Drug Interactions between fluconazole and naltrexone

Naltrexone may cause liver problems, and using it with other medications that can also affect the liver such as ethanol (alcohol) may increase that risk. You should avoid or limit the use of alcohol while being treated with these medications. Call your doctor immediately if you have fever, chills, joint pain or swelling, unusual bleeding or bruising, skin rash, itching, loss of appetite, fatigue, nausea, vomiting, abdominal pain, dark urine, pale stools, and/or yellowing of the skin or eyes, as these may be signs and symptoms of liver damage. Talk to your doctor or pharmacist 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 Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.

The use of naltrexone is contraindicated in patients with active hepatitis or hepatic failure. Naltrexone has caused direct hepatocellular injury when administered at doses less than or equal to 5 times the recommended once daily 50 mg dose. Therapy with naltrexone should be administered cautiously in patients with active hepatic disease. Clinical monitoring of transaminase levels prior to and during naltrexone therapy is recommended.

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.

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.

Opiate antagonists are metabolized by the liver (naltrexone to an active metabolite) and eliminated by the kidney. Hepatic and renal impairment may reduce the metabolism and clearance of opiate antagonists. Dosage adjustment for single dose administration is not necessary, however, repeated doses in patients with hepatic and/or renal dysfunction may require adjustment.

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.

Opiate antagonists are metabolized by the liver (naltrexone to an active metabolite) and eliminated by the kidney. Hepatic and renal impairment may reduce the metabolism and clearance of opiate antagonists. Dosage adjustment for single dose administration is not necessary, however, repeated doses in patients with hepatic and/or renal dysfunction may require adjustment.