Simvastatin with Ranolazine Interaction Details
Brand Names Associated with Simvastatin
- Flolipid®
- Juvisync® (as a combination product containing Simvastatin, Sitagliptin)
- Simcor® (as a combination product containing Niacin, Simvastatin)
- Simvastatin
- Vytorin® (as a combination product containing Ezetimibe, Simvastatin)
- Zocor®
Brand Names Associated with Ranolazine
- Ranexa®
- Ranolazine
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Nov 10, 2023
Interaction Effect
Increased simvastatin exposure and increased risk of rhabdomyolysis
Interaction Summary
The concomitant use of ranolazine and simvastatin increases simvastatin exposure and increases the risk of myopathy and rhabdomyolysis due to inhibition of CYP3A4-mediated simvastatin metabolism. Exposure to simvastatin increased by approximately 80% with coadministration of simvastatin and ranolazine in a pharmacokinetic study. A case report described rhabdomyolysis following coadministration of ranolazine 500 mg/day in a patient already receiving simvastatin 80 mg/day . If it is necessary to coadminister ranolazine and simvastatin, the dose of simvastatin should not exceed 20 mg/day .
Severity
Major
Onset
Unspecified
Evidence
Established
How To Manage Interaction
Concomitant use of ranolazine and simvastatin resulted in increases in plasma concentrations of simvastatin and its active metabolite and may increase the risk of myopathy and rhabdomyolysis. If it is necessary to coadminister ranolazine and simvastatin, the dose of simvastatin should not exceed 20 mg/day.
Mechanism Of Interaction
Inhibition of CYP3A4-mediated simvastatin metabolism by ranolazine
Literature Reports
A) Exposure to simvastatin increased by approximately 80% with coadministration of simvastatin and ranolazine in a pharmacokinetic study. Subjects received ranolazine sustained-release 1000 mg twice daily for 7 days and on day 1 and day 6 through 9 simvastatin 80 mg was administered. The mean ratio (with ranolazine/without ranolazine) of simvastatin was 1.86 for AUC and 1.75 for Cmax. The corresponding ratios for simvastatin acid (beta-hydroxyacid of simvastatin) were 2.26 for AUC and 2.28 for Cmax .
B) Rhabdomyolysis was reported in a 63-year-old patient following the concomitant use of ranolazine and simvastatin. The patient, whose medical history included hyperlipidemia, coronary artery disease, chronic kidney disease, degenerative joint disease, and stroke, was admitted to the hospital with complaints of weakness in both legs that had started 3 days earlier. In addition to extended-release ranolazine 500 mg/day (which had been added 10 days before hospitalization) and simvastatin 80 mg/day, his regimen included furosemide, clopidogrel, hydralazine, metoprolol, isosorbide mononitrate, omeprazole, and nitroglycerin. Lab test results showed increases in creatine kinase (CK) (31,989 units/L; normal 55 to 170 units/L), CK-MB band, troponin, B-type natriuretic peptide, TSH, AST, ALT, and serum creatinine (SCr). The patient was diagnosed with rhabdomyolysis. Ranolazine and simvastatin were withheld. On days 4 and 7 of therapy, his CK and SCr concentrations had improved. By day 18 of hospitalization, serum CK was almost undetectable and Scr remained at baseline. On day 32, he was discharged; no alternative for hyperlipidemia was prescribed. The Drug Interaction Probability Scale rated the interaction between ranolazine and simvastatin with a score of 5 indicating a probable association between the concomitant use of these agents and the rhabdomyolysis .
Simvastatin Overview
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Simvastatin 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. Simvastatin 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. Simvastatin 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). Simvastatin 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.
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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 simvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.
Ranolazine Overview
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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:
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.