Tadalafil: Efficacy Evaluation in Men With Diabetes · Evaluation of Penile Blood Flow • Duplex...
Transcript of Tadalafil: Efficacy Evaluation in Men With Diabetes · Evaluation of Penile Blood Flow • Duplex...
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PDE5 Inhibitors: Onset and Duration of Activity
PDE5 inhibitor Onset (min) Duration (h)
Sildenafil1,2 30-60* 4*
Tadalafil3-5 120 36‡
Vardenafil6-8 25* 4
Avanafil 7 35-45 5
1. Viagra® (sildenafil) prescribing information, September 2002. 2. Boolell M, et al. Int J Impot Res. 1996;8:47-52. 3. Padma-Nathan H. J Urol. 2001;165(suppl):224. Abstract 923. 4. Porst H. J Urol. 2002;167(suppl):176. Abstract 709. 5. Brock GB, et al. J Urol. 2002;168:1332-1336. 6. Vivanza (vardenafil) EU prescribing information, March 2003. 7. Klotz T, et al. World J Urol. 2001;19:32-39. 8. Stark S, et al. Eur Urol. 2001;40:181-188.7. Kedia G et al Avanafil for the treatment of erectile dysfunction: initial data and clinical key properties. TherAdv Urol. 2013 Feb;5(1):35-41
Tadalafil: Efficacy Evaluation inMen With Diabetes*
*Patients with diabetes. Studies LVBN, LVCE, LVCO, and LVDJ. †Did your erection last long enough to have successful intercourse?
‡P<.001 vs placebo.With permission from Saenz de Tejada I, et al. Poster presented at: 16th Congress of European Association of Urology; April 7-10, 2001; Geneva, Switzerland.
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When to refer a patient to a Urologist?
• PDE5i treatment failure
• Daily Cialis 5mg + Viagra 100mg PRN
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Your Patient Has Failed Phosphodiesterase Type 5 (PDE5) Inhibitor Therapy . . . What Now?
• Reeducate and rechallenge with same agent
• Switch to another PDE5 inhibitor
• Try different therapeutic approach– Vacuum erection devices
– Prostaglandin E1 (PGE1) injections
– Implants
Diagnosis and Evaluation of ED post
• Penis – stretched length, plaque location, dimensions
• Discuss patient’s goals
• Determine nature/degree of erectile insufficiency– Duplex ultrasonography (US)
Gholami SS, et al. J Urol. 2003;169:1234-1241. Levine LA. Int J Impot Res. 2003;15:(suppl 5):S113-S120.
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Evaluation of Penile Blood Flow
• Duplex Ultrasonography
– Penile blood flow study (CIS & blood flow measurement by US) is most reliable & least invasive evidence based assessment of ED
• Red = towards probe
• Blue = away from probe
– Can visualize dorsal & cavernous arteries in real time
2nd line - Ultrasound
• Technique
– Measure flow velocities 5-10 min after injection
– Rate erectile quality
– Look at both cavernous arteries
2nd line - Ultrasound
• Peak Systolic Velocity (PSV)
– PSV < 25 correlates with abnormal pudendal arteriography
– Severe unilateral arterial insufficiency >10 cm/s asymmetry
– Severe vascular ED, diameter increase is <75%, diameter rarely exceeds 0.7 mm
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2nd line - Ultrasound
• Veno-occlusive Dysfuntion
– Need to trap blood & limit venous outflow
– Venogenic impotence• High systolic flow (>25 cm/s)
• Persistent end-diastolic flow (EDV) (>5 cm/s)
– Resistive Index (RI)
• RI = PSV – EDV/PSV– Measure 20 min after injection & stimulation
• RI > 0.9 normal
• RI < 0.75 venous leakage
Recommendations on US
• Intracavernosal injection with color duplex Doppler ultrasound
– Most informative diagnostic test
– Least invasive for vascular ED, high vs. low flow priapism, Peyronie’s plaque
– Useful measurements
• PSV, cavernous artery diameter, EDV, RI
• PSV <25 = severe cavernous artery insufficiency
• PSV >35 = normal inflow
• Negative relationship between age & PSV
Vacuum Erection Devices
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Second-Line Therapy: Vacuum Erection Devices (VEDs)
• Lack of interest in drug therapy
• Specific contraindications to drug therapy
• Patient preference
Jardin A, et al, eds. Erectile Dysfunction. Plymouth, United Kingdom: Health Publication, Ltd; 2000:357-404.
