Microsoft word - guideline_4574.doc

Prior Authorization Guideline
Guideline: CSD - Impotence Agents
Therapeutic Class: Cardiovascular Agents
Therapeutic Sub-Class: Vasodilating Agent
Client: County of San Diego
Approval Date: 2/13/1998
Revision Date: 12/6/2005
I. BENEFIT
COVERAGE
Table 1: Formulary status
Non-Formulary Products Formulary
Products
Levitra® (vardenafil) Muse® (alprostadil) Viagra® (sildenafil)
II. INDICATIONS

A. FDA Approved Indications
Cialis, Levitra, Muse or Viagra is indicated for the treatment of erectile dysfunction.1-5
Agents for impotence have been studied for the treatment of erectile dysfunction due to organic, psychogenic Impotence can be caused by drugs, chronic illness (s), surgical procedures, or trauma.26 Underlying cause(s) of impotence should be addressed prior to initiating treatment. These include, but areplacement of offending medications, improvement of glycemic control (in diabetics), androgen replacdeficient), and thyroid, adrenal, or pituary replacement.26 Organic causes of erectile dysfunction are listed below:6-8 Chronic illness which may cause erectile dysfunction (ED): Cardiac Disease Central nervous system disease (i.e. temporal lobe or limbic system disorders) Malignancy Multiple Sclerosis Renal disease Respiratory Disease Medication reported to interfere with male potency: Alcohol Anticancer chemotherapy Anticholinergic agents Antidepressants (TCA, MOAIs, SSRI) Antiparkinson agents Barbiturates & congeners Benzodiazepines Beta blockers Cannabis Cimetidine Clonidine Guanabenz, guanfacine, guanethidine Immunosuppressive agents Diuretics Lithium Opiates Other illness or disorder which may cause ED: Endocrine disorders:
Androgen
Diabetes mellitus Hemachomatosis Hyper/hypogonadism Hyperprolactinemia Thyroid disease Chordee Microphallus/micropenis Peyronie’s disease Priapism Syphilis and/or tabes dorsalis Genital herpes Arterial procedures (i.e. aortic-iliac-femoral bypass) Renal transplantation Urologic procedures (i.e. Radical cystectomy/prostatectomy) Pelvic irradiation Neurologic procedures A. Non-FDA Approved Indications
RevatioTM (sildenafil 20 mg) is the FDA-approved formulation of sildenafil for the treatment of pulmonary arteria


III. GUIDELINE

A. Muse, Viagra, Levitra, or Cialis will be approved, except when excluded as a plan benefit, based on the follo
2. Confirmed diagnosis of organic impotence as defined by one of the following: 6-8
(a) The patient has an underlying condition consistent with organic impotence. A copy of written chart the underlying condition and its causative relationship the patient’s organic impotence is required.6-7 Organic impotence is considered a consequence of chronic medical conditions that result in impaflow or nerve damage, mixed organic/psychogenic causes, or necessary use of medications that candiscontinued.6-7 Underlying conditions include atherosclerosis, cardiac disease (e.g., hypertension, peripheraldiabetes, central nervous system disease, multiple sclerosis, renal disease, hypogonadism, histoprostate cancer, spinal injuries, etc.6-7 (b) The patient’s ED is caused by one of the following drugs that cannot be discontinued or switched. A chart documentation of the causative relationship of the patient’s ED is required.8 (1) Cardiovascular drugs (thiazide diuretics, spironolactone, methyldopa, clonidine, guanaben atenolol, metoprolol, pindolol, propranolol, doxazosin, prazosin, terazosin, phenoxybenzamin
nifedipine, diltiazem, verapamil, disopyramide);8 OR

(2) Anticonvulsants (carbamazepine, phenytoin);8 OR
(3) Antidepressants (TCAs, SSRIs, trazodone, MAO inhibitors);7 OR
(4) Antipsychotics
(phenothiazines);7 OR

