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:

  • It is indicated in the management of atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy.
  • Limitation of use: Eculizumab is not indicated for the treatment of patients with Shiga toxin Escherichia coli-related hemolytic uremic syndrome.

• Refractory Generalized myasthenia gravis:

  • Patients with refractory generalized myasthenia gravis who are anti-acetylcholine receptor antibody-positive can be treated with eculizumab.

• Neuromyelitis Optica spectrum disorder:

  • It is effective in the treatment of Neuromyelitis Optica spectrum disorder in adults who are aquaporin-4-antibody positive.

• Paroxysmal nocturnal hemoglobinuria:

  • It is used in reducing hemolysis 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:

• A meningococcal vaccine should be given at least 2 weeks before starting therapy, revaccination should be done according to current guidelines.
• Two weeks of prophylactic antibiotics should be given in case of urgent eculizumab initiation in <2 weeks after vaccination.
• The meningococcal vaccine should be administered as soon as possible followed by 2 weeks of antibacterial prophylaxis in unvaccinated patients.
• Antimicrobial prophylaxis with oral antibiotics (penicillin, or macrolides if penicillin-allergic) should be prescribed for the duration of eculizumab therapy to minimize the risk of meningococcal disease.
• Eculizumab should be given at the recommended time interval or within 2 days of the interval.

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

• Induction: 900 mg IV weekly for 4 doses.
• Maintenance: 1,200 mg at week 5, then 1,200 mg every 2 weeks thereafter.

• Supplemental dosing for patients receiving plasmapheresis or plasma exchange:

  • If the most recent dose was ≥600 mg, administer 600 mg within 60 minutes after each plasmapheresis or plasma exchange.
  • If the most recent dose was 300 mg, administer 300 mg within 60 minutes after each plasmapheresis or plasma exchange.

• Supplemental dosing for patients receiving fresh frozen plasma infusion:

  • If the most recent dose was ≥300 mg, administer 300 mg within 60 minutes prior to each infusion of fresh frozen plasma.

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

• Induction: 900 mg IV weekly for 4 doses.
• Maintenance: 1,200 mg at week 5, then 1,200 mg every 2 weeks thereafter.

• Supplemental dosing for patients receiving plasmapheresis or plasma exchange:

  • If the most recent dose was ≥600 mg, administer 600 mg within 60 minutes after each plasmapheresis or plasma exchange.
  • If the most recent dose was 300 mg, administer 300 mg within 60 minutes after each plasmapheresis or plasma exchange.

• Supplemental dosing for patients receiving fresh frozen plasma infusion:

  • If the most recent dose was ≥300 mg, administer 300 mg within 60 minutes prior to each infusion of fresh frozen plasma.

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

• Induction: 900 mg IV weekly for 4 doses;
• Maintenance: 1,200 mg at week 5, then 1,200 mg every 2 weeks thereafter.

• Supplemental dosing for patients receiving plasmapheresis or plasma exchange:

  • If the most recent dose was ≥600 mg, administer 600 mg within 60 minutes after each plasmapheresis or plasma exchange.
  • If the most recent dose was 300 mg, administer 300 mg within 60 minutes after each plasmapheresis or plasma exchange.

• Supplemental dosing for patients receiving fresh frozen plasma infusion:

  • If the most recent dose was ≥300 mg, administer 300 mg within 60 minutes prior to each infusion of fresh frozen plasma.

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

• Induction: 600 mg IV weekly for 4 doses.
• Maintenance: 900 mg at week 5; then 900 mg every 2 weeks thereafter.

Eculizumab (Soliris) dose in children:

Note:

• The meningococcal vaccine should be given at least 2 weeks before therapy.
• Vaccination should be given as soon as possible if the risk of treatment delay outweighs the risk of developing a meningococcal infection.
• Revaccination is based according to current guidelines with consideration of eculizumab therapy duration. Treatment should be administered at the recommended time interval although administration may be varied by ± 2 days.

