Pronunciation:

e-poe-PROST-en-ol

Brand Names:

• Flolan
• Veletri

Dosage Forms:

• Powder for Solution

Classifications:

Therapeutic—

Peripheral Vasodilator

Pharmacologic—

Prostaglandin

Uses of This Medicine:

Epoprostenol injection is used to treat pulmonary arterial hypertension (PAH), which is the high blood pressure that occurs in the main artery that carries blood from the right side of the heart (the ventricle) to the lungs. When the smaller blood vessels in the lungs become more resistant to blood flow, the right ventricle must work harder to pump enough blood through the lungs. It works by relaxing these blood vessels and increasing the supply of blood to the lungs, which reduces the workload of the heart.

Epoprostenol belongs to a group of agents called prostaglandins. Prostaglandins occur naturally in the body and are involved in many biological functions. Epoprostenol works by relaxing blood vessels and increasing the supply of blood to the lungs, reducing the workload of the heart.

This medicine is available only with your doctor's prescription.

Before Using This Medicine:

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies—

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Children—

Appropriate studies have not been performed on the relationship of age to the effects of epoprostenol injection in the pediatric population. Safety and efficacy have not been established.

Older adults—

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of epoprostenol injection in the elderly. However, elderly patients are more likely to have age-related liver, kidney, or heart problems, which may require an adjustment in the dose for patients receiving epoprostenol injection.

Breast-feeding—

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Other medicines—

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

• Abrocitinib

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Aceclofenac
• Acemetacin
• Amtolmetin Guacil
• Apixaban
• Argatroban
• Betrixaban
• Bivalirudin
• Bromfenac
• Bufexamac
• Caplacizumab-yhdp
• Celecoxib
• Choline Salicylate
• Citalopram
• Clonixin
• Clopidogrel
• Dabigatran Etexilate
• Danaparoid
• Desirudin
• Desvenlafaxine
• Dexibuprofen
• Dexketoprofen
• Diclofenac
• Diflunisal
• Dipyrone
• Droxicam
• Duloxetine
• Edoxaban
• Escitalopram
• Etodolac
• Etofenamate
• Etoricoxib
• Felbinac
• Fenoprofen
• Fepradinol
• Feprazone
• Floctafenine
• Flufenamic Acid
• Fluoxetine
• Flurbiprofen
• Fluvoxamine
• Fondaparinux
• Heparin
• Ibuprofen
• Indomethacin
• Ketoprofen
• Ketorolac
• Lepirudin
• Levoketoconazole
• Levomilnacipran
• Lornoxicam
• Loxoprofen
• Lumiracoxib
• Meclofenamate
• Mefenamic Acid
• Meloxicam
• Methotrexate
• Milnacipran
• Morniflumate
• Nabumetone
• Naproxen
• Nepafenac
• Niflumic Acid
• Nimesulide
• Nimesulide Beta Cyclodextrin
• Oxaprozin
• Oxyphenbutazone
• Parecoxib
• Paroxetine
• Phenindione
• Phenprocoumon
• Phenylbutazone
• Piketoprofen
• Piroxicam
• Proglumetacin
• Propyphenazone
• Proquazone
• Protein C
• Rivaroxaban
• Rofecoxib
• Salicylic Acid
• Salsalate
• Sertraline
• Sodium Salicylate
• Sulindac
• Tenoxicam
• Tiaprofenic Acid
• Tolfenamic Acid
• Tolmetin
• Valdecoxib
• Venlafaxine
• Vilazodone
• Vortioxetine
• Warfarin

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Digoxin

Other interactions—

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Other medical problems—

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Bleeding problems or
• Hypotension (low blood pressure)—Use with caution. May make these conditions worse.

• Congestive heart failure, severe or
• Pulmonary edema (fluid in the lungs)—Should not be used in patients with these conditions.

Proper Use of This Medicine:

A nurse or other trained health professional will teach you or a caregiver how to give this medicine. It is given as an infusion through a catheter that is placed directly under your skin or into a vein. Do not use more medicine than your doctor tells you to.