(5) Anxiolytics (short-acting barbiturates, benzodiazepines);7 OR
(6) Gastrointestinal drugs (cimetidine, ranitidine, metoclopramide).7 3. The patient is currently NOT taking organic nitrates (e.g., nitroglycerin), if Cialis, Levitra or Viagra is pre
B. The following maximum quantity will be authorized:
Viagra: Max of 6 or 8 tablets per month as per plan design. Levitra: Max of 6 or 8 tablets per month as per plan design. Cialis: Max of 6 or 8 tablets per month as per plan design. CONTRAINDICATIONS AND WARNINGS
A. Contraindications
1. Cialis, Levitra, and Viagra1-3
Nitrates
Administration of Cialis, Levitra, and Viagra with organic nitrates, either regularly or intermittently, incontraindicated, due to potentiation of the hypotensive effects of nitrates. Cialis, Levitra, and Viagra are contraindicated in patients with a known hypersensitivity to any comp
product(s).
Muse is contraindicated in men with any of the following: • Neonatal respiratory distress syndrome • For use with pregnant sexual partners unless a condom is used B. Warnings
1. Cialis, Levitra, and Viagra1-3
a. Cardiovascular
There is some potential cardiac risk of sexual activity in patients with preexisting cardiovascular disea
Levitra, or Viagra, should not generally be used in men for whom sexual activity is inadvisable becau
underlying cardiovascular status.
Patients with left ventricular outflow obstruction (e.g., aortic stenosis and idiopathic hypertrophic subabe sensitive to the action of vasodilators, including PDE5 inhibitors.
There are no controlled clinical data on the safety or efficacy of Cialis, Levitra, or Viagra in the follo
• Patients who have suffered a myocardial infarction (MI), stroke, or life-threatening arrhythmia w • Patients with hypotension (BP <90/50 mmHg) or hypertension (BP >170/110mmHg) • Patients with cardiac failure or coronary artery disease causing unstable angina • Severe hepatic impairment and end-state renal disease requiring renal dialysis (Levitra only) b. Prolonged erection
Prolonged erection and priapism greater than 4 hours have been reported. This requires immediate medpriapism is not treated immediately, penile tissue damage and permanent loss of potency may result. Drug-Drug
Interactions
Cialis, Levitra and Viagra are predominantly metabolized by hepatic enzyme CYP3A4. Dose adjustmerecommended in patients who are taking potent inhibitors of CYP3A4 such as ritonavir, ketoconazole, Because of the potential for symptomatic hypotension and syncope, which occurred in 3% and 0.4%, respeduring in-clinic dosing, Muse titration should be carried out under medical supervision. During post-marksyncope occurring within one hour of administration has been reported. DOSING1-5
mg, taken prior to anticipated sexual activity. Dose may be increased to decreased to 5 mg, based on individual response. Maximum dosing frequeday in most patients. Starting dose: 5 mg not more than once daily Maximum dose: 10 mg no more than once every 48-hour Cialis should be initiated at the lowest recommended dose. Maximum dose of 10 mg, not to exceed every 72 (e.g., ketoconazole, riton 10 mg, taken orally approximately 1 hour beforesexual activity. Dose may20 mg or decreased to 5 mg, based on individual response. Maximum dosonce daily. Starting dose of 5 mg should be considered. Should be initiated at a dose of 5 mg, in patients stabilized on alpha block Ritonavir: 2.5 mg, not to exceed every 72 hours. Indinavir, ketoconazole 400 mg daily, intraconazole 400 mg daily: 2.5 mgperiod. Ketoconazole 200 mg daily, intraconazole 200 mg daily, erythromycin: 5 period. 50 mg taken, approximately 1 hour before sexual activity. Dose may be inmg or decreased to 25 mg, based on individual response. Maximum dosin Starting dose of 2.5 mg should be considered. Starting dose of 2.5 mg should be considered. Starting dose of 2.5 mg should be considered. Doses of 50mg or 100mg of Viagra® should not be taken within 4 hours oblocker. A 25mg dose may be taken at any time. Ketoconazole, erythromycin, saquinavir: starting dose of 2.5 mg should b 125 mcg pr 250 mcg are recommended for initial dosing. Patient should blowest effective dose. AVAILABILITY1-4
Levitra: 2.5mg, 5mg, 10mg, and 20mg tablets Viagra: 25mg, 50mg, and 100mg tablets Muse: 125mcg, 250mcg, 500mcg, 1000mcg urethral suppositories
VII. BACKGROUND

