to attain and/or maintain a penile erection sufficient for

Pharmacologic Treatment of Erectile

Dysfunction

Jeffrey Albaugh, PhD, APRN, CUCNS

Director of Sexual Health

NorthShore University Glenbrook Urology

[email protected]

Slide 2 Disclosures/Conflict of Interest

• None

Slide 3 Erectile Dysfunction

• “The consistent or recurrent inability to attain and/or maintain a penile erection sufficient for sexual performance.”– WHO-ISIR. 1st International Consultation on ED, 1999

Male A&P

Slide 5 Endothelial Dysfunction

Slide 6 Oral Agents

INTERVENTION: MEDICAL TREATMENTS - Oral Therapies

PDE Type 5 inhibitors primary drug class - oral erectile dysfunction therapy

Sildenafil (Viagra)-25-100mgVardenafil (LeVitra) 5-20mg; Vardenafil (Staxyn) 10 mg Tadalafil (Cialis) 5-20mg, also 2.5-5 mg q dayAvanafil (Stendra) 50-200mg

Drugs are potent, selective inhibitors of type 5 phosphodiesterase - improve erectile function by inhibiting breakdown of cyclic GMP - smooth muscle relaxation enhanced Contraindicated with Nitrates, Teach Patient about Non-arteritic anterior ischemic optic neuropathy (NAION)Precautions with Alpha Blockers

Sildenafil (Viagra)

• Dosage: 25-100mg, starting dose 50 mg

• Onset 30-60 mins; peak 60-120 minutes; mostly gone in 8-12

hours; reduced clearance in elderly (start low, go slow); empty

stomach most sensitive to food!

• Contraindications:

– Pt. On any nitrates

– Patients with retinitis pigmentosa

• Precautions: Start @ 25 w/ >65y/o, Caution w/ CHF or MI within

last 6 months, resting hypotension, if on alpha blockers start

low and titrate up as needed; >3 drinks of alcohol

• Side Effects

– Headache, flushing, indigestion, dyspepsia, stuffiness, visual

disturbances

Slide 8 Sildenafil

• Stop & seek medical help if visual acuity or hearing changes

• Hepatic impairment- start low, go slow

• Renal Insufficiency: Volunteers with mild (CLcr=50-80 mL/min)

and moderate (CLcr=30-49 mL/min) renal impairment, the

pharmacokinetics of 1 oral dose of VIAGRA (50 mg) were not

altered. With severe (CLcr=<30 mL/min) renal impairment, sildenafil

clearance was reduced, resulting in approximately doubling of

concentrations compared to age-matched volunteers with no renal

impairment.

• In addition, N-desmethyl metabolite AUC and Cmax values

significantly increased 200% and 79% respectively in subjects with

severe renal impairment compared to subjects with normal renal

function.

– From prescribing information @

http://www.pfizer.com/files/products/uspi_viagra.pdf

Slide 9 Vardenafil

• Dosage: 5-20mg, Starting dose 10 mg

• Contraindicated:

– Patients on nitrates or guanylate cyclase stimulators (riociguat)

– Not for patients with QT prolongation

– Do not use with patients on dialysis as no research done (prescribing info)

• Precautions: Start @ 5 mg if >64; Adjust dose or don’t use w/ moderate-severe renal impairment; start low, go slow with hepatic impairment; hypotension with excessive alcohol

• Drug Interactions

• Adverse Reactions:

– Headache, flushing, stuffy nose, dizzy

• Instruction

– High fat may effect absorption, others similar

Vardenafil Hcl

• Do not take with nitrates

• Caution with alpha- blockers=may drop your blood pressure to an unsafe level, must start at lowest dose- start low, go slow.

• Metabolism through CYP3A4- ritonavir and indinavir increase half LeVitra- use 2.5mg no more than every 72 hours for ritonavir and 2.5 mg in 24 hours with indinavir

• Erthromyacin & Ketoconazole- increase Levitra- use 2.5-5 mg dose

Slide 11 Vardenafil Hcl

• Do not use LEVITRA in patients on renal dialysis as

vardenafil has not been evaluated in such patients.