Your doctor or nurse will teach you how to prepare the medicine and how to use the pump for the infusion. Epoprostenol must be given continuously by a portable pump that is operated by a small computer. The medicine will be delivered directly to the heart through a catheter that will be inserted into a vein in the chest.

Epoprostenol should be reconstituted only with the sterile diluent (eg, pH 12 sterile diluent for Flolan®) that is supplied with this medicine. The reconstituted medicine should not be mixed with other solutions or medicines. Use the following procedure for reconstituting your daily supply:

• Clear an area to work in and clean the area with alcohol. Gather your supplies. Wash your hands thoroughly with soap and water and then open all packages. Remove the vial cap from the vial containing the sterile diluent, clean the tops of the vials with alcohol swabs, and let the vial tops dry before proceeding.

• If not already attached, attach a needle to the syringe. Gently pull the plunger out slightly and push it back to break the syringe seal. Draw air into the syringe that is about equal to the amount of sterile diluent you've been instructed to withdraw from the vial. Insert the needle at an angle, completely through the rubber seal of the vial. Turn the vial and syringe upside down (the syringe-vial unit is now vertical) and carefully press the plunger, injecting some or all of the air into the vial. Then aim the tip of the needle into the fluid and carefully pull the plunger slowly back to withdraw the diluent and/or allow the pressure to fill the syringe with the diluent. Continue pushing the remaining air into the vial, allowing the liquid to enter the syringe until the prescribed amount of diluent has been drawn into the syringe. Without withdrawing the needle, tap the syringe gently so that any air bubbles trapped in the syringe rise toward the top of the syringe. If air bubbles appear, depress the plunger gently to force the air bubbles out (into the vial) and then withdraw enough additional diluent to restore the needed volume in the syringe. (Holding the syringe-vial as a unit in a vertical position and keeping the needle tip in the fluid while withdrawing the diluent may help minimize the amount of air drawn into the syringe.) Once the required volume has been drawn into the syringe, let the syringe-vial pressure equalize and slowly withdraw the needle from the vial.

• Insert the same needle through the rubber seal of the vial of epoprostenol and inject the sterile diluent gently onto the side of the vial. The flow of the sterile diluent should be directed toward the side of the vial and injected slowly in order to prevent the medicine from foaming. Once the pressure has equalized, withdraw the needle from the vial. Gently swirl the vial to mix the epoprostenol. Turn the vial upside down to catch any undissolved powder near the top of the vial. Never shake the vials. Repeat this process if you need to mix more than one vial of epoprostenol.

• Wipe the top of the reconstituted epoprostenol vial with an alcohol swab and let it dry. Change the needle on the syringe and then gently pull back the syringe plunger and fill the syringe with the amount of air that is equal to the amount of reconstituted epoprostenol you have been instructed to withdraw. Insert the needle through the seal of the vial and inject the air into the vial. Be sure to keep the needle tip below the fluid line and then pull the plunger back gently to withdraw the reconstituted epoprostenol into the syringe. Remove any air that may be trapped in the syringe as described above. Withdraw the needle and replace the needle cap on the syringe.

• Remove the end cap from the cassette tubing. Carefully remove the needle from the syringe (be sure to discard the needle in an appropriate manner) and attach the syringe to the cassette tubing. Hold the cassette in one hand and push the plunger to inject the reconstituted solution into the cassette (alternatively, you may find it useful to use a tabletop or other solid structure to steady the plunger while pushing down on the syringe to inject the solution). When the syringe is empty, clamp the cassette tubing near the syringe. Disconnect the syringe and replace the cassette tubing end cap.

• Using a 60 mL syringe, attach a new needle to the syringe and follow the above procedures for breaking the syringe seal and wiping the tops of the sterile diluent vials. Fill the syringe with the amount of air that is equal to the amount of sterile diluent you will remove from the first vial. Insert the needle through the rubber seal and slowly inject some of the air into the vial, allowing the fluid to flow into the syringe. Continue to push air gently into the vial until all of the fluid in the vial has flowed into the syringe. Remove any air that may be in the syringe as described above. Allow the pressure to equalize before you pull the needle out or you may lose fluid from the syringe. (If this occurs, the whole process needs to be repeated.) Withdraw the needle and replace the needle cap on the syringe. You may find it easier to hold the larger syringe in an upside down, vertical position while withdrawing the fluid in the vial.

