(rvulizumb-cwvz) for the tretment of dult ptients with proxysml nocturnl hemoglobinuri (PNH) is dministered once every 8 weeks PATIENTS STARTING WITH NO PRIOR TREATMENT FOR PNH THE RECOMMENDED DOSING REGIMEN IN ADULTS WITH PNH CONSISTS OF A LOADING DOSE FOLLOWED BY MAINTENANCE DOSES 1 PATIENTS SWITCHING FROM ECULIZUMAB TO Strting 2 weeks fter the initil loding dose, mintennce doses re dministered once every 8 weeks. Loding dose of should be dministered 2 weeks fter the lst eculizumb infusion. Mintennce doses re dministered once every 8 weeks, strting 2 weeks fter the loding dose. WEIGHT-BASED DOSING 1,b-d Body Weight Rnge Volume (Vils) Volume of 0.9% NCl Totl Volume (Finl Loding Dose) Mximum Infusion Rte (ml/hr) Loding Dose Administrtion 40 to <60 kg 60 to <100 kg 100 kg 240 ml (8 vils) 270 ml (9 vils) 300 ml (10 vils) 240 ml 270 ml 300 ml 480 ml (2400 mg) 540 ml (2700 mg) 600 ml (3000 mg) 252 317 333 40 to <60 kg 300 ml (10 vils) 300 ml 600 ml (3000 mg) 257 Mintennce Dose Administrtion 60 to <100 kg 100 kg 330 ml (11 vils) 360 ml (12 vils) 330 ml 360 ml 660 ml (3300 mg) 720 ml (3600 mg) 330 327 Withdrw the clculted volume of from the pproprite number of vils nd dilute into n infusion bg using sterile 0.9% NCl injection 1 Gently mix solution nd infuse immeditely 1,e is infused every 8 weeks following loding dose. b Dosing schedule is llowed to occsionlly vry by ±7 dys of the scheduled infusion dy (except for the first mintennce dose of ), but the subsequent dose should be dministered ccording to the originl schedule. 1 c Mesure ptient s body weight prior to ech preprtion nd infusion of. 1 d Sterile single-use vils should only be diluted using 0.9% Sodium Chloride Injection, USP. 1 e Allow dmixture to rech room temperture nd infuse through 0.22-micron filter. The dmixture must not be heted in microwve or with ny other het source. 1 offers weight-bsed dosing with only 6 infusions per yer 1,f f my be infused up to 7 times per yer, depending on when ptient receives 1-time loding dose t the beginning of tretment. INDICATION is indicted for the tretment of dult ptients with proxysml nocturnl hemoglobinuri (PNH). IMPORTANT SAFETY INFORMATION WARNING: SERIOUS MENINGOCOCCAL INFECTIONS Life-thretening meningococcl infections/sepsis hve occurred in ptients treted with. Meningococcl infection my become rpidly life-thretening or ftl if not recognized nd treted erly. Comply with the most current Advisory Committee on Immuniztion Prctices (ACIP) recommendtions for meningococcl vccintion in ptients with complement deficiencies. Immunize ptients with meningococcl vccines t lest 2 weeks prior to dministering the first dose of, unless the risks of delying therpy outweigh the risk of developing meningococcl infection [see Wrnings nd Precutions for dditionl guidnce on the mngement of the risk of meningococcl infection]. Vccintion reduces, but does not eliminte, the risk of meningococcl infections. Monitor ptients for erly signs of meningococcl infections nd evlute immeditely if infection is suspected. is vilble only through restricted progrm under Risk Evlution nd Mitigtion Stgy (REMS). Under the REMS, prescribers must enroll in the progrm [see Wrnings nd Precutions]. Enrollment in the REMS progrm nd dditionl informtion re vilble by telephone: 1-888-765-4747 or t www.ultomirisrems.com. Plese see Importnt Sfety Informtion on the reverse side. Plese see ccompnying full prescribing informtion for, including Boxed WARNING, regrding serious nd life-thretening meningococcl infections/sepsis.
