eculizumab

Action and Spectrum

Actions and spectrum: 

eculizumab is a monoclonal antibody that binds to and inhibits the activity of complement protein C5. It is used to treat two rare blood disorders, paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS).

PNH is a disease characterized by the destruction of red blood cells, leading to anemia, fatigue, and other symptoms. aHUS is a genetic disorder that causes blood clots throughout the body, leading to kidney failure, stroke, and other serious complications.

By inhibiting C5, eculizumab prevents the formation of the membrane attack complex (MAC), a structure that can damage red blood cells and blood vessels and contribute to the symptoms of PNH and aHUS. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Haemolytic Uremic Syndrome 

• Headache (41%) 
• Anemia (35%) 
• URI (29%) 
• Leukopenia (24%) 
• Peripheral edema (18%) 
• Cough (12%) 
• Hypertension (47%) 
• Diarrhea (35%) 
• Vomiting (29%) 
• UTI (24%) 
• Fatigue (18%) 
• Pyrexia (18%)

Paroxysmal Nocturnal Hemoglobinuria 

• Nasopharyngitis (23%) 
• Nausea (16%) 
• Fatigue (12%) 
• Headache (44%) 
• Back pain (19%) 
• Cough (12%)

Generalized myasthenia gravis 

• Nasopharyngitis (24%) 
• Musculoskeletal pain (15%) 
• URTI (11%) 
• Headache (26%) 
• Diarrhea (15%) 
• Arthralgia (12%)

1-10% 

Haemolytic Uremic Syndrome 

• Vertigo 
• Pharyngolaryngeal pain 
• Pain in extremity

Paroxysmal Nocturnal Hemoglobinuria 

• Flu-like illness 
• Pain 
• fatal or serious meningococcal infections 
• Constipation 
• Myalgia 
• Various infections (eg, HSV)

Generalized myasthenia gravis 

• Pyrexia (7%) 
• Contusion (8%) 
• Peripheral edema (8%) 
• Herpes simplex virus (8%) 
• Abdominal pain (8%) 
• Nausea (10%)

Frequency not defined 

Serious or Fatal infections: Neisseria meningitidis, Neisseria spp unspecified, Neisseria gonorrhoeae, Neisseria sicca/subflava 

Black Box Warning

Contraindication / Caution

Contraindication/Caution: 

Contraindication: 

eculizumab is contraindicated in patients with a history of life-threatening allergic reactions to eculizumab or any of its components.  

Caution: 

• Meningococcal infections: eculizumab increases the risk of meningococcal infections, especially in individuals who have not been vaccinated against Neisseria meningitidis. 
• Use in pregnant women: There are limited data on the use of eculizumab in pregnant women.  
• Use in breastfeeding women: The safety of eculizumab in breastfeeding women is unknown.  
• Thrombotic events: eculizumab has been associated with thrombotic events, such as myocardial infarction and stroke. 
• Use in patients with impaired renal function: eculizumab is primarily cleared by the kidneys, and patients with impaired renal function may be at increased risk of adverse effects.  
• Use in patients with hepatic impairment: eculizumab is not extensively metabolized in the liver, and no dosage adjustment is required in patients with hepatic impairment.

Comorbidities: 

eculizumab is indicated for the treatment of several medical conditions that are associated with complement-mediated hemolysis, including atypical hemolytic uremic syndrome (aHUS), paroxysmal nocturnal hemoglobinuria (PNH), and anti-acetylcholine receptor (AChR) antibody-positive generalized myasthenia gravis (gMG). When using eculizumab, caution should be taken in patients with an active systemic infection. In patients with PNH, the drug should be discontinued immediately if meningococcal infection is suspected.

In addition, caution is recommended when administering live vaccines to patients receiving eculizumab, as the medication may interfere with the effectiveness of live vaccines. eculizumab should be used with caution in patients with hepatic impairment or end-stage renal disease, as data on the use of eculizumab in these populations are limited. 

Pregnancy / Lactation

Pregnancy consideration: US FDA pregnancy category: Not assigned. 

Lactation: It is not known whether eculizumab is excreted in human milk.  

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: 

eculizumab is a monoclonal antibody that specifically binds to complement protein C5 and blocks its cleavage into C5a and C5b. This inhibits the formation of the membrane attack complex (MAC) of complement, which plays a key role in the destruction of target cells. By blocking the formation of the MAC, eculizumab helps prevent the destruction of red blood cells in patients with the paroxysmal nocturnal hemoglobinuria (PNH) and also reduces the risk of thrombotic microangiopathy (TMA) in patients with the atypical hemolytic uremic syndrome (aHUS).  

Pharmacodynamics: 

eculizumab is a monoclonal antibody that binds to complement protein C5, which inhibits its cleavage into C5a and C5b, preventing the formation of the membrane attack complex (MAC). The MAC is a group of proteins that insert into cell membranes, leading to cell lysis and death.

By inhibiting MAC formation, eculizumab prevents the destruction of red blood cells and the development of atypical hemolytic uremic syndrome and the paroxysmal nocturnal hemoglobinuria.

It also reduces complement-mediated inflammation in other conditions, like myasthenia gravis and neuromyelitis optica spectrum disorder.  

Pharmacokinetics: 

Absorption 

eculizumab is administered intravenously and therefore directly enters the bloodstream. 

Distribution 

eculizumab has a high molecular weight and therefore has limited distribution to extravascular tissues. 

Metabolism 

eculizumab is not metabolized by the liver or other organs. 

Elimination and excretion 

eculizumab is primarily eliminated by catabolism into small peptides and amino acids, which are eliminated via the kidneys. The terminal half-life of eculizumab is 11-12 days in patients with paroxysmal nocturnal hemoglobinuria (PNH) and 23-25 days in patients with the atypical hemolytic uremic syndrome (aHUS). 

Adminstartion

Administration: 

eculizumab is administered intravenously (IV) over a period of 35 minutes. The recommended starting dose of eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria (PNH) is 900 mg once weekly for the first four weeks, followed by a maintenance dose of 1200 mg once every 2 weeks.

As a treatment of atypical hemolytic uremic syndrome (aHUS), the recommended starting dose is 900 mg once weekly for the first four weeks, then by a maintenance dose of 1200 mg once every 2 weeks.

The dosage and frequency may be adjusted based on the individual patient’s response and clinical condition. eculizumab should be administered under the supervision of a healthcare professional experienced in the treatment of PNH or aHUS. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: eculizumab 

Pronounced: [ E-kue-LIZ-oo-mab ]  

Why do we use eculizumab? 

• Paroxysmal nocturnal hemoglobinuria (PNH): eculizumab is used for the treatment of PNH, a rare and potentially life-threatening blood disorder characterized by the destruction of red blood cells. 
• Atypical hemolytic uremic syndrome (aHUS): eculizumab is used for the treatment of aHUS, another rare and potentially life-threatening disorder characterized by the formation of blood clots in blood vessels, leading to kidney damage and failure. 
• Generalized Myasthenia Gravis (gMG): eculizumab is used for the treatment of gMG, a rare autoimmune disorder that affects the muscles responsible for movement, leading to muscle weakness and fatigue.