CLINICAL USE

Tricyclic antidepressant

DOSE IN NORMAL RENAL FUNCTION

50–300 mg daily in divided doses Elderly: 10–25 mg 3 times daily; half the dose should be sufficient for maintenance

PHARMACOKINETICS

  • Molecular weight                           : 410.5 (as maleate)
  • %Protein binding                           : 95
  • %Excreted unchanged in urine     : 0
  • Volume of distribution (L/kg)       : 31
  • half-life – normal/ESRD (hrs)      : 23/–

    DOSE IN RENAL IMPAIRMENT

    GFR (mL/MIN)

  • 20 to 50     : Dose as in normal renal function
  • 10 to 20     : Dose as in normal renal function
  • <10           : Dose as in normal renal function

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD                : Not dialysed. Dose as in normal renal function
  • HD                     : Not dialysed. Dose as in normal renal function
  • HDF/high flux   : Unknown dialysability. Dose as in normal renal function
  • CAV/VVHD      : 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 alter anticoagulant effect of coumarins
  • Antidepressants: enhanced CNS excitation and hypertension with MAOIs and moclobemide – avoid concomitant use; concentration possibly increased with SSRIs
  • Anti-epileptics: convulsive threshold lowered; concentration reduced by carbamazepine, primidone, barbiturates and possibly phenytoin
  • Antimalarials: avoid concomitant use with artemether/lumefantrine
  • Antipsychotics: increased risk of ventricular arrhythmias especially with pimozide; increased antimuscarinic effects with clozapine and phenothiazines; concentration increased by antipsychotics
  • Antivirals: increased tricyclic side effects with amprenavir; concentration possibly increased with ritonavir
  • Atomoxetine: increased risk of ventricular arrhythmias and possibly 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
  • Sibutramine: increased risk of CNS toxicity – avoid concomitant use
  • Sympathomimetics: increased risk of hypertension and arrhythmias with adrenaline and noradrenaline; metabolism possibly inhibited by methylphenidate

    ADMINISTRATION

    Reconstition

    Route

    Oral

    Rate of Administration

    Comments

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