SOLIRIS

Eculizumab is a monoclonal antibody that targets complement protein C5. 7, 1 Binding to this protein prevents the activation of a complement terminal complex, which is used to treat a number of autoimmune conditions. 7, 1, 2 Eculizumab was granted FDA approval on 16 March 2007.

In Q1 2023, the EMA's Committee for Medicinal Products for Human Use (CHMP) adopted a positive opinion of two formulations of eculizumab indicated for the treatment of paroxysmal nocturnal hemoglobinuria. 9, 10.

Eculizumab is indicated in the

US to treat paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis, atypical hemolytic uremic syndrome to inhibit complement-mediated thrombotic microangiopathy, and neuromyelitis optica spectrum disorder (NMOSD). 6, 2 It is also indicated in EU to treat PNH in both adult and pediatric patients.

Eculizumab is a monoclonal antibody that prevents the activation of terminal complement in some autoimmune conditions. 7, 1, 2 Eculizumab has a long duration of action.

Patients taking this medication should be vaccinated against Neisseria meningiditis as serious meningococcal infections have occurred in the past. 7, 2.

Eculizumab is administered by intravenous infusion so the bioavailability is 100%.

This drug reaches a

C max of 194±76 µg/mL and C trough of 97±60 µg/mL.

AUC was calculated to be 24,467.6 µg*h/mL.

The volume of distribution of eculizumab is 5-8 L.

Eculizumab is a monoclonal antibody and is expected to be metabolized to small peptides and amino acids. 4, 5.

Monoclonal antibodies are not eliminated in the urine, and only a small amount is excreted in bile.

Most monoclonal antibodies are catabolized in lysosomes to amino acids.

The half life of eculizumab is 270-375h 7 or 272±82h.

Pharmacokinetic properties in healthy patients have not been determined.

In patients with rhematoid arthritis, there is an average clearance of 0.26 mL/kg/h.

Improve decision support & research outcomes With structured adverse effects data, including: blackbox warnings, adverse reactions, warning & precautions, & incidence rates.

View sample adverse effects data in our new Data Library! See the data Improve decision support & research outcomes with our structured adverse effects data.

Overdoses of eculizumab are unlikely as it is administered under specialist supervision.

In case of overdose, contact local poison control.

is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection.

BKEMV is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection.

For intravenous infusion only; recommended dosage for: PNH: aHUS and gMG in adults: aHUS in pediatric patients: 2.1 Recommended Vaccination and Prophylaxis for Meningococcal Infection Vaccinate patients against meningococcal infection (serogroups A, C, W, Y and B) according to current ACIP recommendations at least 2 weeks prior to initiation of BKEMV.

If urgent

BKEMV therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible.

Healthcare providers who prescribe BKEMV must enroll in the BKEMV REMS. 2.2 Recommended Dosage for Adults – PNH The recommended dosage of BKEMV for the treatment of PNH in patients 18 years of age and older is administered as an intravenous infusion as follows: 600 mg weekly for the first 4 weeks, followed by 900 mg for the fifth dose 1 week later, then 900 mg every 2 weeks thereafter.

BKEMV at the recommended dosage regimen time points, or within two days of these time points. 2.3 Recommended Dosage for Adults – aHUS and gMG The recommended dosage of BKEMV for the treatment of aHUS and gMG in patients 18 years of age and older is administered as an intravenous infusion as follows: 900 mg weekly for the first 4 weeks, followed by 1,200 mg for the fifth dose 1 week later, then 1,200 mg every 2 weeks thereafter. 2.4 Recommended Dosage for Pediatric Patients – aHUS The recommended dosage of BKEMV for the treatment of aHUS in pediatric patients less than 18 years of age is administered as an intravenous infusion based upon body weight, according to the following schedule (Table 1): Table 1: Dosing Recommendations in Pediatric Patients Less Than 18 Years of Age with aHUS Patient Body Weight Induction Maintenance 40 kg and over 900 mg weekly for the first 4 weeks 1,200 mg at week 5; then 1,200 mg every 2 weeks 30 kg to less than 40 kg 600 mg weekly for the first 2 weeks 900 mg at week 3; then 900 mg every 2 weeks 20 kg to less than 30 kg 600 mg weekly for the first 2 weeks 600 mg at week 3; then 600 mg every 2 weeks 10 kg to less than 20 kg 600 mg single dose at Week 1 300 mg at week 2; then 300 mg every 2 weeks 5 kg to less than 10 kg 300 mg single dose at Week 1 300 mg at week 2; then 300 mg every 3 weeks Administer BKEMV at the recommended dosage regimen time points, or within two days of these time points. 2.5 Dose Adjustment in Case of Plasmapheresis, Plasma Exchange, Fresh Frozen Plasma Infusion or IVIg For adult and pediatric patients with aHUS, and adult patients with gMG, supplemental dosing of BKEMV is required in the setting of concomitant plasmapheresis or plasma exchange, or fresh frozen plasma infusion (PE/PI) (Table 2).

