Effective Date

Date of Origin   

07-01-2025           

04-01-2015

Adcirca®

(tadalafil)

Tablets^

Treatment of pulmonary arterial hypertension (PAH) (*WHO Group 1) to improve exercise ability.  Studies establishing effectiveness included predominately patients with NYHA Functional Class II-III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%)

* – WHO = World Health Organization

^- generic available

1

Adempas®

(riociguat)

Tablets

Treatment of adults with persistent/recurrent chronic thromboembolic pulmonary hypertension (CTEPH), (*WHO Group 4) after surgical treatment, or inoperable CTEPH, to improve exercise capacity and WHO functional class

Treatment of adults with pulmonary arterial hypertension (PAH), (*WHO Group 1), to improve exercise capacity, WHO functional class and to delay clinical worsening.  Efficacy was shown in patients on monotherapy or in combination with endothelin receptor antagonists or prostanoids.  Studies establishing effectiveness included predominately patients with WHO functional class II-III and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (25%)

* – WHO = World Health Organization

2

Letairis® 

(ambrisentan)

Tablets^

Treatment of pulmonary arterial hypertension (PAH) (*WHO Group 1):

• To improve exercise ability and delay clinical worsening
• In combination with tadalafil to reduce the risks of disease progression and hospitalization for worsening PAH, and to improve exercise ability

Studies establishing effectiveness included predominantly patients with WHO Functional Class II-III symptoms and etiologies of idiopathic or heritable PAH (60%) or PAH associated with connective tissue diseases (34%)

* – WHO = World Health Organization

^- generic available

3

Liqrev®

(sildenafil)

Oral suspension

Treatment of pulmonary arterial hypertension (PAH) (*WHO Group 1) in adults to improve exercise ability and delay clinical worsening

* – WHO = World Health Organization

24

Opsumit^®

(macitentan)

Tablets

Treatment of pulmonary arterial hypertension (PAH) (*WHO Group 1) to reduce the risks of disease progression and hospitalization for PAH

Effectiveness was established in a long-term study in PAH patients with predominantly WHO Functional Class II-III symptoms treated for an average of 2 years. Patients had idiopathic and heritable PAH (57%), PAH caused by connective tissue disorders (31%), and PAH caused by congenital heart disease with repaired shunts (8%)

* – WHO = World Health Organization

4

Opsynvi®

(macitentan-tadalafil)

Tablets

Chronic treatment of pulmonary arterial hypertension (PAH) (*WHO Group 1) in adults of WHO functional class (FC) II-III

Individually, macitentan reduces the risk of clinical worsening events and hospitalization, and tadalafil improves exercise ability

* – WHO = World Health Organization

28

Orenitram®

(treprostinil)

Tablets

Treatment of pulmonary arterial hypertension (PAH) (*WHO Group 1) to delay disease progression and to improve exercise capacity. 

The studies that established effectiveness included predominately patients with WHO functional class II-III symptoms and etiologies of idiopathic or heritable PAH (66%) or PAH associated with connective tissue disease (26%). 

* – WHO = World Health Organization

5

Revatio®

(sildenafil citrate)

Tablets^

Oral solution^

Treatment of pulmonary arterial hypertension (PAH) (*WHO Group 1) in adults to improve exercise ability and delay clinical worsening

Treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) in pediatric patients 1 to 17 years of age to improve exercise ability and, in pediatric patients too young to perform standard exercise testing, pulmonary hemodynamics thought to underly improvements in exercise

Limitation of use:  Adding sildenafil to bosentan therapy does not result in any beneficial effect on exercise capacity

* – WHO = World Health Organization

^- generic available

6

Tadliq®

(tadalafil)

Oral suspension

Treatment of pulmonary arterial hypertension (PAH) (*WHO Group 1) to improve exercise ability. Studies establishing effectiveness included predominately patients with NYHA Functional Class II – III symptoms and etiologies of idiopathic or heritable PAH (61%) or PAH associated with connective tissue diseases (23%)

* – WHO = World Health Organization

23

Tracleer®

(bosentan)

Tablets film coated^

Tablets for suspension

Treatment of pulmonary arterial hypertension (PAH) (*WHO Group 1):

• In adults to improve exercise ability and to decrease clinical worsening. Studies establishing effectiveness included predominantly patients with WHO Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (60%), PAH associated with connective tissue diseases (21%), and PAH associated with congenital heart disease with left-to-right shunts (18%).
• In pediatric patients aged 3 years and older with idiopathic or congenital PAH to improve pulmonary vascular resistance (PVR), which is expected to result in an improvement in exercise ability.

* – WHO = World Health Organization

^- generic available

7

Tyvaso®, Tyvaso DPI®

(treprostinil)

Inhalation solution

Inhalation powder

Treatment of pulmonary arterial hypertension (PAH) (*WHO Group 1) to improve exercise ability. Studies establishing effectiveness predominately included patients with NYHA Functional Class III symptoms and etiologies of idiopathic or heritable PAH (56%) or PAH associated with connective tissue diseases (33%).

While there are long-term data on use of treprostinil by other routes of administration, nearly all controlled clinical experience with inhaled treprostinil has been on a background of bosentan (an endothelin receptor antagonist) or sildenafil (phosphodiesterase type 5 inhibitor). The controlled clinical experience was limited to 12 weeks in duration.

Treatment of pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO group 3) to improve exercise ability. The study establishing effectiveness included patients with etiologies of idiopathic interstitial pneumonia (IIP) (45%) inclusive of idiopathic pulmonary fibrosis (IPF), combined pulmonary fibrosis and emphysema (CPFE), and WHO group 3 connective tissue disease (22%).

* – WHO = World Health Organization

8,22

Uptravi^®

(selexipag)

Tablets

Treatment of pulmonary arterial hypertension (PAH, *WHO Group 1) to delay disease progression and reduce the risk of hospitalization for PAH.

Effectiveness was established in a long-term study in PAH patients with WHO Functional Class II-III symptoms.

Patients had idiopathic and heritable PAH (58%), PAH associated with connective tissue disease (29%), PAH associated with congenital heart disease with repaired shunts (10%)

* – WHO = World Health Organization

9

Ventavis®

(iloprost)

Inhalation solution

Treatment of pulmonary arterial hypertension (PAH) (*WHO Group 1) to improve a composite endpoint consisting of exercise tolerance, symptoms (NYHA Class), and lack of deterioration. Studies establishing effectiveness included predominately patients with NYHA Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH (65%) or PAH associated with connective tissue diseases (23%)

* – WHO = World Health Organization

10

Winrevair™ 

(sotatercept-csrk)

Subcutaneous injection

Treatment of pulmonary arterial hypertension (PAH) (*WHO Group 1) in adults to increase exercise capacity to improve exercise ability, improve WHO functional class (FC) and reduce the risk of clinical worsening events  

* – WHO = World Health Organization

27

Pulmonary Hypertension

Pulmonary hypertension (PH) is a hemodynamic condition characterized by elevation in mean pulmonary arterial pressure (mPAP) greater than 20mmHg assessed by right heart catheterization (RHC). The World Health Organization (WHO) has classified pulmonary hypertension (PH) based upon etiology into the following five groups:(11,29)

• Group 1 - Pulmonary arterial hypertension (PAH)
• Group 2 – PH associated with left heart disease
• Group 3 – PH associated with lung disease and/or hypoxemia
• Group 4 – PH associated with pulmonary artery obstruction
• Group 5 – PH with unclear and/or multifactorial mechanisms

