Treatment of the symptoms [ increased urinary frequency and/or urgency and/or urgency incontinence ]
that may occur in adult patients with overactive bladder syndrome.
fesoterodine fumarate
regain control
Urinary urgency
UUI*
(1)
-80%
fesoterodine fumarate
Urgency episodes**
(2)
-45.5% 2 out of 3 patients 1. Chapple C. et al. BJU Int. 2014;114:418-26. 2. Kaplan S.A. et al. BJU Int. 2010;107:1432-1440. 3. Herschom S. et al. BJU Int. 2010;105(1):58-66. * With Toviaz® 8 mg vs BL at Week 12. **Urgency episodes/24 hrs with Toviaz® 4 mg or 8 mg vs BL at Week 12. ***With Toviaz® 8 mg vs BL at Week 12. † 2 out of 3 patients corresponds to 64% of patients who were ‘dry’ with Toviaz® at Week 12. ‡ Diary-dry rate: proportion of patients with > 0 UUI episodes on baseline 3-day bladder diaries who reported 0 UUI episodes on post-baseline diary.
†
are ’dry’ ‡***(3)
at Week 12 (post-hoc analysis)
The recommended starting dose of Toviaz® is 4 mg once daily. Based on individual response, the dose may be increased to 8 mg once daily. Please see the Toviaz® SmPC for dosing guidance. STUDY Information
pharmacological profile
Efficacy on OAB symptoms(1)
WELL BALANCED M2 / M3 Affinity(1)
Limited BLOOD-BRAIN BARRIER CROSSING(2,5)
No significant effect on cognitive function confirmed in clinical trials(3,4,5)*
efficacy/ tolerability ratio
Limited interindividual variability(7,8)
NO 1st PASS HEPATIC metabolism(7)
PROLONGED RELEASE FORMULATION(6)
Once-a-day formulation(6)
*vs Placebo. 1. Cardozo L. et al. BJU Int. 2010;106:816-821. 2. Kerdraon J. et al. Progrès en urologie. 2014;24:672-681. 3. Wagg A. et al. J Am Geriar Soc. 2013;61:185-93. 4. Dubeau CE. et al. J Urol. 2014;191(2):395-404. 5. Kay G.G. et al. Postgrad Med. 2012. 6. Pfizer. Summary of Product Characteristics - Toviaz® (Fesoterodine). 7. García-Baquero R. Actas Urol Esp. 2013;37(2):83-91. 8. Khullar V. et al. Urology. 2008;71:839–843.
STUDY Information
M2 & M3 Receptors fesoterodine fumarate
Balanced M2 / M3 Affinity(3) Detrusor muscle
M2 & M3 receptors predominant in the detrusor muscle (1,2)
Stimulation of M3 receptors by ACh
Contraction
Stimulation of M2 receptors by ACh
Relaxation
Adapted from Chapple C.R. UROLOG Y 55 (Supplement 5A). May 2002.
The recommended starting dose of Toviaz® is 4 mg once daily. Based on individual response, the dose may be increased to 8 mg once daily. Please see the Toviaz® SmPC for full guidance.* * Pfizer. Summary of Product Characteristics - Toviaz® (Fesoterodine). 1. Chapple C.R. UROLOGY 55 (Supplement 5A). May 2002. 2. ABRAMS P. et al. British Journal of Pharmacology. 2006;148:565–578. 3. Cardozo L. et al. BJU Int. 2010;106:816-821.
Blood-brain barrier fesoterodine fumarate
fesoterodine fumarate
No significant effect on cognitive function confirmed in clinical trials (3,4,5)*
lipophilicity (1) P-gp substrate (2)
Adapted from Abbott NJ. et al. Nat Rev Neurosci. 2006;7(1):41-53.
