Drug Interactions between fluconazole and tolterodine

The use of tolterodine is contraindicated in patients with GI obstruction, ileus, or obstructive uropathy. Tolterodine exerts anticholinergic activity by competitive antagonism of muscarinic receptors.

The use of tolterodine is contraindicated in patients with uncontrolled angle-closure (narrow angle) glaucoma. Tolterodine exerts anticholinergic activity and can result in increased intraocular pressure and loss of accommodation.

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 Treatment should be withdrawn if persistent elevations or worsening of liver enzyme levels occur.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 tolterodine is contraindicated in patients with GI obstruction, ileus, or obstructive uropathy. Tolterodine exerts anticholinergic activity by competitive antagonism of muscarinic receptors.

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.

Tolterodine is associated with anticholinergic central nervous system (CNS) effects. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered. Tolterodine should be used with caution in patients with Parkinson's disease and in patients with preexisting dementia treated with cholinesterase inhibitors due to the risk of aggravation of symptoms.

Tolterodine is associated with anticholinergic central nervous system (CNS) effects. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered. Tolterodine should be used with caution in patients with Parkinson's disease and in patients with preexisting dementia treated with cholinesterase inhibitors due to the risk of aggravation of symptoms.

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.

Tolterodine undergoes biotransformation in the liver of extensive metabolizers to an active metabolite. Poor metabolizers have a greater concentration of active parent and less active metabolite, however the net activity of tolterodine is expected to be the same. The pharmacokinetic disposition of tolterodine can be significantly altered in patients with hepatic dysfunction. Therapy with tolterodine should be administered cautiously in patients with severe hepatic impairment and dosage should be reduced to no greater than 1 mg twice daily.

Tolterodine has been associated with QT prolongation. The effect on QT interval correlates with plasma concentration of tolterodine. Caution is recommended when prescribing this agent to patients with a known history of QT prolongation or to patients who are taking Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications.

Tolterodine acts as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors. Caution is recommended when using this agent in patients with myasthenia gravis, a disease characterized by decreased cholinergic activity at the neuromuscular junction.

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 renal elimination of tolterodine and active metabolite is limited and a prolonged half-life is not anticipated in patients with renal impairment. However, the pharmacokinetic disposition of tolterodine has not been evaluated in patients with renal impairment and it is recommended that tolterodine be administered cautiously in patients with compromised renal function.