Drugs in Perspective: Oxytrol goes over-the-counter

Introduction

Antimuscarinic drugs are an option in the treatment of overactive bladder which is defined as urinary urgency with or without urge incontinence, usually accompanied by frequency and nocturia, in the absence of a urinary tract infection or other obvious pathology.¹

Oral oxybutynin has been available by prescription for over 40 years, initially marketed as Ditropan and Ditropan XL although now generically available, in addition to the transdermal patch Oxytrol and transdermal gel Gelnique. As an antagonist at muscarinic receptors, oxybutynin leads to relaxation of the smooth muscle of the bladder which leads to increased bladder capacity, decreased involuntary contractions and decreased urgency and frequency of both voluntary and incontinent episodes.² The suggested dose is 1 patch applied for 4 consecutive days, after which the patch should be removed and a new patch applied.

Relevance

Although the Oxytrol transdermal patch has been available as a prescription product since 2003, in January 2013 FDA approved Oxytrol for Women as an over-the-counter (OTC) product indicated for the treatment of overactive bladder in women ages 18 years and older.³ This represents the first OTC product for this indication, allowing women to take self-care measures to treat overactive bladder. However, given this change in drug status, there are important implications for patient safety and medication therapy management that deserve attention.

Studies

At least 2 trials have evaluated the safety and efficacy of oxybutynin transdermal patch delivering a dose of 3.9 mg/day versus placebo or versus tolteridone LA. Both trials evaluated similar populations of patient with overactive bladder and urge incontinence or mixed incontinence.^4,5 The change in incontinent episodes from baseline to 12 weeks was significantly greater in the oxybutynin group compared to placebo (-19 vs -14.5, P=.0165). There was also a significant decreased in average daily urinary frequency in the oxybutynin group compared to placebo (-2.3±2.5 vs -1.7±3.0, P=.0457).⁴ In the second trial, the change from baseline to week 12 in median number of daily incontinent episodes was significantly greater in the oxybutynin group compared to placebo (-3 versus -2, P=.0137).⁵ In this trial, tolteridone LA 4 mg daily was also used as a comparator and similar results were observed compared to placebo, although there was no significant difference found comparing oxybutynin to tolteridone LA. The most common adverse reaction to the transdermal patch is pruritus which was reported in up to 16.8% of patients in the placebo-controlled trial above, compared to 6% in placebo patients. Additional common side effects in the trial of oxybutynin compared to placebo include dry mouth (9.6% vs 8.3%), dizziness (4.0% vs 3.8%), and dysuria (2.4% vs 0%). In the trial comparing oxybutynin patch to tolteridone LA, more adverse events occurred in the tolteridone group (29 vs 23); incidence of common side effects of dry mouth and constipation were comparable. 

Potential advantages and disadvantages

Oxytrol for Women, being the only drug OTC for treating overactive bladder, increases convenience for patients who may not have medical access. However, there are multiple causes or contributing factors to overactive bladder therefore not all patients are suitable candidate for self-care. The regimen is also advantageous, dosed as 1 patch every 4 consecutive days, as opposed to taken orally daily like many other agents within the class. Practice guidelines from the American Urological Association (AUA) state that there is no compelling evidence to select one antimuscarinic agent over another based on efficacy.⁶ However, they caution that oxybutynin is likely to have greater incidence of dry mouth and/or constipation compared to tolteridone based on pooled data. Using a longer-acting preparation such as Oxytrol patch is likely to reduce the chance of adverse events compared to the immediate release formulation.

Cost

Prescription Oxytrol patches cost significantly more than the OTC version. The average wholesale price for 8 Oxytrol prescription patches is $320.32⁷ while according to www.drugstore.com a box of 8 OTC patches costs $29.99.

Place in therapy

AUA recommends behavioral interventions as the first-line treatment for overactive bladder such as bladder training, pelvic floor exercises, and fluid management.⁶ Oral antimuscarinics, such as oxybutynin, are considered second-line treatment options. However, when selecting between agents, the guidelines suggest choosing a long-acting agent over an immediate-release agents due to lower incidence of dry mouth, since this is the most common reason they cite for nonadherence to therapy. Oxytrol patches are one such option of a longer-acting agent. If patients inadequately respond to one anticholinergic agent, the dose can be changed or another agent can be tried.