• Uncap the clamped cassette tube and carefully remove the needle from the syringe (discarding the needle in an appropriate manner). Attach the syringe to the cassette tubing. Unclamp the cassette tubing and carefully inject the solution into the cassette. When the syringe is empty, clamp the cassette tube near the syringe and disconnect the syringe. Replace the cap on the cassette tube. If more diluent is needed to fill the cassette, repeat steps 6 and 7 with an additional vial of diluent, however, after completing the transfer of all of the required diluent, clamp the tubing, but leave the syringe attached to the cassette tubing while you mix the solution. Gently turn the cassette upside down at least 10 times to thoroughly mix the reconstituted epoprostenol with the additional diluent.

• To remove the air from inside the cassette, slowly turn the cassette until all of the small bubbles of air join to form one air pocket. Tilt the cassette gently so that the air pocket is in the corner where the tubing connects to the cassette. Unclamp the tube and pull back the plunger of the syringe until you see fluid fill the tubing. Clamp the tube near the connector and remove the syringe and replace the cap on the tubing. Label the cassette with the current time and date. Store the cassette in the refrigerator (preferably, on the top shelf to avoid spilling any food or drink on it) until it is time to use it. Make up a new cassette each day and use the cassette you refrigerated the day before so that you will always have a back-up cassette.

• The instructions for the use of the pump may vary depending on the particular make and model of the pump. Your doctor or nurse will give detailed instructions on how to use and care for the particular pump and accessories that you will use for administering your medicine. These instructions should include how to change the pump battery, cassette, and tubing. Remember to change the gel packs every 12 hours or every 8 hours if the surrounding temperature approaches 86 °F.
• Maintain sterile technique at all times. If you suspect that you have contaminated anything, throw away the accessories and begin again.

During use, the mixed solution can be administered by the pump at room temperature for up to 24 hours if you mixed the entire vial with the 5 milliliter (mL) solution provided. If you are using a lower concentration, the mixture is only good for 12 hours. Protect the solution from direct sunlight.

Ask your doctor who to call if you have any problems with the infusion pump. You may be given a second infusion pump to have in case the first pump stops working. Make sure you have access to this pump as a backup at all times.

You will need to continue using this medicine for a long period of time, possibly for many years. Talk with your doctor if you have any concerns about this.

The amount of medicine that you take depends on the concentration of the reconstituted medicine and the rate at which the infusion pump delivers the medicine.

Check the liquid in the vial. If the liquid has flakes or particles in it, or if the liquid is discolored or cloudy, do not use the vial.

Dosing—

The dose of this medicine will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

• For injection dosage form (solution):
  • For pulmonary arterial hypertension:
    • Adults—Dose is based on body weight and must be determined by your doctor. The initial dose is usually 2 nanograms (ng) per kilogram (kg) (0.9 nanogram per pound) of body weight per minute. Your doctor may increase your dose as needed.
    • Children—Use and dose must be determined by your doctor.

Missed dose—

Call your doctor or pharmacist for instructions.

Storage—

Keep out of the reach of children.

Do not keep outdated medicine or medicine no longer needed.

Ask your healthcare professional how you should dispose of any medicine you do not use.

Store the medicine in a closed container at room temperature, away from heat, moisture, and direct light. Keep from freezing.

Store the medicine vial in the original carton at room temperature. Keep the carton away from heat, moisture, and direct light. Do not freeze.

Store the mixed solution in the refrigerator for 5 days, away from direct light. Keep the medicine from freezing. Any medicine that has been frozen should be thrown away. Mixed solutions can be stored at room temperature (up to 25°C) for no more than 48 hours. Discard the mixed solution if it is kept in the refrigerator for more than 5 days or at room temperature for more than 48 hours.

Store the mixed solution in the refrigerator for up to 8 days, away from direct light. Do not freeze. Mixed solutions can be stored up to 3 days at 25°C, 2 days at 30°C, or up to 12 hours at 40°C. Throw away any mixture that has been refrigerated for more than 8 days.

