FroCan Bladder Anticholinergics Be Used Long Term? Question
What are the concerns related to using long-acting or extended-release anticholinergic agents over long time
periods? Are other medications available that would better ameliorate urinary incontinence?
Response from Karen Shapiro, PharmD, BCPS Clinical Pharmacist, Arcadian Health Plan, San Dimas, California
Bladder anticholinergic agents tolterodine and oxybutynin work by blocking the binding of acetylcholine at
bladder muscarinic receptors. Acetylcholine stimulates muscarinic receptors, resulting in contraction of the
bladder detrusor muscle and a sudden urge to urinateBladder anticholinergics are used both short and long
term, but many studies have found high rates of patient discontinuatiWith longer use, the discontinuation
rate increasesThe reasons for discontinuation require further investigatibut may be related to side
effects or cosClinicians should consider these factors in addition to advanced age, comorbidities, and
potential drug-drug interactions when prescribing long-term bladder anticholinergics for their patients.
Anticholinergic side effects are common with these agents and include dry mouth, constipation, headache, and
blurred vision. Clinicians should ensure that patients are counseled regarding measures to prevent or relieve
A primary concern with long-term use of bladder anticholinergics is their effect on cognitive function, which
typically declines with age and with neurologic disease such as dementia. Concurrent use of drugs such as the
bladder anticholinergics can intensify this decline. Regrettably, the cholinesterase inhibitors (CIs) used to treat
dementia can also worsen incontinencrequiring treatment with both classes of drugsA recent study
showed a more rapid functional decline in higher-functioning dementia patients taking both a CI, such as
donepezil, with oxybutynin or tolterodine vs those taking a CI al
In addition, drug-drug interactions may occur with the anticholinergic agents. When entering a prescription for
an anticholinergic agent for urinary incontinence, the medication profile should be scanned for drugs with
anticholinergic properties that the patient is already taking. These include benzodiazepines, psychiatric agents
(including antipsychotics, hypnotics, and normal-to-high doses of tricyclic antidepressants), skeletal muscle
relaxants, antihistamines, and anticonvulsants. In addition, the profile should be screened for agents that cause
constipation (such as opioid analgesics, verapamil, and iron supplements) and agents required for volume
control (such as diuretics) that could possibly be reduced or discontinued. When this is not possible, the risk for
additive side effects should be evaluated. Centrally acting anticholinergics (such as benztropine and
trihexyphenidyl) are sometimes used for psychiatric conditions and to treat early (tremor-predominant)
Parkinson's disease, except in the elderly, for whom they are considered "do-not-use" drugs. Using an
anticholinergic approved for incontinence along with one of the centrally acting agents would be considered
polypharmacy and present an unreasonable risk to the patient.
With long-term use, changes in the patient's organ function may necessitate a dose adjustment of the bladder
anticholinergic agent. For example, the maximum recommended dose of tolterodine is 2 mg/day in the
presence of significant hepatic or renal dysfunctiThe clinician should monitor hepatic and renal function
Immediate-release oxybutynin is available as a generic product and is a frequent choice of formularies. The
longer-acting oral formulation of oxybutynin (Ditropan XL®, often included in formularies) and the transdermal
patch (Oxytrol®, Ortho-McNeil Pharmaceutical, Inc., Titusville, New Jersey) have simpler dosing regimens and
cause fewer side effectsThe flip side is that they are more expensive. The longer-acting formulation of
tolterodine (Detrol® LA, Pfizer, New York, NY) has fewer side effects than the shorter-acting versibut
pricing is not much different. Generic tolterodine will not be available in the United States until at least 2012.
Three new anticholinergics, solifenacin, darifenacin, and trospium, have different side effect profiles and may
be alternatives to tolterodine and oxybutynin. The M3 receptor-specific agents, darifenacin and solifenacin, may
have the least effect on cognitive function. Unfortunately, the M3 receptor is also prevalent in the mouth and
gut wall, which is why dry mouth and constipation remain side effects. Darifenacin is contraindicated in the
presence of severe constipation, ulcerative colitis, and myasthenia grav
There are no other drug classes for the treatment of urinary incontinence. Pelvic floor muscle training is often
recommended for the management of incontinence. Some women will improve with pelvic exercise alone;
others require both drugs and exercises to control urge incontinence. Pelvic floor exercises are easy to do the
wrong way. Patients must be instructed to perform these exercises with proper technique. The Mayo Clinic
Websihas simple instructions for both exercises and bladder training, which may also be helpful. Scheduled
toilet trips, every 2-4 hours, can reduce incontinence episodes. Avoiding acidic foods, which can cause bladder
irritation, and reducing caffeine and alcohol intake may also help.
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