Lofepramine

CLINICAL USE

Tricyclic antidepressant

DOSE IN NORMAL RENAL FUNCTION

140–210 mg daily in 2–3 divided doses

PHARMACOKINETICS

Molecular weight :455.4 (as hydrochloride)

%Protein binding :99

%Excreted unchanged in urine : Mainly as metabolites

Volume of distribution (L/kg) :Large

half-life – normal/ESRD (hrs) :1.7–5/–

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 : Start with a small dose and titrate slowly

DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

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

HD :Unknown dialysability. Dose as in GFR <10 mL/min

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

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 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

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Route

Oral

Rate of Administration

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Comments

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