Evinacumab-dgnb Injection - Uses, Dosage, Precautions, and Mechanism of Action

Overview-

Evinacumab is an angiopoietin-like protein 3 monoclonal antibodies. This angiopoietin-like protein 3 is an inhibitor of low-density lipoprotein and endothelial lipase. A phase 3 clinical trial of Evinacumab was published in New England, a journal of medicine, and on February 11, 2021, it was approved by FDA (Food and Drug Administration). Evinacumab-dgnb works by decreasing the amount of low-density lipoprotein cholesterol production and increasing the breakdown of low-density lipoprotein cholesterol in the body.

Uses of Evinacumab-dgnb:

Evinacumab-dgnb is an adjunct to other low-density lipoprotein cholesterol-lowering therapies for treating adults and children 12 years and above with homozygous familial hypercholesterolemia.

Dosage and Administration:

The recommended dosage is 15 milligrams per kilogram of body weight and administered by intravenous injection over 60 minutes once a month.

Warnings and Precautions:

1. Serious Hypersensitivity Reactions: During the clinical trial, one patient treated with Evinacumab-dgnb experienced anaphylaxis versus zero patients who received a placebo. Evinacumab-dgnb is contraindicated in patients who had a prior history of hypersensitivity reactions with this drug. If signs and symptoms of a hypersensitivity reaction occur, Evinacumab-dgnb is discontinued.

2. Embryo-Fetal Toxicity: Based on the findings of animal reproduction studies, Evinacumab-dgnb can cause fetal harm in pregnant patients. When Evinacumab-dgnb was administered to rabbits at doses below human exposure, it caused an increase in fetal malformations. Before initiating treatment with Evinacuma-dgnb, a pregnancy test should be considered. Patients who may become pregnant are advised to use effective contraception during the treatment with Evinacumab-dgnb for at least five months following the last dose of Evinacumab-dgnb.

Use in Specific Populations:

• Pregnancy: According to animal reproduction studies, Evinacumab-dgnb can cause fetal harm to pregnant patients. The human data available is insufficient to evaluate the drug-associated risk of major birth defects, miscarriages, and adverse maternal or fetal outcomes. Evinacumab-dgnb is a human IgG-4 recombinant monoclonal antibody, and human IgG is known for crossing the placental barrier. Hence, Evinacumab-dgnb has the potential to transmit from the mother to the developing fetus.

• Lactation: The effects of Evinacumab-dgnb in the breastfed infant are unknown. The infant's developmental and overall health benefits should be considered along with the mother’s clinical need for Evinacumab-dgnb. Any potential adverse effects of Evinacumab-dgnb or from the underlying maternal condition on the breastfed infant should be monitored.

• Pregnancy Test: A pregnancy test should be done before initiating treatment with Evinacumab-dgnb.

• Contraception: Patients who may become pregnant should use effective birth control pills during treatment with Evinacumab-dgnb for at least five months following the last dose of Evinacuab-dgnb.

• Pediatric Use: The safety and effectiveness of using Evinacumab-dgnb are unknown in pediatric patients with homozygous familial hypercholesterolemia who are younger than 12 years old. So far, it is indicated for children aged 12 years and older.

• Geriatric Use: Clinical studies of Evinacumab-dgnb have yet to include sufficient numbers of patients 65 years and older in determining whether they respond differently from younger patients.

• Patients with Renal and Hepatic Impairment: No data on patients with renal and hepatic impairment are available.

Drug interaction: Although accurate data is not available about the interaction of Evinacumab-dgnb with other medications, patients are advised to inform their doctor about any medication they are taking.

For Patients:

What Is Cholesterol?

Cholesterol is a fat-like substance made by the liver. The human body needs cholesterol to make hormones, vitamin D, and bile. There are two types of lipoproteins: low-density lipoprotein and high-density lipoprotein. The low-density lipoprotein travels through the bloodstream and delivers cholesterol to cells.

An increase in low-density lipoprotein leads to the accumulation of it in the walls of the arteries. This plaque can narrow the arteries and reduce blood flow. A common place where this plaque accumulates is in the coronary arteries, which are the blood vessels that supply the heart.

