oxybutynin - Ditropan

Oxybutynin is a highly effective anticholinergic drug suitable for the treatment of overactive bladder syndrome.

Oxybutynin is the generic name for this drug.

Dose: 5mg bd or tds (x2 or x3 daily) Max 20mg per day

Oxybutynin is produced by

  • Sanofi-Aventis - Ditropan 2.5mg and 5mg tablets

  • Recordati - Kentera - patch - applied twice weekly

  • Jansen-Cilag - Lyrinel XL 5mg and 10 mg tablets

NICE Guidelines on the management of overactive bladder syndrome - oxybutynin States

"Immediate release non-proprietary oxybutynin should be offered to women with over active bladder (OAB) or mixed urinary incontinence (UI) as first-line drug treatment if bladder training has been ineffective. If immediate release oxybutynin is not well tolerated, darifenacin, solifenacin, tolterodine trospium, or an extended release or transdermal formulation of oxybutynin should be considered as alternatives."

Definition and Symptoms of Overactive Bladder Syndrome

Overactive bladder syndrome (OBS) is characterised by:

  • urgency, with or without urge incontinence,
  • increased Frequency of micturition (>8 voids/day) and
  • nocturia (passing urine during the night) in the absence of another identifiable metabolic or pathological process affecting the lower urinary tract.

Pictures of oxybutynin and Ditropan

 

Prevalence of Overactive Bladder Syndrome

Overactive bladder symptoms in individuals aged >/= 40 years was 16.6% (one person in 6). Frequency (85%) was the most commonly reported symptom, followed by urgency (54%) and urge incontinence (36%). The prevalence of overactive bladder symptoms increased with advancing age. Overall, 60% of respondents with symptoms had consulted a doctor but only 27% were currently receiving treatment.0101

Treatment of Overactive Bladder Syndrome


Treatment options are

  • patient education
  • bladder training
  • pelvic floor exercises
  • medication.

Anticholinergic drugs remain the only commonly prescribed drugs.

Anticholinergic (antimuscarinic) drugs


Medication for Overactive bladder syndrome is based on inhibiting the action of acetylcholine, which stimulates detrusor contraction via muscarinic receptors.

Five subtypes of muscarinic receptors within the parasympathetic system have been identified.

Inhibition of these receptors in the brain disrupts cognitive functions such as learning and memory. This may be a particular problem when these drugs are used in the elderly who may already have a degree of confusion.

Non-selective anticholinergics also interfere with muscarinic function in other organ systems such as the eye and salivary glands resulting in dry eyes and a dry mouth.

Most anticholinergics relieve symptoms and have similar efficacy.0302

Adverse effects vary depending on receptor selectivity, peak serum levels and the route of delivery.

Selectivity of anticholinergics.

Oxybutynin (Ditropan)


In the study by Cardozo and her colleagues, treatment with oxybutynin 5 mg and 10 mg once daily significantly improved all the major symptoms of overactive bladder including Frequency, urgency and incontinence. Oxybutynin 10 mg also decreased the Frequency of nocturia. Oxybutynin therapy was associated with a favorable tolerability profile and a low incidence of dry mouth, especially at the 5 mg starting dose.0403 oxybutynin 5 and 10 mg once daily improved urgency and other symptoms of OAB, and was associated with an acceptable level of anticholinergic side-effects. Oxybutynin demonstrated significantly favourable efficacy to side-effect ratio in treating symptomatic overactive bladder.0404

The STAR trial0702 was a prospective, double blind study comparing 5 mg of oxybutynin with 4 mg of tolterodine ER. Within 4 weeks oxybutynin 5mg was statistically significantly better than tolterodine ER 4 mg in improving incontinence and reducing incontinence pad use. Differences in efficacy in favour of oxybutynin 5 mg were maintained from 4 weeks for the duration of the study for patients choosing to remain on their starting dose.

 

Adverse effects of anticholinergics


The most common adverse effect is dry mouth, with a prevalence of about 30%. Oxybutynin IR is associated with more severe and frequent dry mouth episodes compared with other preparations, while tolterodine ER seems to have the best tolerability profile.

Other adverse effects include:

  • constipation,
  • blurred vision,
  • nausea and vomiting,
  • difficulty in micturition,
  • palpitations,
  • skin reactions,
  • angioedema,
  • arrhythmias and tachycardia.

Effects on the central nervous system (CNS) such as disorientation, hallucination and convulsion can also occur.

Anticholinergics may reduce sweating, leading to hyperthermia and fainting in hot environments.

Cautions

Antimuscarinic drugs require caution in women with autonomic neuropathy, hiatus hernia and hepatic and renal impairment.

They can worsen hyperthyroidism, coronary artery disease, congestive heart failure and arrhythmias.

Contraindications

Myasthenia gravis, glaucoma, significant bladder outflow obstruction or urinary retention, severe ulcerative colitis and gastrointestinal obstruction are contraindications to anticholinergic use.

The role of immediate release and extended release preparations

In a Cochrane Review, Hay-Smith, et al.34 concluded that there were no statistically significant differences for cure/improvement, leakage episodes or micturition Frequency in 24 hours between ER and IR regimens although the numbers in the study were low.

Overall, ER preparations are associated withfewer adverse effects, particularly dry mouth, and may thus be preferable, although the discontinuation rates caused by adverse events were similar between the two formulations. In the current economic climate cost may be a factor in deciding between ER and IR preparations.

The use of anticholinergics in nocturia

Nocturia is a common and troublesome symptom which can be caused by medical conditions such as renal failure, hypercalcaemia and diabetes. Desmopressin, an analogue of antidiuretic hormone, is effective. It can, however, cause fluid overload and hyponatraemia.8 Imipramine, a tricyclic antidepressant with anticholinergic effects, is beneficial.

Anticholinergic use in the elderly

It is worrying that up to 32% of the elderly use two or more drugs with anticholinergic effects. Those that spare M1 receptors have a lower impact on central nervous system function. The extent to which anticholinergics impair CNS function is proportional to their ability to cross the blood´┐Żbrain barrier. Oxybutynin is the one most likely to cross the blood´┐Żbrain barrier. Despite this, it is still widely used to treat overactive bladder syndrome in older patients because of the low cost.

Agents such as tolterodine and darifenacin have low lipophilicity and are thought to be more suitable for older patients. Tolterodine IR and oxybutynin IR have a similar efficacy but the former has fewer adverse effects in patients over 50 years of age. Trospium is the least likely to impair CNS function based on neuropsychological and coordination tests.When considering use of an antimuscarinic agent for the treatment of overactive bladder syndrome in elderly patients, prescribers should routinely consider the agent's receptor selectivity and ability to cross the BBB. The medical history should include all current medications that may contribute to the anticholinergic burden and cognitive impairment.0502

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