Inform patients that there may be an increased risk of other types of infections, particularly those due to encapsulated bacteria. Soliris can lower the ability of your immune system to fight infections. Efficacy evaluations were based on thrombotic microangiopathy (TMA) endpoints. All had signs or symptoms of intravascular hemolysis. Select one or more newsletters to continue. Among 193 patients with PNH treated with Soliris in the single arm, clinical study or the follow-up study, the adverse reactions were similar to those reported in the placebo-controlled clinical study. Soliris is indicated for the treatment of patients with paroxysmal nocturnal hemoglobinuria (PNH) to reduce hemolysis. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. The MG-ADL is a categorical scale that assesses the impact on daily function of 8 signs or symptoms that are typically affected in gMG. counsel you about the risk of meningococcal infection, give you information about the symptoms of meningococcal infection. Patients received meningococcal vaccination prior to receipt of Soliris. TMA complications occurred following a missed dose in 5 patients, and Soliris was reinitiated in 4 of these 5 patients. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Soliris and any potential adverse effects on the breastfed child from eculizumab or from the underlying maternal condition. The serious reactions included infections and progression of PNH. Intravenous immunoglobulin (IVIg) treatment may interfere with the endosomal neonatal Fc receptor (FcRn) recycling mechanism of monoclonal antibodies such as eculizumab and thereby decrease serum eculizumab concentrations. As with all proteins, there is a potential for immunogenicity. 0000019857 00000 n Transfer the recommended dose to an infusion bag. Table 12 summarizes the key baseline clinical and disease-related characteristics of patients enrolled in Study C08-002A/B. [See. Fifty-one patients 65 years of age or older (15 with PNH, 4 with aHUS, 26 with gMG, and 6 with NMOSD) were treated with Soliris in clinical trials in the approved indications. Under the Soliris REMS, prescribers must enroll in the program [see Warnings and Precautions (5.1)]. “Soliris provides the first FDA-approved treatment for neuromyelitis optica spectrum disorder, a debilitating disease that profoundly impacts patients’ lives,” said Billy Dunn, M.D., director of the Division of Neurology Products in the FDA’s Center for Drug Evaluation and Research. %PDF-1.6 %���� Although there were no apparent age-related differences observed in these studies, the number of patients aged 65 and over is not sufficient to determine whether they respond differently from younger patients. are breastfeeding or plan to breastfeed. A total of 19 pediatric patients (ages 2 months to 17 years) received Soliris in Study C09-001r. 0000038511 00000 n Provide two weeks of antibacterial drug prophylaxis to patients if Soliris must be initiated immediately and vaccines are administered less than two weeks before starting Soliris therapy. (Soliris FDA PI, 2019) II. 0000004995 00000 n Soliris ® (eculizumab), a complement inhibitor, is the first and only medication approved by the FDA to treat adults with neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive. 0000038565 00000 n In order to qualify for enrollment, patients were required to have a platelet count < lower limit of normal range (LLN), evidence of hemolysis such as an elevation in serum LDH, and serum creatinine above the upper limits of normal, without the need for chronic dialysis. ... SOLIRIS is a medicine that affects your immune system and can lower the ability of your immune system to fight infections. 121 Seaport Boulevard 0000004839 00000 n All patients had received PT at least once every two weeks, but no more than three times per week, for a minimum of eight weeks prior to the first Soliris dose. Patients in Study C10-003 received Soliris for a minimum of 26 weeks. A total of 35 patients received PE/PI prior to eculizumab. Patients on chronic dialysis were permitted to enroll in Study C08-003A/B. Advise the patient to read FDA-approved patient labeling (Medication Guide). 1899 0 obj <>stream The use of Soliris increases a patient's susceptibility to serious meningococcal infections (septicemia and/or meningitis). A key secondary endpoint in gMG Study 1 was the change from baseline in the Quantitative Myasthenia Gravis (QMG) total score at Week 26. See full prescribing information for ALDURAZYME. 1805 0 obj <> endobj The pharmacokinetics of eculizumab were not affected by age (2 months to 85 years), sex, or race. or intravenous infusion) usually over 35 minutes in adults and 1 to 4 hours in pediatric patients. Following intravenous maintenance doses of 1200 mg once every 2 weeks in patients with gMG, the week 26 observed mean ± SD Cmax was 783 ± 288 mcg/mL and the Ctrough was 341 ± 172 mcg/mL. The safety and efficacy of Soliris in PNH patients with hemolysis were assessed in a randomized, double-blind, placebo-controlled 26 week study (PNH Study 1, NCT00122330); PNH patients were also treated with Soliris in a single arm 52 week study (PNH Study 2, NCT00122304) and in a long-term extension study (E05-001, NCT00122317). No patient required new dialysis with Soliris. There are no data on the effects of eculizumab on milk production. Both patients had previously received a meningococcal vaccine. Plasmapheresis or plasma exchange. 