INDICATION is indicted for the tretment of dult ptients with proxysml nocturnl hemoglobinuri (PNH). IMPORTANT SAFETY INFORMATION WARNING: SERIOUS MENINGOCOCCAL INFECTIONS Life-thretening meningococcl infections/sepsis hve occurred in ptients treted with. Meningococcl infection my become rpidly life-thretening or ftl if not recognized nd treted erly. Comply with the most current Advisory Committee on Immuniztion Prctices (ACIP) recommendtions for meningococcl vccintion in ptients with complement deficiencies. Immunize ptients with meningococcl vccines t lest 2 weeks prior to dministering the first dose of, unless the risks of delying therpy outweigh the risk of developing meningococcl infection [see Wrnings nd Precutions for dditionl guidnce on the mngement of the risk of meningococcl infection]. Vccintion reduces, but does not eliminte, the risk of meningococcl infections. Monitor ptients for erly signs of meningococcl infections nd evlute immeditely if infection is suspected. is vilble only through restricted progrm under Risk Evlution nd Mitigtion Stgy (REMS). Under the REMS, prescribers must enroll in the progrm [see Wrnings nd Precutions]. Enrollment in the REMS progrm nd dditionl informtion re vilble by telephone: 1-888-765-4747 or t www.ultomirisrems.com. CONTRAINDICATIONS is contrindicted inptients with unresolved serious Neisseri meningitidis infection. WARNINGS AND PRECAUTIONS Serious Meningococcl Infections Life-thretening meningococcl infections hve occurred in ptients treted with. The use of increses ptient s susceptibility to serious meningococcl infections (septicemi nd/or meningitis). Meningococcl disese due to ny serogroup my occur. Vccinte for meningococcl disese ccording to the most current Advisory Committee on Immuniztion Prctices (ACIP) recommendtions for ptients with complement deficiencies. Revccinte ptients in ccordnce with ACIP recommendtions considering the durtion of therpy. Immunize ptients without history of meningococcl vccintion t lest 2 weeks prior to receiving the first dose of. If urgent therpy is indicted in n unvccinted ptient, dminister meningococcl vccine(s) s soon s possible nd provide ptients with 2 weeks of ntibcteril drug prophylxis. In clinicl studies, 59 ptients with PNH were treted with less thn 2 weeks fter meningococcl vccintion. All of these ptients received ntibiotics for prophylxis of meningococcl infection until t lest 2 weeks fter meningococcl vccintion. The benefits nd risks of ntibiotic prophylxis for prevention of meningococcl infections in ptients receiving hve not been estblished. Vccintion reduces, but does not eliminte, the risk of meningococcl infections. In clinicl studies, 3 out of 261 PNH ptients developed serious meningococcl infections/ sepsis while receiving tretment with ; ll 3 hd been vccinted. These 3 ptients recovered while continuing tretment with. Closely monitor ptients for erly signs nd symptoms of meningococcl infection nd evlute ptients immeditely if infection is suspected. Inform ptients of these signs nd symptoms nd steps to be tken to seek immedite medicl cre. Meningococcl infection my become rpidly life-thretening or ftl if not recognized nd treted erly. Consider discontinution of in ptients who re undergoing tretment for serious meningococcl infection. REMS Due to the risk of meningococcl infections, is vilble only through restricted progrm under Risk Evlution nd Mitigtion Stgy (REMS). Under the REMS, prescribers must enroll in the progrm. Prescribers must counsel ptients bout the risk of meningococcl infection/sepsis, provide the ptients with the REMS eductionl mterils, nd ensure ptients re vccinted with meningococcl vccines. Enrollment in the REMS nd dditionl informtion re vilble by telephone: 1-888-765-4747 or t www.ultomirisrems.com. Other Infections blocks terminl complement ctivtion; therefore ptients my hve incresed susceptibility to encpsulted bcteri infections, especilly infections cused by Neisseri meningitis but lso Streptococcus pneumonie, Hemophilus influenze, nd to lesser