Epoprostenol Sodium - Uses, Dosage, and Side Effects

Overview:

Epoprostenol Sodium is a sodium salt of the drug Epoprostenol. It is used for the treatment of pulmonary arterial hypertension and pulmonary hypertension in heart surgery with cardiopulmonary bypass. It is available as an injection (to be administered by a healthcare professional only). It functions by widening the blood vessels in the lungs, enhancing blood flow to the lungs, and reducing the heart's workload.

Epoprostenol Sodium was the first drug approved by the FDA "(Food and Drug Administration)" specifically for treating pulmonary hypertension on 14 April 2000.

How Does Epoprostenol Sodium Work?

Epoprostenol Sodium is a naturally occurring prostaglandin and a known metabolite of arachidonic Acid. It directly stimulates the dilation of the blood vessels in the lungs and systemic arterial vascular beds. It also has a platelet inhibiting effect, which results in decreased clotting.

Uses:

Epoprostenol Sodium is used to manage the following conditions:

• Primary Pulmonary Arterial Hypertension: It is a condition of high blood pressure affecting the lung arteries and the right side of the heart.

• Pulmonary Hypertension in People With Heart Failure: The blood pressure is elevated in blood vessels from the heart to the lungs.

Dosage:

Epoprostenol Sodium is administered by a healthcare professional as prescribed by the doctor. The medication's general reconstitution and dilution information of the medication for PAH is as follows:

Warnings:

1. Rebound PAH: Sudden withdrawal or abrupt drug dose reduction can result in the rebound of pulmonary arterial hypertension. Symptoms include extreme weakness, dizziness, and shortness of breath.

2. Pulmonary Edema: It is a condition characterized by over-accumulation of fluid in the lungs. Pulmonary edema has been observed in some people who have been administered the drug. If it happens, discontinue the medication immediately, and medical help is to be taken.

3. Increased Bleeding Risk: Epoprostenol Sodium also prevents platelet aggregation, which increases the risk of bleeding. Caution is required in people with other risk factors for bleeding.

4. Heart Diseases: The dilating effect of Epoprostenol Sodium on the blood vessels can result in a sudden decline in blood pressure. Symptoms include flushing, headache, dizziness, and vomiting. Therefore, blood pressure should be regularly monitored in patients with heart disease and high blood pressure.

5. Pregnancy: The drug's safety in pregnancy is not yet established.

6. Breastfeeding: Safety during breastfeeding is not determined.

7. Elderly Population: The dose will be determined by the doctor.

For Patients

What Do You Need to Know About Pulmonary Artery Hypertension?

Pulmonary arterial hypertension (PAH) is a condition in which the blood pressure in the pulmonary arteries is too high. This can cause the right side of the heart to work harder than usual, leading to heart failure over time. There are many possible causes of PAH, including heart valve problems, lung diseases, blood disorders, and certain medications. Some people are born with a genetic predisposition to PAH. In other cases, it may occur after a viral infection or exposure to certain chemicals. PAH is more common in women than men, and smokers are also at higher risk.

What Are the Causes of Pulmonary Arterial Hypertension?

PAH can be caused by several things, including certain medications, genetic conditions, and connective tissue diseases. Some risk factors for PAH include smoking, being overweight, and high blood pressure. If any of these risk factors are present, it is essential to talk to the doctor about whether or not to be tested for PAH.

What Are the Risk Factors For Pulmonary Arterial Hypertension?

PAH can be caused by several things, including Certain medications, connective tissue disorders, and lung diseases. It is also more common in women than men and usually develops between 20 and 50. In addition, there are several risk factors for PAH, including smoking, being overweight, and having high blood pressure.

What Are the Symptoms of PAH?

The symptoms of pulmonary arterial hypertension (PAH) can vary depending on how much the condition has progressed. In its early stages, PAH may not cause any noticeable symptoms. As the condition worsens, however, patients may start to experience it.

• Shortness of breath.

• Fatigue.

• Chest pain.

• Dizziness.

• Fainting.

• In severe cases, PAH can lead to heart failure and death. If any of these symptoms are experienced, consult a doctor immediately so the condition can be appropriately diagnosed and treated.

Learn More About Epoprostenol Sodium:

When and Why to Take Epoprostenol Sodium?

The doctor will prescribe Epoprostenol Sodium based on the physical assessment and signs and symptoms. It acts as a prostaglandin having a blood vessel dilating effect, which is used for relieving PAH.

