Precautions for Osimertinib Mesylate Tablets/Tagrisso

In the clinical studies of Osimertinib/Tagressa, warnings and precautions such as interstitial lung disease/pneumonitis, QTc interval prolongation, cardiomyopathy, keratitis, allergic reactions, cutaneous vasculitis, aplastic anemia, embryo-fetal toxicity, etc. have emerged. In response to these possible risks, corresponding preventive and response measures need to be taken, such as discontinuing the drug and resuming it at a reduced dose after recovery, or permanently discontinuing it depending on the severity.

1. Interstitial lung disease (ILD)/pneumonia: If the patient's respiratory symptoms worsen during medication, such as dyspnea, cough and fever, he should stop taking osimertinib immediately and seek medical attention promptly to check whether he has ILD. Once ILD/pneumonitis is confirmed, patients should permanently discontinue osimertinib to avoid further disease progression.

2. QTc interval prolongation: Patients receiving osimertinib may experience prolongation of the heart rate corrected QT (QTc) interval. Although no serious cases of QTc-related arrhythmias have been reported, vigilance is still required. In clinical trials, patients with baseline QTc ≥470 msec were not included. Patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or who are taking drugs known to prolong the QTc interval should undergo regular electrocardiogram and electrolyte monitoring to ensure patient safety. If QTc prolongation occurs along with signs/symptoms of life-threatening arrhythmias, patients should permanently discontinue osimertinib.

3. Cardiomyopathy: defined as heart failure, chronic heart failure, congestive heart failure, pulmonary edema, or reduced ejection fraction (LVEF); for patients who will receive osimertinib monotherapy, patients with cardiac risk factors should undergo cardiac monitoring, including assessment of left ventricular ejection fraction (LVEF) at baseline and during treatment. For patients who will receive osimertinib in combination with pemetrexed and platinum-based chemotherapy, all patients should undergo cardiac monitoring, including assessment of LVEF at baseline and during treatment. For patients who develop relevant cardiac signs or symptoms during treatment, LVEF should also be evaluated promptly. Osimertinib should be permanently discontinued in patients with symptomatic congestive heart failure.

4. Keratitis: If the patient develops signs and symptoms suggestive of keratitis, such as eye inflammation, tearing, light sensitivity, blurred vision, eye pain, and/or red eyes, please see an ophthalmologist immediately.

5. Allergic reactions: Clinical studies have reported cases associated with severe erythema multiforme (EMM), Stevens-Johnson syndrome (SJS), and toxic epidermal necrolysis (TEN). If these severe allergic reactions are suspected, osimertinib should be discontinued immediately and medical attention should be sought. If EMM, SJS, or TEN is diagnosed, osimertinib should be permanently discontinued.

6. Cutaneous vasculitis: Postmarketing cases of cutaneous vasculitis, including leukocytoclastic vasculitis, urticarial vasculitis, and vasculitis, have been reported in patients receiving osimertinib.IgA vasculitis. If a patient is suspected of having cutaneous vasculitis, osimertinib should be discontinued and systemic involvement evaluated, and consultation with a dermatologist should be considered.

7. Aplastic anemia (AA): Inform patients of the signs and symptoms of aplastic anemia, including but not limited to new or persistent fever, bruising, bleeding, and paleness. If aplastic anemia is suspected, osimertinib should be discontinued and hematology consultation should be obtained. If confirmed, permanently discontinue osimertinib. Perform a complete blood count and differential count before starting medication, periodically throughout treatment, and more frequently if needed.

8. Embryo-Fetal toxicity: According to animal research data and its mechanism of action, osimertinib taken by pregnant women can cause harm to the fetus. In animal reproduction studies, administration of osimertinib during early development at doses 1.5 times the recommended clinical dose resulted in postimplantation fetal loss. When males were treated prior to mating with untreated females, the increase in plasma exposure to preimplantation embryo loss was approximately 0.5 times the recommended dose of 80 mg once daily.

Therefore, verify the pregnancy status of females of reproductive potential before initiating osimertinib. Inform pregnant women of potential risks to the fetus. It is recommended that women of childbearing potential use effective contraception during treatment and for 6 weeks after the last dose; men with female partners are advised to use effective contraception for 4 months after the last dose.

In summary, when using Osimertinib Mesylate Tablets/Tagrisso, you need to pay attention to many aspects and take corresponding preventive and countermeasures to ensure patient safety and therapeutic effect.