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© The Canadian Journal of Urology™; 18(Supplement 1); April 2011
memory, and self-ratings of alertness -- were seen
for oxybutynin 10 mg versus placebo at Tmax (2 hrs
post-dose).
17
A study by Anderson and colleagues showed that
compared to oxybutynin, long-acting tolterodine
(tolterodine LA) had no negative impact onmemory.
18
Elderly patients are both more likely to have
OAB and to be very susceptible to the side effects
of antimuscarinics. Therefore, if an elderly patient
is prescribed an antimuscarinic drug for OAB, the
patient must be followed carefully and seen soon
after initiation of therapy, to ensure that he or she
does not sustain side effects that are “missed” or
wrongly attributed to the aging process or other
morbidities.
Antimuscarinic drugs have different side effects,
depending on their specificities for differentmuscarinic
receptors. When choosing an antimuscarinic drug to
prescribe for OAB, the physician should adopt the
“ASTEP” approach, which stands for “availability,
safety, tolerability, efficacy and preference.” The
initial drug is usually generic IR oxybutynin. This
is the required initial drug for OAB that must be
offered in provinces where non-generic, newer, long-
acting antimuscarinics are listed as limited use [LU]
drugs. If IR oxybutynin is ineffective or if the side
effects are too bothersome, only then is the physician
authorized to prescribe one of the newer, once-daily
anti-muscarinics. If that drug is ineffective or the side
effects are too great, the dose may be increased, or the
patient may be switched to another drug.
Nonmuscarinic agents
Nonmuscarinic drugs may be used alone or in
combination with an antimuscarinic drug, to treat
OAB. Desmopressin acetate, which is a synthetic
form of the anti-diuretic hormone vasopressin, is a
nonmuscarinic drug that may be used to treat OAB.
Desmopressin acetate is sometimes prescribed for
nocturnal enuresis (bedwetting) in elderly people.
Some elderly people have a decreased secretion of
antidiuretic hormone (ADH), which decreases their
ability to concentrate urine and can lead to high urine
volumes and nocturia. Desmopressin acetate may
reverse this process, but the patient’s serum sodium
levels must be carefully monitored since the drug
can cause hyponatremia. The drug is available as a
“melt” (60 mcg or 120 mcg), a tablet (0.1 mg or 0.2
mg), or nasal spray. In 2008, Health Canada issued
a warning that the desmopressin acetate nasal spray
is contraindicated in primary nocturnal enuresis,
due to risk of hyponatremia. It is now listed as “to be
used with caution,” particularly in elderly patients
who appear to be more predisposed to developing
hyponatremia.
19
The tricyclic antidepressants imipramine (Tofranil)
and amitriptyline (Elavil) are other nonmuscarinic
drugs that may be used to treat OAB. Tricyclic
antidepressants have a central sedating effect, relax
the bladder walls, and, through stimulation of
alpha-adrenergic receptors, cause tightening of the
sphincter, which may be helpful in some patients.
This combination of effects may treat the symptoms
11
TABLE 1.
Antimuscarinic agents for overactive bladder available in Canada
Generic Name
Brand Name
Dosage
First-line agents
oxybutynin IR
–
2.5 mg to 5 mg four times daily
flavoxate*
–
100 mg-200 mg three times daily
Second-line agents
tolterodine IR
Detrol
1 mg or 2 mg twice daily
tolterodine ER
Detrol LA
2 mg or 4 mg once daily
oxybutynin ER
Ditropan XL
15 mg to 30 mg once daily
oxybutynin TDS
Oxytrol
36 mg patch twice weekly
oxybutynin ER
Uromax
10 mg or 15 mg once daily
darifenacin
Enablex
7.5 mg or 15 mg once daily
solifenacin
Vesicare
5 mg or 10 mg once daily
trospium
Trosec
20 mg twice daily, on an empty stomach
ER = extended release; IR = immediate release; LA = long-acting; TDS = transdermal; XL = extended release
*flavoxate is considered to be an “antispasmotic” bladder drug and a very weak anti-cholinergic
Overactive bladder