ravulizumab

Action and Spectrum

Actions and Spectrum: 

ravulizumab is a complement inhibitor that specifically targets and inhibits the C5 protein in the complement system. By inhibiting C5, ravulizumab prevents the formation of the C5a and C5b-9 components of the complement system, thereby blocking their damaging effects. 

Spectrum 

ravulizumab is primarily indicated for the treatment of two specific conditions: 

• Paroxysmal Nocturnal Hemoglobinuria (PNH): PNH is a rare, acquired disorder characterized by the destruction of red blood cells. ravulizumab treats PNH by preventing the breakdown of RBCs and reducing the risk of hemolysis. 
• Atypical Hemolytic Uremic Syndrome (aHUS): aHUS is a rare, life-threatening condition that involves abnormal blood clotting and the destruction of red blood cells. ravulizumab inhibits the complement system and prevents further damage to red blood cells, kidneys, and other organs in patients with aHUS. 

Drug Interaction

Adverse Reaction

Frequency defined 

>10% 

Upper respiratory tract infection (75%) 

Constipation (25%) 

Pain in extremity (25%) 

Abdominal pain (38%) 

Anemia (25%) 

Headache (25%) 

Pyrexia (20%) 

Upper respiratory tract infection (20%) 

Anemia (20%) 

Pyrexia (13%) 

1-10% 

Hypokalemia, all grades (10%) 

Pain in extremities, all grades (10%) 

Muscle spasms, all grades (10%) 

Urinary tract infection, Grade ≥3 (9%) 

Gastrointestinal infection, Grade ≥3 (3%) 

Nausea, Grade ≥3 (3%) 

Diarrhea, Grade ≥3 (3%) 

Vomiting, Grade ≥3 (3%) 

Nausea (9%) 

Diarrhea (9%) 

Pyrexia (7%) 

Pain in extremities (6%) 

Abdominal pain (6%) 

Dizziness (5%) 

Arthralgia (5%)  

<1% 

Infusion-related reactions 

Black Box Warning

Black Box Warning: 

The usage of ravulizumab may lead to fatal meningococcal infections or sepsis. The patients who would be taking ravulizumab, should first get immunized against meningococci.  

Contraindication / Caution

Contraindication/Caution: 

Contraindications 

• Hypersensitivity 

Cautions 

• Meningococcal Infections 
• Liver dysfunction 
• Vaccinations 
• Pregnancy 
• Breastfeeding 
• Pediatric Usage 

Pregnancy / Lactation

Pregnancy consideration:  

No data is available regarding the administration of the drug during pregnancy. 

Breastfeeding warnings:  

No data is available regarding the excretion of drug in breast milk. 

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 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: No data is available for the drug under this category. 

Pharmacology

Pharmacology: 

ravulizumab specifically binds to the C5 protein in the complement system and inhibits its cleavage into C5a and C5b. By inhibiting C5, ravulizumab prevents the generation of the potent pro-inflammatory molecule C5a and the assembly of the membrane attack complex C5b-9. This blockade of C5 prevents the harmful effects of uncontrolled complement activation, such as red blood cell destruction, inflammation, and organ damage. 

Pharmacodynamics: 

ravulizumab’s pharmacodynamics are closely linked to its mechanism of action. By inhibiting the C5 protein, ravulizumab prevents the activation of the terminal complement pathway and subsequent formation of C5a and C5b-9. This leads to reduced inflammation, red blood cell destruction prevention, and protection against tissue and organ damage caused by uncontrolled complement activation. 

Pharmacokinetics: 

Absorption 

The peak plasma concentration is 349ng/ml 

The area under the curve is 3466ng⋅h/mL 

Distribution 

Protein-bound is more than 99% 

The volume of distribution is 5.34 L (for PNH) and 5.22 L (for aHUS) 

Metabolism 

Monoclonal antibodies like ravulizumab are not extensively metabolized in the body. They are primarily broken down into smaller peptides and amino acids. 

Elimination and Excretion 

The half-life is 49.7 days (for PNH) and 51.8 days (for aHUS) 

The rate of clearance is 0.08 L/day (for PNH); 0.08 L/day (for aHUS) 

Adminstartion

Administration: 

ravulizumab is supplied as a concentrated solution for IV infusions. The healthcare professional will prepare the medication according to the instructions provided in the prescribing information.

The solution may need diluted with a compatible infusion solution before administration. ravulizumab is administered as a slow intravenous infusion. It is usually infused over several hours, and the exact duration differs depending on the specific protocol. 

Patient Information Leaflet

Patient information leaflet 

Generic Name: ravulizumab 

Pronounced: RAV-ue-LIZ-ue-mab 

Why do we use ravulizumab? 

ravulizumab (brand name Ultomiris) is used for the treatment of certain rare blood disorders, specifically paroxysmal nocturnal hemoglobinuria & atypical hemolytic uremic syndrome. Here’s why ravulizumab is used in these conditions: 

• Paroxysmal Nocturnal Hemoglobinuria (PNH): PNH is a rare, acquired disorder characterized by the destruction of red blood cells (hemolysis) due to the absence of specific proteins on the surface of blood cells. ravulizumab is used in PNH to prevent the breakdown of red blood cells and reduce the risk of hemolysis. By inhibiting the complement protein C5, ravulizumab blocks the formation of the C5b-9 membrane attack complex. ravulizumab treatment can help improve symptoms, reduce the need for blood transfusions, and prevent complications associated with PNH. 
• Atypical Hemolytic Uremic Syndrome (aHUS): aHUS is a rare, life-threatening condition characterized by abnormal blood clotting and the destruction of red blood cells, leading to kidney damage and other organ complications. ravulizumab is used in aHUS to inhibit the uncontrolled activation of the complement system, specifically by targeting the C5 protein. By blocking the formation of the C5a and C5b-9 components of the complement system, ravulizumab helps to prevent any other destruction to red blood cells, kidneys, and other organs. ravulizumab treatment can help control complement-mediated inflammation and reduce the risk of organ damage associated with aHUS.