Midazolam and Cyclosporine Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Midazolam
No brand names on recordCyclosporine Injection
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
Decreased midazolam clearance and increased midazolam plasma concentrations
Interaction Deep Dive
The concomitant use of CYP3A4 inhibitors, such as cycloSPORINE3, with midazolam (a CYP3A4 substrate) may decreased midazolam clearance, increase midazolam plasma concentrations, and prolong sedation 1. A case-control study of Caucasian patients 1 to 5 years post-kidney transplant found that midazolam clearance was 24% lower when given IV and 31% lower when given orally following concomitant cycloSPORINE administration (n=20) compared with coadministration of midazolam and tacrolimus-matched controls (n=20) 2. Caution should be used if coadministered 1.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated midazolam metabolism by cycloSPORINE
Literature reports
1 report — tap to read
a) Following concomitant administration of midazolam (a CYP3A4 substrate) and cycloSPORINE (a CYP3A4 inhibitor) (n=20), clearance of midazolam was significantly decreased (24% lower (p=0.022) IV midazolam and 31% lower (p=0.013) oral midazolam) compared with coadministration of midazolam and tacrolimus-matched controls (n=20), according to a case-control study of Caucasian adults 1 to 5 years post-kidney transplant. In the cycloSPORINE (n=20), tacrolimus (n=20), and no calcineurin inhibitor (n=6) groups following administration of midazolam 1 mg IV, the midazolam clearance was 269 +/- 73 mL/min, 354 +/- 102 mL/min, and 378 +/-108 mL/min, respectively, and after administration of midazolam 2 mg orally, the midazolam clearance was 479 +/- 190 mL/min, 688 +/- 265 mL/min, and 837 +/- 453 mL/min, respectively. Following concomitant cycloSPORINE and oral midazolam administration, midazolam Tmax and Cmax did not differ significantly between groups 2.
Common questions
Can I take Midazolam and Cyclosporine Injection together?
Decreased midazolam clearance and increased midazolam plasma concentrations Always confirm with your pharmacist or prescriber before making any change.
How serious is the Midazolam and Cyclosporine Injection interaction?
It is rated moderate. Can be significant — usually manageable with monitoring.
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 "established". Well documented — supported by controlled studies or strong clinical data.
Questions for your pharmacist
- Does my dose of Midazolam or Cyclosporine Injection 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 anything you'd monitor while I'm on both?
References (3)
- Product Information: midazolam HCl IM, IV injection solution, midazolam HCl IM, IV injection solution. Hospira, Inc (Per DailyMed), Lake Forest, IL, 2009.
- de Jonge H, de Loor H, Verbeke K, et al: In vivo CYP3A activity is significantly lower in cyclosporine-treated as compared with tacrolimus-treated renal allograft recipients. Clin Pharmacol Ther 2011; 90(3):414-422. PubMed
- Product Information: GENGRAF(R) oral capsules, cyclosporine (modified) oral capsules. Abbott Laboratories (per Manufacturer), North Chicago, IL, 2010. DailyMed
Keep reading about Midazolam
Keep reading about Cyclosporine Injection
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