Amiodarone with Tacrolimus Interaction Details

Brand Names Associated with Amiodarone

  • Amiodarone
  • Cordarone®
  • Pacerone®

Brand Names Associated with Tacrolimus

  • Astagraf XL®
  • Envarsus XR®
  • FK 506
  • Prograf®
  • Tacrolimus

Medical Content Editor
Last updated Feb 27, 2024

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Interaction Effect

Increased tacrolimus exposure and an increased risk of QT interval prolongation

Interaction Summary

Coadministration of amiodarone and tacrolimus should generally be avoided as this may result in increased tacrolimus plasma concentrations and additive effects on the QT interval. Due to the long-half life of amiodarone, this interaction is possible even after discontinuation of amiodarone[1]. If concomitant use cannot be avoided, consider reducing the tacrolimus dose and monitoring tacrolimus whole blood concentrations and QT interval [2]. Also, consider monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment [3].

Severity

Major

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Coadministration of amiodarone and tacrolimus should generally be avoided as this may result in increased tacrolimus plasma concentrations and additive effects on the QT interval. Due to the long-half life of amiodarone, this interaction is possible even after discontinuation of amiodarone[1]. If concomitant use cannot be avoided, consider reducing the tacrolimus dose and monitoring tacrolimus whole blood concentrations and QT interval [2]. Also, consider monitoring electrolytes (magnesium, potassium, calcium) periodically during treatment [3].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated tacrolimus metabolism by amiodarone; inhibition of P-gp-mediated efflux transport of tacrolimus; additive QT interval prolongation

Literature Reports

A) Following a renal transplantation due to chronic glomerulonephritis in 2001, a 73-year-old man was admitted to the hospital for atrial fibrillation in July of 2008. His current medications consisted of amiodarone, prednisoLONE 10 mg/day, and tacrolimus 7 mg/day. Upon admission, the patient's tacrolimus trough concentration level was 63 nanogram/mL (ng/mL) or 78.4 nanomol/L (nmol/L), his desethylamiodarone level was 0.5 mg/L or 0.8 mcmol/L (normal range, 0.5 mg/L to 2.5 mg/L or 0.8 mcmol/L to 4.1 mcmol/L), and serum creatinine was 0.9 mg/dL (80 mcmol/L). His tacrolimus dose was decreased to 2 mg/day, resulting in a normal tacrolimus trough level of 12.9 ng/mL (16.04 nanomol/L) [4].

B) 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 [5].

References

    1 ) Product Information: NEXTERONE(TM) intravenous injection, amiodarone HCl intravenous injection. Baxter Healthcare Corporation (per FDA), Deerfield, IL, 2015.

    2 ) Product Information: ASTAGRAF XL(R) oral extended-release capsules, tacrolimus oral extended-release capsules. Astellas Pharma US Inc (per manufacturer), Northbrook, Il, 2023.

    3 ) Product Information: PROGRAF(R) oral capsules, oral granules for suspension, intravenous injection, tacrolimus oral capsules, oral granules for suspension, intravenous injection. Astellas Pharma US Inc (per FDA), Northbrook, IL, 2023.

    4 ) Kisters K, Cziborra M, Funke C, et al: Amiodarone-tacrolimus interaction in kidney transplantation. Clinical nephrology 2008; 70(6):563-.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

    5 ) 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.

See More information Regarding Amiodarone

Tacrolimus Overview

  • Tacrolimus (Astagraf XL, Envarsus XR, Prograf) is used along with other medications to prevent rejection (attack of a transplanted organ by the immune system of a person receiving the organ) in people who have received a kidney transplant. Tacrolimus (Prograf) is also used along with other medications to prevent rejection in people who have received a liver, lung, or heart transplant. Tacrolimus is in a class of medications called immunosupressants. It works by decreasing the activity of the immune system to prevent it from attacking the transplanted organ.

See More information Regarding Tacrolimus

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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.