skilled tasks (e.g. driving) afterwards. For intravenous
benzodiazepines the risk extends to at least 24 hours
after administration. Responsible persons should be
available to take patients home afterwards. The dangers of
taking alcohol should be emphasised.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oral suspension, oral
solution, solution for injection
EXCIPIENTS: May contain Benzyl alcohol, propylene glycol
Lorazepam 2 mg per 1 ml Lorazepam 2mg/1ml solution for injection
Lorazepam 4 mg per 1 ml Ativan 4mg/1ml solution for injection
ampoules | 10 ampoule P £3.54d
CAUTIONARY AND ADVISORY LABELS 2, 19
EXCIPIENTS: May contain Ethanol
Lorazepam 1 mg per 1 ml Lorazepam 1mg/ml oral solution sugar
free sugar-free | 150 ml P £103.62 DT = £103.62d
CAUTIONARY AND ADVISORY LABELS 2, 19
Lorazepam 1 mg Lorazepam 1mg tablets | 28 tablet P £6.59 DT
Lorazepam 2.5mg tablets | 28 tablet P £11.43 DT = £7.26d
Status epilepticus | Febrile convulsions
▶ Child 1–2 months: 300 micrograms/kg (max. per dose
2.5 mg), then 300 micrograms/kg after 10 minutes
(max. per dose 2.5 mg) if required
▶ Child 3–11 months: 2.5 mg, then 2.5 mg after 10 minutes
▶ Child 1–4 years: 5 mg, then 5 mg after 10 minutes if
▶ Child 5–9 years: 7.5 mg, then 7.5 mg after 10 minutes if
▶ Child 10–17 years: 10 mg, then 10 mg after 10 minutes if
▶ Adult: 10 mg, then 10 mg after 10 minutes if required
Conscious sedation for procedures
▶ BY SLOW INTRAVENOUS INJECTION
▶ Adult: Initially 2–2.5 mg, to be administered
5–10 minutes before procedure at a rate of
approximately 2 mg/minute, increased in steps of 1 mg
if required, usual total dose is 3.5–5 mg; maximum
▶ Elderly: Initially 0.5–1 mg, to be administered
5–10 minutes before procedure at a rate of
approximately 2 mg/minute, increased in steps of
0.5–1 mg if required; maximum 3.5 mg per course
Sedative in combined anaesthesia
▶ INITIALLY BY INTRAVENOUS INJECTION
▶ Adult: 30–100 micrograms/kg, repeated if necessary,
alternatively (by continuous intravenous infusion)
▶ BY DEEP INTRAMUSCULAR INJECTION
▶ Adult: 70–100 micrograms/kg, to be administered
20–60 minutes before induction, for debilitated
▶ Elderly: 25–50 micrograms/kg, to be administered
20–60 minutes before induction
▶ Adult: 1–2 mg, repeated if necessary, to be
administered 5–30 minutes before procedure, for
debilitated patients, use elderly dose
▶ Elderly: 0.5 mg, repeated if necessary, initial dose to be
administered 5–30 minutes before procedure, repeat
Induction of anaesthesia (but rarely used)
▶ BY SLOW INTRAVENOUS INJECTION
▶ Adult: 150–200 micrograms/kg daily in divided doses
(max. per dose 5 mg), dose to be given at intervals of
2 minutes, maximum total dose 600 micrograms/kg, for
debilitated patients, use elderly dose
▶ Elderly: 50–150 micrograms/kg daily in divided doses
(max. per dose 5 mg), dose to be given at intervals of
2 minutes, maximum total dose 600 micrograms/kg
Sedation of patient receiving intensive care
▶ INITIALLY BY SLOW INTRAVENOUS INJECTION
▶ Adult: Initially 30–300 micrograms/kg, dose to be given
in steps of 1–2.5 mg every 2 minutes, then (by slow
intravenous injection or by continuous intravenous
infusion) 30–200 micrograms/kg/hour, reduce dose (or
reduce or omit initial dose) in hypovolaemia,
vasoconstriction, or hypothermia, lower doses may be
adequate if opioid analgesic also used
Adjunct to antipsychotic for confusion and restlessness in
▶ Adult: Initially 10–20 mg/24 hours, adjusted according
to response; usual dose 20–60 mg/24 hours
Convulsions in palliative care
▶ BY CONTINUOUS SUBCUTANEOUS INFUSION
▶ Adult: Initially 20–40 mg/24 hours
l UNLICENSED USE Unlicensed oromucosal formulations are
also available and may have different doses—refer to
▶ In adults Oromucosal solution not licensed for use in adults
▶ In children Oromucosal solution not licensed for use in
children under 3 months. Injection not licensed for use in
status epilepticus or febrile convulsions. Not licensed for
use in children under 6 months for premedication and
conscious sedation. Not licensed for use by mouth. Not
licensed for use by buccal administration for conscious
Benzodiazepines should only be administered for
anaesthesia by, or under the direct supervision of,
personnel experienced in their use, with adequate
training in anaesthesia and airway management.
