Drug Interactions between fluconazole and tacrine

The use of cholinesterase inhibitors has been associated with a constriction of coronary arteries. Therapy with cholinesterase inhibitors should be administered cautiously in patients with coronary artery disease.

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 Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.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 tacrine is contraindicated in patients with a history of tacrine-induced jaundice confirmed by elevated total bilirubin greater than 3.0 mg/dl. Elevations in liver function tests (LFTs) have been reported in as many as 50% of patients receiving tacrine. Twenty-five percent of patients may experience a 3 fold rise in ALT and 7% a 10 fold rise in ALT. LFTs should be monitored prior to initiation of tacrine therapy is initiated and when dosages are altered. Tacrine undergoes extensive first-pass metabolism by the liver (CYP450-1A2) to multiple forms. The metabolic and therapeutic activity of tacrine can be altered in patients with compromised hepatic function and therapy with tacrine should be administered cautiously in these patients.

Cholinesterase inhibitors should be used with caution in patients with parkinsonism. Some of these drugs might be contraindicated in these patients (refer to specific prescribing information). Symptoms of Parkinson's disease may be exacerbated with the increase in cholinergic activity. Caregivers and patients should be advised.

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.

Many of the manifestations of hyperthyroidism may be exacerbated by increased levels of acetylcholine produced by cholinesterase inhibitors. Therapy with cholinesterase inhibitors should be administered cautiously to patients with hyperthyroidism. Monitoring of thyroid levels is recommended.

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.