0000003665 00000 n Although limited published data does not report detectable levels of eculizumab in human milk, maternal IgG is known to be present in human milk. In Study C08-002A/B, mean platelet count (± SD) increased from 109 ± 32 ×109/L at baseline to 169 ± 72 ×109/L by one week; this effect was maintained through 26 weeks (210 ± 68 ×109/L), and 2 years (205 ± 46 ×109/L). After discontinuing Soliris, monitor patients with aHUS for signs and symptoms of thrombotic microangiopathy (TMA) complications for at least 12 weeks. The median duration of Soliris therapy was 16 weeks (range 4 to 70 weeks) for children <2 years of age (n=5), 31 weeks (range 19 to 63 weeks) for children 2 to <12 years of age (n=10), and 38 weeks (range 1 to 69 weeks) for patients 12 to <18 years of age (n=4). Dilute Soliris 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 easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records. adults with a disease called neuromyelitis optica spectrum disorder (NMOSD) who are anti-aquaporin-4 (AQP4) antibody positive. Advise patients that administration of Soliris may result in infusion-related reactions. Expanded Disability Status Scale (EDSS) score ≤ 7 (consistent with the presence of at least limited ambulation with aid). In Study C10-003, 59% (13/22) of patients experienced a serious adverse event (SAE). In Study C10-004, mean platelet count (± SD) increased from 119 ± 66 ×109/L at baseline to 200 ± 84 ×109/L by one week; this effect was maintained through 26 weeks (mean platelet count (± SD) at week 26: 252 ± 70 ×109/L). Two of 161 patients with PNH (1.2%) and 1 of 100 patients with aHUS (1%), and none of the 96 patients with NMOSD had low positive values for neutralizing antibodies. In addition, 3 out of 130 previously vaccinated patients with aHUS developed meningococcal infections while receiving treatment with Soliris [see Adverse Reactions (6.1)]. Patients in this group received eculizumab for a median duration of 38 weeks (range, 2 to 64 weeks). Available information is insufficient to inform the effect of eculizumab on the breastfed infant. Ultomiris Ultomiris, a complement inhibitor, is for the following uses: • Treatment of adult patients with . Timing of Supplemental Soliris Dose. Each item is assessed on a 4-point scale where a score of 0 represents no weakness and a score of 3 represents severe weakness (total score 0-39). In patients with PNH, aHUS, gMG, and NMOSD, free C5 concentrations of < 0.5 mcg/mL was correlated with complete blockade of terminal complement activity. None of the 62 patients with gMG had antibodies to Soliris detected following the 26-week active treatment. Endpoints related to TMA included the following: aHUS Resistant to PE/PI (Study C08-002A/B). See ". See ". Admixed solutions of Soliris are stable for 24 h at 2°-8° C (36°-46° F) and at room temperature. <]>> Administer the Soliris admixture by intravenous infusion over 35 minutes in adults and 1 to 4 hours in pediatric patients via gravity feed, a syringe-type pump, or an infusion pump. Patients enrolled in Study C10-003 were required to have ADAMTS13 activity level above 5%; observed range of values in the trial were 38%-121%. Ensure that patients receive the Medication Guide. The immunogenicity of Soliris has been evaluated using two different immunoassays for the detection of anti-eculizumab antibodies: a direct enzyme-linked immunosorbent assay (ELISA) using the Fab fragment of eculizumab as target was used for the PNH indication; and an electro-chemiluminescence (ECL) bridging assay using the eculizumab whole molecule as target was used for the aHUS, gMG, and NMOSD indications, as well as for additional patients with PNH. 0000015406 00000 n The studies included a total of 47 pediatric patients (ages 2 months to 17 years). 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). 0000007669 00000 n 0000041696 00000 n The data described below reflect exposure to Soliris in 196 adult patients with PNH, age 18-85, of whom 55% were female. SOLIRIS is a medicine that affects your immune system and can lower the ability of your immune system to fight infections. 0000041641 00000 n All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. FULL PRESCRIBING INFORMATION: CONTENTS* 1 INDICATIONS AND USAGE. Soliris is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS). Table 6 summarizes all adverse events reported in at least 10% of patients enrolled in Study C10-003. The median patient age was 28 years (range: 13 to 63 years). Over 95% of patients in each group were receiving acetylcholinesterase (AchE) inhibitors, and 98% were receiving immunosuppressant therapies (ISTs). Meningococcal infections may quickly become life-threatening and cause death if not recognized and treated early. Renal function, as measured by eGFR, was improved and maintained during Soliris therapy. In Study C08-003A/B, responses to Soliris were similar in patients with and without identified mutations in genes encoding complement regulatory factor proteins. For patients 18 years of age and older, Soliris therapy consists of: Administer Soliris at the recommended dosage regimen time points, or within two days of these time points [see Warnings and Precautions (5.4)]. Following intravenous maintenance doses of 900 mg once every 2 weeks in patients with PNH, the week 26 observed mean ± SD serum eculizumab maximum concentration (Cmax) was 194 ± 76 mcg/mL and the trough concentration (Ctrough) was 97 ± 60 mcg/mL. The mean eGFR (± SD) increased from 33 ± 30 mL/min/1.73m2 at baseline to 98 ± 44 mL/min/1.73m2 by 26 weeks. Do not administer as an intravenous push or bolus injection. Learn how to prepare for treatment, what you may expect throughout, and tools and resources available to help you manage your anti-aquaporin-4 (AQP4) antibody-positive neuromyelitis optica spectrum disorder (NMOSD) long-term. Medically reviewed by Drugs.com. The results of the analysis of the MG-ADL and QMG from gMG Study 1 are shown in Table 21. In clinical studies, 2 out of 196 PNH patients developed serious meningococcal infections while receiving treatment with Soliris; both had been vaccinated [see Adverse Reactions (6.1)]. Overall, 96 of the 97 enrolled patients completed the study (one patient died following a thrombotic event). Under the Soliris REMS, prescribers must enroll in the program. The median patient age was 6.5 (range: 5 months to 17 years). Soliris is a medicine used to treat adults and children with paroxysmal nocturnal haemoglobinuria (PNH) and atypical haemolytic uraemic syndrome (aHUS). If you are an adult, you will usually receive a Soliris infusion by your doctor: After each infusion, you should be monitored for one hour for infusion-related reactions.