Itraconazole buspirone

The effects of buspirone are decreased when the drug is administered with fluoxetine Increased serum levels of buspirone occur if the drug is taken with erythromycin or itraconazole Should any of these combinations be required, the dosage of buspirone is decreased to 2.5 mg BID, and the patient is monitored closely. Venlafaxine blood levels increase with a risk of toxicity when administered witii MAOIs or cimetidine There is an increased risk of toxicity when trazodone is administered with the phenothiazines and decreased effectiveness of trazodone when it is administered with carbamazepine Increased serum digoxin levels have occurred when digoxin is administered with trazodone There is a risk for increased phenytoin levels when phenytoin is administered witii trazodone... 

Buspirone generally is well tolerated and does not cause sedation. Most common side effects include dizziness, nausea, and headaches. Drugs that inhibit CYP3A4 (e.g., verapamil, diltiazem, itraconazole, fluvoxamine, nefa-zodone, and erythromycin) can increase buspirone levels. Likewise, enzyme inducers such as rifampin can reduce buspirone levels significantly. Bupirone may increase blood pressure when coadministered with an monoamine oxidase inhibitor (MAOI). 

Verapamil, itraconazole, and fluvoxamine can increase buspirone levels, and rifampin reduces buspirone blood levels by 10-fold. 

Drugs that may be affected by itraconazole include alfentanil, almotriptan, alprazolam, amphotericin B, aripiprazole, benzodiazepines, buspirone, busulfan, calcium blockers, carbamazepine, cilostazol, cisapride, corticosteroids, cyclosporine, digoxin, disopyramide, docetaxel, dofetilide, eletriptan, epierenone, ergot alkaloids, haloperidol, HMG-CoA reductase inhibitors, hydantoins (phenytoin), hypoglycemic agents, oral midazolam, phosphodiesterase type 5 inhibitors, pimozide, polyenes, protease inhibitors, quinidine, rifamycins, sirolimus, tacrolimus, tolterodine, triazolam, trimetrexate, vinca alkaloids, warfarin, and zolpidem. 

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... 

Verapamil, diltiazem, erythromycin, and itraconazole all increase the plasma concentration of buspirone. The plasma concentration is decreased almost 10-fold by rifampicin. Grapefruit juice increases the overall subjective effect of the drug (Mahmood and Saha-jwalla, 1999). 

Itraconazole Alfentanil, alprazolam, astemizole, atorvastatin, buspirone, cisapride, cyclosporine, delavirdine, diazepam, digoxin, felodipine, indinavir, loratadine, lovastatin, midazolam, nisoldipine, phenytoin, quinidine, ritonavir, saquinavir, sildenafil, simvastatin, sirolimus, tacrolimus, triazolam, verapamil, warfarin... 

A4/3A5 Midazolam, buspirone, felodipine, lovastatin, eletriptan, sildenafil, simvastatin, triazolam Atazanavir, clarithromycin, indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, saquinavir, telithromycin Rifampin, carbamazepine... 

Antifungal imidazoles (ketoconazole, itraconazole, and analogues) compete for hepatic oxidative pathways that metabolize most benzodiazepines, as well as zolpidem, zopiclone, and buspirone (SEDA-22, 39, 41-43). 

The interaction of itraconazole with the active l-(2-pyrimidinyl)-piperazine metabolite of buspirone has been studied after a single oral dose of buspirone 10 mg... 

Itraconazole reduced the mean AUC of the metabolite by 50% and the Cmax by 57%, whereas the mean AUC and Cmax of the parent drug were increased 14.5-fold and 10.5-fold respectively. Thus, itraconazole caused relatively minor changes in the plasma concentrations of the active piperazine metabolite of buspirone, although it had major effects on the concentrations of buspirone after a single oral dose. 

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). 

BUSPIRONE ANTIFUNGALS -ITRACONAZOLE, KETOCONAZOLE T buspirone levels Inhibition of CYP3A4-mediated metabolism Warn patients to be aware of additional sedation... 

Itraconazole, an inhibitor of CYP3A, can increase buspirone concentrations (SEDA-22, 39). 

Kivisto KT, Lamberg TS, Neuvonen PJ. Interactions of buspirone with itraconazole and rifampicin effects on the pharmacokinetics of the active l-(2-pyrimidinyl)-pipera-zine metabolite of buspirone. Pharmacol Toxicol 1999 84(2) 94-7. 

A4/3A5 Midazolam, buspirone, felodipine, simvastatin Ketoconazole, itraconazole Rifampin, carbamazepine... 

Kivisto KT, Lam berg TS, Kantola T, Neuvonen PJ. Plasma buspirone concentrations are greatly increased by etyt omycin and itraconazole. Clin Pharmacol Pier (1997) 62, 348-54. 

The plasma levels of buspirone are markedly Increased by Itraconazole. Ketoconazole is predicted to interact similarly. 

In a placebo-controlled study, 8 healthy subjects were given buspirone 10 mg, before and after taking itraconazole 100 mg twice daily for 4 days. It was found that the buspirone maximum plasma levels and its AUC were increased 13-fold and 19-fold, respectively, by itraconazole. These increased buspirone levels caused a moderate impairment of psychomotor performance (digital symbol substitution, body sway, drowsiness, etc.) and an increase in adverse effects. ... 

Itraconazole is a potent inhibitor of the cytochrome P450 isoenzyme CYP3A4, by which buspirone is metabolised. Itraconazole therefore increases buspirone levels and effects. 

Direct information appears to be limited to this study but the interaction would seem to be established. The dosage of buspirone should be greatly reduced if itraconazole is given concurrently. The manufacturers recommend 2.5 mg daily or twice daily. Ketoconazole is predicted to interact similarly because it is also a potent CYP3A4 inhibitor. ... 

Noninterfering acetaminophen, amineptine, amphotericin B, aspirin, bromazepam, buspirone, citalopram, clobazam, diazepam, didanosine, fluconazole, flunitrazepam, flu-voxamine, hydroxyitraconazole, isoniazid, itraconazole, lamivudine, loprazolam, lora-zepam, metronidazole, minalcipram, nordiazepam, omeprazole, paroxetine, pyrimethamine, rifampin, sertraline, stavudine, sulfadiazine, trimethoprim, venlafaxine, zal-citabine, zidovudine, zolpidem, zopiclone... 

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