How Effective Is Epoprostenol Sodium?

Epoprostenol Sodium was given to WHO " (World Health Organization)" group 1 with pulmonary arterial hypertension. It showed 97 % improvement in people with functional symptoms, 49 % in heritable PAH, and 51 % improvement in people with PAH associated with connective tissue conditions.

Things to Inform Your Doctor Before They Prescribe You Epoprostenol Sodium:

Inform the doctor about the following before the doctor prescribes Epoprostenol Sodium

• Previous history of allergy or hypersensitivity reactions to any drugs.

• Prior history of heart failure.

• Bleed or bruised easily.

• Is using medication for high blood pressure, preventing or dissolving blood clots, inflammation, pain, or the drug Digoxin.

How to Take Epoprostenol Sodium?

• Epoprostenol is packaged in a little glass vial as a powder. Before using, the powder must be dissolved.

• This medication will be administered per the doctor's prescription in a hospital or clinic by a healthcare provider. It is always administered as a slow venous infusion (drip).

• The doctor will determine the ideal dosage of Epoprostenol. The specific dosage is provided based on the body weight and the nature of the sickness. The dose can be increased or decreased depending on the response to the treatment.

• It is crucial to keep the region around any "line" inserted into a vein clean to prevent infection. The doctor or nurse will show how to clean the "line" and the area around it. It is crucial that you carefully adhere to the given instructions.

Things to Do After You Start Taking Epoprostenol Sodium:

Once the medication is administered, look for changes in symptoms like

• Chest pain, shortness of breath, or feeling like the heart is pumping more quickly.

• Fainting or dizziness, especially when standing.

• Chills or a fever.

• Bleeding more frequently or for more extended periods, such as nose bleeding.

• If the area where the injection was made becomes tender, painful, or swollen, or if any blistering or skin loss is seen.

Look Out for Side Effects:

Report to the doctor immediately if any of these adverse events appear. The list of side effects is as follows:

Common Side Effects:

• Headache.

• Nausea.

• Vomiting.

• Jaw pain.

• Diarrhea.

• Flushing (reddening of the face).

• Alterations in heartbeat.

• Low blood pressure

• Bruising or bleeding of gums or the nose.

• Joint pain.

• Rash.

• Pain at the injection site.

• Anxious feeling.

Serious Side Effects:

• Swelling around the stomach area.

• Infection at the injection site.

• Accumulation of fluid in the lungs.

There may also be more symptoms that are not listed here. Consult the doctor, describe the symptoms, and get it tested if any change is thought to be an adverse effect of the drug.

Dietary Alterations:

No special dietary changes are necessary when using Epoprostenol Sodium. If the doctor does not ask you to make any dietary modifications, keep taking the regular diet. Be sure to eat a balanced diet full of the vitamins and minerals the body needs to function properly.

What Should Be Done When You Miss a Dose?

Reschedule your appointment immediately by calling the doctor, as the drug must be administered at the scheduled time. Ask the doctor for any more queries concerning the care.

What Should Be Done to Treat Epoprostenol Sodium Overdose?

Chances of overdosing are minimal since Epoprostenol Sodium is administered in a clinical setting. However, contact the doctor or seek immediate medical attention. Side effects like headache, nausea, vomiting, rapid heartbeat, warmth or tingling, or feeling of passing out (fainting or dizziness) after receiving the infusion are experienced.

How to Store Epoprostenol Sodium?

• Keep the medication vial out of reach of children or pets if a home nurse gives it at the house.

• Avoid using the drug after the expiration date, which is noted on the vial label and carton. The last day of that month is referred to as the expiry date.

• Avoid freezing the drug vial.

• Store at two degree Celsius to eight degrees Celsius.

• Keep the drug from direct sunlight.

• It should be used within an hour following reconstitution with the diluent.

• If there are any particles in the reconstituted solution, avoid using this medication.

• Never dispose of medications in wastewater or household garbage. Find out from the pharmacist how to dispose of expired medications.

For Doctors

Indication:

• Epoprostenol Sodium is indicated to treat pulmonary arterial hypertension (PAH) (WHO Group I) in order to increase exercise tolerance.

• It is also used for the treatment of pulmonary hypertension in patients with cardiopulmonary bypass in cardiac surgery.

