Slide 1 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 Slide 4 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)-25-100mg Vardenafil (LeVitra) 5-20mg; Vardenafil (Staxyn) 10 mg Tadalafil (Cialis) 5-20mg, also 2.5-5 mg q day Avanafil (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 Slide 7 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 Slide 10 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 Slide 13 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 Slide 16 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 Slide 19 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.,