Transcript Benign prostatic hyperplasia - GSK Pharma UK | Healthcare

NICE LUTS Clinical Guideline 2010
Lower Urinary Tract Symptoms (LUTS) in men.
NICE Clinical Guideline 97 (2010)
Available on www.nice.org.uk/guidance/CG97
Published 19th May 2010
Prescribing information can be found on the final slide
UK/DUTT/0061j/10/ Date of preparation: April 2012
Content
 Executive summary – 10 key priorities for implementation
 Guideline Development Group members
 Male ‘LUTS’
 Recommendations on diagnosis
 Recommendations on treatment
 Recommendations on referral to secondary care
UK/DUTT/0061j/10/ Date of preparation: April 2012
Summary: NICE 10 Key Priorities for Implementation
- Initial Assessment-
1
At initial assessment, offer men with LUTS an assessment of their general
medical history to identify possible causes of LUTS, and associated
comorbidities. Review current medication, including herbal and over-the-counter
medicines, to identify drugs that may be contributing to the problem.
2
At initial assessment, offer men with LUTS a physical examination guided by
urological symptoms and other medical conditions, an examination of the abdomen
and external genitalia, and a digital rectal examination (DRE).
3
At initial assessment, ask men with bothersome LUTS to complete a urinary
frequency volume chart.
4
Refer men for specialist assessment if they have LUTS complicated by recurrent or
persistent urinary tract infection, retention, renal impairment that is
suspected to be caused by lower urinary tract dysfunction, or suspected
urological cancer.
UK/DUTT/0061j/10/ Date of preparation: April 2012
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http://guidance.nice.org.uk/CG97/QuickRefGuide Accessed 20th May 2010
Summary: NICE 10 Key Priorities for Implementation
- Conservative Management -
5
Offer men with storage LUTS (particularly urinary incontinence)
temporary containment products (for example, pads or collecting
devices) to achieve social continence until a diagnosis and management
plan have been discussed.
6
Offer men with storage LUTS suggestive of overactive bladder (OAB)
supervised bladder training, advice on fluid intake, lifestyle
advice and, if needed, containment products.
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
Summary: NICE 10 Key Priorities for Implementation
- Surgery for Voiding Symptoms-
7
If offering surgery for managing voiding LUTS presumed
secondary to BPE, offer monopolar or bipolar transurethral resection of
the prostate (TURP), monopolar transurethral vaporisation of the
prostate (TUVP) or holmium laser enucleation of the prostate (HoLEP).
Perform HoLEP at a centre specialising in the technique, or with
mentorship arrangements in place.
8
If offering surgery for managing voiding LUTS presumed
secondary to BPE, do not offer minimally invasive treatments
(including transurethral needle ablation [TUNA], transurethral
microwave thermotherapy [TUMT], high-intensity focused ultrasound
[HIFU], transurethral ethanol ablation of the prostate [TEAP] and laser
coagulation) as an alternative to TURP, TUVP or HoLEP (see above
recommendation).
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
Summary: NICE 10 Key Priorities for Implementation
- Providing information -
9
Make sure men with LUTS have access to care that can help with
their emotional and physical conditions and relevant physical,
emotional, psychological, sexual and social issues.
10
Provide men with storage LUTS (particularly incontinence)
containment products at point of need, and advice about relevant
support groups.
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
Guideline Development Group
Formed 2007, Guideline published 2010
Name
Title
Specialist area
Professor Christopher
Chapple
Consultant Urological Surgeon
Guideline Development Group Chair
Mr William Turner
Consultant Urological Surgeon
Consultant Urological Surgeon, Addenbrooke’s Hospital, Cambridge.
Mr Mark Speakman
Consultant Urological Surgeon
and Associate Medical Director
Consulant urologist, Taunton and Somerset NHS Trust. Associate Medical Director for surgical services.
Mr Malcolm Lucas
Consultant Urological Surgeon
Consultant Urological Surgeon, Swansea NHS Trust
Honorary Senior Lecturer in Surgery. Abertawe Bro Morgannwg University local health board.
Professor James N’Dow
Consultant Urological Surgeon
Professor of Urology and Consultant Urological Surgeon, University of Aberdeen and NHS Grampian
Co-ordinating editor on Cochrane Collaboration (Incontinence review group).
