Clonazepam

CLINICAL USE

Benzodiazepine:Anticonvulsant Anxiolytic Restless legs syndrome

DOSE IN NORMAL RENAL FUNCTION

Oral: 0.5–20 mg daily in 3–4 divided doses or as a single dose at night once on maintenance therapy; normal maintenance dose: 4–8 mg dailyIV: 1 mg, repeated if necessary Restless legs syndrome: 0.5–4 mg at night

PHARMACOKINETICS

Molecular weight :315.7

%Protein binding :86

%Excreted unchanged in urine : <0.5

Volume of distribution (L/kg) :3

half-life – normal/ESRD (hrs) :20–60/–

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Start at low dose and increase according to response

10 to 20 : Start at low dose and increase according to response

<10 : Start at low dose and increase according to response

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 GFR <10 mL/min

CAV/VVHD :Not dialysed. Dose as in GFR=10–20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugsAntibacterials: metabolism possibly increased by rifampicinAntipsychotics: increased sedative effects Antivirals: increased risk of prolonged sedation with amprenavir; concentration possibly increased by ritonavirDisulfiram: metabolism inhibited, increased sedative effects Sodium oxybate: enhanced effects of sodium oxybate – avoid

ADMINISTRATION

Reconstition

IV bolus: reconstitute with 1 mL diluent (water for injection) to give 1 mg in 1 mL solution.

IV infusion

: up to 3 mg (3 amps) added to 250 mL sodium chloride 0.9% or glucose 5%

Route

Oral, IV bolus or infusion

Rate of Administration

IV bolus: 0.25–0.5 mg over 1 minute

Comments

IV infusion

of clonazepam is potentially hazardous (especially if prolonged), calling for close and constant observation; best carried out in specialist centres with ICU facilities. Risks include apnoea, hypotension and deep unconsciousness

OTHER INFORMATION

In long-term administration, active metabolites may accumulate and lower doses should be usedClonazepam is one of several agents that are used in restless leg syndrome, and has also been tried in the management of intractable hiccup where chlorpromazine has failede

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