Atorvastatin with Amiodarone Interaction Details

Brand Names Associated with Atorvastatin

Brand Names Associated with Amiodarone

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

An increased risk of myopathy or rhabdomyolysis

Interaction Summary

Myopathy and rhabdomyolysis have been reported in patients receiving simvastatin (a HMG-CoA reductase inhibitor metabolized by CYP3A4 similar to atorvastatin) and amiodarone concomitantly[1][2][3]. Inhibition of CYP 3A4-mediated simvastatin metabolism by amiodarone has been proposed as a possible mechanism for this interaction [4]. Atorvastatin is a member of the HMG-CoA reductase inhibitor class and is principally metabolized by CYP3A4 enzymes [5]. Coadministration of amiodarone and atorvastatin may lead to a similarly increased risk of myopathy/rhabdomyolysis and therefore, if these agents are used concurrently, monitor patients for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness or weakness, dark-colored urine). Additionally, monitor creatine kinase (CK) levels and consider discontinuing use if CK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected. Alternatively, may consider substituting atorvastatin with another HMG-CoA reductase inhibitor, such as pravastatin, which is not metabolized by CYP3A4.

Severity

Moderate

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Coadministration of amiodarone and atorvastatin may result in increased atorvastatin concentrations, thereby increasing the risk of myopathy/rhabdomyolysis. If concurrent therapy is required, monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness). Monitor creatine kinase (CK) levels and consider discontinuing use if CK levels show a marked increase, or if myopathy or rhabdomyolysis is diagnosed or suspected. Alternatively, consider substituting atorvastatin with another HMG-CoA reductase inhibitor such as pravastatin.

Mechanism Of Interaction

Inhibition of CYP3A4-mediated atorvastatin metabolism

Literature Reports

A) In a review of adverse events reported to the US Food and Drug Administration (FDA) adverse events (AE) reporting database for simvastatin, atorvastatin, and pravastatin, muscle toxicity cases were reported with coadministration of atorvastatin and amiodarone. The review analysis included AE reports that affected major organ systems (MOS) such as muscle (myopathy, myalgia, rhabdomyolysis, elevated CPK, myolysis); liver (abnormal liver function tests); pancreas (pancreatitis); and bone marrow (pancytopenia, leukopenia, thrombocytopenia). Rates of MOS reports involving concurrent use of amiodarone with atorvastatin and simvastatin were 0.7% (n=29/3,767) and 1% (n=36/3,651), respectively (p=not significant). Among pravastatin-associated MOS reports, 0.4% of reports involved concurrent amiodarone use (p less than 0.05, compared to simvastatin). The majority of AEs reported with concurrent amiodarone and statin use involved muscle toxicity and occurred in older male patients (mean age 76 years) who were on multiple other medications. Muscle toxicity occurred in 76% and 77% of MOS reports involving concurrent use of amiodarone with atorvastatin (n=29) or simvastatin (n=36), respectively, with no statistically significant differences between the 2 statins. No significant differences were noted with concomitant usage of other cardiovascular medications and incidence of AEs reported among the 3 statins. While this review was limited by its retrospective nature and discrepancies between FDA reporting rates and actual reporting rates, it may be important to monitor for muscle-related complaints in patients taking concomitant amiodarone and statins, such as simvastatin and atorvastatin, particularly in elderly patients on several other concomitant medications. Use of a statin that is not metabolized by CYP3A4 may be preferred in such situations [6].

