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                           :339.5
  • %Protein binding                           :50–65
  • %Excreted unchanged in urine     : 50–75
  • Volume of distribution (L/kg)       :0.8–2.6
  • half-life – normal/ESRD (hrs)      :5–8/12–22

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Oral: 100 mg every 8 hours or 150 mg every 12 hours
  • 10 to 20     : Oral: 100 mg every 12 hours
  • <10           : Oral: 150 mg every 24 hours (monitor levels)

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                :Not dialysed. Dose as in GFR <10 mL/min
  • HD                     :Not dialysed. Dose as in GFR <10 mL/min
  • HDF/high flux   :Unlikely to be dialysed. Dose as in GFR <10 mL/min
  • CAV/VVHD      :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

    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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