Dr Adrian Wagg
Senior Lecturer & Consultant
Geriatrician
Consultant Physician in General and Geriatric Medicine, UCL hospitals foundation NHS Trust and
Camden PCT. Honorary Senior Lecturer in Geriatric Medicine.
Mrs Angela Billington
Director of Continence Services
Director of Continence Services, Bournemouth & Poole PCT.
Running male LUTS clinic, Swanage.
Mr Thomas Ladds
Urology Specialist Nurse
Practioner
Urology specialist nurse practitioner, Central Manchester Hospitals NHS Trust. Honorary Appointment,
University teacher, University of Manchester Medical School.
Dr Jonathan Rees
General Practitioner
General Practitioner, Backwell and Nailsea Medical Group. Works one day a week in Urology in
secondary care, Bristol Urology Associates.
Dr Julian Spinks
General Practitioner
General Practitioner, Court View Surgery, Strood, Kent.
Member of Strategy Board, Incontact.
Mr Roy Latham
Patient Member
Member of Royal College of Physicians Patient Carer Network. Lay member of the Policy Committee,
British Geriatric Society.
Mr Paul Joachim
Patient Member
Chair of the Patient Advisory board, InContact.
Consultant Urological Surgeon, The Royal Hallamshire Hospital, Sheffield. Visiting professor of urology,
Sheffield Hallam University.
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
Male ‘LUTS’
Lower urinary tract symptoms (LUTS) are storage, voiding and postmicturition
symptoms affecting the lower urinary tract.
Bothersome LUTS may occur in up to 30% of men older than 65 years.
Voiding
Storage
(previously ‘obstructive’)
(previously ‘irritative’)
weak or intermittent
urinary stream
urgency
straining
frequency
hesitancy
incontinence
terminal dribbling
Nocturia
Post
Micturition
dribbling
incomplete
emptying
UK/DUTT/0061j/10/ Date of preparation: April 2012
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http://www.nice.org.uk/nicemedia/live/12984/48554/48554.pdf Accessed 20th May 2010
NICE Recommendations on
Initial Assessment
Offer
•
Assessment of general medical history, including a review of current medication
•
General ‘focused’ physical examination
•
Abdominal examination and external genitalia and digital rectal examination
(DRE)
Investigations
Offer
–
Urine dipstick
–
Bothersome LUTS – request patient completes frequency volume chart
–
PSA test –Offer men information, advice and time to decide if they wish to
have prostate specific antigen (PSA) testing if their LUTS are suggestive of
bladder outlet obstruction secondary to BPE or their prostate feels abnormal on
DRE or they are concerned about prostate cancer
–
Serum creatinine – only if indications of renal impairment
–
Offer men considering treatment for LUTS an assessment of their baseline
symptoms with a validated symptom score (for example, the IPSS).
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
NICE Recommendations on
Initial Assessment
Do not routinely offer:
Cystoscopy to men with no evidence of bladder abnormality
Imaging of the upper urinary tract to men with no evidence of bladder
abnormality
Flow-rate measurement
Post void residual volume measurement
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
NICE Recommendations on management of mild
or moderate LUTS
Bothersome or to the patient, or complicated?
No
Active surveillance?
Give reassurance, offer advice on
lifestyle interventions and information on
their condition.
Offer review if symptoms change.
UK/DUTT/0061j/10/ Date of preparation: April 2012
Yes
Active intervention
Conservative management /
drug treatment or surgery
Offer baseline assessment (eg IPSS)
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
NICE Recommendations
Conservative management – storage symptoms
Storage symptoms
OAB
Offer
•
supervised bladder training
•
advice on fluid intake
•
lifestyle advice
•
containment products (if needed)
Stress incontinence caused by prostatectomy
•
Offer supervised pelvic floor muscle training
Offer containment products as appropriate
Do not offer penile clamps
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
NICE Recommendations
Conservative management – voiding symptoms
Voiding symptoms
Offer intermittent bladder catheterisation before indwelling urethral or suprapubic catheterisation
if LUTS cannot be corrected by less invasive measures.
