Fluvoxamine Alprazolam

A larger set of placebo-controlled studies show conclusively that imipramine is also effective for the treatment of panic disorders. Other agents shown to be effective in panic disorders include the SSRIs paroxetine, sertraline, fluvoxamine, fluoxetine and citalopram. Generally, initial treatment of moderate to severe panic disorders may require the initiation of a short course of benzodiazepines e.g. clonazepam (0.5 1 mg twice daily), and an SSRI. The patient will obtain immediate relief from panic attacks with the benzodiazepine whereas the SSRI may take 1 6 weeks to become effective. Once a patient is relieved of initial panic attacks, clonazepam should be tapered and discontinued over several weeks and SSRI therapy continued thereafter. There are no pharmacological treatments available for specific phobias, however controlled trials have shown efficacy for several agents, e.g. phenelzine, moclobemide. clonazepam, alprazolam, fluvoxamine. sertraline and paroxetine in the treatment of social phobia (Roy-Byrne and Cowlev, 2002). 

Alprazolam dose should be reduced by 50% if nefazodone (Serzone) or fluvoxamine is added. 

A meta-analysis (Boyer 1995) has compared some serotonin reuptake inhibitors (paroxetine, fluvoxamine, zimeldine, and clomipramine) with imipramine and alprazolam in the alleviation of panic attacks in patients with DSM-III or DSM-III-R panic disorder. Although all three classes of drugs were shown to be significantly more effective than placebo, the serotonin reuptake inhibitors were also significantly superior to both imipramine and alprazolam. The findings of this meta-analysis highlight the importance of... 

A third important CYP450 enzyme for antidepressants and mood stabilizers is 3A4. Some benzodiazepines (e.g., alprazolam and triazolam) are substrates for 3A4 (Fig. 6—17). Some antidepressants are 3A4 inhibitors, including the SSRIs fluoxetine and fluvoxamine and the antidepressant nefazodone (Fig. 6—18). Administration of a 3A4 substrate with a 3A4 inhibitor will raise the level of the substrate. For example, fluoxetine, fluvoxamine, or nefazodone will raise the levels of alprazolam or triazolam, requiring dose reduction of the benzodiazepine (Fig. 6—18). 

SSRIs and the benzodiazepine alprazolam are often used to treat panic disorder. Pharmacokinetic reactions between them could therefore be important. Alprazolam is metabolized by CYP3A4, which fluvoxamine inhibits (SEDA-22, 13). In 23 out-patients (11 men, 12 women, mean age 39 years) who took alprazolam both as monotherapy (mean dose 1.0 mg/day) and in combination with fluvoxamine (mean dose 34 mg/day), fluvoxamine increased plasma alprazolam concentrations by 58% (97). This was not associated with increased sleepiness, measured by a subjective rating scale, but objective measures of psychomotor function were not carried out and these could have been impaired by raised alprazolam concentrations. 

Suzuki Y, Shioiri T, Muratake T, Kawashima Y, Sato S, Hagiwara M, Inoue Y, Shimoda K, Someya T. Effects of concomitant fluvoxamine on the metabolism of alprazolam in Japanese psychiatric patients interaction with CYP2C19 mutated alleles. Eur J Clin Pharmacol 2003 58 829-33. 

The effects of co-administration of fluvoxamine on plasma concentrations of alprazolam have been studied in 23 Japanese outpatients (46). All patients were taking fluvoxamine (25-100 mg/day) either before or after monotherapy with alprazolam (0.4—1.6 mg/day). Coadministration with fluvoxamine produced on average a 58% increase in plasma alprazolam concentrations. However, there were wide variations in the plasma concentrations of alprazolam. The interaction was attributed to the CYP2C19 genotype. 

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... 

Increased depressive effects when taken with other CNS depressants Inhibitors of CYP450 3A, such as nefazodone, fluvoxamine, fluoxetine, and even grapefruit juice, may decrease clearance of alprazolam and thereby raise alprazolam plasma levels and enhance sedative side effects alprazolam dose may need to be lowered... 

Adding fluvoxamine, fluoxetine, or nefazodone can increase alprazolam levels and make the patient very sleepy unless the alprazolam dose Is lowered by half or more... 

Via CYP450 3A4 inhibition, fluvoxamine may reduce clearance of carbamazepine and benzodiazepines such as alprazolam and triazolam, and thus require dosage reduction... 

Some SSRIs (notably fluvoxamine and to a lesser extent fluoxetine) and their metabohtes inhibit hepatic oxidative enzymes, particularly CYP2C19 and CYP3A, that metabolize most benzodiazepines, as well as zaleplon, zolpidem, zopiclone, and buspirone (SEDA-22, 39) (SEDA-22, 41) (168,169). Apart from fluvoxamine, SSRIs do not generally have a chnically prominent effect on hypnosedative effects studies vary from those that have found that fluoxetine has a moderate but functionally unimportant impact on diazepam concentrations (170) to results that suggest significant aggravation of the cognitive effects of alprazolam when co-prescribed with the SSRI (171). 

Benzodiazepines Sertraline and fluvoxamine may inhibit the metabolism of alprazolam and diazepam, resulting in elevated serum levels potentially causing sedation and psychomotor impairment. 

Fluvoxamine Alprazolam Increased AUC of alprazolam by 96%, increased alprazolam half-life by 71%, and increased psychomotor impairment... 

Also analyzed acebutolol, acepromazine, acetaminophen, acetazolamide, acetophenazine, albuterol, alprazolam, amitriptyline, amobarbital, amoxapine, antip5Tine, atenolol, atropine, azatadine, baclofen, benzocaine, bromocriptine, brompheniramine, brotizolam, bu-pivacaine, buspirone, butabarbital, caffeine, carbamazepine, cetirizine, chlorcyclizine, chlordiazepoxide, chlormezanone, chloroquine, chlorpheniramine, chlorpromazine, chlorpropamide, chlorprothixene, chlorthalidone, chlorzoxazone, cimetidine, cisapride, clomipramine, clonazepam, clonidine, clozapine, cocaine, codeine, colchicine, cyclizine, qyclo-benzaprine, dantrolene, desipramine, diazepam, diclofenac, diflunisal, diltiazem, diphenhydramine, diphenidol, diphenoxylate, dipyridamole, disopyramide, dobutamine, doxapram, doxepin, droperidol, encainide, ethidium bromide, ethopropazine, fenoprofen, fentanyl, flavoxate, fluoxetine, fluphenazine, flurazepam, flurbiprofen, fluvoxamine, fu-rosemide, glutethimide, glyburide, guaifenesin, haloperidol, homatropine, hydralazine, hydrochlorothiazide, hydrocodone, hydromorphone, hydroxychloroquine, hydroxyzine, ibuprofen, imipramine, indomethacin, ketoconazole, ketoprofen, ketorolac, labetalol, le-vorphanol, lidocaine, loratadine, lorazepam, lovastatin, loxapine, mazindol, mefenamic acid, meperidine, mephenytoin, mepivacaine, mesoridazine, metaproterenol, methadone, methdilazine, methocarbamol, methotrexate, methotrimeprazine, methoxamine, methyl-dopa, methylphenidate, metoclopramide, metolazone, metoprolol, metronidazole, mida-... 

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