Beruflich Dokumente
Kultur Dokumente
10
References:
1.Macdiarmid SA.Maximizing the treatment of overactive bladder in the elderly. Rev Urol. 2008 Winter;10(1):6-13. 2.Newman DK. Overactive Bladder: Diagnosis
and Treatment in Primary Care. Accessed from website http://www.medscape.org/viewarticle/571913_print as on 08.08.2013. 3.Tubaro A. Defining overactive
bladder: epidemiology and burden of disease. Urology. 2004 Dec;64(6 Suppl 1):2-6. 4.Ouslander J. Management of Overactive Bladder. N Engl J Med
2004;350:786-99. 5.Correia S, Dinis P, Lunet N. Urinary incontinence and overactive bladder- a Review. ARQUIVOS DE MEDICINA. 2009;23(1):13-21. 6.En
Meng, Wei-Yu Lin, Wei-Chia Lee et al. Pathophysiology of overactive bladder. LUTS 2012;4:48-55. 7.Hesch K. Agents for treatment of overactive bladder: a
therapeutic class review. Proc (Bayl Univ Med Cent) 2007;20(3):307314. 8.Cazzulani P, Panzarasa R, Luca C, Oliva D, Graziani G. Pharmacological studies on the
mode of action of flavoxate. Arch Int Pharmacodyn Ther. 1984;268(2):301-312. 9.Fehrmann-Zumpe P, Karbe K, Blessman G. Using flavoxate as primary
medication for patients suffering from urge symptomatology. Int Urogynecol J Pelvic Floor Dysfunct. 1999;10(2):91-95. 10.Kato S, Kusaka M, Shiroki R et al.
Clinical evaluation of supplemental administration of flavoxat hydrochloride in benign prostatic hyperplasia patients with nocturia resistant to an alpha1adrenoceptor blocker. Hinyokika Kiyo. 2008;54(3):173-177. 11.Wehnert J, Sage S. Comparative studies of the effect of mictonorm (propiverin hydrochloride) and
Spasuret (flavoxate hydrochloride) on the bladder detrusor muscle]. Z Urol Nephrol. 1989;82(5):259-263. 12.Milani R, Scalambrino S, Carrera S et al. Comparison
of flavoxate hydrochloride in daily dosages of 600 versus 1200 mg for the treatment of urgency and urge incontinence. J Int Med Res. 1988;16(3):244-248.
13.Milani R, Scalambrino S, Carrera S et al. Flavoxate hydrochloride for urinary urgency after pelvic radiotherapy: comparison of 600 mg versus 1200 mg daily
dosages. J Int Med Res. 1988;16(1):71-74.
Efficacy in patients suffering from urgency/urge incontinency and in patients with urinary urgency after pelvic
radiotherapy
In a cross over study that comprised 46 patients suffering from urgency/urge incontinency, the efficacy of flavoxate
hydrochloride in comparison to propiverin hydrochloride on the bladder detrusor muscle was evaluated. The duration of the
study was 4 weeks and the dosage was 45 mg/d for propiverin hydrochloride and 300 mg/d for flavoxate hydrochloride. The
results showed that there was a significant reduction in the frequency of micturition and an increase in compliance with both
flavoxate hydrochloride and propiverin hydrochloride. Side effects observed with both drugs were minimal and did not lead
to any disruption in the treatment.11
In a double-blind, randomized, parallel-group trial flavoxate hydrochloride was compared at a daily dosage of 600 mg to a
daily dosage of 1200 mg for the treatment of unstable bladder. Sample size of the trial was 27 patients, the trial was conducted
for a duration of 4 weeks. It was observed that both schedules showed significant results however, 1200 mg/day was found to
be more superior to 600 mg/day. Both regimens were well tolerated. The side-effects were minimal and treatment of urgency
12
and urge incontinence improved the patient's quality of life.
