Nefazodone interactions

Laroudie C, Salazar DE, Cosson JP, Cheuvart B, Istin B, Girault J, Ingrand 1, Decourt JP. Carbamazepine-nefazodone interaction in healthy subjects. J Clin Psychopharmacol 2000 20(l) 46-53. 

Barbey JT. Loratadine/nefazodone interaction. Clin Pharmacol TherQ.OOT) 71, 403. 

Ivfecdonald J, Rawlins S. Neutropenia due to nefazodone, interaction or coincidence ZJPsychiatfy(2000)34,1031-2. 

Many commonly used medications also contain substances that are eliminated by the MAOIs and must not be taken by these patients. The list of medications to be avoided inclndes the narcotic pain reliever meperidine (Demerol), and many over-the-connter cold remedies containing dextromethorphan or pseudoephedrine. Finally, patients taking MAOIs must also avoid medications that elevate serotonin levels. This inclndes certain appetite snppressants and antidepressants including the SSRIs, venlafaxine, duloxetine, mirtazapine, nefazodone, and trazodone. Medications that interact with the MAOIs cannot be taken until at least 2 weeks after the MAOI has been stopped. 

Serotonin-Boosting Antidepressants. The SSRIs have also been studied in the treatment of generalized social anxiety disorder, and paroxetine, sertraline, and venlafaxine are effective. Preliminary data suggests that the serotonin-boosting atypical antidepressants (mirtazapine and nefazodone) may also be helpful. Like the MAOIs, they appear to be effective at doses comparable to those used to treat depression. They may help avoidant patients to gradually increase their social interaction and become more assertive. 

Coadministration with cisapride, pimozide, or carbamazepine (see Warnings and Drug Interactions) patients who were withdrawn from nefazodone because of evidence of liver injury (see Warning box. Warnings) hypersensitivity to nefazodone or other phenylpiperazine antidepressants. 

Potential interaction with drugs that inhibit or are metabolized by cytochrome P-450 (3A4 and 2D6) isozymes Caution is indicated in the combined use of nefazodone with any drugs known to be metabolized by the 3A4 isozyme (in particular, cisapride or pimozide). 

Drug/Food interactions Food delays absorption of nefazodone and decreases the bioavailability by about 20%. 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

Bromocriptine (Parl el) [Antiparkinsonian Agent/Dopamine Receptor Agonist] Uses Parkin on Dz, hyperprolactinemia, acromegaly, pituitary tumors Action Direct-acting on the striatal dopamine receptors X prolactin secretion Dose Initial, 1.25 mg PO bid titrate to effect, w/ food Caution [B, ] Contra Severe ischemic heart Dz or PVD Disp Tabs, caps SE X BP, Raynaud phenomenon (vasospastic disorder resulting in discoloration of the fmgers/toes), dizziness, N, hallucinations Interactions T Effects W/ erythromycin, fluvoxamine, nefazodone, sympathomimetics, antihypertensives X effects W/ phenothiazines, antipsychotics EMS Monitor BP may cause intolerance to EtOH OD May cause NA, severe hypotension give IV fluids symptomatic and supportive... 

NA /D, abd pain, bleeding, fevCT, T QT Interactions t Effects W7 atazanavir, clarithromycin, CT5rthromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfi-navir, ritonavir, saquinavir, telithromycin X effects W7 antacids, carbamazqjine, dexamethasone, phenobarbital, phenytoin, rifampicin, St. John s wort EMS Drug contains lactose, may cause D/abd discomfort in pts w/ lactose intolerance OD Sxs unknown symptomatic and supportive... 

Coadministration with most medications that are metabolized by CYP 3A3/4 should be undertaken with caution, and the doses of the other medications that are CYP 3A3/4 substrates (see Table 1-1) should be reduced. The interaction between nefazodone and MAOIs has not yet been evaluated, but it may be as dangerous as... 

The use of two or more agents concurrently has the potential for possibly deleterious drug interactions. Thus, as noted in subsequent chapters, the addition or elimination of an agent may significantly alter the activity of the concurrent drug treatment (e.g., carbamazepine lowering haloperidol plasma levels nefazodone increasing the levels of triazolam). 

Disadvantages of nefazodone include the need for a twice-a-day dosing schedule and dose adjustment. Work is under way to develop a once-a-day sustained release version of nefazodone. The fact that nefazodone must be started at a lower than usually effective dose and then adjusted to an effective dose is a distinct disadvantage. That is made even more problematic because arguably more variability exists among patients in terms of the optimal dose of nefazodone as far as efficacy and tolerability than for virtually any other antidepressant. Finally, nefazodone produces substantial inhibition of CYP 3A3/4, leading to the potential for adverse pharmacokinetic interactions as well as possible unknown long-term consequences. 

Two open label studies have been done with nefazodone (. 367, 368). As discussed earlier, the value of such open label studies is dubious. Moreover, this strategy is limited by the divided dose schedule recommended for the immediate release formulation of nefazodone, the need for dose adjustment, and the potential for complicated drug-drug interactions, particularly when switching from fluoxetine to nefazodone. 

Because most antidepressants require oxidative metabolism as a necessary step in their elimination, they can be the target of a pharmacokinetic drug-drug interaction, as well as the cause. The CYP enzymes mediating the biotransformation of the various antidepressants are also shown in Table 7-30. CYP 1A2 and 3A3/4 are induced by anticonvulsants such as barbiturates and carbamazepine. As expected, coadministration of these anticonvulsants has been shown to lower plasma levels of TCAs and would be predicted to have the same effect on nefazodone, sertraline, and venlafaxine. 

Because nefazodone does inhibit the 5-HT uptake pump, it has the same class warning against combined use with an MAOl. Nevertheless, there are several reasons to suspect that there may be less risk of this interaction with nefazodone than other serotonin uptake pump inhibitors. First, trazodone, an analogue of nefazodone, is one of the few antidepressants that can be used in combination with an MOAI with minimal risk of an adverse interaction. Second, the most potent action of nefazodone is 5-HT2a receptor blockade, rather than 5-HT uptake inhibition. Nonetheless, we recommend the conservative approach of avoiding this combination, particularly when using high doses (i.e., > 450 mg per day), at which appreciable serotonin uptake inhibition is produced by nefazodone. 

With the important exception of additive effects when combined with other CNS depressants, including alcohol, BZDs interact with very few drugs. Disulfiram (see the section The Alcoholic Patient in Chapter 14) and cimetidine may increase BZD blood levels, and diazepam may increase blood levels of digoxin and phenytoin. Antacids may reduce the clinical effects of clorazepate by hindering its biotransformation to desmethyidiazepam. Coadministration of a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn. Furthermore, as noted earlier, important interactions have been reported among nefazodone, erythromycin, troleandomycin, and other macrolide antibiotics, as well as itraconazole. In each case, metabolism is inhibited, and triazolam levels can increase significantly. 

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