Description1-3
Penile erection is a hemodynamic process initiated by the relaxation of smooth muscle in the corpus caassociated arterioles. During sexual stimulation, nitric oxide is released from nerve endings and endothelial cavernosum. Nitric oxide activates the enzyme guanylate cyclase resulting in increased synthesis of monophosphate (cGMP) in the smooth muscle cells of the corpus cavernosum. The cGMP in turn triggerelaxation, allowing increased blood flow into the penis, resulting in erection. The tissue concentration of cGMboth the rates of synthesis and degradation via phosphodiesterases (PDEs). The most abundant PDE in cavernosum is the cGMP-specific phosphodiesterase type 5 (PDE5); therefore, the inhibition of PDE5 enhanceby increasing the amount of cGMP. Sexual stimulation is required to initiate the local release of nitric oxidePDE5 has no effect in the absence of sexual stimulation. ED agents appear to be similarly effective. The prithe duration of action. Viagra and Levitra have duration-of-action of 4-5 hours, while Cialis has duration- hours. Viagra has the longest safety record of these agents. Clinical
1. ED of Various Etiologies

Eardley et al (2004) compared the efficacy of Cialis to placebo for the treatment ED in a multicenter, ra
blind trial in 220 men in the UK and Italy.9 Subjects with mild to severe ED of organic, psychogenic, or m
age 53) were randomized to Cialis 20mg or placebo for 12 weeks. Subjects were stratified by baseline ED
with a history of ineffective treatment of ED with Viagra were excluded. Outcome was assessed on the I
of Erectile Function (IIEF) and Sexual Encounter Profile (SEP). Three co-primary end points were m
baseline to endpoint in erectile function domain score (IIEF), successful vaginal penetration and succ
attempts. In the Cialis group, successful intercourse attempts increased from 17.4% at baseline to 73
compared to 7.3% and 10.8%, respectively, in the placebo group (p<0.001). Headache and dyspepsia
significantly more patients treated with Cialis compared to placebo. The authors concluded that Cialis
function and was well tolerated in men with mild to severe ED, demonstrating efficacy at 0.5 to 36 hour
study was sponsored by the manufacturer of Cialis.
Porst et al (2003) conducted a multicenter, randomized, double-blind, placebo-controlled, parallel-group
(mean age 57) with mild to severe ED of various etiologies to evaluate the efficacy of Cialis.10 Subjects w
Cialis 20mg or placebo and stratified by severity of ED. The study comprised of two 4-week treatment per
intercourse was attempted 24 hours after dosing and in the other 36 hours after dosing, with an 8 to 10 d
between attempts. The primary efficacy variable was the proportion of successful intercourse attempts. Th
Cialis dosing, 59.2% of intercourse attempts were successful vs. 28.3% in the placebo group (p<0.001).
successful intercourse attempts at approximately 24 hours after treatment was also significantly greater wi
vs. placebo (52.9% vs. 29.1%). Adverse events (headache, flushing, dyspepsia, myalgia) were significa
Cialis group than in the placebo group (all p<0.05). The authors concluded that Cialis 20mg was effective
treatment for ED with a period of responsiveness that began soon after dosing and lasted up to 36 hou
funded by the manufacturer of Cialis.
Stief et al (2004) conducted a multicenter, randomized, parallel group study assessing the long-term safe
Levitra in men aged 22-89 years (mean 55) with ED of various etiologies.11 Severity of ED was not give
who completed an initial 12-month study, 570 were enrolled in a second 12-month follow-up phase.
randomized to Levitra 10 or 20mg in a double-blind, double-dummy fashion. Subjects with a history of u
or intolerance of Viagra were excluded. Sixty percent had previously used Viagra. The co-primary e
erectile function domain score, successful vaginal penetration, and successful intercourse. The 12-mon
was completed by 479 (85%) of the subjects. Overall, Levitra 20mg produced a numerically greater imp
efficacy measures compared to the 10mg dose; however, no formal statistical analysis was performed c
doses. The incidence of adverse events appeared to be greatest during the first few weeks of the study, d
The most common AEs were headache, flushing, and rhinitis in the Levitra group compared to placeb
vision was reported in ≤1% of patients. The authors concluded that Levitra demonstrated long-term safety
a two-year treatment period in men with ED. The study was supported by Bayer.

