Drug Class Monograph. Policy/Criteria:

Transcription

1 Drug Class Monograph Class: Pulmonary Arterial Hypertension Agents Drugs: Adcirca (tadalafil), Adempas (riociguat), Flolan (epoprostenol), Letairis (ambrisentan), Opsumit (macitentan), Orenitram (treprostinil), Remodulin (treprostinil), Revatio (sildenafil), Tracleer (bosentan), Tyvaso (treprostinil), Uptravi (selexipag), Veletri (epoprostenol), Ventavis (Iloprost) Line of Business: Medi-Cal Effective Date: February 15, 2017 Revision Date: February 15, 2017 This policy has been developed through review of medical literature, consideration of medical necessity, generally accepted medical practice standards, and approved by the IEHP Pharmacy and Therapeutic Subcommittee. Policy/Criteria: 1. Adcirca (tadalafil), Revatio (sildenafil) b. Documented WHO Functional Class II or above; c. Prescribed by a cardiologist or a pulmonologist; d. Formulary Position: Revatio (sildenafil) is the preferred phosphodiesterase type 5 enzyme (PDE-5) inhibitor. 2. Adempas (riociguat), Letairis (ambrisentan), Opsumit (macitentan), Orenitram (treprostinil), Tracleer (bosentan), Uptravi (selexipag) b. Documented WHO Functional Class II or above; c. Prescribed by a cardiologist or a pulmonologist; d. Inadequate response or clinically significant adverse effects to one of the PDE-5 inhibitors (Revatio, Adcirca). 3. Flolan (epoprostenol), Remodulin (treprostinil), Veletri (epoprostenol) b. Prescribed by a cardiologist or a pulmonologist; c. One of the following documentation: WHO Functional Class III with evidence of rapid disease progression or other markers of a poor clinical prognosis; WHO Functional Class IV.

2 4. Tyvaso (treprostinil), Ventavis (iloprost) b. Prescribed by a cardiologist or a pulmonologist; c. Member is not a candidate for parenteral prostanoid therapy (e.g. Flolan, Veletri, Remodulin); d. One of the following documentation: WHO Functional Class III with evidence of disease progression, despite therapy with at least one oral PAH agent; WHO Functional Class IV. Clinical Justification: 2014 CHEST Guideline: Pharmacologic Therapy for Pulmonary Arterial Hypertension in Adults Patients with WHO Functional Class II Symptoms: Direct comparisons of available oral therapies for PAH monotherapy for treatment-naïve patients have not been performed, and we do not make recommendations or suggestions of one agent, or class of agent, over another. For treatment-naïve patients with PAH with WHO FC II symptoms who are not candidates for, or who have failed, CCB therapy, we advise monotherapy be initiated with a currently approved ETRA, PDE5 inhibitor or the soluble guanylate cyclase sitmulator riociguat. o We recommend ambrisentan to improve 6MWD (Grade 1C). 10mg of ambrisentan resulted in greater improvement in 6MWD than 5mg without an observed increase in adverse effects. o We suggest bosentan to delay time to clinical worsening (Grade CB) and improve cardiopulmonary Bosentan >125mg bid is associated with greater incidence of transaminase elevation and is not recommended. o We suggest macitentan to delay the time to clinical worsening (Grade CB). o We recommend sildenafil to improve 6MWD (Grade 1C). For patients who fail to demonstrate and maintain an adequate clinical response to 20mg sildenafil tid, we recommend consideration of increasing the dose to a maximum of 80mg tid or adding another agent. o We suggest tadalafil to improve 6MWD (Grade CB) o We suggest riociguat to improve 6MWD (Grade CB), improve WHO FC (Grade CB), delay time to clinical worsening (Grade CB) and improve cardiopulmonary Based upon currently available evidence showing a risk of systemic hypotension when co-administered with a PDE5 inhibitor, male patients treated with riociguat should be cautioned not to use PDE5 inhibitors for erectile dysfunction. We suggest that parenteral or inhaled prostanoids not be chosen as initial therapy for treatment naïve PAH patients with WHO FC II symptoms or as second line agents for PAH patients with WHO FC II symptoms who have not met their treatment goals.

