Drug Interaction Report

Midazolam Injection and Cimetidine: Interaction Details

A pharmacist-reviewed analysis of the Midazolam Injection and Cimetidine interaction: the documented clinical effects, severity rating, onset, mechanism, and management considerations, with cited references throughout.

AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature

Cimetidine

Tagamet
+

Midazolam Injection

Nayzilam Versed® Injection
Dr. Brian Staiger, PharmD, BCPS
Medically reviewed by
Dr. Brian Staiger, PharmD, BCPS
Updated Aug 8, 2026
Editorial policy · Data sources
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Interaction severity
Moderate
Can be significant — usually manageable with monitoring.
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.

Of 276 documented Midazolam Injection interactions, 52 are rated moderate — including this one.
Onset
delayed
Evidence
probable
Severity
Moderate

What happens

Midazolam toxicity (CNS depression, sedation, dizziness, ataxia, weakness, decreased cognition or motor performance)

Interaction Deep Dive

Cimetidine decreases the clearance of benzodiazepines that are metabolized by hydroxylation or dealkylation (eg, diazepam, chlordiazepoxide, clorazepate, flurazepam, prazepam, halazepam, alprazolam, triazolam, midazolam, quazepam, estazolam, bromazepam)7489. Adverse effects such as pronounced sedation and impaired cognitive and psychomotor function have been reported 1. Cimetidine is a known cytochrome P450 3A4 enzyme inhibitor, and midazolam metabolism is mediated by CYP450 3A4 10.

Why it happens (mechanism)

Inhibition of midazolam metabolism by cimetidine

Literature reports

3 reports — tap to read

a) The psychometric recovery from single doses of midazolam before and after one week of cimetidine 400 mg twice daily were evaluated 1. At 2.5 hours after midazolam administration, the cimetidine group had a significantly higher impairment score compared with baseline. Other researchers also measured the absolute bioavailability of midazolam with and without pretreatment with cimetidine and found that the bioavailability of midazolam was more than 30% higher with cimetidine pretreatment 2.

b) The pharmacodynamic responses were significantly different for midazolam with concurrent cimetidine compared to midazolam alone 3. Steady state midazolam plasma levels with and without cimetidine challenge were measured 4. Cimetidine significantly increased the concentration of midazolam from 56.7 +/- 7.8 to 71.3 +/- 19.6 ng/mL (p = 0.004).

c) The pharmacokinetics of midazolam were evaluated with and without cimetidine. Cimetidine was found to have no effect on midazolam pharmacokinetics 5. Others suggested that this study found no effect on midazolam pharmacokinetics because plasma cimetidine concentrations were subtherapeutic 6.

Common questions

Can I take Midazolam Injection and Cimetidine together?

Midazolam toxicity (CNS depression, sedation, dizziness, ataxia, weakness, decreased cognition or motor performance) Always confirm with your pharmacist or prescriber before making any change.

How serious is the Midazolam Injection and Cimetidine interaction?

It is rated moderate. Can be significant — usually manageable with monitoring.

How quickly could this interaction happen?

The documented onset is "delayed". Effects tend to build up gradually over days to weeks.

How strong is the evidence for this interaction?

The evidence is graded "probable". Good supporting evidence, though not definitively proven.

Questions for your pharmacist

  • Does my dose of Midazolam Injection or Cimetidine 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 (10)

  1. Sanders LD, Whitehead C, Gildersleve CD, et al: Interaction of H2-receptor antagonists and benzodiazepine sedation: a double-blind placebo-controlled investigation of the effects of cimetidine and ranitidine on recovery after intravenous midazolam. Anaesthesia 1993; 48:286-292.
  2. Fee JPH, Collier PS, Howard PJ, et al: Cimetidine and ranitidine increase midazolam bioavailability. Clin Pharmacol Ther 1987; 41:80-84. PubMed
  3. Salonen M, Aantaa E, Aaltonen L, et al: Importance of the interaction of miadazolam and cimetidine. Acta Pharmacol Toxicol 1986; 58:91-95.
  4. Klotz U, Arvela P, & Rosenkranz B: Effect of single doses of cimetidine and ranitidine on the steady-state plasma levels of midazolam. Clin Pharmacol Ther 1985; 38:652-655. PubMed
  5. Greenblatt DJ, Locniskar A, Scavone JM, et al: Absence of interaction of cimetidine and ranitidine with intravenous and oral midazolam. Anesth Analg 1986; 65:176-180.
  6. Brown GC: Midazolam and cimetidine: lack of interaction is unproven (letter). Anesth Analg 1987; 66:1196. DOI
  7. Locniskar A, Greenblatt DJ, Harmatz JS, et al: Interaction of diazepam with famotidine and cimetidine, two H2-receptor antagonists. J Clin Pharmacol 1986; 26:299-303.
  8. Desmond PV, Patwardhan RV, Schenker S, et al: Cimetidine impairs elimination of chlordiazepoxide (librium) in man. Ann Intern Med 1980; 93:266-268. PubMed
  9. Pourbaix S, Desager JP, Hulhoven R, et al: Pharmacokinetic consequences of long term coadministration of cimetidine and triazolobenzodiazepines, alprazolam and triazolam, in healthy subjects. Int J Clin Pharmacol Ther Toxicol 1985; 23:447-451.
  10. Product Information: Versed(R), midazolam HCl for injection. Roche Laboratories Inc. Nutley, NJ, 2000. DailyMed
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Cimetidine

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Beyond drug–drug

These medications also interact with supplements

Prescription drugs aren't the whole picture — herbal and dietary supplements can interact with them too. From the evidence-graded Natural Medicines database:

Cimetidine + Activated Charcoal Pu-erh Tea St. John's Wort Adrafinil African Wild Potato Banderol Beer Bitter Melon + 87 more

major · moderate · minor — check everything you take with our drug–supplement interaction checker.

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This information is for education, not a substitute for professional medical advice. Do not start, stop, or change any medication without talking to your pharmacist or prescriber.