This plaque buildup is called coronary artery disease and increases the risk of a heart attack. Plaque buildup in other arteries, such as the neck's carotid artery, can reduce blood flow to the brain and increase the stroke risk. The liver also makes high-density lipoprotein, also known as good cholesterol. High-density lipoprotein helps to remove excess cholesterol from the cells, tissues, and plaque from blood vessels. High-density lipoprotein returns the excess cholesterol to the liver, which removes it from the body.

What Is Homozygous Familial Hypercholesterolemia?

Familial hypercholesterolemia is a monogenic and autosomal dominant disorder resulting in high blood LDL cholesterol levels and normal triglyceride levels. People with familial hypercholesterolemia have a high amount of LDL cholesterol due to a mutation in one of the genes controlling how the body clears cholesterol. As a result, cholesterol builds up in the bloodstream and ultimately accumulates in the walls of the arteries. Cholesterol buildup in the artery wall is called atherosclerosis and can lead to problems such as heart attack. Familial hypercholesterolemia is of two types: homozygous and heterozygous. Heterozygous familial hypercholesterolemia is more common, and LDL cholesterol level is less severe and is frequently greater than 190 milligrams per decilitres in adults and greater than 160 milligrams per decilitres in children or adolescents. Homozygous familial hypercholesterolemia is less common, but LDL cholesterol level is typically more severally elevated. Untreated LDL cholesterol levels can often be greater than 400 milligrams per decilitre.

Why Is Evinacumab-dgnb Prescribed?

Evinacumab-dgnb is combined with other treatments available to reduce the amount of low-density lipoprotein cholesterol, also called bad cholesterol. It also reduces other fatty substances in the blood in patients with homozygous familial hypercholesterolemia. Evinacumab-dgnb comes under the medication called angiopoietin-like protein 3 inhibitor monoclonal antibodies. The accumulation of cholesterol along the walls of arteries can decrease the blood flow and oxygen supply to the heart, brain, and other body parts. Therefore, lowering the blood level of cholesterol with the use of Evinacumab-dgnb can prevent heart diseases, strokes, and chances of a heart attack.

How Should Evinacumab-dgnb Be Used?

• Evinacumab-dgnb comes in a liquid form and is injected slowly intravenously over 60 minutes. It is usually given once every four weeks.

• Evinacumab-dgnb can cause serious reactions during infusion. Hence, a doctor carefully monitors the patients while giving the medication.

• The doctor should be immediately informed if the patient experiences any symptoms like shortness of breath, wheezing, hives, rash, itching, dizziness, nasal congestion, fever, nausea, muscle weakness, swelling of face, throat, tongue, lips, or eyes.

• The doctor will slow down the infusion or even stop the treatment if there are any signs of side effects. Hence, it is necessary to inform the doctor about any symptoms.

What Special Precautions Should Be Taken?

• Allergies- The patient should inform the doctor if they are allergic to Evinacumab, any other medications, or any of the ingredients in Evinacumab preparations.

• Drug History- The doctor should be informed about the prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products the patient is taking or plans to take.

• Pregnancy and Breastfeeding- The doctor should be informed if the patient is pregnant or plans to get pregnant. It is advisable to take a pregnancy test before initiating treatment with Evinacumab. The doctor may advise the patient to use effective birth control to prevent pregnancy during treatment with Evinacumab-dgnb injection and for five months after the final dose. If the patient becomes pregnant while receiving Evinacumab-dgnb, they should inform the doctor immediately.

What Special Dietary Instructions Should Be Followed?

Patients are advised to eat a low-fat and low-cholesterol diet. It is important to follow all the exercise and dietary recommendations the doctor makes.

What Are the Side Effects of Evinacumab-dgnb?

• Runny nose.

• Nasal congestion.

• Sore throat.

• Flu-like symptoms.

• Nausea.

• Dizziness.

• Pain in arms or legs.

• Low energy.

What Should Be Done in Case of Overdose?

In the case of an overdose, the poison control helpline should be contacted immediately. If the patient collapses, experiences seizures, has difficulty breathing, or cannot be awakened, the helpline number should be reached immediately.

Other Information:

• Patients are advised to keep a written list of all the prescription and nonprescription drugs and any vitamin, herbal or dietary supplementation they take.

• Patients should bring the list with them each time they visit the doctor.