Mechanism of Action:

Epoprostenol Sodium acts in PAH by its vasodilatory effect on the systemic and pulmonary vascular beds, acting as a natural prostaglandin. Additionally, it also has inhibitory effects on platelet aggregation.

Pharmacodynamics:

The following pharmacological changes occur in the body after taking Epoprostenol Sodium:

• Increase in the cardiac index (dose-dependent).

• Increase in stroke volume.

• Reduced pulmonary vascular resistance (dose-dependent).

• Decrease in mean systemic arterial pressure.

• Decrease in mean pulmonary arterial pressure.

• Hemodynamic changes, which are returned to baseline upon the termination of the drug infusion.

Ingredients:

1. Active Ingredient:

The only active ingredient present is Epoprostenol Sodium.

2. Inactive Ingredients:

The inactive ingredients present in the drug are;

• Mannitol.

• Glycine.

• Sodium Chloride.

• Sodium Hydroxide to adjust pH.

Adult Dosing:

Starting with two nanograms/kilogram/minute (ng/kg/min) intravenously, which may be titrated upward in two ng/kg/min every 15 minutes or longer until dose-limiting effects or intolerance develops; if symptoms persist or recur after the initial chronic phase, titrate upward by one to two ng/kg/min every 15 minutes. If dose-limiting effects occur, gradually decrease the infusion rate in increments of two ng/kg/min every 15 minutes; avoid abrupt withdrawal of the drug.

Pharmacokinetics:

Absorption/ Distribution:

In blood, Epoprostenol is rapidly hydrolyzed and degraded by the enzymes at neutral pH. To evaluate the in vivo pharmacokinetics of Epoprostenol in humans, no chemical assay is currently available that is sensitive and specific enough. Tritium-labeled Epoprostenol has been used in animal experiments that have revealed high clearance (93 mL/kg/min), a modest volume of distribution (357 mL/kg), and a brief half-life (2.7 minutes).

Metabolism:

Epoprostenol breaks down into two major metabolites: 6,15-diketo-13,14-dihydro-PGF1 (enzymatically generated) and 6-keto-PGF1 (formed by spontaneous degradation), both of which exhibit pharmacological activity that is less potent than epoprostenol in animal test systems. Studies have shown that Epoprostenol is extensively metabolized in humans, as evidenced by the isolation of 14 additional minor metabolites from urine.

Elimination:

The in vivo half-life of Epoprostenol in humans is estimated to be no longer than 6 minutes based on the in vitro half-life of Epoprostenol in human blood at 37°C and pH 7.4.

Toxicity:

Carcinogenicity has not been evaluated thoroughly, and studies revealed no mutagenic effects for the drug. Overdose data are limited. Clinical outcomes are anticipated to be an extension of the adverse effects seen with therapeutic use. Excessive doses may result in flushing, headache, hypotension, tachycardia, nausea, vomiting, and diarrhea. Hypoxemia, hypotension, and respiratory arrest resulting in death have occurred following overdosage of Epoprostenol.

Warning and Precaution:

1. Cardiovascular: Hypotension, flushing, nausea, vomiting, dizziness, and headache may occur due to systemic vasodilation; monitoring is recommended.

2. Hematologic: Increased risk for hemorrhagic complications, particularly in patients with other risk factors for bleeding.

3. Respiratory: The following respiratory problems might occur -

• Pulmonary edema may occur; discontinue the infusion and do not resume therapy.

• Rebound pulmonary hypertension, including fatalities, may occur following abrupt withdrawal, interruptions in drug delivery, or sudden significant dosage reductions; gradually decrease and avoid abrupt or sudden reductions in dosage.

Dosage and Forms:

• Epoprostenol Sodium is administered as an injection. It contains the drug equivalent to either 0.5 mg or 1.5 mg of Epoprostenol in the powder.

• It comes in 17 mL flint glass vials with grey butyl rubber seals as a sterile freeze-dried powder. The sterile diluent is offered in flint glass vials that hold 50 ml of the liquid and have fluororesin-faced butyl rubber closures, aluminum overseals, and yellow plastic flip-off caps.

Administration:

• Reconstitute only with sterile diluent supplied by the manufacturer (24 hours supply).

• Avoid reconstituting or mixing with other parenteral drugs or solutions before or during administration.

• During administration, the reconstituted solution must be filtered with a sterile 0.22 micron or 0.2-micron pore- size filter to remove potential glass particles.

