Are PDE5 inhibitors a reliable treatment

for patients with LUTSBPH

YES

Sidney Glina

Faculdade de Medicina do ABC

Instituto H Ellis

Editor-in-Chief of the International

Brazilian Journal of Urology

(wwwintbrazjurolcombr)

glinasterracombr

Conflict of Interest

In the last 2 years I have been

- Speaker for Besins Lilly Acheacute

Eurofarma

- Member of Advisory Board of Acheacute

Besins EMS and Lilly

Mode of Action PDE5I improves LUTSBPH

bull PDE5 receptors in bladder neck prostate and

prostatic urethra

bull PDE5I acts on smooth muscle relaxation

bull Improvement of arterial flow

bull Modulation of nerve aference

But MOA is unknown

bull However clinical trials have shown benefits

on the treatment of symptoms of LUTSHPB

Fibbi et al J Sex Med 2010759ndash69

4

Immunolocalization of PDE5 in transverse sections

of human lower urinary tract

Fibbi et al J Sex Med 2010759ndash69

PDE Localization in Human Prostate Tissue

PDE5 PDE4D

PDE11 PDE3A

prostatic smooth

muscle

vascular smooth muscle glandular epithelium

prostatic

smooth muscle

Fibbi et al J Sex Med 2010759ndash69

McVary et al J Urol 2007177(4)1401-7

IPSS ndash From 0 to 12 weeks

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 6 Semana 12

Placebo Tadalafila 520 mg

IP

SS

McVary et al J Urol 2007177(4)1401-7

p01

ANCOVA LOCF

Egerdie et al J Sex Med 2011

IPSS Total

bull plt0001

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 2 Semana 4 Semana 8 Semana 12

IP

SS

To

tal

Placebo

Tadalafila 25 mg

Tadalafila 5 mg

a

Egerdie et al J Sex Med 2011

Oelke et al Eur Urol 2012 - Estudo LVID

IPSS Total Average alteration from the beginning

plt005 plt001 ple0001

IPS

S T

ota

l

Iniacutecio Semana 4 Semana 1a Semana 12

Oelke et al Eur Urol 2012 61917-925

Efficacy and safety of the coadministration of Tadalafil once daily with Finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia

Casabeacute A et al J Urol 2013

Time course of LS mean change (SE) from baseline in I-PSS total

score Double dagger indicates p 0001 and number sign indicates

p lt005

-6

0

-2

-4

-7 0 4 26 12

IPP

S

LS

Me

an

Ch

an

ge

(S

E)

fro

m B

as

eli

ne

weeks

PBOFIN

TADFIN

LSTD

-17

-14 -10

Dagger

Dagger

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

Conflict of Interest

In the last 2 years I have been

- Speaker for Besins Lilly Acheacute

Eurofarma

- Member of Advisory Board of Acheacute

Besins EMS and Lilly

Mode of Action PDE5I improves LUTSBPH

bull PDE5 receptors in bladder neck prostate and

prostatic urethra

bull PDE5I acts on smooth muscle relaxation

bull Improvement of arterial flow

bull Modulation of nerve aference

But MOA is unknown

bull However clinical trials have shown benefits

on the treatment of symptoms of LUTSHPB

Fibbi et al J Sex Med 2010759ndash69

4

Immunolocalization of PDE5 in transverse sections

of human lower urinary tract

Fibbi et al J Sex Med 2010759ndash69

PDE Localization in Human Prostate Tissue

PDE5 PDE4D

PDE11 PDE3A

prostatic smooth

muscle

vascular smooth muscle glandular epithelium

prostatic

smooth muscle

Fibbi et al J Sex Med 2010759ndash69

McVary et al J Urol 2007177(4)1401-7

IPSS ndash From 0 to 12 weeks

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 6 Semana 12

Placebo Tadalafila 520 mg

IP

SS

McVary et al J Urol 2007177(4)1401-7

p01

ANCOVA LOCF

Egerdie et al J Sex Med 2011

IPSS Total

bull plt0001

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 2 Semana 4 Semana 8 Semana 12

IP

SS

To

tal

Placebo

Tadalafila 25 mg

Tadalafila 5 mg

a

Egerdie et al J Sex Med 2011

Oelke et al Eur Urol 2012 - Estudo LVID

IPSS Total Average alteration from the beginning

plt005 plt001 ple0001

IPS

S T

ota

l

Iniacutecio Semana 4 Semana 1a Semana 12

Oelke et al Eur Urol 2012 61917-925

Efficacy and safety of the coadministration of Tadalafil once daily with Finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia

