Promethazine and Midazolam Injection: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Promethazine
Midazolam 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
Increased risk of hypoventilation, airway obstruction, desaturation, or apnea
Interaction Deep Dive
Concomitant use of midazolam with promethazine may increase the risk of hypoventilation, airway obstruction, desaturation, or apnea and may contribute to profound and/or prolonged drug effect. Anticipated effects range from mild sedation to deep levels of sedation equivalent to a state of general anesthesia where the patient may require external support of vital functions. Monitor closely and be prepared to manage serious cardiorespiratory adverse reactions, including airway management1. Additionally, concomitant use of promethazine and midazolam (benzodiazepine) may increase the risk of respiratory depression, profound sedation, hypotension, coma, death and opioid overdose. Reserve the concomitant use of promethazine and benzodiazepine to patients for whom alternatives are inadequate. If concomitant use is necessary, use the lowest dose and shortest duration necessary to achieve treatment goals. In patients already receiving promethazine, prescribe a lower initial dose of midazolam than indicated in the absence of an opioid, and titrate based on clinical response. If promethazine is initiated in a patient already taking midazolam, prescribe a lower initial dose of promethazine, and titrate based on clinical response. Closely monitor for sedation and respiratory depression 6.
Why it happens (mechanism)
Additive CNS depression
Literature reports
2 reports — tap to read
a) Observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioid analgesics alone 6.
b) Concomitant administration of IV midazolam and thiopental resulted in synergistic (supra-additive) effects during induction of anesthesia 2. The combination of IV thiopental and midazolam had 1.8 times the expected potency of the individual drugs, and the dose of thiopental required to produce anesthesia was reduced by 50% in another study 3. A 15% reduction in the thiopental induction dose requirement has been observed if it follows IM premedication with midazolam 4. The interaction between midazolam and thiopental may in part be dependent on thiopental dosing 5.
Common questions
Can I take Promethazine and Midazolam Injection together?
Increased risk of hypoventilation, airway obstruction, desaturation, or apnea Always confirm with your pharmacist or prescriber before making any change.
How serious is the Promethazine and Midazolam Injection interaction?
It is rated major. Potentially serious — often needs a change or close 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 "theoretical". Predicted from the drugs' pharmacology; not yet confirmed in people.
From our Q&A
Real reader questions about these medications, each personally answered by our pharmacist:
Questions for your pharmacist
- Does my dose of Promethazine or Midazolam 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 a safer alternative to one of these medications for me?
References (6)
- Product Information: SEIZALAM(TM) intramuscular injection, midazolam HCl intramuscular injection. Meridian Medical Technologies, Inc (per DailyMed), Columbia, MD, 2018.
- Tverskoy M, Fleyshman G, Bradley EL, et al: Midazolam-thiopental anesthetic interaction in patients. Anesth Analg 1988; 67:342-345. DOI
- Short TG, Galletly DC, & Plummer JL: Hypnotic and anaesthetic action of thiopentone and midazolam alone and in combination. Br J Anaesth 1991; 66:13-19. PubMed
- Product Information: Versed(R), midazolam. Roche Laboratories Inc. Nutley, NJ, 2000. DailyMed
- Wilder-Smith OHG, Ravussin PA, Decosterd LA, et al: Hypnotic and anaesthetic action of thiopentone and midazolam alone and in combination. Br J Anaesth 1999; 83:590-595.
- Product Information: MEPERGAN intramuscular, intravenous injection, meperidine HCl, promethazine HCl intramuscular, intravenous injection. West-Ward Pharmaceuticals Corp (per FDA), Eatontown, NJ, 2023.
Keep reading about Promethazine
Keep reading about Midazolam Injection
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