Leeds Overactive Bladder Medicine Treatment Pathway

• Which patients should be initiated on the overactive bladder (OAB) medication pathway?
• General Principles when using OAB drugs
• Contraindications to Antimuscarinic
• Contraindication to Mirabegron
• Additional drug info can be located at
• First line Antimuscarinic drug treatment
• Second line drug treatment
• What constitutes treatment failure? – Always consider referral to secondary care after treatment failure
• What is Mirabegron?
• Which patients should be commenced on Mirabegron?
• Patients not suitable for mirabegron - consider for referral to Urology/Urogynecology
• Summary of Side effects profile for overactive bladder medications
  • Antimuscarinics
  • Beta 3-adrenoceptor agonist (Mirabegron)

Which patients should be initiated on the overactive bladder (OAB) medication pathway?

This pathway is for patients who have failed conservative management for their overactive bladder symptoms. This includes trials of both lifestyle interventions and physical therapies. Patients should have undergone at least 3 months of conservative management prior to the initiation of drug therapy

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General Principles when using OAB drugs

Before treatment starts discuss

• The likelihood of success and common adverse effects including cognitive impairment
• The frequency and route of administration
• Adverse effects such as dry mouth and constipation may indicate that treatment is starting to have an effect.
• That they may not see the full benefits until they have taken the treatment for at least 4 weeks
• the long-term effects of anticholinergic medicines for overactive bladder on cognitive function are uncertain

Do not use Flavoxate, Propantheline or Imipramine for treatment of urinary incontinence or overactive bladder in women.

Do not offer oxybutynin (immediate release) to older women who may be at higher risk of a sudden deterioration in their physical or mental health.

If the first medicine for overactive bladder or mixed urinary incontinence is not effective or well-tolerated, offer another medicine with a low acquisition cost.

Offer a transdermal overactive bladder treatment to women unable to tolerate oral medicines.

The use of Desmopressin may be considered specifically to reduce nocturia in women with urinary incontinence or overactive bladder who find it a troublesome symptom. Use particular caution in women with cystic fibrosis and avoid in those over 65 years with cardiovascular disease or hypertension.

Noqdirna® (Desmopressin Oral lyophilisate): Prescribing GuidanceFor the symptomatic treatment of nocturia due to idiopathic nocturnal polyuria in adults

Do not offer systemic hormone replacement therapy to treat urinary incontinence.

Offer intravaginal oestrogens to treat overactive bladder symptoms in postmenopausal women with vaginal atrophy.

Use caution when prescribing antimuscarinics for patients with Alzheimer’s

Take into account coexisting conditions (such as poor bladder emptying, cognitive impairment or dementia), the use of other existing medication affecting the total anticholinergic load and the risk of adverse effects (For anticholinergic profile of commonly prescribed drugs see https://bmcgeriatr.biomedcentral.com/articles/10.1186/s12877-015-0029-9)

Anticholinergic burden should be considered at every stage

Total anticholinergic burden can be estimated using online calculators such as ACB Calculator or Medichec amongst others. Different calculators give different scores and there is no internationally recognised and approved ACB calculator. These can be useful to help guide treatment decisions but should not be used as absolutes as individual patient context and wishes are important considerations. Generally, the higher the overall anticholinergic burden score, the more likely anticholinergic side effects are and as a rough guide a score of 3 or more is associated with increased mortality.

Offer a face-to-face or telephone review 4 weeks after starting a new medicine for overactive bladder. Ask the woman if she is satisfied with the treatment and:

• If improvement is optimal, continue treatment
• If there is no or suboptimal improvement, or intolerable adverse effects, change the dose or try an alternative medicine for overactive bladder and review again 4 weeks later.

Offer a review before 4 weeks if the adverse events of a medicine for overactive bladder are intolerable.

Offer a further face-to-face or telephone review if a medicine for overactive bladder or urinary incontinence stops working after an initial successful 4-week review.

