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13.1.1 Anticholinergics
Special cases
13.1 Drugs for urinary tract
disorders
Urinary incontinence
There are 3 main types of urinary incontinence,
which may occur separately or in combination:
– urge: involuntary loss of urine accompanied
or preceded by a sudden urge to void
(bladder overactivity)
– stress: involuntary leakage on effort, exertion,
sneezing or coughing
– overflow: urinary retention and bladder
distension caused by outlet obstruction (eg
prostatic enlargement) or detrusor underactivity.
Before starting drug treatment
Ask the patient to keep a bladder diary for three 24hour periods; this may help to identify the type of
incontinence and possible aetiology; tests (eg
urinalysis, urodynamic assessment) may be
necessary.
Manage contributing factors, eg UTI, faecal loading,
excessive fluid intake, unstable diabetes, obesity;
reduce intake of caffeinated or alcoholic drinks.
Also consider drugs as a cause of incontinence, eg
selective alpha-blockers (eg prazosin), diuretics,
anticholinesterases (eg donepezil), sedatives.
Opioids and drugs with anticholinergic effects (see
Table B–2 p 957) may cause urinary retention
(p 519) and overflow incontinence. Drug-induced
incontinence is particularly common in the elderly.
Consider non-drug measures to help bladder
control including pelvic floor exercises and bladder
training (particularly useful for stress and urge
incontinence respectively).
Protective pads and scheduled voiding may be
helpful in managing incontinence, especially in
people with cognitive impairment or limited
mobility.
Rationale for drug use
Incontinence resistant to non-drug measures.
Relieve symptoms, reduce complications of
incontinence and improve quality of life.
Drug choice
Anticholinergics (p 519) reduce bladder muscle
contractility and increase bladder capacity, and are
mainly used for urge incontinence. They may
increase voiding dysfunction, causing hesitancy
and retention in susceptible people.
The benefit from anticholinergics varies between
individuals; on average there is one fewer episode
of incontinence per 48 hours compared with
placebo, with no evidence of superior efficacy with
newer agents (eg solifenacin, darifenacin) compared to oxybutynin. Stop if there is no benefit after
4 weeks of treatment.
Propantheline is no longer recommended for
treatment of urinary incontinence.
Selective alpha-blockers block receptors in bladder
neck and urethra, which may help to reduce
outflow obstruction and overflow incontinence in
males (see Urinary retention p 519) but may
precipitate or worsen incontinence in women.
AMH © 2013
Incontinence in neurological disease is a complex
condition and is best managed by a specialist.
Mainstays of treatment are intermittent selfcatheterisation, behavioural modification, and
anticholinergics. Botulinum toxin (p 842) injected
into the bladder wall, surgery and the use of
urinary appliances may be useful.
Practice points
• intermittent catheterisation is preferred in most
cases of overflow incontinence occurring postoperatively, postpartum or after neurological
damage when improvement with time can be
expected
• evidence suggests vaginal oestrogen may be
effective for incontinence in postmenopausal
women with urogenital symptoms; systemic
oestrogens may worsen incontinence
• surgery is often successful if conservative
measures fail
• specialists sometimes use anticholinergics with
selective alpha-blockers in men with coexisting
urge incontinence and bladder outlet obstruction
Urinary retention
Urinary retention may be acute or chronic.
Causes include outflow obstruction (see also
Benign prostatic hyperplasia p 522), detrusor
hypocontractility, infection or neurological
impairment. Acute urinary retention is common
postpartum and postoperatively. Drugs (eg
anticholinergics, opioids, sympathomimetics) or
constipation may contribute.
Catheterisation is the preferred treatment and is
necessary to preserve bladder and renal functions.
Drug treatment should not be used without first
ensuring that the bladder is emptying with catheterisation; use of parasympathomimetics, such as
bethanechol, is not recommended. A selective
alpha-blocker (eg alfuzosin) given daily for
2–3 days before catheter removal increases the rate
of successful voiding in men >65 years with acute
urinary retention due to BPH. Intermittent catheterisation may be preferred to an indwelling
catheter in chronic retention.
Practice points
• following an episode of acute retention, check
that bladder emptying continues to be satisfactory by measuring post-void residual volume
13.1.1 Anticholinergics
For additional information see Anticholinergics p 684
See also Urinary incontinence p 519
For drug interactions see Anticholinergics p 856
Darifenacin p 520
Oxybutynin p 520
Propantheline p 520
Solifenacin p 521
Tolterodine p 521
Indications
Urinary urge incontinence
519
13
13.1.1 Anticholinergics
Precautions
Treatment with drugs with anticholinergic effects (Table
B-2 p 957)—additive anticholinergic effect increases
therapeutic and adverse effects; avoid combination.
Dementia—anticholinergics are best avoided; they
may worsen symptoms and antagonise therapeutic
effects of anticholinesterases.
Urinary retention
Avoid use in urinary retention or significant
bladder outlet obstruction. Urinary symptoms may
worsen in men with bladder outlet obstruction
(prostatic enlargement increases the risk of urinary
retention).
Measure post-void residual volume in men before
starting treatment; monitor for urinary retention
especially during initial treatment when risk
appears highest.
Elderly
Elderly people may be more sensitive to anticholinergic adverse effects such as urinary retention,
blurred vision, dry mouth, constipation and confusion. Adverse effects are usually dose related; start
with low dosage and increase cautiously to the
lowest effective dose.
Comparative information
13
There is no evidence that any anticholinergic is the
most effective.
Oral oxybutynin has the highest incidence of dry
mouth.
Limited evidence suggests CNS effects may be less
likely to occur with the more selective agents (eg
solifenacin, darifenacin) than with oxybutynin.
Small studies indicate solifenacin has a higher
incidence of constipation than oxybutynin or
tolterodine.
Solifenacin may increase the QT interval, especially
at high doses.
All are available as tablets; oxybutynin is also
available as a patch.
Counselling
This medicine may cause drowsiness, dizziness or
blurred vision; if affected, do not drive or operate
machinery.
Darifenacin
For additional information see Anticholinergics p 519
For drug interactions see Anticholinergics p 856,
Darifenacin p 856
Indications
Urinary urge incontinence
Precautions
Hepatic
Manufacturer recommends reducing dose in
moderate impairment and avoiding use in severe
impairment (no data).
Pregnancy
No human data; Australian category B3.
www.amh.net.au
Do not exceed 7.5 mg daily in people with moderate
hepatic impairment or taking potent CYP3A4
inhibitors (eg itraconazole, ketoconazole, ritonavir).
Counselling
Swallow tablet whole; do not crush or chew.
tab, 7.5 mg (controlled release), 28, Enablex (NV)
tab, 15 mg (controlled release), 28, Enablex (NV)
Oxybutynin
For additional information see Anticholinergics p 519
For drug interactions see Anticholinergics p 856
Indications
Urinary urge incontinence
Precautions
Pregnancy
Little experience; Australian category B1.
Breastfeeding
Unlikely to be of concern.
Adverse effects
Common
facial flushing (more common in children)
Patch, application site reactions (eg rash, itch,
erythema, vesicles)
Dosage
Adult
Oral
Usual range, 2.5–5 mg 2 or 3 times daily; maximum 20 mg daily.
