Drug Interactions between tolterodine and troleandomycin

Troleandomycin is primarily excreted by the liver and may accumulate in patients with impaired hepatic function. In addition, the use of troleandomycin has been associated with an allergic type of cholestatic hepatitis, particularly in patients receiving the drug for more than 2 weeks or given repeated courses. Therapy with troleandomycin should be administered cautiously in patients with liver and/or biliary disease. Liver function tests should be monitored during prolonged or repeated courses of therapy, and the drug discontinued if abnormalities develop.

Clostridioides difficile-associated diarrhea (CDAD), formerly pseudomembranous colitis, has been reported with almost all antibacterial drugs and may range from mild diarrhea to fatal colitis. The most common culprits include clindamycin and lincomycin. Antibacterial therapy alters the normal flora of the colon, leading to overgrowth of C difficile, whose toxins A and B contribute to CDAD development. Morbidity and mortality are increased with hypertoxin-producing strains of C difficile; these infections can be resistant to antimicrobial therapy and may require colectomy. CDAD must be considered in all patients who present with diarrhea after antibacterial use. Since CDAD has been reported to occur more than 2 months after antibacterial use, careful medical history is necessary. Therapy with broad-spectrum antibacterials and other agents with significant antibacterial activity should be administered cautiously in patients with history of gastrointestinal disease, particularly colitis; pseudomembranous colitis (generally characterized by severe, persistent diarrhea and severe abdominal cramps, and sometimes associated with the passage of blood and mucus), if it occurs, may be more severe in these patients and may be associated with flares in underlying disease activity. Antibacterial drugs not directed against C difficile may need to be stopped if CDAD is suspected or confirmed. Appropriate fluid and electrolyte management, protein supplementation, antibacterial treatment of C difficile, and surgical evaluation should be started as clinically indicated.

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.

Troleandomycin is primarily excreted by the liver and may accumulate in patients with impaired hepatic function. In addition, the use of troleandomycin has been associated with an allergic type of cholestatic hepatitis, particularly in patients receiving the drug for more than 2 weeks or given repeated courses. Therapy with troleandomycin should be administered cautiously in patients with liver and/or biliary disease. Liver function tests should be monitored during prolonged or repeated courses of therapy, and the drug discontinued if abnormalities develop.

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.

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.

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.

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.