Paroxetine Ritonavir

Drugs that may affect phenothiazines include anticholinergics, beta-blockers, meperidine, paroxetine, ritonavir, and thiazide diuretics. 

Drugs that may affect aprepitant include CYP 3A4 inhibitors (eg, clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin), CYP3A4 inducers (eg, carbamazepine, phenytoin, rifampin), and paroxetine. 

Aprepitant (Emend) [Centrally Acting Antiemetic] Uses Pre-vents N/V assoc w/ emetogenic CA chemo (eg, cisplatin) (use in combo w/ other antiemetics) Action Substance P/neurokinin l(NKi) receptor antagonist Dose 125 mg PO day 1, 1 h before chemo, then 80 mg PO qAM days 2 3 Caution [B, /-] Contra Use w/ pimozide, Disp Caps SE Fatigue, asthenia, hiccups Interactions T Effects W/ clarithromycin, diltiazem, itraconazole, ketoconazole, nefazodone, nelfinavir, ritonavir, troleandomycin T effects OF alprazolam, astem-izole, cisapride, dexamethasone, methylprednisolone, midazolam, pimozide, terfe-nadine, triazolam, chemo agents, eg, docetaxel, etoposide, ifosfamide, imatinib, irinotecan, paclitaxel, vinblastine, vincristine, vinorelbine i effects W/ paroxetine,... 

Antibacterials Ciprofloxacin Erythromycin Isoniazid Antidepressants Flnoxetine Huvoxamine Paroxetine Antifungal drugs Fluconazole Itraconazole Ketoconazole Miconazole Antiviral drugs Indinavir Ritonavir Saquinavir Cardiovascular drugs Amiodarone Diltiazem Quinidine Verapamil... 

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... 

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. 

PROTEASE INHIBITORS SSRIs t adverse effects of fluoxetine, paroxetine and sertraline when co-administered with ritonavir (with or without lopinavir). Cardiac and neurological events have been reported, including serotonin syndrome Ritonavir is associated with the most significant interaction of the protease inhibitors due to potent inhibition of CYP3A, CYP2D6, CYP2C9 and CYP2C19 isoenzymes Warn patients to watch for t side-effects of SSRIs and consider 1 dose ofSSRI... 

Clinically important, potentially hazardous interactions with alprazolam, astemizole, carbamazepine, cisapride, clarithromycin, dexamethasone, diltiazem, docetaxel, ifosfamide, imatinib, irinotecan, itraconazole, ketoconazole, methylprednisolone, midazolam, nefazodone, oral contraceptives, paroxetine, phenytoin, pimozide, rifampin, ritonavir, terfenadine, tolbutamide, trabectedin, troleandomycin, vinblastine, vincristine, warfarin... 

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... 

Ajmaline, ajamlicine, flecainide, fluoxetine, isoniazid, ketoconazole, lobeline, nefazodone, paroxetine, (7 )-propaphenooe, quinidine, ritonavir, "statins," yohimbine, venlafaxine... 

Mechanism-based enzyme inhibition may be one of the more important types of DDIs, and examples of drugs that inhibit GYP enzymes in this fashion include paroxetine inhibition of GYP2D6, verapamil inhibition of GYP3A4, and the inhibition of GYP3A4 by protease inhibitors such as ritonavir. Some of the other drugs that cause mechanism-based inhibition of GYP enzymes include erythromycin, fluvoxamine, and ethinyl estradiol. 

Some of the clinically important drugs that have been identified to be mechanism-based CYP3A4 inhibitors include antibiotics (e g., erythromycin), anticancer drugs (e.g., irinotecan), antidepressants (e g., fluoxetine and paroxetine), anti-FIIV agents (e.g., ritonavir and... 

CYP2D6 is involved in the biotransformation of 15-20% of drugs undergoing oxidative metabolism. Important inhibitors include cimetidine, fluoxetine, paroxetine, amiodarone, quinidine and ritonavir. 

However, there is one report of a possible decrease in valproate levels in a 30-year-old man after starting lopinavir/ritonavir. This patient, who had been taking valproic acid 375 mg daily as divalproex sodium for 7 months after an episode of mania, had a subtherapeutic valproic acid level of 197 micromol/L, and the dose was increased to 250 mg three times daily. After 25 days his trough valproic acid level was 495 micromol/L, and an antiretroviral regimen of lamivudine, zidovudine, lopinavir/ritonavir was started, and paroxetine for depression. Four days later he was hy-pomanic and the paroxetine was replaced with sertraline, which the patient discontinued. Twenty-one days later he had become increasingly manic, and the valproic acid level was found to be 238 micromol/L, about 50% lower than the previous level. An increase in valproic acid dose to 1.5 g daily was eventually required to achieve a therapeutic level of 392 micromol/L. 

Fluoxetine modestly raised the levels of ritonavir, and ritonavir is predicted to raise levels of fluoxetine, paroxetine and sertraline. A few cases of the serotonin syndrome have been attributed to the use of fluoxetine and ritonavir. The concurrent use of escitalo-pram and ritonavir do not appear to affect the pharmacokinetics of either drug. 

The UK manufacturers of ritonavir predict that it may raise the levels of SSRIs (fluoxetine, paroxetine, sertraline) due to the inhibitory effect of ritonavir on the cytochrome P450 isoenzymes CYP2D6. The US manufacturers do not mention any specific SSRIs. Both manufacturers suggest careful monitoring of adverse effects when these drugs are used with ritonavir a dose reduction of the SSRI may be required. ... 

Actinomycin-D, amitriptyline, amoxapine, amprenavir, apomorphine atazanavir, citalopram, clomipramine, desipramine, dothiepin, doxepin, efavirenz, fluoxetine, imipramine, indinavir, lopinavir, maprotiline, meropenem, mianserin, nelfinavir, nevirapine, norfluoxetine, nortriptyline, pergolide, paroxetine, procarbazine, ritonavir, sertraline, saquinavir, trimipramine, vincristine, zidovudine... 

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