Drug Interactions between troleandomycin and vincristine liposome

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.

The use of vincristine is contraindicated in patients with demyelinating conditions including Charcot-Marie-Tooth syndrome. Neurotoxicity associated with vincristine therapy is dose-related and frequently sequential. Sensorimotor (paresthesia, decreased deep- tendon reflex, ataxia, paralysis), autonomic (constipation and adynamic ileus), and CNS (mental status changes, seizures, coma) neurotoxicity have been reported. Patients with existing neuromuscular or neurologic diseases may be at increased risk for toxicity with vincristine therapy. Therapy with vincristine should be administered cautiously and dosage reduction considered in patients with neurologic dysfunction.

The use of vincristine is contraindicated in patients with demyelinating conditions including Charcot-Marie-Tooth syndrome. Neurotoxicity associated with vincristine therapy is dose-related and frequently sequential. Sensorimotor (paresthesia, decreased deep- tendon reflex, ataxia, paralysis), autonomic (constipation and adynamic ileus), and CNS (mental status changes, seizures, coma) neurotoxicity have been reported. Patients with existing neuromuscular or neurologic diseases may be at increased risk for toxicity with vincristine therapy. Therapy with vincristine should be administered cautiously and dosage reduction considered in patients with neurologic dysfunction.

Acute shortness of breath and bronchospasm, some severe and life-threatening, have been reported with the use of vinca alkaloids. These reactions were observed most often during combination therapy with mitomycin C, occurring within minutes to several hours after administration of the vinca alkaloid or up to 2 weeks following the mitomycin dose. Therapy with vinca alkaloids should be administered cautiously in patients with preexisting pulmonary dysfunction. Aggressive treatment may be necessary, including use of supplemental oxygen, bronchodilators, and/or corticosteroids. In patients who develop progressive dyspnea requiring chronic therapy, vinca alkaloid should not be readministered.

Vincristine induces dose-related myelosuppression. Leukopenia, thrombocytopenia, and anemia have been reported, however vincristine does not appear to have a consistent or significant effect on platelets or red blood cells. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Therapy with vincristine should be administered cautiously in patients with compromised bone marrow reserve. Monitor complete blood counts prior to each dose. If Grade 3 or 4 neutropenia, thrombocytopenia, or anemia develops, consider a dose modification or reduction as well as supportive care measures.

Vincristine can cause constipation. Ileus, bowel obstruction, and colonic pseudo-obstruction have occurred. When using this agent in people at risk of constipation, appropriate measures should be instituted to prevent such complications. A routine prophylactic regimen against constipation is recommended for all patients receiving vincristine.

Vincristine induces dose-related myelosuppression. Leukopenia, thrombocytopenia, and anemia have been reported, however vincristine does not appear to have a consistent or significant effect on platelets or red blood cells. Patients should be instructed to immediately report any signs or symptoms suggesting bone marrow suppression such as fever, sore throat, local infection, or bleeding. Therapy with vincristine should be administered cautiously in patients with compromised bone marrow reserve. Monitor complete blood counts prior to each dose. If Grade 3 or 4 neutropenia, thrombocytopenia, or anemia develops, consider a dose modification or reduction as well as supportive care measures.

Vincristine can cause constipation. Ileus, bowel obstruction, and colonic pseudo-obstruction have occurred. When using this agent in people at risk of constipation, appropriate measures should be instituted to prevent such complications. A routine prophylactic regimen against constipation is recommended for all patients receiving vincristine.

Vincristine induces mild, dose-related myelosuppression. The use of vincristine may be contraindicated in patients with known infectious diseases. All patients should be instructed to immediately report any signs or symptoms suggesting infection such as fever, sore throat, or local infection during therapy with vincristine. Clinical monitoring of hematopoetic function is recommended.

Vincristine is primarily metabolized by the liver. The influence of severe hepatic impairment on the safety and efficacy of vincristine has not been evaluated. Additionally, fatal liver toxicity and elevated levels of aspartate aminotransferase have occurred in clinical trials. Vincristine should be reduced or interrupted if there is evidence of hepatic toxicity. Therapy with vincristine should be administered cautiously and dosages reduced in patients with compromised hepatic function. Close clinical monitoring of hepatic function is recommended.