Clomipramine hydrochloride

CLINICAL USE

Depressive illness Phobic and obsessional states Adjunctive treatment of cataplexy associated with narcolepsy

DOSE IN NORMAL RENAL FUNCTION

10–250 mg dailyCataplexy: 10–75 mg daily

PHARMACOKINETICS

Molecular weight :351.3

%Protein binding :97.6

%Excreted unchanged in urine : 2

Volume of distribution (L/kg) :12–17

half-life – normal/ESRD (hrs) :12–36/–

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Start at lower doses and increase according to response

<10 : Start at lower doses and increase according to response

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 GFR=10–20 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugsAlcohol: increased sedative effect Analgesics: increased risk of CNS toxicity with tramadol; possibly increased risk of side effects with nefopam; possibly increased sedative effects with opioidsAnti-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 propafenoneAntibacterials: increased risk of ventricular arrhythmias with moxifloxacin – avoid concomitant use; concentration possibly reduced by rifampicinAnticoagulants: may alter anticoagulant effect of coumarinsAntidepressants: possibly increased serotonergic effects with duloxetine; enhanced CNS excitation and hypertension with MAOIs and moclobemide; concentration possibly increased with SSRIsAnti-epileptics: convulsive threshold lowered; concentration reduced by carbamazepine, primidone, barbiturates and possibly phenytoinAntimalarials: avoid concomitant use with artemether/lumefantrineAntipsychotics: increased risk of ventricular arrhythmias especially with pimozide; increased antimuscarinic effects with clozapine and phenothiazines; concentration increased by antipsychoticsAntivirals: increased tricyclic side effects with amprenavir; concentration possibly increased with ritonavirAtomoxetine: increased risk of ventricular arrhythmias and possibly convulsionsBeta-blockers: increased risk of ventricular arrhythmias with sotalolClonidine: tricyclics antagonise hypotensive effect; increased risk of hypertension on clonidine withdrawalDopaminergics: avoid use with entacapone; CNS toxicity reported with selegiline and rasagilinePentamidine: increased risk of ventricular arrhythmiasSibutramine: increased risk of CNS toxicity – avoid concomitant use. Sympathomimetics: increased risk of hypertension and arrhythmias with adrenaline and noradrenaline; metabolism possibly inhibited by methylphenidateClomipramine hydrochloride.