The recommended starting dose of Toviaz® is 4 mg once daily. Based on individual response, the dose may be increased to 8 mg once daily. Please see the Toviaz® SmPC for full guidance.** *vs Placebo. **Pfizer. Summary of Product Characteristics - Toviaz® (Fesoterodine). 1. Kerdraon J. et al. Prog Urol. 2014;24(11):672-81. 2. Chancellor MB. et al. Drugs Aging. 2012 1;29(4):259-73. 3. Wagg A. et al. J Am Geriar Soc. 2013;61:185-93. 4. Dubeau CE. et al. J Urol. 2014;191(2):395-404. 5. Kay GG. et al. Postgrad Med. 2012;124(3):7-15.
Tolterodine & Fesoterodine metabolism fesoterodine fumarate
Prodrugs**
Tolterodine
fesoterodine fumarate
Extensive metabolism by hepatic CYP2D6 (1)
Rapid and extensive hydrolysis by ubiquitous plasma esterases (1)
Tolterodine conversion to 5-HMT depends on CYP2D6 expression and activity in patients (1)
The mechanism for converting tolterodine is more complex and less predictable Inter-individual variability in plasma concentration ratio of tolterodine and 5-HMT after tolterodine intake (1)
Conversion to 5-HMT without involving liver cytochrome (1)
Unmetabolised tolterodine Low inter-individual variability (1)
5-HMT
The recommended starting dose of ToviazÂŽ is 4 mg once daily. Based on individual response, the dose may be increased to 8 mg once daily. Please see the ToviazÂŽ SmPC for full guidance.* * Pfizer. Summary of Product Characteristics - ToviazÂŽ (Fesoterodine). ** Both tolterodine and fesoterodine are prodrugs = the active metabolite, 5-HMT, is responsible for antimuscarinic activity(1). 1. Malhotra B. et al. Curr Med Chem. 2009;16(33):4481-9.
Lower variation in efficacy (1) Fewer side effects (1)
proven Efficacy
Improves overactive bladder symptoms Fewer Urge Urinary Incontinence Episodes(1)*
For all appropriate OAB patients
-80%
Fewer
Urgency Episodes(2)**
-45.5% Reduction in Micturition Frequency(3)***
*With Toviaz 8 mg vs BL at Week 12. **Urgency episodes/24 hrs with Toviaz® 4 mg or 8 mg vs BL at Week 12. ***With Toviaz® 8 mg vs BL at Week 12. ****With Toviaz® 8 mg vs BL at Week 12. ®
† 2 out of 3 patients corresponds to 64% of patients who were ‘dry’ with Toviaz® at Week 12. ‡ Diary-dry rate: proportion of patients with > 0 UUI episodes on baseline 3-day bladder diaries who reported 0 UUI episodes on post-baseline diary. 1. Chapple C. et al. BJU Int. 2014;114:418-26. 2. Kaplan S.A. et al. BJU Int. 2010;107:1432-1440. 3. Chapple C. et al. Eur Urol. 2007;52(4):1204-12. 4. Herschom S. et al. BJU Int. 2010;105(1):58-66.
2 out of 3
†
-19%
Patients are
“Dry“
****
‡(4)
STUDY Information
proven Efficacy
Toviaz® 4 mg
Placebo n = 386
LS Mean change from baseline in UUI episodes/24 h
0
n = 790
Toviaz® 8 mg n = 779
BL:
BL:
BL:
4.1
3.9
3.9
-1
-2
-2.2
-74%
-80%
vs BL
vs BL
-2.9
-3.1
-3 p<0.01 -4
BL: Mean Baseline Value
Fewer urge urinary incontinence episodes with Toviaz® 4 mg and Toviaz® 8 mg vs placebo(1)
p = 0.011 p<0.001
LS: Least Squares
Significantly greater improvement in UUI episodes with Toviaz® 8 mg than Toviaz® 4 mg.(1) Reduction from baseline in UUI episodes/24h at Week 12 in the EIGHT study (primary endpoint).(1) The two most common adverse events in all groups were dry mouth and constipation, occuring in 3.4% and 1.8% of patients in the placebo group, 12.9% and 1.5% in the Toviaz® 4 mg group and 26.1% and 4.0% in the Toviaz® 8 mg group respectively. In all groups, most cases were mild to moderate.(1) Toviaz® 8 mg can provide additional efficacy over 4 mg dose.(1) The recommended starting dose of Toviaz® is 4 mg once daily. Based on individual response, the dose may be increased to 8 mg once daily. Please see the Toviaz® SmPC for full guidance.(2) 1. Chapple C. et al. BJU Int. 2014;114:418-26. 2. Pfizer. Summary of Product Characteristics - Toviaz® (Fesoterodine).