Implications

The OTC availability of Oxytrol has significant implications on patient safety and pharmacist counseling. There is a long list of possible causes of the symptoms one may experience due to overactive bladder, and self-care is not always an appropriate means to treating those underlying conditions. The OTC labeling specifically recommends that the following patients refrain from OTC use of the drug: Presence of pain or burning upon urination, blood in urine, unexplained lower back or side pain, and cloudy or fowl smelling urine. Individual who should not use this product include those under aged 18 years; patients in which the only accidental urine loss experienced is upon sneezing, laughing, or coughing; diagnosis of urinary or gastric retention, glaucoma, or hypersensitivity to oxybutynin; and men.⁴ It is important for pharmacists to reinforce these contraindications to self-care since more urgent conditions, such as a urinary tract infection or pyelonephritis, or those that are not indicated for treatment with oxybutynin, such as stress incontinence, may be present. In addition, efficacy and safety data is based on a population of patients with some degree of urge incontinence, which not all patients with overactive bladder will have. Therefore appropriate screening of patients who will maximally benefit from Oxytrol for Women is a role for the pharmacist. Patients in clinical trials were also instructed to follow non-pharmacologic interventions including timed urination, pelvic floor exercises, and fluid management. Therefore, to appreciate the benefit on the given outcomes, a patient who chooses to use Oxytrol OTC should be counseled to participate in such interventions regularly.

Additional counseling points include proper patch application. Patients should apply the patch to a clean, dry, smooth area of the skin on the abdomen, buttocks, or hips. The patch should be worn under clothes and not exposed to sunlight, and not cut into smaller pieces. With each new application, patients should rotate the spot the patch is applied. If the patch falls off and a patient cannot stick it back in place, a new patch should be applied to a new location.⁸ Finally, patients should be informed that the patch should be efficacious within 2 weeks, so that they have realistic expectations and allow a sufficient duration of time for efficacy.⁸

The ever-expanding selection of OTC products reminds us of the importance of asking patients about OTC product use when evaluating their drug profile and while conducting medication therapy management. There may be important duplications of therapy if a prescriber was unaware of a patient’s use of OTC Oxytrol, which could lead to increased adverse events. There are also many other drugs with anticholinergic side effects which could be additive if used along with Oxytrol for Women. Pharmacists are also reminded of the importance of asking patients about their past medical history to assess appropriateness of drug therapy selection. Some existing conditions could be contraindications to use as listed above. 

References

1. Ouslander JG. Management of overactive bladder. NEJM 2004; 350:786-799.

2. Oxybutynin. Micromedex 2.0, (electronic version). Truven Health Analytics, Greenwood Village, Colorado, USA. Available at: http://www.micromedexsolutions.com/ (November 20, 2013).

3. FDA. FDA approves over-the-counter Oxytrol for women to treat overactive bladder. Available at: http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm336815.htm Accessed November 20, 2013.

4. Dmochowski RR, Davila GW, Zinner NR, et al. Efficacy and safety of transdermal oxybutynin in patients with urge and mixed urinary incontinence. J Urol. 2002;168:580-586.

5. Dmochowski RR, Sand PK, Zinner NR, et al. Comparative efficacy and safety of transdermal oxybutynin and oral tolterodine versus placebo in previously treated patients with urge and mixed urinary incontinence. Urology. 2003;62:237-242.

6. Diagnosis and treatment of overactive bladder (non-neurogenic)in adults: AUA/SUFU Guidelines. American Urological Association. Available at: http://www.auanet.org/common/pdf/education/clinical-guidance/Overactive-Bladder.pdf Accessed December 10, 2013.

7. In brief: oxytrol OTC. The Medical Letter Online. Available at: http://secure.medicalletter.org/w1425c. Accessed December 10, 2013.

8. Oxytrol for Women. Available at: http://www.oxytrolforwomen.com/. Accessed December 10, 2013.