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Dyslipidemia – Drug-drug Interactions

Drug-drug Interactions

Many HMG-CoA reductase inhibitors (statins) and some ARV drugs are metabolized by the same cytochrome P450 isoenzyme CYP3A4. Inhibition of CYP3A4 may result in excessively high levels of statins.1 



Summary of drug-drug interactions2

  • Atorvastatin in conjunction with a protease inhibitor (PI)/r can probably be used, at low initial doses.
  • Fluvastatin or pravastatin can be used with PIs or non-nucleoside reverse transcriptase inhibitors (NNRTIs), but higher doses (particularly in the presence of PI/ritonavir) may be necessary to achieve expected therapeutic benefit. The only exception to this is to start with a lower dose of pravastatin when combined with darunavir/ritonavir.
  • Rosuvastatin with PI/r or an NNRTI can probably be used with caution, at low initial doses.
  • Simvastatin should not be used in patients taking protease inhibitors (PIs).
     

Advice on use of statin together with ART (ARV therapy)2


Drug class Drug Dose (mg QD) Use with PI/ritonavir Use with NNRTI
Statin atorvastatin 10–80 Start with low dose* (max. 40 mg) Consider higher dose†
  fluvastatin 20–80 Consider higher dose† Consider higher dose†
  pravastatin 20–80 Consider higher dose†‡ Consider higher dose†
  rosuvastatin 5-40 Start with low dose* (max. 20 mg) Start with low dose*
  simvastatin 10-40 Contraindicated Consider higher dose†
Cholesterol uptake ↓ ezetimibe 10 No known drug-drug interactions with ART  

*The ART drug may inhibit the excretion of the statin (statin toxicity, ↓ dose)
†The ART drug may induce the excretion of the statin (=less effect of statin, ↑ dose gradually to achieve expected benefit)
‡Exception: if used with darunavir/ritonavir, start with lower dose of pravastatin
NNRTI = non-nucleoside reverse transcriptase inhibitor.
Signs of statin toxicity include: gastrointestinal symptoms, headache, insomnia, rhabdomyolysis (rare), toxic hepatitis and myalgia. 



Adapted with permission from the European AIDS Clinical Society Guidelines. Version 6.0.




The use of bile acid sequestrants is not recommended as they are thought to increase triglyceride levels and their effects on the absorption of ARV drugs have not been studied.3




For further information on drug-drug interactions:

References

  1. Tungsiripat M, Aberg JA. Dyslipidemia in HIV patients. Cleve Clin J Med. 2005;72:1113–1120.
  2. European AIDS Clinical Society (EACS) Guidelines. Version 6.0. Accessed 3 July 2012.
  3. The Task Force for the management of dyslipidemias of the European Society of Cardiology (ESC) and the European Atherosclerosis Society (EAS). ESC/EAS Guidelines for the Management of Dyslipidemias. Eur Heart J. 2011;32:1769–1818.