Fluoxetine Clarithromycin

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. 

Delavirdine is extensively metabolized to inactive metabolites by the CYP3A and CYP2D6 enzymes. However, it also inhibits CYP3 A and thus inhibits its own metabolism. In addition to its interactions with other antiretroviral agents (see Table 49 1), delavirdine will result in increased levels of numerous agents (Table 49-3). Dose reduction of indinavir and saquinavir should be considered if they are administered concurrently with delavirdine. Delavirdine plasma concentrations are reduced in the presence of antacids, phenytoin, phenobarbital, carbamazepine, rifabutin, and rifampin concentrations are increased during coadministration with clarithromycin, fluoxetine, dexamethasone, and ketoconazole. 

Drugs that may affect delavirdine include the following Anticonvulsants, antacids, clarithromycin, didanosine, fluoxetine, histamine H2 antagonists, ketoconazole,... 

Buspirone (BuSpar) [Anxiolytic] WARNING Closely monitor for worsening depression or emergence of suicidality Uses Short-term relief of anxiety Action Antianxiety antagonizes CNS serotonin receptors Dose Initial 7.5 mg PO bid T by 5 mg q2-3d to effect usual 20-30 mg/d max 60 mg/d Contra w/ MAOI Caution [B, /-] Avoid w/ severe hepatic/renal insuff Disp Tabs SE Drowsiness, dizziness, HA, N, EPS, serotonin synd, hostility, depression Notes No abuse potential or physical/psychologic d endence Interactions T Effects W/ erythromycin, clarithromycin, itraconazole, ketoconazole, diltiazem, verapamil, grapefruit juice effects W/ carbamazepine, rifampin, phenytoin, dexamethasone, phenobarbital, fluoxetine EMS T Sedation w/ concurrent EtOH use grapefruit juice may T risk of adverse effects OD May cause dizziness, miosis, N/V symptomatic and supportive... 

Deravirdine (Rescnptor) [Antiretroviral/NNRTI] Uses HIV Infxn Action Nonnucleoside RT inhibitor Dose 400 mg PO tid Caution [C, ] CDC recommends HIV-infected mothers not to breast-feed (transmission risk) w/ renal/hepatic impair Contra Use w/ drugs dependent on CYP3A for clearance (Table VI-8) Disp Tabs SE Fat redistribution, immune reconstitution synd, HA, fatigue, rash, T transaminases, N/V/D Interactions T Effects W/ fluoxetine T effects OF benzodiazepines, cisapride, clarithromycin, dapsone, ergotamine, indinavir, lovastatin, midazolam, nifedipine, quinidine, ritonavir, simvastatin, terfena-dine, triazolam, warfarin effects W/ antacids, barbiturates, carbamazepine, cimetidine, famotidine, lansoprazole, nizatidine, phenobarbital, phenytoin, ranitidine, rifabutin, rifampin effects OF didanosine EMS Use of benzodiazepines and CCBs should be avoided may cause a widespread rash located on upper body and arms OD May cause an extension of nl SEs symptomatic and supportive Deferasirox (Exjade) [Iron Chelator] Uses Chronic iron overload d/t transfusion in pts >2 y Action Oral iron chelator Dose Initial 20 mg/kg... 

Intermittent claudication PO 100 mg twice a day at least 30 min before or 2 hr after meals. 50 mg twice a day during concurrent therapy with clarithromycin, diltiazem, erythromycin, fluconazole, fluoxetine, omeprazole, or sertraline. 

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. 

Mayhew et al. predicted that therapeutic unbound plasma concentrations (0.1 mM) of fluoxetine, clarithromycin, and the primary metabolite of diltiazem, /V-desmethyl diltiazem, would reduce the steady-state concentration of hepatic CYP3A4 to approximately 72%, 39%, or 21% of untreated levels, respectively... 

Selective serotonin reuptake inhibitors (SSRIs), such as fluoxetine, interact with drugs including clarithromycin, warfarin, phenelzine, benzotropine, chlorpromazine, diazepam, and cyproheptadine. Cigarette smokers metabolize SSRIs faster. 

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

A 53-year-old Canadian lawyer taking long-term fluoxetine and nitrazepam developed a frank psychosis 1-3 days after starting to take clarithromycin 500 mg/day for a chest infection (175). His symptoms resolved on withdrawal of all three drugs, and did not recur with erythromycin or when fluoxetine and nitrazepam were restarted in the absence of antibiotics. 

The symptoms may have been due to a direct effect of clarithromycin or else inhibition of hepatic cytochrome P450 metabolism, leading to fluoxetine toxicity. Clarithromycin occasionally causes hallucinations. 

Poliak PT, Sketris IS, MacKenzie SL, Hewlett TJ. Delirium probably induced by clarithromycin in a patient receiving fluoxetine. Ann Pharmacother 1995 29(5) 486-8. 

Macrolide antibacterials An isolated case report describes what appeared to be acute fluoxetine intoxication in a man brought about by the addition of clarithromycin. 

Clinically important, potentially hazardous interactions with alcohol, aprepitant, clarithromycin, CNS depressants, delavirdine, digoxin, efavirenz, fluconazole, fluoxetine, fluvoxamine, grapefruit juice, indinavir, itraconazole, ivermectin, kava, ketoconazole, propoxyphene, ritonavir, saquinavir, St John s wort... 

Clinically important, potentially hazardous interactions with amphetamines, aprepitant, astemizole, atazanavir, azithromycin, azole antifungals, clarithromycin, darunavir, dirithromycin, erythromycin, fluoxetine, fosamprenavir, grapefruit juice, imatinib, indinavir, itraconazole, ketoconazole, methylphenidate, nefazodone, nelfinavir, nilotinib, pemoline, phenothiazines, protease inhibitors, quinidine, ritonavir, saquinavir, sertraline, sparfloxacin, sulpiride, telithromycin, thioridazine, tipranavir, tricyclic antidepressants, troleandomycin, voriconazole, zileuton, ziprasidone... 

HIV protease inhibitors Indinavir Nelfinavir Ritonavir Saquinavir Amiodarone not Azithromycin Cimetidme Clarithromycin . Diltiazem Erythromycin Fluoxetine Fluvoxamine Grapefruit Juice Itraconazole Ketoconazole Mibefradil Nefezodone Troleandomydn Verapamil... 

A 53-year-old-man taking fluoxetine 80 mg and nitrazepam 10 mg at bedtime for depression and insomnia, was given clarithromycin 250 mg twice daily for a respiratory infection. Within a day he started to become increasingly contused and after 3 days was admitted to hospital with a diagnosis of psychosis and delirium. When no organic cause for the delirium could be found, all his medications were stopped, and erythromycin was started. His mental state returned to normal after 36 hours. Once the antibacterial course had finished, the fluoxetine and nitrazepam were restarted and no further problems occurred. ... 

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. ... 

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