Safety, Efficacy and Pharmacokinetics of Ritonavir 400mg/Saquinavir 400mg Twice Daily plus Rifampicin Combined Therapy in HIV Patients with Tuberculosis

Abstract

Therapeutic concentrations of the studied drugs and reduction of viral load were achieved; adverse events are the main limitation of use of a ritonavir/saquinavir regimen in treatment-naive patients, but its clinical benefits were evident.

Clinical Relevance of Drug Interactions in HIV-Infected Patients Receiving Antiretroviral Therapy

“…Besides, most treatment guidelines for HIV/AIDS patients extend this contraindication even to PIs combined with ritonavir used as a pharmacokinetic extension agent (enhancer). (DHHS, 2011) However, for saquinavir, (Rolla et al, 2006) atazanavir, and lopinavir, (La Porte et al, 2004) some studies show that adding ritonavir may counteract such effect in to some extent. In these cases, both saquinavir/ritonavir dose must be adjusted to 400/400 mg twice daily, (Aaron et al, 2004;de Jong et al, 2004;Rolla et al, 2006;) and lopinavir/ritonavir to 400/400 mg/12 hours or to 800/200 mg/12 hours.…”

“…(DHHS, 2011) However, for saquinavir, (Rolla et al, 2006) atazanavir, and lopinavir, (La Porte et al, 2004) some studies show that adding ritonavir may counteract such effect in to some extent. In these cases, both saquinavir/ritonavir dose must be adjusted to 400/400 mg twice daily, (Aaron et al, 2004;de Jong et al, 2004;Rolla et al, 2006;) and lopinavir/ritonavir to 400/400 mg/12 hours or to 800/200 mg/12 hours. (Aaron et al, 2004;de Jong et al, 2004;La Porte et al, 2004) Regarding the concomitant administration of saquinavir/ritonavir (1000/100 mg once daily) with rifampicin, because of some reports of liver toxicity, it is recommended to avoid such a combination.…”

“…(Kashuba, 2005) Combined administration of antacids does not seem to significantly affect the amount absorbed of fosamprenavir, (Ford et al, 2005) or raltegravir; however it is recommended to separate the taking of the two drugs when they are used in pharmacological therapy. (Kiser et al, 2010) Aaron et al, 2004;Benator et al, 2007;Blumberg et al, 2003;DeJong et al 2004;Finch et al, 2002;Hamzeh et al, 2003;Kraft et al, 2004;La Porte et al, 2004;Polk et al, 2001;Ribera et al, 2007;Rolla et al, 2006;Spradling et al, 2002) Ritonavir (Aaron et al, 2004;Blumberg et al, 2003;DeJong et al 2004;Finch et al, 2002;Spradling et al, 2002) 1: very high risk 2: high risk Adjust rifabutin dose 150 mg/48 hours, with no change in ritonavir Indinavir (Hamzeh et al, 2003, Kraft et al, 2004 1: very high risk 2: high risk Adjust the dose of rifabutin 150 mg/24 hours and indinavir at 1,000 mg/8 hours Saquinavir (Aaron et al, 2004;Blumberg et al, 2003;DeJong et al 2004;Finch et al, 2002;Ribera et al, 2007;Rolla et al, 2006;Spradling et al, 2002) 1: very high risk 2: high risk Use usual dose of rifabutin (300 mg/day), with no change in saquinavir Nelfinavir (Aaron et al, 2004;Benator et al, 2007;Blumberg et al, 2003;DeJong et al 2004;…”

“…This combination is considered absolutely contraindicated McCance-Katz et al, 2006;Matteelli et al, 2007a;Ramachandran et al, 2006;Ribera et al, 2001) Delavirdine (Borin et al, 1997;DeJong et al 2004;McCance-Katz et al, 2006;Spradling et al, 2002) Nevirapine (Benator et al, 2007;Blumberg et al, 2003;Borin et al, 1997;Burger et al, 2006;Hamzeh et al, 2003;Kraft et al, 2004;La Porte et al, 2004;Polk et al, 2001;Ramachandran et al, 2006;Ribera et al, 2001Ribera et al, , 2007Rolla et al, 2006) 2: high risk 3: medium risk…”

Rifamycin Use in HIV-Infected Patients with Tuberculosis

“…A study of 30 co-infected HIV/TB patients given 400 mg saquinavir and 400 mg ritonavir plus two NRTIs suggests that these doses are able to maintain therapeutic concentrations of rifampin and the PIs; however, the study had a substantial attrition rate with ten patients dropping out during TB therapy and another fifteen patients dropping when ART was added. (Rolla et al, 2006) Hepatotoxicity is one of the primary concerns facing clinicians when using a saquinavircontaining regimen with the rifamycins. A 2009 two-period crossover study consisting of 28 healthy volunteers received either 600 mg rifampin once daily or 1000/100 mg saquinavirritonavir twice daily for two weeks.…”