Amitriptyline hydrochloride
Amitriptyline hydrochloride.JPG

Amitriptyline hydrochloride

CLINICAL USE

Tricyclic antidepressant:
  • Depression, used especially where sedation is required
  • Neuropathic pain

    DOSE IN NORMAL RENAL FUNCTION

    10–200 mg daily depending on indication

    PHARMACOKINETICS

  • Molecular weight                           : 313.9
  • %Protein binding                           : 96
  • %Excreted unchanged in urine     : <2
  • Volume of distribution (L/kg)       : 6–36
  • half-life – normal/ESRD (hrs)      : 9–25/Unchanged

    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      : Not dialysed. 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
  • Antiarrhythmics: 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 possibly reduced by rifampicin
  • Anticoagulants: may alter anticoagulant effect of coumarins
  • Antidepressants: possibly increased serotonergic effects with duloxetine; enhanced CNS excitation and hypertension with MAOIs and moclobemide; concentration possibly increased with SSRIs; concentration reduced by St John’s wort
  • 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

    OTHER INFORMATION

  • Introduce treatment gradually in renal impairment due to dizziness and postural hypotension
  • Withdraw treatment gradually
  • Anticholinergic side effects: causes urinary retention, drowsiness, dry mouth, blurred vision and constipation



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