Flolan

Contraindications

Hypersensitivity to epoprostenol

Chronic use in patients with CHF due to left ventricular systolic dysfunction

Development of pulmonary edema during initial dose titration

Cautions

Patients receiving epoprostenol should receive anticoagulant treatment (unless contraindicated) to decrease the risk of pulmonary thromboembolism or systemic embolism

Use caution in patients with risk factors of bleeding

Serious blood stream infectiosn may develop from chronic infusions requiring an indwelling central venous catherer

Asymptomatic increase in pulmonary artery pressure

Once initiated, duration of IV epoprostenol may be needed for years

Some patients may develop pulmonary edema during dosing adjustments

Rebound pulmonary hypertension may occur with abrupt interruptions or sudden reductions

Flolan is a prescription medication used to pulmonary arterial hypertension (high blood pressure in the lungs.)

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

If you take too much Flolan, call your healthcare provider or local Poison Control Center, or seek emergency medical attention right away.

If Flolan is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

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.

Use exactly as prescribed by your doctor. Do not use in larger or smaller amounts or for longer than recommended. Follow the directions on your prescription label. You may need to use this medication for many years.

Epoprostenol is injected into a vein using a computerized, portable infusion pump to control the rate of medication you receive. Because epoprostenol must be used long-term, it is usually given through a permanent central intravenous (IV) catheter placed into a large vein (such as in your chest).

You may be shown how to use an infusion pump at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles, IV tubing, and other items used to inject the medicine.

You will receive your first dose of this medicine in a hospital or clinic setting to quickly treat any serious side effects that occur. Your blood pressure and heart rate may also need to be monitored whenever your dose is changed.

You may be given other medications to prevent blood clots while you are receiving epoprostenol.

Epoprostenol is a powder medicine that must be mixed with a liquid (diluent) before using it. Use only the diluent provided with your medication and do not mix epoprostenol with any other medications or diluents not approved by your doctor.

If you are using the injections at home, be sure you understand how to properly mix and store the medicine. These directions are different for the Flolan and Veletri brands of this medication. Be sure you understand all mixing and storage directions for the specific brand of epoprostenol you are using.

After mixing Flolan with the diluent, store in the refrigerator and use within 48 hours. After mixing Veletri with the diluent, store in the refrigerator and use within 5 days.

The Veletri and diluent mixture may also be stored at room temperature but you must use it within 48 hours after it was mixed.

Protect the mixed medicine from light and do not freeze. Throw away any epoprostenol and diluent mixture that has become frozen, has changed colors, or has any particles in it. Call your doctor for a new prescription. The epoprostenol and diluent mixture must be protected from light at all times, whether it is in storage or in use.

Do not stop using epoprostenol without first talking to your doctor, even if you feel fine or have no symptoms. Missing doses or stopping suddenly may make your condition worse and you may have symptoms such as dizziness, weakness, or trouble breathing.

Even short breaks in the flow of your medication through the IV can cause the treatment to stop working. To make sure there is no interruption in your treatment, you may need to have a back-up infusion pump in case your first pump fails to work properly. Also keep replacement batteries and extra IV infusion sets on hand at all times. Get your prescription refilled before you run out of medicine completely.

Call your doctor if your symptoms do not improve, or if they get worse while using epoprostenol.

Store unopened vials of epoprostenol and its diluent at cool room temperature (below 77 degrees F), away from moisture, heat, and light. Keep in the original carton.

Epoprostenol can increase your risk of bleeding. This effect is increased when you also use medicines to prevent blood clots, such as:

• heparin or warfarin (Coumadin, Jantoven);

• alteplase (Activase), tenecteplase (TNKase), urokinase (Abbokinase);

• dalteparin (Fragmin), enoxaparin (Lovenox), fondaparinux (Arixtra), tinzaparin (Innohep); or

• abciximab (ReoPro), anagrelide (Agrylin), cilostazol (Pletal), clopidogrel (Plavix), dipyridamole (Persantine, Aggrenox), eptifibatide (Integrelin), prasugrel (Effient), ticlopidine (Ticlid), tirofiban (Aggrastat).

Tell your doctor about all other medications you use, especially:

• digoxin (digitalis, Lanoxin);

• a diuretic (water pill);

• heart or blood pressure medications;

• aspirin or an NSAID (nonsteroidal anti-inflammatory drugs) such as ibuprofen (Advil, Motrin), naproxen (Aleve, Naprosyn, Naprelan, Treximet), celecoxib (Celebrex), diclofenac (Arthrotec, Cambia, Cataflam, Voltaren, Flector Patch, Pennsaid, Solareze), indomethacin (Indocin), meloxicam (Mobic), and others.

This list is not complete and other drugs may interact with epoprostenol. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Vasodilator and platelet-aggregation inhibitor; a naturally occurring prostaglandin.1 2 5 10 21 41

This section provides information on the proper use of a number of products that contain epoprostenol. It may not be specific to Flolan. Please read with care.

Your doctor or nurse will teach you or a caregiver how to give this medicine. The medicine is given as an infusion through a catheter that is placed directly 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 use the pump for the infusion. Epoprostenol must be administered 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 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.

To withdraw the sterile diluent:
• 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.

To reconstitute the epoprostenol:
• 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.

To draw out the reconstituted 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.

To inject the reconstituted epoprostenol into the cassette:
• 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.

To inject the remaining diluent into the partially filled cassette
• 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.

