Treprostinil - Warnings and Precautions

5 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.

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 lowerincidence of BSIs when compared to neutral diluents (sterile water, 0.9% sodium chloride) whenused along with catheter care guidelines.

In an open-label study of an implantable pump (n=60), there were two blood stream infections (BSIs) related to the implant procedure during approximately 265 patient years.

5.2 Worsening PAH upon Abrupt Withdrawal or Sudden Large Dose Reduction Avoid abrupt withdrawal or sudden large reductions in dosage of treprostinil injection, which may result in worsening of PAH symptoms.

5.3 Patients with Hepatic Insufficiency Titrate treprostinil injection slowly in patients with hepatic or renal insufficiency, because such patients will likely be exposed to greater systemic concentrations relative to patients with normal hepatic function [see Dosage and Administration , Use in Specific Populations , and Clinical Pharmacology ] .

5.4 Risk of Symptomatic Hypotension Treprostinil is a pulmonary and systemic vasodilator.

In patients with low systemic arterial pressure, treatment with treprostinil injection may produce symptomatic hypotension.

5.5 Risk of Bleeding Treprostinil injection inhibits platelet aggregation and increases the risk of bleeding.