Hellstrom et al (2003) conducted a 26-week pivotal study, multicenter, 4-arm, parallel-group double-blin
the efficacy and tolerability of Levitra in men with moderate to severe ED (n=805), randomized to Levitra
placebo.12 Previous Viagra treatment was allowed if the patient reported improvement in erectile func
previously failed Viagra were excluded. The primary efficacy variables included the time course of erecti
scores at 4, 8, 12, 18, and 26 weeks of treatment, successful vaginal penetration, and intercourse attempts
IIEF and SEP. Thirty-seven percent of subjects withdrew from the study, with a large percentage in the
5mg group citing lack of efficacy. All doses of Levitra were significantly superior to placebo at all t
variables (p<0.01). The incidence of headache, flushing, and dyspepsia were generally higher for Lev
Adverse events were more frequently observed during the first 4 weeks of the study, and decreased ov
significance not stated). The authors concluded that Levitra produced sustained efficacy in the treatment of
cause or severity) at all doses, with a reduced incidence of nuisance adverse events over time. The stuBayer Corporation, who is affiliated with Levitra. Two published multicenter, double-blind, placebo-controlled studies evaluated the safety and efficacy ovarious etiologies in 1074 men, with a mean age of 57 years.13-14 Subjects were randomized to Viagra placebo up to 24 weeks with dose escalation to 100mg based on efficacy and tolerability. After the dos225 men entered a 32-week, open-label extension study. Efficacy was determined by ability to achieverection, erectile function domain score and intercourse attempts. Viagra was statistically significantly sfor all outcome measures. Erectile function domain scores increased with increasing doses of Viagra instudy (p<0.001), successful intercourse attempts ranged from 64-73% with 25, 50 and 100 mg vs. (p<0.001). The event log data showed a significant dose-response effect for Viagra (72, 80, and 85% for 2respectively, as compared to 50% for placebo; p<0.001) in the proportion of men achieving erections hardintercourse. In terms of successful intercourse attempts, 69% of all attempts were successful with Viagra,with placebo (p<0.001). The incidence of adverse events was 30, 38, and 57 for 25, 50, and 100mg, respec9% with placebo. The most common reported adverse events were headache, flushing, and dyspepsia wdisturbances occurred more often with Viagra compared with placebo, with the highest incidence reported100mg dose. No case of priapism was reported. The authors concluded that Viagra was an effective andED of various etiologies, with a dose-response relationship demonstrated. Treatment failures occurred l50mg dose compared to the 25mg dose with the same incidence of adverse effects, and therefore they suggthe most appropriate starting dose. The study was funded by the manufacturer of Viagra. Nathan et al (1997) conducted a double-blind, placebo-controlled study to evaluate transurethral alpros
ages 27-88, with chronic ED from various organic causes.15 The men were first tested with 4 doses of t
500 and 1000mcg); those who had response were randomized to alprostadil or placebo. During clinic
erections sufficient for intercourse, 961 reported the results of at least one home treatment; 65% had interc
at least once, as compared with 18% who received placebo (p<0.001). The efficacy of Muse was similar r
cause of ED (p<0.001 for all comparisons with placebo). The most common adverse event was mild pen
hypotension (3%) in men receiving Muse. No men had priapism or penile fibrosis. The authors conclude
Muse resulted in erection in the clinic and in intercourse at home.
2. Men with ED and Diabetes

