Drug Interactions between fluconazole and sirolimus protein-bound

Grapefruit juice may increase the blood levels of sirolimus protein-bound. However, this has not been studied, and it is not known to what extent grapefruit juice may interact with sirolimus protein-bound. High blood levels of sirolimus protein-bound can increase side effects such as mouth sores and inflammation, nausea, diarrhea, vomiting, abdominal pain, decreased appetite, increased blood sugar, rash, hair loss, lung or breathing problems, 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. The manufacturer recommends avoiding grapefruit and grapefruit juice during treatment with sirolimus protein-bound. Talk to your doctor if you have any questions or concerns. 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.

The use of fluconazole has been rarely associated with hepatotoxicity. Reversible idiosyncratic hepatitis, cholestasis and fatal fulminant hepatic failure have been reported, the latter occurring primarily in patients with serious underlying medical conditions and taking multiple concomitant medications. Liver function tests should be performed periodically in patients with preexisting hepatic abnormalities, particularly during prolonged therapy. Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.

Some azole antifungals have been associated with prolongation of the QT interval on the ECG. Rare cases of QT prolongation and torsade de pointes have been reported during postmarketing experience; such reports usually involved seriously ill patients with multiple confounding risk factors, such as structural heart disease, electrolyte abnormalities, and concomitant medications. These drugs should be administered with caution to patients with potentially proarrhythmic conditions, such as congenital/acquired QT prolongation, cardiomyopathy (especially when heart failure is present), sinus bradycardia, and existing symptomatic arrhythmias. Concomitant use with other medications that have potential to increase the risk of cardiotoxicity should be avoided.

Sirolimus albumin-bound can cause hyperglycemia. Fasting serum glucose should be monitored prior to starting treatment, and periodically during treatment in diabetic patients. Caution is advised.

Fluconazole is substantially removed by hemodialysis. Plasma levels of fluconazole has been shown to reduce by 50% following 3 hours of dialysis. Fluconazole should be administered after hemodialysis.

The use of sirolimus albumin-bound should be avoided in patients with severe hepatic impairment. Closely monitor patients with mild and moderate impairment for increased liver toxicity. Dosage should be reduced in these patients.

Fluconazole is primarily eliminated by the kidney. Patients with renal impairment may be at greater risk for adverse effects from fluconazole due to decreased drug clearance. Dosage adjustments are recommended for patients with moderate to severe renal impairment (CrCl <= 50 mL/min) receiving multiple doses of the drug.

The effect of severe renal impairment on the pharmacokinetics of sirolimus albumin-bound is unknown. Caution and close monitoring is advised if using in these patients.

Immunizations during treatment with sirolimus albumin-bound may be ineffective. Immunization with live vaccines is not recommended during treatment and close contact with those who have received live vaccines should be avoided. Required immunizations should be updated according to immunization guidelines prior to initiating treatment, if possible. The interval between live vaccinations and treatment initiation should be in accordance with current vaccination guidelines for patients on immunosuppressive therapies.