STUDY Information
proven Efficacy
LS Mean change from baseline to week 12
0 -10
Placebo
Tolterodine ER 4 mg
n = 462
n = 942
Toviaz® 8 mg n = 930
BL:
BL:
BL:
9.5
9.7
9.7
Fewer urgency episodes
-20
-31.0% -30
-45.5%
-37.5%
vs BL
-40
-50
with Toviaz® 8 mg vs tolterodine ER 4 mg & vs placebo(1)*
p<0.05 p<0.05
BL: Mean Baseline Value LS: Least Squares Reduction in urgency episodes after 12 weeks (secondary endpoint).(1)
*Significantly greater reduction in number of urgency episodes/24 h vs BL compared to placebo & tolterodine ER 4 mg at Week 12.(1) The recommended starting dose of Toviaz® is 4 mg once daily. Based on individual response, the dose may be increased to 8 mg once daily. Please see the Toviaz® SmPC for dosing guidance.(2) 1. Kaplan S.A. et al. BJU Int. 2010;107:1432-1440. 2. Pfizer. Summary of Product Characteristics - Toviaz® (Fesoterodine).
STUDY Information
proven Efficacy
Median % change in number of micturitions/24h at week 12
0 -2
Placebo
Tolterodine ER 4 mg
n = 279
n = 283
Toviaz® 4 mg n = 265
Toviaz® 8 mg n = 276
BL:
BL:
BL:
BL:
12.0
11.5
11.6
11.9
-4 -6 -8
-11.1% -10
-13.8%
-12 -14 -16 -18
-16.7%
-18.6%
vs BL
vs BL
Reduction in micturition frequency vs BL(1)*
p = 0.005 p<0.001
-20
p<0.001
BL: Mean Baseline Value
*Reduction in number of micturitions/24 h after 12 weeks ‘treatment with Toviaz®’ (primary endpoint): -16.7% with Toviaz® 4 mg and -18.6% with Toviaz® 8 mg vs BL.(1) Decrease in mean nb of micturitions is statistically significant with Toviaz® 8 mg versus vs placebo and with Toviaz® 4 mg versus placebo. The recommended starting dose of Toviaz® is 4 mg once daily. Based on individual response, the dose may be increased to 8 mg once daily. Please see the Toviaz® SmPC for dosing guidance.(2) 1. Chapple C. et al. Eur Urol. 2007;52(4):1204-12. 2. Pfizer. Summary of Product Characteristics - Toviaz® (Fesoterodine).
STUDY Information
proven Efficacy
Toviaz® 8 mg
n = 619 §
64.0% Dry
Tolterodine ER 4 mg
2 out of 3 patients
n = 626
57.2% Dry
Placebo
36.0% Wet
42.8% Wet
with Toviaz ® 8 mg at Week 12 (1)
n = 307
45% Dry
are ’dry’ *
55.0% Wet
p < 0.001 vs placebo: § p = 0.015 vs tolterodine
More patients are “Dry”* with Toviaz® 8 mg than with tolterodine ER 4 mg. (post-hoc analysis)(1) * Diary-dry rate: proportion of patients with > 0 UUI episodes on baseline 3-day bladder diaries who reported 0 UUI episodes on post-baseline diary. 2 out of 3 patients corresponds to 64% of patients who were “Dry“ with Toviaz® 8 mg at Week 12. Three-day diary-dry rate at Week 12 (post-hoc analysis).(1) Treatment with Toviaz® 8 mg significantly improved UUI episodes at Week 12 (primary endpoint) vs tolterodine ER 4 mg and placebo p= 0.017 and p<0.001 respectively.(1) The recommended starting dose of Toviaz® is 4 mg once daily. Based on individual response, the dose may be increased to 8 mg once daily. Please see the Toviaz® SmPC for dosing guidance.(2) 1. Herschom S. et al. BJU Int. 2010;105(1):58-66. 2. Pfizer. Summary of Product Characteristics - Toviaz® (Fesoterodine).