Casabeacute A et al J Urol 2013

Time course of LS mean change (SE) from baseline in I-PSS total

score Double dagger indicates p 0001 and number sign indicates

p lt005

-6

0

-2

-4

-7 0 4 26 12

IPP

S

LS

Me

an

Ch

an

ge

(S

E)

fro

m B

as

eli

ne

weeks

PBOFIN

TADFIN

LSTD

-17

-14 -10

Dagger

Dagger

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

Mode of Action PDE5I improves LUTSBPH

bull PDE5 receptors in bladder neck prostate and

prostatic urethra

bull PDE5I acts on smooth muscle relaxation

bull Improvement of arterial flow

bull Modulation of nerve aference

But MOA is unknown

bull However clinical trials have shown benefits

on the treatment of symptoms of LUTSHPB

Fibbi et al J Sex Med 2010759ndash69

4

Immunolocalization of PDE5 in transverse sections

of human lower urinary tract

Fibbi et al J Sex Med 2010759ndash69

PDE Localization in Human Prostate Tissue

PDE5 PDE4D

PDE11 PDE3A

prostatic smooth

muscle

vascular smooth muscle glandular epithelium

prostatic

smooth muscle

Fibbi et al J Sex Med 2010759ndash69

McVary et al J Urol 2007177(4)1401-7

IPSS ndash From 0 to 12 weeks

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 6 Semana 12

Placebo Tadalafila 520 mg

IP

SS

McVary et al J Urol 2007177(4)1401-7

p01

ANCOVA LOCF

Egerdie et al J Sex Med 2011

IPSS Total

bull plt0001

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 2 Semana 4 Semana 8 Semana 12

IP

SS

To

tal

Placebo

Tadalafila 25 mg

Tadalafila 5 mg

a

Egerdie et al J Sex Med 2011

Oelke et al Eur Urol 2012 - Estudo LVID

IPSS Total Average alteration from the beginning

plt005 plt001 ple0001

IPS

S T

ota

l

Iniacutecio Semana 4 Semana 1a Semana 12

Oelke et al Eur Urol 2012 61917-925

Efficacy and safety of the coadministration of Tadalafil once daily with Finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia

Casabeacute A et al J Urol 2013

Time course of LS mean change (SE) from baseline in I-PSS total

score Double dagger indicates p 0001 and number sign indicates

p lt005

-6

0

-2

-4

-7 0 4 26 12

IPP

S

LS

Me

an

Ch

an

ge

(S

E)

fro

m B

as

eli

ne

weeks

PBOFIN

TADFIN

LSTD

-17

-14 -10

Dagger

Dagger

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

4

Immunolocalization of PDE5 in transverse sections

of human lower urinary tract

Fibbi et al J Sex Med 2010759ndash69

PDE Localization in Human Prostate Tissue

PDE5 PDE4D

PDE11 PDE3A

prostatic smooth

muscle

vascular smooth muscle glandular epithelium

prostatic

smooth muscle

Fibbi et al J Sex Med 2010759ndash69

McVary et al J Urol 2007177(4)1401-7

IPSS ndash From 0 to 12 weeks

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 6 Semana 12

Placebo Tadalafila 520 mg

IP

SS

McVary et al J Urol 2007177(4)1401-7

p01

ANCOVA LOCF

Egerdie et al J Sex Med 2011

IPSS Total

bull plt0001

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 2 Semana 4 Semana 8 Semana 12

IP

SS

To

tal

Placebo

Tadalafila 25 mg

Tadalafila 5 mg

a

Egerdie et al J Sex Med 2011

Oelke et al Eur Urol 2012 - Estudo LVID

IPSS Total Average alteration from the beginning

plt005 plt001 ple0001

IPS

S T

ota

l

Iniacutecio Semana 4 Semana 1a Semana 12

Oelke et al Eur Urol 2012 61917-925

Efficacy and safety of the coadministration of Tadalafil once daily with Finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia

Casabeacute A et al J Urol 2013

Time course of LS mean change (SE) from baseline in I-PSS total

score Double dagger indicates p 0001 and number sign indicates

p lt005

-6

0

-2

-4

-7 0 4 26 12

IPP

S

LS

Me

an

Ch

an

ge

(S

E)

fro

m B

as

eli

ne

weeks

PBOFIN

TADFIN

LSTD

-17

-14 -10

Dagger

Dagger

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

PDE Localization in Human Prostate Tissue

PDE5 PDE4D

PDE11 PDE3A

prostatic smooth

muscle

vascular smooth muscle glandular epithelium

prostatic

smooth muscle

Fibbi et al J Sex Med 2010759ndash69

McVary et al J Urol 2007177(4)1401-7

IPSS ndash From 0 to 12 weeks

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 6 Semana 12

Placebo Tadalafila 520 mg

IP

SS

McVary et al J Urol 2007177(4)1401-7

p01

ANCOVA LOCF

Egerdie et al J Sex Med 2011

IPSS Total

bull plt0001

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 2 Semana 4 Semana 8 Semana 12

IP

SS

To

tal

Placebo

Tadalafila 25 mg

Tadalafila 5 mg

a

Egerdie et al J Sex Med 2011

Oelke et al Eur Urol 2012 - Estudo LVID

IPSS Total Average alteration from the beginning

plt005 plt001 ple0001

IPS

S T

ota

l

Iniacutecio Semana 4 Semana 1a Semana 12

Oelke et al Eur Urol 2012 61917-925

Efficacy and safety of the coadministration of Tadalafil once daily with Finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia

Casabeacute A et al J Urol 2013

Time course of LS mean change (SE) from baseline in I-PSS total

score Double dagger indicates p 0001 and number sign indicates

p lt005

-6

0

-2

-4

-7 0 4 26 12

IPP

S

LS

Me

an

Ch

an

ge

(S

E)

fro

m B

as

eli

ne

weeks

PBOFIN

TADFIN

LSTD

-17

-14 -10

Dagger

Dagger

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

McVary et al J Urol 2007177(4)1401-7

IPSS ndash From 0 to 12 weeks

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 6 Semana 12

Placebo Tadalafila 520 mg

IP

SS

McVary et al J Urol 2007177(4)1401-7

p01

ANCOVA LOCF

Egerdie et al J Sex Med 2011

IPSS Total

bull plt0001

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 2 Semana 4 Semana 8 Semana 12

IP

SS

To

tal

Placebo

Tadalafila 25 mg

Tadalafila 5 mg

a

Egerdie et al J Sex Med 2011

Oelke et al Eur Urol 2012 - Estudo LVID

IPSS Total Average alteration from the beginning

plt005 plt001 ple0001

IPS

S T

ota

l

Iniacutecio Semana 4 Semana 1a Semana 12

Oelke et al Eur Urol 2012 61917-925

Efficacy and safety of the coadministration of Tadalafil once daily with Finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia

Casabeacute A et al J Urol 2013

Time course of LS mean change (SE) from baseline in I-PSS total

score Double dagger indicates p 0001 and number sign indicates

p lt005

-6

0

-2

-4

-7 0 4 26 12

IPP

S

LS

Me

an

Ch

an

ge

(S

E)

fro

m B

as

eli

ne

weeks

PBOFIN

TADFIN

LSTD

-17

-14 -10

Dagger

Dagger

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

IPSS ndash From 0 to 12 weeks

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 6 Semana 12

Placebo Tadalafila 520 mg

IP

SS

McVary et al J Urol 2007177(4)1401-7

p01

ANCOVA LOCF

Egerdie et al J Sex Med 2011

IPSS Total

bull plt0001

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 2 Semana 4 Semana 8 Semana 12

IP

SS

To

tal

Placebo

Tadalafila 25 mg

Tadalafila 5 mg

a

Egerdie et al J Sex Med 2011

Oelke et al Eur Urol 2012 - Estudo LVID

IPSS Total Average alteration from the beginning

plt005 plt001 ple0001

IPS

S T

ota

l

Iniacutecio Semana 4 Semana 1a Semana 12

Oelke et al Eur Urol 2012 61917-925

Efficacy and safety of the coadministration of Tadalafil once daily with Finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia

Casabeacute A et al J Urol 2013

Time course of LS mean change (SE) from baseline in I-PSS total

score Double dagger indicates p 0001 and number sign indicates

p lt005

-6

0

-2

-4

-7 0 4 26 12

IPP

S

LS

Me

an

Ch

an

ge

(S

E)

fro

m B

as

eli

ne

weeks

PBOFIN

TADFIN

LSTD

-17

-14 -10

Dagger

Dagger

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

Egerdie et al J Sex Med 2011

IPSS Total

bull plt0001

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 2 Semana 4 Semana 8 Semana 12

