REVATIO, Sildenafil Citrate (Pulmonary Hypertension) Form

Sildenafil (Revatio®, Liqrev®) is a phosphodiesterase-5 inhibitor. FDA Approved Indication(s) Revatio and Liqrev are indicated:
• For the treatment of pulmonary arterial hypertension (PAH) (World Health Organization [WHO] Group 1) in adults to improve exercise ability and delay clinical worsening.
Revatio is additionally indicated: • In pediatric patients 1 to 17 years old for the treatment of PAH (WHO Group 1) to improve exercise ability and, in pediatric patients too young to perform standard exercise testing, pulmonary hemodynamics thought to underly improvements in exercise. Policy/Criteria Provider must submit documentation (such as office chart notes, lab results or other clinical information) supporting that member has met all approval criteria.
It is the policy of health plans affiliated with Centene Corporation® that sildenafil is medically necessary when the following criteria are met:
I. Initial Approval Criteria
A. Pulmonary Arterial Hypertension (must meet all):

1. Diagnosis of PAH;
   2. Prescribed by or in consultation with a cardiologist or pulmonologist;
   3. Age ≥ 1 year;
   4. Failure of a calcium channel blocker (see Appendix B), unless member meets one of the following (a or b):
      a. Inadequate response or contraindication to acute vasodilator testing; b. Contraindication or clinically significant adverse effects to calcium channel blockers are experienced;
2. If request is for brands Revatio or Liqrev, member must use generic sildenafil, unless contraindicated or clinically significant adverse effects are experienced;

3. Dose does not exceed the following (a or b):
   a. Adult: one of the following, in divided doses (i or ii): i. 240 mg per day (oral formulation);
   ii. 30 mg per day (intravenous formulation); b. Pediatric: one of the following, in divided doses (i, ii, or iii): Page 1 of 9

   CLINICAL POLICY
   Sildenafil i. Body weight ≤ 20 kg: 30 mg per day (oral formulation);
   ii. Body weight > 20 kg to < 45 kg: 60 mg per day (oral formulation); iii. Body weight ≥ 45 kg: 120 mg per day (oral formulation).
   Approval duration:
   Medicaid/HIM – 6 months Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

4. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or
5. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   II. Continued Therapy A. Pulmonary Arterial Hypertension (must meet all):
   1. Member meets one of the following (a or b): a. Currently receiving medication via Centene benefit or member has previously met initial approval criteria; b. Member is currently receiving medication and is enrolled in a state and product with continuity of care regulations (refer to state specific addendums for CC.PHARM.03A and CC.PHARM.03B);
   2. Member is responding positively to therapy;
   3. If request is for brands Revatio or Liqrev, member must use generic sildenafil, unless contraindicated or clinically significant adverse effects are experienced;

6. If request is for a dose increase, new dose does not exceed the following (a or b):
   a. Adult: one of the following, in divided doses (i or ii): i. 240 mg per day (oral formulation);
   ii. 30 mg per day (intravenous formulation); b. Pediatric: one of the following, in divided doses (i, ii, or iii): i. Body weight ≤ 20 kg: 30 mg per day (oral formulation);
   ii. Body weight > 20 kg to < 45 kg: 60 mg per day (oral formulation); iii. Body weight ≥ 45 kg: 120 mg per day (oral formulation). Approval duration:
   Medicaid/HIM – 12 months Page 2 of 9

   CLINICAL POLICY
   Sildenafil Commercial – 12 months or duration of request, whichever is less B. Other diagnoses/indications (must meet 1 or 2):

7. If this drug has recently (within the last 6 months) undergone a label change (e.g., newly approved indication, age expansion, new dosing regimen) that is not yet reflected in this policy, refer to one of the following policies (a or b): a. For drugs on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the no coverage criteria policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.33 for health insurance marketplace, and CP.PMN.255 for Medicaid; or b. For drugs NOT on the formulary (commercial, health insurance marketplace) or PDL (Medicaid), the non-formulary policy for the relevant line of business: CP.CPA.190 for commercial, HIM.PA.103 for health insurance marketplace, and CP.PMN.16 for Medicaid; or

8. If the requested use (e.g., diagnosis, age, dosing regimen) is NOT specifically listed under section III (Diagnoses/Indications for which coverage is NOT authorized) AND criterion 1 above does not apply, refer to the off-label use policy for the relevant line of business: CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid.
   III. Diagnoses/Indications for which coverage is NOT authorized:
   A. Non-FDA approved indications, which are not addressed in this policy, unless there is sufficient documentation of efficacy and safety according to the off label use policies – CP.CPA.09 for commercial, HIM.PA.154 for health insurance marketplace, and CP.PMN.53 for Medicaid, or evidence of coverage documents.
   IV. Appendices/General Information Appendix A: Abbreviation/Acronym Key CTEPH: chronic thromboembolic pulmonary hypertension FC: functional class FDA: Food and Drug Administration
   NYHA: New York Heart Association PA: physical activity
   PAH: pulmonary arterial hypertension PH: pulmonary hypertension WHO: World Health Organization Appendix B: Therapeutic Alternatives
   This table provides a listing of preferred alternative therapy recommended in the approval criteria. The drugs listed here may not be a formulary agent and may require prior authorization.
   Drug Name Dosing Regimen nifedipine (Adalat® CC, Procardia XL®) Adult: 30 mg PO QD; may increase to 60 to 120 mg BID Dose Limit/ Maximum Dose Adult:
   240 mg/day Pediatric: Pediatric: Page 3 of 9

