Medical Management - UI

Urinary Incontinence - Conservative Treatments

• Conservative therapies are effective, well tolerated, safe, and preferred by many patients.
• It is generally appropriate that the least invasive treatment that takes into account patient preferences and offers a reasonable chance for success be used first.
• Although it is important to rule out serious underlying or associated conditions, invasive testing is rarely required before initiating treatment with conservative measures.

Treatments - Behavioral Therapy

• Behavioral therapy describes a group of treatments founded on the prinicpal that the incontinent patient can be educated about his or her condition and develop strategies to minimize or eliminate UI.
• Education is the core of all the behavioral therapies.
• Pelvic Muscle training - goal is improving muscle strength and control.
• Bladder diary - The largest voided volume on a diary correlates with the cystometric capacity defined by urodynamic testing
• Urge Inhibition - goal is to break the cycle of rushing to the toilet in response to urgency
• Scheduled voiding - goal is to normalize frequency
• Fluid management
• Reinforcement

The different treatment approaches are unified through education focused on normal urinary tract function.

• Pelvic floor muscle training is both a behavioral therapy (education about anatomy and function of the muscles, learning to use the muscles properly to control lower urinary tract function) and a physical therapy (strengthening the muscles to improve function).
• Bladder training starts a patient voiding on a fixed time interval schedule with the intention that the patient will urinate before experiencing urgency and UI.
• It can be used with or without medical therapy.

Patients are classified into three groups based on the assessment of pelvic floor muscle strength at baseline examination: 
(1) those with no or minimal ability to isolate and contract the levator muscles - should be offered biofeedback training and/or passive stimulation.
(2) those who can isolate the correct muscles with poor strength, and
(3) those with good pelvic floor muscle strength and isolation on the initial examination. Those with strong, coordinated muscle contractions will probably require medical or surgical therapy.

• Although surgery is the single most effective treatment for SUI there is a 40% to 50% chance that women can avoid an operation and be satisfied with the outcome by going through PFMT.
• Early surgical intervention is more appropriate for patients with significant associated prolapse (beyond the hymenal ring) that may be corrected at the same time, those who are highly motivated to be completely dry or who have high levels of physical stress due to lifestyle or occupation, those with relatively severe SUI, and especially those with good pelvic floor function on initial examination.
• Most OAB patients can benefit from multimodality therapy including bladder training, PFMT, and medical therapy.
• After appropriate evaluation, sacral neuromodulation, botulinum toxin injections, and surgical reconstruction/diversion are options for refractory OAB.
• There is a grade A recommendation that bladder training is recommended as a first line treatment of UI in women.
• There have been no adequate studies of smoking cessation on prevention or treatment of UI symptoms.
• There is evidence suggesting that decreasing caffeine intake improves continence.
• Epidemiological data support a link between consumption of carbonated beverages with UI. .
• There is evidence that weight improves continence, and the effect appears to be on both SUI and UUI symptoms.
• Weight loss should be first-line therapy for obese patients with UI, particularly SUI. However, effect of weight loss for the overweight population (BMI 25 to 30) is less clear.
• There is evidence that moderate exercise decreases the incidence of UI in middle-aged and older women.
• Although the prevalence of OAB/UUI increases with age it appears that this is due to co-morbid conditions and not aging itself.
• Combinations of conservative therapies have a level A recommendation that women with stress, urge, or mixed incontinence should be offered a conservative management program as first line therapy for UI.

Three primary pieces of information are required to develop a treatment plan for a patient with UI

• the type of UI,
• the baseline voiding diary, and
• an assessment of anatomy with particular emphasis on pelvic floor muscle strength and function.

In most cases, a clinical diagnosis of stress, urge, or mixed UI is easily made.

Antimuscarinic agents commonly used in the management of UI

• Oxybutynin IR 7.5-20 mg daily (2.5-5 mg PO tid-qid)
• Oxybutynin XL 5-30 mg daily (given once daily)
• Oxybutynin patch twice weekly
• Oxybutynin gel
• Tolterodine 2 mg twice daily
• Tolterodine LA 4 mg daily
• Darifenacin (7.5-15 mg qd)
• Solifenacin (5-10 mg qd)
• Trospium (20 mg daily to twice daily; XL qd)
• Fesoterodine

Considerations and Adverse Events

• Regardless of which antimuscarinic is used, urinary retention may develop.
• The most commonly reported adverse effects are dry mouth, constipation, headache, and blurred vision.
• Recent large meta-analyses of the most widely used antimuscarinic drugs have clearly shown these drugs provide a significant clinical benefit.
• More research is needed to decide the best drugs for first-, second-, or third-line treatment.
• None of the commonly used antimuscarinic drugs (darifenacin, fesoterodine, oxybutynin, propiverine, solifenacin, tolterodine and trospium) is an ideal first-line treatment for all OAB/DO patients.

Optimal treatment should be individualized, considering the patient’s co-morbidities, concomitant medications and the pharmacological profiles of the different drugs.

Treatments for neurogenic detrusor overactivity with UI 

• BOTOX® (onabotulinumtoxinA) has been developed as a second-line treatment option (after failure of, or intolerance to, appropriate antimuscarinic therapy) for patients with NDO with urinary incontinence or other neurogenic OAB symptoms and who are able and willing to perform clean intermittent catheterization (CIC).
• A potential adverse effect resulting from the use of onabotulinumtoxinA in patients not using CIC is an increase in post-void residual volume that may result in de novo CIC (6% to 88% of patients), with associated impact on quality of life.
• BOTOX® (onabotulinumtoxinA) is generally well tolerated. Data from a systematic review of the role of BOTOX® (onabotulinumtoxinA) in NDO indicated that the most frequent adverse events are injection site pain, procedure-related urinary tract infection, and mild hematuria.

Desmopressin 

• Desmopressin (DDVAP) was found to be well tolerated and resulted in a significant improvement in UI compared to placebo in reducing nocturnal voids and increasing the hours of undisturbed sleep. 
• Quality of life (QOL) also improved. 
• Hyponatremia is one of the main, clinically important, side-effects of DDVAP administration. 
• Hyponatremia can lead to a range of adverse events from mild headache, anorexia, nausea, and vomiting to loss of consciousness, seizures and death. 
• The risk of hyponatremia has been reported in a meta-analysis as about 7.6% (20) and seems to increase with age, cardiac disease and a high 24-hour urine volume.

References:

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• BOTOX® Prescribing Information on Detrusor Overactivity associated with a Neurologic Condition (1.1) Allergan Inc. 8/2011.
• DETROL® and DETROL® LA (tolterodine tartrate extended release capsules) Prescribing Information, Pfizer Inc. 
• DITROPAN XL® (oxybutynin chloride) Extended Release Tablets Prescribing Information, Ortho-McNeil, 7/2011.
• ENABLEX® Prescribing Information, Warner Chilcott. resourced: 4/2012. 
• GELNIQUE- oxybutynin chloride gel, Watson Pharma Inc. 3/2012.
• SANCTURA XR® (trospium chloride extended release capsules)Prescribing Information, Allegan Inc. 2011
• TOVIAZ® (fesoterodine fumarate) Prescibing Information, Pfizer Inc. 6/2011.
• OXYTROL®, oxybutynin transdermal system Prescribing Information, Watson Pharma Inc. 4/2011.
• VESICARE®, solifenacin Prescribing Information , Astellas Pharma US Inc. 1/2012.