Atorvastatin with Fusidic Acid Interaction Details

Brand Names Associated with Atorvastatin

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

Interaction Effect

Increased plasma concentrations of atorvastatin and fusidic acid

Interaction Summary

Coadministration of atorvastatin and fusidic acid may result in significant elevations of both agents. A case report described an increase in atorvastatin and fusidic acid serum concentrations when fusidic acid therapy was instituted, resulting in an elevation of creatine kinase levels and muscle weakness and pain[1]. Additional case reports have described rhabdomyolysis following concomitant use of atorvastatin and fusidic acid [2][3]. The postulated mechanism of action is a mutual inhibition of both agents. The use of fusidic acid should be avoided in patients treated with atorvastatin [2][1].

Severity

Major

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Concomitant use of atorvastatin and fusidic acid may lead to increased risk of severe or potentially fatal rhabdomyolysis and is not recommended[2][1].

Mechanism Of Interaction

Mutual inhibition of metabolism by glucuronidation pathway

Literature Reports

A) A case series described significant rhabdomyolysis in 4 men (age range, 48 to 71 years) following concurrent treatment with atorvastatin and fusidic acid. All patients received long-term therapy with atorvastatin with later introduction of fusidic acid for treatment of septic arthritis or osteomyelitis. Of the 4 patients in this series, 3 had comorbid conditions including diabetes mellitus (n=3), end stage renal disease (n=2), and ischemic heart disease (n=2). All patients were on atorvastatin as a baseline medication (20 to 40 mg/day) and presented with generalized weakness, myalgia, and/or myopathy 1 to 3 weeks following addition of fusidic acid 1.5 g daily (IV and/or oral). Creatine kinase levels were significantly elevated, with levels peaking at 120,000 to greater than 500,000 international units/L after atorvastatin therapy was stopped. Of the 4 patients, 3 died later from complications of cardiac arrest, ventricular arrhythmia, and multiorgan dysfunction syndrome, respectively. In the remaining patient, following discontinuation of atorvastatin therapy, an aggressive regimen of IV fluids was started along with alkalinization of urine. Kidney function improved and treatment with renal replacement therapy was not warranted [2].

B) A case report described rhabdomyolysis in a 74-year-old man following concomitant use of atorvastatin and fusidic acid. The patient, who had left ventricular dysfunction, coronary artery disease, and moderate aortic stenosis, presented with generalized muscle pain and weakness that had developed 3 days earlier. Examination showed severe proximal muscle weakness and tenderness that affected all 4 extremities. For the past 4 years, he had received atorvastatin 40 mg/day taken at night for hypercholesteremia. Six weeks earlier, he had been initiated on fusidic acid 500 mg orally 3 times daily and flucloxacillin 500 mg 4 times daily for treatment of left foot osteomyelitis. Other medical history included type 2 diabetes mellitus with chronic renal impairment and hypertension. Additional medications included aspirin, clopidogrel, bisoprolol, spironolactone, amlodipine, furosemide, subcutaneous insulin, lansoprazole, and erythropoietin. Upon hospital admission, the patient had a creatine kinase (CK) value of 3817 international units/L with dark urine. He was diagnosed with rhabdomyolysis which resulted in discontinuation of atorvastatin, fusidic acid, and flucloxacillin. Biochemical abnormalities included a peak CK value of 25,800 international units/L, transient hyperkalemia (5.5 mmol/L), hyperphosphatemia (2.03 mmol/L), and a 40% increase in creatinine concentration from baseline (207 micromol/L). However, these values showed quick improvement and CK had returned to normal within 2 weeks following administration of sodium bicarbonate and 0.9% saline infusions. Three weeks later, he was discharged. At 3 months after discharge, the patient was reinitiated on atorvastatin and able to tolerate 20 mg/day orally taken at night [3].

C) A case report described a 66-year-old man who developed progressive muscle weakness and pain in both legs during treatment with atorvastatin and fusidic acid. Serum concentrations of atorvastatin and fusidic acid were above therapeutic range and creatine kinase levels were elevated significantly. He appeared ill and developed pretibial edema and myalgia, with no active movement of his legs 2 weeks after starting fusidic acid therapy. Atorvastatin and fusidic acid were discontinued. The plasma atorvastatin concentrations measured 8.2 mcg/L and fusidic acid concentration was 127.2 mg/L six days after discontinuation. Ten days after discontinuation, atorvastatin concentrations measured 1.9 mcg/L and fusidic acid concentration was 4.9 mg/L. Creatine kinase levels increased after the addition of fusidic acid to atorvastatin therapy and decreased after the discontinuation of both drugs [1].

References

1 ) Wenisch C, Krause R, Fladerer P, et al: Acute rhabdomyolysis after atorvastatin and fusidic acid therapy (letter). Am J Med 2000; 109(1):78.

2 ) Magee CN, Medani SA, Leavey SF, et al: Severe rhabdomyolysis as a consequence of the interaction of fusidic acid and atorvastatin. Am J Kidney Dis 2010; 56(5):e11-e15.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

3 ) O'Mahony C, Campbell VL, Al-Khayatt MS, et al: Rhabdomyolysis with atorvastatin and fusidic acid. Postgraduate medical journal 2008; 84(992):325-327.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.

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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.