Group 1, also known as pulmonary arterial hypertension (PAH), is defined by a pre-capillary pattern in the invasive hemodynamic evaluation, characterized by a mean pulmonary arterial pressure (mPAP) greater than 20 mmHg with a normal pulmonary capillary wedge pressure (PCWP) (i.e., less than or equal to 15 mmHg) and a pulmonary vascular resistance (PVR) greater than 2 Wood units, in the absence of pulmonary parenchymal or thromboembolic disease. Group 1 can occur in isolation or in association with clinical conditions, as noted in the following subcategories: idiopathic, heritable, drug/toxin induced, association with other diseases (i.e., connective tissue disease, HIV infection, portal hypertension, congenital heart diseases, schistosomiasis), long-term responders to calcium channel blockers, with overt features of venous/capillaries (pulmonary veno-occlusive disease [PVOD]/pulmonary capillary haemangiomatosis [PCH]), and persistent PH of the newborn syndrome.(11,29)

Group 3 is pulmonary hypertension (PH) associated with lung disease and/or hypoxia. PH associated with chronic lung disease is linked with reduced functional status and worse outcomes. There are seven subgroups within WHO group 3, one of which is interstitial lung disease (ILD) associated PH (WHO group 3.2). Assessment for PH in the setting of CLD should include evaluation of the following key parts: clinical features such as disease trajectory, increased oxygen requirements and risk factors for PAH, CTEPH and heart failure with preserved ejecting fraction (HFpEF); functional tests such as pulmonary function tests (PFT) including diffusion capacity of the lung for carbon monoxide (DLCO), oxygenation and ventilation by arterial blood gases (ABG), and cardiopulmonary exercise testing (CPET); computed tomography imaging (CT); brain natriuretic peptide (BNP)/N-terminal pro-BNP (NT-proBNP) measurements; and echocardiography. The results of these assessments should be used to confirm if a right heart catheterization (RHC) is needed to aid in management decisions. Prior to starting PAH therapy for the treatment of PH associated with lung disease, the patient’s underlying lung disease should be optimally treated according to current guidelines.(11,29)

Group 4 PH is associated with chronic thrombotic and/or embolic disease and includes chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH is characterized pathologically by organized thromboembolic material and by altered vascular remodeling initiated or potentiated by a combination of defective angiogenesis, impaired fibrinolysis and endothelial dysfunction. These changes lead to PH and ultimately right ventricular failure. PH is defined as a mPAP greater than 20 mmHg, PCWP less than or equal to 15 mmHg, and PVR greater than 2 Woods units.(29) Two different vascular lesions participate in the increase in PVR in CTEPH: an obstruction of pulmonary arteries by unresolved organized fibrothrombotic clots and a secondary microvasculopathy observed in both obstructed and non-obstructed lung areas. Scar-like tissue and vascular remodeling ensue which narrows and stiffens the arteries, resulting in a persistent obstruction of pulmonary arteries.(29) Ventilation/perfusion scan planar images combined with a confirmatory CT pulmonary angiography remain the preferred diagnostic tests for CTEPH despite advances in computed tomography (CT) and magnetic resonance (MR).(29) Right heart catheterization (RHC) and catheter-based pulmonary angiography are still mandatory to confirm the diagnosis.(29) The 7^th World Symposium on Pulmonary Hypertension (WSPH) recommends all patients diagnosed with CTEPH be reviewed by a multidisciplinary CTEPH team and incorporate a multimodal management strategy including sequential combination of at least two of the three treatment strategies. All CTEPH patients should maintain lifelong anticoagulation therapy.(29) Pulmonary endarterectomy (PEA) remains the first line treatment option for CTEPH. WSPH notes that the best treatment is uncertain for patients that may be technically operable but may not benefit from endarterectomy due to comorbidities or other factors. Balloon pulmonary angioplasty (BPA) has become the recommended treatment for inoperable CTEPH patients or patients with residual PH after PEA. Targeted medical therapy is initiated in those patients that are inoperable or those with persistent/recurrent PH following PEA. Patients should be re-evaluated for symptomatic PH 3-6 months after starting treatment for PH.(29)

The diagnosis of PAH requires right heart catheterization (RHC) to demonstrate a mPAP greater than 20 mmHg at rest and a PVR greater than 2 Wood units. Several additional criteria to exclude the remaining categories of PH must also be met:(11,29)

• Mean PCWP less than or equal to 15 mmHg (to exclude PH due to left heart disease [i.e., group 2 PH])
• Chronic lung diseases and other causes of hypoxemia are mild or absent (to exclude PH owing to chronic lung disease or hypoxemia [i.e., group 3 PH])
• Venous thromboembolic disease is absent (to exclude chronic thromboembolic PH [i.e., group 4 PH])
• Certain miscellaneous disorders are absent, including systemic disorders (e.g., sarcoidosis), hematologic disorders (e.g., myeloproliferative diseases), and metabolic disorders (e.g., glycogen storage disease). The purpose is to exclude PH with unclear multifactorial mechanisms (group 5 PH).

World Health Organization (WHO) Functional Classification of Patients with Pulmonary Hypertension include the following:(20,11)

• Class I: Patients with PH without resulting limitation of physical activity. Ordinary physical activity does not cause undue dyspnea, fatigue, chest pain, or near syncope.
• Class II: Patients with PH having slight limitation of physical activity. No discomfort at rest, but ordinary physical activity causes increased dyspnea, fatigue, chest pain, or near syncope.
• Class III: Patients with PH having marked limitation of physical activity. No discomfort at rest, but less than ordinary activity causes increased dyspnea, fatigue, chest pain, or near syncope.
• Class IV: Patients with PH unable to carry out any physical activity without symptoms and may have signs of right ventricular failure. Dyspnea and/or fatigue may be present at rest, with increased discomfort by any physical activity.

The 7^th World Symposium on PH also included recommendations for pediatric patients with PH. The hemodynamic definition of PH in infants and children beyond the first month of life is defined as a mPAP of greater than or equal to 20 mmHg, PCWP less than 15 mmHg, and pulmonary vascular resistance indexed for body surface area (PVRI) of greater than 3.(29) The WS guidelines and the 2015 American Heart Association and American Thoracic Society guidelines note that the definition of PAH in pediatric patients mirrors the adult definition. The guidelines also recommend the same diagnostic testing and algorithm as adult patients, with the inclusion of a full shunt evaluation during RHC to rule out congenital heart disease.(13,29)

Treatment Guidelines

Guidelines recommend that patients be referred to a PAH expert center for diagnosis confirmation and management. Current treatment strategies are based on the severity of newly diagnosed patients, assessed by a risk stratification approach. The risk stratification takes clinical, exercise, right ventricular function, and hemodynamic parameters, and combines them to define a low, intermediate, or high-risk status according to patients expected 1-year mortality. There are various PAH risk stratification tools available and they use a number of different factors to assess risk including: WHO functional class, 6-minute walking distance and natriuretic peptide.(11,13,20,29)

The 7^th World Symposium on Pulmonary Hypertension evidence-based treatment algorithm for adults includes the following recommendations:(29)

