Epoprostenol Sodium

EPOPROSTENOL SODIUM- epoprostenol sodium injection, powder, for solution
STERILE DILUENT- water injection
Teva Parenteral Medicines, Inc.

1 INDICATIONS AND USAGE

Epoprostenol sodium for injection is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group I) to improve exercise capacity. Trials establishing effectiveness included predominantly (97%) patients with New York Heart Association (NYHA) Functional Class III-IV symptoms and etiologies of idiopathic or heritable PAH (49%) or PAH associated with connective tissue diseases (51%).

2 DOSAGE AND ADMINISTRATION

2.1 Reconstitution

Each vial is for single dose only; discard any unused diluent or unused reconstituted solution.

Select a concentration for the solution of epoprostenol sodium for injection that is compatible with the infusion pump being used with respect to minimum and maximum flow rates, reservoir capacity, and the infusion pump criteria listed below [see Dosage and Administration (2.4)].

Using aseptic technique, reconstitute epoprostenol sodium for injection only with STERILE DILUENT for epoprostenol sodium for injection. Table 1 gives directions for preparing several different concentrations of epoprostenol sodium for injection. See Table 2 for storage and administration time limits for the reconstituted epoprostenol sodium for injection.

Table 1. Reconstitution and Dilution Instructions for Epoprostenol Sodium for Injection Using STERILE DILUENT for Epoprostenol Sodium for Injection.

To make 100 mL of solution with final concentration of:

Directions:

3,000 ng/mL

Dissolve contents of one 0.5-mg vial with 5 mL of sterile diluent. Withdraw3 mL and add to sufficient sterile diluent to make a total of 100 mL.

5,000 ng/mL

Dissolve contents of one 0.5-mg vial with 5 mL of sterile diluent. Withdraw entire vial contents and add sufficient sterile diluent to make a total of 100 mL.

10,000 ng/mL

Dissolve contents of two 0.5-mg vials each with 5 mL of sterile diluent. Withdraw entire vial contents and add sufficient sterile diluent to make a total of 100 mL.

15,000 ng/mLa

Dissolve contents of one 1.5-mg vial with 5 mL of sterile diluent. Withdraw entire vial contents and add sufficient sterile diluent to make a total of 100 mL.

a Higher concentrations may be prepared for patients who receive epoprostenol sodium for injection long-term.
Table 2. Storage and Administration Limits for Reconstituted Epoprostenol Sodium for Injection

When Using STERILE DILUENT for Epoprostenol Sodium for Injection

Stability

When used at room temperature,

(15°C to 25°C; 59°F to 77°F)

reconstituted solutions:

  • are stable for up to 8 hours following reconstitution or removal from refrigerated storage.
  • may be stored for up to 40 hours refrigerated at 2°C to 8°C (36°F to 46°F) before use.

When used with a cold pack,

reconstituted solutions:

  • are stable for up to 24 hours use.
  • may be stored refrigerated at 2°C to 8°C (36°F to 46°F) before use as long as the total time of refrigerated storage and infusion does not exceed 48 hours.
  • Change cold packs every 12 hours.
  • Reconstituted solutions can be used immediately. Refrigerate at 2°C to 8°C (36°F to 46°F) if not used immediately.
  • Protect from light.
  • Do not freeze reconstituted solutions.

2.2 Dosage

Initiate intravenous infusions of epoprostenol sodium for injection at 2 ng/kg/min. Alter the infusion by 1- to 2-ng/kg/min increments at intervals sufficient to allow assessment of clinical response. These intervals should be at least 15 minutes.

During dose initiation, asymptomatic increases in pulmonary artery pressure coincident with increases in cardiac output may occur. In such cases, consider dose reduction, but such an increase does not imply that chronic treatment is contraindicated.

Base changes in the chronic infusion rate on persistence, recurrence, or worsening of the patient’s symptoms of pulmonary hypertension and the occurrence of adverse vasodilatory reactions. In general, expect progressive increases in dose.

If dose-related adverse reactions occur, make dose decreases gradually in 2-ng/kg/min decrements every 15 minutes or longer until the dose-limiting effects resolve [see Adverse Reactions ( 6.1, 6.2)]. Avoid abrupt withdrawal of epoprostenol sodium for injection or sudden large reductions in infusion rates [see Warnings and Precautions ( 5.2)].

Following establishment of a new chronic infusion rate, measure standing and supine blood pressure for several hours.

Taper doses of epoprostenol sodium for injection after initiation of cardiopulmonary bypass in patients receiving lung transplants.

2.3 Administration

Initiate epoprostenol in a setting with adequate personnel and equipment for physiologic monitoring and emergency care.

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.

Administer continuous chronic infusion of epoprostenol sodium for injection through a central venous catheter. Temporary peripheral intravenous infusion may be used until central access is established. Do not administer bolus injections of epoprostenol sodium for injection.

The ambulatory infusion pump used to administer epoprostenol sodium for injection should: (1) be small and lightweight, (2) be able to adjust infusion rates in 2-ng/kg/min increments, (3) have occlusion, end-of-infusion, and low-battery alarms, (4) be accurate to ± 6% of the programmed rate, and (5) be positive-pressure-driven (continuous or pulsatile) with intervals between pulses not exceeding 3 minutes at infusion rates used to deliver epoprostenol sodium for injection. The reservoir should be made of polyvinyl chloride, polypropylene, or glass. Use a 60-inch microbore non-di-(2-ethylhexyl)phthalate (DEHP) extension set with proximal antisyphon valve, low-priming volume (0.9 mL), and in-line 0.22-micron filter.

To avoid interruptions in drug delivery, the patient should have access to a backup infusion pump and intravenous infusion sets.

Do not administer or dilute reconstituted solutions of epoprostenol sodium for injection with other parenteral solutions or medications. Consider a multi-lumen catheter if other intravenous therapies are routinely administered.

Select a concentration for the solution of epoprostenol sodium for injection that is compatible with the infusion pump being used with respect to minimum and maximum flow rates, reservoir capacity, and the infusion pump criteria listed above. When administered chronically, prepare epoprostenol sodium for injection in a drug delivery reservoir appropriate for the infusion pump with a total reservoir volume of at least 100 mL, using 2 vials of STERILE DILUENT for epoprostenol sodium for injection.

Generally, 3,000 ng/mL and 10,000 ng/mL are satisfactory concentrations to deliver between 2 to 16 ng/kg/min in adults. Higher infusion rates, and therefore, more concentrated solutions, may be necessary with long-term administration of epoprostenol sodium for injection.

Infusion rates may be calculated using the following formula:

Infusion Rate (mL/h) =

[Dose (ng/kg/min) × Weight (kg) × 60 min/h]

Final Concentration (ng/mL)

Example calculations for infusion rates are as follows:

Example 1: for a 60-kg person at the recommended initial dose of 2 ng/kg/min using a 3,000-ng/mL concentration, the infusion rate would be as follows:

Infusion Rate (mL/h) =

[2 (ng/kg/min) × 60 (kg) × 60 ( min/h)] = 2.4 (mL/h)

3,000 (ng/mL)

Example 2: for a 70-kg person at a dose of 16 ng/kg/min using a 15,000-ng/mL concentration, the infusion rate would be as follows:

Infusion Rate (mL/h) =

[16 (ng/kg/min) × 70 (kg) × 60 ( min/h)] = 4.48 (mL/h)

15,000 (ng/mL)

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