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 &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :333.9 (as hydrochloride)
  • %Protein binding &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :95–96
  • %Excreted unchanged in urine &nbsp &nbsp : <1 (77% as metabolites)

  • Volume of distribution (L/kg) &nbsp &nbsp &nbsp :1640 litres

  • half-life – normal/ESRD (hrs)&nbsp &nbsp &nbsp :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 &nbsp &nbsp &nbsp &nbsp &nbsp : Start at very low dose and increase according to response

    DOSE IN PATIENTS UNDERGOING RENAL REPLACEMENT THERAPIES

  • CAPD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp:Not dialysed. Dose as in GFR
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp : mL/min

  • HD &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp &nbsp :Not dialysed. Dose as in GFR
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp : mL/min
  • HDF/high flux &nbsp :Unlikely to be dialysed. Dose as in GFR
  • <10 &nbsp &nbsp &nbsp &nbsp &nbsp : mL/min
  • CAV/VVHD &nbsp &nbsp &nbsp: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

    –

    Route

    Oral

    Rate of Administration

    –

    Comments

    –

    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
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