datroway

Important safety information

Interstitial Lung Disease (ILD) and Pneumonitis: DATROWAY can cause severe and fatal cases of ILD/pneumonitis. Monitor for new or worsening signs and symptoms of ILD/pneumonitis. If ILD/pneumonitis is suspected, withhold DATROWAY and initiate corticosteroids. Permanently discontinue DATROWAY in patients with confirmed Grade 2 or higher ILD/pneumonitis. ( 5.1 ) Ocular Adverse Reactions: DATROWAY can cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision. Monitor patients for ocular adverse reactions during treatment with DATROWAY. Advise patients to use preservative-free lubricating eye drops and to avoid using contact lenses during treatment with DATROWAY. Withhold, reduce the dose, or permanently discontinue DATROWAY based on the severity of ocular adverse reactions. Refer patients to an eye care professional for any new or worsening ocular signs and symptoms. ( 2.3 , 2.4 , 5.2 ) Stomatitis/Oral Mucositis: DATROWAY can cause stomatitis, including mouth ulcers and oral mucositis. Advise patients to use a steroid-containing mouthwash when starting treatment and to hold ice chips or ice water in mouth during the infusion of DATROWAY. Withhold, reduce the dose, or permanently discontinue DATROWAY based on severity. ( 2.3 , 2.4 , 5.3 ) Embryo-Fetal Toxicity : DATROWAY can cause fetal harm. Advise patients of potential risk to a fetus and to use effective contraception. ( 5.4 , 8.1 , 8.3 ) 5.1 Interstitial Lung Disease/Pneumonitis DATROWAY can cause severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis. Locally Advanced or Metastatic NSCLC In the pooled safety population of 484 patients with NSCLC from TROPION-Lung01, TROPION-Lung05, and TROPION-PanTumor01 [see Adverse Reactions (6.1) ], ILD/pneumonitis occurred in 7% of patients treated with DATROWAY, including 0.6% of patients with Grade 3 and 0.4% with Grade 4. There were 8 (1.7%) fatal cases. The median time to first onset for ILD was 1.4 months (range: 0.2 months to 9 months). Eleven patients (2.3%) had DATROWAY withheld and 20 patients (4.1%) permanently discontinued DATROWAY due to ILD/pneumonitis. Systemic corticosteroids were required in 79% (26/33) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 45% of patients. Unresectable or Metastatic Breast Cancer In the pooled safety population of 841 patients with breast cancer from TROPION-Breast01, TROPION-Breast02, TROPION-PanTumor01 and TROPION-PanTumor02 [see Adverse Reactions (6.1) ], ILD/pneumonitis occurred in 3.0% of patients treated with DATROWAY, including 0.4% of patients with Grade 3. There were two fatal cases (0.2%). The median time to first onset for ILD was 5.3 months (range: 1.1 months to 19.3 months) and with a median duration of 1.2 months (range: 0.3 to 5.2). Eight patients (1.0%) had DATROWAY withheld and 10 patients (1.2%) permanently discontinued DATROWAY due to ILD/pneumonitis. Systemic corticosteroids were required in 64% (16/25) of patients with ILD/pneumonitis. ILD/pneumonitis resolved in 40% of patients. Patients were excluded from clinical studies for a history of ILD/pneumonitis requiring treatment with steroids or for ongoing ILD/pneumonitis. Monitor patients for new or worsening respiratory symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever) during treatment with DATROWAY. For asymptomatic (Grade 1) ILD/pneumonitis, consider corticosteroid treatment (e.g., ≥0.5 mg/kg/day prednisolone or equivalent). For symptomatic ILD/pneumonitis (Grade 2 or greater), promptly initiate systemic corticosteroid treatment (e.g., ≥1 mg/kg/day prednisolone or equivalent) and continue for at least 14 days followed by gradual taper for at least 4 weeks. Withhold DATROWAY in patients with suspected ILD/pneumonitis and permanently discontinue DATROWAY if ≥Grade 2 ILD/pneumonitis is confirmed [see Dosage and Administration (2.4) ]. 