Table 2: Supplemental Dose of BKEMV after Plasmapheresis/PE/PI Type of Plasma Intervention Most Recent BKEMV Dose Supplemental BKEMV Dose with Each Plasma Intervention Timing of Supplemental BKEMV Dose Plasmapheresis or plasma exchange 300 mg 300 mg per each plasmapheresis or plasma exchange session Within 60 minutes after each plasmapheresis or plasma exchange 600 mg or greater 600 mg per each plasmapheresis or plasma exchange session Fresh frozen plasma infusion 300 mg or greater 300 mg per infusion of fresh frozen plasma 60 minutes prior to each infusion of fresh frozen plasma For patients with gMG, a supplemental dose of BKEMV is required in the setting of concomitant use of intravenous immunoglobulin (IVIg) treatment as described in Table 3.

Table 3: Supplemental Dose of BKEMV with concomitant IVIg IVIg Frequency Most Recent BKEMV Dose Supplemental BKEMV Dose per IVIg Cycle Timing of Supplemental BKEMV Dose Acute rescue therapy No supplemental BKEMV dose needed Equal to or more frequent than every 4 weeks 900 mg or more 600 mg At the same time as scheduled BKEMV dose 600 mg or less 300 mg Less frequent than every 4 weeks 900 mg or more 600 mg At the next scheduled BKEMV dose after the last IVIg cycle 600 mg or less 300 mg 2.6 Preparation Dilute BKEMV to a final admixture concentration of 5 mg/mL using the following steps: Withdraw the required amount of BKEMV from the vial into a sterile syringe.

Transfer the recommended dose to an infusion bag.

BKEMV to a final concentration of 5 mg/mL by adding the appropriate amount (equal volume of diluent to drug volume) of 0.9% Sodium Chloride Injection, USP; 0.45% Sodium Chloride Injection, USP; 5% Dextrose in Water Injection, USP; or Ringer's Injection, USP to the infusion bag.

The final admixed

BKEMV 5 mg/mL infusion volume is 60 mL for 300 mg doses, 120 mL for 600 mg doses, 180 mL for 900 mg doses or 240 mL for 1,200 mg doses (Table 4).

Table 4: Preparation and Reconstitution of BKEMV BKEMV Dose Diluent Volume Final Volume 300 mg 30 mL 60 mL 600 mg 60 mL 120 mL 900 mg 90 mL 180 mL 1,200 mg 120 mL 240 mL Gently invert the infusion bag containing the diluted BKEMV solution to ensure thorough mixing of the product and diluent.

Discard any unused portion left in a vial, as the product contains no preservatives.

Prior to administration, the admixture should be allowed to adjust to room temperature [18°C to 25°C (64°F to 77°F).

The admixture must not be heated in a microwave or with any heat source other than ambient air temperature.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit. 2.7 Administration Only administer as an intravenous infusion.

Do not administer as an intravenous push or bolus injection.

Administer the

BKEMV admixture by intravenous infusion over 35 minutes in adults and to 4 hours in pediatric patients via gravity feed, a syringe-type pump, or an infusion pump.

Admixed solutions of

BKEMV are stable for 64 hours at 2°C to 8°C (36°F to 46°F) or 24 hours at room temperature.

If an adverse reaction occurs during the administration of BKEMV, the infusion may be slowed or stopped at the discretion of the physician.

If the infusion is slowed, the total infusion time should not exceed two hours in adults.

