Midazolam
Class: sedative – benzodiazepine
Indications (NB some may be unlicensed): sedation, anaesthetic induction agent, intractable hiccup refractory to other treatment, epilepsy, muscle spasm, dyspnoea, insomnia, agitation or confusion in the last days of life
Contraindications/cautions: avoid sudden withdrawal, respiratory depression; sleep apnoea
Adverse reactions: common: fatigue, drowsiness, amnesia; less common: respiratory depression (high dose), aggression, confusion, hypotension, GI upset
Metabolism/clearance: metabolised by metabolising enzyme CYP3A (major) mainly in the liver
Interactions:
- increased clinical effect/toxicity of midazolam (due to increased blood concentrations) may occur with some CYP metabolising enzyme inhibitors (see above) e.g. clarithromycin, fluconazole, grapefruit juice, itraconazole, ketoconazole
- decreased clinical effect/toxicity of midazolam (due to decreased blood concentrations) may occur with some CYP metabolism enzyme inducers (see above) e.g. carbamazepine, phenobarbitone, phenytoin, rifampicin, St John’s wort
- additive CNS effects with other CNS depressants e.g. other benzodiazepines (e.g. lorazepam), phenothiazines (e.g. chlorpromazine), tricyclic antidepressants (e.g. amitriptyline), opioids, alcohol
| Dosing: | |
|---|---|
| oral: | 7.5 to 15 mg at bed-time (to sleep) |
| subcut: | 5 to 60 mg/24 hours (up to 150 mg in sedation at the end-of-life) — doses adjusted according to response |
| Intractable hiccup: | 2.5 to 10 mg subcut prn – max dose 60 mg daily CSCI 10 mg-60 mg over 24 hours |
| rectal: | not available |
Syringe driver: see syringe driver compatibility chart
Mechanism of action: may enhance the effect of GABA, an inhibitory neurotransmitter in the CNS
Peak concentrations: oral 20 to 50 min subcut 5 to 10 min iv 2 to 3 mins
Duration: 15 minutes to several hours Half life: 2 to 5 hours
Notes:
- midazolam is a very short acting benzodiazepine so dose titration to response is easier than with longer acting benzodiazepines e.g. clonazepam
- IV administration can result in hypotension and transient apnoea
- benzodiazepines may reduce dyspnoea by anxiolytic and sedative effects
- for approximate equivalent oral anxiolytic/sedative doses see clonazepam page
- for pharmacological properties of benzodiazepines and other hypnotics see clonazepam page
- may be used bucally or sublingually
- bioavailability 95% subcut and 85% sublingually