Drug Interactions between taletrectinib and troleandomycin

You should avoid the consumption of foods or drinks containing grapefruit during treatment with taletrectinib. Grapefruit can raise the levels of taletrectinib in your body. This can affect the rhythm of your heart and cause other side effects. In addition, you should take taletrectinib on an empty stomach at about the same time each day, at least 2 hours before or 2 hours after food intake. Food can also raise the levels of taletrectinib in your body. You should seek immediate medical attention if you develop sudden dizziness, lightheadedness, fainting, shortness of breath, or fast or pounding heartbeats during treatment with taletrectinib. Talk to your doctor or pharmacist if you have any questions or concerns.

Troleandomycin is primarily excreted by the liver and may accumulate in patients with impaired hepatic function. In addition, the use of troleandomycin has been associated with an allergic type of cholestatic hepatitis, particularly in patients receiving the drug for more than 2 weeks or given repeated courses. Therapy with troleandomycin should be administered cautiously in patients with liver and/or biliary disease. Liver function tests should be monitored during prolonged or repeated courses of therapy, and the drug discontinued if abnormalities develop.

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

Troleandomycin is primarily excreted by the liver and may accumulate in patients with impaired hepatic function. In addition, the use of troleandomycin has been associated with an allergic type of cholestatic hepatitis, particularly in patients receiving the drug for more than 2 weeks or given repeated courses. Therapy with troleandomycin should be administered cautiously in patients with liver and/or biliary disease. Liver function tests should be monitored during prolonged or repeated courses of therapy, and the drug discontinued if abnormalities develop.

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 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 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.

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 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 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 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.