Atorvastatin with Fluconazole 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 Fluconazole

  • Diflucan®
  • Fluconazole

Medical Content Editor
Last updated Mar 04, 2024


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Interaction Effect

Increased atorvastatin exposure and an increased risk of myopathy and rhabdomyolysis


Interaction Summary

Concomitant use of atorvastatin and fluconazole may increase atorvastatin exposure and increase risk for myopathy and rhabdomyolysis . Fluconazole inhibits P-gp and is a moderate inhibitor of CYP3A4[1]; atorvastatin is a substrate of CYP3A4 and P-gp. Discontinue atorvastatin if markedly elevated creatine kinase (CK) occurs or if myopathy is diagnosed or suspected. Muscle symptoms and CK increases may resolve if atorvastatin is discontinued. Temporarily discontinue atorvastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis [2]. Dose reduction of atorvastatin may be needed. Fluconazole enzyme inhibitory effects may persist for 4 to 5 days after discontinuation due to its long half-life [1]. A case report of acute muscle pain followed by an ICU stay for acute renal failure was reported 1 week following fluconazole initiation in a patient that had been stable on atorvastatin [3].


Severity

Major


Onset

Delayed


Evidence

Probable


How To Manage Interaction

Concomitant use of atorvastatin and fluconazole may increase atorvastatin exposure and increase risk for myopathy and rhabdomyolysis. Discontinue atorvastatin if markedly elevated creatine kinase (CK) occur or if myopathy is diagnosed or suspected. Muscle symptoms and CK increases may resolve if atorvastatin is discontinued. Temporarily discontinue atorvastatin in patients experiencing an acute or serious condition at high risk of developing renal failure secondary to rhabdomyolysis[2]. Dose reduction of atorvastatin may be needed [1].


Mechanism Of Interaction

Inhibition of CYP3A4-mediated metabolism of atorvastatin; inhibition of P-gp-mediated efflux transport of atorvastatin by fluconazole


Literature Reports

A) A 70-year-old woman developed muscle pain and weakness 1 week after initiating fluconazole for Candida tropicalis fungemia. She had been taking atorvastatin 20 mg daily for the preceding 4 years without issue. Serum LDL levels decreased from a baseline of 166 mg/dL to 56 mg/dL with a concomitant change in urine to an orange-red color, and the atorvastatin dosage interval was increased to once every other day due to suspicion of drug-drug interaction. A 10-day ICU stay was required after 2 weeks of combination therapy when acute renal failure and reduced consciousness developed. Atorvastatin was immediately discontinued. Significantly elevated laboratory values were as follows: phosphate 6.4 mg/dL, BUN 143 mg/dL, serum creatinine 4.57 mg/dL, creatine kinase 2948 units/L, AST 421 units/L, ALT 559 units/L, lactate dehydrogenase 619 units/L, serum myoglobin 25,350 nanograms/mL, and urine myoglobin 1522 nanograms/mL. Fluconazole was administered for a total of 4 weeks, and atorvastatin was not reinitiated; liver function and creatine kinase levels returned to normal within 2 months. A Drug Interaction Probability Scale (DIPS) calculation indicated that the interaction between fluconazole and atorvastatin was probable [3].

References

    1 ) Product Information: DIFLUCAN(R) oral tablets, suspension, fluconazole oral tablets, suspension. Roerig (per FDA), New York, NY, 2023.

    2 ) Product Information: LIPITOR(R) oral tablets, atorvastatin calcium oral tablets. Parke-Davis (per FDA), New York, NY, 2020.

    3 ) Hsiao SH, Chang HJ, Hsieh TH, et al: Rhabdomyolysis caused by the moderate CYP3A4 inhibitor fluconazole in a patient on stable atorvastatin therapy: a case report and literature review. J Clin Pharm Ther 2016; 41(5):575-578.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.

See More information Regarding Atorvastatin

Fluconazole Overview

  • Fluconazole is used to treat fungal infections, including yeast infections of the vagina, mouth, throat, esophagus (tube leading from the mouth to the stomach), abdomen (area between the chest and waist), lungs, blood, and other organs. Fluconazole is also used to treat meningitis (infection of the membranes covering the brain and spine) caused by fungus. Fluconazole is also used to prevent yeast infections in patients who are likely to become infected because they are being treated with chemotherapy or radiation therapy before a bone marrow transplant (replacement of unhealthy spongy tissue inside the bones with healthy tissue). Fluconazole is in a class of antifungals called triazoles. It works by slowing the growth of fungi that cause infection.

See More information Regarding Fluconazole

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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.