Midazolam is a fast-acting sedative given by mouth, intravenously or intramuscularly to calm patients before procedures, induce anaesthesia or stop prolonged seizures. It should only be used by trained staff with resuscitation equipment available.
Also known as: Versed, Dormicum
Combining chlorpromazine with midazolam increases the risk of profound sedation, hypotension and respiratory depression.
Additive CNS depression plus inhibition of midazolam metabolism (CYP3A4/2D6) by chlorpromazine.
Level of consciousness, blood pressure and respiratory rate.
Sedation unresponsive to stimuli, slow breathing, hypotension.
Avoid the combination outside monitored settings; reduce the midazolam dose; use only in a clinical setting with airway support.
DailyMed — Thorazine (chlorpromazine) label, CNS depression; EMC-UK — Midazolam SmPC: https://www.medicines.org.uk/emc/product/5682
Promethazine plus midazolam causes additive CNS depression (profound sedation, respiratory depression) and hypotension.
Both depress the CNS through different mechanisms; promethazine also inhibits midazolam metabolism.
Level of consciousness, respiratory rate and saturation.
Extreme drowsiness, slow or shallow breathing.
Avoid the combination outside monitored settings (procedural sedation only with trained team and airway support).
EMC-UK — Phenergan (promethazine) SmPC, CNS depression with benzodiazepines: https://www.medicines.org.uk/emc/product/4941
Hydroxyzine plus midazolam causes additive sedation with respiratory depression risk.
Hydroxyzine (sedating antihistamine) depresses the CNS; midazolam is a short-acting benzodiazepine.
Level of consciousness and respiratory rate after dosing.
Persistent drowsiness, slow breathing.
Avoid outside a controlled setting; reduce doses and monitor breathing.
EMC-UK — Hydroxyzine SmPC, CNS depression with depressants: https://www.medicines.org.uk/emc/product/8740
Propofol plus midazolam adds respiratory depression, profound sedation and hypotension; requires dose reduction and airway support.
Synergism between benzodiazepine and IV anaesthetic at the GABA-A receptor; Diprivan label: reduce maintenance dose by ~25–30% when sedatives are co-administered.
Saturation, capnography, blood pressure, sedation level.
Apnoea, hypotension, rapid desaturation.
Reduce the propofol dose (~25–30%); only in a setting with oximetry, airway support and resuscitation available.
DailyMed — Diprivan (propofol) Injectable Emulsion label [RLD], Warnings: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=5ec25932-6c21-4cd5-8f60-80761f2e20a6; Midazolam HCl Injection label: https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=f051776f-94c5-4e34-80ed-f45b9c36881e
Flumazenil reverses midazolam sedation but may precipitate withdrawal seizures in chronic benzodiazepine users or in mixed overdose, and sedation reappears after reversal (resedation).
Competitive antagonism at the GABA-A benzodiazepine receptor: abrupt reversal removes the depressant effect and unmasks a hyperexcitable state with a lowered seizure threshold; flumazenil has a short half-life (≈1 h), shorter than midazolam, so sedation reappears (Prontuário, Annex 7 — Flumazenil: "the benzodiazepine effect may reappear").
Consciousness, respiratory rate, SpO2 and ECG; reassess sedation over the next 2 h and advise against driving for 24 h (Prontuário, Annex 7).
Seizures, paradoxical agitation, recurrence of respiratory depression.
Use only with a precise indication (benzodiazepine overdose with respiratory depression); exclude mixed overdose with tricyclics or other proconvulsants before administration; titrate in 0.2 mg increments and monitor where airway support and rescue benzodiazepine are available.
Flumazenil Injection USP (Pfizer) label, Warnings — withdrawal seizures in benzodiazepine-dependent patients: https://labeling.pfizer.com/ShowLabeling.aspx?id=684; INFARMED Prontuário Terapêutico (11th ed., 2012), Annex 7 — Flumazenil (benzodiazepine effect may reappear).
No documented food or drink interactions.
Midazolam depresses respiration — contraindicated in severe unventilated respiratory impairment.
Use only with SpO2 monitoring and airway support available.
Site monograph (midazolam — mandatory airway); EMC-UK midazolam SmPC 4.3/4.4.
Benzodiazepines worsen muscle weakness in myasthenia — contraindicated.
If sedation unavoidable, ensure ventilatory support.
EMC-UK — midazolam SmPC 4.3 (myasthenia gravis).
Accumulation of the glucuronidated metabolite and worsened sedation in renal impairment.
Titrate slowly; reduced dose in elderly and renally impaired.
EMC-UK — midazolam SmPC 4.4 (renal impairment).
Short-acting benzodiazepine used for sedation/procedures; Annex 1 records "use before caesarean section has a depressant effect on the newborn; See Benzodiazepines" (factor DM). Avoid near term; if necessary, use the lowest possible dose and be prepared for neonatal resuscitation (respiratory depression, hypotonia — "floppy infant syndrome").
Avoid near term and during labour; use only if clearly necessary for procedures, at the lowest effective dose.
Excreted into milk; preferably avoid breastfeeding for 4–6 hours after a single dose (short half-life) or use an alternative; Annex 2 refers to "Benzodiazepines" (infant drowsiness).
Prontuário Terapêutico INFARMED — Annex 1: "Midazolam — Use before caesarean section has a depressant effect on the newborn; See Benzodiazepines" (l. 41016); Annex 2 (l. 42913). EMC-UK (MHRA) — Midazolam SmPC: https://www.medicines.org.uk/emc/product/5457/smpc (section 4.6).
Clinical and educational support tool. The information does not replace a medical prescription or the opinion of a qualified healthcare professional.
Ultra-short-acting benzodiazepine with robust anterograde amnesia: standard in procedural sedation, but requires strict monitoring due to dose-dependent respiratory depression.
Positive allosteric modulator of the GABA-A receptor: increases the frequency of chloride channel opening in response to GABA, hyperpolarising neurones — anxiolytic, sedative, hypnotic, myorelaxant and anticonvulsant effects. Reversible by flumazenil.
IV: immediate. IM: rapid complete absorption (> 90%, peak 20–30 min). Oral: rapid, but ~40% first pass (bioavailability 30–70%). Intranasal/buccal: good (peak 10–15 min), useful in out-of-hospital status epilepticus.
Almost complete hepatic hydroxylation (CYP3A4/3A5) to 1-hydroxymidazolam (active, ~60–80% of parent potency), glucuronidated and renally excreted; no unchanged drug recovered in urine. Potent CYP3A4 inhibitors (clarithromycin, azoles, diltiazem) multiply exposure.
1.5–3.5 h (healthy adults); prolonged in the elderly (3–4 h), obese, hepatic impairment and neonates (6–12 h).
Medicines from the same therapeutic group (ATC classification) or the same pharmacological class.
