Treprostinil

What it is and how it works

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

Indications

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%). • Patients who require transition from epoprostenol, to reduce the rate of clinical deterioration. The risks and benefits of each drug should be carefully considered prior to transition. Pulmonary Arterial Hypertension Treprostinil injection is indicated for the 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%) .

Dosage and administration (summary)

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. Transition from Epoprostenol: Increase the treprostinil injection dose gradually as the epoprostenol dose is decreased, based on constant observation of response. Administration: Continuous subcutaneous infusion is the preferred mode.

Contraindications

None None

Warnings and precautions

• 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. • Do not abruptly lower the dose or withdraw dosing. • Treprostinil injection may cause symptomatic hypotension. • Treprostinil injection inhibits platelet aggregation and increases the risk of bleeding.

Pregnancy

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) .

Storage and supply

Treprostinil injection is supplied in 20-mL multi-dose vials as sterile solutions in water for injection, individually packaged in cartons. Unopened vials of treprostinil injection are stable until the date indicated when stored at 20° to 25°C (68° to 77°F) .

Source: Treprostinil (Treprostinil) — US FDA prescribing information, 2023-04-06, DailyMed. Summarised and shortened; the full label governs. Iranian registration, indications and labelling may differ.