Elderly, start with 2.5 mg at night and increase
slowly if necessary.
Patch
1 patch applied twice a week (every 3–4 days).
Child >5 years
Oral, initially 2.5 mg twice daily; if necessary,
increase to 5 mg 2 or 3 times daily.
Counselling
Patch
Apply to dry, unbroken skin on your abdomen, hip
or buttock.
Remove and safely dispose of patch after 3–4 days
and put a new patch on a different area (do not
apply to the same place within 7 days).
Practice points
Patch
• dry mouth may be less common than with oral
oxybutynin; however, application site reactions
are common (>10%) and may be intolerable
tab, 5 mg (scored), 100, Ditropan (AV), Oxybutynin (SZ),
PBS-R1
patch, 3.9 mg/24 hours, 8, Oxytrol (HS), PBS-R2
1
2
detrusor overactivity
detrusor overactivity in patients unable to take tablets
Propantheline
Breastfeeding
For additional information see Anticholinergics p 519
For drug interactions see Anticholinergics p 856
No human data.
Indications
Dosage
Adult, initially 7.5 mg once daily; if necessary,
increase dose after at least 2 weeks to 15 mg once
daily.
520
Urinary urge incontinence
Precautions
Pregnancy
Little experience; Australian category B2.
AMH © 2013
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13.1.2 Drugs for nocturnal enuresis
Breastfeeding
Dosage
Unlikely to be of concern.
Adult, 2 mg twice daily; reduce to 1 mg twice daily
if necessary to minimise adverse effects.
Dosage
Adult
15–30 mg 2 or 3 times daily.
Elderly, start with 15 mg twice daily.
Practice points
• propantheline is now rarely used for urinary
incontinence
tab, 15 mg, 100, Pro-Banthine (AS), PBS-R1
1
detrusor overactivity
Solifenacin
For additional information see Anticholinergics p 519
For drug interactions see Anticholinergics p 856,
Solifenacin p 856
Indications
Urinary urge incontinence
Precautions
Risk factors for prolonged QT interval (p 272)—solifenacin may increase the QT interval especially at
doses higher than recommended (eg if concentration increased by a drug interaction or reduced
clearance).
CrCl <30 mL/minute or hepatic impairment
1 mg twice daily.
tab, 1 mg, 56, Detrusitol (PF)
tab, 2 mg, 56, Detrusitol (PF)
13.1.2 Drugs for nocturnal
enuresis
Nocturnal enuresis in children
Involuntary loss of urine (usually nocturnal) is
normal in young children, but can cause concern if
it persists after 5 years of age when micturition
control is normally achieved.
Bed-wetting generally relates to a maturational
delay and usually resolves spontaneously. Most
cases of primary nocturnal enuresis are due to
nocturnal polyuria, sleep arousal difficulties or
bladder dysfunction including low bladder
capacity. Psychological factors may be important
in secondary nocturnal enuresis.
Before starting treatment
No human data.
Wait until the child is at least 5 years old before
starting any treatment (7 years is usual).
Exclude structural abnormalities and other organic
causes, such as UTI, constipation, or diabetes, and
ensure a normal daily fluid intake and toileting
pattern. Assess whether social or emotional problems may be a contributing factor.
There is a significant relapse rate with all treatments; alarms are associated with a lower relapse
rate than drug treatment but are slower to take
effect.
Dosage
Non-drug treatment
Adult, initially 5 mg once daily; if necessary,
increase dose to 10 mg once daily.
Do not exceed 5 mg daily in people with moderate
hepatic impairment, CrCl <30 mL/minute or taking
potent CYP3A4 inhibitors (eg itraconazole, ketoconazole, ritonavir).
Non-drug treatment is preferred initially; rewards
for agreed behaviour and enuresis alarms are often
successful. Although usually used in older
children, alarms may be considered in children
5–7 years old depending on level of understanding
and motivation.
Counselling
When to start drug treatment
Swallow tablet whole; do not crush or chew.
tab, 5 mg, 30, Vesicare (CS)
tab, 10 mg, 30, Vesicare (CS)
After non-drug measures have failed or are
inappropriate.
Special circumstances when more control is
desirable, eg sleeping away from home.
Tolterodine
Drug choice
Renal
Do not exceed initial dose if CrCl <30 mL/minute.
Hepatic
Do not exceed initial dose in moderate impairment;
avoid use in severe impairment.
Pregnancy
No human data; Australian category B3.
Breastfeeding
For additional information see Anticholinergics p 519
For drug interactions see Anticholinergics p 856,
Tolterodine p 856
Indications
Urinary urge incontinence
Precautions
Renal
Reduce dose if CrCl <30 mL/minute.
Hepatic
Reduce dose in hepatic impairment.
Pregnancy
No human data; avoid use; Australian category B3.
Breastfeeding
Desmopressin (p 522): first-line drug treatment; an
antidiuretic hormone analogue that is often
effective with fewer adverse effects than TCAs. Use
with caution if fluid overload is undesirable, eg
renal disease, cardiovascular disease, cystic
fibrosis.
Imipramine (p 759) is often effective but adverse
effects and risks in overdose limit its use to secondline treatment on specialist advice. Recommended
maximum treatment course is 3 months; withdraw
gradually.
Practice points
• refer to a specialist if bedwetting is unresponsive
to an alarm and desmopressin
No human data.
AMH © 2013
521
13
13.2 Drugs for benign prostatic hyperplasia and prostatitis
Desmopressin
For additional information see Desmopressin p 442
See also Nocturnal enuresis in children p 521
tab, 200 mcg (scored), 30, Minirin (FP), PBS-A1
wafer, 120 mcg (sublingual), 30, Minirin Melt (FP), PBS-A1
wafer, 240 mcg (sublingual), 30, Minirin Melt (FP), PBS-A1
nasal spray, 10 mcg/dose, 6 mL, 60 doses, Minirin (FP), PBS-A1
1
Indications
www.amh.net.au
primary nocturnal enuresis in patients >6 years when an
enuresis alarm is contraindicated or ineffective
Nocturnal enuresis in children
Precautions
Intranasal use—hyponatraemia has been reported
more often with intranasal use (mainly associated
with excess fluid intake and inappropriate use); use
only if oral or sublingual route is inappropriate.
Inability to comply with fluid restrictions—avoid use
in children unable or unwilling to restrict fluid
intake for 9 hours; hyponatraemia and seizures can
occur with excess fluid intake.
Adverse effects
Common
headache
Intranasal: nosebleed, rhinitis, nausea, abdominal
pain
Infrequent
hyponatraemia, water intoxication, seizures,
syncope, allergy, emotional disturbances
Dosage
Child 6 years or older
Oral tablet, initially 200 micrograms at bedtime;
increase to 400 micrograms at bedtime if needed.
Sublingual wafer, initially 120 micrograms at
bedtime; increase to 240 micrograms at bedtime if
needed.
Intranasal, initially 20 micrograms at bedtime.
Maintenance 10–40 micrograms at bedtime.
Dose equivalence
120 micrograms sublingual wafer is approximately
equivalent to 200 micrograms oral tablet.
