Atazanavir / ritonavir

Rifampin

Contraindicated.

No pharmaceutical opinion available for this interaction.

Mechanism

Rifampin increases the metabolism (CYP 3A4) and decreases the plasma concentration of Atazanavir / ritonavir.

Atazanavir / ritonavir

Pharmacodynamic effects

Possible decrease of clinical efficacy.

Risk of a possible development of resistance to antiretroviral class.

Recommendations

Alternative solution(s)

Rifampin

Pharmacodynamic effects

Increased risk of hepatotoxicity.

Recommendations

Choose an alternative.

Alternative solution(s)

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.

Monitor

Tests

Pharmacokinetic parameters
Parameters
Reference number
Frequency
Duration (days)
HIV
Dose
AUC 0-24h
Cmin
Cmax
# patients
Rifampin
1634 2396
QD QD
10 8*
- -
600 mg 600 mg**
   
   
   
  14
Atazanavir / ritonavir
1634 2396
QD BID**
10 11**
- -
400/200 mg 300 mg**/100 mg**
+ 10% *  
- 60% *  
- 18%*  
  14
Comment

Ref #1634: Rifampin and desacetyl rifampin exposures were comparable across different regimens of ATV/RTV, but were ~1.6 to 2.5 times higher that with rifampin alone.

* Compared to atazanavir 400 mg daily.

Ref #2324 : Study with 10 patients HIV negative receiving ATV 300 mg BID (stade 1) + Rifampin and ATV 400 mg + RIF 600 mg QD (stade 2) vs. ATV 300 mg BID. Despite the administration twice a day of atazanavir (300 mg BID), the Cmin of atazanavir was 44 ng/ml for patients receiving ATV 300 BID + RIF and 113 ng/ml for patients receiving ATV 400 + RIF compared to 811 ng/ml for patients receiving atazanavir 300 mg BID without rifampin.

Ref #2323 : Study with 71 patients HIV negative receiving 300/100 mg QD of ATV/r vs. ATV/r + RIF 300/100/600 mg vs. ATV/r + RIF 300/200/600 mg vs. ATV/r + RIF 400/200/600 mg.
Results : Cmin of 707, 3 ng/mL in patients under ATV/r vs. 18.1 in ATV/r/RIF 300/100/600 mg vs. 42,7 in ATV/r/RIF 300/200/600 mg vs. 52,9 in ATV/r/RIF 400/200/600 mg.

Réf #2396: Study with 3 stages :
During the 1st stage *, rifampicin 600 mg once a day during 8 days. Stage 2 **: Rifampin 600 mg + Atazanavir/ritonavir 300/100 mg BID during 11 days. Stage 3: Increase in dosage of atazanavir/ritonavir 400/100 mg BID.
Following this increase in dosage, 3 patients had an increase of transaminases and vomiting. The treatment had to be stopped.

Co-administration of rifampicin 600 mg QD with protease inhibitors such as lopinavir/ritonavir, darunavir/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.

Reference
  • 1634
    Burger D, Agarwala S, Child Mutt, et al. Effect of Rifampin on Steady--state Pharmacokinetics of Atazanavir and Ritonavir in Healthy Subjects. 12th Conference on Retroviruses and Opportunistic Infections. Boston. Feb 22-25, 2005. Abstract #657
  • 2323
    Burger DM, Agarwala S, Child M, Been-Tiktak A, Wang Y, Bertz R. Effect of rifampin on steady-state pharmacokinetics of atazanavir with ritonavir in healthy volunteers. Antimicrob Agents Chemother 2006;50:3336–42.
  • 2324
    Acosta EP, Kendall MA,Gerber JG, et al. Effect of concomitantly administered rifampin on the pharmacokinetics and safety of atazanavir administered twice daily. Antimicrob Agents Chemother 2007; 51:3104–10.
  • 2396
    Haas DW, Koletar SL, Laughlin L, et al. Hepatotoxicity and gastrointestinal intolerance when healthy volunteers taking rifampin add twice-daily atazanavir and ritonavir.. J Aquir Immune Defic Syndr, 2009, 50(3): 290-293.
  • 2397
    Mallolas J, Sarasa M, Nomdedeu M, et al Pharmacokinetic interaction between rifampicin and ritonavir-boosted atazanavir in HIV-infected patients. HIV Med, 2007, 8(2): 131-134.
  • 2613
    Atazanavir (Reyataz), Bristol-Myers Squibb, Quebec, Canada, Sept 2013.
  • 3116
    Center for Disease Control and prevention. Managing Drug Interactions in the Treatment of HIV-Related Tuberculosis. Disponible: http://www.cdc.gov/tb/publications/guidelines/tb_hiv_drugs/recommendations03.htm Publié le 22 sept 2014. Consulté le 11 janvier 2018.