Tell men with proven bladder outlet obstruction that bladder training is less effective than
surgery.
Explain to men with post micturition dribble how to perform urethral milking.
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
NICE Recommendations
Drug Treatment - LUTS
Moderate to severe LUTS
Offer an alpha blocker
LUTS and a prostate
estimated to be larger
than 30g or PSA greater
than 1.4 ng/ml, and high
risk of progression
Offer a 5-Alpha reductase inhibitor (5ARI)
Bothersome moderate to
severe LUTS, and a
prostate estimated to be
larger than 30g or PSA
greater than 1.4 ng/ml
Consider combination treatment with an
alpha blocker and a 5ARI
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
NICE Recommendations
Drug treatment – storage symptoms
OAB
Offer an anticholinergic
Storage symptoms despite
treatment with an alpha
blocker alone
Consider adding an anticholinergic
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
NICE recommendations for
drug treatment review
Review men taking drug treatments to assess symptoms, the effect of the drugs on
the patient’s quality of life and to ask about any adverse effects from treatment
(consider IPSS for baseline and subsequent assessments).
Alpha - blockers
Review at 4-6 weeks and then every 6-12 months
5ARI
Review at 3-6 months and then every 6-12 months
Anticholinergic
Review at 4–6 weeks until stable, then every 6–12
months
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
Risk factors for progressive disease
• Age over 70 with LUTS
• Moderate to severe symptoms i.e. IPSS > 7
• PSA > 1.4 ng/ml
• Prostate volume over 30ccs (i.e. feels
enlarged on DRE)
• Flow rate <12 ml/sec
UK/DUTT/0061j/10/ Date of preparation: April 2012
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http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
http://www.nice.org.uk/nicemedia/live/12984/48554/48554.pdf Accessed 20th May 2010
Roehrborn CG et al. J Urol 2000; 163(1):13–20
Emberton M et al. Urology 2003; 61: 267-273
NICE Recommendations on referral
for specialist assessment
Offer referral for specialist assessment if:
Bothersome LUTS have not responded to conservative management or
drug treatment
Refer men for specialist assessment if they have:
- LUTS complicated by recurrent or persistent urinary tract infection, or
- retention, or
- renal impairment you suspect is caused by lower urinary tract
dysfunction or
- suspected urological cancer or
- stress urinary incontinence
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
NICE Recommendations on managing
acute urinary retention
Immediately catheterise men with acute retention
Offer an alpha blocker to men before withdrawing the catheter
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
NICE Recommendations on managing
chronic urinary retention*
* Defined as residual volume of greater than 1 litre or presence of a palpable/percussable bladder
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
NICE Recommendations on surgery for
voiding symptoms
Only offer surgery if:
Voiding symptoms are severe, or drug treatment and conservative
management options have been unsuccessful or are not
appropriate.
Discuss the alternatives to and outcomes from surgery.
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
NICE Recommendations on surgery for
storage symptoms
Only consider in patients whose symptoms
have not responded to conservative
management and drug treatment
Discuss the alternatives of
containment or surgery.
Inform men that effectiveness, side effects
and long-term risks of surgery are uncertain.
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
Back up slides for further information
UK/DUTT/0061j/10/ Date of preparation: April 2012
Digital rectal examination
General overview of DRE
–
A digital rectal examination (DRE) is essential to assess the prostate.
–
The symmetry, size, firmness, surface smoothness, tenderness and the midline
groove should all be assessed.
–
Training and experience will teach the difference between a soft smoothly enlarged
benign feeling prostate and the hard, woody irregular carcinoma.
–
The rectum and pelvis should also be assessed. Faecal loading or impaction, rectal
tumours and other pelvic masses may all be palpated when present.
NICE Guideline recommends a DRE as part of initial
assessment1
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
Urinalysis
General Overview
–
Urinalysis is used as a first line investigation in any setting to identify
haematuria, glycosuria, proteinuria, pyuria, and the presence of urinary
nitrites and leucocytes
–
A dipstick test whilst suggestive of pathology, is useful as a screening test
and abnormal findings need to be confirmed by an MSU sent for
microscopy and culture (and if any growth, sensitivities).
–
Microscopy may reveal bacteria, blood cells (leucocytes and erythrocytes)
and cellular casts (always abnormal and suggestive of renal disease.
