Nefazodone alprazolam

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

Tr/azo/obenzocf/azep/nes-Triazolam and alprazolam, metabolized by cytochrome P-450 3A4, have increased plasma concentrations when administered concomitantly with nefazodone. If triazolam is coadministered with nefazodone, a 75% reduction in the initial triazolam dosage is recommended. It is recommended that triazolam not be used in combination with nefazodone. No dosage adjustment is required for nefazodone. 

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,... 

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). 

Nefazodone is a weak inhibitor of CYP2D6 but a potent inhibitor of CYP3A4 and it increases plasma concentrations of drugs that are substrates of CYP3A4, such as alprazolam, astemizole, carbamazepine, ciclosporin, cisapride, terfenadine, and triazolam. 

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... 

Benzodiazepines for anxiety, but give alprazolam cautiously with nefazodone as alprazolam levels can be much higher in the presence of nefazodone... 

Via CYP450 3A4 inhibition, nefazodone may increase the half-life of alprazolam and triazolam, so their dosing may need to be reduced by half or more... 

Drugs that participate in major CYP3A4 interactions with macrohdes are listed in Table 4. Other drugs that may be affected include alprazolam (138), the water-soluble artemisinin analogue artehnic acid (139), gallopamil (140), lovastatin (141), nefazodone (142), and risperidone... 

Clinically important, potentially hazardous interactions with alprazolam, astemizole, carbamazepine, cisapride, clarithromycin, dexamethasone, diltiazem, docetaxel, ifosfamide, imatinib, irinotecan, itraconazole, ketoconazole, methylprednisolone, midazolam, nefazodone, oral contraceptives, paroxetine, phenytoin, pimozide, rifampin, ritonavir, terfenadine, tolbutamide, trabectedin, troleandomycin, vinblastine, vincristine, warfarin... 

Nefazodone Alprazolam Increased plasma concentrations of alprazolam... 

Greene DS, Salazar DE, Dockens RC et al. Coadministration of nefazodone and benzodiazepines a pharmacokinetic interaction study with alprazolam, j Clin Psychopharmacol 1995 15 399 08. 

Nefazodone Alprazolam, triazolam Increased blood levels of the second drug doses may need to be decreased... 

Fluvoxamine inhibits liver drug-metabolizing enzymes. Dosages of alprazolam, theophylline, and warfarin must be reduced if any of these drugs are given concomitantly with fluvoxamine. Nefazodone may also decrease the metabolism of benzodiazepines, and venlafaxine may inhibit haloperidol metabolism. The answer is (B). 

Nefazodone increases the plasma levels and effects of alprazolam, midazolam, triazolam and zopiclone, but not lorazepam. 

A placebo-controlled study in 12 healthy subjects found that nefazodone 200 mg twice daily caused an almost twofold increase in the plasma levels of alprazolam 1 mg twice daily taken for 7 days. Another study found that impairment of psychomotor performance and increased sedation occurred when nefazodone was given with alprazolam. A case report describes benzodiazepine withdrawal symptoms in a woman taking alprazolam after nefazodone was withdrawn following several years of concurrent use. She needed an alprazolam dosage increase from 500 micrograms to 4 mg daily to control her symptoms. ... 

Nefazodone appears to inhibit the oxidative metabolism of alprazolam, midazolam, triazolam and zopiclone by the cytochrome P450 isoenzyme CYP3A4 so that they accumulate in the body. Lorazepam is unaffected because it is primarily excreted as a conjugate. 

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