CanesOral and Rapamune

In the database of official manuals used in the service creation an interaction registered by statistical results of studies was found, which can either lead to negative consequences for the patient health or strengthen a mutual positive effect. A doctor should be consulted to address the issue of joint drug administration.

Fluconazole may significantly increase the blood levels of sirolimus. This may increase the risk of serious side effects such as infections; lymphoma and other cancers; diabetes; kidney problems; various lung disorders; high blood pressure; high cholesterol and triglycerides; swelling of the face, eyes or mouth; and water retention, especially in the hands, feet, and various tissues such as the sac around the heart or lungs. Talk to your doctor if you have any questions or concerns. Your doctor may be able to prescribe alternatives that do not interact, or you may need a dose adjustment or more frequent monitoring to safely use both medications. Contact your doctor immediately if you develop signs and symptoms of infection such as fever, chills, diarrhea, sore throat, muscle aches, shortness of breath, blood in phlegm, weight loss, red or inflamed skin, body sores, and pain or burning during urination. You should also seek medical attention if you experience nausea, vomiting, loss of appetite, increased or decreased urination, sudden weight gain or weight loss, fluid retention, swelling, shortness of breath, muscle cramps, tiredness, weakness, dizziness, confusion, and irregular heart rhythm, as these may be signs and symptoms of kidney problems. 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.

MONITOR CLOSELY: Coadministration with fluconazole may significantly increase the oral bioavailability of sirolimus. The proposed mechanism is fluconazole inhibition of sirolimus metabolism via intestinal CYP450 3A4. There have been case reports of markedly increased sirolimus blood concentrations following the addition of fluconazole. In one patient with diabetic nephropathy receiving sirolimus following a kidney transplant, trough sirolimus blood concentration increased from approximately 10 ng/mL to 22.8 ng/mL four days after starting fluconazole 200 mg/day for esophageal candidiasis. This increase occurred despite a dosage reduction of sirolimus from 4 mg/day to 3 mg/day at the time fluconazole was initiated in anticipation of the interaction. Sirolimus dosage was further reduced to 2 mg/day on the fifth day of fluconazole therapy, whereupon the trough concentration continued to rise and reached a peak of 35.5 ng/mL before falling to 26.8 ng/mL on day 8 of fluconazole therapy. However, the patient died shortly thereafter from multi-organ failure following development of cardiorespiratory arrest associated with hyperkalemia. In another renal transplant patient receiving sirolimus 2 mg/day, sirolimus predose blood levels increased from 10.26 ng/mL to 48.44 ng/mL after approximately 3 weeks of fluconazole therapy (100 mg/day IV for 10 days, followed by 200 mg/day orally). Fluconazole dosage was reduced to 100 mg/day and sirolimus dosage to 1.5 mg/day, which led to a predose sirolimus blood concentration of 21.26 ng/mL eight days later.

MANAGEMENT: Extreme caution is advised if sirolimus is prescribed with fluconazole. Sirolimus blood levels should be closely monitored and the dosage adjusted accordingly, particularly following initiation, discontinuation, or change of dosage of fluconazole in patients who are stabilized on their antirejection regimen. Patients should be monitored for the development of sirolimus toxicity such as fluid retention, hypertension, hyperlipidemia, renal impairment, proteinuria, interstitial lung disease, infections, and various types of malignancies including lymphoma and skin cancer.

CanesOral

Generic Name: fluconazole

Brand name: Diflucan

Synonyms: Fluconazole

What is CanesOral?

Rapamune

Generic Name: sirolimus

Brand name: Rapamune

Synonyms: n.a.

What is Rapamune?