Simvastatin and Cyclosporine Ophthalmic: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Cyclosporine Ophthalmic
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.
What happens
An increased risk of myopathy or rhabdomyolysis
Interaction Deep Dive
The concomitant use of cycloSPORINE (an inhibitor of CYP3A4 and OATP1B1) and simvastatin (a substrate of CYP3A4 and OATP1B1) may increase plasma concentrations of simvastatin and increase the risk of myopathy or rhabdomyolysis. Coadministration of cycloSPORINE and simvastatin is contraindicated1. Coadministration of cycloSPORINE with ezetimibe/simvastatin is also contraindicated 2.
Why it happens (mechanism)
Inhibition of CYP3A4-substrate metabolism of simvastatin by cycloSPORINE; inhibition of OATP1B1-mediated simvastatin transport by cycloSPORINE
Literature reports
5 reports — tap to read
a) The effect of concurrent administration of a single dose of simvastatin 20 mg with cycloSPORINE in 10 renal transplant patients was investigated. Five patients were treated with cycloSPORINE, azaTHIOprine, and prednisoLONE and five were treated with azaTHIOprine and prednisoLONE. The simvastatin mean area under the concentration-time curve (AUC) was significantly higher and the mean Cmax was higher in the cycloSPORINE-treated group. Time to Cmax was the same in both groups 3.
b) A long-term study followed 26 heart transplant patients taking an average daily dose of simvastatin 10 mg daily and triple immunosuppressive therapy including cycloSPORINE, azaTHIOprine, and corticosteroids. The control group consisted of 26 heart transplant patients also on triple immunosuppressive therapy, but not on simvastatin therapy. After one year, data were available for 21 simvastatin patients and 21 controls. Results indicated that simvastatin 10 mg daily had lowered serum levels of total cholesterol, LDL cholesterol, and triglycerides. These reductions are similar to what can be achieved in the general population using simvastatin at 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 increases in CK were seen following dose increases of simvastatin from 5 mg daily to 10 mg daily, and from 10 mg daily to 15 mg daily, respectively. Both patients recovered completely when simvastatin was reduced to its original dose 4.
c) Rhabdomyolysis was reported in 2 cycloSPORINE-treated heart transplant patients receiving simvastatin 20 mg and 40 mg daily, respectively. Discontinuation of simvastatin, a dose reduction of cycloSPORINE, and intense hydration led to normalization of lab values within 1 week 5.
d) A 55-year-old woman developed fatal rhabdomyolysis after receiving concomitant therapy with simvastatin and cycloSPORINE. The woman had several comorbid diseases including hyperlipidemia, type 2 diabetes mellitus, morbid obesity, chronic renal failure and hypertension. She had taken simvastatin 10 mg/day for an unknown period of time prior to receiving a renal transplant. Simvastatin was discontinued and then reinitiated 4 months after the renal transplant. The dosage of simvastatin was increased 3 months later to 20 mg/day. Three months later the patient presented to the hospital with profound weakness and fatigue. Concomitant use of predniSONE, azaTHIOprine, famotidine, insulin and metoprolol was also noted. Laboratory results were remarkable and demonstrated a greatly increased creatine kinase level, marked hyperkalemia, hypocalcemia, and hyperphosphatemia. A cycloSPORINE level was within the therapeutic range. The patient's muscle weakness continued and despite correction of metabolic imbalances the patient expired 10 days into her hospital course 6.
e) A post-transplant patient on numerous medications including simvastatin and cycloSPORINE experienced generalized weakness and severe muscle pain in his limbs. This was accompanied by elevated CPK (3878 U/L), LDH (585 U/L), and GOT (133U/L), and myoglobin in the urine. Electromyography revealed myopathic changes in the deltoid and vastus lateralis muscles. Tacrolimus replaced the cycloSPORINE and after 8 days of hospitalization the patient's muscle strength returned and muscle enzyme levels were within normal limits 7.
Common questions
Can I take Simvastatin and Cyclosporine Ophthalmic together?
An increased risk of myopathy or rhabdomyolysis Always confirm with your pharmacist or prescriber before making any change.
How serious is the Simvastatin and Cyclosporine Ophthalmic 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 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 Ophthalmic 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 Ophthalmic
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