Indinavir Ritonavir

Peptidases encoded by many viruses play essential roles at various stages of viral replication, including the coordinated assembly and maturation of virons [7a]. Viral peptidases have become important drug targets in the treatment of viral infections. Of note are inhibitors of proteases of the human immunodeficiency virus (HIV), particularly HIV-1 protease (HIV-1 retropepsin, EC 3.4.23.16) and HIV-2 protease [47-50], Drugs in this class, which include indinavir, ritonavir, and saquinavir, are useful in the treatment of AIDS, especially when administered as a cocktail together with one of the drugs that act on the viral retrotranscriptase (e.g., didanosine, stavudine, and zidovudine (AZT)). 

HIV protease inhibitors (eg, indinavir, ritonavir, nelfinavir, saquinavir [see Rifapentine-indinavir interaction above]). 

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... 

This class of antiretrovirals may be considered the most potent therapeutic agents for HIV to date. Protease inhibitors are used in combination regimens and combinations of reverse-transcriptase inhibitors and protease inhibitors have been proven most effective to decrease viral load and prolong survival. However, the protease inhibitors generally show poor penetration into the CNS and thus have no effect on aids dementia. The present Pis available for the treatment of HIV are indinavir, ritonavir, nel-finavir, saquinavir and (fos)amprenavir, atazanavir and lopinavir (in combination with ritonavir as ritonavir improves the bioavailability of lopinavir by inhibiting its metabolism in the liver by CYP3A). 

Efavirenz Nelfinavir Ritonavir Amprenavir Indinavir Ritonavir Saquinavir... 

The protease inhibitors are used in the multidrug therapy of HIV infection. Resistance to the HIV protease inhibitors results from mutations in the protease gene and perhaps the cleavage sites of gag-pol. Although different protease mutations tend to be associated with resistance to individual drugs, resistance to one protease inhibitor is often associated with a less than optimal response to other agents of this class. Indinavir, ritonavir, and lopinavir require more mutations to lose their effectiveness than do the other protease inhibitors. 

Lopinavir Delavirdine, indinavir, ritonavir, darunavir Fosamprenavir, efavirenz, nelfinavir, nevirapine, tenofovir... 

Nelfinavir Fosamprenavir, delavirdine, efavirenz, indinavir, ritonavir, saquinavir ... 

HIV PR inhibitors with acceptable oral availability and pharmacokinetic properties offer great promise for the treatment of HIV infection and AIDS. Efficacy studies of indinavir, ritonavir, or nelfinavir using plasma viral RNA as a marker have demonstrated up to three log reductions in RNA copy numbers that are... 

ALMOTRIPTAN, ELETRIPTAN PROTEASE INHIBITORS -INDINAVIR, NELFINAVIR, RITONAVIR Possibly t adverse effects when almotriptan or eletriptan is coadministered with indinavir, ritonavir (with or without lopinavir), or nelfinavir Inhibition of CYP3A4- and possibly CYP2D6-mediated metabolism of eletriptan, and CYP3A4-mediated metabolism of almotriptan Avoid co-administration... 

ALFENTANIL, BUPRENORPHINE, FENTANYL, TRAMADOL PROTEASE INHIBITORS Possibly t adverse effects when buprenorphine is co administered with indinavir, ritonavir (with or without lopinavir) or saquinavir Inhibition of CYP3A4 (CYP2D6 in the case of tramadol) Halve the starting dose and titrate to effect. For single injection of fentanyl, monitor sedation and respiratoiy function closely. If continued use of fentanyl, i dose may be required. Concomitant use of ritonavir and transdermal fentanyl is not recommended... 

ITRACONAZOLE, KETOCONAZOLE PROTEASE INHIBITORS Possibly t levels of ketoconazole by amprenavir, indinavir and ritonavir (with or without lopinavir). Conversely, indinavir, ritonavir and saquinavir levels t by itraconazole and ketoconazole Inhibition of, or competition for, CYP3A4-mediated metabolism Use itraconazole with caution and monitor for adverse effects. No dose adjustment is recommended for doses <400 mg/day of ketoconazole... 

INDINAVIR RITONAVIR t efficacy and t adverse effects of indinavir. Risk of nephrolithiasis if the dose of indinavir exceeds 800 mg twice a day Inhibition of CYP3A4-mediated metabolism of indinavir Dose of indinavir can be i from 800 mg three times a day to 600 mg twice daily. Adequate hydration and monitoring are essential. Adults must drink at least 1500 mL/24 hours... 

Burger DM, Hugen PW, Aarnoutse RE, Dieleman JP, Prins JM, van der Poll T, ten Veen JH, Mulder JW, Meenhorst PL, Blok WL, van der Meer JT, Reiss P, Lange JM. A retrospective, cohort-based survey of patients using twice-daily indinavir + ritonavir combinations pharmacokinetics, safety, and efficacy J Acquir Immune Defic Syndr 200I 26(3) 218-24. 

Solas C, Basso S, Poizot-Martin I, Ravaux I, Gallais H, Gastaut JA, Durand A, Lacarelle B. High indinavir Cmin is associated with higher toxicity in patients on indinavir-ritonavir 800/100 mg twice-daily regimen. J Acquir Immune Defic Syndr 2002 29(4) 374-7. 

The combination of indinavir + ritonavir 400/400 mg bd plus two NRTIs has been studied in 93 patients in an open, uncontrolled, multicenter trial (7). Raised triglycerides (n = 78) and cholesterol (n = 63) were the commonest adverse effects, followed by nausea (n — 22) and circumoral paresthesia (n = 9). Withdrawal was required in four cases of nausea, four of lipodystrophy, one of diarrhea, and one of osteonecrosis. 

Padberg J, Eritsche L, Bergmann E, Schurmann D, Suttorp N. Nephropathy and renal colic in patients treated with indinavir, ritonavir plus indinavir or ritonavir plus saquinavir. AIDS 1999 13 2173-2174. 

Clinically important, potentially hazardous interactions with indinavir, ritonavir... 

Clinically important, potentially hazardous interactions with amiodarone, anisindione, anticoagulants, corticosteroids, cyclosporine, dicumarol, indinavir, ritonavir, solifenacin, tacrolimus, warfarin... 

HIV protease inhibitors Indinavir Ritonavir Saquinavir Prokinetic ... 

Atazanavir plus lamivudine (or emtricitabine) plus zidovudine (or stavudine) Indinavir-ritonavir plus lamivudine (or emtricitabine) plus zidovudine (or stavudine) Lopinavir-ritonavir p/us emtricitabine plus zidovudine (or stavudine)... 

Inhibit viral aspartate protease Indinavir, ritonavir, saquinavir, nelfinavir... 

---