Hydrastis and Midazolam Nasal Spray: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Midazolam Nasal Spray
Hydrastis
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
Increased plasma concentrations of midazolam
Interaction Deep Dive
Goldenseal, similar to but to a lesser extent as clarithromycin, increased the AUC by 62%, half-life by 57%, and Cmax by 41% of midazolam, in an open-label, randomized study (n=16)1. Observe patients receiving goldenseal and midazolam for enhanced central nervous system effects. Warn patients regarding the potential for drug hangover. Doses of midazolam may need to be reduced.
Why it happens (mechanism)
Inhibition of CYP3A4-mediated midazolam metabolism by goldenseal
Literature reports
1 report — tap to read
a) Goldenseal, similar to but to a lesser extent as clarithromycin, increased the AUC by 62%, half-life by 57%, and Cmax by 41% of midazolam, in an open-label, randomized study (n=16). Healthy adult subjects (mean age, 27 +/- 6 years) received a single oral 8-mg dose of midazolam 24 hours before and after 14 days of oral goldenseal root extract 1323 mg three times daily (standardized to contain 24.1 mg/capsule of isoquinoline alkaloids). Additionally subjects received a single oral 8-mg dose of midazolam 24 hours before and after 7 days of oral clarithromycin 500 mg twice daily. This was performed in a randomized manner with a 30-day washout period between the goldenseal and clarithromycin phases. The mean midazolam pharmacokinetic parameters before and after goldenseal, respectively, were an AUC of 107.9 +/- 43.3 nanograms x hr/mL and 175.3 +/- 74.3 nanograms x hr/mL, p less than 0.001; a half-life of 2.01 +/- 0.42 hr and 3.15 +/- 1.12 hr, p less than 0.001; and a Cmax of 50.6 +/- 26.9 nanograms/mL and 71.2 +/- 50.2 nanograms/mL, p less than 0.05. Comparatively, the mean midazolam pharmacokinetic parameters before and after clarithromycin were an AUC of 102. 4 nanograms x hr/mL and 561.5 +/- 188.6 nanograms x hr/mL, p less than 0.001; a half-life of 2.08 +/- 0.53 hr and 4.08 +/- 2.05 hr, p less than 0.001; and a Cmax of 52.2 +/- 26.7 nanograms/mL and 113.5 +/- 36.2 nanograms/mL, p less than 0.001. The mean 1-hr hydroxymidazolam/midazolam serum ratios were significantly reduced, which was evidence of CYP3A4 inhibition of midazolam by goldenseal 1.
Common questions
Can I take Hydrastis and Midazolam Nasal Spray together?
Increased plasma concentrations of midazolam Always confirm with your pharmacist or prescriber before making any change.
How serious is the Hydrastis and Midazolam Nasal Spray interaction?
It is rated moderate. Can be significant — usually manageable with 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 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 Hydrastis or Midazolam Nasal Spray 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 (1)
- Gurley BJ, Swain A, Hubbard MA, et al: Supplementation with goldenseal (Hydrastis canadensis), but not kava kava (Piper methysticum), inhibits human CYP3A activity in vivo. Clin Pharmacol Ther 2008; 83(1):61-69. PubMed
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