Atorvastatin with Daptomycin Interaction Details

Brand Names Associated with Atorvastatin

Brand Names Associated with Daptomycin

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

Interaction Effect

Increased risk of myopathy or rhabdomyolysis

Interaction Summary

Both daptomycin and an HMG-CoA reductase inhibitor may cause myopathy[1]. In a meta-analysis of 7 studies (4548 patients), there was no difference in the incidence of daptomycin-related myopathy in patients treated with daptomycin with or without concomitant statin therapy, however, in a subgroup analysis, the incidence of rhabdomyolysis in the daptomycin plus statin group was significantly higher compared with the daptomycin only group [2]. Cases of rhabdomyolysis have been reported with concomitant use of daptomycin and simvastatin [3] or simvastatin/ezetimibe [4][5]. Temporarily discontinue HMG-CoA reductase inhibitors in patients starting daptomycin. In patients who continue on both drugs concomitantly, consider more frequent monitoring of CPK levels, and monitor for symptoms of myopathy. Additionally, monitor CPK more frequently in patients with renal insufficiency or who develop unexplained elevations in CPK. Discontinue daptomycin in patients who develop symptoms of myopathy and CPK elevations of greater than 1000 units/L, or in patients without symptoms who have CPK elevations of greater than 2000 units/L [1].

Severity

Major

Onset

Delayed

Evidence

Theoretical

How To Manage Interaction

Consider temporary discontinuation of HMG-CoA reductase inhibitor in patients starting daptomycin as both drugs have the potential to cause myopathy. In patients who continue on both drugs concomitantly, consider more frequent monitoring of CPK levels than the recommended weekly monitoring, as well as monitor patients for symptoms of myopathy including muscle pain or weakness. Additionally, more frequent monitoring of CPK levels is recommended in patients with renal insufficiency or who develop unexplained elevations in CPK. Discontinue daptomycin in patients who develop symptoms of myopathy and CPK elevations of greater than 1000 units/L, or in patients without symptoms with CPK elevations of greater than 2000 units/L[1].

Mechanism Of Interaction

Additive effects of myopathy

Literature Reports

A) In a meta-analysis of 7 studies (4548 patients), there was no difference in the incidence of daptomycin-related myopathy in patients treated with daptomycin with or without concomitant statin therapy (OR, 1.72; 95% CI, 0.95 to 3.12). In a subgroup analysis, the incidence of rhabdomyolysis in the daptomycin plus statin group was significantly higher compared with the daptomycin only group (OR, 3.83; 95% CI, 1.43 to 10.26). A disproportionality analysis using the US Food and Drug Administration Adverse Events Reporting System (FAERS) to further confirm the results of the meta-analysis confirmed the use of statin did significantly increase the reporting OR (ROR) for daptomycin-related myopathy (ROR, 5.69; 95% CI, 4.31 to 7.51) and rhabdomyolysis (ROR, 5.77; 95% CI, 4.33 to 7.68). Higher daptomycin dosing (8 mg/kg/day or greater) was not associated with increased incidence of daptomycin-related musculoskeletal adverse events compared with standard dosing [2].

B) No symptoms of skeletal myopathy were reported in 10 healthy subjects administered simvastatin and daptomycin 4 mg/kg/day for 14 days in a phase 1, placebo-controlled trial. However, CPK elevations of more than 500 units/L were experienced in 5 out of 22 patients on daptomycin who had received prior or concomitant HMG-CoA reductase inhibitor in a phase 3 Staphylococcus aureus bacteremia/endocarditis trial. In this study, overall, CPK elevations were reported in 6.7% (8/120) of daptomycin-treated patients compared with less than 1% (1/116) of comparator-treated patients [1].

C) Symptoms of rhabdomyolysis and progression of renal failure developed within 16 days of starting daptomycin in a patient on simvastatin and extended-release niacin, with subsequent resolution after discontinuation of daptomycin. The patient with a CrCl of 24.6 mL/min, initially received daptomycin IV 7.2 mg/kg daily with subsequent renal adjustment 4 days later to 7.2 mg/kg every 48 hr. The patient's usual medications included simvastatin (80 mg/day), extended-release niacin (500 mg/day), and esomeprazole (20 mg/day), which were continued during hospitalization. On day 16 of daptomycin therapy, the patient experienced weakness, diffuse aches in the proximal thighs and arms, and had a CPK of 8995 International Units/L. The serum creatinine peaked at 3.4 mg/dL. Within 6 days of stopping daptomycin the serum creatinine returned to baseline and, within 7 days, the CPK concentrations decreased to 125 International Units/L. The patient successfully completed a course of linezolid IV followed by oral minocycline [5].

D) In a case report, myopathy and increased CPK concentration were observed after 15 days of daptomycin therapy in a 73-year-old man who was concurrently receiving rosuvastatin, apixaban, ivabradine, metformin, ginkgo biloba, and trimetazidine. The patients medical history included coronary artery disease, hyperthyroidism, and benign prostatic hyperplasia and he was hospitalized for infective endocarditis. Empirical treatment was started and on day 8 of admission, daptomycin was initiated. On day 23, the CPK concentration was 2416 units/L (baseline 22 units/L on day 2 of admission) with no significant change in renal function and he was experiencing moderate muscle pain and fatigue. A drug interaction was suspected between daptomycin and rosuvastatin which may have caused myopathy and increase in CPK concentrations, therefore both were discontinued and linezolid was started instead of daptomycin. After 3 days, the patient's symptoms improved and after 6 days the CPK levels returned to normal [6].

References

1 ) Product Information: Cubicin(R) IV injection, daptomycin IV injection. Cubist Pharmaceuticals, Inc., Lexington, MA, 2010.

2 ) Chuma M, Nakamoto A, Bando T, et al: Association between statin use and daptomycin-related musculoskeletal adverse events: a mixed approach combining a meta-analysis and a disproportionality analysis. Clin Infect Dis 2022; 75(8):1416-1422.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

3 ) Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Merck Sharp & Dohme Corp (per manufacturer), Whitehouse Station, NJ, 2019.

4 ) Product Information: VYTORIN(R) oral tablets, ezetimibe simvastatin oral tablets. Merck Sharp & Dohme Corp (per manufacturer), Whitehouse Station, NJ, 2019.

5 ) Odero RO , Cleveland KO , & Gelfand MS : Rhabdomyolysis and acute renal failure associated with the co-administration of daptomycin and an HMG-CoA reductase inhibitor. J Antimicrob Chemother 2009; 63(6):1299-1300.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

6 ) Durmus M , Bahcecioglu OF , & Gok S : Daptomycin in combination with rosuvastatin induced blood creatine phosphokinase elevation. Eur J Hosp Pharm 2021; 28(4):234-236.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.

Daptomycin Overview

• Daptomycin injection is used to treat certain blood infections or serious skin infections caused by bacteria in adults and children 1 year of age and older. Daptomycin injection is in a class of medications called cyclic lipopeptide antibiotics. It works by killing bacteria.

• Antibiotics such as daptomycin injection will not work for treating colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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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.