• Therapy may be initiated peripherally; an ambulatory infusion pump is administered by continuous IV (intravenous) infusion via a central venous catheter.

• Keeping a backup infusion pump and IV infusion sets are recommended to avoid potential interruptions in therapy.

• The infusion pump must have a total reservoir volume of at least 100 mL and be made of polyvinyl chloride, polypropylene, or glass.

• Before administering at room temperature, refrigerate the reconstituted solution and protect it from light for up to 40 hours; do not freeze.

• A cold pouch must maintain the reconstituted solution's temperature between two and eight degrees C for 12 hours.

• Before and during administration, Epoprostenol must be kept between 32 and 77 degrees F (0 and 25 degrees Celsius) and protected from light.

• Room temperature administration is permitted for a total duration of eight hours. If the administration is needed for up to 24 hours, using two frozen six-ounce gel packs in a cold pouch is required. Change the gel pack every 12 hours.

Contraindications:

Epoprostenol Sodium is contraindicated in patients who have

• Hypersensitivity reactions to the drug.

• Heart failure is caused by reduced left ventricular ejection fraction.

• Concurrent use along with the drug Abrocitinib.

Clinical Studies for Epoprostenol Sodium:

Chronic Infusion in Heritable PAH

Two prospective, open, randomized trials comparing Epoprostenol Sodium with conventional therapy to conventional therapy alone, with study durations of eight and twelve weeks, were conducted on chronic continuous infusions of the drug in patients with idiopathic or heritable PAH. At the conclusion of the studies, the dosage averaged 9.2 ng/kg/min. Depending on the patient, conventional therapy may have contained some or all of the following: oral vasodilators, diuretics, and Digoxin in half to two-thirds of patients and supplemental oxygen in around half of the patients.

Clinical Effects:

On comparing patients receiving continuous intravenous Epoprostenol plus conventional therapy for 8 or 12 weeks (n = 52) to those getting conventional therapy alone (n = 54), a statistically significant improvement in exercise capacity was seen in people using Epoprostenol Sodium plus conventional therapy. The first week of therapy saw changes that were noticeable. According to the Chronic Heart Failure Questionnaire and the Dyspnea Fatigue Index, improvements in dyspnea and fatigue were observed in conjunction with increases in exercise capacity. Eight of the Forty patients receiving conventional therapy alone at the finish of the treatment period died, whereas none of the 41 patients receiving Epoprostenol Sodium survived during the study.

Other Specifications:

Epoprostenol Sodium in Pregnant Women:

Pregnancy Category B: Pregnant women have not been adequately studied. Because the human response to medications is not always predicted by research on animal reproduction, Epoprostenol Sodium should only be used during pregnancy when absolutely necessary.

Epoprostenol Sodium in Lactating Women:

Whether this medication is secreted in human milk is unknown. Many medications are excreted in human milk, and Epoprostenol Sodium may produce major side effects in nursing infants. The drug should only be used if the benefits outweigh the risk to the mother.

Epoprostenol Sodium in PediatricPatients:

Effectiveness and safety have not been completely established in pediatric patients.

Epoprostenol Sodium in Geriatric Patients:

The selection of a dose for an elderly patient should generally be cautious, usually beginning at the low end of the dosing range. This is because elderly patients are more likely to have decreased hepatic, renal, or cardiac function, as well as concurrent disease or other drug therapy, and these conditions are more common. The clinical trials did not include a sufficient geriatric population.

Drug Interactions:

Drug interactions refer to the interaction of drugs with other drugs, food, supplements, or beverages. These can result in unwanted side effects.

The drug interactions of Epoprostenol Sodium are as follows:

1. With Other Drugs:

• Aceclofenac.

• Acemetacin.

• Amtolmetin Guacil.

• Apixaban.

• Argatroban.

• Betrixaban.

• Bivalirudin.

• Bromfenac.

• Bufexamac.

• Caplacizumab.

• Celecoxib.

• Choline Salicylate.

• Citalopram.

• Clonixin.

• 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.

• Lornoxicam.

• Loxoprofen.

• Lumiracoxib.

• Meclofenamate.

• Mefenamic Acid.

• Meloxicam.

• 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.

• Digoxin.

2. With Alcohol: Alcohol should be avoided as it increases the risk for hypotension.

3. With Food: No serious food interactions have been reported for Epoprostenol Sodium.