Simvastatin and Cyclosporine: 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
Cyclosporine
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.
Cyclosporine and simvastatin should not be taken together. Cyclosporine slows down how your body breaks down and clears simvastatin, so the statin can build up to much higher levels than normal. When simvastatin levels get too high, it can seriously irritate your muscles.
The big worry is muscle breakdown (called rhabdomyolysis). Warning signs include unexplained muscle pain, tenderness, weakness, or dark, tea-colored urine. Because this combination is considered off-limits, please don't stop either medicine on your own. Instead, talk with your pharmacist or doctor soon, as they can safely switch you to a different cholesterol medicine that works well with cyclosporine.
Contraindicated combination. CycloSPORINE inhibits both CYP3A4 (simvastatin's primary metabolic pathway) and OATP1B1 (its hepatic uptake transporter). The net effect is markedly increased simvastatin systemic exposure (elevated AUC/Cmax) and a substantially higher risk of myopathy and rhabdomyolysis. Neither agent is a prodrug in a way that reverses this; the direction is clear, increased statin effect and toxicity.
- Evidence: probable; onset unspecified.
- Management: avoid the combination. Coadministration of cycloSPORINE with simvastatin, including ezetimibe/simvastatin, is contraindicated.
- Select an alternative lipid-lowering agent; monitor for muscle symptoms and CK if any statin is used with cycloSPORINE.
What happens
An increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
When cycloSPORINE (which inhibits both CYP3A4 and OATP1B1) is taken together with simvastatin (a substrate for CYP3A4 and OATP1B1), simvastatin plasma levels may rise, elevating the likelihood of myopathy or rhabdomyolysis. Using cycloSPORINE alongside simvastatin is contraindicated1. Likewise, the combination of cycloSPORINE with ezetimibe/simvastatin is contraindicated 2.
Why it happens (mechanism)
Inhibition of CYP3A4-substrate metabolism of simvastatin by cycloSPORINE; inhibition of OATP1B1-mediated simvastatin transport by cycloSPORINE
How to manage this interaction
This pairing is considered off-limits (contraindicated), because cyclosporine can drive simvastatin levels high enough to damage muscle.
- Do not stop either medication on your own. Keep taking what you are prescribed until you speak with your care team.
- Your prescriber will typically switch you to a different cholesterol medicine that is safer with cyclosporine, rather than adjust the simvastatin dose.
- This also applies to combination products containing simvastatin (such as ezetimibe/simvastatin).
- Contact your pharmacist or doctor promptly, and seek care right away if you notice muscle pain, weakness, or dark urine.
Management is individual — confirm any change with your pharmacist or prescriber.
Literature reports
5 reports — tap to read
a) Researchers examined what happened when a single 20 mg dose of simvastatin was given together with cycloSPORINE in 10 renal transplant patients. Five of these patients received cycloSPORINE, azaTHIOprine, and prednisoLONE, while the other five received azaTHIOprine and prednisoLONE. In the group receiving cycloSPORINE, the mean area under the concentration-time curve (AUC) for simvastatin was significantly higher and the mean Cmax was higher. The time to reach Cmax did not differ between the two groups 3.
b) An extended study monitored 26 heart transplant patients who were taking simvastatin at an average dose of 10 mg daily along with triple immunosuppressive therapy that included cycloSPORINE, azaTHIOprine, and corticosteroids. The comparison group was made up of 26 heart transplant patients who were also receiving triple immunosuppressive therapy but were not taking simvastatin. At the one-year mark, data were available for 21 patients on simvastatin and 21 in the control group. The findings showed that simvastatin 10 mg daily reduced serum concentrations of total cholesterol, LDL cholesterol, and triglycerides. These decreases resemble those attainable in the general population with simvastatin doses of 20 mg to 40 mg daily. Two patients in the simvastatin group developed mild myopathies with creatine phosphokinase (CK) levels at 5 and 44 times the upper normal limit. These CK elevations occurred after simvastatin doses were raised from 5 mg daily to 10 mg daily, and from 10 mg daily to 15 mg daily, respectively. Both patients recovered fully once simvastatin was returned to its original dose 4.
