Lopinavir Rifampin

Protease inhibitors (amprenavir, atazanavir, indinavir, lopinavir, nelfinavir, ritonavir, saquinavir) Rifampin... 

Drugs that might decrease plasma concentrations of lopinavir/ritonavir include rifampin, phenobarbital, carbamazepine, phenytoin, azole antifungals, delavirdine, rifabutin, St. John s wort, efavirenz, nevirapine, and corticosteroids. 

Lopinavir is available in the United States only as a fixed-dose combination with ritonavir (Kaletra). In this regimen, a low dose of ritonavir is used to inhibit the rapid inactivation of lopinavir by CYP3A4. Side effects, which are generally mild, include diarrhea, nausea, asthenia, and headache. Pancreatitis occurs rarely. Ritonavir is a potent inhibitor of CYP3A4 and also inhibits CYP2D6. In addition to the drugs contraindicated for all protease inhibitors, fiecainide, propafenone, pimozide, and rifampin should not be given with lopinavir-ritonavir combination therapy. 

Nevirapine is a moderate inducer of CYP3A metabolism, resulting in decreased levels of amprenavir, indinavir, lopinavir, saquinavir, efavirenz, and methadone (Table 49-4). Drugs that induce the CYP3A system, such as tipranavir, rifampin, rifabutin, and St. John s wort, can decrease levels of nevirapine, whereas those that inhibit CYP3A activity, such as fluconazole, ketoconazole, and clarithromycin, can increase nevirapine levels. 

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... 

St. John s wart, rifampin, efavirenz, nevirapine and amprenavir will lower plasma concentrations of lopinavir due to their effect on cytochrome P-450 enzyme CYP3A4. Lopinavir increases plasma concentrations of ergot derivatives, triazolam, midazolam, and propafenone and should not be given together. 

Clinically important, potentially hazardous interactions with amiloride, aminoglycosides, amphotericin B, ampicillin, anisindione, anticoagulants, armodafinil, atorvastatin, azathioprine, azithromycin, bacampicillin, basiliximab, bezafibrate, bosentan, bupropion, carbenicillin, caspofungin, cholestyramine, clarithromycin, cloxacillin, co-trimoxazole, corticosteroids, cyclophosphamide, daclizumab, danazol, dicloxacillin, dicumarol, digoxin, diltiazem, disulfiram, echinacea, erythromycin, ethotoin, etoposide, ezetimibe, flunisolide, fluoxymesterone, fluvastatin, foscarnet, fosphenytoin, gemfibrozil, hemophilus B vaccine, HMG-CoA reductase inhibitors, imatinib, imipenem/cilastatin, influenza vaccines, ketoconazole, lanreotide, lopinavir, lovastatin, mephenytoin, methicillin, methoxsalen, methylphenidate, methylprednisolone, methyltestosterone, mezlocillin, mizolastine, mycophenolate, nafcillin, nisoldipine, NSAIDs, orlistat, oxacillin, penicillins, phellodendron, phenytoin, pravastatin, prednisolone, prednisone, pristinamycin, ranolazine, red rice yeast, rifabutin, rifampin, rifapentine, ritonavir, rosuvastatin, simvastatin, sirolimus, spironolactone, St John s wort, sulfacetamide, sulfadiazine, sulfamethoxazole, sulfisoxazole, sulfonamides, tacrolimus, telithromycin, tenoxicam, testosterone, ticarcillin, tolvaptan, trabectedin, triamterene, troleandomycin, ursodeoxycholic acid, vaccines, vecuronium, warfarin, zofenopril... 

Clinically important, potentially hazardous interactions with albendazole, aminoglutethimide, aspirin, bexarotene, carbamazepine, cyclophosphamide, dasatinib, diuretics, ephedrine, imatinib, itraconazole, lapatinib, live vaccines, lopinavir, methotrexate, phenobarbital, phenytoin, praziquantel, primidone, rifampicin, rifampin, temsirolimus, warfarin... 