PRESCRIBING OF MIDAZOLAM IN PALLIATIVE CARE
The use of high-strength midazolam (5 mg/mL in 2 mL
and 10 mL ampoules, or 2 mg/mL in 5 mL ampoules)
should be considered in palliative care and other
situations where a higher strength may be more
appropriate to administer the prescribed dose, and
where the risk of overdosage has been assessed. It is
advised that flumazenil is available when midazolam is
used, to reverse the effects if necessary.
l CONTRA-INDICATIONS CNS depression . compromised
airway . severe respiratory depression
l CAUTIONS Cardiac disease . children (particularly if
cardiovascular impairment). concentration of midazolam
in children under 15 kg not to exceed 1 mg/mL . debilitated
patients (reduce dose)(in children). hypothermia .
340 Epilepsy and other seizure disorders BNF 78
hypovolaemia (risk of severe hypotension). neonates .risk
of airways obstruction and hypoventilation in children
under 6 months (monitor respiratory rate and oxygen
▶ Recovery when used for sedation Midazolam has a fast onset
of action, recovery is faster than for other benzodiazepines
such as diazepam, but may be significantly longer in the
elderly, in patients with a low cardiac output, or after
l INTERACTIONS → Appendix 1: midazolam
▶ Common or very common Level of consciousness decreased . vomiting
disorders . physical assault.respiratory disorders . vasodilation
▶ Frequency not known Appetite increased . disinhibition
(severe; with sedative and peri-operative use) (in children)
▶ With parenteral use Angioedema . drug abuse . drug
withdrawal seizure . embolism and thrombosis
SIDE-EFFECTS, FURTHER INFORMATION Higher doses are
associated with prolonged sedation and risk of
hypoventilation. The co-administration of midazolam with
other sedative, hypnotic, or CNS-depressant drugs results
in increased sedation. Midazolam accumulates in adipose
tissue, which can significantly prolong sedation, especially
in patients with obesity, hepatic impairment or renal
Overdose There have been reports of overdosage when
high strength midazolam has been used for conscious
sedation. The use of high-strength midazolam (5mg/mL in
2mL and 10mL ampoules, or 2mg/mL in 5mL ampoules)
should be restricted to general anaesthesia, intensive care,
palliative care, or other situations where the risk has been
assessed. It is advised that flumazenil is available when
midazolam is used, to reverse the effects if necessary.
l BREAST FEEDING Small amount present in milk—avoid
breast-feeding for 24 hours after administration (although
amount probably too small to be harmful after single
l HEPATIC IMPAIRMENT For parenteral preparations
manufacturer advises caution in all degrees of impairment.
Dose adjustments For parenteral preparations manufacturer
advises consider dose reduction in all degrees of
l RENAL IMPAIRMENT Use with caution in chronic renal
l DIRECTIONS FOR ADMINISTRATION
▶ With intravenous use in adults For intravenous infusion
(Hypnovel ®), give continuously in Glucose 5% or Sodium
l PRESCRIBING AND DISPENSING INFORMATION
Palliative care For further information on the use of
midazolam in palliative care, see www.medicinescomplete.
com/#/content/palliative/benzodiazepines-and-z-drugs.
l PATIENT AND CARER ADVICE Patients or carers should be
given advice on how and when to administer midazolam
Patients given sedatives and analgesics during minor
outpatient procedures should be very carefully warned
about the risks of undertaking skilled tasks (e.g. driving)
afterwards. For intravenous benzodiazepines the risk
extends to at least 24 hours after administration.