• No dosage adjustment is necessary in patients with

creatinine clearance (CLcr) of 30–80 mL/min. In male

volunteers with CLcr = 50-80 ml/min, the

pharmacokinetics of vardenafil were similar to those

observed in a control group with CLcr >80 mL/min. In

male volunteers with CLcr = 30-50 mL/min or CLcr<30

mL/min, the AUC of vardenafil was 20–30% higher

compared to that observed in a control group with

CLcr>80 mL/min.

– From prescribing information at

http://www.levitra.com/assets/pdf/PI.pdf

Slide 12 Tadalafil

• Dosage: 5-20mg; Starting dose- 10mg; 36 hour duration

• Onset 30-60 mins; peak effect- 60-120 mins

• Contraindication:

– Patients taking nitrates

– Not recommended for men w/ MI last 90 days, stroke last 6

months, Class 2 or > heart failure; uncontrolled arrhythmias,

hypotension <90/50

• Side Effects:

– Headache, dyspepsia, dizziness, flushing, nasal stuffiness, back

pain, myalgia

– Teaching: Can take with foods, but high fat may delay

absorption, same as others; no excessive alcohol (<5units)

– Stop and seek medical help if visual acuity change or hearing

loss

Tadalafil

• Renal Patients:

• Patients with creatinine clearance 30 to 50

mL/min: Dosage adjustment may be needed.

• Patients with creatinine clearance less than

30 mL/min or on hemodialysis: For use as

needed: Dose should not exceed 5 mg every

72 hours. Once daily use is not

recommended.

– From prescribing info @ http://pi.lilly.com/us/cialis-

pi.pdf

Slide 14 Avanafil

• Dosage: 50-200mg; starting dose 100mg

• Onset 20 mins; peak effect 30-45 mins; Short 3 hour duration

• Caution: alpha blockers- should be stable on them and then

start with lowest dose and titrate as tolerated; if NAION

• Can take with food, but delays absorption- empty stomach

• Contraindication:

– Patients taking nitrates- not within 12 hours

• Side Effects:

– Headache, flushing, nasal stuffiness, upper respiratory

infection, back pain, dizziness

– Teach to stop drug if changes in vision or hearing

Slide 15 Avanafil

• Not recommended in men with MI, stroke or

life-threatening arrhythmia or coronary

revascularization within last 6 months, Low

BP < 90/50 or HTN >170/100; heart failure

Class 2 or higher; angina with sex

• No greater than 3 units of alcohol with

avanafil

• Start lower and may go to full dose in geriatric

patients (caution depending on patient)

• No data with severe renal or hepatic

impairment

Avanafil

• Caution with alpha-blockers -may drop your blood pressure to an unsafe level, must start at lowest dose- start low, go slow. Caution with patients with left ventricular outflow obstruction or severely impaired autonomic BP control

• Metabolism through CYP 450 isoform 3A4- Do not use stendra with drugs such as ketoconazole, clarithromyacin, ritonavir, atazanavir and indinavir, etc…

• No higher than 50 mg maximum in 24 hours with erthromyacin, amprenavir, diltiazem, aprepitant, fluconazole, fosamprenavir and verapamil

Slide 17 Comparison of Medications

• No good head to head trials.

• System review and network meta-analysis. 118 trials

included (31,195 individuals). Tadalafil was most

effective followed by vardenafil. Safety analysis did not

reveal any differences amongst agents -Yuan, J et al. (2013).

Comparative effectiveness and safety of oral phosphodiesterase type 5 inhibitors for

erectile dysfunction: A systemic…European Urology, 63(2013), 902-912

• A trade-off network meta-analysis of PDE-5 inhibitors for

ED. 82 trials for efficacy and 72 for adverse events.

Sildenafil 50 mg was treatment of choice for efficacy

and tadalafil 10mg for tolerability. – Chen, L. et al. (2015).

Phosphodiesterase 5 inhibitors for the treatment of erectile dysfunction: A trade-off

network meta-analysis. European Urology, 68(2015), 674-680.

