Does bicalutamide and atorvastatin (Lipitor) have a drug interaction?

Drug Interaction Between Bicalutamide and Atorvastatin

Yes, bicalutamide and atorvastatin have a clinically significant drug interaction, as bicalutamide is an inhibitor of CYP3A4, which is responsible for atorvastatin metabolism. This interaction may lead to increased plasma concentrations of atorvastatin, potentially increasing the risk of adverse effects.

Mechanism of Interaction

• Bicalutamide is an inhibitor of CYP3A4, with in vitro studies showing it has inhibitory effects on CYP3A4 and to a lesser extent on CYP 2C9, 2C19, and 2D6 1.
• Atorvastatin is primarily metabolized by CYP3A4, making it susceptible to interactions with CYP3A4 inhibitors 2.
• When CYP3A4 is inhibited by bicalutamide, atorvastatin metabolism may be reduced, potentially leading to increased plasma concentrations 1.

Clinical Significance

• According to the American Heart Association scientific statement, bicalutamide is listed as a CYP3A4 inhibitor that can affect statin metabolism 2.
• The FDA label for bicalutamide specifically warns that caution should be exercised when bicalutamide is co-administered with CYP3A4 substrates 1.
• Clinical studies have shown that co-administration of bicalutamide with midazolam (another CYP3A4 substrate) increased midazolam levels 1.5-fold (for Cmax) and 1.9-fold (for AUC) 1.

Potential Consequences

• Increased atorvastatin exposure may lead to an elevated risk of statin-associated adverse effects, including:
  • Myopathy and rhabdomyolysis (muscle damage) 2
  • Elevated liver enzymes 2
• The risk may be higher in patients with other risk factors for statin-associated muscle toxicity 2.

Management Recommendations

• Monitor patients closely for signs and symptoms of statin-related adverse effects when using this combination 1:

  • Muscle pain, tenderness, or weakness
  • Elevated liver enzymes
  • Dark urine or jaundice

• Consider these management options:

  • Use the lowest effective dose of atorvastatin when co-administered with bicalutamide 2.
  • Monitor liver function tests and creatine kinase levels more frequently during co-administration 2.
  • Consider using a statin that is less dependent on CYP3A4 metabolism (such as pravastatin, rosuvastatin, or fluvastatin) if clinically appropriate 2.

Important Considerations

• The degree of interaction may vary between patients based on individual factors 2.
• Bicalutamide has a long half-life (approximately 1 week), which means the interaction potential may persist even after discontinuation 3.
• Patients with hepatic impairment may be at higher risk for adverse effects from this interaction, as both drugs can affect liver function 4, 5.

Monitoring Parameters

• Baseline and periodic liver function tests 5
• Creatine kinase levels if muscle symptoms develop 2
• Signs and symptoms of myopathy (muscle pain, weakness, tenderness) 2
• Lipid levels to ensure therapeutic efficacy of atorvastatin despite the interaction 2

This interaction requires clinical awareness and appropriate management to minimize the risk of adverse effects while maintaining the therapeutic benefits of both medications.