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

• Patient weight:

• 5 kg to <10 kg:

  • Induction: 300 mg IV weekly for 1 dose.
  • Maintenance: 300 mg at week 2, then 300 mg every 3 weeks.

• 10 kg to <20 kg:

  • Induction: 600 mg IV weekly for 1 dose.
  • Maintenance: 300 mg at week 2, then 300 mg every 2 weeks.

• 20 kg to <30 kg:

  • Induction: 600 mg IV weekly for 2 doses.
  • Maintenance: 600 mg at week 3, then 600 mg every 2 weeks

• 30 kg to <40 kg:

  • Induction: 600 mg IV weekly for 2 doses.
  • Maintenance: 900 mg at week 3, then 900 mg every 2 weeks

• ≥40 kg:

  • Induction: 900 mg IV weekly for 4 doses.
  • Maintenance: 1,200 mg at week 5, then 1,200 mg every 2 weeks.

• Supplemental dosing for patients receiving plasmapheresis or plasma exchange:

  • If the most recent dose was 300 mg, administer 300 mg within 60 minutes after each plasmapheresis or plasma exchange.
  • If the most recent dose was ≥600 mg, administer 600 mg within 60 minutes after each plasmapheresis or plasma exchange.

• Supplemental dosing for patients receiving fresh frozen plasma infusion:

  • If the most recent dose was ≥300 mg, administer 300 mg within 60 minutes before each infusion of fresh frozen plasma.

Eculizumab Pregnancy Risk Category: C

• Eculizumab can cross the placenta. It has been detected in some cord blood cases.
• There are no safety concerns based on limited data concerning eculizumab's use during pregnancy. Treatment of PNH with Eculizumab has been associated with an increase in fetal survival rates and fewer maternal complications.
• It has been reported that eculizumab can be used to treat aHUS during pregnancy.
• Paroxysmal nocturnal hemomaturia is a condition that causes high rates of maternal and postpartum mortality and morbidity.
• Hemorrhage, infections and miscarriages are all possible adverse maternal outcomes.
• Mothers with aHUS can experience preeclampsia, preterm birth, IUGR, low infant weight and fetal deaths.

Eculizumab use during breastfeeding:

• Breast milk might contain Eculizumab.
• Eculizumab wasn't detected in breast milk samples from 10 women in a study or in a report that included information from three women who had their milk sampled within one hour of the infusion.
• A separate case report revealed that eculizumab could be detected in breast milk samples of a woman but not in subsequent samples.
• According to the manufacturer the decision to breastfeed during therapy is based on the risks to infants, the benefits to the mother and the benefits to the mother.

Soliris Dose adjustment in kidney disease:

There are no dosage adjustments provided in the manufacturer's labeling.

Soliris Dose adjustment in liver disease:

There are no dosage adjustments provided in the manufacturer's labeling. 

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 serious infection that has not been treated
• Patients who are not currently vaccinated for Neisseria meningitidis should be (unless the risks of delayed treatment outweigh any chance of contracting a meningococcal disease).

Canadian labeling:

• Hypersensitivity to eculizumab or murine proteins, as well as any component of the formulation
• Neisseria meningitidis unresolved infection
• Patients who have not been vaccinated against Neisseria Meningitidis are advised to wait at least 2 weeks before receiving any prophylactic antibiotic treatment.

Warnings and precautions

• Infections

  • Eculizumab can cause fatal infections with Neisseria species other than N.
  • meningitides), including disseminated gonococcal infections.
  • Eculizumab therapy can increase the risk of infection with other bacteria, particularly with encapsulated bacteria, due to blockage in terminal complement activation.
  • Aspergillus can be contracted in immunocompromised or neutropenic patients.
  • Children should be vaccinated against S.pneumoniae and H.influenzae according to ACIP guidelines.
  • Patients with a systemic infection should be treated with caution

• Infusion reactions

  • Infusion reactions can occur in patients, including hypersensitivity and anaphylaxis. If a patient experiences a fatal reaction (eg, cardiac instability, respiratory compromise), the therapy should be stopped immediately.
  • After infusion, you will need to monitor for at least 1 hour.