In a non-randomized trial, the efficacy of flavoxate hydrochloride in urinary urgency after pelvic radiotherapy was studied.
Thirty four females received flavoxate hydrochloride for duration of 4 weeks. Twenty one patients were given 600 mg/day of
flavoxate hydrochloride and 1200 mg/day of flavoxate hydrochloride was given to 13 patients. Both regimens showed
comparable results. However, treatment with 1200 mg/day showed urodynamically (first desire volume, bladder capacity and
pressure at capacity) significant results in comparison to 600 mg/day. There was no interruption in the treatment schedules as
flavoxate hydrochloride was well-tolerated by the patients.13
Indications :
For symptomatic relief of dysuria, urgency, nocturia,
suprapubic pain, frequency and incontinence as may occur in
cystitis, prostatitis, urethritis, urethrocystitis/urethrotrigonitis.
35
50
Men
30
Women
40
25
Dosage:
For Adults and children over 12 years of age:
One or two 100 mg tablets 3 or 4 times a day.
30
20
16
16.9
Prevalence* (%)
Over active bladder (OAB) is a highly prevalent disease that causes extreme discomfort to the
patient and very often there is a delay in seeking treatment. The main characteristics of OAB are
increase in frequency of micturition and urgency of passage of urine along with urge incontinence.
Although several therapeutic options exist for the management of OAB, flavoxate hydrochloride
was the first drug in this class approved by the Food and Drug Administration (FDA) to treat OAB.
Flavoxate as an anticholinergic/antispasmodic drug suppresses premature detrusor contractions
and enhances bladder storage thus relieving symptoms of OAB. Flavoxate in particular acts by
superimposition of myotropic, calcium antagonistic and local anaesthetic activity. Numerous
clinical trials have highlighted the efficacy of flavoxate in providing relief to patients suffering from
OAB. Flavoxate hydrochloride was also found to be effective in patients with benign prostatic
hyperplasia (BPH) whose nocturia was not adequately relieved by an 1-adrenoceptor blocker.
Evidence from most clinical trials suggest that flavoxate hydrochloride was well tolerated in dosage
of 600 to 1200 mg/day with minimal side effects.
Overactive bladder syndrome (OAB) is a constellation of lower urinary tract symptoms, including urinary urgency, with
or without urge incontinence, usually associated with frequency and nocturia. OAB is a chronic, debilitating condition
that affects people of all ages, although it is much more prevalent in the elderly. Overactive bladder syndrome may have a
deleterious effect on every aspect of daily life, including impaired mobility, social isolation, impaired work-related
productivity, depression, disturbed sleep, and impaired domestic and sexual function. Its negative impact is potentially
1
more pronounced in the elderly, a population already impaired by other medical comorbidities. According to a study,
OAB is equally prevalent in both men and women and is a more prevalent condition than chronic sinusitis or heart
disease. (Figure 1).2
Prevalence* (%)
Summary
20
15
10
10
5
Men
Women
<25
25-34
35-44
45-54
55-64
65-74
75
Age (years)
* Overall prevalence, with and without urge incontinence; n=5204, p = NS women vs. men
NS : Not Significant
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INTRA LABS
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Flavoxate 200mg Tablets
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Urge incontinence affects only a segment of the OAB patients: OAB with urge incontinence (OAB wet) is seen in 33% of
3
patients, while OAB without urge incontinence (OAB dry) is seen in 66% of patients suffering from OAB (Figure 2).
33%
Increasing evidence has suggested that the urothelium is not just a passive barrier, but is also is a responsive structure that is
capable of detecting thermal, mechanical and chemical stimuli. Transmitters released from the urothelium may alter the
excitability of afferent nerves and affect detrusor muscle contractility. Absence of the urothelium may cause an increase in the
6
spontaneous activity of detrusor.
parasympathetic nerve impulses induce detrusor contraction. Anticholinergic drugs have been proven to be the most
7
effective agents as they suppress premature detrusor contractions, enhance bladder storage thus relieve symptoms. It is
known that flavoxate exerts a selective and direct muscle relaxant activity. Inhibition of cyclic AMP phosphodiesterase leads
to antispasmodic properties of the drug. Flavoxate exerts a PDE inhibitory activity and shows the same local anaesthetic
activity of lidocaine. Hence, the mode of action of flavoxate can be attributed to a superimposition of myotropic, calcium
8
antagonistic and local anaesthetic activity.
