TREPROSTINIL POWDER,INHL
Clinical Criteria Summary
Document 543
Provider & Care Setting Requirements
- Care provided by a VA or VA Community Care provider experienced in the management of PAH
Diagnostic & Hemodynamic Criteria
- Definitive PAH confirmed by right-heart catheterization and hemodynamic diagnosis
- Mean pulmonary artery pressure greater than 20 mmHg
- Pulmonary capillary wedge pressure 15 mmHg or less
- Pulmonary vascular resistance greater than 2 Wood units
Classification & Clinical Status
- World Health Organization (WHO) Group 1 PAH
- Unacceptable or deteriorating clinical status on PAH-directed therapy with, or not a candidate for, an endothelin receptor antagonist (ERA) and phosphodiesterase-5 inhibitor (PDE5i)
- Efficacy established in patients with NYHA Functional Class III symptoms
Formulation & Dosing Preferences
- Nebulized solution preferred if patient requires more than one cartridge or capsule per dose using the DPI (e.g., >64 mcg of TYVASO or >106 mcg of YUTREPIA)
- Dry powder inhalers (DPIs) reserved for patients with documented inability to use the nebulized product
Adjudication & Documentation
- Individual cases that are exceptions to inclusion/exclusion criteria should be adjudicated at the local facility level per P&T committee and pharmacy services policy/procedures
- Product information should be consulted for detailed prescribing information
Document 544
Provider & Care Setting Requirements
- Care must be provided by a VA or VA Community Care provider experienced in the management of pulmonary hypertension (PH).
Diagnosis & Indication Criteria
- Definitive, confirmed diagnosis of interstitial lung disease (ILD) (e.g., diffuse parenchymal lung disease on chest CT).
- Examples of ILD include idiopathic interstitial pneumonia, combined pulmonary fibrosis and emphysema, connective tissue disease, and chronic hypersensitivity pneumonitis.
- Definitive, confirmed diagnosis of WHO Group 3 PH associated with ILD.
Hemodynamic Criteria (via Right-Heart Catheterization)
- Mean pulmonary artery pressure of at least 25 mmHg.
- Pulmonary capillary wedge pressure of 15 mmHg or less.
- Pulmonary vascular resistance greater than 3 Wood units.
Formulation & Dosing Preferences
- Nebulized solution is preferred for patients requiring more than one cartridge per dose using the dry powder inhaler (DPI) (e.g., >64 mcg of TYVASO or >106 mcg of YUTREPIA).
- DPI should be reserved for patients with a documented inability to use the nebulized product.
Adjudication & Clinical Management
- All inclusion criteria must be met.
- Individual cases that are exceptions to exclusion/inclusion criteria or require formulation preference adjustments should be adjudicated at the local facility level per P&T Committee and Pharmacy Services policies/procedures.
Document 545
Indication & Patient Population
- • Pulmonary hypertension associated with interstitial lung disease (PH-ILD; WHO Group 3) to improve exercise ability
- • Pulmonary arterial hypertension (PAH; WHO Group 1) to improve exercise ability
- • PH-ILD patient criteria: ILD diagnosed by chest CT, Group 3 PH confirmed by right heart catheterization (RHC) with pulmonary vascular resistance (PVR) >3 Wood units, pulmonary capillary wedge pressure (PCWP) ≤15 mmHg, mean pulmonary arterial pressure (mPAP) ≥25 mm Hg, and baseline 6-minute walk distance (6MWD) ≥100 m
Dosing & Administration
- • Dry powder inhaler (DPI) strengths: 16 mcg, 32 mcg, 48 mcg, and 64 mcg single-dose color-coded cartridges
- • Dosing frequency: 1 breath per cartridge, 4 times daily, administered about 4 hours apart
- • Titration regimen: Initial dose of 3 breaths (6 mcg per breath) 4 times daily; target dose of 9 breaths; maximum dose of 12 breaths
- • Cartridge-to-strength mapping: 6 to 7 breaths corresponds to 32 mcg, 8 to 10 breaths to 48 mcg, and 11 to 12 breaths to 64 mcg
Safety, Warnings & Monitoring
- • Contraindications: None stated
- • Boxed Warnings: None stated for the drug itself
- • Warnings/Precautions: Risk of symptomatic hypotension, bleeding (due to platelet aggregation inhibition), and bronchospasm; drug interactions with CYP2C8 inhibitors (increased adverse effects) or CYP2C8 inducers (decreased effectiveness)
- • Adverse Reactions: Cough, headache, dyspnea, dizziness, nausea, fatigue, diarrhea
- • Excipient consideration: Contains fumaryl diketopiperazine (FDKP); while FDKP carries a boxed warning for acute bronchospasm risk in chronic lung disease per other products, no bronchospastic adverse events or safety signals were identified in clinical studies
Storage & Device Management
- • Cartridges must be stored in a refrigerator; room temperature excursions are permitted but shorten shelf life
- • DPI should be at room temperature for 10 minutes prior to use
- • Inhaler device is reusable for 7 days, then must be replaced/discarded
Place in Therapy & Efficacy Considerations
- • Indicated based on a placebo-controlled trial demonstrating improved 6MWD, NT-proBNP ratio, and reduced clinical worsening
- • May be considered as an alternative to the liquid inhalation nebulized formulation for patients with PAH or PH-ILD
- • Long-term data are lacking; European guidelines provide a weak recommendation for use in PH-ILD