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                           :321.2
  • %Protein binding                           :85
  • %Excreted unchanged in urine     : <1
  • Volume of distribution (L/kg)       :0.9–1.3
  • half-life – normal/ESRD (hrs)      :
  • 10 to 20
  • /32–70

    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           : Dose as in normal renal function

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Unlikely dialysability. Dose as in normal renal function.
  • HD                     :Not dialysed. Dose as in normal renal function
  • HDF/high flux   :Unknown dialysability. Dose as in normal renal function
  • CAV/VVHD      :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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