• Treatment following initial risk assessment:
  • Efficacy has generally been greater with therapeutic combinations and with parental therapy compared with monotherapy or nonparental therapies and maximal medical therapy is now four-drug therapy. Compared with monotherapy, larger improvements are seen with combination therapy and thus most patients with PAH are candidates for oral or oral plus parental combination therapy from the time of diagnosis, along with early reassessment and escalation in therapy when indicated. Lung transplant remains an option for selected patients with an inadequate response to therapies.
  • Vasoreactive patients (only idiopathic PAH, heritable PAH, or drug-associated PAH):
    • High dose calcium channel blockers (CCB) that have been progressively titrated
    • Response should be evaluated after 3 to 4 months
    • Patients without an adequate response to high dose CCBs should be treated with approved PAH medications according to non-vasoreactive treatment strategy. In some cases, the combination of CCB with approved PAH is required.
  • Non-vasoreactive patients:
    • Not high risk: Combination endothelin receptor antagonist (ERA) and a phosphodiesterase type-5 (PDE5) inhibitor. Tadalafil in combination with macitrentan or ambrisentan is preferred.
    • High risk: Combination intravenous/subcutaneous (IV/SC) prostacylin pathway agent (PPA) (epoprostenol or treprostinil), ERA and PDE5 inhibitor, OR, consider referral for lung transplant
    • Response should be evaluated after 3 to 4 months and repeated frequently
• Treatment following first follow-up reassessment:
  • Low risk at follow up: Continue initial therapy with structured follow up until risk progression
  • Intermediate-low risk: Add activin-signaling inhibitor (sotatercept), oral PPA (selexipag, oral treprostinil) or inhaled PPA. Can consider switch PDE5 inhibitor to soluble guanylyl cyclase stimulator (sGCS) (riociguat).
  • Intermediate-high risk: Add IV/SC PPA or activin-signaling inhibitor
  • High risk: Add IV/SC PPA (First choice if not on) or activin signaling inhibitor
• If patient reassessed as persistent intermediate-high or high at subsequent follow-up maximal prescription of four drug combination: PPA, ERA, PDE5 inhibitor or sGCS, activin-signaling inhibitor, OR, lung transplant is recommended
• Transitioning patients from one PAH-specific therapy to another might be considered for a number of reasons, but transitioning patients that have an extraordinary response to therapy and desire to transition to less invasive therapy is not recommended except in rare circumstances and under close expert care

The 2022 European Society of Cardiology (ESC) and the European Respiratory Society (ERS) guidelines recommend a risk-based, goal-orientated treatment approach in patients with PAH. Risk stratification at diagnosis is done using a three-strata model and follow-up using a four strata model. The recommended treatment algorithm for non-vasoreactive patients or patients unresponsive to CCB is as follows:(11)

• Initial treatment:
  • Patients without cardiopulmonary comorbidities (e.g., obesity, hypertension, diabetes):
    • Low or intermediate prognosis risk: Treat with oral combination therapy with an endothelin receptor antagonist (ERA) and a phosphodiesterase type-5 (PDE5) inhibitor: ambrisentan plus tadalafil, macitentan plus tadalafil, or other ERA and PDE5 combination
    • High prognosis risk: Treat with oral combination therapy with an endothelin receptor antagonist (ERA) plus a phosphodiesterase type-5 (PDE5) inhibitor and IV/SC prostacyclin analogue 
  • Patients with cardiopulmonary comorbidities (all prognosis risk categories)
    • Oral monotherapy with PDE5 inhibitors or ERA
• Response should be evaluated after 3 to 6 months:
  • Patients without cardiopulmonary comorbidities:
    • Low risk at follow up: continue therapy
    • Intermediate to low risk: add prostacyclin receptor agonist (PRA) (selexipag), OR, switch from PDE5 inhibitor to soluble guanylate cyclase stimulator(sGCs) (riociguat)
    • Intermediate to high or high risk: add IV/SC prostacyclin analogue (epoprostenol or treprostinil) and/or evaluate for lung transplant. If adding IV/SC prostacyclin analogue is unfeasible, adding selexipag or switching from PDE5 inhibitor to riociguat may be considered
  • Patients with cardiopulmonary comorbidities:
    • Individualized therapy. Patients that present at intermediate or high risk of death while receiving PDE5 inhibitors or ERA monotherapy, treatment based on individual basis

The 7^th World Symposium on Pulmonary Hypertension pragmatic treatment algorithm in pediatrics includes the following recommendations:(11,29)

• Due to lack of randomized controlled trials in pediatric patients, treatment is based on a combination of real-world data, expert experience and extrapolation from adult clinical trials. Guidelines recommend adopting comparable therapeutic algorithms in children and adults.
• Combination therapy is superior to monotherapy in idiopathic PAH (IPAH), hereditary PAH (HPAH) and drug/toxin-induced PAH (DT-PAH)
• The algorithm is most applicable in children with IPAH and HPAH, as children typically have a more complex and heterogeneous clinical picture due to diversity of diseases associated with PH
• Therapeutic strategy is based on risk stratification and treatment response
• Vasoreactive response positive patients with IPAH, HPAH, or DT-PAH AND who do not have cardiopulmonary conditions:
  • Initiate patients on high-dose oral CCBs and continued if there is sustained and improved response.
  • At serial reassessment, patients with adequate treatment response should continue CCB therapy. Patients with inadequate response, CCB therapy should be optimized and PAH target therapy added.
• Non-vasoreactive patients or those with failed or non-sustained response should undergo risk stratification to determine therapy.
• Vasoreactive response negative patients without cardiopulmonary conditions:
  • Low prognosis risk: Initiation of upfront or rapid sequential dual oral combination therapy ERA (i.e., bosentan, ambrisentan) and a PDE5 inhibitor (i.e., sildenafil, tadalafil) is recommended
  • High prognosis risk: Initiate parental/oral combination therapy, i.e., IV/SC PPA plus ERA and/or PDE5 inhibitor (IV epoprostenol or treprostinil are recommended, and early consideration of lung transplantation in patients with deteriorating high-risk features
  • At serial reassessment, patients responding adequately should continue current therapy. Patients with an inadequate response should be escalated to maximal triple combination therapy (ERA/PDE5 inhibitor or sGC/PPA) and/or consider consult for/treatment with lung transplant, Potts shunt or atrial septotomy
• In patients with cardiopulmonary conditions OR who are vasoreactive response positive and experienced an inadequate response of CCB:
  • If the patient has PAH and developmental lung disorders, initiate initial monotherapy. At serial reassessment, continue current therapy on individual basis if response is adequate. If response is inadequate, consider switching therapy or combination therapy
  • If patient has PAH associated with congenital heart disease:
    • Patients with correctable L-R shunt: individualize treatment for operability with good long term prognosis
    • Patients with Eisenmenger syndrome or non-correctable L-R shunt: Initiate monotherapy with regular serial reassessment and further individualized combination therapy
    • Patients with coincidental shunts, repaired shunts or without initial shunt: Following treatment strategy used for non-vasoreactive patients without cardiopulmonary conditions

The American College of Chest Physicians (CHEST) guideline (2019) states:(20)

• WHO FC II [treatment naïve and not a candidate for or failure to calcium channel blocker (CCB) therapy]:
  • Combination with ambrisentan and tadalafil
  • Patients unable to tolerate or unwilling to take combination therapy: monotherapy with an ERA or PDE5 inhibitor (listed in order of recommendation level and alphabetically)
    • Ambrisentan, sildenafil, bosentan, macitentan, tadalafil, riociguat
  • Parenteral or inhaled prostanoids should not be used as initial or second line therapy

