DrugLib.com — Drug Information Portal

Rx drug information, pharmaceutical research, clinical trials, news, and more

Cognex (Tacrine Hydrochloride) - Drug Interactions, Contraindications, Overdosage, etc



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 (see WARNINGS), 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.


As in any case of overdose, general supportive measures should be utilized. Overdosage with cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved.
Tertiary anticholinergics such as atropine may be used as an antidote for Cognex® overdosage.  Intravenous atropine sulfate titrated to effect is recommended: in adults, initial dose of 1.0 to 2.0 mg IV with subsequent doses based on clinical response. In children, the usual IM or IV dose is 0.05 mg/kg, repeated every 10-30 minutes until muscarinic signs and symptoms subside and repeated if they reappear. Atypical increases in blood pressure and heart rate have been reported with other cholinomimetics when coadministered with quaternary anticholinergics such as glycopyrrolate.
It is not known whether Cognex® or its metabolites can be eliminated by dialysis (hemodialysis, peritoneal dialysis, or hemofiltration).
The estimated median lethal dose of tacrine following a single oral dose in rats is 40 mg/kg, or approximately 12 times the maximum recommended human dose of 160 mg/day. Dose-related signs of cholinergic stimulation were observed in animals and included vomiting, diarrhea, salivation, lacrimation, ataxia, convulsions, tremor, and stereotypic head and body movements.


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.

-- advertisement -- The American Red Cross
Home | About Us | Contact Us | Site usage policy | Privacy policy

All Rights reserved - Copyright DrugLib.com, 2006-2017