Counselling
13
Be careful that the child takes the correct dose and
only sips of fluid (eg no more than a total of one
glass) from 1 hour before the dose to 8 hours after
it.
Do not give the dose if the child is vomiting or has
diarrhoea.
Wafer: place the wafer under your tongue and
allow it to dissolve; do not swallow.
Practice points
• desmopressin should be used only to treat
nocturnal enuresis when an enuresis alarm has
failed or is inappropriate
• treat for 1–3 months, then withdraw to assess for
relapse
• response may improve if dose is given 1–2 hours
before bedtime, but the child must be able to
comply with fluid restriction from 1 hour before
the dose
• if fluid intake is unrestricted water retention
with possible hyponatraemia may occur
• there is no dose equivalence between oral and
intranasal dosage forms
• desmopressin is used overseas to treat adults
with nocturia associated with nocturnal polyuria or MS
522
13.2 Drugs for benign prostatic
hyperplasia and prostatitis
Benign prostatic hyperplasia
Incidence of BPH increases with age. Symptoms
may include voiding symptoms (eg hesitancy,
straining, weak or intermittent urine flow,
sensation of incomplete emptying) and/or bladder
storage symptoms (eg urgency, frequency,
nocturia). The severity of symptoms is not related
to prostate size. Complications such as acute
urinary retention (p 519) or renal impairment may
also occur.
Rationale for drug use
Improve symptoms by decreasing urinary outflow
resistance.
Reduce long-term complications.
Before starting treatment
Assess symptom severity using a scoring system
such as the International Prostate Symptom Score.
It can also be used to monitor progress and
response to treatment.
Assess prostate size.
Look for aggravating factors such as constipation,
diuretics, or drugs with anticholinergic or sedating
effects.
Advise on measures such as reducing caffeine and
alcohol intake, bladder training and reducing fluid
intake at times when urinary frequency is inconvenient (eg at night).
Patients with uncomplicated BPH not bothered by
symptoms may be managed with watchful waiting
(education, reassurance, lifestyle measures and
periodic monitoring).
When to start treatment
Consider drug treatment when symptoms are
troublesome, it is preferred by the patient, and
surgery is not indicated.
Drug choice
Prostate size is the most important factor
influencing drug choice. Symptomatic relief
requires continuous treatment.
Selective alpha-blockers
Can improve symptoms within 48 hours (full effect
in 4–6 weeks) and also improve urinary flow rates.
They appear to be effective regardless of prostate
size.
5-alpha-reductase inhibitors
Are an option when prostate >30–40 cm3. In
addition to improving symptoms and urinary flow
rate, they also reduce prostate size and rates of
acute urinary retention and surgery. However, it
may take 6 months of treatment before symptoms
improve (full effect after 12–18 months).
AMH © 2013
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13.2 Drugs for benign prostatic hyperplasia and prostatitis
Combination treatment
As a selective alpha-blocker relieves symptoms
more rapidly than a 5-alpha-reductase inhibitor,
consider combination treatment when prostate
>30–40 cm3 and rapid relief of troublesome symptoms is required.
Optimal duration of combination treatment is
uncertain. There is some evidence that the selective
alpha-blocker can be stopped after 6–12 months of
combination treatment in most patients without
worsening urinary symptoms. However, some
patients, especially those with severe baseline
symptoms, may benefit from continuing the
combination.
Other treatment
Surgery (such as transurethral resection of the
prostate) is more effective than drug treatment and
is an appropriate option when symptoms are more
severe, when drug treatment is ineffective or not
tolerated and when there are complications such as
urinary retention.
Practice points
• men with a prostate >30–40 cm3 who are not
bothered by their symptoms may be offered a
5-alpha-reductase inhibitor to reduce the risk of
disease progression
• specialists sometimes add an anticholinergic to a
selective alpha-blocker in men who have continuing storage symptoms (bladder overactivity)
• saw palmetto (Serenoa repens) is no more
effective than placebo in improving lower
urinary tract symptoms of BPH (Cochrane
systematic review)
Prostatitis
There are 3 main types:
Acute bacterial prostatitis is associated with an acute
UTI (may follow trauma or bladder outflow
obstruction) with similar pathogens, eg E. coli,
Klebsiella, Enterococci spp. It is a serious, severe
illness; cure is likely, but it may progress to chronic
prostatitis.
Chronic bacterial prostatitis is associated with
chronic or relapsing UTI (same pathogen in urinary
and prostatic fluid); may be asymptomatic between
UTI, but usually there is pain and discomfort. It has
a more favourable prognosis than chronic pelvic
pain syndrome.
Chronic prostatitis/chronic pelvic pain syndrome is not
associated with UTI but has similar symptoms (eg
pelvic pain, lower urinary tract symptoms) to
chronic bacterial prostatitis, and is much more
common.
Rationale for drug use
Provide symptom relief, cure any infection and
reduce likelihood of complications.
Before starting treatment
Obtain urine (and blood, where appropriate) for
culture (avoid prostatic massage in acute
prostatitis).
AMH © 2013
In chronic prostatitis, exclude other causes such as
UTI, prostatic abscess, epididymitis, urethritis, and
cancer.
The National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI) at www.upointmd.
com/NIHCPSIEnglish.pdf may be useful in assessing
symptom severity and response to treatment.
Treatment
Acute bacterial prostatitis
Severe infections require IV antibacterials (eg
ampicillin plus gentamicin) and fluid replacement.
For mild-to-moderate infections, begin empirical
treatment with an oral antibacterial that is effective
against most urinary pathogens, eg ciprofloxacin
(p 129) or trimethoprim (p 152) for 4 weeks
(minimum 14 days). Change the antibacterial
according to urine culture results if necessary.
Most antibacterials will penetrate the inflamed
prostate well.
Ensure adequate hydration, rest and analgesia
(paracetamol or an NSAID); consider bowel
function (constipation may increase pain).
Repeat urine culture after the course is finished to
check whether the infection has cleared; then
investigate for any contributing structural
abnormalities.
Chronic bacterial prostatitis
General measures as for acute bacterial prostatitis;
however, as inflammation is not intense, penetration of antibacterials into prostate tissue may be
poor. Treat for 4–6 weeks with an antibacterial that
penetrates the prostate well, eg trimethoprim,
norfloxacin or ciprofloxacin. Doxycycline may be
used if intracellular bacteria, eg Chlamydia, are
suspected or cultured.
Chronic prostatitis/chronic pelvic pain
syndrome
Although symptoms usually improve over time,
chronic prostatitis frequently relapses and is
difficult to manage.
No treatment has proven benefit; a trial of:
– an antibacterial (as for chronic bacterial
prostatitis) may be worthwhile, especially in
recently diagnosed patients, as there may be
undiagnosed bacterial infection
– adequate analgesia (eg NSAID) and relief of
constipation may help
– one of the selective alpha-blockers (p 524)
may ease pain and improve urinary
symptoms
– quercetin 500 mg twice daily, or pollen extract
(Cernilton®, Prostat/Poltit®), may relieve
symptoms, particularly pain (based on small
placebo-controlled studies).
