Amitriptyline hydrochloride

CLINICAL USE

Tricyclic antidepressant:

  • Depression, used especially wheresedation 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 toxicitywith tramadol; possibly increased risk
    of side effects with nefopam; possibly
    increased sedative effects with opioids
  • Antiarrhythmics: increased risk ofventricular 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 ofventricular arrhythmias with moxifloxacin
    – avoid concomitant use; concentration
    possibly reduced by rifampicin
  • Anticoagulants: may alter anticoagulanteffect of coumarins
  • Antidepressants: possibly increasedserotonergic 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 thresholdlowered; concentration reduced by
    carbamazepine, primidone, barbiturates
    and possibly phenytoin
  • Antimalarials: avoid concomitant use withartemether/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 effectswith 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 antagonisehypotensive effect; increased risk of
    hypertension on clonidine withdrawal
  • Dopaminergics: avoid use withentacapone; CNS toxicity reported with
    selegiline and rasagiline
  • Pentamidine: increased risk of ventriculararrhythmias
  • Sibutramine: increased risk of CNStoxicity – avoid concomitant use.
  • Sympathomimetics: increased risk ofhypertension 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 renalimpairment due to dizziness and postural
    hypotension
  • Withdraw treatment gradually
  • Anticholinergic side effects: causes urinaryretention, drowsiness, dry mouth, blurred
    vision and constipation
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