Tadalafil (Cialis ) for Individual and Family Plans

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Drug and Biologic Coverage Policy

Effective Date ... 4/1/2021 Next Review Date… ... 4/1/2022 Coverage Policy Number ... IP0101

Tadalafil (Cialis

®

) for Individual and Family Plans

Related Coverage Resources

Male Sexual Dysfunction Treatment: Non-pharmacologic

Pulmonary Hypertension (PH) Therapy Quantity Limitations

INSTRUCTIONS FOR USE

The following Coverage Policy applies to health benefit plans administered by Cigna Companies. Certain Cigna Companies and/or lines of business only provide utilization review services to clients and do not make coverage determinations. References to standard benefit plan language and coverage determinations do not apply to those clients. Coverage Policies are intended to provide guidance in interpreting certain standard benefit plans administered by Cigna Companies. Please note, the terms of a customer’s particular benefit plan document [Group Service Agreement, Evidence of Coverage, Certificate of Coverage, Summary Plan Description (SPD) or similar plan document] may differ significantly from the standard benefit plans upon which these Coverage Policies are based. For example, a customer’s benefit plan document may contain a specific exclusion related to a topic addressed in a Coverage Policy. In the event of a conflict, a customer’s benefit plan document always supersedes the information in the Coverage Policies. In the absence of a controlling federal or state coverage mandate, benefits are ultimately determined by the terms of the applicable benefit plan document. Coverage determinations in each specific instance require consideration of 1) the terms of the applicable benefit plan document in effect on the date of service; 2) any applicable laws/regulations; 3) any relevant collateral source materials including Coverage Policies and; 4) the specific facts of the particular situation. Coverage Policies relate exclusively to the administration of health benefit plans. Coverage Policies are not recommendations for treatment and should never be used as treatment guidelines. In certain markets, delegated vendor guidelines may be used to support medical necessity and other coverage determinations.

Overview

This policy supports medical necessity review for tadalafil (Cialis) for the following:

• Erectile Dysfunction

• Benign Prostatic Hyperplasia

• Raynaud’s Disease

• Prophylaxis After Radical Prostatectomy

• High-Altitude Pulmonary Edema (HAPE)

The use of tadalafil (Adcirca®_{, Alyq}™_{) for pulmonary hypertension is addressed in a separate coverage policy.}

Please refer to the related coverage policy link above.

Medical Necessity Criteria

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1. Erectile Dysfunction* [all strengths] BOTH of the following:

A. Treatment of adult male erectile dysfunction B. For Cialis (brand name):

i. Documented intolerance to tadalafil±

±_{Documentation that individual has tried the bioequivalent generic product AND cannot take due to a formulation}

difference in the inactive ingredient(s) [for example, difference in dyes, fillers, preservatives] between the brand and the bioequivalent generic product which, per the prescribing physician, would result in a significant allergy or serious adverse reaction

*Note: Erectile dysfunction therapy is specifically excluded under many benefit plans[both Employer Groups and Individual and Family Plans]. Please refer to the applicable benefit plan document to determine benefit

availability and the terms and conditions of coverage (for example, quantity limitations). Tadalafil (Cialis) for Use as Needed for Erectile Dysfunction

Where covered, a maximum quantity limitation up to 8 tablets per 30 days is allowed of tadalafil (Cialis) 5mg, 10mg, or 20mg.

Tadalafil (Cialis) for Once Daily Use for Erectile Dysfunction

Where covered, a maximum quantity limitation of 30 tablets per 30 days is allowed of tadalafil (Cialis) 2.5 or 5mg.

2. Benign Prostatic Hyperplasia (BPH) [2.5mg or 5mg tablet only]

ALL of the following:

A. Treatment of benign prostatic hyperplasia and EITHER of the following: i. Dosage of tadalafil used will be 5mg once daily OR

ii. Tadalafil 2.5mg tablet daily if an individual is not a candidate for the 5mg daily dosage (for example, creatinine clearance of 30-50 ml/min or concomitant potent inhibitors of CYP3A4, such as ketoconazole or ritonavir)

B. Documentation of inadequate efficacy, contraindication according to FDA label, significant intolerance, or is not a candidate* for BOTH of the following:

i. Alpha1-blocker (for example, doxazosin, terazosin, tamsulosin, alfuzosin)

ii. 5 alpha-reductase inhibitor (for example, finasteride, dutasteride)

[5 alpha-reductase inhibitor/alpha1-blocker combination product, for example

dutasteride-tamsulosin (Jalyn®_{), is also available as a covered alternative]}

C. For Cialis (brand name):

i. Documented intolerance to tadalafil±

*Note: Not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions or is unable to administer and requires this dosage formulation

Tadalafil (Cialis®_{) for Once Daily Use for Benign Prostatic Hyperplasia}

Where covered, a maximum quantity limitation of 30 tablets per 30 days is allowed of tadalafil (Cialis) 2.5 or 5mg.