Practice points
• refer men with unexplained haematuria or longstanding chronic prostatitis to a specialist
• avoid using nitrofurantoin as it penetrates
prostatic tissue poorly
• quercetin should not be used during quinolone
treatment as it may decrease antibacterial
efficacy
523
13
13.2.1 Selective alpha-blockers
13.2.1 Selective alpha-blockers
For additional information see Selective alphablockers p 265
See also Benign prostatic hyperplasia p 522
For drug interactions see Alpha-blockers (selective)
p 854
Alfuzosin p 524
Prazosin p 525
Tamsulosin p 525
Terazosin p 525
Mode of action
Block alpha1 receptors, relaxing smooth muscle in
the bladder neck and prostate, and decreasing
resistance to urinary flow. Tamsulosin is more
selective for the alpha1-receptor subtypes found in
the bladder and prostate.
Prazosin and terazosin are also arterial and
venodilators due to blockade of postsynaptic
alpha1 receptors and therefore inhibition of
catecholamine-mediated vasoconstriction.
Unlike nonselective alpha-blockers (eg phenoxybenzamine), they have little effect on presynaptic
alpha2 receptors and are therefore less likely to
cause reflex tachycardia.
Indications
Symptom relief in BPH
Hypertension (see Selective alpha-blockers p 265)
Precautions
Volume depletion—risk of exacerbation of orthostatic hypotension.
Treatment with antihypertensives—close supervision
required because of possible additive hypotensive
effects; combination with diuretics, beta-blockers,
calcium channel blockers increases risk of first dose
hypotension.
13
Cataract surgery
Selective alpha-blockers (particularly tamsulosin)
are associated with a risk of intra-operative floppy
iris syndrome during cataract surgery. Interrupting
treatment does not appear to reduce this risk; it may
be necessary to modify surgical technique. Increased
rates of postoperative ocular complications have
been associated with tamsulosin use.
Consider use of these agents, especially tamsulosin,
carefully if cataract surgery is contemplated, as these
complications have occurred even after these drugs
were ceased.
Renal
Begin treatment cautiously in impairment as there
may be a profound first dose effect (excessive hypotension).
Hepatic
Use with caution in impairment; alfuzosin is
contraindicated.
Elderly
Use with caution (avoid prazosin); the elderly are
more susceptible to orthostatic hypotension.
Adverse effects
Common
first dose hypotension, orthostatic hypotension,
dizziness (all less frequent with alfuzosin and
tamsulosin); nasal congestion, urinary urgency,
headache, weakness, fatigue, drowsiness
524
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Infrequent
tachycardia, palpitations, oedema, syncope, blurred
vision, urinary incontinence, nausea, vomiting, dry
mouth, increased sweating
Rare
rash, itch, depression, mood changes, dyspnoea,
paraesthesia
Comparative information
Alfuzosin and tamsulosin are only indicated for
BPH; prazosin and terazosin are also indicated for
hypertension.
All selective alpha-blockers appear to be similarly
effective for BPH. Tamsulosin and alfuzosin have
less effect on BP than prazosin or terazosin and may
be a better choice for BPH; dosage titration is
required with prazosin and terazosin to minimise
hypotensive effects. Prazosin has a short duration of
action and needs to be taken twice daily; alfuzosin,
tamsulosin and terazosin can be taken once daily.
Prazosin and terazosin are equally effective for
treating hypertension but are only used third line.
Counselling
Dizziness on standing may occur especially when
starting treatment or when the dose is increased. Get
up gradually from sitting or lying to minimise this
effect; sit or lie down if you become dizzy. Take the
first dose at bedtime, but be careful if you get up
during the night as you may feel dizzy.
This medicine may cause drowsiness or dizziness;
do not drive or operate machinery if affected.
Tell your ophthalmologist you are taking, or have
taken, this medicine if you are going to have cataract
surgery.
Practice points
• add antihypertensives cautiously (particularly if
taking prazosin or terazosin) as BP may fall
sharply
• first dose hypotension is more common with
prazosin and terazosin; it is most serious in the
elderly and in patients with fluid depletion or
who are taking diuretics; for management, see
First dose hypotension p 266
• if treatment with prazosin or terazosin is interrupted for several days, restart and titrate dosage
as if starting for the first time
• monitor BP (lying and standing) and for symptoms of hypotension, particularly during dose
titration of prazosin or terazosin
• stop if there is no improvement in symptoms of
BPH after 4–6 weeks of maximal treatment
• although not a marketed indication, selective
alpha-blockers, usually tamsulosin, have been
used in selected patients with small lower ureteral
stones as they may help stone passage
Alfuzosin
For additional information see Selective alphablockers p 524
For drug interactions see Alpha-blockers (selective)
p 854, Alfuzosin p 854
Indications
Symptom relief in BPH
Precautions
Hepatic
Contraindicated in hepatic impairment.
AMH © 2013
www.amh.net.au
13.2.2 5-Alpha-reductase inhibitors
Dosage
Dosage
10 mg once daily.
Initially, 1 mg daily for 7 days, then 2 mg daily for
7 days; then increase dose according to clinical
response up to 5–10 mg each morning.
Counselling
Swallow whole. Take immediately after a meal for
best absorption.
tab, 10 mg (controlled release), 30, 60, Xatral SR (AV),
RPBS-A[30]1
tab, 2 mg, 28, Hytrin (AB), RPBS-A1
tab, 5 mg, 28, Hytrin (AB), RPBS-A1
tab, 10 mg, 28, Hytrin (AB), RPBS-A1
1
Combination packs
BPH, see PBS
Prazosin
For additional information see Selective alphablockers p 524
For drug interactions see Alpha-blockers (selective)
p 854
Indications
Symptom relief in BPH
Hypertension (see Prazosin p 266)
Adverse effects
Rare
priapism, hallucinations, confusion, nightmares,
pancreatitis
Dosage
0.5 mg twice daily for 3–7 days, then increase
according to clinical response up to 2 mg twice
daily.
tab, 1 mg (scored), 100, Minipress (PF), Prazosin (CH, TW, TX),
PBS
tab, 2 mg (scored), 100, Minipress (PF), Prazosin (CH, TW, TX),
PBS
Tamsulosin
For additional information see Selective alphablockers p 524
For drug interactions see Alpha-blockers (selective)
p 854
Indications
Symptom relief in BPH
Combination with dutasteride
Symptomatic BPH with prostate >30–40 cm3, see
Dutasteride p 526
Adverse effects
Common
abnormal ejaculation
Rare
hypersensitivity reactions, angioedema, urticaria
Dosage
400 micrograms once daily.
Counselling
Swallow whole, do not crush or chew.
tab, 400 mcg (controlled release), 30, Flomaxtra (CS), RPBS-A1
1
BPH where surgery is inappropriate or other drug treatment
has failed or is contraindicated
Terazosin
For additional information see Selective alphablockers p 524
For drug interactions see Alpha-blockers (selective)
p 854
Indications
Symptom relief in BPH
Hypertension (see Terazosin p 266)
AMH © 2013
tab, 1 mg, 7; tab, 2 mg, 7, Hytrin Starter Pack (AB), RPBS-A1
1
BPH where surgery is inappropriate or other drug treatment
has failed or is contraindicated
13.2.2 5-Alpha-reductase
inhibitors
See also Benign prostatic hyperplasia p 522
Dutasteride p 526
Finasteride p 526
Mode of action
Inhibit 5-alpha-reductase, which converts testosterone to dihydrotestosterone (a potent cellular
androgen that stimulates prostate growth). They
reduce prostate size and improve symptoms and
urinary flow rate.
