Lopinavir / ritonavir

Pravastatin

Dosage adjustment may be necessary.

No pharmaceutical opinion available for this interaction.

Mechanism

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

Lopinavir / 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
Duration (days)
AUC
Cmax
Cmin
Lopinavir / ritonavir
1318
12
400/100 mg
BID
14
- 5%
- 2%
- 12%
Pravastatin
1318
12
20 mg
QD
4
+ 33%
+ 26%
 
Comment

The coadministration is generally well tolerated. Start with a low dose of pravastatin because a wide individual variability was reported.

Ref #2380 : Co-administration of pravastatin with darunavir/ritonavir increased pravastatin AUC by 21%.

Réf #2129 : However, in another study with darunavir/ritonavir, an average increase in pravastatin SSC of 81% was observed with increases of up to 5-fold in some subjects.

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

Reference
  • 673
    Norvir Prescribing Information, Abbott Laboratories, February 2010.
  • 1162
    Carr RA, Andre AK, Bertz RJ et al. Concomitant administration of ABT-378/ritonavir (ABT-378/r) results in a clinically important pharmacokinetic (PK) interaction with atorvastatin (ATO) but not pravastatin (PRA). 40th ICAAC. Toronto, Canada, September 17-20, 2000 Abstract 1644.
  • 1318
    Bertz R, Hsu A, Lam L, et al. Pharmacokinetic interactions between Kaletra (lopinavir/ritonavir or ABT-378/r) and other non-HIV drugs. 5th International Congress of Drug Therapy in HIV Infection. Glasgow, Scotland 2000. Abstract 438.
  • 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
  • 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.
  • 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.
  • 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
  • 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.