3. Raynaud’s Disease

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i. Documentation of inadequate efficacy, contraindication according to FDA label, significant intolerance, or is not a candidate* for ONE calcium channel blocker (for example,

amlodipine, felodipine, nifedipine) ii. For Cialis (brand name):

a. Documented intolerance to tadalafil±

*Note: Not a candidate due to being subject to a warning per the prescribing information (labeling), having a disease characteristic, individual clinical factor[s], or other attributes/conditions or is unable to administer and requires this dosage formulation

4. Prophylaxis After Radical Prostatectomy (Early Penile Rehabilitation)

A. Prophylaxis after radical prostatectomy and ALL of the following:

i. Individual had radical prostatectomy within the previous 12 months ii. The medication is prescribed by or in consultation with an urologist. iii. For Cialis (brand name):

±_{Documentation that individual has tried the bioequivalent generic product AND cannot take due to a formulation difference in} the inactive ingredient(s) [for example, difference in dyes, fillers, preservatives] between the brand and the bioequivalent generic product which, per the prescribing physician, would result in a significant allergy or serious adverse reaction

5. Treatment or Prevention of High-Altitude Pulmonary Edema (HAPE)

A. Treatment or prevention of high-altitude pulmonary edema and ALL of the following are met: i. Individual has HAPE or a history of HAPE

ii. EITHER of the following:

a. Individual has tried ONE other pharmacologic therapy for the treatment or prevention of HAPE (for example, nifedipine, salmeterol inhalation powder (Serevent), dexamethasone, acetazolamide)

b. Individual has previously been started on tadalafil and is continuing therapy iii. For Cialis (brand name):

When coverage is available and medically necessary, the dosage, frequency, duration of therapy, and site of care should be reasonable, clinically appropriate, and supported by evidence-based literature and adjusted based upon severity, alternative available treatments, and previous response to therapy.

Note: Receipt of sample product does not satisfy any criteria requirements for coverage.

Reauthorization Criteria

Tadalafil (Cialis) is considered medically necessary for continued use when initial criteria are met AND there is documentation of beneficial response.

Authorization Duration

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Reauthorization approval duration:

• Erectile Dysfunction: up to 12 months

• Benign Prostatic Hyperplasia: up to 12 months • Raynaud’s Disease: up to 12 months

• Prophylaxis After Radical Prostatectomy: not applicable for continuation beyond initial 12 months • High-Altitude Pulmonary Edema (HAPE): not applicable for continuation beyond initial 12 months

Conditions Not Covered

Tadalafil (Cialis) is considered not medically necessary for ANY other use.

Background

OVERVIEW

Tadalafil (Cialis) is indicated for the following uses: • Erectile dysfunction.

• The signs and symptoms of benign prostatic hyperplasia.

• Erectile dysfunction and the signs and symptoms of benign prostatic hyperplasia. Tadalafil has been studied for other indications:

• Raynaud phenomenon. Multiple studies have evaluated the efficacy of tadalafil for Raynaud disease.2-4

Limited information regarding standard dosing is available for the use of Cialis in Raynaud disease.5-7 _In

a study published as an abstract (study design not described), Cialis 20 mg taken two to three times weekly for 4 weeks was compared to pentoxifylline 600 mg twice daily (BID) for 4 weeks in men with severe Raynaud phenomenon associated with autoimmune diseases.5_{Results for Raynaud’s Condition}

Score and attack frequency were more favorable with Cialis than with pentoxifylline. In a double-blind, randomized crossover trial involving 24 patients who were refractory to vasodilators, Cialis 20 mg administered every other day improved symptoms, healed and prevented new digital ulcers, and improved quality of life, compared to placebo.7_{In an open-label study, 20 men with systemic sclerosis}

and Raynaud phenomenon received conventional therapy for Raynaud phenomenon for 12 weeks and then Cialis 10 mg daily for 12 weeks.6_{Cialis decreased the mean number of Raynaud attacks by more}

than 68% (from 158 ± 50 to 108 ± 34.3) and improved the Raynaud Condition Score by more than 70% (from 2.8 ± 0.6 to 2.15 ± 0.6).

• Prophylaxis after radical prostatectomy. Multiple studies have evaluated the efficacy of tadalafil for prophylaxis after radical prostatectomy.8-10_{Phosphodiesterase-5 (PDE5) inhibitors (sildenafil, vardenafil,}

and tadalafil) have been used to improve the return of normal spontaneous erectile function, improve tissue oxygenation and prevent penile fibrosis after nerve-sparing radical prostatectomy. Very limited published information from well-designed controlled trials in a sufficient number of patients and with adequate follow-up is available. According to a recent review article, pharmacological therapy is currently the most attractive option for patients with ED post radical prostatectomy due to the favorable safety profile and ease of use.11_{Cialis 10 mg and 20 mg have been studied on a dosing schedule where}

patients took the drug three days per week whereas Cialis 5 mg is taken daily.12-15