VED: Basic Principles
• Externally applied device mechanically effects penile blood engorgement
• Cylinder/pump placed over penis creates closed chamber; pump creates vacuum, drawing blood into corpora cavernosa
• Constrictive elastic ring then placed at base of penis to restrict flow of suctioned blood
Levine LA, Dimitriou RJ. Urol Clin North Am. 2001;28:335-341.Montague DK, et al, for the AUA Clinical Guidelines Panel on Erectile Dysfunction. J Urol. 1996;156:2007-2011.
VED: Practical Aspects
• Requires manual dexterity1
• Instructional video and/or in-office teaching1
• 30-minute maximum duration of constriction is advised to prevent penile ischemia1
• Precautions necessary in patients on anticoagulant therapy or those easily bruised1,2
• Success rates highest in stable relationships2
1. Montague DK, et al, for the AUA Clinical Guidelines Panel on Erectile Dysfunction. J Urol. 1996;156:2007-2011.2. Levine LA, Dimitriou RJ. Urol Clin North Am. 2001;28:335-341.
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1. Levine LA, Dimitriou RJ. Urol Clin North Am. 2001;28:335-341. 2. Jarow JP. J Urol. 1996;155:1609-1612. 3. The Process of Care Consensus Panel. Int J Impot Res. 1999;11:59-70.
VED: Profile
• Efficacy1
– Uniformly produces erection
– Reported satisfaction rate ~55% (at 2 years)2
• Advantages2,3
– On-demand use
– No systemic side effects
– Cost
• Disadvantages2,3
– Cumbersome
– Unnatural erection
– Possible side effects may include
• Petechiae/ecchymosis
• Penile pain
• Ejaculatory blockage
• Numbness
• Penile hinging
Medicated Urethral System for Erection (MUSE)
Second-Line Therapy: Transurethral System
• Lack of response to oral therapy1
• Contraindications to specific oral drugs1
• Adverse reactions/intolerance to oral drugs1
• Rapid, predictable erection
• Failed penile prostheses2
• Failed intracavernosal therapy3
• Patient preference
1. Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A, et al, eds. Erectile Dysfunction. Plymouth, United Kingdom: Health Publication, Ltd; 2000:711-726. 2. Benevides MD, Carson CC. J Urol. 2000;163:785-787. 3. Engel JD, McVary KT. Urology. 1998;51:687-692.
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Transurethral Alprostadil (MUSE)
Smooth muscle–relaxing urethra suppository mimics physiology of erection (PGE1)
Intraurethral Alprostadil (MUSE): Advantages
• Alleviates need for needles/injections
• High safety, local therapy, no systemic side effects
• No effect on sensation, ejaculation, fertility
• Erection within 5 to 10 minutes
• 75% to 80% of prescriptions covered by medical plans
• No fibrosis, prolonged erections, or curvature
Intraurethral Alprostadil (MUSE): Disadvantages
• Transient penile burning in 32%– Reduced pain with ≥4 administrations reported
– Few discontinue use because of it
• Less effective than injection therapy
• Patients with poor manual dexterity/vision or severe obesity may find administration difficult
• Technique must be taught
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Transurethral Medications
• Method of application: 2-mm pellet into urethra
• Mechanism of action: urethral absorption and distribution into cavernosal tissue → smooth muscle relaxation
• Study results– 66% of 1511 patients had erections in office
– Of these, 65% had successful intercourse at home vs 18.6% with placebo
– Treatment efficacy was similar regardless of age or cause of ED (vascular, diabetes, surgery, or trauma)
• Overall success reported was 30% to 60%
Alprostadil: MUSE
Padma-Nathan H, et al. N Engl J Med. 1997;336:1-7.
Intracavernosal Injection
Smooth muscle–relaxing medication injected directly into the penis(papaverine, phentolamine, PGE1)
Penile Injection Therapy
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Second-Line Therapy: Intracavernosal Injection
• Lack of response to oral therapy1,2
• Contraindications to specific oral drugs1
• Adverse reactions/intolerance to oral drugs1
• More reliable, instant, predictable erection
• Patient preference
1. Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A, et al, eds. Erectile Dysfunction. Plymouth, United Kingdom: Health Publication, Ltd; 2000:711-726. 2. Shabsigh R, et al. Urology. 2000;55:477-480.