IP

SS

To

tal

Placebo

Tadalafila 25 mg

Tadalafila 5 mg

a

Egerdie et al J Sex Med 2011

Oelke et al Eur Urol 2012 - Estudo LVID

IPSS Total Average alteration from the beginning

plt005 plt001 ple0001

IPS

S T

ota

l

Iniacutecio Semana 4 Semana 1a Semana 12

Oelke et al Eur Urol 2012 61917-925

Efficacy and safety of the coadministration of Tadalafil once daily with Finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia

Casabeacute A et al J Urol 2013

Time course of LS mean change (SE) from baseline in I-PSS total

score Double dagger indicates p 0001 and number sign indicates

p lt005

-6

0

-2

-4

-7 0 4 26 12

IPP

S

LS

Me

an

Ch

an

ge

(S

E)

fro

m B

as

eli

ne

weeks

PBOFIN

TADFIN

LSTD

-17

-14 -10

Dagger

Dagger

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

IPSS Total

bull plt0001

-7

-6

-5

-4

-3

-2

-1

0

Iniacutecio Semana 2 Semana 4 Semana 8 Semana 12

IP

SS

To

tal

Placebo

Tadalafila 25 mg

Tadalafila 5 mg

a

Egerdie et al J Sex Med 2011

Oelke et al Eur Urol 2012 - Estudo LVID

IPSS Total Average alteration from the beginning

plt005 plt001 ple0001

IPS

S T

ota

l

Iniacutecio Semana 4 Semana 1a Semana 12

Oelke et al Eur Urol 2012 61917-925

Efficacy and safety of the coadministration of Tadalafil once daily with Finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia

Casabeacute A et al J Urol 2013

Time course of LS mean change (SE) from baseline in I-PSS total

score Double dagger indicates p 0001 and number sign indicates

p lt005

-6

0

-2

-4

-7 0 4 26 12

IPP

S

LS

Me

an

Ch

an

ge

(S

E)

fro

m B

as

eli

ne

weeks

PBOFIN

TADFIN

LSTD

-17

-14 -10

Dagger

Dagger

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

Oelke et al Eur Urol 2012 - Estudo LVID

IPSS Total Average alteration from the beginning

plt005 plt001 ple0001

IPS

S T

ota

l

Iniacutecio Semana 4 Semana 1a Semana 12

Oelke et al Eur Urol 2012 61917-925

Efficacy and safety of the coadministration of Tadalafil once daily with Finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia

Casabeacute A et al J Urol 2013

Time course of LS mean change (SE) from baseline in I-PSS total

score Double dagger indicates p 0001 and number sign indicates

p lt005

-6

0

-2

-4

-7 0 4 26 12

IPP

S

LS

Me

an

Ch

an

ge

(S

E)

fro

m B

as

eli

ne

weeks

PBOFIN

TADFIN

LSTD

-17

-14 -10

Dagger

Dagger

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

IPSS Total Average alteration from the beginning

plt005 plt001 ple0001

IPS

S T

ota

l

Iniacutecio Semana 4 Semana 1a Semana 12

Oelke et al Eur Urol 2012 61917-925

Efficacy and safety of the coadministration of Tadalafil once daily with Finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia

Casabeacute A et al J Urol 2013

Time course of LS mean change (SE) from baseline in I-PSS total

score Double dagger indicates p 0001 and number sign indicates

p lt005

-6

0

-2

-4

-7 0 4 26 12

IPP

S

LS

Me

an

Ch

an

ge

(S

E)

fro

m B

as

eli

ne

weeks

PBOFIN

TADFIN

LSTD

-17

-14 -10

Dagger

Dagger

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

Efficacy and safety of the coadministration of Tadalafil once daily with Finasteride for 6 months in men with lower urinary tract symptoms and prostatic enlargement secondary to benign prostatic hyperplasia

