Atorvastatin with Ranolazine Interaction Details

Brand Names Associated with Atorvastatin

Brand Names Associated with Ranolazine

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

Interaction Effect

Increased atorvastatin exposure and increased risk of myopathy

Interaction Summary

Concomitant use of atorvastatin, a CYP3A4 substrate, and ranolazine, a weak CYP3A4 inhibitor, increased plasma concentrations of atorvastatin by 40% in most healthy patients and by 400% in 1 patient[1], thereby potentially increasing the risk of myopathy [2]. A case report described myopathy following coadministration of ranolazine in a patient already receiving atorvastatin. If concomitant use is necessary, monitor serum creatine kinase levels and perform muscle strength assessment at baseline in patients receiving statins before initiating ranolazine [2].

Severity

Moderate

Onset

Unspecified

Evidence

Theoretical

How To Manage Interaction

Concomitant use of atorvastatin and ranolazine increased plasma concentrations of atorvastatin by 40% in most healthy patients and by 400% in 1 patient[1] and may increase the risk of myopathy. If concomitant use is necessary, monitor serum creatine kinase levels and perform muscle strength assessment at baseline prior to initiating ranolazine in patients receiving statins [2].

Mechanism Of Interaction

Inhibition of CYP3A4-mediated atorvastatin metabolism by ranolazine

Literature Reports

A) Mean exposure to atorvastatin 80 mg daily was increased 40% following concomitant use with ranolazine 1000 mg twice daily in healthy volunteers. One patient experienced an approximate 400% increase in atorvastatin exposure following concomitant use with ranolazine [1].

B) Concurrent use of ranolazine and atorvastatin led to myopathy with increased creatine kinase (CK) levels in an 86-year-old woman. The patient's medical history was complicated and included hyperlipidemia, coronary artery disease, and pulmonary hypertension, among other conditions. The patient was restarted on atorvastatin, after having been off simvastatin for a year, and had no issues for 4 months; however, within 1 week of adding ranolazine, she presented with progressive back and leg pain, weakness in both legs, and a change in gait. Examination revealed leg and hip muscle weakness on both sides. Lab test results showed increased CK (1875 units/L; baseline, 64 to 101 units/L). Muscle membrane instability and small short-duration motor unit potentials were evident on electromyography and edema in multiple muscles was noted on MRI. Within 1 week of discontinuing both drugs, her CK levels declined to 151 units/L. One month later, the patient had symptomatic and neurological improvement. Two months later, her serum CK level was 85 units/L and her edema decreased. Even though the patient had several comorbidities and was receiving multiple medications, based on the timing of myopathy onset upon adding ranolazine, and the improvement upon discontinuing both drugs, the interaction between atorvastatin and ranolazine was considered the primary etiology of the reaction. Although CYP3A4 inhibition by ranolazine is weak, the interaction could become clinically significant in the elderly [2].

References

1 ) Product Information: RANEXA(R) oral extended release tablets, ranolazine oral extended release tablets. Gilead Sciences, Inc. (per FDA), Foster City, CA, 2013.

2 ) Correa D & Landau M: Ranolazine-induced myopathy in a patient on chronic statin therapy. J Clin Neuromuscul Dis 2013; 14(3):114-116.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.

Ranolazine Overview

• Ranolazine is used alone or with other medications to treat chronic angina (ongoing chest pain or pressure that is felt when the heart does not get enough oxygen). Ranolazine is in a class of medications called anti-anginals. The exact way that ranolazine works is not known at this time.

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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.