• Meningococcal Infection: [US Boxed Warn]

  • Eculizumab can cause fatal meningococcal infections (Neisseria Meningitides), which should be treated immediately.
  • Meningococcal infections should be monitored closely and the appropriate treatment should begin.
  • Patients suffering from complement deficiencies should adhere to current recommendations for meningococcal vaccinations.
  • Vaccination can reduce the risk of developing meningococcal infection.
  • Meningococcal vaccinations should be administered 2 weeks prior to therapy, unless the risks associated with delaying eculizumab are greater than the chance of developing meningococcal infections. The eculizumab treatment duration dictates that revaccinations should be done in accordance with current guidelines.
  • In case of an urgent need for eculizumab treatment in less than two weeks, prophylactic antibiotics can be administered for up to two weeks.
  • Unvaccinated patients should receive a meningococcal vaccination as soon as possible. If urgent treatment is needed, antibacterial prophylaxis should be continued for 2 weeks.
  • Some patients developed meningococcal infection despite being vaccinated.
  • In clinical trials, prophylactic antibiotics were given until at least two weeks after vaccination.
  • To reduce the chance of developing meningococcal diseases, antimicrobial prophylaxis should be done with oral antibiotics (penicillin or macrolides if penicillin allergic) during eculizumab treatment.
  • Eculizumab should not be used to treat serious meningococcal infection.
  • Eculizumab has a 2,000-fold higher risk of developing meningococcal diseases (compared to the general population).

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
• Early signs/symptoms of meningococcal infection(assess meningococcal vaccination status prior to initiation).
• Signs and symptoms of an infusion reaction (during infusion and for 1 hour after infusion complete).
• After discontinuation: aHUS:
• Thrombocytopenia (platelet decrease by ≥25% compared to baseline or peak)
• The occurrence of two or repeated measurement of any one of the following: Serum creatinine elevation (≥25% from baseline or nadir), serum LDH elevation (≥25% from baseline or nadir),
• Signs/symptoms of thrombotic microangiopathy complications (monitor for at least 12 weeks after treatment discontinuation), including angina, dyspnea, mental status changes, seizure, or thrombosis;
• PNH: 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:

• Before administration, room temperature should be attained.
• It should be infused over 35 minutes in adults and over 1 to 4 hours in pediatric patients.
• IV push or bolus is not recommended.
• In the case of infusion reactions, the infusion rate should be reduced or therapy should be discontinued.
• The infusion should not exceed a maximum 2-hour duration in adults.
• Monitoring for at least 1 hour following completion of infusion (for signs/symptoms of infusion reaction).
• Vaccination status should be checked before starting therapy.
• The meningococcal vaccine should be administered at least 2 weeks before treatment.
• Two weeks of antibiotic prophylaxis is required in case of urgent eculizumab therapy in less than 2 weeks after vaccination.
• The meningococcal vaccine should be given as soon as possible followed by 2 weeks of antibacterial prophylaxis in the case of unvaccinated patients.

Mechanism of action of Eculizumab (Soliris):

• Eculizumab, a monoclonal humanized IgG antibody, is not cleaved into C5a or C5b. It binds to the complement protein C5.
• Blocking the formation C5b is a way to stop the formation terminal complex C5b-9/MAC.
• Paroxysmal nocturnal hemoglobinuria's key clinical feature is terminal complement-mediated intravascular halylysis.
• It causes the formation of membrane attack complex (MAC), which results in hemoglobin stabilization, and a decreased need for RBC transfusions.
• Atypical hemolytic uremic Syndrome is characterized by uncontrolled complement activation. This can be caused by impaired complement activity regulation.

The onset of action:

• PNH: Reduced hemolysis: ≤1 week.

Half-life elimination:

• 270 to 414 hours (during plasma exchange the half-life is reduced to 1.26 hours).

International Brands of Eculizumab:

• Soliris

Eculizumab Brand Names in Pakistan:

No Brands Available in Pakistan.