Darunavir / ritonavir

Pravastatin

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

Darunavir / ritonavir may inhibit the transporters (OATP1B1 and OATP1B3) and increase the plasma concentration Pravastatin.

Darunavir / ritonavir

Pharmacodynamic effects

Recommendations

Alternative solution(s)

Pravastatin

Pharmacodynamic effects

Possible increased risk of HMG CoA inhibitor toxicity.

Recommendations

Use this combination with caution.

Start with a small dosage. Monitor closely for signs and symptoms of toxicity and adjust dosage as a function of efficacy and tolerance.

Alternative solution(s)

Monitor

Symptoms of toxicity associated with hypolipidemic agents : gastrointestinal effects, fatigue and muscular weaknesses, myalgias, muscular cramps, myopathies, rhabdomyolysis and myoglobinuria leading to renal insufficiency.

Tests

AST

ALT

CK

Lipidic profile

Pharmacokinetic parameters
Parameters
Reference number
# patients
Dose
Frequency
AUC
Cmax
HIV
Duration (days)
Pravastatin
2129 2380
14 28
40 mg 40 mg
QD QD
+ 81% + 21%
+ 63%  
+ -
  1-4; 15-18*
Darunavir / ritonavir
2129 2380
14 28
600/100 mg 600/100 mg
BID BID
   
   
+ -
7 12-14; 15-18*
Comment

Ref #2129: Wide variations in pravastatin concentrations between patients.
**The coadministration is generally well tolerated but due to wide variabilities between individuals, it is still recommended to start with a low dose of Pravastatin
** 4 patients on 14 have had an increase of AUC of 200% for Pravastatin.

Ref #2380: * Subjects received pravastatin (40 mg daily) on days 1-4, darunavir/ritonavir (600/100 mg twice daily) on days 12-14 and all drugs on days 15-18. Across all subjects, DRV/R increased pravastatin AUC by 21% (90% Cl=1.04-1.41). The effect of DRV/R on pravastatin AUC was less in this study than previously reported.

Réf #3391 : Case report of rhabdomyolysis in a patient on elvitegravir/cobicistat and pravastatin/fenofibrate.

Reference
  • 2107
    Darunavir (Prezista), Janssen, Ontario, Canada, 23 mai 2018.
  • 2129
    Sekar VJ, Spinosa-Guzman S, Marien K, et al. Interaction between the new HIV protease inhibitor darunavir (TMC114) and the lipid-lowering agent pravastatin. 8th International Workshop on Clinical Pharmacology of HIV Therapy, 16-18 April 2007, Budapest, Hungary. Abstract 54.
  • 2211
    Burger D, Stroes E, Reiss P et al. Drug interactions between statins and antiretroviral agents. Current opinion in HIV and AIDS 2008;3:247-251.
  • 2212
    Neuvonen PJ, Niem M and Backman JT. Drug interaction with lipid-lowering drugs: mecanisms and clinical relevance. Clin Pharmacol Ther 2006;80:565-581
  • 2380
    Aquilante, C. Kiser, J. Anderson, P. et al. DRV/R, pravastatin and pharmacogenetics: Influence of SL01B1 polymorphisms on pharmacokinetic variability in the drug-drug interaction between darunavir/ritonavir and pravastatin. Drug Interaction & Pharmacology Presentations at the 50th Interscience Conference on Antimicrobial Agents and Chemotherapy, Boston, September 2010. Abstract A1 2007
  • 2793
    Pravastatin (Pravachol), Bristol-Myers Squibb Canada, Québec, Canada, 18 octobre 2017.
  • 2787
    Jacobson TA. Comparative Pharmacokinetic Interaction Profiles of Pravastatin, Simvastatin and Atorvastatin When Coadministered Whit Cytochrome P450 Inhibitors. Am J Cardiol 2004; 94 : 1140-1146.
  • 1492
    Moyle GJ, Buss NE, and Gazzard B. Pravastatin 40-mg qd Does not Alter Protease Inhibitor (PI) Exposure or Virological Efficacy over 24 Weeks Therapy. 9th Conference on Retroviruses and Opportunistic Infections. Seattle, Washington. February 2002. Abstract 446-W
  • 2983
    Chauvin B, Drouot S, Barrail-Tran A and Taburet AM. Drug-Drug Interactions between HMG-coA reductase inhibitors (Statins) and Antiretroviral Protease Inhibitors. Clin Pharmacokinet 2013; 52: 815-831.
  • 3391
    Suttels V, Florence E, Leys J, et al. A 68-year old male presenting with rhabdomyolysis-associated acute kidney injury following concomitant use of elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate and pravastatin/fenofibrate: a case report. J Med Case Rep, 2015, 9: 190.