• WHO FC III [treatment naïve, not a candidate for or failure to calcium channel blocker (CCB) therapy, and no evidence of rapid progression of their disease or poor prognosis]:
  • Combination with ambrisentan and tadalafil
  • Patients unable to tolerate or unwilling to take combination therapy: monotherapy with an ERA or PDE5 inhibitor (listed in order of recommendation level and alphabetically)
    • Ambrisentan, bosentan, sildenafil, macitentan, tadalafil, riociguat
• WHO FC III [treatment naïve with evidence of rapid progression of their disease, or other markers of a poor clinical prognosis]:
  • Initial treatment with IV or SC prostanoid
  • There is no recommendation for patients unwilling to manage PAH with IV or SC prostanoid, so may consider addition of inhaled or oral prostanoid
• 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]: addition of a parenteral or inhaled prostanoid
  • Suggest the addition of inhaled prostanoid (i.e., treprostinil, iloprost) in patients that remain symptomatic on stable and appropriate doses of an ERA or PDE5 inhibitor
• WHO FC IV [treatment naïve]: monotherapy with a parenteral prostanoid agent
• WHO FC IV [treatment naïve and unable/or do not desire parenteral prostanoid therapy]: an inhaled prostanoid in combination with an ERA and PDE5 inhibitor
• WHO FC III or IV [with unacceptable or deteriorating clinical status despite established PAH pharmacotherapy]: a second or third class of PAH therapy should be started
• Due to insufficient evidence, recommendations cannot be made for or against the use of selexipag
• There is no evidence to support the use of oral treprostinil as add-on or combination therapy

The AHA/ATS guidelines for the treatment of pediatric pulmonary hypertension state:(13)

• Oral therapy in children with lower-risk PAH is recommended and should include either a PDE5 inhibitor or an ERA
• A goal-targeted therapy approach in which PAH-specific drugs are added progressively to achieve specified therapeutic targets can be useful
• Intravenous and subcutaneous prostacyclin or its analogs should be initiated without delay for patients with higher-risk PAH

The Chest guideline recognizes that there is still a lack of head-to-head comparisons of pharmacologic agents for the treatment of PAH, and because of their differing burdens and risks to patients, it is recommended that drug therapy be chosen on the basis of a methodical evaluation of disease severity and the risk for further short-term deterioration. The optimal method of evaluation has not been studied. No one agent can be definitively recommended preferentially. Additionally, it notes that adding a second class of PAH therapy for patients whose clinical status remains unacceptable despite established PAH-specific monotherapy requires that the clinician assess whether the patient has received an adequate trial of the initial monotherapy. At present, this assessment combines evaluation of the duration of monotherapy, the expected response to the monotherapy, the observed response to the monotherapy, and the patient’s severity of illness and pace of decline. Unacceptable clinical status will vary for individual patients and clinicians, but symptomatic limitation of desired physical activities usually guides these decisions.(20)

Efficacy of Winrevair (sotatercept)

The safety and efficacy of sotatercept was evaluated in the STELLAR trial. This was a multicenter, double-blinded, randomized phase three trial. Eligible adult patients had symptomatic PAH Group 1 confirmed by right heart catheterization (RHC) and  classified as WHO FC II or III. Patients were on stable background therapy for at least 90 days. Background PAH therapy refers to combination therapy consisting of drugs from two or more of the following drug classes: an endothelin-receptor antagonist (ERA), a phosphodiesterase 5(PDE5) inhibitor, a soluble guanylate cyclase stimulator, and/or a prostacyclin analogue or receptor agonist. Excluded criteria included: pregnancy or breastfeeding, uncontrolled systemic hypertension of greater than 160/100 mmHg, and baseline systolic blood pressure under 90 mmHg.(25-26)

Patients were randomly assigned in a 1:1 ratio to receive subcutaneous sotatercept (starting dose, 0.3 mg per kilogram of body weight; target dose, 0.7 mg per kilogram) or placebo every 3 weeks. The primary end point was the change from baseline at week 24 in the 6-minute walk distance. There were nine secondary end points: multicomponent improvement, change in pulmonary vascular resistance (PVR), change in N-terminal pro–B-type natriuretic peptide (NT-proBNP) level, improvement in WHO FC, time to death or clinical worsening event, French risk score, and changes in the Pulmonary Arterial Hypertension–Symptoms and Impact (PAH-SYMPACT), Cardiopulmonary Symptoms, and Cognitive/Emotional Impacts domain scores. All were assessed at week 24 except time to death or clinical worsening, which was assessed when the last patient completed the week 24 visit. (25-26)

A total of 163 patients were assigned to receive sotatercept and 160 to receive placebo. The median change from baseline at week 24 in the 6-minute walk distance was 34.4 m (95% confidence interval [CI], 33.0 to 35.5) in the sotatercept group and 1.0 m (95% CI, −0.3 to 3.5) in the placebo group. The first eight secondary end points were significantly improved with sotatercept as compared with placebo, whereas the PAH-SYMPACT Cognitive/Emotional Impacts domain score was not. Adverse events that occurred more frequently with sotatercept than with placebo included epistaxis, dizziness, telangiectasia, increased hemoglobin levels, thrombocytopenia, and increased blood pressure.(25-26)

Safety

Adcirca(1), Tadliq(23)

Tadalafil has the following contraindications:

• Concomitant organic nitrates
• Concomitant Guanylate Cyclase (GC) stimulator
• History of known serious hypersensitivity reaction to tadalafil (Adcirca, Cialis, or Tadliq)

Adempas(2)

Riociguat has the following contraindications:

• Pregnancy
• Co-administration with nitrates or nitric oxide donors (e.g., amyl nitrite) in any form
• Concomitant use with specific phosphodiesterase (PDE) inhibitors (e.g., sildenafil, tadalafil, vardenafil) or nonspecific PDE inhibitors (e.g., dipyridamole, theophylline)
• Concomitant use with other soluble guanylate cyclase (sGC) stimulators
• Pulmonary hypertension associated with idiopathic interstitial pneumonias (PH-IIP)

Boxed warnings include:

• Do not administer Adempas to a pregnant female because it may cause fetal harm. Adempas was consistently shown to have teratogenic effects when administered to animals. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
• Females of reproductive potential: exclude pregnancy before the start of treatment, monthly during treatment, and 1 month after stopping treatment. To prevent pregnancy, females of reproductive potential must use effective forms of contraception during treatment and for one month after stopping treatment.
• For females, Adempas is available only through a restricted program called the Adempas REMS Program.

