Eculizumab (Soliris) is a monoclonal antibody that prevents the activation of complement by blocking C5. It used to treat complement-mediated hemolysis.

Indications of Eculizumab (Soliris):

• Atypical hemolytic uremic syndrome:
  • Eculizumab is used to treat atypical hemolytic uremic syndrome by blocking thrombotic microangiopathy caused by complement.
  • Limitation of use: Eculizumab cannot be used to treat patients with hemolytic uremic syndrome caused by Shiga toxin-producing E. coli.
• Refractory Generalized myasthenia gravis:
  • Eculizumab can be used to treat patients with anti-acetylcholine receptor antibody-positive refractory generalized myasthenia gravis.
• Neuromyelitis Optica spectrum disorder:
  • Eculizumab is effective for treating Neuromyelitis Optica spectrum disorder in adults with aquaporin-4-antibody positivity.
• Paroxysmal nocturnal hemoglobinuria:
  • It helps reduce the breakdown of red blood cells in paroxysmal nocturnal hemoglobinuria.

Eculizumab in COVID-19 infection:

Eculizumab has been studied in cases series of patients with COVID-19 infection (in combination with vitamin C, Hydroxychloroquine, lopinavir/ritonavir, and anticoagulants. The authors of the study suggested that Eculizumab should be tried in COVID-19 infections as its use resulted in a rapid drop in the inflammatory markers [Ref]. Numerous studies are also ongoing to evaluate its efficacy in patients with COVID-19 infection.

Eculizumab (Soliris) dose in adults:

Note:

• Patients should receive a meningococcal vaccine at least two weeks before beginning therapy, and revaccination should adhere to current guidelines.
• Urgent initiation of eculizumab within two weeks of vaccination requires two weeks of prophylactic antibiotics.
• In unvaccinated patients, the meningococcal vaccine should be administered as soon as possible, followed by two weeks of antibacterial prophylaxis.
• To minimize the risk of meningococcal disease, antimicrobial prophylaxis with oral antibiotics (such as penicillin or macrolides for penicillin-allergic patients) should be prescribed for the duration of eculizumab therapy.
• Eculizumab should be administered within the recommended time interval or within two days of the interval.

Eculizumab (Soliris) dose in the treatment of Atypical hemolytic uremic syndrome:

• For induction, administer 900 mg intravenously once a week for four doses.
• For maintenance, give 1,200 mg at week 5, and then repeat the same dose every 2 weeks thereafter.

• Patients receiving plasmapheresis or plasma exchange:
  • Administer 600 mg within 60 minutes after each plasmapheresis or plasma exchange if the last dose was ≥600 mg
  • Administer 300 mg within 60 minutes after each plasmapheresis or plasma exchange if the most recent dose was 300 mg.
• Patients receiving fresh frozen plasma infusion:
  • Administer 300 mg within 60 minutes before each infusion of fresh frozen plasma if the most recent dose was ≥300 mg.

Eculizumab (Soliris) dose in the treatment of refractory Generalized myasthenia gravis:

• For induction, administer 900 mg intravenously once a week for four doses.
• For maintenance, give 1,200 mg at week 5, then follow with 1,200 mg every two wee
• Patients receiving plasmapheresis or plasma exchange:
  • Administer 600 mg within 60 minutes after each plasmapheresis or plasma exchange if the last dose was ≥600 mg
  • Administer 300 mg within 60 minutes after each plasmapheresis or plasma exchange if the most recent dose was 300 mg.
• Patients receiving fresh frozen plasma infusion:
  • Administer 300 mg within 60 minutes before each infusion of fresh frozen plasma if the most recent dose was ≥300 mg.

