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Lipid-Lowering Medications: ARV Interactions

for Health Care Providers

Lipid-Lowering Medications: ARV Interactions

Note: Some medications mentioned in this chapter may not be available on the VHA National Formulary. Consult VA pharmacists for alternatives.

Lipid-Lowering Medications: ARV Interactions

PIs and NNRTIs can affect hepatic metabolism of HMG-coenzyme A reductase inhibitors (statins). ARVs do not generally affect the metabolism of other classes of lipid-lowering agents.

PIsNNRTIs
Most PIs inhibit the metabolism of most statins and can significantly increase serum statin levels, thus increasing the risk of toxicity, including myopathy and rhabdomyolysis.NNRTI effects vary according to specific NNRTI.
The degree to which statin metabolism is affected by PIs varies according to the statin as well as the specific PI.EFV generally induces statin metabolism, resulting in lower serum statin levels.
In general, the potential for inhibition of statin metabolism is as follows: simvastatin and lovastatin > atorvastatin >> fluvastatin, pravastatin, rosuvastatin.NVP has not been studied well in combination with statins, but its interactions with statins would be expected to be similar to those of EFV.
Fluvastatin and rosuvastatin have few recognized interactions with PIs.ETR has not been studied thoroughly in combination with statins. Its interactions are expected to depend on the specific statin.
DLV inhibits hepatic cytochrome P450 metabolism. Thus, DLV increases statin levels and the risk of statin-related adverse effects.

Medical providers should consult with a clinical pharmacist or review published information on drug interactions before prescribing statins for patients taking PIs or NNRTIs, as dosage adjustments are frequently required and some combinations are contraindicated.

Other classes of ARVs (NRTIs, fusion inhibitors, chemokine coreceptor antagonists, and integrase inhibitors) do not have recognized interactions with statins. Other types of lipid-lowering medications are not metabolized by hepatic cytochrome P450 and are not affected by ARVs.

Lipid-Lowering MedicationConsiderations
Statins
  • Atorvastatin
  • Hepatic metabolism including CYP 3A4 metabolism.
  • PIs: significant ↑ in atorvastatin levels with most PIs (Cmax ↑ 100-300%).
  • Start with lowest dosage (10 mg). Monitor antilipid activity and titrate the statin dosage cautiously.
  • TPV/r: atorvastatin Cmax ↑ 760%. Consider alternative statin. If prescribed, use lowest possible dosage, monitor carefully.
  • EFV: ↓ in atorvastatin levels (↓ AUC 58%); may need ↑ dosage.
  • ETR: ↓ in atorvastatin levels (↓ AUC 37%); may need ↑ dosage.
  • Fluvastatin
  • Metabolized by CYP 2C9 (75%), CYP 3A4 (20%).
  • Not well studied; no known significant interactions with most PIs; theoretic risk of ↓ NFV levels.
  • ETR, DLV may ↑ fluvastatin.
  • Lovastatin
  • Extensively metabolized by CYP 3A4.
  • PIs: substantial ↑ in statin levels, high risk of adverse effects.
  • Do not use in patients taking PIs or DLV.
  • Pravastatin
  • Renal excretion and some hepatic metabolism.
  • PIs: variable effects; moderate ↑ pravastatin AUC and Cmax with most. No dosage adjustment of pravastatin is required. Exceptions:
    • DRV/r: pravastatin AUC ↑ 80-500%. Consider alternative statin. If prescribed, use lowest possible dosage, monitor carefully.
    • SQV + RTV: pravastatin AUC ↓ 35- 50%. May need to ↑ pravastatin dosage to reach lipid goals.
    • NFV: pravastatin AUC ↓ 46%. May need to ↑ pravastatin dosage to reach lipid goals.
  • EFV: pravastatin AUC ↓ 40%. May need to ↑ pravastatin dosage to reach lipid goals.
  • Rosuvastatin
  • Metabolized by CYP 2C9 and CYP 2C19. Mostly excreted in bile.
  • No significant interactions expected with most PIs or NNRTIs; studies under way. Exceptions:
    • DRV/r: rosuvastatin expected to ↑. Use lowest possible dosage (5 mg/day), monitor carefully.
    • LPV/r: rosuvastatin Cmax ↑ 466%. Consider alternative statin. If prescribed, use lowest possible dosage (5 mg/day), monitor carefully.
    • TPV/r: rosuvastatin Cmax ↑ 123%. Use lowest possible dosage (5 mg/day), monitor carefully.
  • Simvastatin
  • Extensively metabolized by CYP 3A4.
  • PIs: substantial ↑ in simvastatin levels, high risk of adverse effects (eg, simvastatin Cmax and AUC ↑ 3,000% with SQV + RTV).
  • Do not use in patients taking PIs or DLV.
  • EFV: ↓ simvastatin AUC >50%. May need to ↑ simvastatin dosage to reach lipid goals.
Fibrates
  • No significant interactions with ARVs expected.
Bile Acid Sequestrants
  • No drug interactions with ARVs, but may interfere with absorption of ARVs. Avoid in patients who take ARVs.
Ezetimibe
  • Not metabolized by hepatic P450 system; no significant interactions with ARVs.
Niacin
  • Not metabolized by hepatic P450 system; no significant interactions with ARVs.
N-3 (Omega-3) Fatty Acids
  • Not metabolized by hepatic P450 system; no significant interactions with ARVs.
Representation of a table grid

Recommendations for Coadministration of PIs and NNRTIs with Statin Medications

(See full table)

References