Nefazodone Cimetidine

Certain medications (e.g., cimetidine, diltiazem, erythromycin, fluoxetine, fluvoxamine, isoniazid, itraconazole, ketoconazole, nefazodone, propoxyphene, and verapamil) added to carbamazepine therapy may cause carbamazepine toxicity. 

Drugs that may affect HMG-CoA reductase inhibitors include alcohol, amiodarone, antacids, azole antifungals, bile acid sequestrants, cimetidine, cyclosporine, diltiazem, erythromycin, gemfibrozil, isradipine, nefazodone, niacin, nicotinic acid, omeprazole, phenytoin, propranolol, protease inhibitors, ranitidine, rifampin, St. John s wort, and verapamil. 

Drugs that may affect antihistamines include aluminum/magnesium-containing acids, cimetidine, erythromycin, ketoconazole, MAO inhibitors, and rifamycins (eg, rifampin). Drugs that may be affected by antihistamines include alcohol and CNS depressants, beta-blockers, MAO inhibitors, metyrapone, nefazodone, selective serotonin reuptake inhibitors (SSRIs), and venlafaxine. 

Drugs that can increase carbamazepine serum levels include cimetidine, danazol, diltiazem, erythromycin, felbamate, clarithromycin, fluoxetine, isoniazid, niacinamide, propoxyphene, ketaconazole, itraconazole, verapamil, valproate, troleandomycin, loratadine, nicotinamide, tricyclic antidepressants, SSRIs, nefazodone, protease inhibitors. 

Drugs that may affect tacrolimus include nephrotoxic agents (aminoglycosides, amphotericin B, cisplatin, cyclosporine), antifungals, bromocriptine, calcium channel blockers, cimetidine, clarithromycin, danazol, diltiazem, erythromycin, methylprednisolone, metoclopramide, carbamazepine, phenobarbital, phenytoin, rifamycins, cisapride, chloramphenicol, metronidazole, nefazodone, omeprazole, protease inhibitors, macrolide antibiotics, fosphenytoin, and St. John s wort. 

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a BZD and another drug known to induce seizures may possibly increase seizure risk, especially if the BZD is abruptly withdrawn.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. 

Drugs that may inhibit cytochrome P450 metabolism of other drugs include amiodarone, androgens, atazanavir, chloramphenicol, cimetidine, ciprofloxacin, clarithromycin, cyclosporine, delavirdine, diltiazem, diphenhydramine, disulfiram, enoxacin, erythromycin, fluconazole, fluoxetine, fluvoxamine, furanocoumarins (substances in grapefruit juice), indinavir, isoniazid, itraconazole, ketoconazole, metronidazole, mexile-tine, miconazole, nefazodone, omeprazole, paroxetine, propoxyphene, quinidine, ritonavir, sulfamethizole, verapamil, voriconazole, zafirlukast, and zileuton. 

A Atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin Amprenavir, aprepitant, diltiazem, erythromycin, fluconazole, fosamprenavir, grapefruit juice", verapamil Cimetidine... 

CYP3A4 Inhibition Amiodarone, clarithromycin, erythromycin, cimetidine, cyclosporine, fluoxetine fluvoxamine, itraconazole, ketoconazole, nefazodone, verapamil, diltiazem HIV antivirals delaviridine, indanavire, nelfmavire, ritonavire, sequinavire Atorvastatin Lovastatin Simvastatin ... 

Omeprazole, like cimetidine, can impair benzodiazepine metabolism and lead to adverse effects (SEDA-18, 43). Other drugs, including antibiotics (erythromycin, chloramphenicol, isoniazid), antifungal drugs (ketoconazole, itraconazole, and analogues), some SSRIs (fluoxetine, paroxetine), other antidepressants (nefazodone), protease inhibitors (saquinavir), opioids (fentanyl), calcium channel blockers (diltiazem, verapamil), and disulfiram also compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22,39) (SEDA-22,41). 

Clinically important, potentially hazardous interactions with alcohol, cimetidine, CNS depressant, erythromycin, ethanol, ketoconazole, nefazodone, nelfinavir, olanzapine, rifampin, ritonavir, tricyclic antidepressants... 

After single-dose administration, the mean bioavailability of quetiapine is 9% with significant interindividual variation. If a CYP 3A4 inhibitor (e.g., cimetidine, ketoconazole, nefazodone, grapefruit juice, or erythromycin) is added to quetiapine, increased side effects (e.g., sedation or orthostasis) may occur. Fluoxetine may also decrease clearance of a medication such as quetiapine metabolized through CYP 3A4. However, with fluoxetine, it is the long-acting metabolite norfluoxetine, and not fluoxetine, that is the primary inhibitor of 3 A4 metabolism. If an enzyme inducer such as carbamazepine or St. lohn s wort is added to quetiapine, then decreased antipsychotic effects may occur. ... 

A4 Amiodarone, azole antifungals, cimetidine, clarithromycin, cyclosporine, erythromycin, fluoroquinolones, grapefruit juice, HIV protease inhibitors, metronidazole, quinine. SSRIs, tacrolimus Antiarrhythmics, antidepressants, azole antifungals, benzodiazepines, calcium channel blockers, cyclosporine, delavirdine, doxorubicin, efavirenz, erythromycin, estrogens, HIV protease inhibitors, nefazodone. paclitaxel, proton pump inhibitors, HMG-CoA reductase inhibitors, rifabutin, rifampin, sildenafil, SSRIs, tamoxifen, trazodone, vinca anticancer agents... 

In view of these effects the US manufacturers suggest halving the dose of cilostazol in the presence ofCYP3A4 inhibitors such as erythromycin, diltiazem, itraconazole, and ketoconazole. However, the UK manufacturers contraindicate CYP3A4 inhibitors, and they specifically name erythromycin, diltiazem, ketoconazole, cimetidine, and the protease inhibitors. Just why these recommendations differ is not clear. The US manufacturers suggest that other CYP3A4 inhibitors, such as azole anti-fungals (fluconazole, miconazole), SSRIs (fluoxetine, fluvoxamine, sertraline) and nefazodone, may also interact. ... 

Buspirone does not appear to interact with amitriptyline, cimetidine or terfenadine. An isolated report describes mania when an alcoholic patient taking huspirone was given disulfiram. Nefazodone greatly increases huspirone levels. 

CYP3A4 inhibitors Maerolldes e.g. Ciarithromycin, Erythromycin Azole antifungals e.g. Ketoconazoie Protease Inhibitors Nefazodone Diitiazem Cimetidine See aiso Tabie i. 4, p. 6 hcreased levels of cisapride result In an Increase in the risk of QT prolongation and life-threatening ventricular arrhythmias e.g. torsade de pointes. Avoid. 1, 11-20... 

No changes in the steady-state pharmacokinetics of either cimeti-dine or nefazodone were seen in a week long study in 18 healthy subjects given cimetidine 300 mg four times daily and nefazodone 200 mg every 12 hours. No special precautions would seem to be necessary if both drugs are used concurrently. ... 

Barbha a RH, Shukla UA, Greene DS. Lack of interaction between nefazodone and cimetidine a steatfy state pharmacokinetic sbufy in humans. rJC7znP ormaco/(1995) 40,161-5. 

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