Eculizumab

FDA Drug Information • Also known as: Soliris

Brand Names: Soliris
Dosage Form: LIQUID
Product Type: DRUG FOR FURTHER PROCESSING

⚠ Boxed Warning (Black Box)

WARNING: SERIOUS MENINGOCOCCAL INFECTIONS SOLIRIS, a complement inhibitor, increases the risk of serious infections caused by Neisseria meningitidis [see Warnings and Precautions (5.1) ] . Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. These infections may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of SOLIRIS, unless the risks of delaying therapy with SOLIRIS outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for vaccinations against meningococcal bacteria in patients receiving a complement inhibitor. See Warnings and Precautions (5.1) for additional guidance on the management of the risk of serious infections caused by meningococcal bacteria. Patients receiving SOLIRIS are at increased risk for invasive disease caused by Neisseria meningitidis , even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of serious meningococcal infections and evaluate immediately if infection is suspected. Because of the risk of serious meningococcal infections, SOLIRIS is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ULTOMIRIS and SOLIRIS REMS [see Warnings and Precautions (5.2) ] . WARNING: SERIOUS MENINGOCOCCAL INFECTIONS See full prescribing information for complete boxed warning SOLIRIS increases the risk of serious and life-threatening infections caused by Neisseria meningitidis . Complete or update meningococcal vaccination at least 2 weeks prior to the first dose of SOLIRIS, unless the risks of delaying SOLIRIS outweigh the risk of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients receiving a complement inhibitor. ( 5.1 ) Patients receiving SOLIRIS are at increased risk for invasive disease caused by N. meningitidis , even if they develop antibodies following vaccination. Monitor patients for early signs and symptoms of meningococcal infections, and evaluate immediately if infection is suspected. ( 5.1 ) SOLIRIS is available only through a restricted program called the ULTOMIRIS and SOLIRIS REMS. ( 5.2 )

Description

11 DESCRIPTION Eculizumab, a complement inhibitor, is a recombinant humanized monoclonal IgG2/4 κ antibody produced by murine myeloma cell culture and purified by standard bioprocess technology. Eculizumab contains human constant regions from human IgG2 sequences and human IgG4 sequences and murine complementarity-determining regions grafted onto the human framework light- and heavy-chain variable regions. Eculizumab is composed of two 448 amino acid heavy chains and two 214 amino acid light chains and has a molecular weight of approximately 148 kDa. SOLIRIS (eculizumab) injection is a sterile, clear, colorless, preservative-free 10 mg/mL solution for intravenous infusion and is supplied in 30-mL single-dose vials. The product is formulated at pH 7 and each 30 mL vial contains 300 mg of eculizumab, polysorbate 80 (6.6 mg) (vegetable origin), sodium chloride (263.1 mg), sodium phosphate dibasic (53.4 mg), sodium phosphate monobasic (13.8 mg), and Water for Injection, USP.

What Is Eculizumab Used For?

1 INDICATIONS AND USAGE SOLIRIS is a complement inhibitor indicated for: the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. ( 1.1 ) the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy. ( 1.2 ) Limitation of Use SOLIRIS is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). the treatment of generalized myasthenia gravis (gMG) in adult and pediatric patients six years of age and older who are anti-acetylcholine receptor (AChR) antibody positive. ( 1.3 ) the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive. ( 1.4 ) 1.1 Paroxysmal Nocturnal Hemoglobinuria (PNH) SOLIRIS is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. 1.2 Atypical Hemolytic Uremic Syndrome (aHUS) SOLIRIS is indicated for the treatment of patients with atypical hemolytic uremic syndrome (aHUS) to inhibit complement-mediated thrombotic microangiopathy. Limitation of Use SOLIRIS is not indicated for the treatment of patients with Shiga toxin E. coli related hemolytic uremic syndrome (STEC-HUS). 1.3 Generalized Myasthenia Gravis (gMG) SOLIRIS is indicated for the treatment of generalized myasthenia gravis (gMG) in adult and pediatric patients six years of age and older who are anti-acetylcholine receptor (AChR) antibody positive. 1.4 Neuromyelitis Optica Spectrum Disorder (NMOSD) SOLIRIS is indicated for the treatment of neuromyelitis optica spectrum disorder (NMOSD) in adult patients who are anti-aquaporin-4 (AQP4) antibody positive.