Indications
BPH
Adverse effects
Common
impotence, decreased libido, ejaculation disorder
(including decreased ejaculate volume)
Infrequent
breast tenderness or enlargement
Rare
allergic reaction
Comparative information
Dutasteride has a long half-life (3–5 weeks) compared with finasteride (6 hours) and can still be
detected 4–6 months after stopping treatment.
Finasteride inhibits the type 2 isoenzyme of 5alpha-reductase and dutasteride inhibits both the
type 1 and type 2 isoenzymes. Although dutasteride reduces serum dihydrotestosterone by
about 90% compared with 70% with finasteride,
limited evidence from short-term studies suggests
there are no major differences between them in
terms of reduction of prostate size, symptom
improvement, urinary flow rate or adverse effects.
Practice points
• women who are or may become pregnant should
not handle capsules or broken or crushed tablets
without gloves (Australian category X)
• efficacy depends on prostate size; men with a
smaller prostate (<30 cm3) are unlikely to benefit
• it may take >6 months of treatment before
symptoms improve
• long-term use of 5-alpha-reductase inhibitors
reduces the risk of acute urinary retention and the
need for surgery; finasteride also reduces the risk
of recurrence of haematuria
• after 6 months of dutasteride or 1 year of
finasteride (5 mg daily) prostate specific antigen
(PSA) concentration is reduced by an average of
50% (further reductions may occur with longer
therapy, particularly with dutasteride); take into
consideration when measuring PSA
525
13
13.3 Drugs for erectile dysfunction
• if PSA concentration begins to rise at all during
treatment, assess for prostate cancer (it is unclear
whether there is an increased risk of high-grade
tumours in men taking 5-alpha-reductase
inhibitors)
• 6 months after stopping treatment, PSA concentrations have generally returned to baseline
Dutasteride
For additional information see 5-Alpha-reductase
inhibitors p 525
Indications
Symptomatic BPH with prostate >30–40 cm3
(includes combination with tamsulosin)
Precautions
Combination with tamsulosin—the incidence of
orthostatic hypotension may be higher when
taking the combination capsule compared to taking
dutasteride and tamsulosin separately due to
differences in formulation.
Dosage
500 micrograms once daily.
Combination with tamsulosin
For additional information see Tamsulosin p 525
1 capsule once daily.
Counselling
Swallow whole; do not open or chew the capsules
as the contents may irritate your mouth and throat.
Combination with tamsulosin
Swallow whole.
Take this medicine about 30 minutes after a meal.
Do not take it on an empty stomach as this may
increase the risk of side effects, eg dizziness on
standing.
cap, 500 mcg, 30, Avodart (GK), PBS-A1
Combination products
13
cap, dutasteride 500 mcg, tamsulosin (controlled release)
400 mcg, 30, Duodart (GK), PBS-A1
1
urinary tract symptoms due to BPH, see PBS
Finasteride
For additional information see 5-Alpha-reductase
inhibitors p 525
Indications
Symptomatic BPH with prostate >30–40 cm3
Androgenetic alopecia in men (see Finasteride
p 382)
Dosage
5 mg once daily.
Practice points
• breast cancer has been reported in men taking
finasteride; the association between finasteride
and increased risk of breast cancer is unclear;
monitor for any changes in breast tissue
tab, 5 mg, 28, Finpro (RZ), RPBS-A1
tab, 5 mg, 30, Finasta (SZ), Proscar (MK), RPBS-A1
tab, 5 mg, 30, Finnacar (AS), Finasteride (CR, RA, TX)
1
BPH, see PBS
526
www.amh.net.au
13.3 Drugs for erectile
dysfunction
Erectile dysfunction
Rationale for drug use
Achievement of penile erection adequate for sexual
intercourse.
Before starting treatment
Determine and treat underlying cause if possible. It
is often associated with conditions such as cardiovascular disease, diabetes and hypertension, and
may be an indicator for unrecognised disease.
Assess cardiovascular status in relation to the
stress induced by sexual activity; for most people
this will be roughly equivalent to mild-tomoderate exercise, an exercise test may be useful.
Erectile dysfunction is often due to a combination
of organic and psychogenic problems:
– organic causes include neurological, vascular,
endocrine, structural, drug-induced (eg betablockers, alcohol misuse)
– psychogenic: may respond to counselling or
behaviour therapy; attention to psychological
factors is important in all cases.
If irreversible organic causes are implicated, the
3 main treatments are drug treatment, vacuum
pump (which induces erection by negative
pressure) and prostheses.
Drug choice
Phosphodiesterase 5 inhibitors are taken orally;
other drug treatments require penile injection.
Phosphodiesterase 5 inhibitors (sildenafil, tadalafil,
vardenafil) are the drugs of choice due to their
effectiveness and ease of use; onset of effect is
about 30 minutes to 1 hour and they are generally
well tolerated. Most clinical experience has been
gained with sildenafil. They should be used alone
as safety and efficacy are not well established for
combination treatments, although some studies
suggest that combining alprostadil with sildenafil
may be helpful. They are contraindicated in men
taking nitrates.
Alprostadil is effective alone or with other agents; of
the injectable products, it is least likely to cause
penile fibrosis or priapism.
Papaverine may be used alone or in combination;
consider only if intracavernosal alprostadil is
inappropriate.
Phentolamine (p 448) must be used with papaverine
and/or alprostadil injection to be effective.
Practice points
• ideal dose should produce an erection that lasts
no more than 1 hour
• a smaller dose is required to maintain adequate
erection at home than in the clinic
• regular medical review during treatment course
is necessary
• discourage ‘social’ use by men who do not have
potency problems, since they have a greater risk
of priapism
• consider surgery if there is continued failure of
drug treatment
AMH © 2013
www.amh.net.au
13.3.1 Phosphodiesterase 5 inhibitors
Priapism
Eyes
• explain treatment of priapism to patient
• if erection lasts >2 hours taking two 60 mg
pseudoephedrine (p 393) tablets may help
• emergency medical treatment is necessary if
erection lasts more than 4 hours; continued
erection requires aspiration of 20–50 mL of
blood from the corpus cavernosum via a 19 or
21 gauge butterfly needle; this may be repeated
on the other side if necessary
• if still unsuccessful, urgent urological review is
necessary
Contraindicated with a history of non-arteritic
anterior ischaemic optic neuropathy (NAION).
Avoid use if there is significant vision loss in one
eye due to the risk of serious ocular adverse effects
in other eye (see NAION below).
The effect of PDE5 inhibitors on retinal phosphodiesterase in patients with hereditary degenerative
retinal disorders (eg retinitis pigmentosa) is
unknown; avoid use in these patients.
