nortriptyline

CLINICAL USE

Tricyclic antidepressant

DOSE IN NORMAL RENAL FUNCTION

30–150 mg daily in single or divided doses

PHARMACOKINETICS

Molecular weight :263.4 (299.8 as hydrochloride)

%Protein binding :95

%Excreted unchanged in urine : <5

Volume of distribution (L/kg) :15–23

half-life – normal/ESRD (hrs) :25–38/15–66

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. Start with small dose

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

CAPD :Not dialysed. Dose as in GFR <10 mL/min

HD :Not dialysed. Dose as in GFR <10 mL/min

HDF/high flux :Unknown dialysability. Dose as in GFR <10 mL/min

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

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 TAD 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

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Route

Oral

Rate of Administration

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Comments

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OTHER INFORMATION

All metabolites are highly lipophilic .

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