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Active ingredient: Tacrine - Brands, Medical Use, Clinical Data

Brands, Medical Use, Clinical Data

Drug Category

  • Cholinesterase Inhibitors
  • Nootropic Agents
  • Parasympathomimetics

Dosage Forms

  • Not Available

Brands / Synonyms

Cognex; Romotal; Tetrahydroaminacrine; Tetrahydroaminoacridine; Tetrahydroaminocrin; Tetrahydroaminocrine ; THA

Indications

For the treatment of mild to moderate dementia of the Alzheimer's type.

Pharmacology

Tacrine is a parasympathomimetic, specifically, a reversible cholinesterase inhibitor. Tacrine is indicated for the treatment of mild to moderate dementia of the Alzheimer's type. Tacrine is postulated to exert its therapeutic effect by enhancing cholinergic function. This is accomplished by increasing the concentration of acetylcholine through reversible inhibition of its hydrolysis by acetylcholinesterase. If this proposed mechanism of action is correct, tacrine's effect may lessen as the disease process advances and fewer cholinergic neurons remain functionally intact. There is no evidence that tacrine alters the course of the underlying dementing process.

Mechanism of Action

Tacrine acts by elevating acetylcholine concentrations in the cerebral cortex by slowing the degradation of acetylcholine released by still intact cholinergic neurons. It does so by reversibly binding acetylcholinesterase.

Absorption

Tacrine is rapidly absorbed. Absolute bioavailability of tacrine is approximately 17 ± 13%.

Toxicity

Not Available

Biotrnasformation / Drug Metabolism

Hepatic. Cytochrome P450 1A2 is the principal isozyme involved in tacrine metabolism. The major metabolite, 1-hydroxy-tacrine (velnacrine), has central cholinergic activity.

Contraindications

Cognex® is contraindicated in patients with known hypersensitivity to tacrine or acridine derivatives.

Cognex® is contraindicated in patients previously treated with Cognex® who developed treatment-associated jaundice: a serum bilirubin >3 mg/dL; and/or those exhibiting clinical signs or symptoms of hypersensitivity (eg, rash or fever) in association with ALT/SGPT elevations.

Drug Interactions

Drug-Drug Interactions

Possible metabolic basis for interactions: Tacrine is primarily eliminated by hepatic metabolism via cytochrome P450 drug metabolizing enzymes. Drug-drug interactions may occur when Cognex is given concurrently with agents such as theophylline that undergo extensive metabolism via cytochrome P450 IA2.

Theophylline. Coadministration of tacrine with theophylline increased theophylline elimination half-life and average plasma theophylline concentrations by approximately 2-fold. Therefore, monitoring of plasma theophylline concentrations and appropriate reduction of theophylline dose are recommended in patients receiving tacrine and theophylline concurrently. The effect of theophylline on tacrine pharmacokinetics has not been assessed.

Cimetidine. Cimetidine increased the Cmax and AUC of tacrine by approximately 54% and 64%, respectively.

Anticholinergics. Because of its mechanism of action, Cognex has the potential to interfere with the activity of anticholinergic medications.

Cholinomimetics and Cholinesterase Inhibitors. A synergistic effect is expected when Cognex is given concurrently with succinylcholine, cholinesterase inhibitors, or cholinergic agonists such as bethanechol.

Fluvoxamine. In a study of 13 healthy, male volunteers, a single 40 mg dose of tacrine added to fluvoxamine 100 mg/day administered at steady-state was associated with five- and eight-fold increases in tacrine Cmax and AUC, respectively, compared to the administration of tacrine alone. Five subjects experienced nausea, vomiting, sweating, and diarrhea following coadministration, consistent with the cholinergic effects of tacrine.

Other Interactions. Rate and extent of tacrine absorption were not influenced by the coadministration of an antacid containing magnesium and aluminum. Tacrine had no major effect on digoxin or diazepam pharmacokinetics or the anticoagulant activity of warfarin.

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