%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