Monitor the patient for at least one hour following completion of the infusion for signs or symptoms of an infusion-related reaction.

(eculizumab-aeeb) injection is a sterile, preservative-free, clear to opalescent, colorless to slightly yellow solution supplied as one 300 mg/30 mL (10 mg/mL) single-dose vial per carton (NDC 55513-180-01).

BKEMV vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of use.

BKEMV vials may be stored in the original carton at controlled room temperature [not more than 25°C (77°F)] for only a single period up to 7 days.

Do not use beyond the expiration date stamped on the carton.

Refer to Dosage and

Administration for information on the stability and storage of diluted solutions of BKEMV.

BKEMV vials refrigerated at 2°C to 8°C (36°F to 46°F) in the original carton to protect from light until time of use.

BKEMV vials may be stored in the original carton at controlled room temperature [not more than 25°C (77°F)] for only a single period up to 7 days.

Do not use beyond the expiration date stamped on the carton.

Refer to Dosage and

Administration for information on the stability and storage of diluted solutions of BKEMV.

Limited data on outcomes of pregnancies that have occurred following eculizumab use in pregnant women have not identified a concern for specific adverse developmental outcomes.

There are risks to the mother and fetus associated with untreated paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) in pregnancy.

Animal studies using a mouse analogue of the eculizumab molecule (murine anti-C5 antibody) showed increased rates of developmental abnormalities and an increased rate of dead and moribund offspring at doses 2-8 times the human dose.

The estimated background risk of major birth defects and miscarriage for the indicated populations is unknown.

All pregnancies have a background risk of birth defect, loss, or other adverse outcomes.

In the

U.S. general population, the estimated background risk of major birth defect and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively.

Disease-associated maternal and/or fetal/neonatal risk PNH in pregnancy is associated with adverse maternal outcomes, including worsening cytopenias, thrombotic events, infections, bleeding, miscarriages and increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery. aHUS in pregnancy is associated with adverse maternal outcomes, including pre-eclampsia and preterm delivery, and adverse fetal/neonatal outcomes, including intrauterine growth restriction (IUGR), fetal death and low birth weight.

A pooled analysis of prospectively (50.3%) and retrospectively (49.7%) collected data in more than 300 pregnant women with live births following exposure to eculizumab have not suggested safety concerns.

However, these data cannot definitively exclude any drug-associated risk during pregnancy, because of the limited sample size.

Animal reproduction studies were conducted in mice using doses of a murine anti-C5 antibody that approximated 2-4 times (low dose) and 4-8 times (high dose) the recommended human eculizumab dose, based on a body weight comparison.

When animal exposure to the antibody occurred in the time period from before mating until early gestation, no decrease in fertility or reproductive performance was observed.

When maternal exposure to the antibody occurred during organogenesis, two cases of retinal dysplasia and one case of umbilical hernia were observed among 230 offspring born to mothers exposed to the higher antibody dose; however, the exposure did not increase fetal loss or neonatal death.

When maternal exposure to the antibody occurred in the time period from implantation through weaning, a higher number of male offspring became moribund or died (1/25 controls, 2/25 low dose group, 5/25 high dose group).

Surviving offspring had normal development and reproductive function.

PNH Safety and effectiveness of BKEMV for the treatment of PNH in pediatric patients have not been established. aHUS The safety and effectiveness of BKEMV for the treatment of aHUS have been established in pediatric patients.

Use of

BKEMV in pediatric patients for this indication is supported by evidence from four adequate and well-controlled clinical studies assessing the safety and effectiveness of eculizumab for the treatment of aHUS.

The studies included a total of 47 pediatric patients (ages 2 months to 17 years).

The safety and effectiveness of eculizumab for the treatment of aHUS appear similar in pediatric and adult patients.

Administer vaccinations for the prevention of infection due to Neisseria meningitidis, Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) according to ACIP guidelines.

Fifty-one patients 65 years of age or older (15 with PNH, 4 with aHUS, 26 with gMG, and with another indication) were treated with eculizumab in clinical trials in the approved indications.

Although there were no apparent age-related differences observed in these studies, the number of patients aged and over is not sufficient to determine whether they respond differently from younger patients.