Drug Interactions between troleandomycin and zanubrutinib

Grapefruit juice and Seville orange juice can increase the blood levels of zanubrutinib. This may increase side effects such as rash, diarrhea, constipation, cough, hemorrhage, development of other cancers, abnormal heart rhythm, and impaired bone marrow function resulting in low numbers of different types of blood cells. You may also be more likely to develop anemia, bleeding problems, or infections due to low blood cell counts. You should avoid the consumption of grapefruit, grapefruit juice, Seville oranges (a citrus relative of the grapefruit), and Seville orange juice during treatment with zanubrutinib. You may need a dose adjustment, interruption, or more frequent monitoring to safely use both medications. Be sure to take the medication at approximately the same time(s) every day to maintain consistent blood levels and effects. Talk to your doctor or pharmacist if you have questions on how to take this or other medications you are prescribed. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.

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.

Fatal and serious hemorrhage have occurred in patients with hematological malignancies treated with zanubrutinib monotherapy. Bleeding has occurred in patients with and without concomitant antiplatelet or anticoagulation therapy. Special care should be taken when this agent is coadministered with antiplatelet or anticoagulant medications as coadministration may further increase the risk of hemorrhage. It is recommended to monitor for signs/symptoms of bleeding and to discontinue zanubrutinib if intracranial hemorrhage of any grade occurs. The benefit-risk of withholding zanubrutinib for 3 to 7 days before and after surgery (depending on the type of surgery and the risk of bleeding) should be considered.

Cytopenias (including neutropenia, thrombocytopenia, and anemia [based on laboratory measurements]) were reported in patients treated with zanubrutinib monotherapy. Care should be taken when using this agent in patients with hematological abnormalities. It is recommended to monitor complete blood counts during therapy and interrupt treatment, reduce the dose, or discontinue zanubrutinib as warranted. Growth factor or transfusions should be used as treatment, as needed.

Serious cardiac arrhythmias have been reported with zanubrutinib. Atrial fibrillation and atrial flutter have occurred in patients treated with zanubrutinib monotherapy. Care should be exercised when using this agent in patients with cardiac risk factors, hypertension, and acute infections as they may be at increased risk of cardiac arrhythmias. It is recommended to monitor for signs/symptoms of cardiac arrhythmias, manage appropriately, and consider the risks and benefits of continued treatment with zanubrutinib.

The effect of dialysis on zanubrutinib pharmacokinetics is unknown. Patients on dialysis should be monitored for zanubrutinib adverse reactions. No dosage modification is recommended in patients with mild, moderate, or severe renal dysfunction (CrCl at least 15 mL/min, estimated by Cockroft-Gault).

Serious cardiac arrhythmias have been reported with zanubrutinib. Atrial fibrillation and atrial flutter have occurred in patients treated with zanubrutinib monotherapy. Care should be exercised when using this agent in patients with cardiac risk factors, hypertension, and acute infections as they may be at increased risk of cardiac arrhythmias. It is recommended to monitor for signs/symptoms of cardiac arrhythmias, manage appropriately, and consider the risks and benefits of continued treatment with zanubrutinib.

Serious cardiac arrhythmias have been reported with zanubrutinib. Atrial fibrillation and atrial flutter have occurred in patients treated with zanubrutinib monotherapy. Care should be exercised when using this agent in patients with cardiac risk factors, hypertension, and acute infections as they may be at increased risk of cardiac arrhythmias. It is recommended to monitor for signs/symptoms of cardiac arrhythmias, manage appropriately, and consider the risks and benefits of continued treatment with zanubrutinib.

Fatal and serious infections (including bacterial, viral, or fungal infections) and opportunistic infections have occurred in patients with hematological malignancies treated with zanubrutinib monotherapy. Infections due to hepatitis B virus reactivation have occurred. Prophylaxis for herpes simplex virus, Pneumocystis jirovecii pneumonia, and other infections according to standard of care should be considered in patients who are at increased risk for infections. Patients should be monitored and evaluated for fever or other signs/symptoms of infection and treated appropriately.

The safety of zanubrutinib has not been evaluated in patients with severe liver dysfunction (Child-Pugh C); dosage modification of zanubrutinib is recommended in these patients. The recommended dosage for patients with severe liver dysfunction is 80 mg orally twice a day. No dosage modification is recommended in patients with mild to moderate liver dysfunction (Child-Pugh A and B). Patients with liver dysfunction should be monitored for zanubrutinib adverse reactions.

The effect of dialysis on zanubrutinib pharmacokinetics is unknown. Patients on dialysis should be monitored for zanubrutinib adverse reactions. No dosage modification is recommended in patients with mild, moderate, or severe renal dysfunction (CrCl at least 15 mL/min, estimated by Cockroft-Gault).