Saenz de Tejada et al (2002) evaluated the safety and efficacy of Cialis in men with Type I and II dia
moderate to severe ED in a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial
seven percent of the participants had a history of hypertension. Patients with a glycosylated hemoglobin (H
recent ketoacidosis, or ≥ 3 hypoglycemic episodes requiring intervention were excluded. Patients were in
irrespective of previous response to ED therapy, including Viagra. Subjects were assigned to three 12-weCialis 10mg, 20mg, or placebo. Three co-primary efficacy variables were erectile function domain score, vrates, and successful intercourse rates, as assessed by the IIEF and SEP. All primary efficacy variablessignificantly improved in patients receiving Cialis compared to placebo, regardless of HbA1c level (p<0 were taking concomitant antihypertensive medication appeared to respond better to the 20mg dose. Headawere more commonly reported in Cialis vs. placebo group with no visual disturbances reported. The authCialis significantly enhanced erectile function in men with diabetes and ED, regardless of ED severity ostudy was funded by the manufacturer of Cialis. Goldstein et al (2003) conducted a multicenter, double-blind, placebo-controlled, parallel-group stud
efficacy and safety of Levitra for the treatment of ED in men with Type I or II diabetes (n=452) who ha
and >50% of patients had severe ED.17 Subjects were randomized to Levitra 10, 20mg, or placebo for 12
criteria were previous failure or significant side effects with Viagra. The primary measures of efficacy we
domain score, successful vaginal penetration/intercourse attempts as assessed by the IIEF and SEP. B
significantly enhanced the rates of successful penetration and successful intercourse compared with placeb
men who were naïve to Viagra, the responses were similar to those who had previously taken it. The mos
events were headache, flushing, and rhinitis. No color disturbances were reported, however transient vi
noted infrequently. The authors concluded that Levitra significantly improved erectile function in diabeticED severity or HbA1c level. The study was funded by Bayer Corporation, who is affiliated with Levitra. Rendell et al (1999) conducted a 12-week, multicenter, double-blind, placebo-controlled trial to asse
efficacy of Viagra for the treatment of ED in men with stable Type I or II diabetes (n=268).18 Subjects w
Viagra 50mg or placebo, with an option to adjust the dose to 25 or 100mg based on efficacy and tolerab
outcome measures were ability to achieve and maintain an erection. Viagra was statistically significantly s
in improving the ability to achieve and maintain an erection (p<0.001). Adverse events that were reported
Viagra group compared to placebo were headache, dyspepsia, flushing, rhinitis, and abnormal vision. No
were reported. The authors concluded that Viagra was an effective and well-tolerated treatment for ED in
study was funded by the manufacturer of Viagra.
3. ED Due to Radical Prostatectomy

Montorsi et al (2004) conducted a 12-week multicenter, randomized, double-blind, placebo-controlled tr
safety and efficacy of Cialis 20mg in men with mild to severe ED following bilateral nerve sparing
prostatectomy (BNSRRP).19 A total of 303 men (mean age 60) with preoperative normal erectile functi
BNSRRP 12-48 months prior to the study were randomized to Cialis 20mg or placebo. The three co-prima
mean change from baseline in erectile function domain score, successful vaginal penetration, and succ
Cialis patients significantly greater improvements in all efficacy variables compared to placebo (p<0.00
Cialis reported significantly more headache, dyspepsia, and myalgia compared to those taking plac
concluded that Cialis was an effective and well-tolerated treatment for ED in patients with BNSRR
supported by the manufacturer of Cialis.
Brock et al (2003) conducted a multicenter, randomized, parallel-group study comparing Levitra to placeb
ED following unilateral or bilateral nerve sparing radical prostatectomy (NS-RRP).20 Subjects were rand
10, 20, or placebo for 12 weeks. 72% of patients had severe ED. Exclusion criteria included non-response
to adverse events to Viagra. The primary efficacy variables were erectile function domain score and succ
penetration/intercourse. At the end of the study, both doses of Levitra were statistically significantly sup
all efficacy variables (p<0.0001). The most common adverse events occurring more frequently with Levitr
headache, flushing, and rhinitis. Vision-related adverse events reported in the Levitra groups were incre
light. The authors concluded that Levitra significantly improved erectile function in men with severe ED a
study was funded by Bayer, who is affiliated with Levitra.
Raina et al (2004) performed an evaluation of 174 men with ED post radical prostatectomy (RP) who
Viagra after a mean of 3 months post surgery.21 The starting dose was 50mg titrated to 100mg. The resp
using an abbreviated 5-question version of the IIEF (SHIM) at baseline and one year after Viagra
questionnaire, which is a measure of patient satisfaction with treatment, was also completed by the patients
successful intercourse: 76% in the bilateral NSRP group, 53.5% in the unilateral NSRP group, and 14.
group. SHIM analysis showed a greater magnitude of improvement in the bilateral NSRP group compare
groups (p<0.020). Review of the data revealed four factors that were associated statistically with a succe
presence of at least one neurovascular bundle, a preoperative SHIM score of 15 or greater, age ≤ 65 years
RP to start of Viagra of more than 6 months (p<0.001). The most common adverse events were hdizziness, and dyspepsia. The authors concluded that the efficacy of Viagra after RP correlated neurovascular bundle preservation, preoperative erectile function status, age, and interval before starting tthe study investigators were affiliated with Pfizer. 4. ED Due to Spinal Cord Injury

