Erythromycin SSRIs

BZD hypnotics such as midazolam and triazolam are primarily metabolized via the P450 3A3/4 microenzyme system. Other BZDs often used as hypnotics, such as diazepam, can also be metabolized by CYP 33/4 and CYP 2C19. Any drugs that act as inhibitors or inducers of these isoenzymes could increase or decrease BZD levels, respectively (350). Thus, ketoconazole, macrolide antibiotics (e.g., erythromycin), SSRIs (e.g., fluoxetine-norfluoxetine and fluvoxamine), and other antidepressants (especially nefazodone) may decrease clearance and increase BZD levels to potentially toxic ranges. Conversely, rifampacin, CBZ, and dexamethasone may increase clearance and decrease BZD levels to potentially subtherapeutic ranges. 

Remember some of those drugs that are key enzyme inducers (e.g. phenytoin, barbiturates, rifampicin, etc) or enzyme inhibitors (e.g. azole antifungals, HIV-protease inhibitors, erythromycin, SSRIs). 

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. 

Uses Obesity Action Blocks uptake of norepinephrine, serotonin, dopamine Dose 10 mg/d PO, may to 5 mg after 4 wk Caution [C, -] w/ SSRIs, Li, dextromethorphan, opioids Contra MAOI w/in 14 d, uncontrolled HTN, arrhythmias Disp Caps SE HA, insomnia, xerostomia, constipation, rhinitis, tach, HTN Interactions T Risk of serotonin synd W/ dextromethorphan, ergots, fentanyl, Li, meperidine, MAOIs, naratriptan, pentazocine, rizatriptan, sumatriptan, SSRIs, tryptophan, zolmitriptan, St. John s wort effects W/ cimetidine, erythromycin, ketoconazole T CNS depression W/ EtOH EMS Use fentanyl w/ caution, may T risk of serotonin synd concurrent EtOH use can T CNS depression OD May cause tach, HTN, diaphoresis, HA, fever, agitation, muscle tremors, and Szs symptomatic and supportive... 

Several factors increase the risk of thioridazine toxicity pre-existing cardiac disease, hypokalemia, a glucose load, alcohol, exercise, and concomitant therapy with tricyclic antidepressants, erythromycin, co-trimoxazole, cisapride, risperidone, hydroxyzine, and drugs that inhibit CYP2D6 (some SSRIs, fluphenazine, and perphenazine) (11). 

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 amiodarone, azithromycin, bepredil, bosentan, bretylium, cisapride, clarithromycin, disopyramide, erythromycin, erythromycin fluconazole, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ketoconazole, metronidazole, miconazole, nefazodone, nilotinib, paroxetine, pimozide, probucol, procainamide, quinidine, quinine, ritonavir, saquinavir, sertraline, sotalol, SSRIs, terfenadine, troleandomycin, voriconazole, zileuton, ziprasidone... 

A4 Barbiturates, carbamazepine, corticosteroids, efavirenz, phenytoin, rifampin, troglitazone Antiarrhythmics, antidepressants, azole antifungals, benzc iazepines, 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. ... 

The authors attribute what was seen to fluoxetine toxicity in the first case, and to the serotonin syndrome in the second case. They postulated that erythromycin (a known and potent inhibitor of cytochrome P450 isoenzyme CYP3A4) and the related macrolide clarithromycin, reduced the metabolism of the SSRIs, thereby raising their serum levels and precipitating the observed toxicity. ... 

A second large class of agents known to form mechanism-based quasi-irreversible P450-MI complex es [15, 24, 25, 138, 139, 223-228] includes alkyl and aromatic amines, such as the monoamine oxidase inhibitor cloigyhne [223], the SSRI sertraline [228], and many clinically useful macrolide antibiotics such as troleando-mycin (TAO), clarithromycin, and erythromycin (Fig. 5.6 [229-235]). These amines are oxidized... 

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