Drug Interactions between sirolimus and troleandomycin

Grapefruit and grapefruit juice may interact with sirolimus and could lead to potentially dangerous effects. Avoid eating grapefruit or drinking grapefruit juice while you are taking sirolimus. Also, you should preferably take sirolimus at least one hour before eating. If you do take it with food, you should take it each time with food to avoid changes in sirolimus levels. The oral liquid form of sirolimus must be mixed with water or orange juice only. Do not use grapefruit juice to mix this medication.

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.

Immunosuppressive agents may increase the risk of progressive multifocal leukoencephalopathy (PML). Certain agents are contraindicated in patients who have or have had PML. Patients receiving chronic immunosuppressant or immunomodulatory therapy or who have systemic medical conditions resulting in significantly compromised immune system function should not be treated with these agents. Health care professionals should monitor patients for any new sign or symptom suggestive of PML. Therapy dosing should be withheld immediately and an appropriate diagnostic evaluation should be performed at the first sign or symptom suggestive of PML.

Serious and sometimes fatal infections have been reported in patients receiving immunosuppressive agents. Patients receiving immunosuppressants are at increased risk of developing bacterial, viral, fungal, and protozoal infections, and new or reactivated viral infections including opportunistic infections. Caution should be exercised when considering their use in patients with severe or chronic infections. It is recommended to interrupt therapy in patients who develop a new infection while undergoing treatment and to monitor these patients closely for any sign or symptom indicative of infection.

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.

Sirolimus has been associated with the development of angioedema. Patients at risk of developing angioedema and those using concomitant drugs known to cause angioedema, such as ACE inhibitors, may be at increased risk of developing angioedema. Care should be taken when prescribing this agent in patients at risk and close monitoring is recommended.

The use of sirolimus may increase serum cholesterol and triglycerides. Care should be taken when prescribing this agent to hyperlipidemic patients. It is recommended to assess the risk/benefit carefully when considering this agent in patients with established hyperlipidemia before initiating therapy. It is recommended to monitor patients regularly for elevated lipids.

Sirolimus is extensively metabolized in the intestinal wall and liver and undergoes counter-transport from enterocytes of the small intestine into the gut lumen. The maintenance dose of sirolimus should be reduced by approximately one third in patients with mild or moderate hepatic impairment and by approximately one half in patients with severe hepatic impairment. It is not necessary to modify the sirolimus loading dose. Care should be taken when prescribing this agent to patients with liver impairment and close monitoring is recommended.

The use of sirolimus in lung transplant patients is not recommended as the safety and efficacy of this agent as immunosuppressive therapy has not been established in these patients. Cases of bronchial anastomotic dehiscence, most fatal, have been reported in de novo lung transplant patients when sirolimus has been used as part of an immunosuppressive regimen.

The use of sirolimus is not recommended in liver transplant patients as its safety and efficacy has not been established in these patients. The use of sirolimus has been associated with adverse outcomes in patients following liver transplantation, including excess mortality, graft loss and hepatic artery thrombosis.

Interstitial Lung Disease (ILD)/Pneumonitis, including pneumonitis, bronchiolitis obliterans organizing pneumonia, and pulmonary fibrosis, some fatal, with no identified infectious etiology have occurred with the use of sirolimus. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis and discontinue sirolimus and assess patients developing ILD or pneumonitis.

Renal function should be closely monitored during the co-administration of sirolimus with cyclosporine, because long-term administration of the combination has been associated with deterioration of renal function. It is recommended to adjust therapy regimen, including discontinuation of sirolimus and/or cyclosporine in patients with elevated or increasing serum creatinine levels. Caution should be exercised when using agents (e.g., aminoglycosides and amphotericin B) that are known to have a deleterious effect on renal function. Periodic monitoring of renal function is recommended, including quantitative monitoring of urinary protein excretion.