Atorvastatin with Clarithromycin Interaction Details

Brand Names Associated with Atorvastatin

Brand Names Associated with Clarithromycin

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

Interaction Effect

Increased atorvastatin exposure and an increased risk of myopathy or rhabdomyolysis

Interaction Summary

Coadministration of clarithromycin with atorvastatin significantly increased atorvastatin exposure[1]. Clinically significant rhabdomyolysis has been cited in case reports of patients treated concomitantly with atorvastatin and clarithromycin [2][3]. Therefore, evaluate the benefit/risk of concomitant use [1]. Use caution if used together, and do not exceed atorvastatin doses of 20 mg daily [4]. Evaluate patients to ensure that the lowest necessary dose of atorvastatin is being used. Monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness). If myopathy or rhabdomyolysis is diagnosed or suspected, or if creatine kinase (CK) levels show a marked increase, temporarily withhold or discontinue atorvastatin [1]. When possible, substitute atorvastatin with a statin not dependent on CYP3A metabolism, such as fluvastatin [5].

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Evaluate the benefit/risk of concomitant use of atorvastatin with clarithromycin[1]. Use caution if used concomitantly and do not exceed atorvastatin doses of 20 mg daily due to an increased risk of myopathy/rhabdomyolysis [4][1]. Evaluate patients to ensure that the lowest necessary dose of atorvastatin is being used. Monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness), particularly during the initial months of therapy and during upward dosage titration of either drug. Lower starting and maintenance doses of atorvastatin should be considered. If myopathy or rhabdomyolysis is diagnosed or suspected, or if creatine kinase (CK) levels show a marked increase, temporarily withhold or discontinue atorvastatin [1]. When possible, substitute atorvastatin for a statin that is not dependent on CYP3A metabolism, such as fluvastatin [5].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated atorvastatin metabolism by clarithromycin

Literature Reports

A) In a retrospective, population-based cohort study of adults older than 65 years taking a statin metabolized by CYP3A (atorvastatin, 73%; simvastatin, 24%; lovastatin, 3%), concomitant administration with clarithromycin (n=72,591) or erythromycin (n=3267) was associated a rate of hospitalization for rhabdomyolysis of 0.03% and a rate of hospitalization for acute kidney injury of 0.46%. Corresponding rates with concomitant administration of azithromycin (n=68,478) were 0.01% and 0.26%, respectively. The all-cause mortality rate was 0.7% in the clarithromycin/erythromycin group and 0.45% in the azithromycin group [6].

B) Subjects receiving atorvastatin 80 mg daily for 8 days who were coadministered clarithromycin 500 mg twice daily for 9 days had a 4.4-fold increase in atorvastatin AUC and a 5.4-fold increase in Cmax [1].

C) The coadministration of clarithromycin with atorvastatin significantly increased atorvastatin exposure. In a randomized study, healthy subjects (N=36) received atorvastatin 10 mg daily for 8 days. On study days 6 through 8, subjects received one of 3 concomitant treatments: clarithromycin 500 mg twice daily, azithromycin 500 mg once daily, or placebo. Coadministration of clarithromycin with atorvastatin significantly increased atorvastatin mean Cmax and AUC (by 56% and 82%, respectively). No significant changes from baseline were observed during placebo or azithromycin co-treatment [7].

D) Severe rhabdomyolysis associated with 3rd degree heart block developed in a 51-year-old woman receiving a multidrug regimen comprising atorvastatin, esomeprazole, and clarithromycin. The patient had previously taken atorvastatin 10 mg daily without incident for over a year, prior to presenting with symptoms of severe weakness, dyspnea, chest pain, and bradycardia. Electrocardiographic exam revealed a 3rd degree heart block pattern and serum creatine kinase (CK) was 7348 units/L, with a CK-MB (muscle-brain) concentration of 186 units/L. Urinalysis confirmed the presence of myoglobinuria. The patient reported having symptoms of increasing fatigue, mild chest pain and dyspnea that began with the coadministration of esomeprazole, approximately 6 weeks prior to admission. Clarithromycin 500 mg twice daily was added to her therapy regimen 2 days before admission (3 dose total) for treatment of respiratory symptoms. Despite the withdrawal of all medications, CK and CK-MB continued to rise, peaking above 40,000 units/L and 396 units/L, respectively. Electrolyte hydration and forced diuresis was initiated and a permanent cardiac pacemaker was eventually required. Although the authors determined esomeprazole had the highest probability of causing increased atorvastatin exposure, they also suggested clarithromycin contributed to the event [2].

E) Rhabdomyolysis developed in a 35-year-old man with HIV after clarithromycin was added to a longstanding regimen of atorvastatin and HIV protease inhibitors. The patient had previously tolerated chronic use of the combination of atorvastatin 40 mg with lopinavir/ritonavir. Approximately 8 days after starting clarithromycin 500 mg twice daily for treatment of pneumonia (at which time his liver enzymes were within normal range), the patient developed continuous sharp muscle pain in both lower limbs. Physical examination revealed bilateral hip flexor/extensor weakness, and laboratory analysis revealed a serum creatine kinase (CK) concentration of 10,298 units/L accompanied by elevations in serum ALT (281 units/L) and alkaline phosphatase (850 units/L). Urinalysis confirmed the presence of myoglobin. Atorvastatin and clarithromycin were discontinued, an alkaline diuresis was initiated, and the CK concentration declined to within normal limits by day 7 of treatment [3].

References

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

2 ) Sipe BE, Jones RJ, & Bokhart GH: Rhabdomyolysis causing AV blockade due to possible atorvastatin, esomeprazole, and clarithromycin interaction. Ann Pharmacother 2003; 37:808-811.

3 ) Ming JB & Gill MJ: Drug-induced rhabdomyolysis after concomitant use of clarithromycin, atorvastatin, and lopinavir/ritonavir in a patient with HIV. AIDS Patient Care and STDs 2003; 17(5):207-210.

4 ) Product Information: VOQUEZNA(TM) TRIPLE PAK(TM) oral kit, vonoprazan oral tablets, amoxicillin oral capsules, clarithromycin oral tablets kit. Phathom Pharmaceuticals (per FDA), Buffalo Grove, IL, 2023.

5 ) Product Information: BIAXIN(R) Filmtab(R) oral tablets, clarithromycin oral tablets. Abbott Laboratories (per manufacturer), North Chicago, IL, 2011.

6 ) Patel AM , Shariff S , Bailey DG , et al: Statin toxicity from macrolide antibiotic coprescription: a population-based cohort study. Ann Intern Med 2013; 158(12):869-876.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

7 ) Amsden GW, Kuye O, & Wei GC: A study of the interaction potential of azithromycin and clarithromycin with atorvastatin in healthy volunteers. J Clin Pharmacol 2002; 42:444-449.

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.

Clarithromycin Overview

• Clarithromycin is used to treat certain bacterial infections, such as pneumonia (a lung infection), bronchitis (infection of the tubes leading to the lungs), and infections of the ears, sinuses, skin, and throat. It also is used to treat and prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. It is used in combination with other medications to eliminate H. pylori, a bacterium that causes ulcers. Clarithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as clarithromycin will not work for colds, flu, or other viral infections. Taking 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.