Federal Employee Program 1310 G Street, N.W. Washington, D.C. 20005 202.942.1000 Fax 202.942.1125 5.06.15 Subject: Sildenafil Citrate Powder Page: 1 of 6 Last Review Date: December 3, 2015 Sildenafil Citrate Powder Description Sildenafil citrate powder Background Pulmonary arterial hypertension is a rare disorder of the pulmonary arteries in which the pulmonary arterial pressure rises above normal levels in the absence of left ventricular failure. This condition can progress to cause right-sided heart failure and death (1). Sildenafil citrate is indicated for oral treatment of pulmonary arterial hypertension (PAH) which is classified by WHO as Group 1 (2). Oral sildenafil citrate is used to treat pulmonary arterial hypertension (PAH, high blood pressure in the lungs) to improve the exercise ability (2). Sildenafil citrate, at different dosages, is currently also marketed as Viagra for the treatment of erectile dysfunction (2). The World Health Organization (WHO) has classified pulmonary hypertension into five different groups(3): Pulmonary arterial hypertension (PAH) makes up the first group, referred to as WHO Group I, and includes: (4,5) Idiopathic (IPAH) Familial (FPAH) Association with other diseases (APAH) such as: o Collagen vascular disease, scleroderma, congenital shunts between the systemic and pulmonary circulation, portal hypertension, HIV infection, drugs, and toxins. o Thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders, and splenectomy. o Associated with significant venous or capillary involvement
Subject: Sildenafil Citrate Powder Page: 2 of 6 o Pulmonary veno-occlusive disease (PVOD) o Pulmonary capillary hemangiomatosis (PCH) The American College of Chest Physicians (ACCP) has published an updated clinical practice guideline for treating PAH (6). These guidelines use the New York Heart Association (NYHA) functional classification of physical activity scale to classify PAH patients in classes I-IV based on the severity of their symptoms. Sildenafil citrate is indicated for patients with NYHA Functional Class II, III, or IV (2). Class I Class II Class III Class IV Patients with pulmonary hypertension but without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea or fatigue, chest pain or near syncope. Patients with pulmonary hypertension resulting in slight limitation of physical activity. These patients are comfortable at rest, but ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope. Patients with pulmonary hypertension resulting in marked limitation of physical activity. These patients are comfortable at rest, but less than ordinary physical activity causes undue dyspnea or fatigue, chest pain or near syncope. Patients with pulmonary hypertension resulting in inability to perform any physical activity without symptoms. These patients manifest signs of right heart failure. Dyspnea and/or fatigue may be present at rest, and discomfort is increased by any physical activity. (7,8)(3-4) These guidelines recommend that oral therapy with Sildenafil citrate be used as first-line therapy for Class II and III patients (6). Sildenafil citrate should not be used alone or as a firstline therapy for Class IV patients unless the patient refuses to use or is believed not to be capable of managing the complex delivery systems for intravenous, subcutaneous, or inhaled medications (6). Sildenafil citrate is the same therapeutic class as Adcirca (tadalafil) and has the same indication for PAH (WHO group 1) (6). Regulatory Status FDA-approved indication: Sildenafil citrate powder is a phosphodiesterase 5 (PDE5) inhibitor indicated for the oral treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening. Studies establishing effectiveness included predominately patients with NYHA Functional Class II-III symptoms. Etiologies were idiopathic (primary) pulmonary hypertension (71%) or pulmonary hypertension associated with connective tissue disease (25%) (2).
