Taletrectinib Disease Interactions

Taletrectinib can cause QTc interval prolongation, which can increase the risk for ventricular tachyarrhythmias (e.g., torsades de pointes) or sudden death. In patients with risk factors for QT prolongation such as long QT syndromes, clinically significant bradyarrhythmias, or severe/uncontrolled heart failure, the frequency of monitoring should be adjusted accordingly. Prior to therapy, monitor ECGs and electrolytes in all patients and then periodically as indicated.

Taletrectinib can increase the risk of skeletal fractures. In clinical studies, some fractures occurred in the setting of predisposing factors such as osteoporosis, bone metastasis, and age-related degenerative conditions. There are no data on the effects of taletrectinib on healing of known fractures and risk of future fractures. Promptly evaluate patients with signs/symptoms of fractures (e.g., pain, changes in mobility, deformity).

Taletrectinib can cause severe, life-threatening, or fatal interstitial lung disease (ILD) or pneumonitis. Monitor patients for new or worsening pulmonary symptoms indicative of ILD/pneumonitis. Immediately withhold therapy in patients with suspected ILD/pneumonitis; dose reduction or permanent discontinuation of taletrectinib may be required based on severity.

The effect of moderate liver dysfunction (total bilirubin greater than 1.5 to 3 x ULN with any AST) or severe liver dysfunction (total bilirubin greater than 3 x ULN with any AST) on the pharmacokinetics (PK) of taletrectinib is unknown. No clinically significant PK differences were observed based on mild liver dysfunction. Taletrectinib can cause hepatotoxicity, including drug-induced liver injury. Monitor liver function tests including ALT, AST, and total bilirubin at baseline and as recommended by the manufacturer.

The effect of dialysis or severe renal dysfunction (estimated GFR less than 30 mL/min) on the pharmacokinetics of taletrectinib is unknown. No clinically significant pharmacokinetic differences were observed based on mild or moderate renal dysfunction.