Letairis(3)

Ambrisentan has the following contraindications:

• Pregnancy
• Idiopathic pulmonary fibrosis (including IPF patients with pulmonary hypertension [WHO group 3])

Boxed warnings include:

• Do not administer Letairis to a pregnant female because it may cause fetal harm. Letairis is very likely to produce serious birth defects if used by pregnant females, as this effect has been seen consistently when it is administered to animals. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the fetus.
• Exclude pregnancy before the initiation of treatment with Letairis. Females of reproductive potential must use acceptable methods of contraception during treatment with Letairis and for one month after treatment. Obtain monthly pregnancy tests during treatment and 1 month after discontinuation of treatment.
• Because of the risk of embryo-fetal toxicity, for all female patients, Letairis is only available through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Ambrisentan REMS

Opsumit(4)

Macitentan has the following contraindications:

• Pregnancy
• History of hypersensitivity reaction to macitentan or any component of the product

Boxed warnings include:

• Do not administer Opsumit to a pregnant female because it may cause fetal harm. Opsumit was consistently shown to have teratogenic effects when administered to animals. If Opsumit is used during pregnancy, advise the patient of the potential risk to a fetus. 
• Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and 1 month after stopping treatment. Prevent pregnancy during treatment and for one month after stopping treatment by using acceptable methods of contraception.
• For all female patients, OPSUMIT is available only through a restricted program called the Macitentan- Containing Products Risk Evaluation and Mitigation Strategy (REMS)

Opsynvi(28)

Macitentan-tadalafil has the following contraindications:

• Pregnancy
• History of hypersensitivity reaction to macitentan, tadalafil or any component of the product
• Concomitant organic nitrates
• Concomitant guanylate cyclase (GC) stimulators

Boxed warnings include:

• Do not administer Opsynvi to a pregnant female because it may cause fetal harm. Macitenan was consistently shown to have teratogenic effects when administered to animals. If Opsynvi is used during pregnancy, advise the patient of the potential risk to a fetus. 
• Females of reproductive potential: Exclude pregnancy before the start of treatment, monthly during treatment, and 1 month after stopping treatment. Prevent pregnancy during treatment and for one month after stopping treatment by using acceptable methods of contraception.
• For all female patients, Opsynvi is available only through a restricted program called Macitentan-Containing Products Risk Evaluation and Mitigation Strategy (REMS).

Orenitram(5)

Treprostinil have the following contraindication:

• Severe hepatic impairment (Child-Pugh Class C)

Revatio(6) Liqrev (24)

Sildenafil has the following contraindications:

• Concomitant use of organic nitrates in any form, either regularly or intermittently, because of the greater risk of hypotension
• Concomitant use of riociguat
• Known hypersensitivity to sildenafil or any component of the tablet, injection, or oral suspension

Tracleer(7)

Bosentan has the following contraindications:

• Pregnancy
• Use with cyclosporine A
• Use with glyburide
• Hypersensitivity to bosentan or any component of the product

Boxed warnings include:

Hepatotoxicity

In clinical studies, Tracleer caused at least 3-fold upper limit of normal (ULN) elevation of liver aminotransferases (ALT and AST) in about 11% of patients, accompanied by elevated bilirubin in a small number of cases. Because these changes are a marker for potential serious hepatotoxicity, serum aminotransferase levels must be measured prior to initiation of treatment and then monthly. In the post marketing period, in the setting of close monitoring, rare cases of unexplained hepatic cirrhosis were reported after prolonged (greater than 12 months) therapy with Tracleer in patients with multiple comorbidities and drug therapies. There have also been reports of liver failure. The contribution of Tracleer in these cases could not be excluded. In at least one case, the initial presentation (after greater than 20 months of treatment) included pronounced elevations in aminotransferases and bilirubin levels accompanied by nonspecific symptoms, all of which resolved slowly over time after discontinuation of Tracleer. This case reinforces the importance of strict adherence to the monthly monitoring schedule for the duration of treatment and the treatment algorithm, which includes stopping Tracleer with a rise of aminotransferases accompanied by signs or symptoms of liver dysfunction.

Elevations in aminotransferases require close attention. Tracleer should generally be avoided in patients with elevated aminotransferases (greater than 3 × upper limit of normal [ULN]) at baseline because monitoring for hepatotoxicity may be more difficult. If liver aminotransferase elevations are accompanied by clinical symptoms of hepatotoxicity (such as nausea, vomiting, fever, abdominal pain, jaundice, or unusual lethargy or fatigue) or increases in bilirubin greater than or equal to 2 × ULN, treatment with Tracleer should be stopped. There is no experience with the reintroduction of Tracleer in these circumstances.

Embryo-Fetal Toxicity

Tracleer is likely to cause major birth defects if used by pregnant females based on animal data. Therefore, pregnancy must be excluded before the start of treatment with Tracleer. Throughout treatment and for one month after stopping Tracleer, females of reproductive potential must use two reliable methods of contraception unless the patient has an intrauterine device (IUD) or tubal sterilization, in which case no other contraception is needed. Hormonal contraceptives, including oral, injectable, transdermal, and implantable contraceptives should not be used as the sole means of contraception because these may not be effective.

Uptravi(9)

Selexipag has the following contraindications:

• Hypersensitivity to the active substance or to any of the excipients
• Concomitant use of a strong CYP2C8 inhibitor (e.g., gemfibrozil)

Winrevair (27)

Sotatercept-csrk has no contraindications

1

Adcirca prescribing information. Eli Lilly and Company. June 2023.

2

Adempas prescribing information. Bayer HealthCare. January 2023.

3

Letairis prescribing information. Gilead. December 2020.

4

Opsumit prescribing information.  Actelion Pharmaceuticals, Inc. April 2024.

5

Orenitram prescribing information.  United Therapeutics Corporation. November 2023.

6

Revatio prescribing information. Pfizer. January 2023.

7

Tracleer prescribing information. Actelion Pharmaceuticals, Inc. February 2024.

8

Tyvaso Prescribing Information. United Therapeutics Corp. September 2024.

9

Uptravi Prescribing Information. Actelion Pharmaceuticals, Inc.  July 2024.

10

Ventavis Prescribing Information. Actelion Pharmaceuticals, Inc. July 2022.

11

Humbert, Marc, et. al. 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension: Developed by the Task Force for the Diagnosis and Treatment of Pulmonary Hypertension of the European Society of Cardiology (ESC) and the European Respiratory Society (ERS): Endorsed by: International Society for Heart and Lung Transplantation (ISHLT) and the European Reference Network on Rare Respiratory Diseases (ERN-LUNG).  European Heart Journal, Volume 43, Issue 38, 7 October 2022, Pages 3618–3731, https://doi.org/10.1093/eurheartj/ehac237.

12

Reference no longer used.

13

Abman SH, Hansmann G, et al. Pediatric pulmonary hypertension – guidelines from the American Heart Association and American Thoracic Society. Circulation. 2015;132:2037-2099.

14

Reference no longer used.

15

Reference no longer used.

16

Reference no longer used.

17

Reference no longer used.

18

Reference no longer used.

19

Reference no longer used.

20

Klinger, James R. et al. (2019). Therapy for Pulmonary Arterial Hypertension in Adults. CHEST, 155(3):565 - 586.

21

Reference no longer used.

22

Tyvaso DPI prescribing information. United Therapeutics Corp. August 2024. 

23

Tadliq prescribing information. CMP Pharma, Inc. October 2023. 

24

Liqrev prescribing information. CMP Pharma, Inc. May 2024. 

25

Reference no longer used.

26

Reference no longer used.

27

Winrevair prescribing information. Merck Sharp and Dohme LLC. March 2024.

28

Opsynvi Prescribing Information. Actelion Pharmaceuticals US, Inc.  April 2024.

29

Humbert, M., Galiè, N., Rubin, L. J., Simonneau, G., & McLaughlin, V. V. (2024). The Seventh World Symposium on pulmonary hypertension: Our journey to Barcelona. European Respiratory Journal, 64(4), 2401222. https://doi.org/10.1183/13993003.01222-2024.