Other drugs that are known to be efficacious in relieving OAB symptoms are oxybutynin and tolterodine. New drugs such as
7
darifenacin, solifenacin, and trospium have also emerged. In this review, we highlight the efficacy of Flavoxate - the first drug
that was approved by USFDA for the management of OAB.
Several clinical studies have been conducted in the past that highlight the efficacy of Flavoxate in OAB.
66%
Pathophysiology of OAB
Uroepithelial factor:
Overactive bladder (OAB) is characterized by frequency and urgency of passage of urine with or without urge
incontinence (Figure 3) . These symptoms are seen alone or in combination. The frequency of voiding urine is eight or
more times in a 24-hour period, along with nocturia (awakening two or more times at night to void). Increase in the
frequency of daytime voiding is the complaint by the patient who considers that he/she voids too often by day.
Nocturia is the complaint that the person has to get up at night one or more times to void and urgency is a sudden
compelling need to pass urine which is difficult to differ.4,5
Neurogenic factor:
Abnormal afferent
excitability
Abnormal central
sensory processing
Specific conditions
BOO
Metabolic syndrome and DM
Inflamation
Over Active
Bladder
(OAB)
Nocturia
Daytime urge
Figure 4. Possible pathophysiology of overactive bladder Ach, acetylcholine; ATP, adenosine triphosphate;
BOO, bladder outlet obstruction; DM diabetes mellitus; NGF, nerve growth factor; TRPV1, transient
receptor potential vanilloid 1.
-10
-20
Patients with OAB experience a devastating impact on quality of life, with fear of wetting accidents leading to social isolation
and depression. Patients may become increasingly reluctant to leave home, severely limiting independence and potentially
increasing their incident disability secondary to lack of physical activity. Recurrent urinary tract infections and urinary
dermatitis are more prevalent among patients with urge incontinence versus those suffering from other symptoms of OAB or
controls. The risk of falls and associated nonspine fractures is significantly increased by the presence of urge incontinence,
1
presumably occasioned by urge-motivated haste in attempting to reach the bathroom or toilet.
Urge
Incontinence
It was observed that in 89.2% of patients the residual urine volume was stable or reduced. Better results were seen in patients
who received flavoxate four times daily (800 mg), in comparison to those patients who were given flavoxate three times daily
(600 mg). Side effects occurred in less than 2% of cases.
Reduction of
Dysuria
Urgency
Frequency
Sensor molcculars,
Ach, ATP, NGF, TRPV1
Ion channel change
Myogenic factor:
Detrusor spontaneous
contraction,
hypersensitivity to
incoming signals
% values
-30
-40
-37
-50
-60
-53
-61
-70
-69
-80
Flavoxate improves nocturia and QOL in BPH patients resistant to an 1-adrenoceptor blocker
Flavoxate hydrochloride was found to be effective in patients with benign prostatic hyperplasia (BPH) whose nocturia was
not adequately relieved by an 1-adrenoceptor blocker. The study comprised 52 patients who were suffering from two or
more episodes of nocturnal micturition after administration of tamsulosin hydrochloride or naftopidil for 4 weeks or
more. These patients received 400-600 mg of flavoxate hydrochloride in addition to an 1-adrenoceptor blocker for a
period of 8-12 weeks. Following administration of flavoxate hydrochloride, there was significant improvement in the
number of nocturnal micturition, total International Prostate Symptom Score, quality of life score and BPH impact index.