Diltiazem and Simvastatin: Interaction Details
AI-assisted, pharmacist-reviewed · AI content regenerated Jul 11, 2026 · Source data updated Jul 4, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Diltiazem
Simvastatin
How we grade severity & evidence
Severity levels
- Contraindicated: These should generally not be used together.
- Major: Potentially serious — often needs a change or close monitoring.
- Moderate: Can be significant — usually manageable with monitoring.
- Minor: Usually limited clinical impact.
Evidence grades
- Established: Well documented — supported by controlled studies or strong clinical data.
- Probable: Good supporting evidence, though not definitively proven.
- Suspected: Some evidence suggests this interaction, but it is not well established.
- Possible: Limited or conflicting evidence; the interaction may occur.
- Theoretical: Predicted from the drugs' pharmacology; not yet confirmed in people.
Ratings come from the documented interaction literature and are reviewed by a pharmacist. They describe the documented risk of the combination, not what will necessarily happen to you — your dose, timing, and health picture all matter.
These two medicines can interact. Diltiazem (for blood pressure or heart rate) slows down the liver enzyme that breaks down simvastatin (a cholesterol medicine). When that enzyme is blocked, more simvastatin builds up in your body than usual.
Higher simvastatin levels can raise the chance of muscle problems. Watch for unexplained muscle pain, tenderness, weakness, or dark-colored urine. In rare cases severe muscle breakdown can happen. The good news is your care team can manage this easily, often by keeping your simvastatin dose low. Keep taking both as prescribed, and tell your pharmacist or doctor right away if you notice new muscle aches.
Mechanism: Diltiazem inhibits CYP3A4, reducing first-pass and systemic metabolism of simvastatin (a CYP3A4 substrate). Neither is a prodrug in a way that reverses this; simvastatin exposure rises.
- Magnitude: Simvastatin AUC increased ~3.1-fold and Cmax ~2.88-fold (simvastatin acid AUC ~2.69-fold) with diltiazem 120 mg BID.
- Effect: Increased risk of myopathy/rhabdomyolysis.
- Onset: Rapid. Evidence: Established.
Management: If coadministered, do not exceed simvastatin 10 mg/day and diltiazem 240 mg/day. Monitor for muscle symptoms and CK if suspected; discontinue if myopathy is diagnosed or suspected. Consider a non-CYP3A4 statin alternative.
What happens
Increased simvastatin exposure and an increased risk of myopathy and rhabdomyolysis
Interaction Deep Dive
Taking dilTIAZem alongside simvastatin raises simvastatin exposure and can heighten the likelihood of myopathy or rhabdomyolysis. When the two must be given together, keep simvastatin at no more than 10 mg per day and dilTIAZem at no more than 240 mg per day3. Should myopathy be diagnosed or suspected, therapy should be stopped 1. In a study where simvastatin 80 mg was given on day 10 in combination with dilTIAZem 120 mg twice daily over 10 days, the AUC of simvastatin and simvastatin acid rose 3.10-fold and 2.69-fold, while their Cmax increased 2.88-fold and 2.69-fold, respectively 2.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated metabolism of simvastatin
How to manage this interaction
This is manageable with the right dose and monitoring. Keep taking both medicines exactly as prescribed unless your care team tells you otherwise.
- Your team often keeps the simvastatin dose low (guidance is not to exceed 10 mg daily) and diltiazem at or below 240 mg daily when the two are used together.
- They may monitor you more closely for muscle symptoms.
- In some cases a different cholesterol medicine that does not interact may be chosen.
Call your pharmacist or doctor promptly if you get new muscle pain, tenderness, weakness, or dark urine. Do not start or stop either drug on your own.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
6 reports — tap to read
a) In a crossover study involving 10 healthy volunteers, giving sustained-release (SR) dilTIAZem 120 mg twice daily for 14 days along with a single 20 mg dose of simvastatin produced a 5-fold rise in mean simvastatin AUC relative to simvastatin given alone. Moreover, participants who showed a higher average steady-state exposure to dilTIAZem experienced a greater rise in simvastatin exposure. Computer simulations using dilTIAZem SR 480 mg daily indicated an 8- to 9-fold mean increase in simvastatin AUC. In contrast, in a randomized, 4-way, crossover study (n=10), giving dilTIAZem SR 120 mg daily for 2 weeks together with pravastatin 20 mg produced no significant change in pravastatin AUC or Cmax. DilTIAZem plasma concentrations were not significantly altered when it was given together with pravastatin 3.
b) Simvastatin AUC rose by up to 5-fold when simvastatin and dilTIAZem were given together in a pharmacokinetic study. Subjects took dilTIAZem 120 mg twice daily for 10 days, and on day 10 a single 80 mg dose of simvastatin was given. The mean ratio (with dilTIAZem/without dilTIAZem) of simvastatin was 3.1 for AUC and 2.88 for Cmax. The corresponding ratios for simvastatin acid (beta-hydroxyacid of simvastatin) were 2.69 for AUC and 2.69 for Cmax. In a comparable study (differing in that dilTIAZem was given for 14 days and the simvastatin dose was 20 mg), the ratios were 4.6 for AUC and 3.6 for Cmax 1.