extent, Neisseri gonorrhoee. If therpy is dministered to ptients with ctive systemic infections, monitor closely for signs nd symptoms of worsening infection. Monitoring Disese Mnifesttions fter Discontinution After discontinuing tretment with, closely monitor for signs nd symptoms of hemolysis, identified by elevted LDH long with sudden decrese in PNH clone size or hemoglobin, or re-ppernce of symptoms such s ftigue, hemoglobinuri, bdominl pin, shortness of breth (dyspne), mjor dverse vsculr event (including thrombosis), dysphgi, or erectile dysfunction. Monitor ny ptient who discontinues for t lest 16 weeks to detect hemolysis nd other rections. If signs nd symptoms of hemolysis occur fter discontinution, including elevted LDH, consider restrting tretment with. Thromboembolic Event Mngement The effect of withdrwl of nticogulnt therpy during tretment hs not been estblished. Therefore, tretment with should not lter nticogulnt mngement. Infusion Rections Administrtion of my result in infusion rections. In clinicl trils, 3 out of 222 ptients with PNH treted with experienced infusion rections (lower bck pin, drop in blood pressure nd infusion-relted pin) during dministrtion. These rections did not require discontinution of. Interrupt infusion nd institute pproprite supportive mesures if signs of crdiovsculr instbility or respirtory compromise occur. Adverse Rections Adverse rections reported in 5% or more of ptients treted with vs. ws Upper respirtory trct infection (39% vs 39%), Hedche (32% vs. 26%), Dirrhe (9% vs. 5%), Nuse (9% vs. 9%), Pyrexi (7% vs 8%), Pin in extremity (6% vs. 5%), Abdominl pin (6% vs. 7%), Dizziness (5% vs. 6%), Arthrlgi (5% vs. 5%). The serious dverse rections in ptients treted with included hyperthermi nd pyrexi. Plese see ccompnying full prescribing informtion for, including Boxed WARNING, regrding serious nd life-thretening meningococcl infections/sepsis. Reference: 1. [prescribing informtion]. Boston, MA: Alexion Phrmceuticls; 2018. Alexion is registered trdemrk of Alexion Phrmceuticls, Inc. is trdemrk of Alexion Phrmceuticls, Inc. 2018, Alexion Phrmceuticls, Inc. All rights reserved. US/ULT-PNH/0003
HIGHLIGHTS OF PRESCRIBING INFORMATION These highlights do not include ll the informtion needed to use sfely nd effectively. See full prescribing informtion for. (rvulizumb-cwvz) injection, for intrvenous use Initil U.S. Approvl: 2018 WARNING: SERIOUS MENINGOCOCCAL INFECTIONS See full prescribing informtion for complete boxed wrning Life-thretening meningococcl infections/sepsis hve occurred in ptients treted with nd my become rpidly life-thretening or ftl if not recognized nd treted erly (5.1). Comply with the most current Advisory Committee on Immuniztion Prctices (ACIP) recommendtions for meningococcl vccintion in ptients with complement deficiencies (5.1). Immunize ptients with meningococcl vccines t lest 2 weeks prior to dministering the first dose of, unless the risks of delying therpy outweigh the risks of developing meningococcl infection. (See Wrnings nd Precutions (5.1) for dditionl guidnce on the mngement of the risk of meningococcl infection.)vccintion reduces, but does not eliminte, the risk of meningococcl infection. Monitor ptients for erly signs of meningococcl infections, nd evlute immeditely if infection is suspected. is vilble only through restricted progrm under Risk Evlution nd Mitigtion Stgy (REMS). Under the REMS, prescribers must enroll in the progrm (5.1). INDICATIONS AND USAGE is complement inhibitor indicted for the tretment of dult ptients with proxysml nocturnl hemoglobinuri (PNH). (1) Weight-Bsed Dosge Regimen: (2.1) Body Weight Rnge (kg) Loding Dose (mg) Mintennce Dose (mg) greter 40 to less thn 60 2,400 3,000 60 to less thn 100 2,700 3,300 100 3,000 3,600 See Full