B) Rhabdomyolysis, accompanied by renal failure and possible hepatotoxicity, developed in a 72-year-old man after simvastatin 80 milligrams/day (mg/day), a HMG-CoA reductase inhibitor metabolized by CYP3A4 similar to atorvastatin, was added to an established regimen of amiodarone 200 mg/day which was initiated after a coronary artery bypass. The patient had a history of diabetes, hypertension, hyperlipidemia, and mild azotemia and had previously taken pravastatin 20 to 40 mg/day and fluvastatin 40 to 80 mg/day without any adverse effects. Approximately 1 month after initiation of simvastatin, the patient developed symptoms of thigh weakness, achiness, and dark urine. Laboratory analysis showed an elevated CK level of 19,620 units/liter (U/L) (reference range 60-224 U/L), AST level of 912 U/L (30-60 U/L), ALT level of 748 U/L (30-60 U/L), and highly elevated serum and urine myoglobin levels. In addition, serum creatinine level (2.6 mg/dL or 230 mcmol/L) and BUN (50 mg/dL or 18 mmol/L) were also elevated and the 24-hour urine protein level was 549 mg. Both simvastatin and amiodarone were immediately discontinued and the patient was hydrated with forced alkaline diuresis. After 13 days, hepatic enzyme levels dropped significantly and 3 months later, ALT, AST, and CK levels were 49, 32, and 640 U/L, respectively. Inhibition of CYP 3A4-mediated simvastatin metabolism by amiodarone was proposed as a possible mechanism for this interaction [4].

C) Rhabdomyolysis developed in a 63-year-old man after amiodarone (1 gram/day for 10 days, followed by 200 milligrams (mg)/day)) was added to an established treatment regimen that included simvastatin 40 mg daily, a HMG-CoA reductase inhibitor metabolized by CYP3A4 similar to atorvastatin. Approximately 11 days after beginning amiodarone therapy, the patient showed signs of rapid exertional exhaustion, followed 5 days later by complaints of diffuse muscle pain and generalized weakness. Laboratory analysis revealed a creatine phosphokinase (CK) serum concentration of 18,852 units/liter (U/L) accompanied by an aspartate aminotransferase and lactic dehydrogenase serum concentrations of 438 U/L and 807 U/L, respectively. Despite the discontinuation of simvastatin, serum CK concentration continued to rise, reaching a peak of 40,392 U/L 3 days later. Amiodarone and phenprocoumon were both stopped and pravastatin 20 mg daily was substituted for simvastatin, after which the patient's CK serum concentration declined to within normal limits and the patient showed a slow improvement in muscle strength. The case study authors assign to the proposed interaction a Naranjo causal probability relationship of 'probable'[3].

References

1 ) Product Information: Cordarone(R), amiodarone hydrochloride tablets. Wyeth Laboratories, Philadelphia, PA, 2003.

2 ) Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Merck & Co., Whitehouse Station, NJ, 2005.

3 ) Roten L, Schoenenberger RA, Krahenbuhl S, et al: Rhabdomyolysis in association with simvastatin and amiodarone.. Ann Pharmacother 2004; 38:978-981.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

4 ) Ricaurte B, Guirguis A, Taylor HC, et al: Simvastatin-amiodarone interaction resulting in rhabdomyolysis, azotemia, and possible hepatotoxicity. Ann Pharmacother 2006; 40(4):753-757.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

5 ) Product Information: LIPITOR(R) tablets, atorvastatin calcium tablets. Pfizer Ireland Pharmaceuticals, Dublin, Ireland, 2005.

6 ) Alsheikh-Ali AA & Karas RH: Adverse events with concomitant amiodarone and statin therapy. Prev Cardiol 2005; 8(2):95-97.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

Atorvastatin Overview

• Atorvastatin is used together with diet, weight loss, and exercise to reduce the risk of heart attack and stroke and to decrease the chance that heart surgery will be needed in people who have heart disease or who are at risk of developing heart disease. Atorvastatin is also used to decrease the amount of fatty substances such as low-density lipoprotein (LDL) cholesterol ('bad cholesterol') and triglycerides in the blood and to increase the amount of high-density lipoprotein (HDL) cholesterol ('good cholesterol') in the blood. Atorvastatin may also be used to decrease the amount of cholesterol and other fatty substances in the blood in children and teenagers 10 to 17 years of age who have familial heterozygous hypercholesterolemia (an inherited condition in which cholesterol cannot be removed from the body normally). Atorvastatin is in a class of medications called HMG-CoA reductase inhibitors (statins). It works by slowing the production of cholesterol in the body to decrease the amount of cholesterol that may build up on the walls of the arteries and block blood flow to the heart, brain, and other parts of the body.

• Accumulation of cholesterol and fats along the walls of your arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to your heart, brain, and other parts of your body. Lowering your blood level of cholesterol and fats with atorvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.

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.

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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:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

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.