NICE Guideline Recommends:
At initial assessment, offer men with LUTS a urine dipstick test
to detect blood, glucose, protein, leucocytes and nitrites1
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
PSA testing
General Overview

Offer men information, advice and time to decide if they wish to have a PSA
test if their:
–
LUTS are suggestive of bladder outlet obstruction secondary to BPE
or
–
Prostate feels abnormal on DRE or
–
Concern is about prostate cancer
NICE Guideline Recommends: Manage suspected prostate
cancer in men with LUTS in line with ‘Prostate cancer:
diagnosis and management’ (NICE clinical guideline 58) and
‘Referral guidelines for suspected cancer’ (NICE clinical
guideline 27) 1
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
Frequency Volume Charts

Voiding diaries are simple, non-invasive tools that are frequently part of the initial
evaluation of patients complaining of LUTS, particularly those who have storage
symptoms such as increased urinary frequency and incontinence.

These diaries give an indication of the voiding pattern, the severity of symptoms and
they add objectivity to the history.
NICE Guideline recommends: At initial and specialist assessment and
on specialist referral, ask men with bothersome LUTS to complete a
urinary frequency volume chart1
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
International Prostate Symptom Score (IPSS)
•
Mild symptoms 0 - 7
•
Moderate 8 – 19
•
Severe 20-35
A copy of the IPSS score pad as a pdf can be downloaded from www.health.gsk.co.uk
NICE Guideline recommends: Offer men considering any treatment for
LUTS an assessment of their baseline symptoms to allow assessment
of subsequent symptom change1
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
A copy of the IPSS score pad as a pdf can be downloaded from www.health.gsk.co.uk
UK/DUTT/0061j/10/ Date of preparation: April 2012
NICE Recommendations on surgery for
voiding LUTS presumed secondary to BPE
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
NICE Recommendations on surgery for
storage symptoms
If considering offering surgery for storage LUTS, refer men to a urologist to discuss:
– the surgical and non-surgical options appropriate for their circumstances and
– the potential benefits and limitations of each option, particularly long-term results.
Do not offer myectomy to manage detrusor overactivity.
6 At the time of publication (May 2010), botulinum toxin did not have UK marketing authorisation for this indication. Informed
consent should be obtained and documented.
UK/DUTT/0061j/10/ Date of preparation: April 2012
1. http://guidance.nice.org.uk/CG97/QuickRefGuide/pdf/English. Accessed 20th May 2010
Some common comparisons to help assess
prostate size
Not to scale
•
A DRE typically underestimates the prostate size as verified by transrectal ultrasound
(TRUS) by up to 55%, with the degree of underestimation increasing with increasing prostate
size.1
UK/DUTT/0061j/10/ Date of preparation: April 2012
Roehborn CG, Sech S, Montoya J et al. Interexaminer reliability and validity of a three
dimensional model to assess prostate volume by digital rectal examination. Urology 2001;
32
56(6): 1087-1092.
Prescribing Information (PI)
(Please refer to the full Summary of Product Characteristics before
prescribing).
Combodart®▼ 0.5 mg/0.4 mg hard capsules (dutasteride 0.5 mg/
tamsulosin hydrochloride 0.4 mg)
Uses - The treatment of moderate to severe symptoms of benign
prostatic hyperplasia (BPH). Reduction in the risk of acute urinary
retention (AUR) and surgery in patients with moderate to severe
symptoms of BPH.
Dosage and administration (adults including elderly) - The
recommended dose of Combodart is one capsule (0.5 mg/0.4 mg) taken
orally approximately 30 minutes after the same meal each day. The
capsules should be swallowed whole and not chewed or opened. No
dose adjustment is necessary in the elderly. Caution in patients with mild
to moderate hepatic impairment. In patients with severe hepatic
impairment, the use of Combodart is contraindicated. Where
appropriate, Combodart may be used to substitute concomitant
dutasteride and tamsulosin hydrochloride in existing dual therapy to
simplify treatment. Where clinically appropriate, direct change from
dutasteride or tamsulosin hydrochloride monotherapy to Combodart
may be considered.