Clinically important, potentially hazardous interactions with alprazolam, amiodarone, amphotericin B, arbutamine, bendroflumethiazide, benzthiazide, bisacodyl, bumetanide, carbimazole, chlorothiazide, chlorthalidone, cholestyramine, clarithromycin, conivaptan, cyclosporine, cyclothiazide, dan-shen, demeclocycline, devil s claw, dexmedetomidine, doxycycline, erythromycin, esomeprazole, ethacrynic acid, flunisolide, furosemide, ginseng, glycopyrrolate, glycopyrronium, hawthorn (fruit, leaf, flower extract), horsetail, hydrochlorothiazide, hydroflumethiazide, indapamide, licorice, lopinavir, mepenzolate, methyclothiazide, metolazone, minocycline, mistletoe, oxprenolol, oxytetracycline, paroxetine, phenylbutazone, polythiazide, propafenone, propantheline, quinethazone, quinidine, rabeprazole, rifampin, roxithromycin, sarsaparilla, senna, Siberian ginseng, squill, St John s wort, telithromycin, teriparatide, tetracycline, thiazide diuretics, tolvaptan, trichlormethiazide, verapamil... 

Clinically important, potentially hazardous interactions with amiodarone, atorvastatin, bepridil, carbamazepine, delavirdine, dihydroergotamine, etravirine, flecainide, itraconazole, ketoconazole, lidocaine, lopinavir, lovastatin, midazolam, phenobarbital, phenytoin, pimozide, propafenone, quinidine, rifabutin, rifampin, sildenafil, simvastatin, St John s wort, triazolam, vardenafil, warfarin... 

Clinically important, potentially hazardous interactions with alfuzosin, alprazolam, amphotericin B, anisindione, antacids, aprepitant, astemizole, atorvastatin, bosentan, ciclesonide, cimetidine, clorazepate, conivaptan, cyproterone, dasatinib, dexamethasone, dicumarol, didanosine, eplerenone, erythromycin, ethotoin, fentanyl, fesoterodine, fosamprenavir, fosphenytoin, grapefruit juice, HMG-CoA reductase inhibitors, imatinib, ixabepilone, lapatinib, lopinavir, lovastatin, mephenytoin, methylprednisolone, micafungin, midazolam, nilotinib, pimozide, prednisolone, prednisone, quinidine, rifampin, rimonabant, rivaroxaban, sildenafil, silodosin, simvastatin, sirolimus, solifenacin, temsirolimus, terfenadine, tolvaptan, triazolam, vardenafil, vinblastine, vincristine, warfarin... 

Clinically important, potentially hazardous interactions with amprenavir, aprepitant, atazanavir, carbamazepine, chlorpheniramine, cimetidine, clarithromycin, clorazepate, CNS depressants, darunavir, delavirdine, dexamethasone, efavirenz, erythromycin, esomeprazole, fluconazole, fluoxetine, fosamprenavir, grapefruit juice, griseofulvin, imatinib, indinavir, itraconazole, ivermectin, ketoconazole, lopinavir, nelfinavir, nevirapine, phenobarbital, phenytoin, primidone, rifabutin, rifampin, ritonavir, roxithromycin, saquinavir, St John s wort, telithromycin, tipranavir... 

Clinically important, potentially hazardous interactions with epirubicin, grapefruit juice, imatinib, lopinavir, micafungin, mizolastine, rifampin, ritonavir... 

Rifampicin (Rifampin). Rifampicin 600 mg daily for 10 days decreased the AUC of lopinavir (given as lopinavir/ritonavir 400/100 mg twice daily) by 75% in a study in healthy subjects. " A dose titration of lopinavir/ritonavir was earried out in healthy subjects to try and overcome the interaction with rifampicin. In 10 evaluable subjects, use of rifampicin 600 mg daily with lopinavir/ritonavir 800/200 mg twice daily decreased the minimum lopinavir level by 57% without affecting the maximum level, when compared with lopinavir/ritonavir 400/100 mg twice daily without rifampicin. In another 9 evaluable subjects, rifampicin 600 mg daily with lopinavir/ritonavir 400/400 mg twice daily did not alter the maximum or minimum level of lopinavir, but markedly increased ritonavir levels, when compared with lopinavir/ritonavir 400/100 mg twice daily without rifampicin. Of 29 subjects who received the adjusted doses of lopinavir/ritonavir with rifampicin, 9 subjects had grade 2 to 3 elevations in liver enzymes, and this was more eommon in the lopinavir/ritonavir 400/400 mg group than the lopinavir/ritonavir 800/200 mg group. 

Rifampin (potent CYP3A4 inducer) Ketoconazole (strong CYP3A4 inhibitor) Isoniazid/pyrazi namide Nevirapine Kaletra (lopinavir/nton avir)... 

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