Eculizumab (Soliris) dose in the treatment of Neuromyelitis Optica spectrum disorder:

• Starting dose: Administer 900 mg of the drug intravenously once a week for four weeks.
• Maintenance dose: Administer 1,200 mg of the drug intravenously at week 5, and then every 2 weeks thereafter.
• Patients receiving plasmapheresis or plasma exchange:
  • Administer 600 mg within 60 minutes after each plasmapheresis or plasma exchange if the last dose was ≥600 mg
  • Administer 300 mg within 60 minutes after each plasmapheresis or plasma exchange if the most recent dose was 300 mg.
• Patients receiving fresh frozen plasma infusion:
  • Administer 300 mg within 60 minutes after each infusion of fresh frozen plasma if the most recent dose was 300 mg.

Eculizumab (Soliris) dose in the treatment of Paroxysmal nocturnal hemoglobinuria:

• During the induction phase, 600 mg of the drug should be administered intravenously every week for a total of 4 doses.
• For maintenance, administer 900 mg in the 5th week, and then 900 mg every 2 weeks subsequently.

Eculizumab (Soliris) dose in children:

Note:

• The meningococcal vaccine should be administered 2 weeks prior to starting therapy. If the risk of delayed treatment is greater than the risk of contracting a meningococcal infection, vaccination should be given as soon as possible.
• Revaccination should be based on current guidelines and should take into account the duration of eculizumab therapy.
• The recommended dosing interval should be followed, although administration may be varied by ± 2 days.

Eculizumab (Soliris) dose in the treatment of Atypical hemolytic uremic syndrome:

Patient weight:

• For patients weighing between 5 kg and less than 10 kg:
  • For induction, a single dose of 300 mg should be administered intravenously (IV) once a week.
  • For maintenance, 300 mg should be administered at week 2, followed by 300 mg every 3 weeks.
• Children weighing between 10 kg or less than 20 kg:
  • A starting dose of 600 mg given intravenously once a week for the first dose is recommended.
  • After the initial dose, a maintenance dose of 300 mg should be administered on the second week, followed by 300 mg every two weeks thereafter.
• For patients weighing between 20 kg or less than 30 kg:
  • The initial treatment would be 600 mg given intravenously (IV) on a weekly basis for two doses.
  • After the initial treatment, the maintenance dose would be 600 mg given at the third week, and then every two weeks after that.
• For patients weighing between 30 kg and less than 40 kg:
  • An initial dose of 600 mg will be given intravenously once a week for two doses during the induction phase.
  • For maintenance, 900 mg will be given at week 3, followed by a dosage of 900 mg every 2 weeks.
• For patients weighing 40 kg or more:
  • Initial treatment: 900 mg administered intravenously once per week for a total of 4 doses.
  • Maintenance treatment: 1,200 mg administered intravenously at week 5, followed by 1,200 mg every 2 weeks.
• Additional dosing for patients undergoing plasmapheresis or plasma exchange:
  • If the previous dose was 300 mg, give 300 mg within an hour after each plasmapheresis or plasma exchange.
  • If the previous dose was ≥600 mg, give 600 mg within an hour after each plasmapheresis or plasma exchange.
• Additional dosing for patients undergoing fresh frozen plasma infusion:
  • If the previous dose was ≥300 mg, give 300 mg within an hour before each fresh frozen plasma infusion.

Eculizumab Pregnancy Risk Category: C

• Eculizumab can pass through the placenta and has been detected in some cord blood cases.
• Limited data is available on the safety of eculizumab use during pregnancy, but there are no safety concerns.
• Treatment of PNH with eculizumab has been linked to increased fetal survival rates and fewer maternal complications.
• Eculizumab can also be used to treat aHUS during pregnancy.
• Paroxysmal nocturnal hemoglobinuria (PNH) can cause high maternal and postpartum mortality and morbidity.
• Mothers with aHUS can experience adverse outcomes such as preeclampsia, preterm birth, intrauterine growth restriction (IUGR), low infant weight, fetal deaths, hemorrhage, and infections.