Throw away used needles in a hard, closed container that the needles cannot poke through. Keep this container away from children and pets.

Precautions While Using This Medicine:

It is important that your doctor check your progress at regular visits. This will allow your doctor to make sure the medicine is working properly and to change the dosage if needed. Blood tests may be needed to check for unwanted effects.

Report any signs of infection or reaction at the catheter site to your doctor right away. Also, if you develop a sudden fever, contact your doctor as soon as possible.

Check with your doctor right away if you have blue lips and fingernails, chest pain, coughing that sometimes produces a pink frothy sputum, difficult, fast, or noisy breathing, increased sweating, pale skin, or swelling in the legs and ankles. These may be symptoms of pulmonary edema (fluid in the lungs).

This medicine may increase your risk of bleeding. Be extra careful to avoid injuries. Stay away from rough sports or other situations where you could be bruised, cut, or injured. Gently brush and floss your teeth. Be careful when using sharp objects, including razors and fingernail clippers.

Prepare this medicine exactly as directed. Do not add anything or use any substitutions when mixing the solution.

This medicine may cause your blood pressure to decrease. Check with your doctor right away if you have a feeling of warmth or heat, flushing or redness of the skin, especially on the face and neck, headache, feeling faint, dizzy, or lightheadedness, or sweating.

Do not suddenly stop using this medicine. Stopping or changing the dose of this medicine suddenly may bring on symptoms of your condition and can be dangerous. Check with your doctor before stopping or changing your dose.

Your doctor may want you to carry a medical identification card stating that you are using this medicine.

Do not take other medicines unless they have been discussed with your doctor. This includes prescription or nonprescription (over-the-counter [OTC]) medicines and herbal or vitamin supplements.

Side Effects of This Medicine:

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common

Arm, back, or jaw pain

bladder pain

bleeding gums

bloating or swelling of the face, arms, hands, lower legs, or feet

bloody or cloudy urine

blurred vision

changes in skin color

chest pain, discomfort, tightness or heaviness

chills

cold hands and feet

confusion

constipation

cough or hoarseness

coughing up blood

decreased urine

depression

diarrhea

difficult, burning, or painful urination

difficulty with breathing or swallowing

dilated neck veins

dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position

dry mouth

fast, pounding, or irregular heartbeat or pulse

feeling of warmth

fever

headache

incoherent speech

increased menstrual flow or vaginal bleeding

increased thirst

increased urination

local infection at the catheter site

loss of appetite

metallic taste

muscle pain, cramps, or weakness

nausea or vomiting

nosebleeds

numbness or tingling in the hands, feet, or lips

pain at the injection site

pain, redness, or swelling in the arm or leg

paleness of the skin

prolonged bleeding from cuts

rapid weight gain

red or black, tarry stools

redness of the face, neck, arms, and occasionally, upper chest

seizures

stomach pain

sweating

swelling of the face, fingers, feet, or lower legs

unusual tiredness or weakness

weight gain or loss

Less common

Altered or abnormal touch sensation or sensitivity

blue lips and fingernails

burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings

coughing that sometimes produces a pink frothy sputum

difficult, fast, or noisy breathing

inability to speak

pain or discomfort in the arms, jaw, back, or neck

slurred speech

temporary blindness

weakness in the arm or leg on one side of the body, sudden and severe

weakness or heaviness of the legs

Incidence not known

Feeling of fullness

pinpoint red spots on the skin

sensitivity to heat

sores, ulcers, or white spots on the lips or in the mouth

swollen glands

trouble sleeping

trouble breathing

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common

Change in vision

difficulty having a bowel movement (stool)

difficulty with moving

heartburn

hives or welts, itching

joint pain

lack or loss of strength

loss of interest or pleasure

muscle pains or stiffness

redness of the skin

shakiness in the legs, arms, hands, or feet

skin rash, encrusted, scaly and oozing

sores on the skin

swollen joints

trembling or shaking of the hands or feet

trouble concentrating

Less common

Acid or sour stomach

belching

excess air or gas in the stomach or intestines

indigestion

leg cramps

passing gas

sleepiness or unusual drowsiness

stomach discomfort or upset

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.