Protease inhibitors Dexamethasone

Other than RIF and Taxol, many other commonly used clinical drugs have also been shown to activate PXR. These include peptide-mimetic HIV protease inhibitors [53], the cholesterol-lowering lovastatin and the anti-inflammatory dexamethasone [54]. A more comprehensive analysis of the effect of commonly used clinical drugs on PXR activation has recently been published by Sinz and colleagues [55]. 

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... 

Diabetes mellitus in a 36-year-old man with acute pancreatitis could not be controlled with continuous subcutaneous insulin infusion, even with doses up to 1800 U/ day, because of insulin resistance (168). Intravenous insulin by pump had to be stopped because of a catheter infection. The continuous subcutaneous infusion of freeze-dried insulin and the addition of aprotinin, a protease inhibitor, soluble dexamethasone or prednisolone, and intravenous immunoglobulin was ineffective. An implantable pump for intraperitoneal delivery established good regulation at a dosage of 30 U/day. 

CORTICOSTEROIDS PROTEASE INHIBITORS-RITONAVIR t plasma levels of betamethasone, dexamethasone, hydrocortisone, prednisolone and both inhaled and intranasal budesonide and fluticasone with ritonavir (with or without lopinavir) Inhibition of CYP3A4-mediated metabolism Monitor closely for signs of corticosteroid toxicity and immunosupression, and i dose as necessaiy. Consider using inhaled bedometasone... 

Clinically important, potentially hazardous interactions with amiodarone, amprenavir, anisindione, antacids, anticoagulants, aprepitant, atazanavir, atovaquone, beclomethasone, buprenorphine, corticosteroids, cortisone, cyclosporine, cyproterone, dabigatran, dapsone, darunavir, delavirdine, dexamethasone, dicumarol, digoxin, eszopiclone, flunisolide, fosamprenavir, gadoxetate, gestrinone, halothane, imatinib, isoniazid, itraconazole, ketoconazole, lapatinib, lorcainide, methylprednisolone, midazolam, nelfinavir, nifedipine, oral contraceptives, phenylbutazone, prednisone, protease inhibitors, pyrazinamide, ramelteon, ritonavir, saquinavir, solifenacin, sunitinib, tacrolimus, telithromycin, temsirolimus, tipranavir, tolvaptan, trabectedin, triamcinolone, triazolam, voriconazole, warfarin, zaleplon... 

Anthracyclines Vinca alkaloids Digoxin Cyclosporine Protease inhibitors Dexamethasone... 

Some inducers of CYP3A4 are also inducers of P-glycoprofein These include dexamethasone, rifampin and St. John s wort. The last two have been implicated in the induction of the metabolism of cyclosporin, certain HMG-CoA reductase inhibitors (statins) and several HIV protease inhibitors, with resulting loss of efficacy of these compounds. 

In another study possibly relating to the mechanism of action of retinoic acid on these myeloid cells, Takenaga et al. (1980) using the murine myeloid leukemia cell line M-1 have shown that retinoic acid is able to inhibit in a reversible manner the dexamethasone-dependent differentiation of these cells, and that retinoic acid induces the M-1 cells to synthesize and release into the medium a protease-sensitive inhibitor of differentiation (Takenaga et al., 1981). 

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