Trazodone Ritonavir

Drugs that may be affected by indinavir include antiarrhythmics, clarithromycin, dihydropyridine calcium channel blockers, HMG-CoA reductase inhibitors, immunosuppressant agents, phosphodiesterase type 5 inhibitors, pimozide, saquinavir, trazodone, cisapride, amiodarone, benzodiazepines, ergot alkaloids, fentanyl, rifamycins, ritonavir. 

Drugs that might be affected by amprenavir include antiarrhythmics, anticonvulsants, azole antifungals, benzodiazepines, calcium channel blockers, cisapride, clarithromycin, cyclosporine, ergot alkaloids, fentanyl, HMG-CoA reductase inhibitors, indinavir, methadone, nelfinavir, oral contraceptives, pimozide, rifabutin, ritonavir, saquinavir, sildenafil, tacrolimus, trazodone, tricyclic antidepressants, warfarin, and zidovudine. 

Others Acetaminophen, amiodarone, carbamazepine, delavirdine, efavirenz, nevirapine, quinidine, repaglinide, sildenafil, tadalafil, trazodone, vardenafil Amiodarone, amprenavir, atazanavir, ciprofloxacin, cisapride, clarithromycin, diltiozem, erythromycin, fluconazole, fluvoxamine, grapefruit juice (in high ingestion), indinavir, itraconazole, ketoconazole, nefazodone, nelfinavir, norfloxacin, ritonavir, telithromycin, troleandomycin, verapamil, voriconazole Carbamazepine, efavirenz, glucocorticoids, macrolide antibiotics, nevirapine, phenytoin, phenobarbital, rifabutin, rifapentine, rifampin, St. John s wort... 

D6 Tricyclic antidepressants (TCAs), benztropine, perphenazine, clozapine, haloperidol, codeine/oxycodone, risperidone, class Ic antiarrhythmics, 3 blockers, trazodone, paroxetine, maprotiline, amoxapine, duloxetine, mirtazapine (partly), venlafaxine, bupropion Fluoxetine, paroxetine, duloxetine, hydroxybupropion, methadone, cimetidine, haloperidol, quinidine, ritonavir Phenobarbital, rifampin... 

Trazodone is a substrate but not a potent inhibitor of CYP3A4. As a result, combining trazodone with potent inhibitors of CYP3A4, such as ritonavir or ketoconazole, may lead to substantial increases in trazodone levels. 

Two cases of serotonin syndrome were attributed to adding ritonavir to established fluoxetine treatment. In one patient this was managed by halving the fluoxetine dose, and in the other ritonavir was withdrawn. Other cases of the serotonin syndrome have been seen in patients taking ritonavir or indinavir with fluoxetine. One involved the additional use of trazodone , (p.l229), and the other involved large quantities of grapefruit , (p.1217). 

An in vitro study demonstrated that the metabolism of trazodone to its principal metabolite, meta-chlorophenylpiperazine (mCPP), was inhibited by ritonavir, which is a potent inhibitor of the cytochrome P450 isoenzyme CYP3A4. Indinavir was also a strong inhibitor of mCPP formation, whereas saquinavir and nelflnavir were considerably less potent inhibitors. ... 

Trazodone is a substrate for CYP3A4 and inhibitors of this enzyme such as ritonavir and indinavir may inhibit its metabolism, leading to substantial increases in trazodone plasma concentrations with the potential for adverse effects. ... 

Ritonavir impairs the clearance of trazodone with an increased potential for adverse effects. Other protease inhibitors may interact similarly. 

The FDA in the US and the manufacturers of trazodone recommend that a lower dose of trazodone should be considered if it is given with potent CYP3A4 inhibitors sueh as the protease inhibitors ritonavir and indina-vir. However, the UK manufaeturer also suggests that the eombination should be avoided where possible. ... 

Greenblatt DJ, von Moltke LL, Harmatz JS, Fogeknan SM, Chen G, Graf JA, Mertzanis P, Byron S, Culm KE, Granda BW, Daily JP, Shader RI. Short-term exposure to low-dose ritonavir impairs clearance and enhances adverse effects of trazodone. J Clin Pharmacol (2003) 43, 414-22. 

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