Usual Adult Dose for Pulmonary Hypertension

Initial dose: 2 ng/kg/min via continuous IV infusion and titrate up in increments of 2 ng/kg/min every 15 minutes or longer until a tolerance limit is established or further increases in infusion rate not clinically warranted

Comments:

• If the initial infusion rate is not tolerated, a lower dose may be used.
• If dose-limiting pharmacologic effects occur, decrease infusion rate until this drug is tolerated.

Use: For the treatment of PAH (WHO Group 1) to improve exercise capacity; studies establishing efficacy included predominately patients with New York Heart Association (NYHA) Class III to IV symptoms and etiologies of idiopathic or heritable PAH or PAH associated connective tissue disorders

Renal Dose Adjustments

Data not available

Liver Dose Adjustments

Data not available

Dose Adjustments

Changes in the chronic infusion rate should be based on persistence, recurrence, or worsening of the patient's symptoms of pulmonary hypertension and the occurrence of adverse events due to excessive doses of epoprostenol. In general, increases in dose from the initial chronic dose should be expected.

PAH symptoms which persist or recur after improving:

• Consider increasing the infusion in increments of 1 to 2 ng/kg/min at intervals of at least 15 minutes
• Following establishment of a new chronic infusion rate, observe patient and monitor standing and supine blood pressure and heart rate for several hours to ensure that the new dose is tolerated.

Occurrence of dose-limiting pharmacologic events:

• Dose decreases should occur gradually in 2 ng/kg/min decrements every 15 minutes or longer until dose-limiting effects are resolved
• Adverse events may occasionally resolve without dose adjustments
• Avoid abrupt withdrawal or sudden large reductions in infusion rates

Patients receiving lung transplants: Taper dose after initiation of cardiopulmonary bypass

Elderly: Cautious dose selection recommended due to increased likelihood of concomitant hepatic, renal, or cardiac dysfunctions or concomitant disease or other drug therapy.

Precautions

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Once prepared as directed, administer by continuous IV infusion via a central venous catheter using an ambulatory infusion pump; may be administered temporarily using peripheral IV infusion during initiation until central access is established.
• Each vial for single use only; any unused solution should be discarded.
• Use immediately after reconstitution and immediate dilution to final concentration.
• Infusion sets with an in-line 0.22-micron filter should be used.
• To avoid potential interruptions in drug delivery, the patient should have immediate access to a backup infusion pump and IV infusion sets.
• Do not mix Veletri(R) with any other parenteral medications or solutions prior to or during administration.
• The ambulatory infusion pump should be small and lightweight, be able to adjust infusion rates in 2 ng/kg/min increments, have occlusion, end-of-infusion, and low-battery alarms, be accurate to +/-6% of the programmed rate, and be positive-pressure-driven (continuous or pulsatile) with intervals between pulses not exceeding 3 minutes at infusion rates used to deliver this drug.
• The reservoir should be made of polyvinyl chloride, polypropylene, or glass.
• The manufacturer product information should be consulted for appropriate infusion rates and further administration advice.

Storage requirements:

• Unopened vials are stable until the date on the package when stored at room temperature in the carton and protected from light.
• Avoid exposing diluted solutions to direct sunlight.
• Refrigerated at 2C to 8C (35.6F to 46.4F) if not used immediately.
• Do not freeze.
• The manufacturer product information should be consulted for maximum administration of fully diluted solutions.

Reconstitution/preparation techniques:

• Reconstitute Veletri(R) only as directed using sterile water for injection USP, or sodium chloride 0.9% injection USP.
• Reconstitute Flolan(R) with the supplied diluent.
• All products must be reconstituted as directed by the manufacturer of individual products; the manufacturer product information should be consulted for dilution instructions.

IV compatibility: The manufacturer product information should be consulted.

General:

• Initiate in a setting with adequate personnel and equipment for physiologic monitoring and emergency care.
• Except in life-threatening situations, (e.g., unconsciousness, collapse), infusion rates should only be adjusted under direction of a physician.

Monitoring:

• Cardiovascular: Monitor blood pressure regularly during initiation and following dose changes; monitor standing and supine blood pressure and heart rate closely for several hours following dose adjustments.

Patient advice:

• Adhere to sterile technique in preparing this drug for administration as well as in caring for the catheter.