Treprostinil

Remodulin 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.

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

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. 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 Remodulin dose gradually as the epoprostenol dose is decreased, based on constant observation of response. Administration: Continuous subcutaneous infusion is the preferred mode. Use intravenous (IV) infusion if subcutaneous infusion is not tolerated.

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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. Remodulin may cause symptomatic hypotension. Remodulin inhibits platelet aggregation and increases the risk of bleeding.

The following adverse reactions are discussed elsewhere in labeling: Infections associated with intravenous administration. Most common adverse reactions (incidence >3%) reported in clinical studies with Remodulin: subcutaneous infusion site pain and reaction, headache, diarrhea, nausea, jaw pain, vasodilatation, edema, and hypotension.

Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn. Effect of CYP2C8 Inhibitors and Inducers on Treprostinil Dose adjustment of treprostinil may be necessary when co-administered with CYP2C8 inducers or inhibitors. Human pharmacokinetic studies with an oral formulation of treprostinil (treprostinil diolamine) indicated that co-administration of the cytochrome P450 (CYP) 2C8 enzyme inhibitor gemfibrozil increases exposure (both C max and AUC) to treprostinil. Co-administration of the CYP2C8 enzyme inducer rifampin decreases exposure to treprostinil. It has not been determined if the changes in exposure of treprostinil with inhibitors or inducers of CYP2C8 observed for the oral administration of treprostinil would be similar for treprostinil administered via the parenteral route.