Penile Injection Therapy: Advantages
• Highly effective
• Mimics natural physiology of erection
• No effect on sensation, ejaculation, fertility
• Higher level of discretion, thus spontaneity
Penile Injection Therapy: Disadvantages
• Poor long-term tolerability (dropout rate >60%)• Bruising, prolonged erection, cavernosal fibrosis,
pain at injection site, penile deformity (rare)• Cumbersome, especially for patients with poor
manual dexterity/vision or severe obesity• Requires training, follow-up, and dosing
adjustments• May be risky with heart disease, previous strokes,
or liver or blood disorders• May not be covered by insurance
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Low Intensity Shockwave Therapy
• Not incorporated into AUA guidelines yet
• Shockwaves at 1/10th the dose of traditional ESWL for stones
Vardi Y, et al.. Can low-intensity extracorporeal shockwave therapy improve erectile function? European Urology. 2010;58: 243-48
Low Intensity Shockwave Therapy
• Meta-analysis: combined improvement in IIEF-EF score is 4.28
• Greater than the minimal clinically important difference (MCID) of 4 IIEF points as described by Rosen et al.
• Zero adverse effects
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Should We Doing Implants Earlier?
Clavijo RI, et al Time course and predictors of use of erectile dysfunction treatment in a Veterans Affairsmedical center. Int J Impot Res. 2016 May 19.
Penile Prosthesis Implantation
Types of Prostheses
• Malleable/semirigid (AMS, Mentor)
• Mechanical rod (Duraphase)
• Inflatable– 2-piece (Ambicor)
– 3-piece – AMS (CX, CXM)
– Coloplast ( Titan )
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www.amselabeling.com
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Penile Implant Indications
• Oral drug (PDE5 inhibitor) failure– Radical prostatectomy– Diabetes mellitus
• Scarred penis– Priapism– Previous implant– Trauma
• Peyronie’s disease• Severe venous leak
Issues Regarding Informed Consent
• Size of penis—stretched penile length• Possible need for revision surgery
– Infection– Malfunction– Tissue damage
• Sensation• Ejaculation• Discuss alternative treatments, eg, vacuum constriction
device (VCD), Medicated Urethral System for Erections(MUSE), etc
• Variety of prostheses• Reduced erectile function if device removed
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Reliability—Device Survival
Montague Ultrex 78% 5 yearsLevine Ambicor 93% 3-5 yearsChoi CXM 90% 5 yearsCarson CX 86% 5 yearsMontorsi AMS700 96% 5 yearsWilson Mentor Alpha-1 93% 5 yearsGovier AMS 91% 3 yearsDhabuwala Mentor 96% 5 years
AMS 84% 5 years
Penile Implant -Satisfaction
• In contemporary series, satisfaction is >80%
Bernal, R et al. Adv in Uro. 2012
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Reasons for Dissatisfaction With Penile Implant
• Loss of penile length
• Reduced sexual spontaneity
• Unrealistic expectations
• Malfunction
• Infection- 1-4%
Penile Prosthesis
Pros• High patient satisfaction rate
• 7 to 10 years average functional prosthesis life
• Higher spontaneity
• Discreet, normal appearance
• Erection longevity controllable
• Significant clinical data on procedure and results
Penile Prosthesis (cont’d)
Cons• Potential for infection, device malfunction
• Surgical procedure, postoperative pain, irreversible
• Additional surgery at product end-of-life
• Potential decreased sensation, glans sensitivity, ability to ejaculate/reach orgasm
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Implant Surgical Technique
• Infrapubic approach– Familiar surgical approach for urologists– Easy placement of reservoir– Potential injury to dorsal penile nerve
• Penoscrotal approach– Easy dissection and corporal dilation– Penile nerves not in surgical field– Blind placement of reservoir sometimes
difficult
Synchronous Prosthetic Implantation Through Transscrotal Incision
• Multi-institutional evaluation from 2000 to 2003 revealed 22 patients undergoing synchronous IPP and AUS
• 14% revision rate: 2 urethral erosions and 1 reservoir migration, no infections; postoperation <1 pad/day urinary leakage
• Risk factors: diabetes, hypertension, radiation therapy
• Advantage of single anesthetic and single transcrotal incision in high-risk, complex genitourinary patients should encourage widespread acceptance of this technique
Shaw MB, et al. J Urol. 2004:171:898A.
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Post-Op Care:
• Foley catheter for 24 hours
• Bed rest from 48 hours
• Cylinder straight, up and deflated
• Warm baths bid starting on post-op day #3
• Prosthesis cycling at 6 to 8 weeks
Keys to Successful IPP Surgery:
• Dedicated set of instruments• Penile pack
• Full inventory of devices• Strategy to decrease skin bacteria flora
• Strategy to prevent contact with the skin during the procedure
Conclusions
• ED can be identified and managed in the primary care setting—detection is key!
• Effective treatments are available
• Treatment efficacy can be optimized by establishing its proper usage and pursuing risk-factor modification and vascular disease treatment