evolocumab

Action and Spectrum

Actions and spectrum: 

evolocumab is a monoclonal antibody used to treat adults having clinical atherosclerotic cardiovascular disease (ASCVD) or heterozygous familial hypercholesterolemia (HeFH) who need additional lowering of low-density lipoprotein cholesterol (LDL-C) levels in addition to diet and maximally tolerated statin therapy.

evolocumab binds to and inhibits proprotein convertase subtilisin/kexin type 9 (PCSK9), a protein that promotes the degradation of LDL receptors. By inhibiting PCSK9, evolocumab increases the LDL receptors on the surface of liver cells, which leads to increased clearance of LDL cholesterol from the blood. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Nasopharyngitis (4-10.5%)  

1-10% 

Contusion (1%) 

Muscle spasms (1.3%) 

Fatigue (1.6%) 

Nausea (1.8%) 

Arthralgia (1.8%) 

Cough (1.2-4.5%) 

Influenza (1.2-7.5%) 

UTI (1.3-4.5%) 

URTI (2.1-9.3%) 

Back pain (2.3-6.2%) 

Gastroenteritis (3%) 

Diarrhea (3%) 

Hypertension (3.2%) 

Injection site reactions (3.2-5.7%) 

Musculoskeletal pain (3.3%) 

Dizziness (3.7%) 

Myalgia (4%) 

Headache (4%) 

Sinusitis (4.2%) 

Allergic reaction (5.1%) 

Oropharyngeal pain (7%)  

Post marketing Reports 

Allergic reactions: Angioedema 

Black Box Warning

Black Box Warning: 

There is no black box warning associated with the use of evolocumab. 

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

evolocumab is contraindicated in patients with a hypersensitivity to the drug or any of its components. There are no other absolute contraindications to the use of evolocumab; however, caution should be exercised in certain patient populations.  

Caution: 

• Hypersensitivity reactions: Hypersensitivity reactions, including rash, urticaria, and angioedema, have been reported with evolocumab. If any signs or symptoms of allergic reactions occur, discontinue evolocumab immediately and initiate appropriate treatment. 
• Hepatitis B virus (HBV) reactivation: In patients treated with evolocumab who chronic carriers of HBV are and who discontinue evolocumab, closely monitor for evidence of hepatitis flare or HBV reactivation. Initiate appropriate therapy and closely monitor liver function. 
• Use with statins: The use of evolocumab with higher doses of statins than those commonly used with an increased risk of diabetes mellitus may increase the risk of muscle-related adverse reactions. 
• Immunosuppressive therapy: The safety and efficacy of evolocumab in patients receiving immunosuppressive therapy have not been evaluated. Use evolocumab with caution in these patients. 
• Pregnancy: The effects of evolocumab on fetal development are unknown.  
• Lactation: It is not known whether evolocumab is excreted in human milk.

Comorbidities: 

• Hypercholesterolemia 
• Familial hypercholesterolemia 
• Cardiovascular disease 
• Atherosclerosis 
• Diabetes mellitus 
• Obesity 
• Metabolic syndrome 

Pregnancy / Lactation

Pregnancy consideration: pregnancy category is not assigned 

Lactation: safety and efficacy not established  

Pregnancy category: 

• Category A: Satisfactory and well-controlled studies show no risk to the fetus in the first or later trimester. 
• Category B: There is no evidence of risk to the fetus found in animal reproduction studies and there are not enough studies on pregnant women. 
• Category C: Adverse effects on the fetus found with evidence in animal reproduction studies and no adequate evidence for an effect in humans, care must be taken for potential risks in pregnant women. 
• Category D: There is adequate data available with sufficient evidence of human fetal risk from various platforms, but despite potential risks may be used only in emergency cases for potential benefits. 
• Category X: Drugs listed in this category outweigh risks over benefits These category drugs should be prohibited for pregnant women. 
• Category N: There is no data available for the drug under this category. 

Pharmacology

Pharmacology: 

evolocumab is a monoclonal antibody that selectively binds with proprotein convertase subtilisin/kexin type 9 in circulation. PCSK9 binds to low-density lipoprotein (LDL) receptors on hepatocytes, leading to their lysosomal degradation, resulting in decreased clearance of LDL-cholesterol from circulation.

By binding to PCSK9, evolocumab prevents its binding to LDL receptors, resulting in increased recycling of LDL receptors and increased clearance of LDL-cholesterol from circulation. 

evolocumab is a fully human IgG2 monoclonal antibody produced in Chinese hamster ovary (CHO) cells by recombinant DNA technology. It has a molecular weight of approximately 145 kDa. 

evolocumab has a half-life of approximately 11-17 days and is eliminated primarily through catabolism.  

Pharmacodynamics: 

A human monoclonal antibody called evolocumab binds to and inhibits the liver enzyme proprotein convertase subtilisin/kexin type 9 (PCSK9). PCSK9 is responsible for promoting the degradation of low-density lipoprotein (LDL) receptors, which results in increased levels of LDL cholesterol (LDL-C) in the blood.

By inhibiting PCSK9, evolocumab increases the number of LDL receptors on hepatocytes, leading to increased clearance of LDL-C from the blood. 

evolocumab also decreases the serum concentrations of other atherogenic lipoproteins, including very low-density lipoprotein cholesterol (VLDL-C), intermediate-density lipoprotein cholesterol (IDL-C), and lipoprotein (a) [Lp(a)]. 

The onset of action of evolocumab is rapid, with significant reductions in LDL-C observed as early as 2 hours post-administration. The maximum effect is reached within 4 to 8 weeks of initiation of treatment.  

Pharmacokinetics: 

Absorption 

As a large protein molecule, evolocumab is administered by subcutaneous injection, where it is absorbed slowly and steadily into circulation. 

Distribution 

The volume of distribution of evolocumab is not well defined. It is expected to distribute into the extravascular space but not cross the blood-brain barrier. 

Metabolism 

evolocumab is metabolized via proteolysis into amino acids and small peptides, which are then recycled. 

Elimination and excretion 

The elimination half-life of evolocumab is approximately 11-17 days. It is eliminated primarily via catabolism and proteolysis, with a minor contribution from renal elimination. 

Adminstartion

Administration: 

evolocumab is administered by subcutaneous injection. The recommended dose and frequency depend on the specific indication being treated. For example, for the treatment of primary hyperlipidemia, the recommended dose is 140 mg every two weeks or 420 mg once monthly. The recommended dose is 140 mg every two weeks to prevent from cardiovascular events.

Patient Information Leaflet

Patient information leaflet 

Generic Name: evolocumab 

Pronounced: (ee-voe-loe-KUE-mab)  

Why do we use evolocumab? 

evolocumab is a medication used for the treatment of high cholesterol levels in the blood. It is specifically indicated for the treatment of: 

• Primary hyperlipidemia (including heterozygous familial hypercholesterolemia) 
• Homozygous familial hypercholesterolemia 
• Cardiovascular risk reduction in patients with established cardiovascular disease.