5.2 Ocular Adverse Reactions DATROWAY can cause ocular adverse reactions including dry eye, keratitis, blepharitis, meibomian gland dysfunction, increased lacrimation, conjunctivitis, and blurred vision. In the pooled safety population [see Adverse Reactions (6.1) ] , ocular adverse reactions occurred in 38% of patients treated with DATROWAY. Forty-two patients (3.1%) experienced Grade 3 ocular adverse reactions, which included keratitis and dry eye, and four patients (0.3%) experienced a Grade 4 ocular adverse reaction of keratitis, corneal epithelium defect, corneal lesion, and conjunctival hemorrhage. The most common (≥5%) ocular adverse reactions were dry eye (18%), keratitis (16%), increased lacrimation (6%), and conjunctivitis (5%). The median time to first onset for ocular adverse reactions was 2.3 months (range: 0.03 months to 30 months) and with a median duration of 2.3 months (range: 0.03 to 19.5). Of the patients who experienced ocular adverse reactions, 39% had complete resolution, and 8% had partial improvement (defined as a decrease in severity by one or more grades from the worst grade at last follow up). Ocular adverse reactions led to dosage interruption in 4.3% of patients, dosage reductions in 2.8% of patients, and permanent discontinuation of DATROWAY in 0.9% of patients. Patients with clinically significant corneal disease were excluded from clinical studies. Advise patients to use preservative-free lubricant eye drops at least four times daily and as needed for prophylaxis. Advise patients to avoid use of contact lenses unless directed by an eye care professional [see Dosage and Administration (2.3) ] . Refer patients to an eye care professional for an ophthalmic exam including visual acuity testing, slit lamp examination (with fluorescein staining), intraocular pressure, and fundoscopy at treatment initiation, at end of treatment, and as clinically indicated. While on treatment, conduct visual acuity testing and slit lamp examination every 3 cycles. Promptly refer patients to an eye care professional for any new or worsening ocular adverse reactions. Monitor patients for ocular adverse reactions during treatment with DATROWAY, and if diagnosis is confirmed, withhold, reduce the dose, or permanently discontinue DATROWAY based on severity [see Dosage and Administration (2.4) ] . 5.3 Stomatitis DATROWAY can cause stomatitis, including mouth ulcers and oral mucositis. In the pooled safety population [see Adverse Reactions (6.1) ], stomatitis occurred in 63% of patients treated with DATROWAY, including 8% of patients with Grade 3 events and one patient with a Grade 4 reaction. The median time to first onset of stomatitis was 0.5 months (range: 0.03 months to 19.8 months) and with a median duration of 1.1 months (range: 0.03 to 33.2). Stomatitis led to dosage interruption in 5% of patients, dosage reductions in 11% of patients, and permanent discontinuation of DATROWAY in 0.4% of patients. In patients who received DATROWAY in TROPION-Breast01 and TROPION-Breast02, 39% and 51% respectively used a mouthwash containing corticosteroid for management or prophylaxis of stomatitis/oral mucositis at any time during the treatment. Advise patients to use a steroid-containing mouthwash for prophylaxis and treatment of stomatitis. Instruct the patient to hold ice chips or ice water in the mouth throughout the infusion of DATROWAY. Monitor patients for signs and symptoms of stomatitis. If stomatitis occurs, increase the frequency of mouthwash and administer other topical treatments as clinically indicated. Based on the severity of the adverse reaction, withhold, reduce the dose, or permanently discontinue DATROWAY [see Dosage and Administration (2.4) ]. 5.4 Embryo-Fetal Toxicity Based on its mechanism of action, DATROWAY can cause embryo-fetal harm when administered to a pregnant woman because the topoisomerase inhibitor component of DATROWAY, DXd [see Description (11) ] , is genotoxic and affects actively dividing cells [see Use in Specific…