13.3.1 Phosphodiesterase 5
inhibitors
See also Erectile dysfunction p 526
For drug interactions see Phosphodiesterase 5
inhibitors p 924
Sildenafil p 528
Tadalafil p 528
Vardenafil p 529
Mode of action
Sexual stimulation increases cyclic guanosine
monophosphate (cGMP) levels, resulting in
smooth muscle relaxation, inflow of blood to the
corpus cavernosum and penile erection.
These agents inhibit the breakdown of cGMP by
phosphodiesterase type 5 (PDE5), increasing blood
flow to the penis during sexual stimulation.
Indications
Erectile dysfunction
Pulmonary arterial hypertension, see
Phosphodiesterase 5 inhibitors p 295
Precautions
Migraine—there are reports of these agents
inducing migraine.
Anatomical deformation of penis, sickle cell anaemia,
myeloma, leukaemia—increases risk of priapism.
Bleeding disorders, active peptic ulcer—platelets
contain PDE5; no safety data.
Other drugs
Contraindicated with nitric oxide donors, organic
nitrates or nitrites (including glyceryl trinitrate in
any form, isosorbide mononitrate, isosorbide
dinitrate, sodium nitroprusside, amyl nitrite,
nicorandil) due to risk of profound hypotension or
MI. If a nitrate is required, allow at least 24 hours
(48 hours with tadalafil) after a dose of PDE5
inhibitor before giving a nitrate. A longer period
may be required if elimination of the PDE5
inhibitor is delayed (eg due to drug interaction,
renal or hepatic impairment, in the elderly).
Monitor response carefully.
Treatment with drugs that can cause hypotension,
particularly selective alpha-blockers, may add to
hypotension caused by PDE5 inhibitors. Consider
starting with a low dose of PDE5 inhibitor. Patient
should be stabilised on alpha-blocker therapy
before starting a PDE5 inhibitor; if using prazosin
or terazosin, separate doses by at least 4 hours
(6 hours with vardenafil).
AMH © 2013
Cardiovascular
Contraindicated in men for whom sexual intercourse is inadvisable due to cardiovascular risk
factors, eg unstable angina.
Consider cardiovascular status in relation to stress
risk arising from sexual activities, particularly as
nitrates cannot be used readily; for most people this
will be roughly equivalent to mild-to-moderate
exercise; an exercise test may be useful.
There are few or no safety data for men with hypotension (BP <90/50 mm Hg), uncontrolled hypertension, stroke or MI within the last 3–6 months,
other severe cardiovascular disease (eg heart
failure, uncontrolled arrhythmias).
MI, TIA and stroke, including intracerebral
bleeding, have occurred; association with PDE5
inhibitors is difficult to assess.
Consider undiagnosed cardiovascular disorders
before prescribing these agents.
Adverse effects
Frequency of adverse effects appears to be dose
related.
Common
headache (>10%), dizziness, flushing, dyspepsia,
nasal congestion/rhinitis
Rare
priapism (infrequent with vardenafil), vision loss
due to NAION (below), migraine, seizures, sudden
hearing loss (may be associated with tinnitus,
vertigo or dizziness), transient amnesia, hypersensitivity
NAION
Vision loss due to NAION has been reported; cases
include patients treated for pulmonary hypertension, some of whom were female. However,
causality is unclear. Risk factors for NAION are
similar to those for erectile dysfunction and incidence is similar to that in general population of men
>50 years.
Comparative information
Efficacy: limited data suggest that sildenafil, tadalafil and vardenafil have similar efficacy. All are
effective in erectile dysfunction due to diabetes,
nerve-sparing prostatectomy or spinal cord injury,
although efficacy rates are lower in diabetes or
prostatectomy.
Onset and duration of action: onset is about 30 minutes
to 1 hour; sildenafil and vardenafil are short-acting
and tadalafil is long-acting. Food delays the onset of
action of sildenafil and vardenafil.
Adverse effects: although headache is common for
these drugs, that caused by tadalafil lasts for
3–8 hours. Sildenafil is most likely to cause visual
changes. Vardenafil has prolonged the QT interval
in healthy volunteers.
527
13
13.3.1 Phosphodiesterase 5 inhibitors
Counselling
Do not take this medication if you already take
nitrates as the combination may cause a serious drop
in your blood pressure. This can happen even if you
take them on different days. Tell your health
professional (even in a medical emergency) that you
take this medicine before taking any new medicines.
This medication may cause visual disturbances and
dizziness. If you are affected do not drive or operate
machinery.
Tell your doctor immediately if you have any
sudden loss of hearing or vision.
Taking this medication may worsen any dizziness or
faintness if you are already taking medication to
lower your blood pressure. If also taking prazosin or
terazosin, separate doses by at least 4 hours (6 hours
if taking vardenafil).
Practice points
• safety and efficacy with other treatments for
erectile dysfunction are not well studied,
although some data suggest that combining
sildenafil with alprostadil may be helpful in men
refractory to monotherapy
• as PDE5 inhibitors can overcome erectile dysfunction due to organic and psychogenic causes
there is concern that such symptomatic treatment
may lead to curable or serious diseases not being
investigated
• they are ineffective in the absence of sexual
stimulation
Sildenafil
For additional information see Phosphodiesterase 5
inhibitors p 527
For drug interactions see Phosphodiesterase 5
inhibitors p 924, Sildenafil p 925
Indications
13
Erectile dysfunction
Pulmonary arterial hypertension (see Sildenafil
p 295)
Precautions
Renal
Consider starting with a low dose if CrCl <30 mL/
minute.
Hepatic
www.amh.net.au
Dosage
Take about 1 hour before sexual activity; no more
than 1 dose daily.
Start with 50 mg; decrease dose to 25 mg or increase
to a maximum of 100 mg depending on response
and tolerability.
Elderly, CrCl <30 mL/minute or mild-to-moderate
hepatic impairment, consider starting with 25 mg,
increasing to 50–100 mg as required and if tolerated.
With erythromycin, ketoconazole, itraconazole or saquinavir, consider starting with 25 mg.
With ritonavir, limit dose to 25 mg every 48 hours.
Counselling
If you take sildenafil with food it may take longer to
work.
tab, 25 mg, 4, Viagra (PF), RPBS-A1
tab, 50 mg, 4, Viagra (PF), RPBS-A1
tab, 100 mg, 4, 12, Viagra (PF), RPBS-A[4]1
1
erectile dysfunction, see PBS
Tadalafil
For additional information see Phosphodiesterase 5
inhibitors p 527
For drug interactions see Phosphodiesterase 5
inhibitors p 924, Tadalafil p 925
Indications
Erectile dysfunction
Pulmonary arterial hypertension (see Tadalafil
p 296)
Precautions
Renal
Intermittent use: reduce dose when CrCl <30 mL/
minute.
Daily use: not recommended when CrCl <30 mL/
minute.
Hepatic
Intermittent use: reduce dose in mild-to-moderate
impairment (Child-Pugh class A or B). Limited data
in severe impairment (Child-Pugh class C).
Daily use has not been evaluated in hepatic impairment.
Adverse effects
More common with 20 mg dose; usually transient
and decrease with continued use.
Consider starting with a low dose in mild-tomoderate hepatic impairment; manufacturer
contraindicates use in severe impairment (no data).
