icosapent

Action and Spectrum

Mechanism of action 

The mechanism of action of icosapent is not well understood. Still, it is thought to work by reducing the production of very low-density lipoprotein (VLDL) and increasing the activity of enzymes involved in the breakdown of triglycerides. It also may act by reducing the activity of enzymes involved in synthesizing triglycerides. 

It is a highly purified form of the omega-3 fatty acid EPA, found in fish oil. Its main activity targets the reduction of triglycerides; it is effective in reducing triglyceride levels in adults with severe hypertriglyceridemia (triglyceride levels ≥500 mg/dL) who are at risk for pancreatitis. 

Drug Interaction

Adverse Reaction

Frequency defined:  

>10% 

Bleeding event 

1-10% 

Peripheral edema 

Gout 

Serious bleeding event 

Musculoskeletal pain 

Constipation 

Atrial fibrillation 

Post-marketing reports 

Blood TG increased 

Pain in extremities 

Diarrhea 

Abdominal discomfort 

Black Box Warning

Contraindication / Caution

Contraindications 

• Hypersensitivity to icosapent or any of its ingredients 
• Allergic to fish or shellfish  
• Pregnancy and breastfeeding women  
• Patients with liver disease should use it with caution 

Caution 

• Patients with liver disease should use it with caution, as icosapent may cause an increase in liver enzymes.  
• Patients taking blood thinners, such as warfarin, should use icosapent with caution, as EPA can increase the risk of bleeding. 
• Patients taking statins should use icosapent with caution as the combination may increase the risk of muscle damage (rhabdomyolysis). 
•  Patients taking aspirin or non-steroidal anti-inflammatory drugs (NSAIDs) should use icosapent with caution, as the combination may increase the risk of bleeding.  
• Patients with a history of bleeding disorders or who are taking blood thinners should use icosapent with caution as it may increase the risk of bleeding.  
• Pregnant or breastfeeding patients should not use icosapent as safety information is unavailable 

Pregnancy / Lactation

Pregnancy consideration: Insufficient data available 

Lactation: Excretion of the drug in human breast milk is unknown 

Pregnancy category: 

Category A: well-controlled and Satisfactory studies show no risk to the fetus in the first or later trimester.   

Category B: there was no evidence of risk to the fetus in animal studies, and there were not enough studies on pregnant women. 

Category C: there was evidence of risk of adverse effects in animal reproduction studies, and no adequate evidence in human studies must take care of potential risks in pregnant women.    

Category D: adequate data available with sufficient evidence of human fetal risk from various platforms, but despite the potential risk, and used only in emergency cases for potential benefits.    

Category X: Drugs listed in this category outweigh the risks over benefits. Hence these categories of drugs need to be avoided by pregnant women.    

Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology 

It is a prescription medication used to lower high levels of triglycerides, a type of fat found in the blood of adults. It is a form of omega-3 fatty acid derived from fish oil, specifically eicosapentaenoic acid (EPA). It works by decreasing the production of triglycerides in the liver and increasing the breakdown of triglycerides in the blood. It is usually taken twice daily with food and should be combined with a healthy diet and exercise program. Common side effects include belching, upset stomach, and fishy aftertaste. It is important to note that icosapent should not be used as a substitute for fish oil supplements or in place of prescription medications to lower cholesterol or triglycerides. 

Pharmacodynamics 

The pharmacodynamic mechanism of icosapent has yet to be fully understood. However, it is known that EPA competes with arachidonic acid (AA) for the same enzyme pathways, producing different eicosanoids. EPA produces less proinflammatory eicosanoids, while AA produces more proinflammatory eicosanoids. This means that EPA reduces inflammation in the body, which can be beneficial in conditions like cardiovascular disease, rheumatoid arthritis, and other inflammatory conditions 

Pharmacokinetics 

Absorption 

It is de-esterified during absorption to active EPA, which is then absorbed in the small intestine. The peak plasma time of icosapent is around 5 hours after administration 

Distribution 

It is highly protein bound, with more than 99% of unesterified EPA bound to proteins in the blood. The volume of distribution (Vd) of icosapent is around 88 liters 

Metabolism 

It is mainly metabolized by the liver via beta-oxidation, similar to dietary fatty acids’ metabolism. There is also a minor metabolism of icosapent via the CYP450 enzyme system 

Elimination/excretion 

The elimination half-life of icosapent is approximately 89 hours, and it does not undergo renal excretion. The total plasma clearance of icosapent is 684 mL/hr 

Adminstartion

Administration 

Oral administration 

It is important to swallow the icosapent capsule whole and not to break, open, dissolve, crush or chew it. The capsule is designed to protect the medicine from stomach acid and to release it gradually in the small intestine for optimal absorption. If the capsule is broken, opened, dissolved, crushed, or chewed, the medicine may be released too quickly, reducing its effectiveness and increasing the risk of side effects 

Storage 

It is essential to store icosapent at a controlled room temperature of 20-25ºC (68-77ºF), and excursions are permitted between 15-30ºC (59-86ºF). This is because icosapent is a sensitive medication that can be affected by heat, light, and humidity. Storing it at the correct temperature helps to ensure that it remains stable and effective. 

It is also recommended to keep icosapent in its original container, tightly closed, and out of reach of children. Avoid storing it in humid or damp areas such as bathrooms or a sink. It is also essential to check the medication’s expiration date and discard any expired medication 

Patient Information Leaflet

Patient information leaflet 

Generic Name: icosapent 

Pronounced: [ eye-KOE-sa-pent ] 

Why do we use icosapent? 

It is used in combination with other medications (such as statins) to lower the risk of heart attack, stroke, and other heart conditions that necessitate hospitalization in adults