Veletri
(Epoprostenol)Dosage & Administration
VELETRI is
Use after reconstitution and immediate dilution to final concentration.
Use at room temperature (77°F/25°C)
VELETRI solution reconstituted with 5 mL of Sterile Water for Injection, USP or Sodium Chloride 0.9% Injection
| Final concentration range | Immediate administration | If stored for up to 8 days at 36° to 46°F (2° to 8°C) |
|---|---|---|
0.5 mg vial | ||
| ≥3,000 ng/mL and <15,000 ng/mL | 48 hours | 24 hours |
1.5 mg vial | ||
| ≥15,000 ng/mL and <60,000 ng/mL | 48 hours | 48 hours |
| ≥60,000 ng/mL | 72 hours | 48 hours |
Use at higher temperatures >77°F up to 104°F (>25° to 40°C)
Temperatures greater than 77°F and up to 86°F (>25°C to 30°C): A single reservoir of fully diluted solution of 60,000 ng/mL or above of VELETRI prepared as directed can be administered (either immediately or after up to 8 days storage at 36° to 46°F (2° to 8°C)) for up to 48 hours. For diluted solutions of less than 60,000 ng/mL, pump reservoirs should be changed every 24 hours.
Temperatures up to 104°F (40°C): Fully diluted solutions of 60,000 ng/mL or above of VELETRI, prepared as directed, can be immediately administered for periods up to 24 hours.
Do not expose this solution to direct sunlight.
A concentration for the solution of VELETRI should be selected 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. VELETRI, when administered chronically, should be prepared in a drug delivery reservoir appropriate for the infusion pump. Outlined in Table 2 are directions for preparing different concentrations of VELETRI.
Each vial is for single-dose; discard any unused solution.
| To make 100 mL of solution with Final Concentration (ng/mL) of: | Directions |
|---|---|
Using the 0.5 mg vial | |
| 3,000 ng/ml | Dissolve contents of one 0.5 mg vial with 5 mL of Sterile Water for Injection, USP or Sodium Chloride 0.9% Injection, USP.Withdraw 3 mL of the vial contents and add to a sufficient volume of the identical 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 Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP.Withdraw entire vial contents and add to a sufficient volume of the identical 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 Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP.Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 100 mL. |
Using the 1.5 mg vial | |
| 15,000 ng/mLHigher concentrations may be prepared for patients who receive VELETRI long-term. | Dissolve contents of one 1.5 mg vial with 5 mL of Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP.Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 100 mL. |
| 30,000 ng/mL | Dissolve contents of two 1.5 mg vials each with 5 mL of Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP.Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 100 mL. |
Infusion rates may be calculated using the following formula:
Infusion Rate (mL/hr)= | [Dose (ng/kg/min)×Weight (kg)×60 min/hr] |
Final Concentration (ng/mL) |
Tables 3 to 7 provide infusion delivery rates for doses up to 16 ng/kg/min based upon patient weight, drug delivery rate, and concentration of the solution of VELETRI to be used. These tables may be used to select the most appropriate concentration of VELETRI that will result in an infusion rate between the minimum and maximum flow rates of the infusion pump and that will allow the desired duration of infusion from a given reservoir volume. For infusion/dose rates lower than those listed in Tables 3 to 7, it is recommended that the pump rate be set by a healthcare professional such that steady state is achieved in the patient, keeping in mind the half-life of epoprostenol is no more than six minutes. Higher infusion rates, and therefore, more concentrated solutions may be necessary with long-term administration of VELETRI.