• Pulmonary arterial hypertension. Adcirca (and generics) contain the same active ingredient as tadalafil (Cialis) and are indicated for the treatment of pulmonary arterial hypertension. Tadalafil (Cialis) is available in 2.5 mg, 5 mg, 10 mg, and 20 mg tablets. Adcirca is available as a 20 mg tablet. Tadalafil (Cialis) has been used in multiple studies for pulmonary arterial hypertension.16-18

• High-altitude pulmonary edema. Published guidelines for the prevention of high-altitude pulmonary edema recommend nifedipine as the preferred pharmacologic treatment option.19_{Other pharmacologic}

therapies include salmeterol, sildenafil, dexamethasone, or acetazolamide. For tadalafil, published guidelines recommend a dose of 10 mg twice daily for prevention of HAPE.19

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References

1. Cialis®_{tablets [prescribing information]. Indianapolis, IN: Eli Lilly; June 2020.}

2. Levien TL. Phosphodiesterase inhibitors in Raynaud's phenomenon. Ann Pharmacother. 2006;40:1388-1393.

3. Rosato E, Letizia C, Proietti M, et al. Plasma adrenomedullin and endothelin-1 levels are reduced and Raynaud's phenomenon improved by daily tadalafil administration in male patients with systemic sclerosis. J Biol Regul Homeost Agents. 2009;23:23-29.

4. Schiopu E, Hsu VM, Impens AJ, et al. Randomized placebo-controlled crossover trial of tadalafil in Raynaud's phenomenon secondary to systemic sclerosis. J Rheumatol. 2009;36(10):2264-2268.

5. Levien T. Advances in the Treatment of Raynaud’s Phenomenon. Vasc Health Risk Manag. 2010: (6)167-168

6. Rosato E, Letizia C, Proietti M, et al. Plasma adrenomedullin and endothelin-1 levels are reduced and Raynaud's phenomenon improved by daily Tadalafil administration in male patients with systemic sclerosis. J Biol Regul Homeost Agents. 2009;23:23-29. 43.

7. Shenoy PD, Kumar S, Jha LK, et al. Efficacy of tadalafil in secondary Raynaud's phenomenon resistant to vasodilator therapy: a double-blind randomized cross-over trial. Rheumatology (Oxford). 2010

Dec;49(12):2420-8.

8. Aydogdu O, Gokce MI, Burgu B, et al. Tadalafil rehabilitation therapy preserves penile size after bilateral nerve sparing radical retropubic prostatectomy. Int Braz J Urol. 2011;37:336-346.

9. Montorsi F, Brock G, Stolzenburg JU, Mulhall J, et al. Effects of tadalafil treatment on erectile function recovery following bilateral nerve-sparing radical prostatectomy: a randomized placebo-controlled study (REACTT). Eur Urol. 2014;65:587-596.

10. Mulhall JP, Brock G, Oelke M, et al. Effects of tadalafil once-daily or on-demand vs. placebo on return to baseline erectile function after bilateral nerve-sparing radical prostatectomy – results from a randomized controlled trial (REACTT). J Sex Med. 2016;13:679-683.

11. Magheli A, Burnett AL. Erectile dysfunction following prostatectomy: prevention and treatment. Nat. Rev. urol. 2009;6:415-427.

12. Montorsi F, Brock G, Stolzenburg JU, Mulhall J, et al. Effects of tadalafil treatment on erectile function recovery following bilateral nerve-sparing radical prostatectomy: a randomized placebo-controlled study (REACTT). Eur Urol. 2014;65:587-596.

13. Aydogdu O, Gokce MI, Burgu B, et al. Tadalafil rehabilitation therapy preserves penile size after bilateral nerve sparing radical retropubic prostatectomy. Int Braz J Urol. 2011;37:336-346.

14. Cathala N, Mombet A, Sanchez-Salas R, et al. Evaluation of erectile function after laparoscopic radical prostatectomy in a single center. Can J Urol. 2012;19(4):6328–6335.

15. Megas G, Papadopoulos G, Stathouros G, et al. Comparison of efficacy and satisfaction profile, between penile prosthesis implantation and oral PDE5 inhibitor Tadalafil therapy, in men with nerve-sparing radical prostatectomy erectile dysfunction. BJU Int. 2012 Dec 18.

16. Adcirca tablets [package insert]. Indianapolis, IN: Eli Lilly (marketed by United Therapeutics); December 2019.

17. Tay EL, Geok-Mui MK, Poh-Hoon MC, et al. Sustained benefit of tadalafil in patients with pulmonary arterial hypertension with prior response to sildenafil: A case series of 12 patients. Int J Cardiol. 2008;125:416-417. 18. Palmieri EA, Affuso F, Fazio S, et al. Tadalafil in primary pulmonary arterial hypertension. Ann Intern Med.

2004;141:743-744.

19. Luks AM, Auerbach PS, , Freer L, et al. Wilderness Medical Society Consensus Guidelines for the Prevention and Treatment of Acute Altitude Illness: 2019 Update. Available at:

https://www.wemjournal.org/article/S1080-6032(19)30090-0/fulltext.

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Tadalafil (Cialis ) for Individual and Family Plans

Drug and Biologic Coverage Policy