Treprostinil and water

Patients with Renal Impairment No dose adjustments are required in patients with renal impairment. Treprostinil is not cleared by dialysis [see Clinical Pharmacology ] .

Patients with Hepatic Insufficiency In patients with mild or moderate hepatic insufficiency, decrease the initial dose of Remodulin to 0.625 ng/kg/min ideal body weight. Remodulin has not been studied in patients with severe hepatic insufficiency [see Warnings and Precautions , Use in Specific Populations , and Clinical Pharmacology ] .

General Remodulin can be administered with or without further dilution with Sterile Diluent for Remodulin or similar approved high-pH glycine diluent (e.g., Sterile Diluent for Flolan or Sterile Diluent for Epoprostenol), Sterile Water for Injection, or 0.9% Sodium Chloride Injection prior to administration. See Table 1 below for storage and administration time limits for the different diluents.

Diluted Remodulin has been shown to be stable at ambient temperature when stored for up to 14 days using high-pH glycine diluent at concentrations as low as 0.004 mg/mL (4,000 ng/mL). [See table below.] Sterile Water for Injection 0.9% Sodium Chloride for Injection 4 hours at room temperature or 24 hours refrigerated 48 hours at 40°C

Initial Dose for Patients New to Prostacyclin Infusion Therapy Remodulin is indicated for subcutaneous (SC) or intravenous (IV) use only as a continuous infusion. Remodulin 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, reduce the infusion rate to 0.625 ng/kg/min.

Initial Dose for Patients Transitioning to an Implantable Intravenous Infusion Pump The initial dose of Remodulin should be the same as the current dose the patient is receiving using the external infusion pump at the time of transition.

Administration Inspect parenteral drug products for particulate matter and discoloration prior to administration whenever solution and container permit. If either particulate matter or discoloration is noted, do not use. Preparation Remodulin is administered by subcutaneous or intravenous infusion at a calculated rate based on a patient's dose (ng/kg/min), weight (kg), and the Remodulin concentration (mg/mL).

For administration of Undiluted Remodulin the rate is calculated using the following formula: [See table below.] For administration of Diluted Remodulin, the concentration is calculated using the following formula: Step 1 [See table below.] The volume of Remodulin Injection needed to make the required diluted Remodulin concentration for the given reservoir size can then be calculated using the following formula: Step 2 [See table below.] The calculated volume of Remodulin Injection is then added to the reservoir along with the sufficient volume of diluent to achieve the desired total volume in the reservoir.

Subcutaneous Infusion Remodulin is administered subcutaneously by continuous infusion, via a subcutaneous catheter, using an infusion pump designed for subcutaneous drug delivery. The infusion pump should: be adjustable to approximately 0.002 mL/hour, have occlusion/no delivery, low battery, programming error and motor malfunction alarms, have delivery accuracy of ±6% or better, be positive pressure-driven, and have a reservoir made of polyvinyl chloride, polypropylene or glass.

Alternatively, use an infusion pump cleared for use with Remodulin. To avoid potential interruptions in drug delivery, the patient must have immediate access to a backup infusion pump and subcutaneous infusion sets. Intravenous Infusion External Intravenous Infusion Pump: Remodulin is administered intravenously by continuous infusion via a surgically placed indwelling central venous catheter using an external infusion pump designed for intravenous drug delivery.

If clinically necessary, a temporary peripheral intravenous cannula, preferably placed in a large vein, may be used for short term administration of Remodulin. Use of a peripheral intravenous infusion for more than a few hours increases the risk of thrombophlebitis. The infusion pump used to administer Remodulin should: have occlusion/no delivery, low battery, programming error and motor malfunction alarms, have delivery accuracy of ±6% or better, be positive pressure driven, and have a reservoir made of polyvinyl chloride, polypropylene or glass.

Alternatively, use an infusion pump cleared for use with Remodulin. To avoid potential interruptions in drug delivery, the patient must have immediate access to a backup infusion pump and infusion sets. Infusion sets with an in-line 0.22- or 0.2-micron pore size filter should be used. Implantable Intravenous Infusion Pump: Use an implantable intravenous infusion pump approved for use with Remodulin, such as the Implantable System for Remodulin ® (ISR).

Refer to the pump manufacturer's manual for specific instructions regarding preparation, programing, implantation, and refilling.