| Patient weight (kg) | Dose or Drug Delivery Rate (ng/kg/min) | |||
|---|---|---|---|---|
| 2 | 3 | 4 | 5 | |
Infusion Delivery Rate (mL/hr) | ||||
| 20 | – | 1.2 | 1.6 | 2.0 |
| 30 | 1.2 | 1.8 | 2.4 | 3.0 |
| 40 | 1.6 | 2.4 | 3.2 | 4.0 |
| 50 | 2.0 | 3.0 | 4.0 | – |
| 60 | 2.4 | 3.6 | – | – |
| 70 | 2.8 | – | – | – |
| 80 | 3.2 | – | – | – |
| 90 | 3.6 | – | – | – |
| 100 | 4.0 | – | – | – |
| Patient weight (kg) | Dose or Drug Delivery Rate (ng/kg/min) | ||||||
|---|---|---|---|---|---|---|---|
| 2 | 4 | 6 | 8 | 10 | 12 | 14 | |
Infusion Delivery Rate (mL/hr) | |||||||
| 20 | – | 1.0 | 1.4 | 1.9 | 2.4 | 2.9 | 3.4 |
| 30 | – | 1.4 | 2.2 | 2.9 | 3.6 | – | – |
| 40 | 1.0 | 1.9 | 2.9 | 3.8 | – | – | – |
| 50 | 1.2 | 2.4 | 3.6 | – | – | – | – |
| 60 | 1.4 | 2.9 | – | – | – | – | – |
| 70 | 1.7 | 3.4 | – | – | – | – | – |
| 80 | 1.9 | 3.8 | – | – | – | – | – |
| 90 | 2.2 | – | – | – | – | – | – |
| 100 | 2.4 | – | – | – | – | – | – |
| Patient weight (kg) | Dose or Drug Delivery Rate (ng/kg/min) | ||||||
|---|---|---|---|---|---|---|---|
| 4 | 6 | 8 | 10 | 12 | 14 | 16 | |
Infusion Delivery Rate (mL/hr) | |||||||
| 20 | – | – | 1.0 | 1.2 | 1.4 | 1.7 | 1.9 |
| 30 | – | 1.1 | 1.4 | 1.8 | 2.2 | 2.5 | 2.9 |
| 40 | 1.0 | 1.4 | 1.9 | 2.4 | 2.9 | 3.4 | 3.8 |
| 50 | 1.2 | 1.8 | 2.4 | 3.0 | 3.6 | – | – |
| 60 | 1.4 | 2.2 | 2.9 | 3.6 | – | – | – |
| 70 | 1.7 | 2.5 | 3.4 | – | – | – | – |
| 80 | 1.9 | 2.9 | 3.8 | – | – | – | – |
| 90 | 2.2 | 3.2 | – | – | – | – | – |
| 100 | 2.4 | 3.6 | – | – | – | – | – |
| Patient weight (kg) | Dose or Drug Delivery Rate (ng/kg/min) | ||||||
|---|---|---|---|---|---|---|---|
| 4 | 6 | 8 | 10 | 12 | 14 | 16 | |
Infusion Delivery Rate (mL/hr) | |||||||
| 20 | – | – | – | – | 1.0 | 1.1 | 1.3 |
| 30 | – | – | 1.0 | 1.2 | 1.4 | 1.7 | 1.9 |
| 40 | – | 1.0 | 1.3 | 1.6 | 1.9 | 2.2 | 2.6 |
| 50 | – | 1.2 | 1.6 | 2.0 | 2.4 | 2.8 | 3.2 |
| 60 | 1.0 | 1.4 | 1.9 | 2.4 | 2.9 | 3.4 | 3.8 |
| 70 | 1.1 | 1.7 | 2.2 | 2.8 | 3.4 | 3.9 | – |
| 80 | 1.3 | 1.9 | 2.6 | 3.2 | 3.8 | – | – |
| 90 | 1.4 | 2.2 | 2.9 | 3.6 | – | – | – |
| 100 | 1.6 | 2.4 | 3.2 | 4.0 | – | – | – |
| Patient weight (kg) | Dose or Drug Delivery Rate (ng/kg/min) | |||||
|---|---|---|---|---|---|---|
| 6 | 8 | 10 | 12 | 14 | 16 | |
| 30 | – | – | – | – | – | 1.0 |
| 40 | – | – | – | 1.0 | 1.1 | 1.3 |
| 50 | – | – | 1.0 | 1.2 | 1.4 | 1.6 |
| 60 | – | 1.0 | 1.2 | 1.4 | 1.7 | 1.9 |
| 70 | – | 1.1 | 1.4 | 1.7 | 2.0 | 2.2 |
| 80 | 1.0 | 1.3 | 1.6 | 1.9 | 2.2 | 2.6 |
| 90 | 1.1 | 1.4 | 1.8 | 2.2 | 2.5 | 2.9 |
| 100 | 1.2 | 1.6 | 2.0 | 2.4 | 2.8 | 3.2 |
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Veletri Prescribing Information
VELETRI is indicated for the treatment of pulmonary arterial hypertension (PAH) (WHO Group 1) to improve exercise capacity. Studies establishing effectiveness included predominantly patients with NYHA Functional Class III–IV symptoms and etiologies of idiopathic or heritable PAH or PAH associated with connective tissue diseases.