Eculizumab use during breastfeeding:

• Eculizumab may be present in breast milk.
• A study of 10 women and a report of 3 women who had breast milk sampled within one hour of infusion did not detect eculizumab.
• However, a separate case report found eculizumab in the breast milk of one woman but not in subsequent samples.
• The manufacturer recommends that the decision to breastfeed during therapy should be based on weighing the risks to the infant, the benefits to the mother, and the benefits of therapy.

Soliris Dose adjustment in kidney disease:

The manufacturer's labelling does not include any instructions for adjusting the dosage in kidney disease.

Soliris Dose adjustment in liver disease:

The manufacturer's labelling does not include any recommended changes to the dosage in liver disease.

Common Side Effects of Eculizumab (Soliris):

• Cardiovascular:
  • Hypertension
  • Tachycardia
  • Peripheral Edema
  • Hypotension
• Central Nervous System:
  • Headache
  • Insomnia
  • Fatigue
  • Dizziness
• Dermatologic:
  • Skin Rash
  • Pruritus
• Endocrine & Metabolic:
  • Hypokalemia
• Gastrointestinal:
  • Diarrhea
  • Vomiting
  • Nausea
  • Abdominal Pain
  • Gastroenteritis
• Genitourinary:
  • Urinary Tract Infection
  • Urinary Tract Symptoms
  • Proteinuria
• Hematologic & Oncologic:
  • Anemia
  • Neoplasm
  • Leukopenia
• Infection:
  • Infection
  • Influenza
• Local:
  • Catheter Infection
• Neuromuscular & Skeletal:
  • Asthenia
  • Back Pain
  • Arthralgia
  • Musculoskeletal Pain
  • Muscle Spasm
• Ophthalmic:
  • Eye Disease
• Renal:
  • Renal Insufficiency
• Respiratory:
  • Cough
  • Nasopharyngitis
  • Nasal Congestion
  • Upper Respiratory Tract Infection
  • Rhinitis
  • Bronchitis
• Miscellaneous:
  • Fever

Rare Side Effects Of Eculizumab (Soliris):

• Cardiovascular:
  • Severe Hypertension
• Central Nervous System:
  • High Fever
  • Paresthesia
• Dermatologic:
  • Alopecia
  • Cellulitis
• Gastrointestinal:
  • Viral Gastroenteritis
  • Constipation
  • Decreased Appetite
• Genitourinary:
  • Cystitis
  • Chronic Renal Failure
• Hematologic & Oncologic:
  • Bruise
  • Lymphocytopenia
• Immunologic:
  • Antibody Development
• Infection:
  • Herpes Simplex Infection
  • Meningococcal Infection
• Neuromuscular & Skeletal:
  • Limb Pain
  • Myalgia
• Ophthalmic:
  • Conjunctivitis
  • Hordeolum
  • Cataract
• Respiratory:
  • Pharyngitis
  • Respiratory Tract Infection
  • Oropharyngeal Pain
  • Sinusitis
  • Flu-Like Symptoms

Contraindications to Eculizumab (Soliris):

US Labeling

• Neisseria meningitidis is a severe infection that can become life-threatening if left untreated.
• Patients who have not been vaccinated against Neisseria meningitidis are recommended to get vaccinated unless the risk of delayed treatment outweighs the chance of contracting a meningococcal disease.

Canadian labeling:

• Eculizumab should not be given to patients who have a hypersensitivity to eculizumab or murine proteins, or to any component of the formulation.
• Eculizumab should not be given to patients who have an unresolved infection with Neisseria meningitidis.
• Patients who have not been vaccinated against Neisseria meningitidis should wait at least 2 weeks before receiving any prophylactic antibiotic treatment.

Warnings and precautions

Infections

• Eculizumab can cause dangerous infections with bacteria other than N. meningitides.
• This includes gonorrhea infections that spread throughout the body.
• Eculizumab can also increase the chance of getting infections from other kinds of bacteria because it blocks the body's natural defense system.
• Sometimes, people with weak immune systems can get a fungal infection called Aspergillus.
• Children should get vaccinated against S.pneumoniae and H.influenzae according to doctor's orders.
• If someone already has an infection, doctors will be careful when treating them with eculizumab.

