disopyramide

CLINICAL USE

Ventricular and supraventricular arrhythmias

DOSE IN NORMAL RENAL FUNCTION

Oral: 300–800 mg daily in divided doses IV: 2 mg/kg over 5 minutes to a maximum of 150 mgInfusion: 400 mcg/kg/hour, maximum 300 mg in 1st hour and 800 mg daily

PHARMACOKINETICS

Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :339.5

%Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :50–65

%Excreted unchanged in urine &nbsp &nbsp : 50–75

Volume of distribution (L/kg) &nbsp &nbsp &nbsp :0.8–2.6

half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :5–8/12–22

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 &nbsp &nbsp : Oral: 100 mg every 8 hours or 150 mg every 12 hours

10 to 20 &nbsp &nbsp : Oral: 100 mg every 12 hours

<10 &nbsp &nbsp &nbsp &nbsp &nbsp : Oral: 150 mg every 24 hours (monitor levels)

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Not dialysed. Dose as in GFR <10 mL/min

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

HDF/high flux &nbsp :Unlikely to be dialysed. Dose as in GFR <10 mL/min

CAV/VVHD &nbsp &nbsp &nbsp:Unknown dialysability. Dose as in GFR 10 to 20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugsAnti-arrhythmics: increased myocardial depression with other anti-arrhythmics; amiodarone increases risk of ventricular arrhythmias – avoid concomitant useAntibacterials: concentration possibly increased by clarithromycin and erythromycin (risk of toxicity); increased risk of ventricular arrhythmias with moxifloxacin and quinupristin/dalfopristin – avoid concomitant use; concentration reduced by rifampicinAntidepressants: increased risk of ventricular arrhythmias with tricyclicsAntifungals: increased risk of ventricular arrhythmias with ketoconazole – avoid concomitant useAntihistamines: increased risk of ventricular arrhythmias with mizolastineAntihypertensives: increased myocardial depression and asystole with beta-blockers or verapamil; increased risk of ventricular arrhythmias with sotalol – avoidAntimalarials: avoid concomitant use with artemether/lumefantrineAntipsychotics: increased risk of ventricular arrhythmias with antipsychotics that prolong the QT interval and phenothiazines; increased risk of ventricular arrhythmias with amisulpride, pimozide and sertindole – avoid concomitant useAntivirals: concentration possibly increased by ritonavir, increased risk of toxicityAtomoxetine: increased risk of ventricular arrhythmiasCiclosporin: may increase risk of nephrotoxicity with ciclosporinDiuretics: increased cardiac toxicity if hypokalaemia occurs5HT 3 antagonists: increased risk of ventricular arrhythmias with dolasetron – avoid concomitant use; use tropisetron with cautionIvabradine: increased risk of ventricular arrhythmias

ADMINISTRATION

Reconstition

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Route

Oral, IV

Rate of Administration

20–30 mg/hour (0.4 mg/kg/hour)

Comments

May be given by peripheral

IV infusion

in glucose 5%, sodium chloride 0.9% or compound sodium lactate.240 DISOPYRAMIDe

OTHER INFORMATION

Use with caution in patients with impaired renal functionDo not give renally impaired patients sustained release preparationsOptimum therapeutic plasma level 2–6 mg/LHaemoperfusion can be used in cases of severe poisoning.

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