VELETRI is
Use after reconstitution and immediate dilution to final concentration.
Use at room temperature (77°F/25°C)
VELETRI solution reconstituted with 5 mL of Sterile Water for Injection, USP or Sodium Chloride 0.9% Injection
| Final concentration range | Immediate administration | If stored for up to 8 days at 36° to 46°F (2° to 8°C) |
|---|---|---|
0.5 mg vial | ||
| ≥3,000 ng/mL and <15,000 ng/mL | 48 hours | 24 hours |
1.5 mg vial | ||
| ≥15,000 ng/mL and <60,000 ng/mL | 48 hours | 48 hours |
| ≥60,000 ng/mL | 72 hours | 48 hours |
Use at higher temperatures >77°F up to 104°F (>25° to 40°C)
Temperatures greater than 77°F and up to 86°F (>25°C to 30°C): A single reservoir of fully diluted solution of 60,000 ng/mL or above of VELETRI prepared as directed can be administered (either immediately or after up to 8 days storage at 36° to 46°F (2° to 8°C)) for up to 48 hours. For diluted solutions of less than 60,000 ng/mL, pump reservoirs should be changed every 24 hours.
Temperatures up to 104°F (40°C): Fully diluted solutions of 60,000 ng/mL or above of VELETRI, prepared as directed, can be immediately administered for periods up to 24 hours.
Do not expose this solution to direct sunlight.
A concentration for the solution of VELETRI should be selected 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. VELETRI, when administered chronically, should be prepared in a drug delivery reservoir appropriate for the infusion pump. Outlined in Table 2 are directions for preparing different concentrations of VELETRI.
Each vial is for single-dose; discard any unused solution.
| To make 100 mL of solution with Final Concentration (ng/mL) of: | Directions |
|---|---|
Using the 0.5 mg vial | |
| 3,000 ng/ml | Dissolve contents of one 0.5 mg vial with 5 mL of Sterile Water for Injection, USP or Sodium Chloride 0.9% Injection, USP.Withdraw 3 mL of the vial contents and add to a sufficient volume of the identical 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 Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP.Withdraw entire vial contents and add to a sufficient volume of the identical 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 Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP.Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 100 mL. |
Using the 1.5 mg vial | |
| 15,000 ng/mLHigher concentrations may be prepared for patients who receive VELETRI long-term. | Dissolve contents of one 1.5 mg vial with 5 mL of Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP.Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 100 mL. |
| 30,000 ng/mL | Dissolve contents of two 1.5 mg vials each with 5 mL of Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP.Withdraw entire vial contents and add to a sufficient volume of the identical diluent to make a total of 100 mL. |
Infusion rates may be calculated using the following formula:
Infusion Rate (mL/hr)= | [Dose (ng/kg/min)×Weight (kg)×60 min/hr] |
Final Concentration (ng/mL) |
Tables 3 to 7 provide infusion delivery rates for doses up to 16 ng/kg/min based upon patient weight, drug delivery rate, and concentration of the solution of VELETRI to be used. These tables may be used to select the most appropriate concentration of VELETRI that will result in an infusion rate between the minimum and maximum flow rates of the infusion pump and that will allow the desired duration of infusion from a given reservoir volume. For infusion/dose rates lower than those listed in Tables 3 to 7, it is recommended that the pump rate be set by a healthcare professional such that steady state is achieved in the patient, keeping in mind the half-life of epoprostenol is no more than six minutes. Higher infusion rates, and therefore, more concentrated solutions may be necessary with long-term administration of VELETRI.
