Midazolam Injection and Echinacea: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Midazolam Injection
Echinacea
No brand names on record
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
Alterations in midazolam effectiveness
Interaction Deep Dive
The concomitant use of midazolam with Echinacea purpurea significantly decreased t(1/2), and increased clearance of midazolam in a systematic review and meta-analysis1. Significant changes in drug disposition may be due to inhibition of intestinal CYP3A activity and induction of hepatic CYP3A activity. As the effect of echinacea on CYP3A activity is difficult to predict, caution should be used when echinacea is coadministered with drugs dependent on CYP3A for their elimination 2.
Why it happens (mechanism)
Induction and/or inhibition of CYP3A-mediated midazolam metabolism
Literature reports
2 reports — tap to read
a) In a systematic review and meta-analysis that identified 11 studies of drug-herb interactions in 152 healthy subjects, coadministration of Echinacea purpurea and midazolam (2 studies) resulted in a significant increase in the clearance of midazolam 11.9 L/hr (95% CI, 2.8 to 21 L/hr) and a significant decrease in t(1/2) -1.6 hours (95% CI, -3.1 to -0.1 hours). Cmax and AUC of midazolam were not significantly affected. The 2 studies used Echinacea purpurea root or fresh liquid extract 8:1 (250 mg) 1.
b) A fixed-order, open-label study showed that echinacea (400 mg 4 times daily for 8 days) significantly increased the systemic clearance of midazolam, a CYP3A substrate, by 34% (90% CI, 116% to 150%). Twelve healthy volunteers who followed a restricted diet before and during the study were administered an oral combination of caffeine 200 mg, tolbutamide 500 mg) dextromethorphan hydrobromide 30 mg, and IV midazolam 0.05 mg/kg over 30 minutes. Blood and urine samples were taken prior to and intermittently throughout the study. Approximately 5 to 7 days following the competition of the first phase of the study, volunteers began an 8-day course of echinacea. During echinacea dosing, oral doses of caffeine, tolbutamide, dextromethorphan, and oral and IV midazolam were administered, and again blood and urine samples were intermittently collected. Systemic clearance of IV midazolam was increased by 42% with a decrease in the AUC of 23% (127 to 102 mcg x hr/L; 90% CI, 63% to 88%). Volume of distribution, oral clearance, and AUC after oral dosing were not significantly affected by echinacea administration. Oral bioavailability of midazolam significantly increased (90% CI, 108% to 159%), hepatic availability was significantly reduced by 18%, while intestinal availability significantly increased from 0.33 to 0.61. Echinacea administration increased hepatic extraction of midazolam significantly from 0.28 to 0.39, suggesting that hepatic CYP3A activity was increased 2.
Common questions
Can I take Midazolam Injection and Echinacea together?
Alterations in midazolam effectiveness Always confirm with your pharmacist or prescriber before making any change.
How serious is the Midazolam Injection and Echinacea 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 "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 Midazolam Injection or Echinacea 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 (2)
- Awortwe C, Bruckmueller H, & Cascorbi I: Interaction of herbal products with prescribed medications: a systematic review and meta-analysis. Pharmacol Res 2019; 141:397-408. PubMed
- Gorski JC, Huang SM, Pinto A, et al: The effect of echinacea (Echinacea purpurea root) on cytochrome P450 activity in vivo. Clin Pharmacol Ther 2004; 75(1):89-100. PubMed
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