Slide 18 Treatment: MUSE

Urethral suppository •Dosage: 125 to 1000 mcg•Onset: 5-10 mins; Duration 30-60mins•Contraindications: Hypersensitivity, Abnormally formed penis, conditions that can lead to priapism like sickle cell, multiple myeloma, leukemia, or if the patient has a penile implant•Caution if patient has low blood pressure or history of fainting•50% efficacy at best- may need to combine with orals

•Adverse Reactions: penile pain, hypotension, prolonged

erections, lightheadedness, or dizziness•http://www.muserx.com/pdf/muse-full-prescribing-information.pdf

MUSE

Always dose in the clinic and check vitals before and after

medication

Check applicator that medication present

Keep penis upright during instillation process

After administration, ensure that pellet delivered

Roll penis for 10-30 seconds and watch tip to make sure pellet does

come out of penis

Walk to promote increased blood flow to penis

Restrictive device placed at base of penis to decrease venous return

from penis can not be on longer than 30 mins

Lie down if dizzy, change positions slowly

Do not give to patients with low blood pressure

Slide 20 MUSE & Oral Agents

• Oral agent 1 hour before MUSE

• Synergistic effect improves efficacy

• 23 patients unsatisfied w/ Sildenafil (100mg) alone, added MUSE 500mcg. 83% reported improved penile rigidity and sexual function, erection sufficient for penetration 80% of the time-Raina, R., Nandipati, K.C., et al. (2005). Combination therapy: medicated urethral system for erection enhances sexual satisfaction in sildenafil citrate failure following nerve-sparing radical prostatectomy. Journal of Andrology, 26(6), 757-760.

• 28 patients failed MUSE & Viagra as single agent- used MUSE 500mcg with sildenafil 100mg @ 30 months all 28 patients reported erections sufficient for penetration– Nebra, A. et al. (2002). Rationale for combination thereapy of intraurethral prostaglandin

E1 & sildenafil in the salvage of erectile dysfunction patients desiring noninvasive therapy. International Journal of Impotence Research, 14 (Supp 1), S38-42.

• 26 patients failed MUSE & Viagra as single agents- combo MUSE 500mcg & Sildenafil 100mg- Improved efficacy in combination-Nehra, A., Hakim, L.S., Barrett, D.M., Blute, M.L., & Moreland, R.B. (2000). Combination of sildenafil and intraurethral prostaglandin E1 salvaged a selected population of men with ED. Abstract submitted to the 95th Annual Meeting of the American Urological Association in Atlanta.

Slide 21 Treatment of ED: Injections

Intracavernosal Injection Therapy (PGE1 & Trimix): alprostadil sterile powder and alprostadil alfadex, both synthetic formulations of prostaglandin E1Trimix (off-label/non-FDA approved)-PGE1, phentolamine,

& papavarine

•Dosage: alprostadil-5-40 mcg w/ PGE; Doses vary w/

trimix and bimix

•Onset: 5-20 mins; duration: 30 mins-4hours

•Contraindicated: drug hypersensitivity, risk for priapism

(e.g. sickle cell disease, hypercoagulable states) &

women/children

•Adverse Reactions: prolonged erections or priapism,

penile pain, and fibrosis with chronic use, ecchymosis,

hematoma

Precautions Obese abdomen

History vaso-vagal response

Dexterity problems

Uncontrolled hypertension

Severe Deformity of the penis/Peyronie’s Disease

– www.caverject.com/prescribingInfo.aspx

– http://www.edex.com/filebin/pdf/Edex_Full_Prescribing_Information.pdf

Contraindications

Concurrent use of MAO Inhibitors

Penile prosthesis

Sexual activity is inadvisable or contraindicated

Predisposition to priapism due to hematologic disorders (e.g., sickle cell anemia, multiple myeloma, leukemia)

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Slide 23 Advantages

High efficacy rate

Reliable

Suitable for travel but agents with PGE1

requires refrigeration

Disadvantages Invasiveness and

anxiety of injecting needle into penis

Cost/insurance coverage

Side effects:• Priapism

• Bruising/bleeding

• Hematoma

• PGE1 pain

Papaverine may test (+) for opiates on urine screen1

Albaugh (2010) Urological Nursing, 30, 167-177.1Pierpaoli & Mulhall (1998). Journal of Urology, 159, 1299.

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Slide 24 Summary

• There are several treatment pharmacological

options for erectile dysfunction including oral

agents (pills), intraurethral agents and

intracavernosal injections

• Patients need to understand all treatment

options to determine what they want to do

• Instructions and teaching can make a big

difference in success and continuation of

medications

to attain and/or maintain a penile erection sufficient for

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