliferation and transformation; the T790M mutation is the most common mechanism of resistance to EGFR tyrosine kinase inhibitors.
Therapeutic Effect(s):
Decreased spread of NSCLC
Pharmacokinetics
Absorption: Well absorbed following oral administration.
Distribution: Extensively distributed to tissues.
Protein Binding: 95%.
Metabolism and Excretion: Mostly metabolized by the liver (CYP3A4 enzyme system) to 2 active metabolites; 68% excreted in feces (2% as unchanged drug); 14% excreted in urine (2% as unchanged drug).
Half-life: 48 hr.
TIME/ACTION PROFILE (blood levels)
ROUTE
ONSET
PEAK
DURATION
Oral
unknown
6 hr
24 hr
Contraindication/Precautions
Contraindicated in:
Concurrent use of strong CYP3A4 inhibitors or inducers;
OB: Pregnancy (may cause fetal harm);
Lactation: Breast feeding should be avoided during treatment and for 2 wk after therapy.
Use Cautiously in:
Congenital long QT syndrome, HF, electrolyte abnormalities, or taking QT interval prolonging medications;
End-stage renal disease (CCr <15 mL/min);
Severe hepatic impairment;
Rep: Women of reproductive potential and men with female partners of reproductive potential;
QT interval prolonging drugs may ↑ risk of torsade de pointes; avoid concurrent use.
May ↑ levels of P-gp substrates, including fexofenadine.
May ↑ levels of breast cancer resistant protein (BCRP) substrates, including rosuvastatin.
Drug-Natural Products:
St. John's wort may ↓ levels and its effectiveness; avoid concurrent use.
Route/Dosage
PO (Adults): 80 mg once daily until disease progression or unacceptable toxicity
Availability
Tablets: 40 mg, 80 mg
Assessment
Assess for worsening respiratory symptoms (dyspnea, coughing, fever) during therapy; may indicate interstitial lung disease or pneumonitis. If signs and symptoms occur, permanently discontinue osimertinib.
Monitor cardiac status (ECG, electrolytes) periodically during therapy, especially in patients with congenital long QTc syndrome, HF, electrolyte abnormalities, or taking medications that prolong QTc interval. If QTc interval >500 msec on at least 2 separate ECGs, withhold therapy until QTc interval is <481 msec or recovery to baseline if baseline is ≥481 msec, resume at 40 mg dose. If QTc interval prolongation occurs with signs and symptoms of life threatening arrhythmia, permanently discontinue therapy.
Assess for signs and symptoms of cardiomyopathy (cardiac failure, pulmonary edema, ejection fraction decreased, stress cardiomyopathy) by echo cardiogram, multigated acquisition (MUGA) scan prior to starting therapy and every 3 mo during therapy. If asymptomatic and absolute decrease in LVEF of 10% from baseline and below 50%, withhold therapy for up to 4 wk. If improved to baseline, resume. If not improved to baseline, permanently discontinue. If symptomatic HF develops, permanently discontinue therapy.
Lab Test Considerations:
Obtain a negative pregnancy test before starting therapy.
Monitor CBC with differential periodically during therapy. May cause lymphopenia, thrombocytopenia, anemia, and neutropenia. If ≥Grade 3 reaction occurs, withhold osimertinib for up to 3 wk. If improved to Grade 0–2, resume at 80 mg or 40 mg daily. If no improvement in 3 wk, permanently discontinue osimertinib.
For patients with difficulty swallowing, disperse tablet in 4 tbsp (50 mL) of only non-carbonated water. Stir until tablet is completely dispersed and swallow or administer through NG tube immediately; do not crush, heat, or ultrasonicate during preparation. Rinse container with 4–8 oz of water and drink or administer through NG tube immediately.
Patient/Family Teaching
Instruct patient to take osimertinib as directed. If dose missed, omit and take next dose as scheduled. Advise patient to read Patient Information prior to starting therapy and with each Rx dose refill in case of changes.
Advise patient to notify health care professional if signs and symptoms of lung problems (worsening lung symptoms, trouble breathing, shortness of breath, cough, fever) or heart problems (pounding or racing heart, shortness of breath, swollen ankles or feet, lightheadedness) occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and consult health care professional before taking any new medications.
Rep: May be teratogenic and may impair fertility in males and females. Caution women of reproductive potential to use effective contraception during and for at least 6 wk after final dose. Advise males with female partners of reproductive potential to use effective contraception during and for at least 4 mo after final dose. Advise females patient to avoid breast feeding during and for at least 2 wk after final dose.
Evaluation/Desired Outcomes
Decreased spread of NSCLC.
osimertinibis the Davis's Drug Guide Word of the day!