Prescribing Informtion for importnt preprtion nd dministrtion instructions (2.2, 2.3). DOSAGE FORMS AND STRENGTHS Injection: 300 mg/30 ml (10 mg/ml) in single-dose vil (3). CONTRAINDICATIONS is contrindicted in ptients with unresolved Neisseri Meningitidis infection (4). WARNINGS AND PRECAUTIONS Use cution when dministering to ptients with ny other systemic infection (5.2). ADVERSE REACTIONS The most frequent dverse drug rections (>10%) were upper respirtory infection nd hedche (6.1). To report SUSPECTED ADVERSE REACTIONS, contct Alexion Phrmceuticls, Inc. t) 1-844-259-6783- or FDA t 1-800-FDA-1088 or www.fd.gov/medwtch. See 17 PATIENT COUNSELING INFORMATION nd Mediction Guide. Revised: 12/2018 Only dminister s n intrvenous infusion. DOSAGE AND ADMINISTRATION FULL PRESCRIBING INFORMATION: CONTENTS* WARNING: SERIOUS MENINGOCOCCAL INFECTIONS 1 INDICATIONS AND USAGE 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Vccintion nd Prophylxis 2.2 Recommended Weight-Bsed Dosge Regimen 2.3 Preprtion nd Administrtion 3 DOSAGE FORMS AND STRENGTHS 4 CONTRAINDICATIONS 5 WARNINGS AND PRECAUTIONS 5.1 Serious Meningococcl Infections 5.2 Other Infections 5.3 Monitoring Disese Mnifesttions fter Discontinution 5.4 Thromboembolic Event Mngement 5.5 Infusion Rections 6 ADVERSE REACTIONS 6.1 Clinicl Tril Experience 6.2 Immunogenicity 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnncy 8.2 Lcttion 8.4 Peditric Use 8.5 Geritric Use 11 DESCRIPTION 12 CLINICAL PHARMACOLOGY 12.1 Mechnism of Action 12.2 Phrmcodynmics 12.3 Phrmcokinetics 13 NONCLINICAL TOXICOLOGY 13.1 Crcinogenesis, Mutgenesis, Impirment of Fertility 14 CLINICAL STUDIES 14.1 Study in Complement-Inhibitor Nïve Ptients with PNH 14.2 Study in -Experienced Ptients with PNH 16 HOW SUPPLIED/STORAGE AND HANDLING 17 PATIENT COUNSELING INFORMATION *Sections or subsections omitted from the full prescribing informtion re not listed FULL PRESCRIBING INFORMATION WARNING: SERIOUS MENINGOCOCCAL INFECTIONS Life-thretening meningococcl infections/sepsis hve occurred in ptients treted with. Meningococcl infection my become rpidly life-thretening or ftl if not recognized nd treted erly [see Wrnings nd Precutions (5.1)]. Comply with the most current Advisory Committee on Immuniztion Prctices (ACIP) recommendtions for meningococcl vccintion in ptients with complement deficiencies. Immunize ptients with meningococcl vccines t lest 2 weeks prior to dministering the first dose of, unless the risks of delying therpy outweigh the risk of developing meningococcl infection [see Wrnings nd Precutions (5.1) for dditionl guidnce on the mngement of the risk of meningococcl infection]. Vccintion reduces, but does not eliminte, the risk of meningococcl infections. Monitor ptients for erly signs of meningococcl infections nd evlute immeditely if infection is suspected. is vilble only through restricted progrm under Risk Evlution nd Mitigtion Stgy (REMS). Under the REMS, prescribers must enroll in the progrm [see Wrnings nd Precutions (5.1)]. Enrollment in the REMS progrm nd dditionl informtion re vilble by telephone: 1-844-259-6783 or t www.ultomirisrems.com. 1 INDICATIONS AND USAGE is indicted for the tretment of dult ptients with proxysml nocturnl hemoglobinuri (PNH). 2 DOSAGE AND ADMINISTRATION 2.1 Recommended Vccintion nd Prophylxis Vccinte ptients for meningococcl disese ccording to current ACIP guidelines to reduce the risk of serious infection [see Wrnings nd Precutions (5.1, 5.2)]. Provide 2 weeks of ntibcteril drug prophylxis to ptients if must be initited immeditely nd vccines re dministered less thn 2 weeks before strting therpy. Helthcre professionls who prescribe must enroll in the REMS [see Wrnings nd Precutions (5.1)]. 