Letairis

ambrisentan tab

10 MG ; 5 MG

M ; N ; O ; Y

O ; Y

Tracleer

bosentan tab  ; bosentan tab for oral susp

125 MG ; 32 MG ; 62.5 MG

M ; N ; O ; Y

N ; O ; Y

Ventavis

Iloprost Inhalation Solution 10 MCG/ML

10 MCG/ML

M ; N ; O ; Y

N

Ventavis

Iloprost Inhalation Solution 20 MCG/ML

20 MCG/ML

M ; N ; O ; Y

N

Opsumit

macitentan tab

10 MG

M ; N ; O ; Y

N

Opsynvi

macitentan-tadalafil tab

10-20 MG ; 10-40 MG

M ; N ; O ; Y

N

Adempas

riociguat tab

0.5 MG ; 1 MG ; 1.5 MG ; 2 MG ; 2.5 MG

M ; N ; O ; Y

N

Revatio

sildenafil citrate for suspension

10 MG/ML

M ; N ; O ; Y

O ; Y

Liqrev

sildenafil citrate oral susp

10 MG/ML

M ; N ; O ; Y

N

Revatio

sildenafil citrate tab

20 MG

M ; N ; O ; Y

O ; Y

Winrevair

sotatercept-csrk for subcutaneous soln kit

2 x 45 MG ; 2 x 60 MG ; 45 MG ; 60 MG

M ; N ; O ; Y

N

Tadliq

tadalafil oral susp

20 MG/5ML

M ; N ; O ; Y

N

Adcirca

tadalafil tab

20 MG

M ; N ; O ; Y

O ; Y

Orenitram ; Orenitram titration kit m

treprostinil diolamine tab er  ; treprostinil tab er titr pk (mo ; treprostinil tab er titr pk(mo

0.125 & 0.25 &1 MG ; 0.125 & 0.25 MG ; 0.125 MG ; 0.25 MG ; 1 MG ; 2.5 MG ; 5 MG

M ; N ; O ; Y

N

Tyvaso dpi institutional ; Tyvaso dpi maintenance ki ; Tyvaso dpi titration kit

treprostinil inh powd  ; treprostinil inh powder

112 x 16MCG & 84 x 32MCG ; 112 x 32MCG & 112 x48MCG ; 16 & 32 & 48 MCG ; 16 MCG ; 32 MCG ; 48 MCG ; 64 MCG

M ; N ; O ; Y

N

Tyvaso ; Tyvaso refill kit ; Tyvaso starter kit

Treprostinil Inhalation Solution 0.6 MG/ML

0.6 MG/ML

M ; N ; O ; Y

N

Uptravi

selexipag tab

1000 MCG ; 1200 MCG ; 1400 MCG ; 1600 MCG ; 200 MCG ; 400 MCG ; 600 MCG ; 800 MCG

M ; N ; O ; Y

N

Uptravi titration pack

selexipag tab therapy pack

200 & 800 MCG

M ; N ; O ; Y

N

Adcirca

tadalafil tab

20 MG

60

Tablets

30

DAYS

Adempas

riociguat tab

0.5 MG ; 1 MG ; 1.5 MG ; 2 MG ; 2.5 MG

90

Tablets

30

DAYS

Letairis

ambrisentan tab

10 MG ; 5 MG

30

Tablets

30

DAYS

Liqrev

sildenafil citrate oral susp

10 MG/ML

244

mLs

30

DAYS

Opsumit

macitentan tab

10 MG

30

Tablets

30

DAYS

Opsynvi

macitentan-tadalafil tab

10-20 MG

30

Tablets

30

DAYS

Opsynvi

macitentan-tadalafil tab

10-40 MG

30

Tablets

30

DAYS

Orenitram titration kit m

treprostinil tab er titr pk (mo

0.125 & 0.25 MG

1

Pack

180

DAYS

Orenitram titration kit m

treprostinil tab er titr pk (mo

0.125 & 0.25 MG

1

Pack

180

DAYS

Orenitram titration kit m

treprostinil tab er titr pk(mo

0.125 & 0.25 &1 MG

1

Pack

180

DAYS

Revatio

sildenafil citrate for suspension

10 MG/ML

2

Bottles

30

Revatio

sildenafil citrate tab

20 MG

90

Tablets

30

DAYS

Tadliq

Tadalafil Oral Susp

20 MG/5ML

300

mLs

30

DAYS

Tracleer

bosentan tab

125 MG ; 62.5 MG

60

Tablets

30

DAYS

Tracleer

bosentan tab for oral susp

32 MG

120

Tablets

30

DAYS

Tyvaso

treprostinil inhalation solution

0.6 MG/ML

7

Packages

28

DAYS

66302020603

Tyvaso dpi institutional ; Tyvaso dpi maintenance ki

Treprostinil Inh Powder

16 MCG

112

Cartridges

28

DAYS

Tyvaso dpi institutional ; Tyvaso dpi maintenance ki

Treprostinil Inh Powder

32 MCG

112

Cartridges

28

DAYS

Tyvaso dpi institutional ; Tyvaso dpi maintenance ki

Treprostinil Inh Powder

48 MCG

112

Cartridges

28

DAYS

Tyvaso dpi institutional ; Tyvaso dpi maintenance ki

Treprostinil Inh Powder

64 MCG

112

Cartridges

28

DAYS

Tyvaso dpi maintenance ki

Treprostinil Inh Powder

112 x 32MCG & 112 x48MCG

224

Cartridges

28

DAYS

Tyvaso dpi titration kit

Treprostinil Inh Powd

16 & 32 & 48 MCG

252

Cartridges

180

DAYS

Tyvaso dpi titration kit

Treprostinil Inh Powder

112 x 16MCG & 84 x 32MCG

196

Cartridges

180

DAYS

Tyvaso refill kit

treprostinil inhalation solution

0.6 MG/ML

28

Packages

28

DAYS

66302020602

Tyvaso starter kit

treprostinil inhalation solution

0.6 MG/ML

1

Kit

180

DAYS

66302020601

Tyvaso starter kit

treprostinil inhalation solution

0.6 MG/ML

1

Kit

180

DAYS

66302020604

Uptravi

selexipag tab

1000 MCG ; 1200 MCG ; 1400 MCG ; 1600 MCG ; 200 MCG ; 400 MCG ; 600 MCG ; 800 MCG

60

Tablets

30

DAYS

Uptravi

selexipag tab

200 MCG

60

Tablets

30

DAYS

66215060206

Uptravi

selexipag tab

200 MCG

140

Tablets

180

DAYS

66215060214

Uptravi titration pack

selexipag tab therapy pack

200 & 800 MCG

1

Package

180

DAYS

Ventavis

Iloprost Inhalation Solution 10 MCG/ML

10 MCG/ML

270

Ampules

30

DAYS

Ventavis

Iloprost Inhalation Solution 20 MCG/ML

20 MCG/ML

270

Ampules

30

DAYS

Winrevair

sotatercept-csrk for subcutaneous soln kit

45 MG

1

Kit

21

DAYS

Winrevair

sotatercept-csrk for subcutaneous soln kit

60 MG

1

Kit

21

DAYS

Winrevair

sotatercept-csrk for subcutaneous soln kit

2 x 45 MG

1

Kit

21

DAYS

Winrevair

sotatercept-csrk for subcutaneous soln kit

2 x 60 MG

1

Kit

21

DAYS

Adcirca

tadalafil tab

20 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Adempas

riociguat tab

0.5 MG ; 1 MG ; 1.5 MG ; 2 MG ; 2.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Letairis

ambrisentan tab

10 MG ; 5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Liqrev

sildenafil citrate oral susp

10 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Opsumit

macitentan tab

10 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Opsynvi

macitentan-tadalafil tab

10-20 MG ; 10-40 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Orenitram ; Orenitram titration kit m

treprostinil diolamine tab er  ; treprostinil tab er titr pk (mo ; treprostinil tab er titr pk(mo

