CLINICAL USE


Anti-arrhythmic agent:Ventricular arrhythmias Paroxysmal supraventricular tachyarrhythmias, (including paroxysmal atrial flutter or fibrillation, and paroxysmal re-entrant tachycardias involving the AV node or accessory pathway) where standard therapy has failed or is unsuitable

DOSE IN NORMAL RENAL FUNCTION

>70 kg: 150–300 mg 3 times dailyIf <70 kg start with a lower dose

PHARMACOKINETICS

  • Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :377.9
  • %Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :>95
  • %Excreted unchanged in urine &nbsp &nbsp : <1
  • Volume of distribution (L/kg) &nbsp &nbsp &nbsp :1.9–3
  • half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :2–10 (10–32 hours in slow metabolisers)/Unchanged

    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. Use with caution

    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 :Unknown dialysability. Dose as in GFR <10 mL/min
  • CAV/VVHD &nbsp &nbsp &nbsp:Not dialysed. Dose as in normal renal function

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs
  • Anti-arrhythmics: increased myocardial depression with other anti-arrhythmics
  • Antibacterials: increased metabolism with rifampicin (reduced effect)
  • Anticoagulants: enhanced anticoagulant effect of coumarins
  • Antidepressants: increased risk of arrhythmias with tricyclics; metabolism of propafenone possibly inhibited by paroxetine (increased risk of toxicity)Antihistamines: increased risk of ventricular arrhythmias with mizolastine– avoid concomitant use
  • Antipsychotics: increased risk of ventricular arrhythmias with antipsychotics that prolong the QT interval
  • Antivirals: concentration of propafenone increased by amprenavir and ritonavir, increased risk of ventricular arrhythmias – avoid concomitant use
  • Beta-blockers: increased myocardial depression; increased concentration of metoprolol and propranololCardiac glycosides: increased digoxin concentration – halve digoxin dose
  • Ciclosporin: possibly increased ciclosporin concentration5HT 3 antagonists: increased risk of ventricular arrhythmias with dolasetron – avoid concomitant use; avoid with tropisetron
  • Ulcer-healing drugs: levels increased by cimetidine

    ADMINISTRATION

    Reconstition

    Route

    Oral

    Rate of Administration

    Comments

    OTHER INFORMATION

    Half-life depends on acetylator status of patientEnsure that electrolyte disturbances are corrected before commencing treatmentMetabolised by CYP2D6 isoenzyme Therapeutic plasma concentrations are 150–1500 ng/mL