Amiodarone with Sirolimus Interaction Details
Brand Names Associated with Amiodarone
- Amiodarone
- Cordarone®
- Pacerone®
Brand Names Associated with Sirolimus
- Rapamune®
- Rapamycin
- Sirolimus
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Feb 27, 2024
Interaction Effect
Elevated sirolimus concentrations and increased risk of sirolimus toxicity
Interaction Summary
Concomitant administration of amiodarone and sirolimus may result in increased sirolimus levels, possibly due to inhibition of sirolimus metabolism through CYP3A4 by amiodarone[1].
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
Monitor sirolimus levels and adjust sirolimus dosage as necessary. Monitor patients for sirolimus toxicity during concomitant therapy[1].
Mechanism Of Interaction
Inhibition of CYP 3A4-mediated sirolimus metabolism
Literature Reports
A) Following an ABO-incompatible heart transplant at age 4 months, a 2-year-old girl was hospitalized with anemia, renal dysfunction, and moderate liver dysfunction. Immunosuppressant therapy included oral tacrolimus 0.8 mg every 12 hours and mycophenolate mofetil 100 mg every 12 hours. Tacrolimus was held on day 2 for 5 days for trough blood levels greater than 30 mcg/L. Only one-fourth of the pre-admission dose of tacrolimus was needed to keep trough levels within target range (8 to 10 mcg/L or 9.9 to 12 nanomol/L). On day 7, nadolol and amiodarone were started for arrhythmia control. Tacrolimus trough levels were within target range on days 8 and 10, and liver transaminases were normal. Oral sirolimus 0.06 mg/kg/day was initiated to heighten immunosuppression and increased to 0.12 mg/kg/day after 2 days. Sirolimus trough level was 52.7 mcg/L or 57.65 nanomol/L (target, 10 mcg/L or 10.9 nanomol/L) and tacrolimus trough level was 12.9 mcg/L (16.04 nanomol/L). Sirolimus was held and tacrolimus was discontinued, but sirolimus trough levels remained above target for 14 more days. Once trough levels normalized, sirolimus was restarted at 0.03 mg/kg/day. After 2 doses, the trough was 17.2 mcg/mL (18.81 mcmol/L), and the dose was decreased to 0.02 mg/kg/day. Trough levels (13.4 mcg/L or 14.66 nanomol/L) remained high after 5 days. Amiodarone serum concentrations were not analyzed. The patient continued to deteriorate. Extra corporeal membrane oxygenation support (ECMO) was started on day 21. The patient died due to ECMO complications on day 42 [1].
References
1 ) Nalli N, Stewart-Teixeira L, & Dipchand AI: Amiodarone-sirolimus/tacrolimus interaction in a pediatric heart transplant patient. Pediatr Transplant 2006; 10(6):736-739.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...
Amiodarone Overview
-
Amiodarone is used to treat and prevent certain types of serious, life-threatening ventricular arrhythmias (a certain type of abnormal heart rhythm when other medications did not help or could not be tolerated. Amiodarone is in a class of medications called antiarrhythmics. It works by relaxing overactive heart muscles.
Sirolimus Overview
-
Sirolimus is used in combination with other medications to prevent rejection of kidney transplants. Sirolimus is in a class of medications called immunosuppressants. It works by suppressing the body's immune system.
Return To Our Drug Interaction Homepage
Feedback, Question Or Comment About This Information?
Ask Dr. Brian Staiger, PharmD, our medical editor, directly! He's always more than happy to assist.
Definitions
Severity Categories
Contraindicated
These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.
Major
This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.
Moderate
This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.
Minor
While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.
Onset
Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.
Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.
Evidence
Level of documentation of the interaction.
Established: The interaction is documented and substantiated in peer-reviewed medical literature.
Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.
How To Manage The Interaction
Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.
It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.
Mechanism Of Interaction
The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.
Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.
Where Does Our Information Come From?
Information for our drug interactions is compiled from several drug compendia, including:
The prescribing information for each drug, as published on DailyMED, is also used.
Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.
The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.