ph-991089
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Erectile Dysfunction - Phosphodiesterase Type 5 Inhibitors, Topical Prostaglandin Quantity Limit

Policy Number: PH-991089

This program applies to Blue Partner, Commercial, NetResults A series, SourceRx, and Health Insurance Marketplace formularies. 

Self-funded groups may exclude this class of medications from coverage or have varying age and/or quantity limitations. Group specific policies will supersede this general policy when applicable. Refer to member’s benefit plan for further details regarding erectile dysfunction medications (may be referred to as Impotence Drugs).

Erectile Dysfunction - Phosphodiesterase Type 5 Inhibitors, Topical Prostaglandin Quantity Limit

TARGET AGENT(S)

Cialis® (tadalafil)a

Levitra® (vardenafil)a

Staxyn® (vardenafil)a

Stendra® (avanafil)

Viagra® (sildenafil)a

a – Generic available

 

Brand (generic)

GPI

Multisource Code

Quantity per month

Cialis (tadalafil)

  2.5 mg tablet

40304080000302

M, N, O, or Y

30a

(cumulative)

  5 mg tablet

40304080000305

M, N, O, or Y

  10 mg tablet

40304080000310

M, N, O, or Y

8^b

(cumulative)

  20 mg tablet

40304080000320

M, N, O, or Y

Levitra (vardenafil)

  2.5 mg tablet

40304090100310

M, N, O, or Y

  5 mg tablet

40304090100320

M, N, O, or Y

  10 mg tablet

40304090100330

M, N, O, or Y

  20 mg tablet

40304090100340

M, N, O, or Y

Staxyn (vardenafil)

  10 mg orally disintegrating tablet

40304090107230

M, N, O, or Y

Stendra (avanafil)

  50 mg tablet

40304015000320

M, N, O, or Y

  100 mg tablet

40304015000330

M, N, O, or Y

  200 mg tablet

40304015000340

M, N, O, or Y

Viagra (sildenafil)

  25 mg tablet

40304070100310

M, N, O, or Y

  50 mg tablet

40304070100320

M, N, O, or Y

  100 mg tablet

40304070100330

M, N, O, or Y

^ Some groups cover less than or more than 8 tablets per month. Group specific policies will supersede this policy when applicable. Please refer to member’s benefit plan. Only 1 oral agent will be covered per month.

a - Quantity of 30 tablets per month is cumulative for Cialis/tadalafil 2.5 mg and 5 mg

b All agents (except for Cialis/tadalafil 2.5 mg and 5 mg) are limited to 8 doses per month. The quantity of 8 doses per month is cumulative.

CRITERIA FOR APPROVAL                       

Increased quantities will be approved when the following is met:

  1. The requested agent is a phosphodiesterase type 5 (PDE5) inhibitor and ALL of the following:
    1. The patient will NOT be using the requested agent in combination with another phosphodiesterase type 5 (PDE5) inhibitor for the requested indication

AND

    1. The requested agent has been prescribed for preservation of erectile function following a radical retropubic prostatectomy

AND

    1. The quantity requested is less than or equal to 30 tablets per month

Length of Approval: 

Preservation of erectile function following a radical retropubic prostatectomy – 30 tablets per month for 12 months

FDA APPROVED INDICATIONS AND DOSAGE1-4,8

Agent(s)

Indication(s)

Dosage

Cialis® (tadalafil)

Tableta

Erectile Dysfunction (ED)

As needed: Initially, 10 mg taken prior to anticipated sexual activity. Increase to 20 mg or decrease to 5 mg based upon individual efficacy and tolerability. Maximum recommended dosing frequency is once per day.c

Once daily: Initially, 2.5 mg once daily, at approximately the same time each day, without regard to timing of sexual activity. May increase to 5 mg once daily based upon individual efficacy and tolerability.

Benign Prostatic Hyperplasia (BPH)b

5 mg once daily, at approximately the same time each day

ED and BPH

5 mg once daily, at approximately the same time each day, without regard to timing of sexual activity.

Levitra® (vardenafil)

Tableta

Erectile Dysfunction

For most patients, the starting dose is 10 mg, approximately 60 minutes before sexual activity.d May be increased to a maximum dose of 20 mg, or decreased to 5 mg, based on efficacy and side effects. Maximum frequency is once per day.

Staxyn® (vardenafil)

ODTa tablet

Erectile Dysfunction

10 mg, on the tongue without liquid, approximately 60 minutes before sexual activity.d The maximum dose is one tablet per day. Staxyn is not interchangeable with vardenafil film-coated 10 mg tablets (Levitra), which provides higher systemic exposure.

Stendra® (avanafil)

Tablet

Erectile Dysfunction

Initially 100 mg, approximately 15 minutes before sexual activity.d May be increased to 200 mg, or decreased to 50 mg, based on individual efficacy and tolerability. Maximum frequency is once per day.

