Quinidine Protease inhibitors

Indinavir levels are raised by interleukin-2, but not affected by influenza vaccine or quinidine. Protease inhibitors are predicted to increase quinidine levels. Nelfinavir does not appear to interact with pancreatic enzyme supplements. In one case report, the combination of ritonavir/saquinavir and fusidic acid raised plasma levels of all three drugs. 

Use of a hERG blocker in a patient also taking CYP3A4 inhibitors (e.g. antibacterial macrolides, azole antifungals, HIV protease inhibitors) or CYP2D6 inhibitors (quinidine, halofantrine, fluoxetine, paroxetine, thioridazine, terbinafine) the hERG blocker, if mostly metabolized by these CYP isoforms, may accumulate because... 

Naproxen Olanzapine Tacrine Tertiary TCAs Theophylline Warfarin Type 1C antiarrhythmics Codeine Erythromycin Estrogen Quinidine Phosphodiesterase-5 inhibitors Protease inhibitors TCAs Terfenadine Zolpidem... 

Drugs affected by voriconazole include the following benzodiazepines, calcium channel blockers, cisapride, coumarin anticoagulants, cyclosporine, ergot alkaloids, HMG-CoA reductase inhibitors, NNRTIs, phenytoin, protease inhibitors, pimozide, proton pump inhibitors, quinidine, prednisolone, rifabutin, sirolimus, sulfonylureas, tacrolimus, vinca alkaloids. 

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. 

Rifampin is known to induce the hepatic microsomal enzymes that metabolize various drugs such as acetaminophen, oral anticoagulants, barbiturates, benzodiazepines, beta blockers, chloramphenicol, clofibrate, oral contraceptives, corticosteroids, cyclosporine, disopyramide, estrogens, hydantoins, mexiletine, quinidine, sulfones, sulfonylureas, theophyllines, tocainide, verapamil, digoxin, enalapril, morphine, nifedipine, ondansetron, progestins, protease inhibitors, buspirone, delavirdine, doxycycline, fluoroquinolones, losartan, macrolides, sulfonylureas, tacrolimus, thyroid hormones, TCAs, zolpidem, zidovudine, and ketoconazole. The therapeutic effects of these drugs may be decreased. 

Drugs that might be affected by lopinavir/ritonavir include ergot derivatives, oral contraceptives, antiarrhythmics, HMG-CoA reductase inhibitors, HIV protease inhibitors, atovaquone, calcium channel blockers, ketoconazole, itraconazole, pimozide, cisapride, clarithromycin, disulfiram, metronidazole, immunosuppressants, midazolam, triazolam, narcotic analgesics, rifabutin and rifabutin metabolite, sildenafil, warfarin, bupropion, clozapine, desipramine, piroxicam, quinidine, theophylline, and zolpidem. 

WARNING Co administration w/ ritonavir assoc w/ Hep hepatic decomp w/ fatalities. D/C w/ S/Sxs of H Uses HIV 1 Infxn w/ highly Tx-experienced pts or HIV 1 strains resistant to multiple protease inhibitors. Must be used w/ ritonavir 200 mg Action Antiretroviral HIV-1 protease inhibitor Dose 500 mg PO bid w/ food, administer w/ ritonavir 200 mg PO bid Caution [C, -] Sulfa aU gy, Uvct Dz Contra Mod-severe hepatic insuff concomitant use w/ amiodarone, astemizole, bepridil, cisapride, ergots, flecainide, lovastatin, midazolam, pimozide, propafenone, quinidine, rifampin, simvastatin, terfenadine, triazolam, St. John s wort Disp Caps SE HA, GI distress, rash, fati e, fat redistribution, hyperglycemia, Hep, liver Dz, lipid elevations Interactions T Effects OF anticoagulants, antipits, azole antifun-... 

Nelfinavir (Viracept) is probably the most commonly used protease inhibitor because of its low incidence of serious adverse effects. Its most common side effects are diarrhea and flatulence these may resolve with continued use. In addition to the drugs contraindicated for use with all protease inhibitors, amiodarone, rifampin, and quinidine are contraindicated in patients taking nelfinavir. 

Lopinavir/Ritonavir (Kaletra) [Anrirelroviral/Protease Inhibitor] Uses HIV Infxn Action Protease inhibitor Dose Adults. Tx naive 2 tab PO daily or 1 tab PO bid Tx experiencedpt 1 tab PO bid (T dose if w/ amprenavir, efavirenz, fosamprenavir, nelfinavir, nevirapine) Peds. 7-15 kg 12/3 mg/kg PO bid 15-40 kg 10/2.5 mg/kg PO bid >40 kg Adult dose w/ food Caution [C, /-] Numerous interactions Contra w/drugs dependent on CYP3A/CYP2D6 (Table VI-8) Disp Tab, soln SE Avoid disulfiram (soln has EtOH), metronidazole GI upset, asthenia, T cholesterol/triglycerides, pancreatitis protease metabolic synd Interactions T Effects Wl clarithromycin, erythromycin T effects OF amiodarone, amprenavir, azole andfungals, bepridil, cisapride, cyclosporine, CCBs, ergot alkaloids, flecainide, flurazepam, HMG-CoA reductase inhibitors, indinavir, lidocaine, meperidine, midazolam, pimozide, propafenone, propoxyphene, quinidine, rifabutin, saquinavir, sildenafil, tacrolimus, terfenadine, triazolam, zolpidem 1 effects Wl barbiturates, carbamazepine, dexamethasone, didanosine, efavirenz, nevirapine, phenytoin, rifabutin, rifampin, St. John s wort 1 effects OF OCPs, warfarin EMS Use andarrhythmics and benzodiazepines... 

Inhibitors of OATP transport are typically ster-ically bulky compounds, including anions, cations, and neutral compounds (95). Various medications have been shown to interact with OATPs, including HMG CoA reductase inhibitors, cyclosporine, quinidine, rifampin, ketoconazole, verapamil, and certain protease inhibitors. Cyclosporine and rifampin have relatively high ratios of plasma concentration to Ki, suggesting the potential for clinically significant drug-drug interactions via modulation of OATP. On the other hand, plasma concentrations of pravastatin are... 

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... 

Clearance of quinidine depends on CyP 3A4. Induction of this system by drugs such as carbamazepine, phenytoin, and St. John s Wort leads to enhanced clearance of quinidine. Diminished organ perfusion, CyP 3A4 inhibition by grapefruit juice or erythromycin, or co-administration with protease inhibitors results in decreased clearance. Quinidine itself has been reported to dilate peripheral blood vessels, resulting in mild to moderate hypotension and reduced clearance over the short term. Quinidine affects the rate of clearance of digoxin, Quinidine is analyzed by either HPLC or immunoassay. Fluorescence techniques should be considered obsolete. 

The concept of a proteolytic mechanism in the production of inflammatory manifestations is supported by the demonstration of anti-inflammatory activity in various protease inhibitors, e.g. the trypsin inhibitors of the pancreas, soya bean, ovomucoid and potato . It is interesting to note that the inhibitor from potatoes exerts its effect even after the inflammation is well established , suggesting that protease action is a continuing feature of inflammation and not simply an initiating process. Various esterase inhibitors (dyflos, quinine, quinidine and chloroquine) also reduce capillary permeability induced by heat and the permeability globulins . 

Von Mohke LL, Greenblatt DJ, Duan SX, Daily JP, Hannatz JS, Shader RI. Inhibiticn of desqnamine hydrcc lation (cytochreme P450-2DQ in vitro 1 quinidine and by viral protease inhibitors rel onto dn interactions in vivo. JPho/m iS ci (1 8) 87,1184-9. 

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