duloxetine

CLINICAL USE

Moderate to severe stress urinary incontinenceDepression Diabetic peripheral neuropathy

DOSE IN NORMAL RENAL FUNCTION

Incontinence: 20–40 mg twice daily Depression and diabetic peripheral neuropathy: 60 mg daily

PHARMACOKINETICS

Molecular weight :333.9 (as hydrochloride)

%Protein binding :95–96

%Excreted unchanged in urine : <1 (77% as metabolites)

Volume of distribution (L/kg) :1640 litres

half-life – normal/ESRD (hrs) :8–17/Unchanged

DOSE IN RENAL IMPAIRMENT

GFR (mL/MIN)

30–50 Dose as in normal renal function; start with a low dose10–30 Start at low dose and increase according to response

<10 : Start at very low dose 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 :Unlikely to be dialysed. Dose as in GFR

<10 : mL/min

CAV/VVHD :Not dialysed. Dose as in GFR =10–30 mL/min

IMPORTANT DRUG INTERACTIONS

Potentially hazardous interactions with other drugs

Antibacterials: metabolism inhibited by ciprofloxacin – avoid concomitant use

Other CNS medication: enhanced effect

Antidepressants: avoid concomitant use with MAOIs, moclobemide, St John’s wort, tryptophan, venlafaxine, amitriptyline, clomipramine and SSRIs due to increased risk of serotonin syndrome; increased risk of side effects with tricyclic antidepressants; fluvoxamine decreases the clearance of duloxetine by 77% – avoid concomitant use

Antimalarials: avoid concomitant use with artemether/lumefantrine

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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OTHER INFORMATION

In CKD 5 there is a 2-fold increase in C max and AUC. The renally excreted metabolites 4-hydroxy duloxetine glucuronide and 5-hydroxy, 6-methoxy duloxetine sulphate were 7–9 times higher than in people with normal renal function

Contraindicated in uncontrolled hypertension due to potential risk of hypertensive crisis

See how to identify renal failure stages according to GFR calculation

See how to diagnose irreversible renal disease

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