OBJECT DRUGS

HMG-CoA Reductase Inhibitors:

• Atorvastatin (Lipitor)
• Pitavastatin (Livalo)
• Pravastatin (Pravachol)
• Rosuvastatin (Crestor)

PRECIPITANT DRUGS

OATP Inhibitors:

• Cyclosporine (Neoral, etc.)
• Eltrombopag (Promacta)
• Lopinavir (Kaletra)
• Rifampin (Rifadin, etc.)
• Ritonavir (Norvir)

Comment:

Pitavastatin, pravastatin, and rosuvastatin are substrates for the transporter OATP, and inhibitors of OATP may increase the risk of myopathy. Combining pitavastatin with either ritonavir/lopinavir or cyclosporine is contraindicated in the pitavastatin product information. Some evidence suggests that lopinavir is a potent inhibitor of OATP1B1, which may be the mechanism for its ability to increase pitavastatin and rosuvastatin plasma concentrations. Eltrombopag has been shown to substantially increase rosuvastatin plasma concentrations, and it probably would affect pitavastatin and pravastatin as well. Rifampin can inhibit OATP if concurrently administered with OATP substrate.

Class 2: Use Only if Benefit Felt to Outweigh Risk

• Use Alternative:
• HMG-CoA Reductase Inhibitors: Both cyclosporine and ritonavir/lopinavir are likely to increases systemic exposure to all statins, although the risk of myopathy may be less with pravastatin (Pravachol).
• Ritonavir/Lopinavir: The effect of other protease inhibitors on pitavastatin or rosuvastatin is not well studied. Atazanavir (Reyataz) may modestly increase pitavastatin plasma concentrations, and other protease inhibitors may also interact to varying degrees.
• Monitor: Patients receiving pitavastatin or rosuvastatin and an OATP inhibitor should be monitored for evidence of myopathy (muscle pain or weakness) and myoglobinuria (dark urine). Myopathy is usually associated with increased serum CK concentrations.