c) Rhabdomyolysis was described in 2 cycloSPORINE-treated heart transplant patients who were receiving simvastatin at 20 mg and 40 mg daily, respectively. Stopping simvastatin, reducing the cycloSPORINE dose, and providing intensive hydration brought lab values back to normal within 1 week 5.
d) A 55-year-old woman experienced fatal rhabdomyolysis after being treated with simvastatin and cycloSPORINE at the same time. The woman had several coexisting conditions, including hyperlipidemia, type 2 diabetes mellitus, morbid obesity, chronic renal failure, and hypertension. She had been taking simvastatin 10 mg/day for an unknown length of time before undergoing a renal transplant. Simvastatin was stopped and then restarted 4 months after the renal transplant. Three months afterward the simvastatin dose was raised to 20 mg/day. Three months later the patient came to the hospital with severe weakness and fatigue. She was also noted to be taking predniSONE, azaTHIOprine, famotidine, insulin, and metoprolol concurrently. Laboratory findings were notable, showing a greatly elevated creatine kinase level, marked hyperkalemia, hypocalcemia, and hyperphosphatemia. A cycloSPORINE level fell within the therapeutic range. The patient's muscle weakness persisted, and despite correction of the metabolic imbalances, the patient died 10 days into her hospital stay 6.
e) A post-transplant patient taking many medications, among them simvastatin and cycloSPORINE, developed generalized weakness and severe muscle pain in his limbs. This occurred along with elevated CPK (3878 U/L), LDH (585 U/L), and GOT (133 U/L), as well as myoglobin in the urine. Electromyography showed myopathic changes in the deltoid and vastus lateralis muscles. Tacrolimus was substituted for cycloSPORINE, and after 8 days in the hospital the patient's muscle strength returned and muscle enzyme levels were within normal limits 7.
Common questions
Can I take Simvastatin and Cyclosporine together?
Cyclosporine and simvastatin should not be used together because simvastatin can build up and cause serious muscle damage; ask your doctor or pharmacist about a safer cholesterol medicine. Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Cyclosporine interaction?
It is rated contraindicated. These should generally not be used together.
How quickly could this interaction happen?
The documented onset is "unspecified". The timing of this interaction is not well characterized.
How is the Simvastatin and Cyclosporine interaction managed?
This pairing is considered off-limits (contraindicated), because cyclosporine can drive simvastatin levels high enough to damage muscle. Do not stop either medication on your own. Keep taking what you are prescribed until you speak with your care team. Your prescriber will typically switch you to a different cholesterol medicine that is safer with cyclosporine, rather than adjust the simvastatin d… Management is individual — always follow your own care team's guidance.
How strong is the evidence for this interaction?
The evidence is graded "probable". Good supporting evidence, though not definitively proven.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Simvastatin or Cyclosporine 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
- Arnadottir M, Eriksson L, Thysell H, et al: Plasma concentration profiles of simvastatin 3-hydroxy-3- methyl-glutaryl-coenzyme A reductase inhibitory activity in kidney transplant recipients with and without ciclosporin. Nephron 1993; 65:410-413.
- Vanhaecke J, Van Cleemput J, Van Lierde J, et al: Safety and efficacy of low dose simvastatin in cardiac transplant recipients treated with cyclosporine. Transplantation 1994; 58:42-45. DOI
- Meier C, Stey C, Brack T, et al: Rhabdomyolyse be simvastatin und ciclosporin behandelten patienten: rolle der aktivitaet des cytochrom-P-450 enzymsystems der leber. Schweiz Med Wochenschr 1995; 125:1342-1346.
- Weise W & Possidente CJ: Fatal rhabdomyolysis associated with simvastatin in a renal transplant patient (letter). Am J Med 2000; 108:351-352. PubMed
- Cohen E, Kramer MR, Maoz C, et al: Cyclosporin drug-interaction-induced Rhabdomyolysis. A report of two cases in lung transplant recipients. Transplantation 2000; 70:119-122.
Keep reading about Cyclosporine
Keep reading about Simvastatin
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