Giuliano (1999) conducted a multicenter, double-blind trial assessing the safety and efficacy of Viagr
resulting from traumatic spinal cord injury (SCI).22 A total of 178 men with a mean age of 38 were random
cross-over design to placebo or Viagra 50mg, with an option to titrate the dose up to 100mg or down
efficacy and tolerability. Each treatment was given for 6 weeks, with a wash-out interval of 2 weeks betwe
distribution of the neurological level of the SCI was balanced between the two sequence groups. Thevariable was proportion with residual erectile function at baseline reporting improved erections and treSecondary variables included proportion of all subjects, including those with no residual erectile improved erections and a treatment preference. Of the men with residual baseline erectile function, 78% erections and a preference for Viagra over placebo. For all patients, including those with no baseline erecreported improved erections and a preference for Viagra. In the patients with no baseline residual erecreported improved erections and a preference for Viagra. For all patients (regardless of residual erectile fuproportion of successful intercourse attempts was 55% with Viagra compared to 0% with placebo. No p The most frequently reported adverse event with Viagra were headache, flushing, and dyspepsia. Transienvision were reported in 2% of Viagra users and none in placebo. The authors concluded that Viagra wawell-tolerated treatment for ED secondary to SCI. The study was funded by the manufacturer of Viagra. 5. Men Previously Unresponsive to Viagra

