Treprostinil

The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds, and inhibition of platelet aggregation.

• Treprostinil injection is a prostacyclin mimetic indicated for: • Treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%).ICD-10: I27.0

• None Nonecontraindicated

PAH WHO Group 1 in patients with NYHA Class II-IV symptoms: • Initial dose for patients new to prostacyclin infusion therapy: 1.25 ng/kg/min; increase based on clinical response (increments of 1.25 ng/kg/min per week for the first 4 weeks of treatment, later 2.5 ng/kg/min per week). Avoid abrupt cessation. (2.2, 2.4) • Mild to moderate hepatic insufficiency: Decrease initial dose to 0.625 ng/kg/min. Severe hepatic insufficiency: No studies performed. (2.5) Transition from Epoprostenol: • Increase the Treprostinil injection dose gradually as the epoprostenol dose is decreased, based on constant observation of response. (2.7) Administration: Continuous subcutaneous infusion is the preferred mode. Use intravenous (IV) infusion if subcutaneous infusion is not tolerated. (2.1, 2.6) 2.1 General Treprostinil injection can be administered with or without further dilution with Sterile Diluent for Treprostinil injection or similar approved high-pH glycine diluent (e.g., Sterile Diluent for Flolan or Sterile Diluent for Epoprostenol), Sterile Water for Injection, or 0.9% Sodium Chloride Injection prior to administration. See Table 1 below for storage and administration time limits for the different diluents. Diluted Treprostinil injection has been shown to be stable at ambient temperature when stored for up to 14 days using high-pH glycine diluent at concentrations as low as 0.004 mg/mL (4,000 ng/mL).

• Chronic intravenous infusions delivered using an external infusion pump with an indwelling central venous catheter are associated with the risk of blood stream infections (BSIs) and sepsis, which may be fatal. (5.1) • Do not abruptly lower the dose or withdraw dosing. (5.2) • Treprostinil injection may cause symptomatic hypotension. (5.4) • Treprostinil injection inhibits platelet aggregation and increases the risk of bleeding. (5.5) 5.1 Risk of Catheter-Related Bloodstream Infection Chronic intravenous infusions of Treprostinil injection delivered using an external infusion pump with an indwelling central venous catheter are associated with the risk of blood stream infections (BSIs) and sepsis, which may be fatal. Therefore, continuous subcutaneous infusion is the preferred mode of administration. In an open-label study of IV treprostinil (n=47) using an external infusion pump, there were seven catheter-related line infections during approximately 35 patient years, or about 1 BSI event per 5 years of use. A CDC survey of seven sites that used IV treprostinil for the treatment of PAH found approximately 1 BSI (defined as any positive blood culture) event per 3 years of use. Administration of IV Treprostinil injection with a high pH glycine diluent has been associated with a lower incidence of BSIs when compared to neutral diluents (sterile water, 0.9% sodium chloride) when used along with catheter care guidelines.

The following adverse reactions are discussed elsewhere in labeling: Infections associated with intravenous administration [see Warnings and Precautions (5.1)] . Most common adverse reactions (incidence >3%) reported in clinical studies with Treprostinil injection: subcutaneous infusion site pain and reaction, headache, diarrhea, nausea, jaw pain, vasodilatation, edema, and hypotension. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals, Inc. at 1-866-210-9797 or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch . 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse Events with Subcutaneously Administered Treprostinil injection Patients receiving Treprostinil injection as a subcutaneous infusion reported a wide range of adverse events, many potentially related to the underlying disease (dyspnea, fatigue, chest pain, right ventricular heart failure, and pallor). During clinical trials with subcutaneous infusion of Treprostinil injection, infusion site pain and reaction were the most common adverse events among those treated with Treprostinil injection. Infusion site reaction was defined as any local adverse event other than pain or bleeding/bruising at the infusion site and included symptoms such as erythema, induration, or rash.

8.1 Pregnancy Risk Summary Limited case reports of treprostinil use in pregnant women are insufficient to inform a drug- associated risk of adverse developmental outcomes. However, there are risks to the mother and the fetus associated with pulmonary arterial hypertension ( see Clinical Considerations ). In animal studies, no adverse reproductive and developmental effects were seen in rats at about 123 and 48 times the human exposure based on C max and AUC, respectively. In rabbits, external fetal and soft tissue malformations and skeletal malformations were observed at about 7 and 5 times the human exposure based on C max and AUC, respectively ( see Data ). The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. Clinical Considerations Disease-associated maternal and embryo-fetal risk Pulmonary arterial hypertension is associated with an increased risk of maternal and fetal mortality. Data Animal reproduction studies have been conducted with treprostinil via continuous subcutaneous administration and with treprostinil diolamine administered orally.

Metabolism

The pharmacokinetics of continuous subcutaneous Treprostinil injection are linear over the dose range of 2.5 to 125 ng/kg/min (corresponding to plasma concentrations of about 260 pg/mL to 18,250 pg/mL) and can be described by a two-compartment model. Dose proportionality at infusion rates greater than 125 ng/kg/min has not been studied.

Signs and symptoms of overdose with Treprostinil injection during clinical trials are extensions of its dose-limiting pharmacologic effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events were self-limiting and resolved with reduction or withholding of Treprostinil injection. In controlled clinical trials using an external infusion pump, seven patients received some level of overdose and in open-label follow-on treatment seven additional patients received an overdose; these occurrences resulted from accidental bolus administration of Treprostinil injection, errors in pump programmed rate of administration, and prescription of an incorrect dose. In only two cases did excess delivery of Treprostinil injection produce an event of substantial hemodynamic concern (hypotension, near-syncope). One pediatric patient was accidentally administered 7.5 mg of Treprostinil injection via a central venous catheter. Symptoms included flushing, headache, nausea, vomiting, hypotension, and seizure-like activity with loss of consciousness lasting several minutes. The patient subsequently recovered.

