Tacrine Fluvoxamine

Smoking cessation, with or without nicotine substitutes, may alter response to concomitant medication in ex-smokers. Smoking may affect alcohol, benzodiazepines, beta-adrenergic blockers, caffeine, clozapine, fluvoxamine, olanzapine, tacrine, theophylline, clorazepate, lidocaine (oral), estradiol, flecanide, imipramine, heparin, insulin, mexiletine, opioids, propranolol, catecholamines, and cortisol. 

A2 Acetaminophen, antipyrine, caffeine, clomipramine, phenacetin, tacrine, tamoxifen, theophylline, warfarin Smoking, charcoal-broiled foods, cruciferous vegetables, omeprazole Galangin, furafylline, fluvoxamine... 

Fluvoxamine and other CYP4501A2 inhibitors may increase plasma levels of tacrine... 

Tacrine Fluvoxamine Decreased metabolism of tacrine Avoid use of interacting medications ... 

Tacrine Fluvoxamine inhibits the metabolism of tacrine use alternative SSRI. 

CYP1A2 Antidepressants amitriptyline, clomipramine, imipramine, fluvoxamine Neuroleptics haloperidol, phenothiazines, thiothixene, clozapine, olanzapine Others tacrine, caffeine, theophylline, acetaminophen, phenacetin No report of polymorphism until 1999 significance of following findings remains unclear 1C reduced activity 23% in Japanese 1F higher inducibility 32% in Caucasians... 

Fluvoxamine markedly increases the levels of tacrine, and increases its cholinei ic adverse effects, whereas fluoxetine, paroxetine, and sertraline are not expected to interact. Paroxetine and fluoxetine may increase donepezil and galantamine levels. Sertraline does not appear to have a pharmacokinetic interaction with donepezil, and concurrent use seems generally well tolerated however, one report describes hepatotoxicity, possibly as a result of their concurrent use. Rivastigmine and fluoxetine appear not to interact. 

Fluvoxamine is an inhibitor of cytochrome P450 isoenzyme CYPl A2, the main isoenzyme involved in the metaholism of tacrine. In vitro study showed that fluvoxamine is a potent inhibitor of tacrine metabolism, and it was therefore predicted that fluvoxamine may dramatically increase tacrine plasma levels in patients. This prediction was confirmed in a placebo-controlled study in 13 healthy subjects who had an eightfold increase in the mean AUC of a single 40-mg dose of tacrine after taking fluvoxamine 100 mg for 6 days. A very large increase in the AUC of the hydroxy-lated metabolites of tacrine, and an eightfold fall in the clearance of tacrine... 

Becquemont L, Le Bot MA, Riche C, Beaune P. Influence of fluvoxamine on tacrine metabolism in vitro potential implication for the hepatotoxicity in vivo. Fundam Clin Pharmacol (1996) 10, 156-7. 

Becquemont L, Ragueneau I, Le Bot MA, Riche C, Funck-Brentano C, JaiUon P. Influence of the CYP1A2 inhibitor fluvoxamine on tacrine pharmacokinetics in humans. Clin Pharmacol Ther 991)6, 6 9-21. 

Larsen JT, Hansen LL, Brosen K. Tacrine-fluvoxamine interaction study in healthy volunteers. EurJ Clin Pharmacol (1997) 52 (Suppl), A136. 

Larsen JT, Hansen LL, Spigset O, Brosen K. Fluvoxamine is a potent inhibitor of tacrine metabolism in vivo. Eur j Clin Pharmacol (1999) 55, 375-82. 

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