Casabeacute A et al J Urol 2013

Time course of LS mean change (SE) from baseline in I-PSS total

score Double dagger indicates p 0001 and number sign indicates

p lt005

-6

0

-2

-4

-7 0 4 26 12

IPP

S

LS

Me

an

Ch

an

ge

(S

E)

fro

m B

as

eli

ne

weeks

PBOFIN

TADFIN

LSTD

-17

-14 -10

Dagger

Dagger

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

PDE-5i and LUTSBPH

22062016

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

Tadalafil for LUTSBPH

Tadalafil half life of 175 hs

1 pill a day

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

Activity of phosphodiesterase type 5 inhibitors in

patients with lower urinary tract symptoms due to

benign prostatic hyperplasia

bull Men with LUTSBPH submitted to endoscopic

resection of the prostate who received a single dose

of tadalafil and udenafil one hour before surgery

bull Concentration of both PDE5i was significantly higher

in prostate tissue than in plasma and both

significantly raised the AMP and cyclic GMP levels in

the plasma and prostate tissue

bull Zhao C et al BJUI 2011

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi Z

Wang G Zhang Z Han C

Urol Int 201391(1)10-8

bull 8 trials 2913 patients (2007-2012)

bull LUTSBPH or LUTSBPH + ED placebo controlled

bull Follow-up 12 weeks

bull BPH -235 IPSS

bull BPHED-189

bull p lt000001 (compared to placebo)

IIEF bull BPH +493 ( 374 a 613)

bull BPHED + 455 (379 a 532)

bull p lt000001(compared to placebo)

Efficacy and safety of tadalafil monotherapy for lower urinary

tract symptoms secondary to benign prostatic hyperplasia a

meta-analysis Dong Y Hao L Shi Z Wang G Zhang Z Han C

Urol Int 201391(1)10-8

Q maacutex

bull 2188 patients

bull Tadalafil + 026 mlseg (p=014)

Efficacy and safety of tadalafil monotherapy for lower urinary tract symptoms

secondary to benign prostatic hyperplasia a meta-analysis Dong Y Hao L Shi

Z Wang G Zhang Z Han C

Urol Int 201391(1)10-8

Yuan JQ Mao C Wong SY Yang ZY Fu XH Dai XY Tang JL Comparative Effectiveness and

Safety of Monodrug Therapies for Lower Urinary Tract Symptoms Associated With Benign

Prostatic Hyperplasia A Network Meta-analysis Medicine (Baltimore) 2015 Jul94(27)e974

bull Metanalysis Network about sobre a monotherapy for

LUTS

bull PDE5I improvement of IPSS IIEF but no action on

Q maacutex

Gacci M Corona G Salvi M Vignozzi L McVary KT Kaplan SA Roehrborn CG Serni S Mirone V

Carini M Maggi MA systematic review and meta-analysis on the use of phosphodiesterase 5

inhibitors alone or in combination with α-blockers for lower urinary tract symptoms due to

benign prostatic hyperplasia Eur Urol 2012 May61(5)994-1003

bull 12 papers 3214 men

bull 7 PDE5I X placebo e 5 combined treatment

bull PDE5I only

bull IPSS ndash 28 (plt00001)

bull IIEF = 55 (plt00001)

bull Q maacutex -000 mlseg

Proportion of tadalafil-treated patients

with clinically meaningful improvement

bull 4 placebo controlled trials ( 1499 patients)

bull Improvement of at least 3 points on IPSS or gt 25 initial symptoms

bull 711 X 56 - IPSS

bull 61 X 455 - gt 25 initial symptoms

bull Conclusion 23 of patients responded to treatment

bull Nickel et al 2015 ndash BJU Int 2015 115815-21

PDE5I and nocturia

4 placebo controlled trials

Improvement of 475 X 413 ( p=0002)

Statistical significance but clinical improvement

Oelke M et al -World J Urol 2014 Oct32(5)1109-17

EAU guidelines-2015

bull PDE5I can be used in men with

moderate or severe LUTSBPH

bull Evidence level 1a

bull Grade A

Summary

bull Tadalafil is effective on IPSS reduction in

patients with LUTSBPH

bull Effect on nocturia and Q maacutex are minimum

PDE5I and nocturia

4 placebo controlled trials

Improvement of 475 X 413 ( p=0002)

Statistical significance but clinical improvement

Oelke M et al -World J Urol 2014 Oct32(5)1109-17

EAU guidelines-2015

bull PDE5I can be used in men with

moderate or severe LUTSBPH

bull Evidence level 1a

bull Grade A

Summary

bull Tadalafil is effective on IPSS reduction in

patients with LUTSBPH

bull Effect on nocturia and Q maacutex are minimum

EAU guidelines-2015

bull PDE5I can be used in men with

moderate or severe LUTSBPH

bull Evidence level 1a

bull Grade A

Summary

bull Tadalafil is effective on IPSS reduction in

patients with LUTSBPH

bull Effect on nocturia and Q maacutex are minimum

Summary

bull Tadalafil is effective on IPSS reduction in

patients with LUTSBPH

bull Effect on nocturia and Q maacutex are minimum