Interruptions for longer periods may require the dose of Remodulin to be re-titrated. In patients with mild or moderate liver dysfunction, the initial dose of Remodulin should be decreased to 0.625 ng/kg/min ideal body weight and should be increased cautiously. Remodulin has not been studied in patients with severe liver dysfunction. No studies have been performed in patients with kidney dysfunction. No specific advice about dosing in patients with renal impairment can be given. Inhaled form
The inhaled form of treprostinil was approved by the FDA in July 2009 and is marketed as the trade name Tyvaso. The inhaled form is used with a proprietary inhalation device supplied by the manufacturer. Patients use one ampule with inhalation solution a day, four times a day at least four hours apart. Oral form
The oral form of treprostinil was approved by the FDA in December 2013 and is marketed as the trade name Orenitram. Orenitram is taken 2 or 3 times daily with food. History
During the 1960s a U.K. research team, headed by Professor John Vane  began to explore the role of prostaglandins in anaphylaxis and respiratory diseases. Working with a team from the Royal College of Surgeons, Vane discovered that aspirin and other oral anti-inflammatory drugs worked by inhibiting the synthesis of prostaglandins. This finding opened the door to a broader understanding of the role of prostaglandins in the body. Vane and a team from the Wellcome Foundation had identified a lipid mediator they called “PG-X,” which inhibited platelet aggregation.
Dosage and administration
For infusion
Treprostinil may be administered as a continuous subcutaneous infusion or continuous intravenous infusion via a small infusion pump that the patient must wear at all times. Treprostinil can be given subcutaneously by continuous infusion using an infusion set connected to an infusion pump, but also may be given intravenously via a central venous catheter if the patient is unable to tolerate subcutaneous administration because of severe site pain or reaction. Remodulin is supplied in 20 mL vials, containing treprostinil in concentrations of 1 mg/mL, 2.5 mg/mL, 5 mg/mL, and 10 mg/mL. Treprostinil can be administered subcutaneously as supplied. It must be diluted for intravenous infusion with either sterile water or a 0.9% sodium chloride solution prior to administration. The infusion rate is normally initiated at 1.25 ng/kg/min for new patients, but may be reduced to 0.625 ng/kg/min if the normal rate provokes unwanted side effects in the patient. The infusion rate of treprostinil should be increased no more than 1.25 ng/kg/min per week for the first month, then 2.5 ng/kg/min per week for the remaining duration of infusion. The infusion rate should ideally be high enough to improve symptoms of pulmonary hypertension, while minimizing unpleasant side effects (headache, nausea, emesis, restlessness, anxiety and infusion site pain or reaction). Dosage adjustments may be undertaken more often if tolerated. There is little experience with doses >40 ng/kg/min. Abrupt cessation of infusion should be avoided. Restarting a Remodulin infusion within a few hours after an interruption can be done using the same dose rate.