• May 21, 2002NDANDA021272United Therap
• Jul 30, 2009NDANDA022387United Therap
• Dec 20, 2013NDANDA203496United Therap
• Nov 30, 2017ANDAANDA203649Sandoz
• Sep 26, 2019ANDAANDA206648Teva Pharms Usa
• May 22, 2020ANDAANDA210214Dr Reddys
• May 23, 2022NDANDA214324United Therap
• May 23, 2025NDANDA213005Liquidia Tech

1. 1Dyspnoea20,80217%
2. 2Headache16,72514%
3. 3Diarrhoea13,42411%
4. 4Nausea12,10510.0%
5. 5Cough11,0359.1%
6. 6Dizziness9,1647.5%
7. 7Fatigue9,1027.5%
8. 8Death8,8787.3%
9. 9Vomiting6,1975.1%
10. 10Infusion Site Pain5,5994.6%
11. 11Hypotension5,5624.6%
12. 12Pneumonia5,5204.5%
13. 13Malaise5,4934.5%
14. 14Fluid Retention5,0224.1%
15. 15Pain In Extremity4,8304.0%

The 10 most recently updated of 151 ClinicalTrials.gov registrations naming Treprostinil as an intervention. Registration is not evidence of efficacy or safety — reference crosswalk only.

• A Study to Evaluate the Pharmacokinetics (PK) and Safety of a Single Dose of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Normal Hepatic Function and Participants With Hepatic Impairment
  Not yet recruiting · Phase 1 · Interventional · 30 enrolled · Insmed Incorporated
  NCT07643155updated 2026-06-11
• A Study to Evaluate the Efficacy and Safety of Once Daily Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Arterial Hypertension (PAH)
  Recruiting · Phase 3 · Interventional · 344 enrolled · Insmed Incorporated
  NCT07481981updated 2026-06-10
• DeciPHer-ILD: A Real-world Patient Registry in Group 3 Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)
  Recruiting · Observational · 900 enrolled · United Therapeutics
  NCT06388421updated 2026-06-10
• An Expanded Access Study to Assess Treprostinil Palmitil Inhalation Powder (TPIP) for Participants With Pulmonary Arterial Hypertension (PAH) and Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)
  Available · Expanded access · Insmed Incorporated
  NCT06939647updated 2026-06-10
• Study of the Efficacy and Safety of Inhaled Treprostinil in Subjects With Progressive Pulmonary Fibrosis (TETON-PPF)
  Recruiting · Phase 3 · Interventional · 698 enrolled · United Therapeutics
  NCT05943535updated 2026-06-04
• Inhaled Treprostinil for Dyspnea and Exercise Intolerance in Mild COPD
  Active not recruiting · Phase 2 · Interventional · 20 enrolled · University of Alberta
  NCT06969573updated 2026-06-04
• A Phase 3 Study to Evaluate the Safety and Efficacy L606 in Participants With PH-ILD
  Recruiting · Phase 3 · Interventional · 344 enrolled · Liquidia Technologies, Inc.
  NCT07285655updated 2026-06-02
• An Extension Study of Treprostinil Palmitil Inhalation Powder (TPIP) for Pulmonary Arterial Hypertension (PAH)
  Active not recruiting · Phase 2 · Phase 3 · Interventional · 91 enrolled · Insmed Incorporated
  NCT05649748updated 2026-05-28
• Inhaled Treprostinil in Participants With Pulmonary Hypertension Due to Chronic Obstructive Pulmonary Disease (PH-COPD)
  Terminated · Phase 3 · Interventional · 41 enrolled · United Therapeutics
  NCT03794583updated 2026-05-27
• Efficacy and Safety Study of Treprostinil Palmitil Inhalation Powder (TPIP) in Participants With Pulmonary Hypertension Associated With Interstitial Lung Disease (PH-ILD)
  Recruiting · Phase 3 · Interventional · 344 enrolled · Insmed Incorporated
  NCT07179380updated 2026-05-27

Frequently asked questions

How does Treprostinil work?

The major pharmacologic actions of treprostinil are direct vasodilation of pulmonary and systemic arterial vascular beds, and inhibition of platelet aggregation.

What is Treprostinil used for?

According to FDA labeling, Treprostinil carries indications including: Treprostinil injection is a prostacyclin mimetic indicated for: • Treatment of pulmonary arterial hypertension (PAH; WHO Group 1) to diminish symptoms associated with exercise. Studies establishing effectiveness included patients with NYHA Functional Class II-IV symptoms and etiologies of idiopathic or heritable PAH (58%), PAH associated with congenital systemic-to-pulmonary shunts (23%), or PAH associated with connective tissue diseases (19%).. This is a reference summary of labeled uses, not medical advice or a treatment recommendation.

What class of drug is Treprostinil?

Treprostinil is classified as Platelet aggregation inhibitors excl. heparin, Prostacycline Vasodilator, Prostaglandin Receptor Agonists, Decreased Blood Pressure, Decreased Platelet Aggregation, Pulmonary Arterial Vasodilation, Systemic Arterial Vasodilation, Vasodilation.

What are the brand names for Treprostinil?

Treprostinil is marketed under brand names including Orenitram, Remodulin, Tyvaso, Yutrepia.

What are the contraindications for Treprostinil?

Treprostinil labeling lists contraindications including: None None. Always consult the full prescribing information and a clinician.