Osimertinib requires careful monitoring because rare or serious adverse reactions can occur.
Interstitial lung disease and pneumonitis
Osimertinib can cause ILD/pneumonitis, including fatal cases. The U.S. label reports ILD/pneumonitis in 4% of patients receiving monotherapy without recent definitive chemoradiation, with 0.4% fatal cases.
New or worsening cough, shortness of breath, fever or other respiratory changes should be reported promptly.
QTc prolongation
Osimertinib can prolong the QTc interval. Patients with risk factors for QT prolongation or those taking other QT-prolonging medicines may require ECG and electrolyte monitoring.
Cardiomyopathy
Cardiomyopathy is another recognized risk. The U.S. label reports cardiomyopathy in 3.8% of patients and recommends cardiac monitoring, including LVEF assessment, for patients with cardiac risk factors.
Eye toxicity
Keratitis can occur. Eye pain, redness, excessive tearing, sensitivity to light or visual changes should be evaluated promptly.
Severe skin reactions
Erythema multiforme major, Stevens-Johnson syndrome and toxic epidermal necrolysis are serious skin reactions associated with osimertinib. Treatment should be withheld when these conditions are suspected and permanently discontinued if confirmed under U.S. labeling.
Aplastic anemia
Aplastic anemia is a rare but serious bone-marrow toxicity. The U.S. label recommends withholding treatment when suspected and permanent discontinuation if confirmed.
Hepatitis B reactivation
In 2025, the EMA’s PRAC issued updated product-information wording regarding hepatitis B virus reactivation with osimertinib. Patients with evidence of positive HBV serology may require monitoring for clinical and laboratory evidence of reactivation.
Pregnancy
Osimertinib can cause fetal harm. The U.S. label advises females of reproductive potential to use effective contraception during treatment and for six weeks after the final dose, and males with female partners of reproductive potential to use effective contraception during treatment and for four months afterward.
Breastfeeding
The U.S. prescribing information advises against breastfeeding during treatment with osimertinib because of the potential for serious adverse reactions in a breastfed child.
Drug interactions
Strong CYP3A4 inducers can reduce osimertinib exposure and should generally be avoided. Medicines that prolong QT can also increase clinical concern about cardiac effects.
Patients should provide the healthcare team with a complete list of prescription medicines, non-prescription medicines, supplements and herbal products.
Contraindications
The U.S. prescribing information lists no formal contraindications. This does not mean the medicine is appropriate for every person. Individual risk assessment remains essential.