for ED and LUTS/BPH Pierre Sarkis, M.D. Assistant Professor Fellow of the European Board of Urology

Transcription

1 Tadalafil 5 mg once daily for ED and LUTS/BPH Pierre Sarkis, M.D. Assistant Professor Fellow of the European Board of Urology

2 Why this conference? Not promotional but educational The pharmacist regularly encounters patients who have been prescribed BPH/LUTS medications. The pharmacist regularly encounters patients who have been prescribed erectile dysfunction medications. The pharmacist regularly encounters patients who have been prescribed medications for the two conditions. The pharmacist have to know the rationale for the use of these medications prescribed very frequently and should be ready to answer patients questions. The pharmacist should be aware about any new indication such as Tadalafil 5mg daily for LUTS and ED.

3 Answers to common questions What is erectile dysfunction (ED)? What is «Lower urinary tract symptoms and Benign prostatic hyperplasia (LUTS/BPH)»? Is there a link between the two entities? What is the treatment of men with the two conditions simultaneously? Two medications or one for both?

4 Erectile Dysfunction: Introduction Erectile dysfunction (ED) is characterized by the consistent inability to attain or maintain an erection sufficient for satisfactory sexual intercourse 1 ED often 2-4 : Reduces motivation for sexual activity Creates a conscious focus on ED by the affected man Inhibits partner initiation of sexual activity 1. NIH Consensus Conference. JAMA 1993;270(1): Perelman M et al. J Sex Med 2005;2: Fisher W et al. J Sex Med 2005;2: Cameron A et al. J Sex Marital Ther 2005;31:

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6 Erectile dysfunction: Causes Male sexual arousal is a complex process that involves the brain, hormones, emotions, nerves, muscles and blood vessels. ED can result from a problem with any of these. Likewise, stress and mental health problems can cause or worsen ED. Sometimes a combination of physical and psychological issues causes erectile dysfunction.

7 Erectile dysfunction: Consequences An unsatisfactory sex life Stress or anxiety Embarrassment or low self-esteem Marital or relationship problems Inability to get your partner pregnant

8 Erectile dysfunction: Treatment Check medications that could be causing or worsening ED (Ex. Beta Blockers.) Lifestyle change (Alcohol, Tobacco) Improve communication with the partner and consider couples or marriage counseling.

9 Erectile dysfunction: Treatment Phosphodiesterase inhibitors (PDE5I): The only oral drugs approved for use in ED Intracavernous injections of papaverine and Prostaglandin Intraurethral prostaglandin Penile prosthesis

10 Mechanism of erection Anatomy of the penis

11 Mechanism of erection Role of GMPc

12 Mechanism of erection Role of PDE5

13 Mechanism of erection Role of PDE5 Inhibitors

14 The central role of Nitric Oxide (NO) in erectile function Cavernous nerve Adrenergic fibres Norepinephrine p Non-adrenergic non-cholinergic fibres Cholinergic fibres Acetylcholine SMC CONTRACTION RELAXATION SMC (corpus cavernosum) NO SMC (local arteries) Endothelial cell RELAXATION BLOOD INFLOW Engorgement of sinusoidal spaces NO, nitric oxide SMC, smooth muscle cells INTRACAVERNOUS PRESSURE ERECTION VENOUS COMPRESSION ( BLOOD OUTFLOW) Dean RC, Lue TF. Urol Clin North Am. 2005;32(4):379-v.

15 How does Nitric Oxide (NO) affect smooth muscle cell relaxation? NO-cGMP signaling pathway causes a decrease in cytosolic Ca 2+ that directly leads to SMC Relaxation. Regulated by phospodiesterase-5 (PDE-5) breakdown of cgmp. cgmp, cyclic guanosine monophosphate GTP, guanosine triphosphate NO, nitric oxide PDE-5, phospodiesterase-5 SMC, smooth muscle cell Dean RC, Lue TF. Urol Clin North Am. 2005;32(4):379-v.

16 Mechanism of action of PDE5I

17 Tadalafil 20mg: What s beyond the 36 hours efficacy?

18 Tadalafil 20mg Men with ED were randomized to Tadalafil 20mg (n=1143) and placebo (n=538)

19 Do patients use the 36 hour window offered by tadalafil? Tadalafil 20mg

20 Tadalafil Men who reported successful intercourse with tadalafil were significantly more satisfied with the hardness of their erection than men who reported successful intercourse with Placebo

21 Why the Once-Daily Option Oral PDE5 inhibitors successfully treat ED 1 ; however, Ameliorating the full psychological impact of ED remains a challenge 2 One complication is the lack of a clear pattern of timing of sexual activity for many couples 2 Once-daily dosing would offer an alternative for couples who prefer spontaneous instead of scheduled sexual activities, or for those who anticipate frequent sexual activities 1. Eardley I et al. J Sex Med 2010;7: Fisher W et al. J Sex Med 2005;2:

22 tadalafil tadalafil

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25 LUTS/BPH: Definition LUTS: obstructive and/or irritative symptoms May be secondary to prostatic obstruction or bladder problems Prostatic obstruction is due to Benign prostatic hyperplasia (BPH) LUTS/BPH is the right nomination

26 Link between ED and BPH-LUTS

27 Relationship between comorbidities and ED Cross-sectional study of men (n=2,476) aged 25 to 70 years in Spain Martin-Morales A, et al. J Urol. 2001;166(2):

28 LUTS severity correlates with the rate of ED Multinational Survey of the Aging Male (MSAM-7) in men (n=12,815) aged 50 to 80 years (US & EU) LUTS Severity Frequency (%) Age Cohort Association between increased severity of LUTS, rate of ED and age Base: Total sample years years years Net reduction of stiffness No, I cannot get an erection Rosen R, et al. Eur Urol. 2003;44(6):

29 The role of Nitric Oxide (NO) in the lower urinary tract Prostate, urethra and bladder neck: Densely supplied by nitric i oxide (NO)-synthase-containing i nerves 1 In the bladder and urethra: NO relaxes smooth muscle of the bladder neck and urethra during voiding 2,3 May also potentiate detrusor contraction during micturition 3 May also control afferent activity in the outlet region 2 In the prostate: NO regulates prostate smooth muscle tone 4 Also regulates local l blood flow 4 1. Hedland P. World J Urol. 2005;23(6): Andersson KE, Persson K. Scand J Urol Nephrol Suppl. 1995;175: Kajioka S, et al. Cell Calcium. 2008;44(2): Kedia GT, et al. World J Urol. 2008;26:603-9.

30 Strong epidemiological evidence supports a link between BPH-LUTS and ED A number of pathophysiological mechanisms are common to both conditions The nitric oxide/cyclic guanosine monophosphate h (NO/cGMP) signalling pathway has been widely implicated

31 The NO-cGMP pathway, with its action on smooth muscle tone, plays a central role in ED and is also involved in various aspects of LUT function this pathway is regulated by phosphodiesterase enzymes (PDE), providing a target for treatment with PDE-5 inhibitors Gacci M, et al. Eur Urol. 2011;60(4):

32 New approach to BPH-LUTS/ED In patients presenting with BPH-LUTS In patients presenting with ED Proactively inquire about co-morbid ED Proactively inquire about co-morbid LUTS The presence of co morbid BPH LUTS and ED has important implications on how each are managed Enables a comprehensive and integrated management plan to be developed May be jointly addressed d with combination drug therapy or single specific therapy Chitale S, et al. JSex Med. 2007;4:

33 20. Egerdie RB, et al. J Sex Med 2012; 9(1):

34 20. Egerdie RB, et al. J Sex Med 2012; 9(1):

35 European association of Urology Guidelines 2014 PDE5I in LUTS/BPH PDE5I reduce moderate-to-severe (storage and voiding) LUTS in men with or without erectile dysfunction ((Grade A recommandation) Only tadalafil (5 mg once daily) hasbeenlicensedfor y g y the treatment of male LUTS.

36 Tadalafil: Safety profile

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39 ELaC1

40 Slide 39 ELaC1 remove reference 2 and 3 remove AEs after myalgia Eli Lilly and Company, 18/06/2012

41 Take home message With concomitant BPH-LUTS and ED, consider the effects of treatments on each of these conditions. Recent experimental and clinical data point to a role for PDE5I inhibitors inbph-lus. PDE5 inhibitor monotherapy may improve LUTS while also treating concomitant ED. PDE5 i hibit th i ED hil PDE5 inhibitor monotherapy may improve ED while also treating concomitant LUTS.

42 Take home message What should I advise my patients while dispensing a prescription of Tadalafil 5mg? Take tadalafil 5mg orally, once a day, at approximately the same time each day with or without food. A response to ED can be observed within 5 days of once a day dosing as this is when steady-state plasma concentrations are attained. Tadalafil has been shown to improve urinary symptoms as early as 1-2 weeks after commencing treatment. Seftel A. et al. zed, J Urol Jan; 185(1):243-8

43 10. Carson CC, et al. BJU Int. 2004;93: Cialis spc

44 FAQs What are the most common side effects of tadalafil? A. Headache, dyspepsia, ypp back pain B. Headache, flushing, back pain C. Headache, dyspepsia, flushing D. Nausea, dyspepsia, back pain

45 FAQs What should I advise my patients t while dispensing i a prescription of tadalafil 20mg? A. Take tadalafil 20mg orally at any time with or without food B. You should have coverage from 30minutes post dose up to 36 hours. C. Remember that Sexual stimulation is required for you to obtain an erection. D. All of the above

46 FAQs What should I advise my patients while dispensing a prescription of Tadalafil 5mg? A. Take tadalafil 5mg orally, once a day, at approximately the same time each day with or without food. B. A response to ED can be observed within 5 days of once a day dosing as this is when steady-state plasma concentrations are attained. C. Tadalafil has been shown to improve urinary symptoms as early as 1-2 weeks after commencing treatment. D. All of the above

47 Thank You