Lorazepam

CLINICAL USE

Benzodiazepine:Short-term use in anxiety or insomnia Status epilepticus Perioperative

DOSE IN NORMAL RENAL FUNCTION

Anxiety: 1–4 mg daily in divided doses Insomnia associated with anxiety: 1–2 mg at bedtimeAcute panic attacks: (IV/IM): 25–30 mcg/ kg; repeat 6 hourly if required; usual range 1.5–2.5 mgStatus epilepticus: 4 mg IV repeated once after 10 minutes

PHARMACOKINETICS

Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :321.2

%Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :85

%Excreted unchanged in urine &nbsp &nbsp : <1

Volume of distribution (L/kg) &nbsp &nbsp &nbsp :0.9–1.3

half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :

10 to 20

/32–70

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 &nbsp &nbsp : Dose as in normal renal function

10 to 20 &nbsp &nbsp : Dose as in normal renal function

<10 &nbsp &nbsp &nbsp &nbsp &nbsp : Dose as in normal renal function

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Unlikely dialysability. Dose as in normal renal function.

HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Not dialysed. Dose as in normal renal function

HDF/high flux &nbsp :Unknown dialysability. Dose as in normal renal function

CAV/VVHD &nbsp &nbsp &nbsp:Not dialysed. Dose as in normal renal function

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antibacterials: metabolism possibly increased by rifampicin

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

Antivirals: concentration possibly increased by ritonavirDisulfiram: metabolism inhibited, increased sedative effectsSodium oxybate: enhanced effects of sodium oxybate – avoid

Ulcer-healing drugs: metabolism inhibited by cimetidine

ADMINISTRATION

Reconstition

Route

Oral, IV, IM, sublingual

Rate of Administration

Slow IV bolus

Comments

Onset of effect after IM injection is similar to oral administrationIV route preferred over IM route Dilute 1:1 with sodium chloride 0.9% or water for injectionCan be used undiluted. (UK Critical Care Group, Minimum Infusion Volumes for fluid restricted critically ill patients, 3rd Edition, 2006)

OTHER INFORMATION

Patients with impaired renal or hepatic function should be monitored frequently and have their dosage adjusted carefully according to response. Lower doses may be sufficient in these patientsLorazepam as intact drug is not removed by dialysis. The glucuronide metabolite is highly dialysable, but is pharmacologically inactiveIncreased CNS sensitivity in patients with renal impairment.

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