Osimertinib

Lymphopenia, thrombocytopenia, neutropenia, and anemia may occur (usually grades 1 and 2) with osimertinib.

Cardiomyopathy (cardiac failure, congestive heart failure, pulmonary edema, decreased ejection fraction, or stress cardiomyopathy) has been observed; some events were fatal. In patients who had baseline and at least one follow up assessment, a left ventricular ejection fraction (LVEF) decline of ≥10% and a drop to below 50% was noted. Assess LVEF prior to treatment, while on treatment in patients with cardiac risk factors, and in patients who develop cardiac signs/symptoms during treatment. Permanently discontinue for symptomatic heart failure or persistent, asymptomatic left ventricular dysfunction that does not resolve within 4 weeks. Prolongation of the QTc interval may occur; QTc >500 msec and an increase from baseline of >60 msec have been reported, although no QTc-related arrhythmias have been reported. Patients with a baseline QTc of ≥470 were excluded from clinical trials. Monitor ECG and electrolytes periodically in patients with a history of congenital long QTc syndrome, heart failure, electrolyte abnormalities, and/or those taking concurrent medications known to prolong the QTc interval. Permanently discontinue in patients who develop QTc interval prolongation with signs/symptoms of life-threatening arrhythmia.

Skin reactions, including rash, dry skin, and itching may occur. Nail toxicity may also occur.

Osimertinib may impair fertility; effects may be reversible in females.

Diarrhea (usually grades 1 and 2) was observed in almost half the patients receiving osimertinib.

Keratitis has been reported (rarely) in clinical trials. Promptly refer patients for ophthalmologic evaluation if signs/symptoms of keratitis (eye inflammation, lacrimation, light sensitivity, blurred vision, eye pain and/or red eye) develop.

Interstitial lung disease (ILD) and pneumonitis was observed in clinical studies; some events were fatal. Withhold treatment with worsening respiratory symptoms (dyspnea, cough, fever) which may be indicative of ILD; permanently discontinue if ILD is confirmed. Concurrent drug therapy issues:

Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Other warnings/precautions:

Confirm the presence of a T790M epidermal growth factor receptor (EGFR) mutation in tumor sample or plasma specimen prior to treatment initiation. Mutation status should be determined from tumor sample; if tumor was not biopsied, a plasma sample may be used. Circulating tumor cells from plasma sample may be used as a surrogate marker for detection of T790M in tumor tissue (Remon 2017). If mutation is not detected in plasma sample, re-evaluate the feasibility of tumor biopsy for tissue testing. Information on diagnostic tests approved for detection of T790M mutations may be found at www.fda.gov/companiondiagnostics.