Carson (2004) evaluated the efficacy of Levitra in 584 men previously unresponsive to Viagra (by history
double-blind, placebo-controlled, flexible-dose study of 12 weeks duration.23 During the first 4 weeks of
were randomized to placebo or Levitra 10mg with the option to titrate the dose by one dose level (5, 10,
efficacy and tolerability at 4 and 8 weeks. Thirty-four percent of subjects receiving Levitra and 25% rece
diabetes. The primary efficacy endpoints were the erectile function domain score, or discontinuation
successful vaginal penetration and successful intercourse attempts. A total of 395 patients completed the s
the study, 1% of patients in the Levitra group reduced their dose to 5mg, 20% remained on 10mg, and 7
dose to 20mg. Levitra was statistically significantly superior to placebo throughout the study for all efficac
rates of successful completion of intercourse with Levitra were 2.5 to 4-fold higher than those of placeb
interval (p<0.001); the overall mean success rate increased from a baseline of 10.5% to 46.1%. Levitra w
tolerated, with a low incidence of adverse events. The authors concluded that Levitra is an effective
including in men with a history of non-response to Viagra. The study was funded by Bayer Corporation
with Levitra.
C. National Guidelines
1. American Urological Association (AUA) (2005)24
American Urological Association Education and Research updated the Erectile Dysfunction Guidelifollowing recommendations standard: • The management of ED begins with the identification of organic comorbidities and psychosexual should be appropriately treated or their care triaged. • Current therapies that should be considered for the treatment of ED include: PDE5 inhibitors (C Viagra), intra-urethral alprostadil (Muse), intracavernous vasoactive drug injection, vacuum constripenile prosthesis implantation. The patient and, when possible, his partner should be informed of the options and their associated risks and benefits. The choice of treatment should be made jointly by the and partner, when possible, taking into consideration patient preferences and something is missing her • Cialis, Levitra, or Viagra are first-line of therapy for ED and are contraindicated in patients who nitrates. Monitor for efficacy, adverse effects, and any significant change in health status including meproceeding to other therapies, patients who failed Cialis, Levitra or Viagra therapy should be evaluwhether the trial was adequate, be informed of the benefits and risks of other therapies, including thePDE5 inhibitor, alprostadil intra-urethral suppositories, intracavernous drug injection, vacuum constrpenile prostheses. • The initial trial dose of Muse should be administered under healthcare provider supervision due to the • Patients and partner considering penile prosthesis implants should be informed of the following: ty possibility and consequences of infection and erosion, mechanical failure, and resulting reoperation; dnormal flaccid and erect penis, including penile shortening; and potential reduction of the effetherapies if the device is subsequently removed. Arterial reconstructive surgery is a treatment optioindividuals with recently acquired ED to a focal arterial occlusion and in the absence of any evidevascular disease. The following are not recommended for treatment of ED: trazodone, testosterone in the patient normal level, yohimbine, or herbal therapies, surgeries performed to limit the venous outflow of the penis. The above recommendations are defined as standard by the committee. The guideline is a standardoutcomes of the alternative interventions are sufficiently well-known to permit meaningful decisions, andunanimity about which intervention is preferred. 2. American Association of Clinical Endocrinologists (AACE) (2003)25
At this time, there is insufficient evidence to support the superiority of one agent over the otherspharmacokinetic and adverse event profiles do exist. Viagra and Levitra have very similar pharmacokinetime to achieve maximum serum levels (Tmax) of approximately 1 hour and a serum half-life of approxicontrast, Cialis has a Tmax of approximately 2 hours and a half-life of approximately 18 hours. Ametabolized by the liver, so the dosage should be adjusted in those patients with altered hepatic functionmedication, especially those that affect cytochrome P450. The side effect profiles of the three drugs arthree medications have side effects due to peripheral vasodilation such as facial flushing, nasal congestidyspepsia. Both Viagra and Levitra, but not Cialis, have some cross-reactivity with PDE-6 and thus may peffects. Back pain has been reported in a limited number of patients, especially those taking Cialis, and thof this adverse effect is unknown. AACE Male Sexual Dysfunction Task Force medical guidelines for clinical practice for the evaluation recommends the following (System of Care for Male Sexual Dysfunction): Step 1: Accurate history (preferably with the couple) - Make sure concerns are not just aging-rela
relationship problems, question about performance anxiety. Action: Send to sex therapist or do nocturnal p
Step 2: Outline medical risk factors and medications; change or discontinue medications and stop any subs
Step 3: General examination should be perform on a regular basis (i.e.: blood pressure, breasts for gyneco
sex characteristics, peripheral circulation, genital examination, especially for penile fibrosis, t
bulbocavernosal reflex; rectal examination: assess prostate, follow-up on abnormal findings--that is, cardio
suspected endocrine diseases, or abnormal prostate).
Step 4: Laboratory tests to assess: plasma glucose, prolactin, free testosterone, luteinizing hormone and f
hormone if testicular atrophy suspected, thyroid-stimulating hormone or free thyroxine (or both) if
suspected, and other tests (depending on history and physical examination).
Step 5: Treatments (related to risk factors)
Control Diabetes, stop any substance abuse, change medications, treat abnormal hormones, a 3-month teindicated), nocturnal penile tumescence and rigidity testing if risk factors changed and nonresponspsychologic factors. If good erections but early detumescence the use venous constriction ring is recommended. Nonspecific treatments include: Viagra, Levitra, Cialis, Muse, Yohimbine, phentolamine, apomorphinurethral system, penile injections (papaverine/phentolamine, papaverine/phentolamine/alprostadil, alprpenile implants (as last resort). Surgical referrals (urologist) are recommended for severe Peyronie's disease, penile injections, implant, oarterial damage or venous ligation. VIII. REFERENCES

