Atorvastatin with Diltiazem 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 Diltiazem
- Cardizem®
- Cardizem® CD
- Cardizem® LA
- Cardizem® SR
- Cartia® XT
- Dilacor® XR
- Dilt-CD®
- Diltiazem
- Diltzac®
- Taztia® XT
- Teczem® (as a combination product containing Diltiazem, Enalapril)
- Tiamate®
- Tiazac®
Medical Content Editor Dr. Brian Staiger, PharmD
Last updated
Mar 04, 2024
Interaction Effect
An increased risk of rhabdomyolysis
Interaction Summary
Atorvastatin is metabolized primarily by the CYP3A4 isoenzyme system, and diltiazem competes for this same metabolic pathway[1][2][3]. Coadministration of atorvastatin and diltiazem resulted in rhabdomyolysis and subsequent renal failure in one case report [4].
Severity
Major
Onset
Delayed
Evidence
Probable
How To Manage Interaction
If concurrent therapy is required, monitor the patient for signs and symptoms of myopathy or rhabdomyolysis (muscle pain, tenderness, or weakness, or discolored urine). If myopathy or rhabdomyolysis is diagnosed or suspected, monitor creatine kinase (CK) levels and discontinue use if CK levels show a marked increase.
Mechanism Of Interaction
Inhibition by diltiazem of cytochrome P450 3A4-mediated atorvastatin metabolism
Literature Reports
A) One case report describes a 60-year old man who developed acute renal failure secondary to rhabdomyolysis, which was diagnosed 3 weeks after the addition of diltiazem XL 180 mg twice a day to his drug regimen. The patient had been maintained on atorvastatin 20 mg/day, metoprolol 100 mg twice a day, digoxin 1.25 mg/day, benazepril 40 mg/day, furosemide 40 mg twice a day, warfarin 7.5 mg/day, aspirin 325 mg/day, insulin 70/30 twice a day, and sublingual nitroglycerin as needed. Upon admission, relevant laboratory values were as follows: creatinine kinase (CK) 1898 units/L with MB fraction 1.3%, troponin-I less than 1.0 nanogram/mL, serum myoglobin 674.7 mg/mL, urine myoglobin negative, sodium 131 mEq/L (131 mmol/L), potassium 6.3 mEq/L (6.3 mmol/L), phosphorus 8.2 mg/dL (2.65 mmol/L), blood urea nitrogen (BUN) 48 mg/dL (17.1 mmol/L), serum creatinine (SCr) 3.4 mg/dL (300 mcmol/L), prothrombin time (PT) 46.5 seconds, international normalized ratio (INR) 19.7, total bilirubin 0.7 mg/dL (12 mcmol/L), direct bilirubin 0.4 mg/dL (7 mcmol/L), aspartate transaminase (AST) 1236 units/L, alanine transaminase (ALT) 1610 units/L, alkaline phosphatase (ALP) 287 units/mL, and digoxin 1.3 nanogram/mL (1.66 nanomol/L). Acute hepatitis was added to the diagnosis; all medications except aspirin, digoxin and furosemide were discontinued. With appropriate treatment, gradually the patient's renal function returned to baseline (SCr 1.1 mg/dL or 97 mcmol/L), CK decreased to 623 units/L, and liver function tests normalized. He did denied any muscle fatigue or weakness during his hospitalization. Diltiazem was reinstated to control his heart rate, and he was treated as an outpatient for his hypercholesterolemia [4].
References
1 ) Product Information: Lipitor oral tablets, atorvastatin oral tablets. Parke-Davis, New York, NY, 2005.
2 ) Product Information: Cardizem (R) LA, diltiazem hydrochloride extended release tablets. Biovail Pharmaceuticals, Inc, Bridgewater, NJ, 2004.
3 ) Jacobson TA: Comparative pharmacokinetic interaction profiles of pravastatin, simvastatin, and atorvastatin when coadministered with cytochrome P450 inhibitors. Am J Cardiol 2004; 94(9):1140-1146.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...
4 ) Lewin JJ, Nappi JM, & Taylor MH: Rhabdomyolysis with concurrent atorvastatin and diltiazem. Ann Pharmacother 2002; 36(10):1546-1549.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...
Atorvastatin Overview
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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.
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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 atorvastatin has been shown to prevent heart disease, angina (chest pain), strokes, and heart attacks.
Diltiazem Overview
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Diltiazem is used to treat high blood pressure and to control angina (chest pain). Diltiazem is in a class of medications called calcium-channel blockers. It works by relaxing the blood vessels so the heart does not have to pump as hard. It also increases the supply of blood and oxygen to the heart.
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High blood pressure is a common condition, and when not treated it can cause damage to the brain, heart, blood vessels, kidneys, and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.
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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.