Remodulin is a prostacyclin vasodilator 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%) (1.1)
• Patients who require transition from Flolan®, to reduce the rate of clinical deterioration. The risks and benefits of each drug should be carefully considered prior to transition. (1.2)

PAH 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, 2.3)
• Mild to moderate hepatic insufficiency: Decrease initial dose to 0.625 ng/kg/min. Severe hepatic insufficiency: No studies performed. (2.4)

Transition from Flolan:

Increase the Remodulin dose gradually as the Flolan dose is decreased, based on constant observation of response. (2.6)

Administration: Continuous subcutaneous infusion (undiluted) is the preferred mode. Use intravenous (IV) infusion (dilution required) if subcutaneous infusion is not tolerated. (2.1, 2.5)

None (4)
WARNINGS AND PRECAUTIONS

• For intravenous infusion use an indwelling central venous catheter. This route is 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)

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. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact United Therapeutics Corp. at 1-866-458-6479 or contact FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

• Blood pressure lowering drugs (e.g., diuretics, antihypertensive agents, or vasodilators): Risk of increased reduction in blood pressure (7.1)
• Remodulin inhibits platelet aggregation. Potential for increased risk of bleeding, particularly among patients on anticoagulants. (7.2)
• Remodulin dosage adjustment may be necessary if inhibitors or inducers of CYP2C8 are added or withdrawn. (7.6)