Veletri

Veletri is a prescription medication used to treat pulmonary arterial hypertension in order to improve exercise capacity.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

• Actelion Pharmaceuticals US, Inc.

Serious side effects have been reported with Veletri including the following:

• Withdrawal effects. Veletri can cause serious withdrawal side effects. To avoid withdrawal side effects, do not suddenly stop taking Veletri. Your doctor will slowly decrease your dose before stopping this medicine altogether. Sudden and dramatic changes in dose may lead to unstable blood pressure, a return of pulmonary hypertension symptoms, or fatal low blood pressure.
• Sepsis. Veletri may cause a serious complication resulting from an infection in your bloodstream. Tell your doctor immediately if you develop signs of symptoms of a severe infection, such as fever, chills, low blood pressure, difficulty breathing, or fast heart rate. To reduce the risk of infection in the bloodstream, it is important to know how to properly care for the catheter and infusion pump.

Veletri can cause dizziness. Do not drive or operate heavy machinery until you know how Veletri affects you.

Do not take Veletri if you:

• are allergic to Veletri or to any of its ingredients
• have heart failure due to severe left heart disease
• have pulmonary edema (fluid in your lungs)

Before taking Veletri, tell your doctor about all of your medical conditions. Especially tell your doctor if you:

• are allergic to Veletri or to any of its ingredients
• have congestive heart failure (a condition in which the heart doesn't pump blood as well as it should) due to severe left heart disease
• have pulmonary edema
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements.

Take this medication exactly as prescribed by your doctor. Follow the directions given to you carefully.

The initial dose your doctor recommends will be based on your weight and how you tolerate this medication. Your doctor will also determine the amount of Veletri you need on a continuous basis. This dose may change during the course of your therapy based on how you respond to this medication and if your symptoms persist. If side effects become intolerable, your doctor may lower your dose. Your portable infusion pump will control the rate of medication you receive. 

All dose changes must be closely monitored by your healthcare provider. Do not lower your dose of Veletri or stop taking it without talking to your doctor.

• Veletri is only carried by specialty pharmacies and is not available through retail pharmacies.
• Each vial of Veletri is for single use only; discard any unused medication.
• Follow your healthcare provider's directions on how to prepare and store Veletri.
• Use Veletri at room temperature.
• Do not expose Veletri solution to direct sunlight.
• Keep this and all medications out of the reach of children.

Epoprostenol is a prostaglandin (a hormone-like substance that occurs naturally in the body). Prostaglandins help to control functions in the body such as blood pressure and muscle contractions.

Epoprostenol is used to treat pulmonary arterial hypertension (PAH). It improves your ability to exercise.

Epoprostenol may also be used for purposes not listed in this medication guide.

• If you have an allergy to epoprostenol or any other part of Veletri (epoprostenol).
• If you are allergic to any drugs like this one, any other drugs, foods, or other substances. Tell your doctor about the allergy and what signs you had, like rash; hives; itching; shortness of breath; wheezing; cough; swelling of face, lips, tongue, or throat; or any other signs.
• If you have heart failure (weak heart).
• If you have ever gotten fluid in the lungs with use of this medicine.

This is not a list of all drugs or health problems that interact with Veletri.

Tell your doctor and pharmacist about all of your drugs (prescription or OTC, natural products, vitamins) and health problems. You must check to make sure that it is safe for you to take this medicine with all of your drugs and health problems. Do not start, stop, or change the dose of any drug without checking with your doctor.

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.

Important Note: Reconstitute Veletri only as directed with Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. Do not dilute reconstituted solutions of Veletri or administer it with other parenteral solutions or medications [see Warnings and Precautions (5.1)].

Dosage

Prepare continuous chronic infusion of Veletri as directed, and administer through a central venous catheter. Temporary peripheral intravenous infusion may be used until central access is established. Initiate chronic infusion of Veletri at 2 ng/kg/min and increase in increments of 2 ng/kg/min every 15 minutes or longer until a tolerance limit to the drug is established or further increases in the infusion rate are not clinically warranted. If dose-limiting pharmacologic effects occur, then decrease the infusion rate until Veletri is tolerated. In clinical trials, the most common dose-limiting adverse events were nausea, vomiting, hypotension, sepsis, headache, abdominal pain, or respiratory disorder (most treatment-limiting adverse events were not serious). If the initial infusion rate of 2 ng/kg/min is not tolerated, use a lower dose.

In the controlled 12-week trial in PAH/SSD, for example, the dose increased from a mean starting dose of 2.2 ng/kg/min. During the first 7 days of treatment, the dose was increased daily to a mean dose of 4.1 ng/kg/min on day 7 of treatment. At the end of week 12, the mean dose was 11.2 ng/kg/min. The mean incremental increase was 2 to 3 ng/kg/min every 3 weeks.

Dosage Adjustments

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 events due to excessive doses of Veletri. In general, expect increases in dose from the initial chronic dose.

Consider increments in dose if symptoms of pulmonary hypertension persist or recur. Adjust 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. In clinical trials, incremental increases in dose occurred at intervals of 24 to 48 hours or longer. Following establishment of new chronic infusion rate, observe the patient, and monitor standing and supine blood pressure and heart rate for several hours to ensure that the new dose is tolerated.

During chronic infusion, the occurrence of dose-limiting pharmacological events may necessitate a decrease in infusion rate, but the adverse event may occasionally resolve without dosage adjustment. Make dosage decreases gradually in 2-ng/kg/min decrements every 15 minutes or longer until the dose-limiting effects resolve. Avoid abrupt withdrawal of Veletri or sudden large reductions in infusion rates. Except in life-threatening situations (e.g., unconsciousness, collapse, etc.), infusion rates of Veletri should be adjusted only under the direction of a physician.

In patients receiving lung transplants, doses of epoprostenol were tapered after the initiation of cardiopulmonary bypass.

Administration

Veletri, once prepared as directed [see Reconstitution (2.4)], is administered by continuous intravenous infusion via a central venous catheter using an ambulatory infusion pump. During initiation of treatment, Veletri may be administered peripherally.

Infusion sets with an in-line 0.22 micron filter should be used.

The ambulatory infusion pump used to administer Veletri 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 Veletri. The reservoir should be made of polyvinyl chloride, polypropylene, or glass. The infusion pump used in the most recent clinical trials was the CADD-1 HFX 5100 (SIMS Deltec). A 60-inch microbore non-DEHP extension set with proximal antisyphon valve, low priming volume (0.9 mL), and in-line 0.22 micron filter was used during clinical trials.

To avoid potential interruptions in drug delivery, the patient should have access to a backup infusion pump and intravenous infusion sets. Consider a multi-lumen catheter if other intravenous therapies are routinely administered.

Reconstitution

Veletri is stable only when reconstituted as directed using Sterile Water for Injection, USP, or Sodium Chloride 0.9% Injection, USP. Do not reconstitute or mix Veletri with any other parenteral medications or solutions prior to or during administration. Each vial is for single use only; discard any unused solution.

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, and immediately diluted to the final concentration in the drug delivery reservoir can be administered at room temperature per the conditions of use as outlined in Table 1.

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 use only; discard any unused solution.

Infusion rates may be calculated using the following formula:

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.

NDC 66215-403-01
Single Dose Vial
Discard Unused Portion

Veletri®
epoprostenol for Injection

0.5 mg (500,000 ng)/vial

Sterile, Lyophilized Product
For Intravenous Infusion Only

Rx Only
ACTELION