c) In a fixed-order, 2-arm study, dilTIAZem significantly raised the serum concentration of simvastatin when the two were given together to 10 healthy adults (5 males and 5 females; mean age of 27 years). In the first arm, participants received a single oral dose of simvastatin 20 mg, followed by a 2-week washout period between arms 1 and 2. In the second arm, patients received a single oral dose of simvastatin after 2 weeks of dilTIAZem 120 mg twice daily. Following an overnight fast, simvastatin was given at 8 am and a standard lunch was provided on the day of the study. Blood samples were collected at 0, 1/4, 1/2, 3/4, 1, 11/2, 2, 21/2, 3, 4, 6, 8, 12, and 24 hours after dosing to measure simvastatin serum concentrations. Serum concentrations of dilTIAZem were measured using blood samples taken at 0, 1, 4, 8, 12, and 24 hours. Giving dilTIAZem together with simvastatin produced a significant increase in the AUC and Cmax by 4.8-fold and 3.6-fold, respectively. Concurrent use of dilTIAZem and simvastatin significantly lengthened the simvastatin half-life by 2.3-fold. There was no change in the time to reach Cmax 4.
d) The combination of simvastatin and dilTIAZem may lead to severe myositis and rhabdomyolysis. One case report described a 75-year-old male who reported extreme weakness and diffuse muscle pain and who had a history of stable angina pectoris, myocardial infarction, hyperlipidemia, and impaired renal function. The patient was taking simvastatin 80 mg/day and dilTIAZem 240 mg daily. On admission, his serum creatinine was 8.5 mg/dL (750 mcmol/L) and myoglobin was positive in serum and urine. Simvastatin-induced rhabdomyolysis was diagnosed, and all medications were stopped. The patient's muscle pain resolved and concentrations of CPK and transaminases returned to normal after hemodialysis and intensive physiotherapy. However, the patient remained hemodialysis-dependent. The authors conclude that dilTIAZem raises the serum concentration of simvastatin, resulting in rhabdomyolysis. Close clinical monitoring of patients on combination therapy with dilTIAZem and simvastatin is warranted 5.
e) Nineteen patients receiving simvastatin and dilTIAZem had a 33.3% decrease in cholesterol levels, compared with 116 patients not receiving dilTIAZem who had a 24.75% reduction in cholesterol with simvastatin. These findings suggest that patients receiving dilTIAZem may require a lower starting dose of simvastatin, since the synergistic effect on cholesterol reduction may also raise the risk of myopathy 6. However, only one patient enrolled in the Scandinavian Simvastatin Survival Study experienced myopathy, and she was also receiving dilTIAZem 7.
f) In a drug interaction study, giving simvastatin 80 mg on day 10 together with dilTIAZem 120 mg twice daily for 10 days increased simvastatin and simvastatin acid AUC by 3.10-fold and 2.69-fold and Cmax by 2.88-fold and 2.69-fold, respectively 2.
Common questions
Can I take Diltiazem and Simvastatin together?
Diltiazem raises simvastatin levels and the risk of muscle injury, so doses are kept low (simvastatin no more than 10 mg daily) and you should report any new muscle pain or dark urine to your care team. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Diltiazem and Simvastatin interaction?
It is rated major. Potentially serious — often needs a change or close monitoring.
How quickly could this interaction happen?
The documented onset is "rapid". Effects can appear quickly, often within about 24 hours of combining the drugs.
How is the Diltiazem and Simvastatin interaction managed?
This is manageable with the right dose and monitoring. Keep taking both medicines exactly as prescribed unless your care team tells you otherwise. Your team often keeps the simvastatin dose low (guidance is not to exceed 10 mg daily) and diltiazem at or below 240 mg daily when the two are used together. They may monitor you more closely for muscle symptoms. In some cases a different cholesterol me… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "established". Well documented — supported by controlled studies or strong clinical data.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Diltiazem or Simvastatin need adjusting while I take them together?
- What symptoms should prompt me to call you or my prescriber right away?
- Does the timing of my doses matter for this combination?
- Is there a safer alternative to one of these medications for me?
References (7)
- Product Information: ZOCOR(R) oral tablets, simvastatin oral tablets. Organon & Co (per FDA), Jersey City, NJ, 2022. DailyMed
- Product Information: VYTORIN(R) oral tablets, ezetimibe simvastatin oral tablets. Organon LLC (per FDA), Jersey City, NJ, 2024. DailyMed
- Product Information: CARDIZEM(R) direct compression oral tablets, diltiazem hydrochloride direct compression oral tablets. BTA Pharmaceuticals, Inc, Bridgewater, NJ, 2010.
- Mousa O, Brater DC, Sundblad KJ, et al: The interaction of diltiazem with simvastatin. Clin Pharmacol Ther 2000; 67:267-274. PubMed
- Peces R & Pobes A: Rhabdomyolysis associated with concurrent use of simvastatin and diltiazem. Nephrom 2001; 89:117-118. DOI
- Yeo KR, Yeo WW, Wallis EJ, et al: Enhanced cholesterol reduction by simvastatin in diltiazem-treated patients. Br J Clin Pharmacol 1999; 48:610-615. PubMed
- Neuvonen PJ, Kantola T, & Kivisto KT: Calcium channel blocker-simvastatin interaction. Reply (letter). Clin Pharmacol Ther 1999; 65:583-585.
Keep reading about Diltiazem
Keep reading about Simvastatin
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