0.125 & 0.25 &1 MG ; 0.125 & 0.25 MG ; 0.125 MG ; 0.25 MG ; 1 MG ; 2.5 MG ; 5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Revatio

sildenafil citrate for suspension

10 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Revatio

sildenafil citrate tab

20 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tadliq

tadalafil oral susp

20 MG/5ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tracleer

bosentan tab  ; bosentan tab for oral susp

125 MG ; 32 MG ; 62.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso ; Tyvaso refill kit ; Tyvaso starter kit

Treprostinil Inhalation Solution 0.6 MG/ML

0.6 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso dpi institutional ; Tyvaso dpi maintenance ki ; Tyvaso dpi titration kit

treprostinil inh powd  ; treprostinil inh powder

112 x 16MCG & 84 x 32MCG ; 112 x 32MCG & 112 x48MCG ; 16 & 32 & 48 MCG ; 16 MCG ; 32 MCG ; 48 MCG ; 64 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Uptravi

selexipag tab

1000 MCG ; 1200 MCG ; 1400 MCG ; 1600 MCG ; 200 MCG ; 400 MCG ; 600 MCG ; 800 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Uptravi titration pack

selexipag tab therapy pack

200 & 800 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Ventavis

Iloprost Inhalation Solution 10 MCG/ML

10 MCG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Ventavis

Iloprost Inhalation Solution 20 MCG/ML

20 MCG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Winrevair

sotatercept-csrk for subcutaneous soln kit

2 x 45 MG ; 2 x 60 MG ; 45 MG ; 60 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Adcirca

tadalafil tab

20 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Adempas

riociguat tab

0.5 MG ; 1 MG ; 1.5 MG ; 2 MG ; 2.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Letairis

ambrisentan tab

10 MG ; 5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Liqrev

sildenafil citrate oral susp

10 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Opsumit

macitentan tab

10 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Opsynvi

macitentan-tadalafil tab

10-40 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Opsynvi

macitentan-tadalafil tab

10-20 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Orenitram titration kit m

treprostinil tab er titr pk (mo

0.125 & 0.25 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Orenitram titration kit m

treprostinil tab er titr pk (mo

0.125 & 0.25 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Orenitram titration kit m

treprostinil tab er titr pk(mo

0.125 & 0.25 &1 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Revatio

sildenafil citrate for suspension

10 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Revatio

sildenafil citrate tab

20 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tadliq

Tadalafil Oral Susp

20 MG/5ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tracleer

bosentan tab

125 MG ; 62.5 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tracleer

bosentan tab for oral susp

32 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso

treprostinil inhalation solution

0.6 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso dpi institutional ; Tyvaso dpi maintenance ki

Treprostinil Inh Powder

16 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso dpi institutional ; Tyvaso dpi maintenance ki

Treprostinil Inh Powder

32 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso dpi institutional ; Tyvaso dpi maintenance ki

Treprostinil Inh Powder

64 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso dpi institutional ; Tyvaso dpi maintenance ki

Treprostinil Inh Powder

48 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso dpi maintenance ki

Treprostinil Inh Powder

112 x 32MCG & 112 x48MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso dpi titration kit

Treprostinil Inh Powd

16 & 32 & 48 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso dpi titration kit

Treprostinil Inh Powder

112 x 16MCG & 84 x 32MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso refill kit

treprostinil inhalation solution

0.6 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso starter kit

treprostinil inhalation solution

0.6 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Tyvaso starter kit

treprostinil inhalation solution

0.6 MG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Uptravi

selexipag tab

200 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Uptravi

selexipag tab

200 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Uptravi

selexipag tab

1000 MCG ; 1200 MCG ; 1400 MCG ; 1600 MCG ; 200 MCG ; 400 MCG ; 600 MCG ; 800 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Uptravi titration pack

selexipag tab therapy pack

200 & 800 MCG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Ventavis

Iloprost Inhalation Solution 10 MCG/ML

10 MCG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Ventavis

Iloprost Inhalation Solution 20 MCG/ML

20 MCG/ML

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Winrevair

sotatercept-csrk for subcutaneous soln kit

2 x 45 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Winrevair

sotatercept-csrk for subcutaneous soln kit

45 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Winrevair

sotatercept-csrk for subcutaneous soln kit

60 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Winrevair

sotatercept-csrk for subcutaneous soln kit

2 x 60 MG

Blue Partner ; Commercial ; GenPlus ; Health Insurance Marketplace ; NetResults A Series ; SourceRx

Initial Evaluation

Target Agent(s) will be approved when ALL of the following are met: 

1. ONE of the following:
   1. BOTH of the following:
      1. The requested agent is eligible for continuation of therapy AND ONE of the following:

