dosulepin hydrochloride

CLINICAL USE

Tricyclic antidepressant

DOSE IN NORMAL RENAL FUNCTION

50–225 mg daily

PHARMACOKINETICS

Molecular weight :331.9

%Protein binding :84

%Excreted unchanged in urine : 56 (mainly as metabolites)

Volume of distribution (L/kg) :45

half-life – normal/ESRD (hrs) :14–24/–

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

20 to 50 : Dose as in normal renal function

10 to 20 : Start with small dose, and titrate according to response

<10 : Start with small dose, and titrate 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 :Unknown dialysability. Dose as in GFR 10 to 20 mL/min

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 tricyclic 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

–

Comments

–dosulepin hydrochloride (dothiepin).DOSULePIN HYDROCHLORIDe (DOtHIePIN) 251

OTHER INFORMATION

Metabolites are active and partly renally excretedMetabolites accumulate and cause excessive sedation25–50 mg usually effective without too much sedation.

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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