Common
Elderly
Infrequent
Half-life is increased; consider starting with a low
dose.
headache lasting 3–8 hours, back pain (unrelated to
physical activity), muscle aches
conjunctival hyperaemia, sensations of eye pain,
swollen eyelids
Adverse effects
Common
Rare
rash, diarrhoea, UTIs, abnormal vision (below)
Dosage
Intermittent use
Take 30 minutes – 12 hours before sexual activity
(may be effective for up to 36 hours); no more than
1 dose daily. If required at least twice a week
consider daily use (below).
Start with 10 mg; decrease dose to 5 mg or increase
to a maximum of 20 mg depending on response and
tolerability.
With ketoconazole or ritonavir, initially 5 mg; maximum 10 mg in 72 hours.
Rare
tachycardia, hypotension, syncope
Abnormal vision
Mild, transient retinal effects including blue-green
colour tinge, light sensitivity, blurred vision. More
common at doses of 100 mg and above. Long-term
effects unknown.
Serous macular detachment has very rarely been
associated with sildenafil.
528
changes in colour vision
AMH © 2013
www.amh.net.au
Renal impairment
CrCl <30 mL/minute, limit dose to 10 mg daily.
Hepatic impairment
Mild-to-moderate, limit dose to 10 mg daily.
Daily use
Consider when intermittent use is tolerated and
taken at least twice a week.
2.5–5 mg once daily.
With ketoconazole or ritonavir, maximum 2.5 mg
once daily.
Practice points
• regularly reassess need for daily dosing as data
on long-term effects of PDE5 inhibition in men
with erectile dysfunction are limited
tab, 5 mg, 28, Cialis (LY)
tab, 10 mg, 4, Cialis (LY), RPBS-A1
tab, 20 mg, 4, 8, Cialis (LY), RPBS-A[4]1
1
erectile dysfunction, see PBS
Vardenafil
For additional information see Phosphodiesterase 5
inhibitors p 527
For drug interactions see Phosphodiesterase 5
inhibitors p 924, Vardenafil p 925
Indications
Erectile dysfunction
Precautions
Prolonged QT interval or risk factors for prolonged QT
interval (p 272)—vardenafil may prolong the QT
interval and increase the risk of arrhythmia; avoid
use if risk factors cannot be corrected.
Treatment with HIV PIs or >200 mg daily of ketoconazole or itraconazole—contraindicated by the manufacturer.
Hepatic
Avoid in severe hepatic impairment (Child-Pugh
class C); reduce dose in moderate impairment
(Child-Pugh class B).
Elderly
May be unable to tolerate maximum dose of 20 mg
(increased frequency of headaches and dizziness
compared with younger patients).
Adverse effects
More common with 20 mg dose; usually transient,
mild-to-moderate and decrease with continued
use.
Common
nausea
Infrequent
abdominal pain, back pain, photosensitivity,
abnormal vision, eye pain, facial oedema,
hypertension, palpitation, tachycardia, arthralgia,
myalgia, rash, itch
Rare
hypotension, peripheral oedema, anaphylaxis
Dosage
Take 30–60 minutes before sexual activity; no more
than 1 dose daily.
Start with 10 mg; decrease dose to 5 mg or increase
to a maximum of 20 mg depending on response
and tolerability.
AMH © 2013
13.3.2 Other drugs for erectile dysfunction
With itraconazole or ketoconazole 200 mg daily or
erythromycin, limit dose to 5 mg daily.
With itraconazole or ketoconazole 400 mg daily, HIV
PIs (except ritonavir) or clarithromycin, limit dose to
2.5 mg daily.
With ritonavir, limit dose to 2.5 mg in 72 hours.
Hepatic impairment
Moderate, start with 5 mg; increase to 10 mg,
depending on response and tolerability.
Counselling
You can take vardenafil with or without food, but
if you take it with a fatty meal, it takes longer to
work.
Practice points
• the difference between a 10 mg and 20 mg dose
is most likely to be evident in those who are
more severely affected or have diabetes, nervesparing prostatectomy, or longer duration of
erectile dysfunction
tab, 5 mg, 4, Levitra (BN)
tab, 10 mg, 4, Levitra (BN), RPBS-A1
tab, 20 mg, 4, 8, Levitra (BN), RPBS-A[4]1
1
erectile dysfunction, see PBS
13.3.2 Other drugs for erectile
dysfunction
Alprostadil p 529
Papaverine p 530
Alprostadil
See also Erectile dysfunction p 526
Also known as prostaglandin E1.
Mode of action
Dilates cavernosal arteries. Relaxes smooth muscle
of corpus cavernosum and spongiosum.
Indications
13
Erectile dysfunction, treatment and diagnostic
testing
Maintenance of the patent ductus arteriosus in
neonates with congenital heart defects, until
surgery can be performed (Prostin VR®, seek
specialist advice)
Precautions
Conditions predisposing to priapism (sickle cell
anaemia, myeloma, leukaemia)—contraindicated.
Men for whom sexual intercourse is inadvisable—
contraindicated.
HIV, hepatitis B or C—bleeding at injection site may
increase risk of transmission of disease to partner.
Genitourinary
Contraindicated in patients with penile fibrosis or
penile implant.
Patients with anatomical deformation of the penis,
eg Peyronie’s disease, require urological assessment; painful erections are more likely to occur and
fibrosis may result from treatment.
Adverse effects
Common
penile pain, erection lasting 4–6 hours, fibrotic
change (may be more likely with increasing
duration of use)
529
13.4 Urinary alkalinisers and acidifiers
Infrequent
Mode of action
paroxysmal tachycardia) may occur. Manufacturer
recommends obtaining ECG before starting treatment in elderly patients.
Genitourinary
Contraindicated in patients with penile fibrosis or
penile implant.
Patients with anatomical deformation of penis, eg
Peyronie’s disease, may require urological assessment; painful erections are more likely to occur.
Hepatic
Avoid use in severe impairment.
Adverse effects
Systemic effects are rare.
Loss of penile sensation and difficulty in obtaining
an erection may occur.
Common
pain and bruising on injection, priapism, penile
fibrosis (related to injection volume >1 mL and
minimal if used with alprostadil)
Infrequent
penile pain
Rare
dizziness, tachycardia, hepatitis, allergy
Dosage
Intracavernosal injection, initially 5–15 mg; adjust up
to 60 mg according to response. Use the lowest
effective dose, which may be as low as 2.5 mg.
Usual range
30–60 mg.
Administration advice
See material available from manufacturer. The first
dose should be given by a medical practitioner and
the procedure for self-administration explained.
Counselling
Be careful when getting up from sitting or lying as
this injection may make you feel dizzy.
Tell your doctor if you have increased or new pain
in your penis, or if you notice lumps or bending of
the penis.
Practice points
• check on dosage being used and possible
development of fibrosis at regular follow-up
visits
• stop treatment if fibrosis develops
• tolerance may develop, requiring an increase in
dosage
Relaxation of all vascular components of the penile
erectile system.
inj, 12 mg/mL, 10 mL, 5, Papaverine (HS)
inj, 30 mg/mL, 1 mL, 5, Papaverine (HS)
fainting, painful erection, erection lasting >6 hours,
testicular pain, bruising, injection site reactions,
hypotension, dizziness
Dosage
Give by intracavernosal injection.