Offer a review in primary care to women who remain on long-term medicine for overactive bladder or urinary incontinence every 12 months, or every 6 months if they are aged over 75.

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Contraindications to Antimuscarinic

Angle closure glaucoma
Myasthenia gravis
Severe ulcerative colitis
Intestinal obstruction
Toxic megacolon

Contraindication to Mirabegron

Uncontrolled hypertension systolic BP≥180mmHg and /diastolic ≥110mmHg

Additional drug info can be located at:

http://www.leedsformulary.nhs.uk/
http://www.medicines.org.uk/emc/
http://www.nice.org.uk/cg97
http://guidance.nice.org.uk/CG171
https://www.gov.uk/drug-safety-update/mirabegron-betmiga-risk-of-severe-hypertension-and-associated-cerebrovascular-and-cardiac-events

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First line Antimuscarinic drug treatment

Offer solifenacin 5-10mg OD for OAB or mixed urinary incontinence

If the first dose of 5mg is ineffective consider an increase to 10mg at the review at 4 weeks.

Second line drug treatment

Mirabegron 50mg OD

Patients considered not be candidate for NICE recommended first line treatment or failed first line treatment, can be initiated on mirabegron in line with NICE TA290 - ‘Mirabegron is recommended as an option for treating the symptoms of overactive bladder only for people in whom antimuscarinic drugs are contraindicated or clinically ineffective, or have unacceptable side effects.’

What constitutes treatment failure? – Always consider referral to secondary care after treatment failure

• Unsatisfactory reduction in number or 24 hour voids
• Unsatisfactory reduction in number of episodes of frequency, urgency, and urge incontinence
• Intolerable side effects
• Unsatisfactory improvement in patient’s quality of life

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What is Mirabegron?

Mirabegron is a B3 adrenoceptor agonist, which activates B3 adrenoceptors causing the bladder to relax which helps it to fill and store urine.

 http://guidance.nice.org.uk/TA290

Which patients should be commenced on Mirabegron?

Mirabegron is recommended as an option for treating the symptoms of overactive bladder for people in whom antimuscarinic drugs are contraindicated or clinically ineffective, or have unacceptable side effects.

Mirabegron is also recommended when the risk of anticholinergic burden (ACB) outweighs the expected benefit of starting OAB anticholinergic therapy Offer referral to secondary care if the patient does not want to try another drug but would like to consider further treatment

Mirabegron dose needs to be adjusted in patients with renal or hepatic impairment (Check BNF for the appropriate dose before prescribing)

Patients not suitable for mirabegron - consider for referral to Urology/Urogynecology

• Patients with severe renal impairment (eGFR 15 to 29 mL/min/1.73 m2) concomitantly receiving strong CYP3A inhibitors
• patients with severe hepatic impairment (Child-Pugh Class C) or patients with moderate hepatic impairment (Child-Pugh B) concomitantly receiving strong CYP3A inhibitors
• Patients with severe uncontrolled hypertension (SBP ≥ 180 mm Hg and/or DBP ≥ 110 mm Hg). Data is limited in patients with stage 2 Hypertension (SBP ≥ 160mmHg or DBP ≥ 100mmHg). Mirabegron can increase blood pressure therefore blood pressure should be monitored at baseline and periodically.
• Caution use in patients with a known history of QT prolongation or in patients who are taking medications which are known to prolong the QT interval.

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Summary of Side effects profile for overactive bladder medications

Antimuscarinics

• Dry mouth/eyes
• Blurred vision
• Urinary retention
• Constipation

Beta 3-adrenoceptor agonist (Mirabegron)

• Urinary tract infection
• Tachycardia

Anticholinergic medicines also have other important adverse effects in older people including physical impairment, falls and are associated with increased mortality (Ref: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8605959/ )
There is also a possible association between anticholinergics and cognitive impairment but causation has not been proved (Ref: https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD013540.pub2/full and associated commentary https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.ED000154/full)

For additional information see SPC (http://www.medicines.org.uk/emc/)

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