Midazolam Nasal Spray and Roxithromycin: Interaction Details
AI-assisted, pharmacist-reviewed · Source data updated Aug 8, 2026 · Sources: FDA labeling, DDInter 2.0, cited literature
Midazolam Nasal Spray
Roxithromycin
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 benzodiazepine toxicity (CNS depression, ataxia, lethargy)
Interaction Deep Dive
Macrolide antibiotics may inhibit hepatic enzymes responsible for benzodiazepine metabolism, leading to increased plasma concentrations of benzodiazepines through reduced clearance, prolonged half-life, and increased volume of distribution6231.
Why it happens (mechanism)
Decreased midazolam metabolism and clearance
Literature reports
4 reports — tap to read
a) An 8-year-old boy undergoing adenoidectomy was premedicated with oral midazolam 0.5 mg/kg and oral atropine 0.03 mg/kg, followed in one hour by erythromycin 400 mg intravenously. The patient lost consciousness 40 minutes later after 200 mg of erythromycin had been infused; other vital signs remained normal, and he regained consciousness after 45 minutes. At 170 minutes post-medication, his midazolam plasma concentration was 134 ng/mL. Six other children who were similarly premedicated (midazolam 0.5 mg/kg and atropine 0.03 mg/kg) but did not receive erythromycin had a mean midazolam level of 73 ng/mL 1.
b) A double-blind, placebo-controlled study of healthy volunteers has found that clearance of intravenously administered midazolam is reduced by about 50% following five days of erythromycin therapy versus placebo 3.
c) One study analyzed the effects of roxithromycin on a single dose of midazolam in a double-blind, randomized crossover study of two phases separated by ten days. Ten healthy volunteers were given oral roxithromycin 300 mg or matched placebo once a day for six days. On the sixth day, they also received midazolam 15 mg orally with 150 mL of water two hours after the ingestion of roxithromycin. Results showed that roxithromycin administration caused a 47% increase in the mean area under the concentration-time curve (AUC) of midazolam compared to placebo. The elimination half-life of midazolam was also increased, from 1.7 hours to 2.2 hours. No statistical differences were noted in mean maximum concentration (Cmax) or time to maximum concentration (Tmax) between the treatment phases. The only midazolam pharmacodynamic parameter affected by roxithromycin administration was the digit symbol substitution test. The authors concluded that although the effect of roxithromycin on the pharmacokinetics of midazolam appears to be small and clinically insignificant, the lowest effective dose of midazolam should be used in patients receiving concurrent roxithromycin therapy 5.
d) To determine the effect of macrolide antibiotic and benzodiazepine therapy on human performance, 223 healthy medical students participated in four double-blind, placebo-controlled studies. Subjects received triazolam 0.25 mg, midazolam 5 mg, 10 mg, or 15 mg with and without erythromycin 750 mg or roxithromycin 300 mg. The effects of macrolide antibiotic and benzodiazepine coadministration were assessed objectively using the digit symbol substitution test, letter cancellation test, and the flicker fusion test. Subjective parameters included memory, drowsiness, mental slowness, and clumsiness. Coadministration of roxithromycin and midazolam resulted in enhanced midazolam effects in terms of increased number of variables significantly impaired as compared with placebo. Erythromycin proved to be more potent than roxithromycin in enhancing the effects of midazolam 4.
Common questions
Can I take Midazolam Nasal Spray and Roxithromycin together?
Increased benzodiazepine toxicity (CNS depression, ataxia, lethargy) Always confirm with your pharmacist or prescriber before making any change.
How serious is the Midazolam Nasal Spray and Roxithromycin 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 Nasal Spray or Roxithromycin 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 (6)
- Hiller A, Olkkola KT, Isohanni P, et al: Unconsciousness associated with midazolam and erythromycin. Br J Anaesth 1990; 65:826-828. PubMed
- Phillips JP, Antal EJ, & Smith RB: A pharmacokinetic drug interaction between erythromycin and triazolam. J Clin Psychopharmacol 1986; 6:297-299. DOI
- Olkkola KT, Aranko K, Luurila H, et al: A potentially hazardous interaction between erythromycin and midazolam. Clin Pharmacol Ther 1993; 53:298-305. PubMed
- Mattila MJ, Idanpaan-Heikkila JJ, Tornwall M, et al: Oral single doses of erythromycin and roxithromycin may increase the effects of midazolam on human performance. Pharmacol Toxicol 1993; 73:180-185. PubMed
- Backman JT, Aranko K, Himberg JJ, et al: A pharmacokinetic interaction between roxithromycin and midazolam. Eur J Clin Pharmacol 1994; 46:551-555. PubMed
- Warot D, Bergougnan L, Lamiable D, et al: Troleandomycin-triazolam interaction in healthy volunteers: pharmacokinetic and psychometric evaluation. Eur J Clin Pharmacol 1987; 32:389-393. DOI
Keep reading about Midazolam Nasal Spray
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