Viagra® (sildenafil)

Tableta

Erectile Dysfunction

For most patients, 50 mg as needed, approximately 1 hour before sexual activity. May be taken anywhere from 30 minutes to 4 hours before sexual activity. Based on effectiveness and toleration, may be increased to a maximum dose of 100 mg, or decreased to 25 mg. Maximum frequency is once per day.

ODT = orally disintegrating tablet
a – Generic available

b – Limitation of Use: If Cialis is used with finasteride to initiate BPH treatment, such use is recommended for up to 26 weeks because the incremental benefit of Cialis decreases from 4 weeks until 26 weeks, and the incremental benefit of Cialis beyond 26 weeks is unknown.

c – As-needed use was shown to improve erectile function vs placebo up to 36 hours following dosing.

d – Sexual stimulation is required for a response to treatment.

CLINICAL RATIONALE

Efficacy – Erectile Dysfunction (ED)

The American Urological Association (AUA) guideline on ED (2018) states the following:5

  • There is insufficient literature to constitute an evidence base for diagnosis of ED in clinical practice
  • Any type of treatment for ED is a valid choice
  • Oral medications are the least invasive option
  • Oral phosphodiesterase type 5 inhibitors (PDE5i) have the highest graded level evidence (Grade B) for recommendation in use of ED treatment
  • PDE5i’s have similar efficacy in the general ED population

The American Family Physician guideline on the management of ED states the following:7

  • There is no preferred, first-line diagnostic test for ED, and routine screening is not recommended
  • History and physical examination are sufficient in making an accurate diagnosis of ED in most cases
  • PDE5i’s are the most effective oral drugs in the treatment of ED and should be considered first-line therapy
  • PDE5i’s are considered to be relatively similar in effectiveness and there is no rigorous data to suggest that one is superior to another

Sexual behavior studies indicate that commonly prescribed PDE5 inhibitor quantities range from 3 to 6 tablets per patient per month.6

Efficacy – Benign Prostatic Hyperplasia (BPH)

Alpha-1-adrenergic antagonists are initial treatment option for the treatment of BPH.9,10 Alternative agents that may be used to treat lower urinary tract symptoms (LUTS) associated with BPH include 5-alpha-reductase inhibitors (5-ARIs), anticholinergics, and phosphodiesterase-5 inhibitors. Tadalafil is a reasonable option for patients who have erectile dysfunction and mild to moderate symptoms of BPH.9 The efficacy and safety of Cialis (tadalafil) for once daily use for the treatment of the signs and symptoms of BPH was evaluated in 3 randomized, double-blinded, placebo-controlled, efficacy and safety studies of 12 weeks duration. Two of these studies were in men with BPH and one study was specific to men with both ED and BPH. The first study randomized 1058 patients to receive either Cialis 2.5 mg, 5 mg, 10 mg or 20 mg for once daily use or placebo. The second study randomized 325 patients to receive either Cialis 5 mg for once daily use or placebo. The primary efficacy endpoint in the two studies that evaluated the effect of Cialis on lower urinary tract symptoms (LUTS) of BPH was the International Prostate Symptom Score (IPSS), a four week recall questionnaire that was administered at the beginning and end of a placebo run-in period and subsequently at follow-up visits after randomization. The IPSS assesses the severity of irritative (frequency, urgency, nocturia) and obstructive symptoms (incomplete emptying, stopping and starting, weak stream, and pushing or straining), with scores ranging from 0 to 35; higher numeric scores representing greater severity. In each of these 2 trials, Cialis 5 mg for once daily use resulted in statistically significant improvement in the total IPSS compared to placebo.1,5

Preservation of Erectile Function following Prostatectomy

Penile sensation and the ability to have an orgasm are preserved even if the erectile nerves are removed during radical prostatectomy, leaving several options for treatment of erectile dysfunction.  These include the use of oral phosphodiesterase-5 inhibitors, vacuum-assisted erection devices, penile self-injection (prostaglandin E1, papaverine, phentolamine), and intraurethral alprostadil.  Phosphodiesterase inhibitors are most helpful in men who have undergone a nerve-sparing procedure. In one study of 91 men presenting with erectile dysfunction following radical prostatectomy, the response rates to sildenafil in men who had undergone bilateral nerve-sparing, unilateral nerve-sparing, and a non-nerve sparing approach were 72, 50, and 15 percent, respectively.11 A study of 174 men showed  a response rate to sildenafil in men who had undergone bilateral nerve-sparing, unilateral nerve-sparing, and non-nerve-sparing were 76%, 53.5%, and 14.2% respectively.13

The response to sildenafil increases with time following radical prostatectomy.11 The recovery of erectile function can require as long as 18 to 24 months.  Initial failures of therapy might be followed by successful re-challenge at 18 to 24 months postoperatively.12 In a study in which 95 percent of men had undergone nerve-sparing procedures, 60 percent reported benefit from sildenafil at 18 to 24 months after surgery, significantly higher than the 29 percent who reported benefit in the first six months after surgery.11