Contra-indications - Use in women, children and adolescents. Known
hypersensitivity to dutasteride, other 5-alpha reductase inhibitors,
tamsulosin (including tamsulosin induced angio-edema), soya, peanut or
any of the other excipients. Patients with a history of orthostatic
hypotension. Patients with severe hepatic impairment.
Special Warnings and Precautions - Combination therapy should be
prescribed after careful benefit: risk assessment due to the potential
increased risk of adverse events (including cardiac failure) and after
consideration of alternative treatment options including monotherapies.
In two 4-year clinical studies, the incidence of cardiac failure (a
composite term of reported events, primarily cardiac failure and
congestive cardiac failure) was higher among subjects taking the
combination of dutasteride and an alpha blocker, primarily tamsulosin,
than it was among subjects not taking the combination. In these two
studies, the incidence of cardiac failure was low (≤1%). Digital rectal
examination, must be performed on patients prior to initiating therapy
with Combodart and periodically thereafter. Women, children and
adolescents must avoid contact with leaking capsules. If contact is made
with leaking capsules, the contact area should be washed immediately
with soap and water. Use with caution in patients with mild to moderate
hepatic impairment. Combodart causes a decrease in mean serum PSA
levels by approximately 50%, after 6 months of treatment. Patients
receiving Combodart should have a new PSA baseline established after
6 months of treatment with Combodart. It is recommended to monitor
PSA values regularly thereafter. Any confirmed increases from lowest
PSA level while on Combodart may signal the presence of prostate
cancer (particularly high grade cancer) or noncompliance to therapy and
should be carefully evaluated. Treatment with Combodart does not
interfere with the use of PSA as a tool to assist in the diagnosis of
prostate cancer after a new baseline has been established. Total serum
PSA levels return to baseline within 6 months of discontinuing treatment.
The ratio of free to total PSA remains constant even under the influence
of Combodart. If electing to use percent free PSA as aid to prostate
cancer detection in men undergoing Combodart therapy, no adjustment
to its value appears necessary. Results of one clinical study in men at
increase risk of prostate cancer (REDUCE), revealed a higher incidence of
Gleason 8 – 10 prostate cancers in dutasteride treated men compared to
placebo. The relationship between dutasteride and high grade prostate
cancer is not clear. Men taking Combodart should be regularly evaluated
for prostate cancer risk including PSA testing. Treatment of severely
renally impaired patients should be approached with caution as these
patients have not been studied. As with other alpha-blockers, a reduction
in blood pressure can occur during treatment with tamsulosin, as a result
of which, rarely, syncope can occur. Patients beginning treatment with
Combodart should be cautioned to sit or lie down at the first signs of
orthostatic hypotension until the symptoms have resolved.
Intraoperative Floppy Iris Syndrome has been observed during cataract
surgery in some patients on or previously treated with tamsulosin. This
may lead to increased procedural complications during the operation.
The initiation of therapy with Combodart in patients for whom cataract
surgery is scheduled is therefore not recommended. Breast cancer has
been reported in men taking dutasteride in clinical studies and during the
post-marketing period. Physicians should instruct their patients to
promptly report any changes in their breast tissue such as lumps or
nipple discharge. Currently it is not clear if there is a causal relationship
between the occurrence of male breast cancer and long term use of
dutasteride. In the double blind 2 year monotheraphy clinical studies and
the 2 year open label extension, there were 2 cases of breast cancer
reported in dutasteride-treated patients and 1 case in a patient who
received placebo. In the 4 year CombAT and REDUCE clinical studies
there were no cases of breast cancer reported in any treatment groups.
Interactions - There have been no drug interaction studies for
Combodart. Dutasteride: In vitro studies: Dutasteride mainly eliminated
via metabolism by CYP3A4 and CYP3A5. Long-term combination of
dutasteride with potent inhibitors of CYP3A4 (e.g. ritonavir, indinavir,
nefazodone, itraconazole, ketoconazole administered orally) may
increase serum concentrations of dutasteride. No effect on the
pharmacokinetics of warfarin, digoxin, tamsulosin or terazosin.
