Midazolam – kdc

CLINICAL USE

Benzodiazepine:Sedation with amnesia in conjunction with local anaesthesia, premedication, induction

DOSE IN NORMAL RENAL FUNCTION

See SPC for dosing guidelines

PHARMACOKINETICS

Molecular weight :325.8 (362.2 as hydrochloride)

%Protein binding :96–98

%Excreted unchanged in urine : <1

Volume of distribution (L/kg) :0.7–1.2

half-life – normal/ESRD (hrs) :2–7/Unchanged

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Dose as in normal renal function

<10 : Use sparingly and titrate according to response. Only bolus doses, not continuous infusion

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Unlikely to be dialysed. Dose as in GFR <10 mL/min

HD :Not dialysed. Dose as in GFR <10 mL/min

HDF/high flux :Unknown dialysability. Dose as in GFR <10 mL/min

CAV/VVHD :Unknown dialysability. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antibacterials: concentration increased by erythromycin, clarithromycin, telithromycin and quinupristin/dalfopristin (profound sedation); metabolism possibly accelerated by rifampicin

Antifungals: concentration increased by itraconazole, ketoconazole, posaconazole and fluconazole (prolonged sedative effect)

Antipsychotics: increased sedative effects; increased risk of hypotension, bradycardia and respiratory depression when parenteral benzodiazepines are given with IM olanzapine

Antivirals: atazanavir, efavirenz, nelfinavir, saquinavir, ritonavir, amprenavir and indinavir increase risk of prolonged sedation with midazolam, avoid with atazanavir

Ciclosporin: in vitro studies suggested that ciclosporin could inhibit the metabolism of midazolam. However, blood ciclosporin concentrations in patients given ciclosporin to prevent graft rejection were considered too low to result in an interactionSodium oxybate: enhanced effects of sodium oxybate – avoid

ADMINISTRATION

Reconstition

Route

IV, IM

Rate of Administration

1–10 mL/hour according to response

Comments

Can be used undiluted Compatible with glucose 5%, sodium chloride 0.9%

OTHER INFORMATION

Protein binding of midazolam is decreased in ERF; hence more unbound drug is available to produce CNS effects, so a decrease in dose is recommendedCSM has received reports of respiratory depression, sometimes associated with severe hypotension, following intravenous administrationCaution when used for sedation in severe renal impairment especially when used with opiates and/or neuromuscular blocking agents – monitor sedation and titrate to responseIncreased CNS sensitivity in patients with renal impairmentOne study reports midazolam as having a sieving coefficient = 0.06 and unlikely to be removed by haemofiltration.

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