To inject the sterile diluent into the cassette:
• 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 air from the cassette:
• 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.

To use the pump:
• 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 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.

Look at the liquid in the vial (glass container). If the liquid has solid pieces or specks in it or if the liquid has changed color, do not use the vial.

Use only the supplies provided in the medication kit to inject Flolan®. The mixed medicine must be injected using the provided infusion tubing, which has a filter to remove any solid pieces or specks (eg, glass particles) in the liquid.

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 primary pulmonary hypertension and pulmonary hypertension secondary to scleroderma spectrum of disease:
    • 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 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 degrees 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.

Do not reuse syringes and needles. Put used syringes and needles in a puncture-resistant disposable container, or dispose of them as directed by your doctor.

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:

• Abdominal or stomach pain
• 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 congestion
• chest pain or discomfort
• chest tightness or heaviness
• chills
• cold hands and feet
• confusion
• constipation
• convulsions
• 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
• extreme fatigue
• 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 or cramps
• muscle 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
• sweating
• swelling of the face, fingers, feet, or lower legs
• tightness in the chest
• tingling of the hands or feet
• unusual tiredness or weakness
• weight gain or loss

• 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
• increased sweating
• numbness or tingling in the hands, feet, or lips
• pain or discomfort in the arms, jaw, back, or neck
• seizures
• severe or sudden headache
• severe pain in the chest
• slurred speech
• sudden onset of severe breathing
• temporary blindness
• weakness in the arm or leg on one side of the body, sudden and severe
• weakness or heaviness of the legs

• Feeling of fullness
• high fever
• 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
• troubled breathing with exertion

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:

• Change in vision
• difficulty having a bowel movement (stool)
• difficulty with moving
• heartburn
• hives or welts
• impaired vision
• itching
• joint pain
• lack of appetite
• 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
• tiredness
• trembling or shaking of the hands or feet
• trouble concentrating

• Acid or sour stomach
• belching
• blurred vision or other changes in vision
• 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.

Reconstitution

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

Select a concentration for the solution of Flolan 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 Flolan only with STERILE DILUENT for Flolan or pH 12 STERILE DILUENT for Flolan. Table 1 gives directions for preparing several different concentrations of Flolan. See Table 2 for storage and administration time limits for the reconstituted Flolan.

Dosage

Initiate intravenous infusions of Flolan 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)]. Avoid abrupt withdrawal of Flolan 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 Flolan after initiation of cardiopulmonary bypass in patients receiving lung transplants.

Administration

Initiate Flolan 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 Flolan through a central venous catheter. Temporary peripheral intravenous infusion may be used until central access is established. Do not administer bolus injections of Flolan.

The ambulatory infusion pump used to administer Flolan 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 Flolan. 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 Flolan 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 Flolan 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 Flolan 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 Flolan or 2 vials of pH 12 STERILE DILUENT for Flolan.

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 Flolan.

Infusion rates may be calculated using the following formula:

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.

Adverse reactions are shown in Table 3 and are generally related to vasodilatory effects.

Adverse Events Attributable to the Drug Delivery System

Chronic infusions of Flolan are delivered using a small, portable infusion pump through an indwelling central venous catheter. During controlled PAH trials of up to 12 weeks’ duration, the local infection rate was about 18%, and the rate for pain was about 11%. During long‑term follow‑up, sepsis was reported at a rate of 0.3 infections/patient per year in patients treated with Flolan.

Postmarketing Experience

The following events have been identified during postapproval use of Flolan. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to estimate reliably their frequency or establish a causal relationship to drug exposure.

Blood and Lymphatic

Anemia, hypersplenism, pancytopenia, splenomegaly, thrombocytopenia.

Endocrine and Metabolic

Hyperthyroidism.

Gastrointestinal

Hepatic failure.

Respiratory, Thoracic, and Mediastinal

Pulmonary embolism.

Applies to epoprostenol: intravenous powder for solution

Along with its needed effects, epoprostenol (the active ingredient contained in Flolan) 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 while taking epoprostenol:

• Abdominal or stomach pain
• 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 congestion
• chest pain or discomfort
• chest tightness or heaviness
• chills
• cold hands and feet
• confusion
• constipation
• convulsions
• 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
• extreme fatigue
• 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 or cramps
• muscle 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
• sweating
• swelling of the face, fingers, feet, or lower legs
• tightness in the chest
• tingling of the hands or feet
• unusual tiredness or weakness
• weight gain or loss

• 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
• increased sweating
• numbness or tingling in the hands, feet, or lips
• pain or discomfort in the arms, jaw, back, or neck
• seizures
• severe or sudden headache
• severe pain in the chest
• slurred speech
• sudden onset of severe breathing
• temporary blindness
• weakness in the arm or leg on one side of the body, sudden and severe
• weakness or heaviness of the legs

• Feeling of fullness
• high fever
• 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
• troubled breathing with exertion

Some side effects of epoprostenol 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:

• Change in vision
• difficulty having a bowel movement (stool)
• difficulty with moving
• heartburn
• hives or welts
• impaired vision
• itching
• joint pain
• lack of appetite
• 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
• tiredness
• trembling or shaking of the hands or feet
• trouble concentrating

• Acid or sour stomach
• belching
• blurred vision or other changes in vision
• excess air or gas in the stomach or intestines
• indigestion
• leg cramps
• passing gas
• sleepiness or unusual drowsiness
• stomach discomfort or upset