No pharmaceutical opinion available for this interaction.
Rifampin may induce the hepatic metabolism (CYP 3A4) and decrease the plasma concentration of Lopinavir / ritonavir.
3A4 (major), 13 identified metabolites, 5 of these metabolites are linked to the metabolism of ritonavir, transporters: MRP1, MRP2, OATP1A2, OATP1B1, P-gp
2C19 (strong), 1A2, 2C9 (moderate) UGT (moderate)
3A4 and 2D6 (strong), transporters: BCRP, MRP2, OATP1A2, OATP1B1, OATP1B3, OATP2B1, P-gp
Possible decrease of clinical efficacy.
Risk of a possible development of resistance to antiretroviral class.
1A2, 2C9, 2E1, P-gp
1A2, 2C9, 2C19, 3A4-7, UGT 1A1, P-gp
Increased risk of hepatotoxicity.
Choose an alternative.
Rifabutin either 150 mg QD, every 2 days or 3 times a week (see rifabutin with PIs) or choose an antibiotic that does not interact with PIs.
Hepatotoxicity: elevation of hepatic transaminases by 3 to 5 fold, fatigue, unusual weakness, nausea, vomiting, anorexia, abdominal pains, pale stools, dark urine, jaundice.
|400/100 mg||*||600/150mg/800/200 mg|
|- 55%||- 2%/- 7% **||- 28%/+ 13% ††|
|- 99%||- 57%/+ 3% **|
|- 75%||- 16%/- 2% **||- 37%/+ 2% ††|
|600 mg||600 mg||600 mg|
|10||14 (11-24)||21 (2-22)|
Ref #673: Refers to the PK parameters of lopinavir.
Ref #1444: * All patients received lopinavir/r 400/100 mg BID for 15 days. For the next nine days group 1 received lopinavir/r 800/200 mg BID and group 2 lopinavir/r 400/400 mg BID.
** Ratios based on lopinavir concentrations on day 24 relative to day 10.
Nine subjetcs experimented an increase of hepatic enzymes of grade 2. Seven (21%) of them stopped the therapy. The study was made in such a way that it is difficult to determine if the hepatotoxicity is more frequent than with the use alone of rifampicin for the same population.
Ref #2178: Study not completed in 11 healthy patients receiving lopinavir/r 600/150 mg or 800/200 mg BID with rifampin 600 mg QD, because 10 subjects suffered from severe No/Vo and an increase of hepatic enzymes (AST/ALT).
Ref #2398 : † In the early study, lopinavir / ritonavir (400/100 mg BID) increased to 600/150 mg BID on day 9, and 800/200 mg BID on day 16.
†† Compared to lopinavir / ritonavir (400/100 mg BID) alone in early treatment.
With the standard dose of lopinavir/ritonavir (400/100 mg BID), the addition of rifampicin decreased lopinavir AUC and Cmax by 68% and 54%, respectively. Median lopinavir trough concentrations at baseline were 4.3 mg/L and decreased to 0.2 mg/L after 1 week of rifampicin. After the first lopinavir/ritonavir dose increase trough concentrations were 1.7 mg/L, and 3.7 mg/L after the second dose increase. There were no significant differences in lopinavir AUC, Cmax, C0h or C12h between baseline and the double dose. Treatment was generally well tolerated with only two subjects developing asymptomatic grade 3/4 alanine aminotransferase elevations. The authors concluded that doubling the dose of the tablet formulation of lopinavir/ritonavir overcomes the induction by rifampicin and there was less hepatotoxicity than previously seen in healthy volunteer studies.
Ref #2663 : In this study with 30 patients VIH+ in Vietnam, the association of "super-boosted" lopinavir/ritonavir (400/400 mg BID) with rifampicin (450-600 mg QD weight-based) seemed safe, though only 8 patients showed increased ALT. Authors concluded that this combination can be used as it appears to be well tolerated and until rifabutin becomes available in developing countries.
Ref #2894 : In a cohort of children receiving lopinavir/ritonavir plus additional ritonavir (to a ratio of LPV:RTV, 1:1), Lopinavir Cmin was similar between the 2 groups (n=15 children without and n=13 with rifampicin). In all 28 children, lopinavir Cmin was above the minimum therapeutic level (1 mg/L). As with adults this study found that additional ritonavir can be used to mitigate accelerated lopinavir elimination, overcoming the reduction of lopinavir levels caused by rifampicin.
Co-administration of rifampicin 600 mg QD with protease inhibitors such as darunavir/ritonavir, atazanavir/ritonavir and atazanavir alone also causes a decrease in AUC and Cmin of approximately 75% to 80%.
Ref #3116 : To increase the chance of achieving therapeutic serum levels and reduce the development of resistance and treatment failures some experts, as well as the CDC, recommend a 150mg QD dose. See rifabutin + PIs.