STUDY Information
Good safety & tolerability profile
Adverse events, %(1)
Placebo n = 393
n = 392
Dry mouth
5.3
33.9
Mild
3.8
24.2
Moderate
1.3
7.1
Severe
0.3
2.6
Constipation
2.5
8.9
Dizziness
1.0
3.6
Nasopharyngitis
2.3
3.1
Headache
1.3
2.8
Urinary tract infection
1.8
2.6
Diarrhoea
1.3
2.6
Dyspepsia
0.5
2.3
Fatigue
2.5
2.3
Nausea
1.0
2.3
Hypertension
2.0
1.8
Back pain
2.0
0.5
Discontinuations due to all-causality AEs
5.6
11.7
Mild to moderate dry mouth(1)
Low level of constipation(1)
No significant effect on cognitive functions confirmed in clinical trials(1,2,3)*
Frequency of treatment-emengent adverse events in the 12-week sofia trial. Treatment-emergent AEs occuring in > 2% of patients in any group and discontinuations due to AEs.
*vs. Placebo. 1. Wagg A. et al. J Am Geriar Soc. 2013;61:185-93. 2. Dubeau CE. et al. J Urol. 2014;191(2):395-404. 3. Kay GG. et al. Postgrad Med. 2012;124(3):7-15.
STUDY Information
The only OAB Treatment classified B
LUTS â&#x20AC;&#x201C; FORTA Classification(1)
Antimuscarinics Darifenacin
C
Fesoterodine
B
Oxybutynin immediate release
D
Oxybutynin low dose/extended release
C
Propiverine
D
Solifenacin
C
Tolterodine
C
Trospium
C
The FORTA (Fit fOR The Aged) A
Absolutely
Beneficial C Careful B
D
Don't
LUTS = Lower Urinary Tract Symptoms FORTA = Fit for the Aged
β3 - agonist Mirabegron
1. Oelke M. Age and Ageing. 2015;LUTS-FORTA.
C
Classification system that helps guide physicians as to the suitability of medicines for older patients in an everyday clinical setting. Forta classifies drugs into 4 categories: A, B, C, D.
STUDY Information
Patient Satisfaction
97%
61% of patients continued on Toviaz® for 24 months (256/417)(1)
Satisfied patients(1)
16.7% Extremely satisfied
46.0% Very satisfied
34.3% Satisfied
97% of patients were satisfied with Toviaz in a long-term open-label study(1)
®
n=239 Treatment satisfaction at 24 months
The primary endpoints of this study were safety and tolerability, including patient-reported treatment tolerance(1)
Treatment satisfaction was a secondary endpoint and was rated by patients who remained on Toviaz® for 24 months and completed the satisfaction scale (n = 239/417)(1)*
61% of patients continued on Toviaz® for 24 months (256/417)(1)
*4 point scale: My overall satisfaction is: (1= ‘extremely satisfied’ 2 = ‘very satisfied’ 3 = ‘satisfied’ 4 = ‘not satisfied’) with the treatment. 1. Van Kerrebroeck PEV. et al. Int J Clin Pract. 2010;64(5):584-93.
STUDY Information
fesoterodine fumarate The only latest-generation antimuscarinic with clear evidence of dose-dependent efficacy (unique among antimuscarinics)(2)
Flexible DOSING Dosage can be adjusted to optimise the balance between efficacy and tolerability for each patient(1,2)
The recommended starting dose of Toviaz® is 4 mg once daily. Based on individual response, the dose may be increased to 8 mg once daily. Please see the Toviaz® SmPC for dosing guidance. 1. Toviaz® Summary of Product Characteristics. 2. Chapple C. et al. BJU Int. 2014;114:418-426.
STUDY Information