What are the potential interactions between Cresemba (isavuconazonium sulfate) and amiodarone?

Potential Interactions Between Cresemba (Isavuconazonium Sulfate) and Amiodarone

Cresemba (isavuconazonium sulfate) should not be co-administered with amiodarone due to the risk of serious drug-drug interactions involving CYP3A4 and P-glycoprotein pathways, which could lead to increased toxicity of both medications.

Mechanism of Interaction

The potential interaction between Cresemba and amiodarone involves multiple pharmacokinetic pathways:

1. CYP3A4 Enzyme System:

   • Amiodarone and its metabolite (desethylamiodarone) are inhibitors of CYP3A4 1
   • This inhibition could potentially increase isavuconazole levels in the bloodstream

2. P-glycoprotein (P-gp) Transport System:

   • Both medications interact with the P-gp efflux transporter 1
   • Amiodarone inhibits P-gp in a reversible manner
   • This inhibition could affect the distribution and elimination of isavuconazole

Clinical Implications

Cardiovascular Risks

• Sofosbuvir-based regimens (another medication with similar interaction pathways) are contraindicated with amiodarone due to risk of life-threatening arrhythmias 1
• By extension, similar concerns exist for isavuconazole when combined with amiodarone
• Bradycardia and other cardiac rhythm disturbances are possible outcomes

Increased Drug Levels

• The interaction may lead to increased plasma concentrations of both medications
• Amiodarone has been shown to increase concentrations of multiple drugs that share metabolic pathways 1, 2
• This could potentially lead to toxicity from either or both medications

Toxicity Concerns

• Amiodarone has a very long half-life (weeks to months)
• Even after discontinuation, interaction potential remains for an extended period 1
• If a patient has no cardiac pacemaker, it is recommended to wait three months after discontinuing amiodarone before starting medications with similar interaction profiles 1

Management Recommendations

1. Avoid Concurrent Use:

   • The safest approach is to avoid concurrent use of these medications
   • Consider alternative antifungal agents if a patient requires amiodarone

2. If Co-administration Cannot Be Avoided:

   • Close cardiac monitoring is essential
   • ECG monitoring for QT prolongation and bradycardia
   • Monitor for signs of toxicity from both medications
   • Consider dose adjustments of one or both medications

3. Monitoring Parameters:

   • Regular ECG monitoring
   • Liver function tests (both medications can affect hepatic function)
   • Thyroid function (for amiodarone toxicity)
   • Clinical assessment for signs of toxicity from either medication

Special Considerations

• Long Half-life of Amiodarone: Due to amiodarone's extremely long half-life (up to several months), the interaction potential persists long after discontinuation 1

• Patient-Specific Factors: Elderly patients and those with renal or hepatic impairment may be at higher risk for adverse effects from this interaction 3

• Alternative Antifungals: Consider non-azole antifungals if antifungal therapy is necessary in patients taking amiodarone

This interaction represents a significant clinical concern that warrants careful consideration of alternative therapeutic strategies whenever possible.