1. Cialis® Prescribing Information, Eli Lilly and Company, August 2005. 2. Levitra® Prescribing Information, Bayer Pharmaceuticals, July 2005. 3. Viagra® Prescribing Information, Pfizer Inc., July 2005. 4. Muse® Prescribing Information, Vivus Inc., Month 2003. 5. Drug Facts and Comparisons. Available at: http://www.efactsonline.com. Accessed 10/30/2005. 6. Merck Manual of Diagnosis and Therapy 17th Ed. (1999) Centennial Edition. Available at http://0online.statref.com.library.uchsc.edu/Document.aspx?DocId=679&FxId=21&SessionId=594E94WVGR=1&Index=4 Assessed November 10, 2005. 7. Thompson JF. Geriatric Urologic disorder. Applied Therapeutics. 8th Edition 2005;101:5-101:6. 8. Current Medical Diagnosis & Treatment - 44th Ed. (2005) 23. Urology. Marshall L. Stoller, & Peter R. Carroll evaluation, male erectile dysfunction. Available at http://0-online.statref.com.library.uchsc.edu:80/document.aspx?fxid=27&docid=277 Assessed ovember 10, 2005. 9. Eardley I, Gentile V, Austoni E, et al. Efficacy and safety of tadalafil in a western European population of men dysfunction. BJU International 2004;94:871-877. 10. Porst H, Nathan HD, Guillano F, et al. Efficacy of tadalafil for the treatment of erectile dysfunction at 24 and 3 dosing: a randomized controlled trial. Adult Urology 2003;62(1):121-125. 11. Steif C, Porst H, Saenz de Tejada I, et al. Sustained efficacy and tolerability with vardenafil over 2 years of tre erectile dysfunction. Int J Clin Pract 2004;58(3):230-239. 12. Hellstrom WJG, Gittelman, M, Karlin G, et al. Sustained efficacy and tolerability of vardenafil, a highly poten phosphodiesterase type 5 inhibitor, in men with erectile dysfunction: results of a randomized, double-blind, 26controlled pivotal trial. Urology 2003:61(Suppl4A0:8-14. 13. Montorsi F, Nathan HP, McCullough A, et al. Tadalafil in the treatment of erectile dysfunction following bilat radical retropubic prostatectomy: a randomized, double-blind, placebo controlled trial. J Urol 2004;172:1036-1 14. Goldstein I, Lue TF, Padma-Nathan, H, et al. Oral sildenafil in the treatment of erectile dysfunction. NEJM 199 15. Nathan HP, Hellstrom WJG, Kaiser FE, et al. Treatment of Men with Erectile Dysfunction with Transurethral 16. Saenz de Tejada I, Knight JR, Anglin G, et al. Effects of tadalafil on erectile dysfunction in men with diabetes.
17. Goldstein I, Young JM, Fischer J, et al. Vardenafil, a new phosphodiesterase type 5 inhibitor, in the treatment dysfunction in men with diabetes. Diabetes Care 2003;26(3):777-783. 18. Rendell MS, Rajfer J, Wicker PA, et al. Sildenafil for treatment of erectile dysfunction in men with diabetes. JA 19. Montorsi F, McDermott TED, Morgan R, et al. Efficacy and safety of fixed-dose oral sildenafil in the treatmen dysfunction of various etiologies. Adult Urology 1999;53(5):1011-1018. 20. Brock G, Nehra A, Lipschultz, LI, et al. Safety and efficacy of vardenafil for the treatment of men with erectile radical retropubic prostatectomy. Journal of Urology 2003;170:1278-1283. 21. Raina R, Lakin MM, Agarwal A, et al. Efficacy and factors associated with successful outcome of sildenafil ci erectile dysfunction after radical prostatectomy. Adult Urology 2004;63(5):960-966. 22. Giuliano F, Hutling C, Masry WE, et al. Randomized trial of sildenafil for the treatment of erectile dysfunction injury. American Neuro Assoc 1999;46(1):15-21. 23. Carson C, Hatzichristou DG, Carrier S, et al. Erectile response with vardenafil in sildenafil nonresponders: a m blind, 12-week, flexible dose, placebo-controlled erectile dysfunction clinical trial. BJU International 2004;94: 24. American Urological Association (AUA) the management of Erectile Dysfunction clinical guideline: an update http://www.auanet.org/timssnet/products/ guidelines/main_reports/ed.pdf 25. Accessed October 312005. 26. McEnvoy GK. AHFS Drug Information 2005. Bethesda, MD: American Society of Health-System Pharmacist IX. ENDNOTES

a. Cialis, Levitra, Muse or Viagra are approved by FDA for treatment of ED in male only.1-4 b. Muse and organic nitrate combination use is not contraindicated.4 This Prior Authorization Guideline represents the recommendation of Prescription Solutions’ Pharmacy and Therapeutics (P&T) Committee. It is based upon the P&T Committee’s review of the available evidence as of the date of drafting or revision of this Prior Authorization Guideline. It is subject to updating from time to time, based upon changes in scientific knowledge and information. This Prior Authorization Guideline is intended as a resource for making coverage decisions for Health Plan members, but it does not replace an individualized case-by-case review and medical necessity determination for each Health Plan member. Copyright 2005 by Prescription Solutions. All rights reserved. This Prior Authorization Guideline is intended for use by Prescription Solutions and Health Plan employees and applicable contracted providers and practitioners only. The information contained in this Prior Authorization Guideline is confidential and proprietary to Prescription Solutions and shall not be used, reproduced, or transferred in whole or in part without Prescription Solutions’ prior written consent.

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