2.2 Recommended Weight-Bsed Dosge Regimen The recommended dosing regimen for dult ptients ( 18 yers of ge) with PNH consists of loding dose followed by mintennce dosing, dministered by intrvenous infusion. Administer the doses bsed on the ptient s body weight, s shown in Tble 1. Strting 2 weeks fter the loding dose dministrtion, begin 1 mintennce doses t once every 8-week intervl. The dosing schedule is llowed to occsionlly vry within 7 dys of the scheduled infusion dy (except for the first mintennce dose of ) but the subsequent dose should be dministered ccording to the originl schedule. For ptients switching from eculizumb to, dminister the loding dose of 2 weeks fter the lst eculizumb infusion, nd then dminister mintennce doses once every 8 weeks, strting 2 weeks fter loding dose dministrtion, s shown in Tble 1. Tble 1: Weight-Bsed Dosing Regimen Body Weight Rnge (kg) Loding Dose (mg) Mintennce Dose (mg) 40 to less thn 60 2,400 3,000 60 to less thn 100 2,700 3,300 100 3,000 3,600 2.3 Preprtion nd Administrtion Preprtion of Ech vil of is intended for single-dose only. requires dilution to finl concentrtion of 5 mg/ml. Use septic technique to prepre s follows: 1. The number of vils to be diluted is determined bsed on the individul ptient s weight nd the prescribed dose [see Dosge nd Administrtion (2.2)]. 2. Prior to dilution, visully inspect the solution in the vils; the solution should be free of ny prticulte mtter or precipittion. Do not use if there is evidence of prticulte mtter or precipittion. 3. Withdrw the clculted volume of from the pproprite number of vils nd dilute in n infusion bg using 0.9% Sodium Chloride Injection, USP to finl concentrtion of 5 mg/ml. Refer to the dministrtion reference tbles below. The product should be mixed gently. Do not shke. Protect from light. Do not freeze. 4. Administer the prepred solution immeditely following preprtion. Refer to the dministrtion reference tbles below for minimum infusion durtion. Infusion must be dministered through 0.22 micron filter. 5. If the diluted infusion solution is not used immeditely, storge under refrigertion t 2 C 8 C (36 F 46 F) must not exceed 24 hours tking into ccount the expected infusion time. Once removed from refrigertion, dminister the diluted infusion solution within 6 hours.
Administrtion of Only dminister s n intrvenous infusion. Dilute to finl concentrtion of 5 mg/ml. Administer only through 0.22 micron filter. Tble 2: Body Weight Rnge (kg) 40 to less thn 60 60 to less thn 100 100 Loding Dose Administrtion Reference Tble Loding Dose (mg) Body weight t time of tretment Volume (ml) Volume of NCl Diluent b (ml) Totl Volume (ml) Mximum Infusion Rte (ml/hr) 2,400 240 240 480 252 2,700 270 270 540 317 3,000 300 300 600 333 b Dilute only using 0.9% Sodium Chloride Injection, USP. Tble 3: Body Weight Rnge (kg) 40 to less thn 60 60 to less thn 100 100 Mintennce Dose Administrtion Reference Tble Mintennce Dose (mg) Body weight t time of tretment Volume (ml) Volume of NCl Diluent b (ml) Totl Volume (ml) Mximum Infusion Rte (ml/hr) 3,000 300 300 600 257 3,300 330 330 660 330 3,600 360 360 720 327 b Dilute only using 0.9% Sodium Chloride Injection, USP. Prior to dministrtion, llow the dmixture to djust to room temperture (18-25 C, 64-77 F). Do not het the dmixture in microwve or with ny het source other thn mbient ir temperture. Prenterl drug products should be inspected visully for prticulte mtter nd discolortion prior to dministrtion, whenever solution nd continer permit. If n dverse rection occurs during the dministrtion of, the infusion my be slowed or stopped t the discretion of the physicin. Monitor the ptient for t lest one hour following completion of the infusion for signs or symptoms of n infusion rection. 