• It is important to carry the list in case of emergencies.

For Doctors:

Indications:

Evinacumab-dgnb is an adjunct to other low-density lipoprotein cholesterol-lowering therapies for homozygous familial hypercholesterolemia in adults and children 12 years and older.

Mechanism of Action:

The Evinacumab-dgnb is a monoclonal antibody that binds and inhibits the angiopoietin-like protein 3.Angiopoietin-like protein 3 is a diverse group of proteins involved in several physiological processes, including the regulation of lipoprotein metabolism. Loss-of-function mutations in angiopoietin-like protein three and angiopoietin-like protein 4 have resulted in hypolipidemia and reduced the risk of coronary artery disease. In contrast, the increase in the levels of these proteins appears to be associated with cardiovascular risk.While these observations have made angiopoietin-like proteins desirable as a class target in treating hyperlipidemic disorders,angiopoietin-like protein is the first to be targeted pharmacologically for lipid-lowering therapy. This angiopoietin-like protein three is expressed mainly in the liver and helps regulate lipid metabolism by inhibiting lipoprotein lipase and endothelial lipase. When Evinacumab-dgnb inhibits the angiopoietin-like protein 3, it reduces low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides.

Pharmacodynamics:

Evinacumab-dgnb exerts its hypolipidemic and antiatherogenic effects by decreasing circulating levels of triglycerides, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, apolipoprotein B, and total cholesterol. Evinacumab has a relatively long duration of action that allows for its administration via intravenous injection once a month.

Pharmacokinetics:

Absorption: The mean steady-state trough concentration is approximately 241 milligrams per liter, and the maximum concentration at the end of infusion is approximately 689 milligrams per liter.

Volume of Distribution: Volume of distribution of Evinacumab-dgnb was estimated to be around 4.8 liters.

Metabolism: The biotransformation of Evinacumab-dgnb has yet to be characterized. The monoclonal antibodies, as a class, are typically degraded through catabolic pathways into smaller peptides and amino acids.

Route of Elimination: The monoclonal antibodies are typically eliminated through cell uptake and subsequent catabolism by lysosomal degradation. Due to their larger size, they are eliminated renally under pathologic conditions.

Half-life: The elimination half-life of Evinacumab-dgnb varies as it is a function of its serum concentration. Two parallel pathways eliminate Evinacumab-dgnb. At higher concentrations, it is eliminated by a non-saturable proteolytic pathway; at lower concentrations, it is eliminated through a saturable target-mediated pathway.

Preparation Instructions for Intravenous Infusion:

• Calculate the dosage and total volume of Evinacumab-dgnb required and the number of vials required based on the patient’s current body weight.

• Before administering, the doctor should visually inspect the solution for discoloration, cloudiness, or particulate matter. Evinacumab-dgnb appears clear to slightly opalescent and colorless to pale yellow solution. It should not be administered if it appears discolored or cloudy or if any particulate matter is present.

• The doctor is advised not to shake the vial and should withdraw the required volume from the vials of Evinacumab-dgnb and transfer it into an intravenous infusion bag containing a maximum volume of 250 milliliters of 0.9 % sodium chloride injection, USP, or 5 % dextrose injection. The diluted solution should be mixed gently and should not be shaken.

• The final concentration of the diluted solution should be between 0.5 milligrams per milliliter and 20 milligrams per milliliter based on the patient’s current body weight.

Administration Instructions For Intravenous Instructions:

• If the diluted solution is refrigerated, it should be allowed to come to room temperature before administering.

• Administer Evinacumab-dgnb diluted solution via Intravenous infusion through an intravenous line that contains a sterile, in-line, or add-on, 0.2-micron to 5-micron filter over 60 minutes.

• Evinacumab-dgnb should not be mixed with other medications and should not be administered concomitantly through the same infusion line.

• Evinacumab-dgnb can be administered without regard to lipoprotein apheresis timing.

Storage and Disposal:

• It should be stored at 2 to 8 degrees Celsius for no longer than 24 hours from the preparation time. The diluted solution can also be stored at room temperature at 25 degrees Celsius for 6 hours. The diluted solution should be fresh.

• The diluted solution should be administered immediately after preparation, and any unused portion left in the vial should be discarded.