Tamsulosin:. Concomitant administration of tamsulosin hydrochloride
with drugs which can reduce blood pressure, including anaesthetic
agents and other alpha-1 adrenergic blockers could lead to enhanced
hypotensive effects. Dutasteride-tamsulosin should not be used in
combination with other alpha-1 adrenergic blockers. Caution should be
used when dutasteride-tamsulosin is used in combination with
cimetidine. Caution should be exercised with concomitant administration
of warfarin and tamsulosin hydrochloride. No interactions at the level of
hepatic metabolism have been seen during in vitro studies with liver
microsomal fractions, involving amitriptyline, salbutamol and
glibenclamide. Diclofenac however, may increase the elimination rate of
tamsulosin.
Pregnancy and lactation - Combodart is contraindicated in women.
There have been no studies to investigate the effect of Combodart on
pregnancy, lactation and fertility. Fertility: Dutasteride: Reported to
affect semen characteristics (reduction in sperm count, semen volume,
and sperm motility) in healthy men. Possibility of reduced male fertility
cannot be excluded. Tamsulosin:. Effects of tamsulosin hydrochloride on
sperm counts or sperm function have not been evaluated. Pregnancy:
Dutasteride: Small amounts of dutasteride have been found in semen of
subjects receiving dutasteride 0.5 mg. As with all 5-alpha reductase
inhibitors, a condom is recommended for use in patients when their
partner is or may potentially become pregnant to avoid exposure to
semen. Tamsulosin: Administration of tamsulosin hydrochloride to
pregnant female rats and rabbits showed no evidence of foetal harm.
Lactation: Not known whether dutasteride or tamsulosin is excreted in
human milk.
Effects on ability to drive and use machines - No studies on the effects
of Combodart on the ability to drive and use machines have been
performed. However, patients should be informed about the possible
occurrence of symptoms related to orthostatic hypotension such as
dizziness when taking Combodart.
Side effects - There have been no therapeutic clinical studies conducted
with Combodart; however bioequivalence of Combodart with coadministered dutasteride and tamsulosin has been demonstrated. A 30%
reduction on Cmax was observed for the tamsulosin component in the
fed state compared to the fasted state. Food had no effect on AUC of
tamsulosin. Dutasteride monotherapy clinical studies: Higher incidence
with dutasteride than placebo groups: Impotence, altered (decreased)
libido, ejaculation disorders, breast disorders (including breast
enlargement and/or breast tenderness). Post marketing reports: Allergic
reactions including rash, pruritus, urticaria, localised oedema and
angioedema. Alopecia (primarily body hair loss), hypertrichosis.
Dutasteride in combination with the alpha blocker tamsulosin - 4 year
clinical data (CombAT): Higher incidence in the combination therapy
group in the first year of treatment due to higher incidence of
reproductive disorders, specifically ejaculation disorders. Other
reproductive disorders: Impotence, altered (decreased) libido, breast
disorders (includes enlargement and/or tenderness), dizziness. Cardiac
failure: Dutasteride in combination with the alpha blocker tamsulosin –
4 year clinical data (CombAT): the incidence of the composite term
cardiac failure in the combination group (14/1610, 0.9%) was higher than
in either monotherapy group: dutasteride, (4/1623, 0.2%) and
tamsulosin, (10/1611, 0.6%). In a separate 4-year study in 8231 men aged
50 to 75, there was a higher incidence of the composite term cardiac
failure in subjects taking dutasteride 0.5 mg once daily (30/4105, 0.7%)
compared to subjects taking placebo (16/4126, 0.4%).
Legal category: POM.
Presentation and Basic NHS cost Combodart 0.5 mg dutasteride and
0.4 mg tamsulosin hydrochloride (hard capsules) £19.80 per 30 capsule
pack.
Product licence number 19494/0046
Product licence holder GlaxoSmithKline UK Ltd, Stockley Park West,
Middlesex, UB11 1BT.
Prescribing information updated: March 2012. UK/DUTT/0003/12
Adverse events should be reported. Reporting forms and information
can be found at:- http://www.mhra.gov.uk/yellowcard Adverse
events should also be reported to GlaxoSmithKline on 0800 221 441.
Combodart is a registered trademark of the GlaxoSmithKline group of companies
UK/DUTT/0061j/10/ Date of preparation: April 2012