1. 1. 1. 1. The patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days OR
         2. The prescriber states the patient has been treated with the requested agent (starting on samples is not approvable) within the past 90 days AND is at risk if therapy is changed AND
      2. The patient has an FDA labeled indication for the requested agent and route of administration OR
   2. The patient has a diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH), WHO Group 4 and ALL of the following:
      1. The requested agent is Adempas AND
      2. The patient’s diagnosis has been confirmed by a ventilation-perfusion scan and a confirmatory selective pulmonary angiography AND
      3. The patient has a mean pulmonary artery pressure of greater than 20 mmHg AND
      4. The patient has a pulmonary capillary wedge pressure less than or equal to 15 mmHg AND
      5. The patient has a pulmonary vascular resistance greater than 2 Wood units AND
      6. ONE of the following:
         1. The patient is NOT a candidate for surgery OR
         2. The patient has had a pulmonary endarterectomy AND has persistent or recurrent disease AND
      7. The patient will NOT be using the requested agent in combination with a PDE5 inhibitor (e.g., tadalafil [Adcirca or Cialis] or sildenafil [Revatio or Viagra]) OR
   3. The patient has a diagnosis of pulmonary arterial hypertension (PAH), WHO Group 1 and ALL of the following:
      1. The patient’s diagnosis has been confirmed by right heart catheterization (medical records required) AND
      2. The patient’s mean pulmonary arterial pressure is greater than 20 mmHg AND
      3. The patient has a pulmonary capillary wedge pressure less than or equal to 15 mmHg AND
      4. The patient has a pulmonary vascular resistance greater than 2 Wood units AND
      5. If the requested agent is Winrevair (sotatercept), then the patient is not pregnant or planning to become pregnant while on therapy with the requested agent AND
      6. If the requested agent is Adcirca, Adempas, Liqrev, Opsynvi, Revatio, sildenafil, Tadliq, or tadalafil, the patient will NOT be using the requested agent in combination with a/another PDE5 inhibitor (e.g., tadalafil [Adcirca or Cialis] or sildenafil [Revatio or Viagra]) AND
      7. ONE of the following:
         1. The requested agent is not Winrevair (sotatercept) and it will be utilized as monotherapy OR
         2. The requested agent will be utilized as part of dual therapy AND ONE of the following: 
            1. Therapy will consist of 1 agent from 2 of the following therapeutic classes: an endothelin receptor antagonist (ERA), phosphodiesterase 5 inhibitor (PDE5i) and prostanoid OR
            2. Therapy will consist of an ERA plus a soluble guanylate cyclase inhibitor (sGC) (Adempas) AND the patient has had an unacceptable response to therapy with an ERA plus a PDE5i OR
         3. The requested agent will be utilized as part of triple therapy AND ONE of the following:
            1. Therapy will consist of an endothelin receptor antagonist (ERA) plus phosphodiesterase 5 inhibitor (PDE5i) plus a prostanoid AND the patient has been assessed as high risk using a PAH risk stratification tool or is WHO functional class IV OR
            2. Therapy will consist of an ERA plus PDE5i plus an activin-signaling inhibitor (Winrevair), or, an ERA plus a PDE5i plus a prostanoid AND the patient has had an inadequate response to established PAH pharmacotherapy with at least 2 or more of the following drug classes: ERA, PDE5i, and/or prostacyclin analogue or receptor agonist OR
         4. The requested agent will be utilized as part of quadruple therapy and ALL of the following:
            1. The patient has been assessed as high risk using a PAH risk stratification tool or is WHO functional class IV AND
            2. All four agents in the quadruple therapy are from a different therapeutic class AND
            3. The patient has had an inadequate response to established PAH pharmacotherapy with at least 3 or more of the following drug classes: ERA, PDE5i, activin-signaling inhibitor and prostacyclin analogue/receptor agonist AND
            4. ONE of the following:
               1. A prostanoid has been started as one of the agents in the triple therapy OR
               2. The patient has an intolerance, FDA labeled contraindication, or hypersensitivity to ALL prostanoids OR
   4. The patient has a diagnosis of pulmonary hypertension associated with interstitial lung disease (PH-ILD, WHO group 3) AND ALL of the following:
      1. The requested agent is Tyvaso AND
      2. The patient’s diagnosis has been confirmed by right heart catheterization (medical records required) AND
      3. The patient’s mean pulmonary arterial pressure is greater than 20 mmHg AND
      4. The patient has a pulmonary capillary wedge pressure less than or equal to 15 mmHg AND
      5. The patient has a pulmonary vascular resistance greater than 2 Wood units AND
      6. The patient's PH-ILD was assessed using key parts (e.g., risk factors for PAH and CTEPH, clinical features including disease trajectory, pulmonary function tests [PFT], brain natriuretic peptide [BNP]/N-terminal pro-BNP [NT-proBNP], cross-sectional imaging, and echocardiography) AND
      7. The patient has extensive parenchymal changes on computed tomography (CT) AND
      8. BOTH of the following:
         1. The patient is currently treated with standard of care therapy for ILD (e.g., Ofev) AND
         2. The patient will continue standard of care therapy for ILD (e.g., Ofev) OR
   5. The patient has another FDA labeled indication for the requested agent and route of administration AND
2. If the patient has an FDA labeled indication, then ONE of the following:
   1. The patient’s age is within FDA labeling for the requested indication for the requested agent OR
   2. There is support for using the requested agent for the patient’s age for the requested indication and route of administration AND
3. If the request is for ONE of the following brand agents with an available generic equivalent (listed below), then ONE of the following:

3. 1. The patient has an intolerance or hypersensitivity to the generic equivalent that is not expected to occur with the brand agent OR
   2. The patient has an FDA labeled contraindication to the generic equivalent that is not expected to occur with the brand agent OR
   3. There is support for the use of the requested brand agent over the generic equivalent AND
4. If the request is for Tadliq, then one of the following:​​​​​​
   1. The patient has tried and had an inadequate response to generic tadalafil tablets OR
   2. The patient has an in intolerance or hypersensitivity to generic tadalafil tablets that is not expected to occur with the requested agent OR
   3. The patient has an FDA labeled contraindication to generic tadalafil tablets that is not expected to occur with the requested agent AND
5. If the request is for Liqrev, then one of the following:
   1. The patient has tried and had an inadequate response to generic sildenafil oral suspension OR
   2. The patient has an intolerance or hypersensitivity to the generic sildenafil oral suspension that is not expected to occur with the requested agent OR
   3. The patient has an FDA labeled contraindication to generic sildenafil oral suspension that is not expected to occur with the requested agent AND
6. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist, pulmonologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
7. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

*Step therapy requirement may not apply if a prior health plan paid for the medication - documentation of a paid claim may be required.

Renewal Evaluation

Target Agent(s) will be approved when ALL of the following are met:

1. The patient has been previously approved for the requested agent through the plan’s Prior Authorization process [NOTE: Patients not previously approved for the requested agent will require initial evaluation review] AND
2. The patient has had clinical benefit with the requested agent (e.g., stabilization, decreased disease progression) (medical records required) AND
3. If the requested agent is Tyvaso for a diagnosis of pulmonary hypertension associated with interstitial lung disease (PH-ILD, WHO group 3), then the patient will continue standard of care therapy for ILD (e.g., Ofev) AND
4. If the request is for ONE of the following brand agents with an available generic equivalent (listed below), then ONE of the following: 

4. 1. The patient has an intolerance or hypersensitivity to the generic equivalent that is not expected to occur with the brand agent OR
   2. The patient has an FDA labeled contraindication to the generic equivalent that is not expected to occur with the brand agent OR
   3. There is support for the use of the requested brand agent over the generic equivalent AND
5. If the request is for Tadliq, then one of the following:​
   1. The patient has tried and had an inadequate response to generic tadalafil tablets OR
   2. The patient has an in intolerance or hypersensitivity to generic tadalafil tablets that is not expected to occur with the requested agent OR
   3. The patient had an FDA labeled contraindication to generic tadalafil tablets that is not expected to occur with the requested agent AND
6. If the request is for Liqrev, then one of the following:
   1. The patient has tried and had an inadequate response to generic sildenafil oral suspension OR
   2. The patient has an intolerance or hypersensitivity to the generic sildenafil oral suspension that is not expected to occur with the requested agent OR
   3. The patient has an FDA labeled contraindication to generic sildenafil oral suspension that is not expected to occur with the requested agent AND
7. The prescriber is a specialist in the area of the patient’s diagnosis (e.g., cardiologist, pulmonologist) or the prescriber has consulted with a specialist in the area of the patient’s diagnosis AND
8. The patient does NOT have any FDA labeled contraindications to the requested agent

Length of Approval:  12 months

NOTE: If Quantity Limit applies, please refer to Quantity Limit Criteria.

Quantity Limit for the Target Agent(s) will be approved when ONE of the following is met:

1. The requested quantity (dose) does NOT exceed the program quantity limit OR
2. The requested quantity exceeds the program quantity limit AND ONE of the following:
   1. BOTH of the following:
      1. The requested agent does NOT have a maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication OR
   2. BOTH of the following:
      1. The requested quantity (dose) does NOT exceed the maximum FDA labeled dose for the requested indication AND
      2. There is support for why the requested quantity (dose) cannot be achieved with a lower quantity of a higher strength that does not exceed the program quantity limit OR
   3. BOTH of the following:
      1. The requested quantity (dose) exceeds the maximum FDA labeled dose for the requested indication AND
      2. There is support for therapy with a higher dose for the requested indication

Length of Approval: Up to 12 months