| Patient weight (kg) | Dose or Drug Delivery Rate (ng/kg/min) | |||
|---|---|---|---|---|
| 2 | 3 | 4 | 5 | |
Infusion Delivery Rate (mL/hr) | ||||
| 20 | – | 1.2 | 1.6 | 2.0 |
| 30 | 1.2 | 1.8 | 2.4 | 3.0 |
| 40 | 1.6 | 2.4 | 3.2 | 4.0 |
| 50 | 2.0 | 3.0 | 4.0 | – |
| 60 | 2.4 | 3.6 | – | – |
| 70 | 2.8 | – | – | – |
| 80 | 3.2 | – | – | – |
| 90 | 3.6 | – | – | – |
| 100 | 4.0 | – | – | – |
| Patient weight (kg) | Dose or Drug Delivery Rate (ng/kg/min) | ||||||
|---|---|---|---|---|---|---|---|
| 2 | 4 | 6 | 8 | 10 | 12 | 14 | |
Infusion Delivery Rate (mL/hr) | |||||||
| 20 | – | 1.0 | 1.4 | 1.9 | 2.4 | 2.9 | 3.4 |
| 30 | – | 1.4 | 2.2 | 2.9 | 3.6 | – | – |
| 40 | 1.0 | 1.9 | 2.9 | 3.8 | – | – | – |
| 50 | 1.2 | 2.4 | 3.6 | – | – | – | – |
| 60 | 1.4 | 2.9 | – | – | – | – | – |
| 70 | 1.7 | 3.4 | – | – | – | – | – |
| 80 | 1.9 | 3.8 | – | – | – | – | – |
| 90 | 2.2 | – | – | – | – | – | – |
| 100 | 2.4 | – | – | – | – | – | – |
| Patient weight (kg) | Dose or Drug Delivery Rate (ng/kg/min) | ||||||
|---|---|---|---|---|---|---|---|
| 4 | 6 | 8 | 10 | 12 | 14 | 16 | |
Infusion Delivery Rate (mL/hr) | |||||||
| 20 | – | – | 1.0 | 1.2 | 1.4 | 1.7 | 1.9 |
| 30 | – | 1.1 | 1.4 | 1.8 | 2.2 | 2.5 | 2.9 |
| 40 | 1.0 | 1.4 | 1.9 | 2.4 | 2.9 | 3.4 | 3.8 |
| 50 | 1.2 | 1.8 | 2.4 | 3.0 | 3.6 | – | – |
| 60 | 1.4 | 2.2 | 2.9 | 3.6 | – | – | – |
| 70 | 1.7 | 2.5 | 3.4 | – | – | – | – |
| 80 | 1.9 | 2.9 | 3.8 | – | – | – | – |
| 90 | 2.2 | 3.2 | – | – | – | – | – |
| 100 | 2.4 | 3.6 | – | – | – | – | – |
| Patient weight (kg) | Dose or Drug Delivery Rate (ng/kg/min) | ||||||
|---|---|---|---|---|---|---|---|
| 4 | 6 | 8 | 10 | 12 | 14 | 16 | |
Infusion Delivery Rate (mL/hr) | |||||||
| 20 | – | – | – | – | 1.0 | 1.1 | 1.3 |
| 30 | – | – | 1.0 | 1.2 | 1.4 | 1.7 | 1.9 |
| 40 | – | 1.0 | 1.3 | 1.6 | 1.9 | 2.2 | 2.6 |
| 50 | – | 1.2 | 1.6 | 2.0 | 2.4 | 2.8 | 3.2 |
| 60 | 1.0 | 1.4 | 1.9 | 2.4 | 2.9 | 3.4 | 3.8 |
| 70 | 1.1 | 1.7 | 2.2 | 2.8 | 3.4 | 3.9 | – |
| 80 | 1.3 | 1.9 | 2.6 | 3.2 | 3.8 | – | – |
| 90 | 1.4 | 2.2 | 2.9 | 3.6 | – | – | – |
| 100 | 1.6 | 2.4 | 3.2 | 4.0 | – | – | – |
| Patient weight (kg) | Dose or Drug Delivery Rate (ng/kg/min) | |||||
|---|---|---|---|---|---|---|
| 6 | 8 | 10 | 12 | 14 | 16 | |
| 30 | – | – | – | – | – | 1.0 |
| 40 | – | – | – | 1.0 | 1.1 | 1.3 |
| 50 | – | – | 1.0 | 1.2 | 1.4 | 1.6 |
| 60 | – | 1.0 | 1.2 | 1.4 | 1.7 | 1.9 |
| 70 | – | 1.1 | 1.4 | 1.7 | 2.0 | 2.2 |
| 80 | 1.0 | 1.3 | 1.6 | 1.9 | 2.2 | 2.6 |
| 90 | 1.1 | 1.4 | 1.8 | 2.2 | 2.5 | 2.9 |
| 100 | 1.2 | 1.6 | 2.0 | 2.4 | 2.8 | 3.2 |
VELETRI contains epoprostenol sodium equivalent to 0.5 mg (500,000 ng) or 1.5 mg (1,500,000 ng) epoprostenol and is supplied as a sterile lyophilized material in a 10 mL vial.