Safety

Cialis is contraindicated in the following:1

  • Administration of Cialis to patients using any form of organic nitrate is contraindicated. Cialis was shown to potentiate the hypotensive effect of nitrates.
  • History of known serious hypersensitivity reaction to Cialis or Adcirca
  • Administration with guanylate cyclase (GC) stimulators, such as riociguat

Levitra is contraindicated in the following:2

  • Administration with nitrates and nitric oxide donors
  • Administration with guanylate cyclase (GC) stimulators, such as riociguat

Staxyn is contraindicated in the following:4

  • Administration with nitrates and nitric oxide donors
  • Administration with guanylate cyclase (GC) stimulators, such as riociguat

Stendra is contraindicated in the following:8

  • Administration of Stendra to patients using any form of organic nitrate is contraindicated
  • Hypersensitivity to any component of the Stendra tablet
  • Administration with guanylate cyclase (GC) stimulators, such as riociguat


Viagra is contraindicated in the following:3

  • Administration of Viagra to patients using nitric oxide donors, such as organic nitrates or organic nitrites in any form. Viagra was shown to potentiate the hypotensive effect of nitrates.
  • Known hypersensitivity to sildenafil or any component of tablet
  • Administration with guanylate cyclase (GC) stimulators, such as riociguat

For additional clinical information see Prime Therapeutics Formulary Chapter 5.10C: Impotence Agents.

REFERENCES

  1. Cialis prescribing information. Eli Lilly and Company. February 2018.
  2. Levitra prescribing information. GlaxoSmithKline. August 2017.
  3. Viagra prescribing information. Pfizer Inc. December 2017.
  4. Staxyn prescribing information. Bayer HealthCare Pharmaceuticals Inc. August 2017.
  5. Erectile Dysfunction: American Urological Association (AUA) Guideline (2018). Available at https://www.auanet.org/guidelines/male-sexual-dysfunction-erectile-dysfunction-(2018). Accessed January 2021.
  6. Pharmacy Benefits Management Services – Medical Advisory Panel. Phosphodiesterase Type 5 Inhibitors for the Treatment of BPH/LUTS and Penile Rehabilitation: Evidence Summary and Recommendations. Pharmacy Benefits Management Strategic Healthcare Group, Veterans Health Administration, Department of Veterans Affairs. December 2014. Available at: https://www.pbm.va.gov/clinicalguidance/clinicalrecommendations/PDE5I_BPH_LUTS_Evidence_Summary_and_Recommendations.pdf. Accessed January 2021.
  7. Heidelbaugh JJ. Management of Erectile Dysfunction. Am Fam Physician 2010;81(3):305-312. Available at https://www.aafp.org/afp/2010/0201/p305.pdf.  Accessed January 2021.
  8. Stendra prescribing information. Metuchen Pharmaceuticals, LLC. September 2019.
  9. Cunningham GR, Kadmon D, et al. Medical treatment of benign prostatic hyperplasia. UpToDate. Last updated May 2019. Literature review current through January 2020. Accessed February 2020.
  10. Management of Benign Prostatic Hyperplasia: American Urological Association (AUA) Guideline (2014). Available at: https://www.auanet.org/guidelines/benign-prostatic-hyperplasia-(bph)-guideline/benign-prostatic-hyperplasia-(2010-reviewed-and-validity-confirmed-2014). Accessed February 2020.
  11. McCullough AR. Sexual dysfunction after radical prostatectomy. Rev Urol. 2005;7 Suppl 2(Suppl 2):S3-S10. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1477599/. Accessed January 2021.
  12. McCullough AR. Sexual Dysfunction after Radical Prostatectomy. Rev Urol 2005;7(Suppl 2):S3-S10. Available at: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1477599/#!po=31.8182. Accessed January 2021.
  13. Raina R, Lakin MM, Agarwal A, et al. Efficacy and factors associated with successful outcome of sildenafil citrate use for erectile dysfunction after radical prostatectomy. Urol J 2004;63(5):960-966. Accessed January 2021.

This pharmacy policy is not an authorization, certification, explanation of benefits or a contract. Eligibility and benefits are determined on a case-by-case basis according to the terms of the member’s plan in effect as of the date services are rendered. All pharmacy policies are based on (i) information in FDA approved package inserts (and black box warning, alerts, or other information disseminated by the FDA as applicable); (ii) research of current medical and pharmacy literature; and/or (iii) review of common medical practices in the treatment and diagnosis of disease as of the date hereof. Physicians and other providers are solely responsible for all aspects of medical care and treatment, including the type, quality, and levels of care and treatment.
 
The purpose of pharmacy policies are to provide a guide to coverage. Pharmacy policies are not intended to dictate to physicians how to practice medicine. Physicians should exercise their medical judgment in providing the care they feel is most appropriate for their patients.

 
Neither this policy, nor the successful adjudication of a pharmacy claim, is guarantee of payment

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