3 DOSAGE FORMS AND STRENGTHS Injection: 300 mg/30 ml (10 mg/ml) s cler to trnslucent, slight whitish color solution in single-dose vil. 4 CONTRAINDICATIONS is contrindicted in ptients with unresolved Neisseri meningitidis infection [see Wrnings nd Precutions (5.1)]. 5 WARNINGS AND PRECAUTIONS 5.1 Serious Meningococcl Infections Risk nd Prevention Life-thretening meningococcl infections hve occurred in ptients treted with. The use of increses ptient s susceptibility to serious meningococcl infections (septicemi nd/or meningitis). Meningococcl disese due to ny serogroup my occur. Vccinte for meningococcl disese ccording to the most current Advisory Committee on Immuniztion Prctices (ACIP) recommendtions for ptients with complement deficiencies. Revccinte ptients in ccordnce with ACIP recommendtions considering the durtion of therpy. Immunize ptients without history of meningococcl vccintion t lest 2 weeks prior to receiving the first dose of. If urgent therpy is indicted in n unvccinted ptient, dminister meningococcl vccine(s) s soon s possible nd provide ptients with 2 weeks of ntibcteril drug prophylxis. In clinicl studies, 59 ptients with PNH were treted with less thn 2 weeks fter meningococcl vccintion. All of these ptients received ntibiotics for prophylxis of meningococcl infection until t lest 2 weeks fter meningococcl vccintion. The benefits nd risks of ntibiotic prophylxis for prevention of meningococcl infections in ptients receiving hve not been estblished. Vccintion reduces, but does not eliminte, the risk of meningococcl infections. In clinicl studies, 3 out of 261 PNH ptients developed serious meningococcl infections/sepsis while receiving tretment with ; ll 3 hd been vccinted. These 3 ptients recovered while continuing tretment with. Closely monitor ptients for erly signs nd symptoms of meningococcl infection nd evlute ptients immeditely if infection is suspected. Inform ptients of these signs nd symptoms nd steps to be tken to seek immedite medicl cre. Meningococcl infection my become rpidly life-thretening or ftl if not recognized nd treted erly. Consider discontinution of in ptients who re undergoing tretment for serious meningococcl infection. REMS Due to the risk of meningococcl infections, is vilble only through restricted progrm under Risk Evlution nd Mitigtion Stgy (REMS). Under the REMS, prescribers must enroll in the progrm. Prescribers must counsel ptients bout the risk of meningococcl infection/sepsis, provide the ptients with the REMS eductionl mterils, nd ensure ptients re vccinted with meningococcl vccines. Enrollment in the REMS nd dditionl informtion re vilble by telephone: 1-888-765-4747 or t www.ultomirisrems.com. 2 5.2 Other Infections blocks terminl complement ctivtion; therefore, ptients my hve incresed susceptibility to encpsulted bcteri infections, especilly infections cused by Neisseri meningitidis but lso Streptococcus pneumonie, Hemophilus influenze, nd to lesser extent, Neisseri gonorrhoee. If therpy is dministered to ptients with ctive systemic infections, monitor closely for signs nd symptoms of worsening infection. 5.3 Monitoring Disese Mnifesttions fter Discontinution After discontinuing tretment with, closely monitor for signs nd symptoms of hemolysis, identified by elevted LDH long with sudden decrese in PNH clone size or hemoglobin, or re-ppernce of symptoms such s ftigue, hemoglobinuri, bdominl pin, shortness of breth (dyspne), mjor dverse vsculr event (including thrombosis), dysphgi, or erectile dysfunction. Monitor ny ptient who discontinues for t lest 16 weeks to detect hemolysis nd other rections. If signs nd symptoms of hemolysis occur fter discontinution, including elevted LDH, consider restrting tretment with. 5.4 Thromboembolic Event Mngement The effect of withdrwl of nticogulnt therpy during tretment hs not been estblished. Therefore, tretment with should not lter nticogulnt mngement. 