Limited published data from case series and case reports with VELETRI have not established a drug associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes when used during pregnancy. There are risks to the mother and fetus from untreated pulmonary arterial hypertension (
Pregnant women with untreated pulmonary arterial hypertension are at risk for heart failure, stroke, preterm delivery, and maternal and fetal death.
Embryo-fetal development studies have been performed in rats and rabbits during organogenesis. Epoprostenol sodium doses up to 100 mcg/kg/day, a dose that was maternally toxic in rabbits but not in rats, (600 mcg/m2/day in rats, 2.5 times the MRHD, and 1,180 mcg/m2/day in rabbits, 4.8 times the MRHD based on body surface area), had no effect on the fetus.
In a postnatal development study, epoprostenol sodium was administered subcutaneously to female rats for 2 weeks prior to mating through weaning and to male rats for 60 days prior to and through mating at a male and female toxic dose of up to 100 mcg/kg/day (600 mcg/m2/day, 2.5 times the MRHD based on body surface area). There was no effect on growth and development of the offspring.
The estimated background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
A large study evaluating the effect of epoprostenol on survival in NYHA Class III and IV patients with congestive heart failure due to severe left ventricular systolic dysfunction was terminated after an interim analysis of 471 patients revealed a higher mortality in patients receiving epoprostenol plus conventional therapy than in those receiving conventional therapy alone. The chronic use of VELETRI in patients with congestive heart failure due to severe left ventricular systolic dysfunction is therefore contraindicated.
Some patients with pulmonary hypertension have developed pulmonary edema during dose initiation, which may be associated with pulmonary veno-occlusive disease. VELETRI should not be used chronically in patients who develop pulmonary edema during dose initiation.
VELETRI is also contraindicated in patients with known hypersensitivity to the drug or to structurally related compounds.
- Do not abruptly lower the dose or withdraw dosing. All dosing initiation and changes should be closely monitored. (,
5.2 Chronic Use and Dose AdjustmentDuring chronic use, deliver VELETRI continuously on an ambulatory basis through a permanent indwelling central venous catheter. Unless contraindicated, administer anticoagulant therapy to patients receiving VELETRI to reduce the risk of pulmonary thromboembolism or systemic embolism through a patent foramen ovale. To reduce the risk of infection, use aseptic technique in the reconstitution and administration of VELETRI and in routine catheter care. Because epoprostenol is metabolized rapidly, even brief interruptions in the delivery of VELETRI may result in symptoms associated with rebound pulmonary hypertension including dyspnea, dizziness, and asthenia. Intravenous therapy with VELETRI will likely be needed for prolonged periods, possibly years, so consider the patient's capacity to accept and care for a permanent intravenous catheter and infusion pump.
Based on clinical trials, the acute hemodynamic response (reduction in pulmonary artery resistance) to epoprostenol did not correlate well with improvement in exercise tolerance or survival during chronic use of epoprostenol. Adjust dosage of VELETRI during chronic use at the first sign of recurrence or worsening of symptoms attributable to pulmonary hypertension or the occurrence of adverse events associated with epoprostenol
[see Dosage and Administration (2.2)]. Following dosage adjustments, monitor standing and supine blood pressure and heart rate closely for several hours.)5.3 Withdrawal EffectsAbrupt withdrawal (including interruptions in drug delivery) or sudden large reductions in dosage of VELETRI may result in symptoms associated with rebound pulmonary hypertension, including dyspnea, dizziness, and asthenia. In clinical trials, one Class III primary pulmonary hypertension patient's death was judged attributable to the interruption of epoprostenol. Avoid abrupt withdrawal.