Remodulin

/ Rafa

Treprostinil can be administered as supplied or diluted for intravenous infusion with Sterile Water for Injection or 0.9% Sodium Chloride Injection, prior to administration.
Initial Dose for Patients New to Prostacyclin Infusion Therapy: Treprostinil is indicated for subcutaneous (SC) or intravenous (IV) use only as a continuous infusion. Treprostinil is preferably infused subcutaneously, but can be administered by a central intravenous line if the subcutaneous route is not tolerated, because of severe site pain or reaction. The infusion rate is initiated at 1.25 ng/kg/min. If this initial dose cannot be tolerated because of systemic effects, the infusion rate should be reduced to 0.625 ng/kg/min.
Dosage Adjustments: The goal of chronic dosage adjustments is to establish a dose at which PAH symptoms are improved, while minimizing excessive pharmacologic effects of Treprostinil (headache, nausea, emesis, restlessness, anxiety and infusion site pain or reaction). The infusion rate should be increased in increments of 1.25 ng/kg/min per week for the first four weeks of treatment and then 2.5 ng/kg/min per week for the remaining duration of infusion, depending on clinical response. Dosage adjustments may be undertaken more often if tolerated. Abrupt cessation of infusion should be avoided. Restarting a Treprostinil infusion within a few hours after an interruption can be done using the same dose rate. Interruptions for longer periods may require the dose of Treprostinil to be re-titrated.
Patients with Hepatic Insufficiency: In patients with mild or moderate hepatic insufficiency, the initial dose of Treprostinil should be decreased to 0.625 ng/kg/min ideal body weight and should be increased cautiously. Treprostinil has not been studied in patients with severe hepatic insufficiency.
Patients with Renal Insufficiency: No studies have been performed in patients with renal insufficiency. No specific advice about dosing in patients with renal impairment can be given.
Administration: Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration whenever solution and container permit. If either particulate matter or discoloration is noted, Treprostinil should not be administered.
Subcutaneous Infusion: Treprostinil is administered subcutaneously by continuous infusion, via a self-inserted subcutaneous catheter, using an infusion pump designed for subcutaneous drug delivery. To avoid potential interruptions in drug delivery, the patient must have immediate access to a backup infusion pump and subcutaneous infusion sets. The ambulatory infusion pump used to administer Treprostinil should: (1) be small and lightweight, (2) be adjustable to approximately 0.002 mL/hr, (3) have occlusion/no delivery, low battery, programming error and motor malfunction alarms, (4) have delivery accuracy of ±6% or better and (5) be positive pressure driven. The reservoir should be made of polyvinyl chloride, polypropylene or glass. For subcutaneous infusion, Treprostinil is delivered without further dilution at a calculated Subcutaneous Infusion Rate (mL/hr) based on a patient’s Dose (ng/kg/min), Weight (kg), and the Vial Strength (mg/mL) of Treprostinil being used. During use, a single reservoir (syringe) of undiluted Treprostinil can be administered up to 72 hours at 37ċ. For the subcutaneous infusion rate calculation: See prescribing information for full details.

Indicated as a continuous subcutaneous infusion or intravenous infusion (for those not able to tolerate a subcutaneous infusion) for the treatment of Primary pulmonary arterial hypertension, Pulmonary arterial hypertension associated with connective tissue disorders, Pulmonary arterial hypertension associated with congenital systemic to pulmonary shunts.

Known hypersensitivity to the drug or to structurally related compounds.  

Risks attributable to the drug delivery system: Chronic intravenous infusions of treprostinil are delivered using an indwelling central venous catheter. This route is associated with the risk of blood stream infections (BSIs) and sepsis, which may be fatal. Therefore, continuous subcutaneous infusion (undiluted) is the preferred mode of administration.
General conditions of use: Remodulin should be used only by clinicians experienced in the diagnosis and treatment of PAH. Remodulin is a potent pulmonary and systemic vasodilator. Initiation of treprostinil must be performed in a setting with adequate personnel and equipment for physiological monitoring and emergency care. Therapy with treprostinil may be used for prolonged periods, and the patient’s ability to administer treprostinil and care for an infusion system should be carefully considered.
Dose Modification: Dose should be increased for lack of improvement in, or worsening of, symptoms and it should be decreased for excessive pharmacologic effects or for unacceptable infusion site symptoms.
See prescribing information for full details.

Infusion site reactions, diarrhea, nausea, headache.
See prescribing information for full details.

Antihypertensive Agents or Other Vasodilators: Concomitant administration of treprostinil with diuretics, antihypertensive agents or other vasodilators may increase the risk of symptomatic hypotension.
Anticoagulants: Since treprostinil inhibits platelet aggregation, there may be an increased risk of bleeding, particularly among patients receiving anticoagulants.

Pregnancy: The drug should be used during pregnancy only if clearly needed.
Lactation: It is not known whether treprostinil is excreted in human milk or absorbed systemically after ingestion.
See prescribing information for full details.

Signs and symptoms of overdose with Treprostinil during clinical trials are extensions of its dose-limiting pharmacologic effects and include flushing, headache, hypotension, nausea, vomiting, and diarrhea. Most events were self-limiting and resolved with reduction or withholding of Treprostinil.
In controlled clinical trials, seven patients received some level of overdose and in open-label follow-on treatment seven additional patients received an overdose; these occurrences resulted from accidental bolus administration of Treprostinil, errors in pump programmed rate of administration, and prescription of an incorrect dose. In only two cases did excess delivery of Treprostinil produce an event of substantial hemodynamic concern (hypotension, near-syncope).
One pediatric patient was accidentally administered 7.5 mg of Treprostinil via a central venous catheter. Symptoms included flushing, headache, nausea, vomiting, hypotension and seizure-like activity with loss of consciousness lasting several minutes. The patient subsequently recovered.

Storage: Shelf life after first opening – 30 days. Shelf life after dilution – 48 hours During use, a single reservoir (syringe) of undiluted treprostinil can be administered up to 72 hours at 37°C.