Usual range, 10–20 micrograms; maximum dose
60 micrograms. Use no more than 1 injection in
24 hours; may be used up to 3 times a week.
Erectile dysfunction of predominantly psychogenic or unknown aetiology
Initially, 2.5 micrograms; increase in increments of
2.5 micrograms according to response.
Erectile dysfunction of organic origin,
including vasculopathy
Initially, 5 micrograms; increase in increments of
5 micrograms according to response.
Adjunct in diagnosis of impotence
Initially, 2.5 micrograms; increase in increments of
2.5 micrograms.
Administration advice
See pack insert and material available from
manufacturer. The first dose should be given by a
medical practitioner and the procedure for selfadministration explained.
Counselling
Tell your doctor if you have increased or new pain
in your penis, or if you notice lumps or bending of
the penis.
Store below 25C; once solution is made use it as
soon as possible (but you can keep it in the fridge for
up to 24 hours if necessary).
Practice points
• check on dosage being used and possible
development of fibrosis at regular follow-up
visits
• stop treatment if fibrosis develops
13
www.amh.net.au
inj, 10 mcg, 0.5 mL (syringe), 2, Caverject Impulse (PF),
RPBS-A[6]1
inj, 20 mcg, 0.5 mL (syringe), 2, Caverject Impulse (PF),
RPBS-A[6]1
inj, 500 mcg/mL, 1 mL, 5, Prostin VR (PF)
1
erectile dysfunction, see PBS
Papaverine
See also Erectile dysfunction p 526
Indications
Erectile dysfunction
Precautions
Conditions predisposing to priapism (sickle cell anaemia,
myeloma, leukaemia)—contraindicated.
Men for whom sexual intercourse is inadvisable—contraindicated.
HIV, hepatitis B or C—bleeding at injection site may
increase risk of transmission of disease to partner.
Cardiovascular
Contraindicated in patients with complete atrioventricular block.
Use with caution in cardiac conduction disorders or
unstable cardiovascular disease as transient ectopic
rhythms of ventricular origin (eg premature beats,
530
13.4 Urinary alkalinisers and
acidifiers
Alkalinisation
May relieve the discomfort of UTIs, help treat
certain types of renal stones, or be used in specialist
settings to treat some metabolic and renal
disorders.
Alkalinisation is not possible if CrCl is <30 mL/
minute.
Drug choice
See Table 13–1 Urinary alkalinisers p 531
AMH © 2013
www.amh.net.au
13.6 Bladder instillations
Table 13–1 Urinary alkalinisers
Product
Ingredients
size,
Electrolyte content Pack
PBS status
sodium bicarbonate, citric acid, tartaric acid,
sodium saccharin
24.5 mmol (564 mg)
28
sodium bicarbonate, citric acid, tartaric acid
(contains sucrose 720 mg/sachet)
17.3 mmol (397 mg)
28
28.3 mmol (650 mg)
28, RPBS-R2
28 mmol (644 mg)
28, RPBS-R2
Sodium-containing1
Citralite® sachet (AV)
®
Citravescent sachet (AV)
Uracol® sachet (GM)
Ural®
sachet (AS)
Uricalm® sachet (CG)
Sodibic® capsule (AS)
sodium bicarbonate, sodium citrate, citric acid,
tartaric acid, sodium saccharin
28.3 mmol (650 mg)
28
sodium bicarbonate 840 mg
10 mmol (230 mg)
100, PBS
potassium citrate 1.08 g
10 mmol (390 mg)
100
Potassium-containing
Urocit-K® tablet (OA)
1
2
use with caution or avoid in people who require sodium restriction
for relief of urinary symptoms when antibacterial or other therapy alone is inappropriate
Combination of citric acid, tartaric acid, sodium bicarbonate and sucrose/saccharin: use 1–2 sachets in a glass
of water 3 or 4 times daily for symptomatic relief of
UTI.
Sodium bicarbonate capsules: use alone as an
alkaliniser, eg in the treatment of renal tubular
acidosis. Dose according to response (1–6 capsules
daily).
Potassium citrate: use 3–6 tablets daily in 2 or
3 doses, with or after food, to prevent calcium or
uric acid kidney stones. Avoid in people with, or at
risk of, hyperkalaemia.
Acidification
May rarely be used to increase the excretion of
lipid-soluble basic drugs, treat certain types of
renal stones, or in combination with hexamine
hippurate. Products used include ammonium
chloride and ascorbic acid. Evidence for efficacy is
limited.
Prevention
Recurrence rate is high. Increasing fluid intake (to
achieve a urine output of >2 L daily if possible) is
important in prevention. Dietary measures may
also help, eg a low-oxalate diet for those at risk of
calcium stones.
When fluid and dietary measures are ineffective,
consider drug treatment to prevent formation of
new stones or growth of existing stones; seek
specialist advice.
Allopurinol decreases urinary urate; used for uric
acid or calcium oxalate stones in people with
hyperuricosuria.
Potassium citrate increases urine pH and citrate
concentration and inhibits crystal formation; used
for uric acid or calcium stones, especially in people
with hypocitraturia.
Thiazide diuretics reduce calcium excretion; used for
calcium stones in people with hypercalciuria.
13
Effect of drugs on kidney stones
13.5 Drugs for kidney stones
Kidney stones
These are common and renal colic due to movement of a stone into the ureter is the most common
symptom: 70–80% consist of calcium oxalate
and/or calcium phosphate, with 5–10% containing
uric acid.
Treatment of acute renal colic
Relieve pain (see Renal colic p 41). For nausea and
vomiting use metoclopramide (p 491) or
prochlorperazine (p 492). Normal fluid intake is
recommended; increasing urine output through
high fluid intake is likely to increase the risk of
obstruction and worsen pain.
Up to 80% of ureteral stones <5 mm will pass
spontaneously, usually within 4 weeks. Selective
alpha-blockers (usually tamsulosin) have been
used to help passage of lower ureteral stones
<10 mm in selected patients with controlled
symptoms.
AMH © 2013
Whether ascorbic acid increases the risk of calcium
oxalate stone formation is unclear; doses >1 g daily
should be avoided.
The effect of calcium supplementation on risk of
stone recurrence is unclear; use calcium and
vitamin D supplements with caution, and take
calcium with food to bind oxalate and decrease
urinary oxalate excretion.
Carbonic anhydrase inhibitors, eg acetazolamide,
topiramate, can increase risk of calcium phosphate
stones; probenecid can increase risk of uric acid
stones.
Renally excreted drugs with low solubility at urine
pH, eg triamterene, may crystallise in the urinary
tract forming stones, especially at high doses.
13.6 Bladder instillations
Solutions of chemicals or drugs may be instilled into
the bladder for a variety of indications, including
postoperative irrigation (glycine), clot retention
(sodium chloride 0.9%), treatment of infection
(chlorhexidine), interstitial or haemorrhagic cystitis
(dimethyl sulfoxide, oxychlorosene), and the treatment of local neoplastic conditions.
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