Fluvoxamine, drug interactions

Alfaro CL, Nicolson R, Lenane M, Rapoport JL. Carbamazepine and/or fluvoxamine drug interaction with... 

DeMaria PA, Serota RD. A therq>eutic use of the methadone fluvoxamine drug interaction. JAMctDis( 9 ) 18, 5-12. 

Becquemont L, Le Bot MA, Riche C, Funck-Bren-tano C, Jaillon P, Beaune P (1998) Use of heterolo-gously expressed human cytochrome P450 1A2 to predict tacrine-fluvoxamine drug interaction in man. Pharmacogenetics 8 101-108... 

It may be fair to ask, Is this much ado about nothing Although test tube studies have shown that particular drugs interact, it is seldom that this causes problems for patients taking the medications. For example, the antidepressant fluvoxamine inhibits the enzyme that deactivates the antipsychotic haloperidol (Haldol). Does this mean that fluvoxamine and haloperidol cannot be taken together By no means. Although this would probably raise the blood level of haloperidol somewhat, the main effect if any would be that a smaller dose of haloperidol would be more effective. 

Another practical example of a pharmacokinetic drug interaction concerns the incidence of seizures in patients given a standard (300 mg/ day) dose of clozapine. Should the patient be given an SSRI antidepressant (such as fluoxetine, fluvoxamine, sertraline or paroxetine) concurrently then the clearance of clozapine could be reduced by up to 50%, an effect which would be comparable with a doubling of the dose. This could lead to a threefold increase in the risk of the patient suffering a seizure. 

Wagner, W. and Vause, E.W. (1995) Fluvoxamine. A review of global drug-drug interaction data. Clin Pharmacokinet 29 Suppl 1 26-31. 

The major distinguishing characteristic among the SSRIs is CYP enzyme inhibition. Fluvoxamine, fluoxetine, and paroxetine produce substantial inhibition of one or more CYP enzymes, whereas citalopram and sertraline do not (Table 7-29). In fact, fluvoxamine, fluoxetine, and paroxetine have all caused fatal drug-drug interactions via such CYP enzyme inhibition (339, 496, 497). 

In comparison with TCAs, SSRIs cause fewer pharmacodynamic drug-drug interactions but some (i.e., fluvoxamine, fluoxetine, paroxetine) cause more CYP enzyme mediated pharmacokinetic drug-drug interactions. Unlike TCAs, SSRIs do not potentiate alcohol and perhaps even slightly antagonize its acute CNS effects. Nevertheless, there are some important adverse interactions. 

Fluoxetine and paroxetine are potent inhibitors of the CYP2D6 isoenzyme, and this contributes to potential drug interactions (see drug interactions). In contrast, fluvoxamine is an inhibitor of CYP3A4, whereas citalopram, escitalopram, and sertraline have more modest CYP interactions. 

An example of a potentially important drug interaction is that which occurs when fluvoxamine is given along with theophyllin (Figure 6—13). In that case, the theo-phyllin dose must be lowered or else the blood levels of theophyllin will rise and possibly cause side effects, even toxic side effects such as seizures. The same may occur with caffeine. Fluvoxamine also affects the metabolism of atypical anti-psychotics. 

A meta-analysis of 20 short-term studies of five SSRIs (citalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline) has been published (8). There were no overall differences in efficacy, but fluoxetine had a slower onset of action. Citalopram and sertraline were least likely to cause drug interactions, but citalopram was implicated more often in fatal overdoses. 

Chang WH, Augustin B, Lane HY, ZumBrunnen T, Liu HC, Kazmi Y, Jann MW. In-vitro and in-vivo evaluation of the drug-drug interaction between fluvoxamine and clozapine. Psychopharmacology (Berl) 1999 145(l) 91-8. 

The addition of low-dose fluvoxamine (50-100 mg/day) to neuroleptic drug treatment may improve the negative symptoms in patients with schizophrenia, but involves a risk of a drug interaction. In 12 in-patients with schizophrenia receiving 6 mg/day of haloperidol, incremental doses of fluvoxamine (25, 75, and 150 mg/day for 2 weeks each) respectively increased haloperidol plasma concentrations by 120%, 139%, and 160% of those before fluvoxamine co-administration in spite of the increase, there were no particular adverse effects (50). 

Albers LJ, Ozdemir V, Marder SR, Raggi MA, Aravagiri M, Endrenyi L, Reist C. Low-dose fluvoxamine as an adjunct to reduce olanzapine therapeutic dose requirements a prospective dose-adjusted drug interaction strategy. J Clin Psychopharmacol 2005 25 170-4. 

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