Infusion reactions

• Sometimes, patients can have bad reactions during their treatment.
• These can include things like allergies or difficulty breathing.
• If a patient has a very serious reaction, like their heart or breathing becoming unstable, the treatment should stop right away.
• After the treatment is done, the patient should be watched closely for at least an hour.

Meningococcal Infection: [US Boxed Warn]

• Eculizumab can cause meningococcal disease, which is a serious infection.
• Complement (a type of protein) deficient patients should get vaccinated against meningococcal disease before starting eculizumab treatment.
• The vaccine should be given at least 2 weeks before starting eculizumab, but in some cases, it may not be possible to wait that long.
• Antibiotics may be needed to prevent infection in people who need to start eculizumab treatment immediately.
• During eculizumab treatment, antibiotics should be taken to reduce the risk of meningococcal disease.
• Despite the vaccine and antibiotics, some people may still get meningococcal disease while taking eculizumab.
• Eculizumab should not be used to treat meningococcal disease as it can make the infection worse.

Eculizumab: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• CBC with differential
• LFTs
• RFTs
• Lactic dehydrogenase(LDH)
• Urine RE
• • Before starting treatment, assess the patient's meningococcal vaccination status and be aware of early signs and symptoms of meningococcal infection.
• During and up to 1 hour after infusion, monitor for signs and symptoms of infusion reactions.
• After discontinuing eculizumab treatment for aHUS, monitor for thrombocytopenia (platelet decrease of ≥25% compared to baseline or peak).
• After discontinuing eculizumab treatment for aHUS, monitor for serum creatinine elevation (≥25% from baseline or nadir), serum LDH elevation (≥25% from baseline or nadir), and signs/symptoms of thrombotic microangiopathy complications (monitor for at least 12 weeks after treatment discontinuation), including angina, dyspnea, mental status changes, seizures, or thrombosis.
• After discontinuing eculizumab treatment for PNH, monitor for signs and symptoms of intravascular hemolysis (monitor for at least 8 weeks after discontinuation), including anemia, fatigue, pain, dark urine, dyspnea, or thrombosis.

How to administer Eculizumab (Soliris)?

IV:

• Eculizumab should be kept at room temperature before administration.
• The infusion time for adults should be 35 minutes, and for pediatric patients, it should be 1 to 4 hours. IV push or bolus is not recommended.
• If infusion reactions occur, the infusion rate should be reduced, or therapy should be stopped.
• Infusion should not last longer than 2 hours in adults, and patients should be monitored for at least 1 hour after infusion for any signs of reaction.
• Before starting therapy, vaccination status should be checked, and the meningococcal vaccine should be given at least 2 weeks before treatment.
• Antibiotic prophylaxis for 2 weeks is required if urgent eculizumab therapy is needed within 2 weeks of vaccination.
• Unvaccinated patients should receive the meningococcal vaccine as soon as possible followed by 2 weeks of antibacterial prophylaxis.

Mechanism of action of Eculizumab (Soliris):

• Eculizumab is a type of antibody that blocks the formation of the terminal complement complex C5b-9/MAC.
• It works by binding to the complement protein C5 and preventing its cleavage into C5a and C5b.
• Paroxysmal nocturnal hemoglobinuria is a condition in which terminal complement-mediated intravascular hemolysis occurs.
• This leads to the formation of membrane attack complex (MAC), which stabilizes hemoglobin and reduces the need for RBC transfusions.
• Atypical hemolytic uremic syndrome is characterized by uncontrolled complement activation, often caused by impaired complement activity regulation.

The onset of action:

• In PNH, hemolysis can be reduced in as little as one week.

Half-life elimination:

• During plasma exchange, the half-life is reduced to 1.26 hours, compared to 270 to 414 hours without it.

International Brands of Eculizumab:

• Soliris

Eculizumab Brand Names in Pakistan:

No Brands Available in Pakistan.