Atorvastatin with Colchicine Interaction Details

Brand Names Associated with Atorvastatin

  • Atorvastatin
  • Caduet® (as a combination product containing Amlodipine, Atorvastatin)
  • Lipitor®
  • Liptruzet® (as a combination product containing Atorvastatin, Ezetimibe)

Brand Names Associated with Colchicine

  • Colchicine
  • Colcrys®
  • Gloperba®

Medical Content Editor
Last updated Mar 04, 2024

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Interaction Effect

Increased colchicine exposure and an increased risk of myopathy and rhabdomyolysis

Interaction Summary

Concomitant use of atorvastatin (P-gp inhibitor) and colchicine (P-gp substrate) may result in increased colchicine exposure[1] and additional risk for myopathy/rhabdomyolysis. Analysis of the LoDoCo2 trial found no significant difference in creatine kinase (CK) elevations with statins plus colchicine 0.5 mg/day vs statins only. May consider concomitant use in appropriate patients, with monitoring for signs/symptoms of myopathy/rhabdomyolysis, particularly during initial months and with dosage titration of either drug. If myopathy/rhabdomyolysis is diagnosed/suspected or if CK levels markedly increase, temporarily withhold or discontinue atorvastatin or colchicine. Consider dosage reduction in patients with renal impairment [2][3] and consider if benefit of using lipid modifying colchicine dosage (1 g/day or greater) concurrent with atorvastatin outweighs increased risk of myopathy and rhabdomyolysis [4].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Concomitant use may be considered in appropriate patients with monitoring for signs/symptoms of myopathy/rhabdomyolysis (muscle pain, tenderness, weakness), particularly during initial months of use, during dosage titration of either drug, and when colchicine dose is 1 g/day or greater. If myopathy/rhabdomyolysis is diagnosed/suspected or if creatine kinase (CK) levels markedly increase, temporarily withhold or discontinue atorvastatin or colchicine[2][3][5][6]. Consider colchicine dosage reduction for patients with renal impairment [3] and consider if benefit of lipid modifying colchicine dosage (1 g/day or greater) concurrent with atorvastatin outweighs added risk of myopathy and rhabdomyolysis [4].

Mechanism Of Interaction

Inhibition of P-gp-mediated efflux transport of colchicine by atorvastatin

Literature Reports

A) In a separate analysis of the LoDoCo2 trial, numerically more patients receiving concurrent therapy with atorvastatin and colchicine 0.5 mg/day (n=397) than atorvastatin alone (n=379) had creatine kinase (CK) levels between 191 and 285 units/L (less than 1.5x ULN; 14.1% vs 11.9%); additionally, more patients receiving any statin concurrently (n=841) developed elevated CK levels than those receiving placebo (n=832; 190 vs 146 patients). These differences did not reach significance. No patient had more than mild renal impairment (all patients had estimated GFR 50 mL/min/1.73 m(2) or greater). The authors recommend considering interruption or discontinuation of colchicine in patients with elevated CK or experiencing myotoxicity [2].

B) The American Heart Association states that concurrent usage of atorvastatin and colchicine may be considered in appropriate patients. Dose reductions may be considered for either atorvastatin or colchicine when these drugs are used concurrently due to the potential for competitive inhibition with CYP3A and competitive P-gp-mediated efflux; reduced dosages of colchicine should be considered for patients with renal impairment. Monitoring for muscle-related signs and symptoms of myopathy or rhabdomyolysis is recommended [3].

C) Concomitant use of steady-state atorvastatin 40 mg once daily for 14 days (P-gp inhibitor), with a single colchicine 0.6 mg dose (P-gp substrate) resulted in a 24% increase in colchicine AUC (0 to infinity) and a 31% increase in colchicine Cmax in a randomized, open-label study of healthy adults (N=24). There were no adverse events reported and no effect on Tmax or absorption [1].

D) Cases of myopathy/rhabdomyolysis have been reported with atorvastatin coadministered with lipid modifying doses (1 g/day or greater) of colchicine [4].

References

    1 ) Davis MW & Wason S: Effect of steady-state atorvastatin on the pharmacokinetics of a single dose of colchicine in healthy adults under fasted conditions. Clin Drug Investig 2014; 34(4):259-267.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

    2 ) van Broekhoven A, Eikelboom JW, Nidorf SM, et al: Elevations in creatine kinase are not related to the choice or dose of statins in patients taking colchicine 0.5 mg daily: insights from the LoDoCo2 trial. Clin Drug Investig 2023; 43(7):575-577.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

    3 ) Wiggins BS, Saseen JJ, Page RL, et al: Recommendations for management of clinically significant drug-drug interactions with statins and select agents used in patients with cardiovascular disease: a scientific statement from the American Heart Association. Circulation 2016; 134(21):e468-e495.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

    4 ) Product Information: ATORVALIQ(R) oral suspension, atorvastatin calcium oral suspension. CMP Pharma Inc (per FDA), Farmville, NC, 2023.

    5 ) Product Information: LIPITOR(R) oral tablets, atorvastatin calcium oral tablets. Pfizer (Per FDA), New York, NY, 2012.

    6 ) Product Information: COLCRYS(R) oral tablets, colchicine oral tablets. AR Scientific, Inc. (per FDA), Philadelphia, PA, 2011.

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.

See More information Regarding Atorvastatin

Colchicine Overview

  • Colchicine is used to prevent gout attacks (sudden, severe pain in one or more joints caused by abnormally high levels of a substance called uric acid in the blood) in adults. Colchicine (Colcrys) is also used to relieve the pain of gout attacks when they occur. Colchicine (Colcrys) is also used to treat familial Mediterranean fever (FMF; an inborn condition that causes episodes of fever, pain, and swelling of the stomach area, lungs, and joints) in adults and children 4 years of age and older. Colchicine is not a pain reliever and cannot be used to treat pain that is not caused by gout or FMF. Colchicine is in a class of medications called anti-gout agents. It works by stopping the natural processes that cause swelling and other symptoms of gout and FMF.

See More information Regarding Colchicine

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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.