5.5 Infusion Rections Administrtion of my result in infusion rections. In clinicl trils, 3 out of 222 ptients with PNH treted with experienced infusion rections (lower bck pin, drop in blood pressure nd infusionrelted pin) during dministrtion. These rections did not require discontinution of. Interrupt infusion nd institute pproprite supportive mesures if signs of crdiovsculr instbility or respirtory compromise occur. 6 ADVERSE REACTIONS The following cliniclly significnt dverse rections re discussed in greter detil in other sections of the lbeling: Serious Meningococcl Infections [see Wrnings nd Precutions (5.1)] Other Infections [see Wrnings nd Precutions (5.2)] Monitoring PNH Disese Mnifesttions fter Discontinution [see Wrnings nd Precutions (5.3)] Infusion Rections [see Wrnings nd Precutions (5.5)] 6.1 Clinicl Tril Experience Becuse clinicl trils re conducted under widely vrying conditions, dverse rection s observed in the clinicl trils of drug cnnot be directly compred to s in the clinicl trils of nother drug nd my not reflect the s observed in prctice. The dt described below reflect exposure of 441 dult ptients with PNH in Phse 3 studies who received (n 222) or eculizumb (n 219) t the recommended dosing regimens with medin tretment durtion of 6 months for nd 6 months for eculizumb. The most frequent dverse drug rections (>10%) with were upper respirtory trct infection nd hedche. Tble 4 describes dverse rections tht occurred t of 5% or more mong ptients treted with. Serious dverse rections were reported in 15 (6.8%) ptients receiving. The serious dverse rections in ptients treted with included hyperthermi nd pyrexi. No serious dverse rection ws reported in more thn 1 ptient treted with. One ftl cse of sepsis ws identified in ptient treted with. Tble 4: Adverse Rections Reported In 5% or More of Treted Ptients in Complement Inhibitor Nïve nd -Experienced Ptients with PNH Body System Adverse Rection (n222) Number of Ptients (n219) Gstrointestinl disorders Dirrhe 19 (9) 12 (5) Nuse 19 (9) 19 (9) Abdominl pin 13 (6) 16 (7) Generl Disorders nd Administrtion Site Conditions Pyrexi 15 (7) 18 (8) Infections nd Infesttions Upper respirtory trct infection 86 (39) 86 (39) Musculoskeletl nd Connective Tissue Disorders Pin in extremity 14 (6) 11 (5) Arthrlgi 11 (5) 12 (5) Nervous System Disorders Hedche 71 (32) 57 (26) Dizziness 12 (5) 14 (6) Grouped term includes: Nsophryngitis, Upper respirtory trct infection, Orophryngel pin, Virl upper respirtory trct infection, Rhinitis, Respirtory trct infection, Rhinorrhoe, Phryngitis, nd Upper respirtory trct inflmmtion 6.2 Immunogenicity As with ll therpeutic proteins, there is potentil for immunogenicity. The detection of ntibody formtion is highly dependent on the sensitivity nd specificity of the ssy. Additionlly, the observed incidence of ntibody (including neutrlizing ntibodies) positivity in n ssy my be influenced by severl fctors including ssy methodology, smple hndling, timing of smple collection, concomitnt medictions nd underlying disese. For these resons, comprison of the incidence of ntibodies in the studies described below with the incidence of ntibodies in other studies or to other rvulizumb products my be misleding. The immunogenicity of rvulizumb-cwvz hs been evluted using n enzyme linked immunosorbent ssy (ELISA) for the detection of binding nti-rvulizumb-cwvz ntibodies. For ptients whose ser tested positive in the screening immunossy, n in vitro biologicl ssy ws performed to detect neutrlizing ntibodies. In clinicl studies of ptients with PNH, tretment-emergent ntibodies to rvulizumb-cwvz were detected in 1 of 206 (0.5%) ptients. No pprent correltion of ntibody development to ltered phrmcokinetic profile, clinicl response, or dverse events ws observed. 