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Severe, life-threatening, and fatal interstitial lung disease (ILD) / pneumonitis can occur in patients treated with Pralsetinib. Pneumonitis occurred in 12% of patients who received Pralsetinib, including 3.3% with Grade 3-4, and 0.2% with fatal reactions.
Monitor for pulmonary symptoms indicative of ILD/pneumonitis. Withhold Pralsetinib and promptly investigate for ILD in any patient who presents with acute or worsening of respiratory symptoms which may be indicative of ILD (e.g., dyspnea, cough, and fever). Withhold, reduce dose or permanently discontinue Pralsetinib based on severity of confirmed ILD.
Hypertension occurred in 35% of patients, including Grade 3 hypertension in 18% of patients. Overall, 8% had their dose interrupted and 4.8% had their dose reduced for hypertension. Treatment-emergent hypertension was most commonly managed with anti-hypertension medications.
Do not initiate Pralsetinib in patients with uncontrolled hypertension. Optimize blood pressure prior to initiating Pralsetinib. Monitor blood pressure after 1 week, at least monthly thereafter and as clinically indicated. Initiate or adjust anti-hypertensive therapy as appropriate. Withhold,reduce dose, or permanently discontinue Pralsetinib based on the severity.
Serious hepatic adverse reactions occurred in 1.5% of patients treated with Pralsetinib. Increased AST occurred in 49% of patients, including Grade 3 or 4 in 7% and increased ALT occurred in 37% of patients, including Grade 3 or 4 in 4.8%. The median time to first onset for increased AST was 15 days (range: 5 days to 2.5 years) and for increased ALT was 24 days (range: 7 days to 3.7 years).
Monitor AST and ALT prior to initiating Pralsetinib, every 2 weeks during the first 3 months, then monthly thereafter and as clinically indicated. Withhold, reduce dose or permanently discontinue Pralsetinib based on severity.
Serious, including fatal, hemorrhagic events can occur with Pralsetinib. Grade ≥ 3 hemorrhagic events occurred in 4.1% of patients treated with Pralsetinib including one patient with a fatal hemorrhagic event.
Permanently discontinue Pralsetinib in patients with severe or life-threatening hemorrhage.
Cases of tumor lysis syndrome (TLS) have been reported in patients with medullary thyroid carcinoma receiving Pralsetinib. Patients may be at risk of TLS if they have rapidly growing tumors, a high tumor burden, renal dysfunction, or dehydration. Closely monitor patients at risk, consider appropriate prophylaxis including hydration, and treat as clinically indicated.
from FDA，2024.03