Responsible persons should be available to take patients
home afterwards. The dangers of taking alcohol should be
Medicines for Children leaflet: Midazolam for stopping seizures
www.medicinesforchildren.org.uk/midazolam-stopping-seizures
l NATIONAL FUNDING/ACCESS DECISIONS
Scottish Medicines Consortium (SMC) decisions
The Scottish Medicines Consortium has advised (November
2017) that midazolam oromucosal solution (Epistatus ®) is
accepted for use within NHS Scotland for the treatment of
prolonged, acute, convulsive seizures in patients aged
10 years to less than 18 years.
l MEDICINAL FORMS There can be variation in the licensing of
different medicines containing the same drug. Forms available
from special-order manufacturers include: oromucosal
solution, solution for injection, solution for infusion
Midazolam (as Midazolam hydrochloride) 1 mg per
Midazolam (as Midazolam hydrochloride) 2 mg per
1 ml Midazolam 10mg/5ml solution for injection ampoules |
10 ampoule P £6.75 DT = £6.86 (Hospital only)c | 10 ampoule P £7.60 DT = £6.86c
Midazolam (as Midazolam hydrochloride) 5 mg per
10 ampoule P £7.65 DT = £6.13c ▶ Hypnovel (Roche Products Ltd)
Midazolam (as Midazolam hydrochloride) 5 mg per 1 ml Hypnovel
10mg/2ml solution for injection ampoules | 10 ampoule P £7.11
Midazolam (as Midazolam hydrochloride) 1 mg per
1 ml Midazolam 50mg/50ml solution for infusion vials | 1 vial P £9.56–£12.00c
Midazolam (as Midazolam hydrochloride) 2 mg per
1 ml Midazolam 100mg/50ml solution for infusion vials | 1 vial P £9.05–£13.50c
CAUTIONARY AND ADVISORY LABELS 2
EXCIPIENTS: May contain Ethanol
▶ Buccolam (Shire Pharmaceuticals Ltd)
Midazolam (as Midazolam hydrochloride) 5 mg per
1 ml Buccolam 10mg/2ml oromucosal solution pre-filled oral syringes
sugar-free | 4 unit dose P £82.00 DT = £82.00c ▶ Epistatus (Veriton Pharma Ltd)
Midazolam (as Midazolam maleate) 10 mg per 1 ml Epistatus
10mg/1ml oromucosal solution pre-filled oral syringes sugar-free | 1 unit dose P £45.76 DT = £45.76c
p. 362 . Paroxetine, p. 366 . Pericyazine, p. 388 . Pregabalin,
p. 324 . Trazodone hydrochloride, p. 370 . Trifluoperazine,
ANTIDEPRESSANTS › SEROTONIN RECEPTOR
Buspirone hydrochloride 13-Jun-2018
▶ Adult: 5 mg 2–3 times a day, increased if necessary up
to 45 mg daily, dose to be increased at intervals of
2–3 days; usual dose 15–30 mg daily in divided doses
DOSE ADJUSTMENTS DUE TO INTERACTIONS
▶ Manufacturer advises reduce dose to 2.5 mg twice daily
with concurrent use of potent inhibitors of CYP3A4.
l CAUTIONS Does not alleviate symptoms of benzodiazepine
CAUTIONS, FURTHER INFORMATION A patient taking a
benzodiazepine still needs to have the benzodiazepine
withdrawn gradually; it is advisable to do this before
l INTERACTIONS → Appendix 1: buspirone
congestion . nausea . paraesthesia . skin reactions . sleep
disorders .tachycardia .tinnitus .tremor. vision disorders . vomiting
l HEPATIC IMPAIRMENT Manufacturer advises caution; avoid
Dose adjustments Manufacturer advises titrate individual
dose carefully in cirrhosis—consult product literature.
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