Lofepramine

CLINICAL USE


Tricyclic antidepressant

DOSE IN NORMAL RENAL FUNCTION

140–210 mg daily in 2–3 divided doses

PHARMACOKINETICS

  • Molecular weight &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :455.4 (as hydrochloride)
  • %Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :99
  • %Excreted unchanged in urine &nbsp &nbsp : Mainly as metabolites
  • Volume of distribution (L/kg) &nbsp &nbsp &nbsp :Large
  • half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :1.7–5/–

    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 : Start with a small dose and titrate slowly

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Unknown dialysability. Dose as in GFR <10 mL/min

  • HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Unknown dialysability. 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:Unknown dialysability. Dose as in normal renal function

    IMPORTANT DRUG INTERACTIONS

    Potentially hazardous interactions with other drugs
  • Alcohol: increased sedative effect
  • Analgesics: increased risk of CNS toxicity with tramadol; possibly increased risk of side effects with nefopam; possibly increased sedative effects with opioids
  • Anti-arrhythmics: increased risk of ventricular arrhythmias with amiodarone – avoid concomitant use; increased risk of ventricular arrhythmias with drugs that prolong the QT interval; increased risk of arrhythmias with propafenone
  • Antibacterials: increased risk of ventricular arrhythmias with moxifloxacin – avoid concomitant use; concentration reduced by rifampicin
  • Anticoagulants: may enhance or reduce anticoagulant effect of coumarins
  • Antidepressants: enhanced CNS excitation and hypertension with MAOIs and moclobemide; concentration possibly increased with SSRIs
  • Anti-epileptics: convulsive threshold lowered; some anti-epileptics may lower plasma concentration of some tricyclics
  • Antimalarials: avoid concomitant use with artemether/lumefantrine
  • Antipsychotics: increased risk of ventricular arrhythmias and antimuscarinic effects; concentration increased by tricyclics
  • Antivirals: increased tricyclic side effects with amprenavir; concentration possibly increased with ritonavir
  • Atomoxetine: increased risk of ventricular arrhythmias; possibly increased risk of convulsions
  • Beta-blockers: increased risk of ventricular arrhythmias with sotalol
  • Clonidine: tricyclics antagonise hypotensive effect; increased risk of hypertension on clonidine withdrawal
  • Dopaminergics: avoid use with entacapone; CNS toxicity reported with selegiline and rasagiline
  • Pentamidine: increased risk of ventricular arrhythmias
  • Sympathomimetics: increased risk of hypertension and arrhythmias with adrenaline and noradrenaline; metabolism possibly inhibited by methylphenidate
  • Sibutramine: increased risk of CNS toxicity – avoid concomitant use

    ADMINISTRATION

    Reconstition

    Route

    Oral

    Rate of Administration

    Comments