Fluvoxamine drug interactions with

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

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. 

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. 

The most common interactions with SSRIs are pharmacokinetic interactions. For example, paroxetine and fluoxetine are potent CYP2D6 inhibitors (Table 30-4). Thus, administration with 2D6 substrates such as TCAs can lead to dramatic and sometimes unpredictable elevations in the tricyclic drug concentration. The result may be toxicity from the TCA. Similarly, fluvoxamine, a CYP3A4 inhibitor, may elevate the levels of concurrently administered substrates for this enzyme such as diltiazem and induce bradycardia or hypotension. Other SSRIs, such as citalopram and escitalopram, are relatively free of pharmacokinetic interactions. The most serious interaction with the SSRIs are pharmacodynamic interactions with MAOIs that produce a serotonin syndrome (see below). 

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. 

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). 

LITHIUM SSRIs Lithium may enhance the pharmacologic effects of SSRIs and potentiate the risk of serotonin syndrome. Excessive somnolence has been reported with fluvoxamine. However, there are reports of both T and l plasma concentrations of lithium. There are reports of lithium toxicity and of serotonergic effects Lithium is a direct stimulant of 5-HT receptors, while SSRIs i the reuptake of 5- HT these are considered to t the effects of serotonin in the brain. Seizures are a neurotoxic effect of lithium and could occur even with plasma lithium concentrations within the normal range. SSRIs and lithium may have additive effects to cause seizures Be aware of the possibility of serotonin syndrome. Also need to monitor lithium levels with appropriate dose adjustments during co-administration > For signs and symptoms of serotonin toxicity, see Clinical Features of Some Adverse Drug Interactions, Serotonin toxicity and serotonin syndrome... 

FLUOXETINE, FLUVOXAMINE, PAROXETINE BZDs - ALPRAZOLAM, DIAZEPAM, MIDAZOLAM t in plasma concentrations of these BZDs. Likely t sedation and interference with psychomotor activity Alprazolam, diazepam and midazolam are subject to metabolism by CYP3A4. Fluvoxamine, fluoxetine and possibly paroxetine are inhibitors of CYP3A4 sertraline is a weak inhibitor. SSRIs are relatively weak compared with ketoconazole, which is possibly 100 times more potent as an inhibitor Warn patients about risks associated with activities that require alertness. Consider use of alternatives such as oxazepam, lorazepam and temazepam, which are metabolized by glucuronidation >- For signs and symptoms of CNS depression, see Clinical Features of Some Adverse Drug Interactions, Central nervous system depression... 

Clinically important, potentially hazardous interactions with citalopram, dihydroergotamine, ergot-containing drugs, escitalopram, fluoxetine, fluvoxamine, isocarboxazid, MAO inhibitors, methysergide, naratriptan, nefazodone, paroxetine, phenelzine, rizatriptan, sertraline, sibutramine, St John s wort, tranylcypromine, venlafaxine, zolmitriptan... 

Antidepressants are commonly used in combination with antipsychotics to treat depressive symptoms in individuals with schizophrenia. Different antidepressants have been reported to inhibit metabolism of different P450 pathways. Table 66-10 summarizes the potential metabolic drug interactions between antidepressants and SGAs. Potential enzyme inhibitor interactions with clozapine are the most clinically significant. Increased clozapine serum concentrations with a CYP 1A2 inhibitor such as fluvoxamine may precipitate seizures. With the newer atypical antipsychotics, enzyme inhibitors are more likely to cause side effects such as increased sedation, orthostatic hypotension, or increased risk of akathisia and other extrapyramidal side effects. 

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