   CLINICAL POLICY
   Sildenafil Drug Name Dosing Regimen diltiazem (Dilt-XR®, Cardizem® CD, Cartia XT®, Tiazac®, Taztia XT®, Cardizem® LA, Matzim® LA) amlodipine (Norvasc®) 0.3 to 0.6 mg/kg/dose PO QD; may increase to 2 to 3 mg/kg/day Adult: 60 mg PO BID; may increase to 120 to 360 mg BID Dose Limit/ Maximum Dose 180 mg/day
   Adult: 720 mg/day Pediatric: 0.75 mg/kg/dose PO BID; may increase to 3 to 5 mg/kg/day Adult: 5 mg PO QD; may increase to 15 to 30 mg/day Pediatric: 360 mg/day Adult:
   30 mg/day Pediatric: 0.1 to 0.3 mg/kg/dose PO QD; may increase to 2.5 to 7.5 mg/day Pediatric: 10 mg/day Therapeutic alternatives are listed as Brand name® (generic) when the drug is available by brand name only and generic (Brand name®) when the drug is available by both brand and generic. Appendix C: Contraindications/Boxed Warnings • Contraindication(s):
   o Use with organic nitrates or riociguat o History of hypersensitivity reaction to sildenafil or any component of the tablet, injection, or oral suspension • Boxed warning(s): none reported Appendix D: Pulmonary Hypertension: WHO Classification • Group 1: PAH
   • Group 2: PH due to left heart disease • Group 3: PH due to lung disease and/or hypoxemia • Group 4: CTEPH (chronic thromboembolic pulmonary hypertension) • Group 5: PH due to unclear multifactorial mechanisms Heart Failure Appendix E: Pulmonary Hypertension: WHO/NYHA Functional Classes (FC) Treatment Approach* Status at Rest PA Limitations FC Tolerance of Physical Activity (PA) I Monitoring for progression of PH and treatment of co- existing conditions Comfortable at rest No limitation Ordinary PA does not cause undue dyspnea or fatigue, chest pain, or near syncope. Page 4 of 9

   CLINICAL POLICY
   Sildenafil Treatment Approach* FC Status at Rest II III IV Advanced treatment of PH with PH- targeted therapy

   • see Appendix F Tolerance of Physical Activity (PA) Slight limitation Comfortable at rest Comfortable at rest Marked limitation Dyspnea or fatigue may be present at rest Inability to carry out any PA without symptoms PA Limitations Heart Failure Ordinary PA causes undue dyspnea or fatigue, chest pain, or near syncope. Less than ordinary PA causes undue dyspnea or fatigue, chest pain, or near syncope. Discomfort is increased by any PA.
     Signs of right heart failure *PH supportive measures may include diuretics, oxygen therapy, anticoagulation, digoxin, exercise, pneumococcal vaccination. Advanced treatment options also include calcium channel blockers. Appendix F: Pulmonary Hypertension: Targeted Therapies Mechanism of Action Drug Subclass Drug Class Drug Brand/Generic Formulations Reduction of pulmonary arterial pressure through vasodilation Prostacyclin pathway agonist Prostacyclin Member of the prostanoid class of fatty acid derivatives. Synthetic prostacyclin analog Non-prostanoid prostacyclin receptor (IP receptor) agonist Selective receptor antagonist Nonselective dual action receptor antagonist Endothelin receptor antagonist (ETRA) Nitric oxide- cyclic guanosine Phosphodiesterase type 5 (PDE5) inhibitor Epoprostenol Veletri (IV) Flolan (IV) Flolan generic (IV) Treprostinil Orenitram (oral tablet) Remodulin (IV) Tyvaso (inhalation) Ventavis (inhalation) Uptravi (oral tablet) Iloprost Selexipag Ambrisentan Letairis (oral Bosentan Macitentan Sildenafil tablet) Tracleer (oral tablet) Opsumit (oral tablet) Revatio (IV, oral tablet, oral suspension) Page 5 of 9

   CLINICAL POLICY
   Sildenafil Mechanism of Action Drug Class Drug Subclass Drug monophosphate enhancer Tadalafil Riociguat Guanylate cyclase stimulant (sGC) V. Dosage and Administration
   Indication Dosing Regimen PAH Adult: Tablet and oral suspension: 20 mg to 80 mg PO TID Injection: 10 mg TID as an IV bolus Pediatric: Tablet and oral suspension:
   Body weight ≤ 20 kg: 10 mg PO TID Body weight > 20 kg to < 45 kg: 20 mg PO TID
   Body weight ≥ 45 kg: 20 mg to 40 PO TID
   Brand/Generic Formulations Adcirca (oral tablet) Adempas (oral tablet) Maximum Dose Adult: Tablet and oral suspension: 240 mg/day Injection: 30 mg/day Pediatric: See dosing regimen VI. Product Availability
   • Tablet: 20 mg • Oral suspension: 10 mg/mL (equivalent to 14 mg sildenafil citrate) • Single-use vial: 10 mg/12.5 mL VII.