epidermal growth factor receptor (EGFR) inhibitors
- 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.
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.
Decreased spread of NSCLC
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)
|Oral||unknown||6 hr||24 hr|
- 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;
- Pedi: Safety and effectiveness not established.
Adverse Reactions/Side Effects
CNS: STROKE, fatigue, headache
CV: CARDIOMYOPATHY, QT INTERVAL PROLONGATION, VENOUS THROMBOEMBOLISM
Derm: dry skin, nail disorders, pruritus, rash
EENT: blepharitis, blurred vision, cataracts, dry eye, eye pain, ↑ lacrimation, keratitis
F and E: hypermagnesemia, hyponatremia
GI: constipation, ↓ appetite, diarrhea, nausea, stomatitis
Hemat: NEUTROPENIA, THROMBOCYTOPENIA, anemia, lymphopenia
MS: back pain
Resp: INTERSTITIAL LUNG DISEASE, cough
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
- Strong CYP3A4 inhibitors, including itraconazole, nefazodone, and ritonavir may ↑ levels and the risk of toxicity; avoid concurrent use.
- Strong CYP3A4 inducers, including carbamazepine, rifampin, and phenytoin may ↓ levels and its effectiveness; avoid concurrent use.
- May ↑ or ↓ carbamazepine, cyclosporine, ergot derivatives, fentanyl, phenytoin, or quinidine ; avoid concurrent use.
- 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.
St. John's wort may ↓ levels and its effectiveness; avoid concurrent use.
PO (Adults): 80 mg once daily until disease progression or unacceptable toxicity
Tablets: 40 mg, 80 mg
- 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.
- May cause hyponatremia and hypermagnesemia.
- PO Administer once daily without regard to food.
- 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.
- 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.
Decreased spread of NSCLC.
osimertinibis the Emergency Central Word of the day!