Dosage and Administration

2 DOSAGE AND ADMINISTRATION For intravenous infusion only; recommended dosage for: PNH: ( 2.2 ) aHUS, gMG, and NMOSD in adults: ( 2.3 ) aHUS and gMG in pediatric patients: ( 2.4 ) 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 SOLIRIS [see Warnings and Precautions (5.1) ] . If urgent SOLIRIS 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 SOLIRIS must enroll in the ULTOMIRIS and SOLIRIS REMS [see Warnings and Precautions (5.2) ] . 2.2 Recommended Dosage for Adults – PNH The recommended dosage of SOLIRIS for the treatment of PNH in patients 18 years of age and older is administered as an intravenous infusion [see Dosage and Administration (2.7) ] 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. Administer SOLIRIS at the recommended dosage regimen time points, or within two days of these time points [see Warnings and Precautions (5.4) ] . 2.3 Recommended Dosage for Adults – aHUS, gMG, and NMOSD The recommended dosage of SOLIRIS for the treatment of aHUS, gMG, or NMOSD in patients 18 years of age and older is administered as an intravenous infusion [see Dosage and Administration (2.7) ] as follows: 900 mg weekly for the first 4 weeks, followed by 1200 mg for the fifth dose 1 week later, then 1200 mg every 2 weeks thereafter. 2.4 Recommended Dosage for Pediatric Patients – aHUS and gMG The recommended dosage of SOLIRIS for the treatment of aHUS in pediatric patients less than 18 years of age or gMG in pediatric patients 6 years of age and older 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 and Pediatric Patients 6 Years of Age and Older with gMG Patient Body Weight Induction Maintenance 40 kg and over 900 mg weekly for the first 4 weeks 1200 mg at week 5; then 1200 mg every 2 weeks 30 kg to less than 40 kg 600 mg 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 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 SOLIRIS 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...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of the labeling: Serious Meningococcal Infections [see Warnings and Precautions (5.1) ] Other Infections [see Warnings and Precautions (5.3) ] Monitoring Disease Manifestations after SOLIRIS Discontinuation [see Warnings and Precautions (5.4) ] Thrombosis Prevention and Management [see Warnings and Precautions (5.5) ] Infusion-Related Reactions [see Warnings and Precautions (5.6) ] The most frequently reported adverse reactions in the PNH randomized trial (≥10% overall and greater than placebo) are: headache, nasopharyngitis, back pain, and nausea. ( 6.1 ) The most frequently reported adverse reactions in aHUS single arm prospective trials (≥20%) are: headache, diarrhea, hypertension, upper respiratory infection, abdominal pain, vomiting, nasopharyngitis, anemia, cough, peripheral edema, nausea, urinary tract infections, pyrexia. ( 6.1 ) The most frequently reported adverse reaction in the gMG placebo-controlled clinical trial (≥10%) in adult patients is musculoskeletal pain. ( 6.1 ) The most frequently reported adverse reactions in the NMOSD placebo- controlled trial (≥10%) are: upper respiratory infection, nasopharyngitis, diarrhea, back pain, dizziness, influenza, arthralgia, pharyngitis, and contusion. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Alexion Pharmaceuticals, Inc. at 1-844-259-6783 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trial Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Meningococcal infections are the most important adverse reactions experienced by patients receiving SOLIRIS. In PNH clinical studies, two patients experienced meningococcal sepsis. Both patients had previously received a meningococcal vaccine. In clinical studies among patients without PNH, meningococcal meningitis occurred in one unvaccinated patient. Meningococcal sepsis occurred in one previously vaccinated patient enrolled in the retrospective aHUS study during the post-study follow-up period [see Warnings and Precautions (5.1) ] . PNH The data described below reflect exposure to SOLIRIS in 196 adult patients with PNH, age 18-85, of whom 55% were female. All had signs or symptoms of intravascular hemolysis. SOLIRIS was studied in a placebo-controlled clinical study (PNH Study 1, in which 43 patients received SOLIRIS and 44, placebo); a single arm clinical study (PNH Study 2); and a long term extension study (E05-001). 182 patients were exposed for greater than one year. All patients received the recommended SOLIRIS dose regimen. Table 5 summarizes the adverse reactions that occurred at a numerically higher rate in the SOLIRIS group than the placebo group and at a rate of 5% or more among patients treated with SOLIRIS. Table 5: Adverse Reactions Reported in 5% or More of SOLIRIS Treated Patients with PNH and Greater than Placebo in the Controlled Clinical Study Reaction SOLIRIS (N=43) N (%) Placebo (N=44) N (%) Headache 19 (44) 12 (27) Nasopharyngitis 10 (23) 8 (18) Back pain 8 (19) 4 (9) Nausea 7 (16) 5 (11) Fatigue 5 (12) 1 (2) Cough 5 (12) 4 (9) Herpes simplex infections 3 (7) 0 Sinusitis 3 (7) 0 Respiratory tract infection 3 (7) 1 (2) Constipation 3 (7) 2 (5) Myalgia 3 (7) 1 (2) Pain in extremity 3 (7) 1 (2) Influenza-like illness 2 (5) 1 (2) In the placebo-controlled clinical study, serious adverse reactions occurred among 4 (9%) patients receiving SOLIRIS and 9 (21%) patients receiving placebo. The serious reactions included infections and progression of PNH. No deaths occurred in the study and no patients receiving SOLIRIS experienced a thrombotic event; one thrombotic event occurred in a patient receiving placebo. Among 193 patients with PNH treated with SOLIRIS in...

