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DULOXETINE Hydrochloride (hcl)
Duloxetine (brand names
Cymbalta, Yentreve) is a serotonin-norepinephrine
reuptake inhibitor (SNRI) used for major
depressive disorder (MDD), generalized anxiety
disorder (GAD), pain related to diabetic
neuropathy and in some countries for stress
urinary incontinence (SUI).
Indications
Moderate to severe stress urinary
incontinence in women.
Stress urinary incontinence is
involuntary loss of urine when the
bladder comes under stress, e.g. from
coughing, sneezing or other movements
that increase the intra-abdominal
pressure. Duloxetine was first reported
to improve outcomes in SUI in 1998.[17]
Systematic reviews with meta-analysis,
conducted in 2005 (Cochrane)[18]
and 2008 (University of Minnesota),[19]
each found ten controlled trials. Both
systematic reviews concluded that
duloxetine did not lead to cure of
stress urinary incontinence in the
vast majority of people, but that
episodes of incontinence were reduced by
about 50%. This was associated with an
improvement in
quality of life measurements. Mild
side-effects were common, and about a
fifth had to discontinue the medication
because of poor tolerance.
Cautions
-
elderly
-
cardiac disease
-
hypertension (avoid
if uncontrolled)
-
history of mania
history of seizures
-
raised intra-ocular
pressure, susceptibility to
angle-closure glaucoma
-
bleeding disorders or
concomitant use of drugs that
increase risk of bleeding
Withdrawal
of duloxetine HydrochlorideNausea, vomiting,
headache, anxiety, dizziness,
paraesthesia, sleep disturbances,
and tremor are the most common
features of abrupt withdrawal or
marked reduction of the dose; dose
should be reduced over at least 1?2
weeks
Dose of Duloxetine
- Adult over 18 years, 40 mg
twice daily, assess for benefit and tolerability after
2?4 weeks
- Initial dose of 20 mg
twice daily for 2 weeks can minimise side-effects
Side-effects of Duloxetine
nausea, vomiting,
dyspepsia, constipation, diarrhoea,
abdominal pain, weight changes,
decreased appetite, flatulence, dry
mouth; palpitation, hot flush; insomnia,
abnormal dreams, paraesthesia,
drowsiness, anxiety, headache,
dizziness, fatigue, weakness, tremor,
nervousness, anorexia; sexual
dysfunction; visual disturbances;
sweating, pruritus; less commonly
gastritis, halitosis, hepatitis, bruxism,
tachycardia, hypertension, postural
hypotension, syncope, raised
cholesterol, vertigo, taste disturbance,
cold extremities, impaired temperature
regulation, impaired attention, movement
disorders, muscle twitching,
musculoskeletal pain, thirst, stomatitis,
hypothyroidism, urinary disorders, and
photosensitivity; rarely mania
and angle-closure glaucoma; also
reported supraventricular
arrhythmia, chest pain, hallucinations,
suicidal behaviour (see
Suicidal Behaviour and Antidepressant
Therapy), seizures, hypersensitivity
reactions including urticaria,
angioedema, rash (including
Stevens-Johnson syndrome) and
anaphylaxis, hyponatraemia (see
Hyponatraemia and Antidepressant Therapy)
Interactions
-
5HT1 Agonists possible increased
serotonergic effects when duloxetine given with
5HT1 agonists
-
Amitriptyline possible increased serotonergic effects when
duloxetine given with amitriptyline
-
Antidepressants, SSRI possible increased serotonergic
effects when duloxetine given with SSRIs
-
Ciprofloxacin metabolism of duloxetine inhibited by
ciprofloxacin ?avoid concomitant use
-
Clomipramine possible increased serotonergic effects when
duloxetine given with clomipramine
-
Fluvoxamine metabolism of duloxetine inhibited by
fluvoxamine ?avoid concomitant use
-
MAOIs
duloxetine should not be started until 2 weeks after stopping
MAOIs , also MAOIs should not be started until at least 5 days
after stopping duloxetine
-
Moclobemide possible increased serotonergic effects when
duloxetine given with moclobemide
-
Pethidine possible increased serotonergic effects when
duloxetine given with pethidine
-
St John's Wort possible increased serotonergic effects when
duloxetine given with St John's wort
-
Tramadol possible increased serotonergic effects when
duloxetine given with tramadol
Tryptophan
possible increased serotonergic effects when duloxetine given
with tryptophan
-
Venlafaxine possible increased serotonergic effects when
duloxetine given with venlafaxine
Literature
Trials in North America and Europe
have provided
evidence for the safety and efficacy of duloxetine as a pharmacological
treatment for stress incontinence of urine in women.
--------------------
A new form of drug treatment with a
serotonin-noradrenaline reuptake
inhibitor (SNRI), duloxetine, may now
have a place in treatment of this
condition.0501
- All randomised or
quasi-randomised controlled
trials of treatment for SUI
or MUI, in which at least
one management arm involved
a SNRI.
- Nine randomised trials
were included, involving
3327 adults with
predominantly SUI,
randomised to receive
duloxetine or placebo.
- Treatment duration was
between three weeks and 12
weeks.
- Duloxetine was
significantly better than
placebo in terms of
improving patients' quality
of life (and perception of
improvement.
- Individual studies
demonstrated a significant
reduction in the
Incontinence Episode
Frequency (IEF) by
approximately 50% during
treatment with duloxetine.
- With regard to objective
cure, however, meta-analysis
of stress pad test and 24
hour pad weight change
failed to demonstrate a
benefit for duloxetine over
placebo though data were
relatively few.
- Subjective cure favoured
duloxetine, albeit with a
small effect size (3%).
- Although significant
side effects were commonly
associated with duloxetine,
they were reported as
acceptable.
- Adverse effects are
common but not serious.
About one in three
participants allocated
duloxetine reported adverse
effects (most commonly
nausea) related to
treatment, and about one in
eight allocated duloxetine
stopped treatment as a
conse quence.
   
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