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Cyclosporine-amiodarone interaction
K K Chitwood1, A J Abdul-Haqq, K L Heim-Duthoy
1Drug Evaluation Unit, Hennepin County Medical Center, Minneapolis.
Insights
A potential drug interaction between cyclosporine (CsA) and amiodarone was observed in a kidney transplant patient. Close monitoring of CsA levels and dose adjustments are recommended when these medications are used together.
Area of Science:
- Pharmacology
- Nephrology
- Cardiology
Background:
- Kidney transplant recipients often require immunosuppression with cyclosporine (CsA).
- Ventricular tachycardia is a serious post-transplant complication requiring treatment.
- Amiodarone is an antiarrhythmic medication used to treat ventricular tachycardia.
Observation:
- A kidney transplant recipient on CsA developed ventricular tachycardia and was treated with amiodarone.
- CsA levels more than doubled after amiodarone initiation.
- CsA dosage reduction normalized CsA concentrations without toxicity.
Findings:
- A significant drug interaction between CsA and amiodarone is likely.
- Potential mechanisms include altered protein binding or cytochrome P-450 metabolism.
- This interaction has also been reported in heart transplant recipients.
Implications:
- Concurrent use of CsA and amiodarone necessitates close therapeutic drug monitoring of CsA.
- Dosage adjustments of CsA may be required to maintain target levels and avoid toxicity.
- Understanding this interaction is crucial for managing transplant patients on both medications.
Objective:
To report a possible interaction between cyclosporine (CsA) and amiodarone in a kidney transplant recipient.
Case Summary:
A 66-year-old kidney transplant recipient with a history significant for hypertension, moderate mitral valve insufficiency, and decreased left ventricular function developed ventricular tachycardia posttransplant and was eventually treated with amiodarone. Maintenance immunosuppression included prednisone, azathioprine, and CsA. CsA concentrations before amiodarone initiation were stable (range 100-150 ng/mL). After amiodarone initiation, the CsA concentration increased more than twofold. Following CsA dosage reduction, concentrations returned to the desired range. The patient did not experience any toxicity with the increased concentration of CsA.
Discussion:
The possible mechanisms of an interaction between CsA and amiodarone are reviewed. Reports of this interaction in heart transplant recipients are also reviewed. Changes in protein binding, changes in metabolism, or both may explain the interaction. Both CsA and amiodarone are protein bound and metabolized by the cytochrome P-450 enzyme system.
Conclusions:
It is likely that there is an interaction between CsA and amiodarone. The exact mechanism of this interaction has not been fully determined. When CsA is administered concurrently with amiodarone, CsA concentrations should be monitored closely and the CsA dosage should be adjusted as necessary.