SOLIFEN

BRIEF REFRESHER
Urinary Incontinence & Overactive Bladder
Urinary Incontinence (UI)
• Unwanted release of urine.
• Urinary incontinence isn’t a condition;
it’s a symptom. Incontinence could be
a sign of something simple like too
much fluid consumption. But, it also
can signal a more serious problem, like
a urinary tract infection (UTI).
Overactive Bladder (OAB)
• Overactive bladder (OAB) is a
condition in which the bladder can no
longer hold urine normally.
• If you have an overactive bladder, you
might often feel a sudden urge to
urinate or experience an accident.
 Incontinence

Urinary Incontinence Types

Involuntary leakage accompanied or immediately preceded by urgency, and is most

Urge Incontinence
commonly associated with overactive bladder

Involuntary leakage associated with physical activities that increase intra abdominal
Stress
pressure, such as coughing, sneezing, or laughing, or upon effort or exertion, such as
Incontinence
lifting objects or exercising.

Mixed
Involves the coexistence of urge and stress incontinence.
Incontinence
Overactive Bladder

“Overactive bladder (OAB) has been defined by

International Continence Society (ICS) as:

Urgency with or without Urge Incontinence

usually with Frequency
& Nocturia”
 Overactive Bladder (OAB)

“Urgency, with or without urge incontinence, usually with frequency & nocturia”

Symptoms
A Worldwide problem

About 50–100 million people worldwide are estimated to be

affected by overactive bladder (OAB) syndrome.

It is more common than diabetes mellitus or peptic ulcer

Similar prevalence to asthma or chronic bronchitis

2 0 0 5 B J U I N T E R N A T I O N A L | 9 5 , 8 1 – 8 5 |doi:10.1111/j.1464-410X.2005.05255.x
 A Not So Discussed Problem
Urinary Incontinence is observed as frequent health problem among women in
Pakistan 2

40% of Pakistani women face hindrance in daily life by experiencing once or more
leakages during a day 1

Overactive Bladder is perceived as part of ageing process rather than disease thus
goes untreated despite of affecting quality of life and restricting mobility of patient 3

Despite burdening billions of rupees globally, Overactive Bladder goes unrecognized

due to reluctance to seek medical attention 4

Only 15% (approx.) women consult doctors for urinary leakages

Pathophysiology Of OAB

 Bladder contraction is mediated by acetylcholine

 A neurotransmitter which acts on muscarinic receptors of

the detrusor muscle.

 Of the five known muscarinic receptor subtypes (M1–M5),

M2 and M3 receptors are found in the bladder and M3
receptors appears to be the most important for bladder
contractility.
 Diagnosis
Patients presents with symptoms
suggestive of OAB

Patient History
(past genitourinary
disorders)

Physical Examination
(inflammation, prolapse, masses)

Urine Analysis
(Urinary Tract Infections)

In The Absence of Proven Infection or other Pathologies,

Adapted from: treat as OAB
Current Opinion in Urology
Curr Opin Urol. 2005 Jul;15(4):222-6.
Medical Therapy

The recommendation for first-line medical treatment of OAB is the use of

Anticholinergic Drugs
Older Agents-Conventional
Newer Agents Others
Agents
Flavoxate Solifenacin Imipramine
Oxybutynin Darifenacin Estrogens
Tolterodine Trospium
Fesoteridone
Propeverine
 Medical Therapy

• Antimuscarinic agents block the muscarinic receptors that are found in the
urinary bladder muscles and prevent Acetylcholine binding to muscarinic
Receptors.

• Thus antimuscarinics relax the urinary bladder muscle and ultimately reduce:

• The premature contraction of urinary bladder

• Thus making the filling normal and relieve symptoms of urgency, frequency, nocturia &
urinary leakage.
 Mode of Action

Muscarinic receptors play an important role in contractions of urinary bladder smooth

muscle

Solifenacin is a competitive inhibitor of the muscarinic M3 subtype receptor and

prevents Ach. to bind with M3 receptors, preventing contraction of the detrusor
smooth muscle

14
 Effective Bladder Control
80% 75.20%
% Mean improvement from base line

70% 64.60%
60% 52.90%
50%
41.80%
40%
30%
20% 15.60%
12.30%
10%
0%
Urgency Incontinence Frequency
Solifenacin Placebo

Solifenacin (Solifen) shows significant improvement in key symptoms of overactive

bladder UROLOGY 73: 14 –18, 2009
 Significant reduction in Urinary Symptoms versus Tolterodine
Micturition Urgency Urge
Frequency Episodes Incontinence Incontinence Nocturia
0
Mean change from base line

-0.5 -0.4
-0.5

-1 -0.9 -0.9

-1.2
-1.3
-1.5
-1.5
-1.7 -1.7 Solifenacin 5mg
-2
-2 Tolterodine ER 4mg

Solifenacin 5mg provided 44% additional improvement in resolving OAB symptoms as compared to
Tolterodine ER
 4mg
European Urology, Volume 52 Issue 4, October 2007, Pages 1195-1203
 COMPARISON OF SOLIFENACIN 5 MG AND TOLTERODINE ER 4 MG IN THE STAR OAB STUDY
A Better Treatment Option than Flavoxate

Recommends NOT to use Flavoxate for Urinary Incontinence or Overactive Bladder

treatment in women

Solifenacin Flavoxate
Anti muscarinic Drug with mixed action
Level of evidence for OAB
management
1 (Randomized control clinical trials) 4 (Case studies)
Grade of recommendation A (Highly recommended) D (Not recommended)
Dose frequency O.D. T.i.d.

Based on meta-analysis findings and OD dose benefit Solifenacin has strong evidence and level of
recommendation as a treatment option in Overactive

Bladder management than Flavoxate.
NICE. Urinary incontinence in women pathway, 11 Oct 2016
 Chapple C. The contemporary pharmacological management of overactive bladder. BJOG 2006;113(Suppl. 2):19–28
 Drugs.com
Pharmacokinetic Profile Of Anticholinergics

Molecule Flavoxate Oxybutynin Solifenacin Tolterodine

Bioavailability N/A 6% 90% 77%

Excretion-Renal 57% <0.1% 3%–6% 77%

Product Profile

Tmax 3-8 hours

Bioavailability Approximately 90%
Plasma protein binding 98% principally to ∝1-acid glycoprotein

Distribution To non-CNS tissues, having a mean steady-state volume of distribution of

600L
Excretion 69.2% Urine & 22.5% Feces
Half-life 45-68 hours
Pregnancy & Breastfeeding Category “C” – Should not be administered to nursing mothers

Adverse Effects Dry mouth & Constipation

Solifenacin may be administered without regard to meals