3 Patients with WHO Functional Class III Symptoms: Direct comparison of available oral therapies for PAH monotherapy for treatment-naïve patients have not been performed, and we do not make recommendations or suggestions of one agent, or class of agent, over another. For treatment-naïve PAH patients with WHO FC III symptoms who are not candidates for, or who have failed CCB therapy, we advise monotherapy be initiated with a currently approved ETRA, a PDE5 inhibitor, or the soluble guanylate cyclase stimulator riociguat. More specifically in these patients: o We recommend the use of bosentan to improve 6MWD (Grade 1B). o We suggest the use of bosentan to decrease hospitalization related to PAH in the shortterm (Grade 2C), and to improve cardiopulmonary o We recommend the use of ambrisentan to improve 6MWD (Grade 1C). o We suggest macitentan to improve WHO FC (Grade CB) and delay the time to clinical worsening (Grade CB). o We recommend the use of sildenafil to improve 6MWD (Grade 1C) and to improve WHO FC (Grade CB). We suggest the use of sildenafil to improve cardiopulmonary o We suggest the use of tadalafil to improve 6MWD (Grade CB), to improve WHO FC (Grade CB), to delay time to clinical worsening (Grade CB) and to improve cardiopulmonary o We suggest riociguat to improve 6MWD (Grade CB), improve WHO FC (Grade CB), delay the time to clinical worsening (Grade CB) and improve cardiopulmonary For treatment naïve PAH patients with WHO FC III symptoms who have evidence of rapid progression of their disease, or other markers of a poor clinical prognosis, we advise consideration of initial treatment with a parenteral prostanoid. More specifically in these patients: o We suggest continuous IV epoprostenol to improve FC (Grade CB), improve 6MWD (Grade CB), and improve cardiopulmonary o We suggest continuous IV treprostinil to improve 6MWD (Grade CB). o We suggest continuous subcutaneous treprostinil to improve 6MWD (Grade CB) and improve cardiopulmonary For PAH patients in WHO FC III who have evidence of progression of their disease, and/or markers of poor clinical prognosis despite treatment with one or two classes of oral agents, we advise consideration of the addition of a parenteral or inhaled prostanoid. More specifically in these patients: o We suggest IV epoprostenol to improve WHO FC (Grade CB), improve 6MWD (Grade CB), and improve cardiopulmonary o We suggest IV treprostinil to improve 6MWD (Grade CB) and improve cardiopulmonary o In patients with PAH who remain symptomatic on stable and appropriate doses of an ETRA or an PDE5 inhibitor, we suggest the addition of inhaled treprostinil to improve 6MWD (Grade 2C).

4 o In patients with PAH who remain symptomatic on stable and appropriate doses of an ETRA or a PDE5 inhibitor, we suggest the addition of inhaled iloprost to improve WHO FC (Grade CB) and delay the time to clinical worsening (Grade CB). Patients with WHO FC IV Symptoms For treatment naïve PAH patients in WHO FC IV, we advise initiation of monotherapy with a parenteral prostanoid agent. More specifically in these patients: o We suggest continuous IV epoprostenol to improve WHO FC (Grade CB), improve 6MWD (Grade CB), and improve cardiopulmonary o We suggest continuous IV treprostinil to improve 6MWD (Grade CB). o We suggest continuous subcutaneous treprostinil to improve 6MWD (Grade CB) and improve cardiopulmonary For treatment naïve PAH patients in WHO FC IV who are unable or do not desire to manage parenteral prostanoid therapy, we advise treatment with an inhaled prostanoid in combination with an ETRA. More specifically in these patients: o We suggest bosentan to improve 6MWD (Grade 2B) and cardiopulmonary o We suggest inhaled iloprost to improve 6MWD (Grade CB), and improve WHO FC (Grade CB). o We suggest inhaled treprostinil (in combination only) to improve 6MWD (Grade CB) CHEST Guideline: Pharmacologic Therapy for Pulmonary Arterial Hypertension in Adults

5 2015 ESC/ERS Guidelines for the Diagnosis and Treatment of Pulmonary Hypertension Reference: 1. GalieN, Humbert M, Vachiery JL, et al. Eur Heart J 2016;37(1): Taichman DB, Ornelas J, Chung L, et al. CHEST 2014; 146: Orenitram (treprostinil tablet, extended release) [Package Insert]. Research Triangle Park, NC: United Therapeutics Corp; Uptravi (selexipag tablet) [Package Insert]. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; Adempas (riociguat tablet) [Package Insert]. Whippany, NJ: Bayer HealthCare Pharmaceuticals Inc.; Letairis (ambrisentan tablet) [Package Insert]. Foster City, CA: Gilead Sciences, Inc.; Tracleer (bosentan tablet) [Package Insert]. South San Francisco, CA: Actelion Pharmaceuticals US, Inc.; 2016.

6 Change Control Date Change 02/15/2017 PDE-5 inhibitor (e.g. Revatio) is the preferred non-formulary oral PAH agent for Orenitram and Uptravi Revised criteria for inhaled prostacyclin agents (e.g. Tyvaso, Ventavis): o Pulmonary arterial hypertension, WHO functional class III with evidence of disease progression, despite therapy with at least one oral PAH agent