Drug Interactions

7 DRUG INTERACTIONS 7.1 Plasmapheresis, Plasma Exchange, Fresh Frozen Plasma Infusion or IVIg Concomitant use of SOLIRIS with plasma exchange (PE), plasmapheresis (PP) , fresh frozen plasma infusion (PE/PI), or in patients with gMG on concomitant IVIg treatment can reduce serum eculizumab concentrations and requires a supplemental dose of SOLIRIS [see Dosage and Administration (2.5) ]. 7.2 Neonatal Fc Receptor Blockers Concomitant use of SOLIRIS with neonatal Fc receptor (FcRn) blockers may lower systemic exposures and reduce effectiveness of SOLIRIS. Closely monitor for reduced effectiveness of SOLIRIS.

Contraindications

4 CONTRAINDICATIONS SOLIRIS is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection [see Warnings and Precautions (5.1) ] . SOLIRIS is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection. ( 4 )

Pregnancy and Breastfeeding

8.1 Pregnancy Risk Summary Limited data on outcomes of pregnancies that have occurred following SOLIRIS use in pregnant women have not identified a concern for specific adverse developmental outcomes ( see Data ). There are risks to the mother and fetus associated with untreated paroxysmal nocturnal hemoglobinuria (PNH) and atypical hemolytic uremic syndrome (aHUS) in pregnancy ( see Clinical Considerations ). Animal studies using a mouse analogue of the SOLIRIS 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 ( see Data ) . 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. Clinical Considerations 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. Data Human Data 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 SOLIRIS have not suggested safety concerns. However, these data cannot definitively exclude any drug-associated risk during pregnancy, because of the limited sample size. Animal Data Animal reproduction studies were conducted in...

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING SOLIRIS (eculizumab) injection is a sterile, preservative-free, clear, colorless solution supplied as one 300 mg/30 mL (10 mg/mL) single-dose vial per carton (NDC 25682-001-01). Store SOLIRIS vials refrigerated at 2°-8° C (36°-46° F) in the original carton to protect from light until time of use. SOLIRIS 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 3 days. Do not use beyond the expiration date stamped on the carton. Refer to Dosage and Administration (2) for information on the stability and storage of diluted solutions of SOLIRIS. DO NOT FREEZE. DO NOT SHAKE.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.