Subject: Sildenafil Citrate Powder Page: 3 of 6 The oral use of sildenafil citrate is contraindicated in patients who are using any form of organic nitrate, either regularly or intermittently. Sildenafil citrate potentiates the hypotensive effect of nitrates. This potentiation is thought to result from the combined effects of nitrates and sildenafil citrate on the nitric oxide/cgmp pathway (2). The efficacy of oral sildenafil citrate has not been adequately evaluated in patients taking bosentan concurrently. Sildenafil citrate is not recommended for patients younger than 18 years of age (2). The use of sildenafil for the treatment of erectile dysfunction (ED) remains a plan exclusion. Off-label (non-fda approved) compounded topical preparations of sildenafil citrate have been used off-label for erectile or sexual dysfunction. Related policies Policy This policy statement applies to clinical review performed for pre-service (Prior Approval, Precertification, Advanced Benefit Determination, etc.) and/or post-service claims. Sildenafil citrate powder may be considered medically necessary for the oral treatment of patients with pulmonary arterial hypertension, WHO Group I and NYHA functional classification of physical activity II, III, or IV who are not receiving organic nitrate medications, no concurrent (dual) therapy with PDE-5 inhibitors, the requested oral dose does not exceed 20mg / unit, the requested strength is not commercially available and the requested dosage form is not being used topically. Sildenafil citrate powder may be considered investigational for patients with other diagnoses, or who are being treated with nitrates, and for topical use. The use for the treatment of erectile or sexual dysfunction is not a covered benefit. Prior-Approval Requirements Diagnoses
Subject: Sildenafil Citrate Powder Page: 4 of 6 Patient must have BOTH of the following 1. Pulmonary Arterial Hypertension - WHO Group I 2. NYHA functional classification of physical activity - Class II, III, or IV AND ALL of the following: 1. NO concurrent use with nitrate medication 2. NO concurrent (dual) therapy with PDE-5 inhibitors 3. The requested oral dose does not exceed 20mg / unit 4. The requested strength is NOT commercially available 5. The requested dosage form is NOT being used topically Prior Approval Renewal Requirements Same as above OR PAH WHO Group I and NYHA Class I, who was previously NYHA Class II and has improved due to previous therapy AND ALL of the following: Policy Guidelines 1. NO concurrent use with nitrate medication 2. NO concurrent (dual) therapy with PDE-5 inhibitors 3. The requested oral dose does not exceed 20mg / unit 4. The requested strength is NOT commercially available 5. The requested dosage form is NOT being used topically Pre - PA Allowance None Prior - Approval Limits Duration 12 months
Subject: Sildenafil Citrate Powder Page: 5 of 6 Prior Approval Renewal Limits Duration 12 months Rationale Summary Sildenafil citrate powder is a phosphodiesterase 5 (PDE5) inhibitor indicated for the oral treatment of pulmonary arterial hypertension (PAH) (WHO Group I) in adults to improve exercise ability and delay clinical worsening. Studies establishing effectiveness included predominately patients with NYHA Functional Class II-III symptoms. The use of Sildenafil citrate is contraindicated in patients who are using any form of organic nitrate, either regularly or intermittently. Sildenafil citrate is not recommended for patients younger than 18 years of age. The use of sildenafil for the treatment of erectile dysfunction (ED) remains a plan exclusion (1-8). Prior authorization is required to ensure the safe, clinically appropriate and cost effective use of Sildenafil citrate powder while maintaining optimal therapeutic outcomes. References 1. Lee AJ, Chiao TB, Tsang MP. Sildenafil for pulmonary hypertension. Ann Pharmacother. 2005 May; 39(5):869-84. 2. Revatio [package insert]. New York, NY. Pfizer Inc. March 2014. 3. Farber HW, Loscalzo J. Pulmonary arterial hypertension. N Engl J Med. 2004; 351:1655-65. 4. Simonneau G, Robbins IM, Beghetti M, et al. Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol. 2009; 54(suppl 1):S43-S54. 5. The Venice 2003 revised Classification system; Simonneau G, Galiè N, Rubin LJ et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004; 43: Suppl S: 5s- 12s. 6. Badesch DB, Abman SH, Simonneau G, Rubin LJ, McLaughlin VV. Medical therapy for pulmonary arterial hypertension: updated ACCP evidence-based clinical practice guidelines. Chest. 2007; 131:1917-1928. 7. Trenton D. Nauser, M.D., Steven Stites, M.D. Am Fam Physician. 2001 May 1; 63(9):1789-1799. 8. The Criteria Committee of the New York Heart Association. Nomenclature and Criteria for Diagnosis of Diseases of the Heart and Great Vessels. 9th ed. Boston, Mass: Little, Brown & Co; 1994:253-256.
Subject: Sildenafil Citrate Powder Page: 6 of 6 Policy History Date December 2013 December 2013 December 2014 December 2015 Action New addition to PA Annual editorial review Annual editorial review and reference update Addition of no concurrent (dual) therapy with PDE-5 inhibitors Annual review Keywords This policy was approved by the FEP Pharmacy and Medical Policy Committee on December 3, 2015 and is effective January 1, 2016. Deborah M. Smith, MD, MPH