8 USE IN SPECIFIC POPULATIONS 8.1 Pregnncy Risk Summry There re no vilble dt on use in pregnnt women to inform drug-ssocited risk of mjor birth defects, miscrrige, or dverse mternl or fetl outcomes. There re risks to the mother nd fetus ssocited with untreted proxysml nocturnl hemoglobinuri (PNH) in pregnncy (see Clinicl Considertions). Animl studies using mouse nlogue of the rvulizumb-cwvz molecule (murine nti-c5 ntibody) showed incresed s of developmentl bnormlities nd n incresed of ded nd moribund offspring t doses 0.8-2.2 times the humn dose (see Dt).
The estimted bckground risk of mjor birth defects nd miscrrige for the indicted popultion is unknown. All pregnncies hve bckground risk of birth defect, loss, or other dverse outcomes. In the U.S. generl popultion, the estimted bckground risk of mjor birth defects nd miscrrige in cliniclly recognized pregnncies is 2-4% nd 15-20%, respectively. Clinicl Considertions Disese-ssocited mternl nd/or fetl/neontl risk PNH in pregnncy is ssocited with dverse mternl outcomes, including worsening cytopenis, thrombotic events, infections, bleeding, miscrriges, nd incresed mternl mortlity, nd dverse fetl outcomes, including fetl deth nd premture delivery. Dt Animl Dt Animl reproduction studies were conducted in mice using doses of murine nti-c5 ntibody tht pproximted 1-2.2 times (loding dose) nd 0.8-1.8 times (mintennce dose) the recommended humn dose, bsed on body weight comprison. When niml exposure to the ntibody occurred in the time period from before mting until erly gesttion, no decrese in fertility or reproductive performnce ws observed. When mternl exposure to the ntibody occurred during orgnogenesis, two cses of retinl dysplsi nd one cse of umbilicl herni were observed mong 230 offspring born to mothers exposed to the higher ntibody dose; however, the exposure did not increse fetl loss or neontl deth. When mternl exposure to the ntibody occurred in the time period from implnttion through wening, higher number of mle offspring becme moribund or died (1/25 controls, 2/25 low dose group, 5/25 high dose group). Surviving offspring hd norml development nd reproductive function. Humn IgG re known to cross the humn plcentl brrier, nd thus my potentilly cuse terminl complement inhibition in the fetl circultion. 8.2 Lcttion Risk summry There re no dt on the presence of rvulizumb-cwvz in humn milk, the effect on the brestfed child, or the effect on milk production. Since mny medicinl products nd immunoglobulins re secreted into humn milk, nd becuse of the potentil for serious dverse rections in nursing child, brestfeeding should be discontinued during tretment nd for 8 months fter the finl dose. 8.4 Peditric Use The sfety nd efficcy of in peditric ptients hve not been estblished. 8.5 Geritric Use Clinicl studies of did not include sufficient numbers of subjects ged 65 nd over to determine whether they respond differently from younger subjects. Other reported clinicl experience hs not identified differences in responses between the elderly nd younger ptients. 11 DESCRIPTION Rvulizumb-cwvz, complement inhibitor, is humnized monoclonl ntibody (mab) produced in Chinese hmster ovry (CHO) cells. Rvulizumb-cwvz consists of 2 identicl 448 mino cid hevy chins nd 2 identicl 214 mino cid light chins nd hs moleculr weight of pproximtely 148 kd. The constnt regions of rvulizumb-cwvz include the humn kpp light chin constnt region, nd the protein engineered IgG2/4 hevy chin constnt region. The hevy chin CH1 domin, hinge region, nd the first 5 mino cids of the CH2 domin mtch the humn IgG2 mino cid sequence, residues 6 to 36 in the CH2 region (common to both humn IgG2 nd IgG4 mino cid sequences), while the reminder of the CH2 domin nd the CH3 domin mtch the humn IgG4 mino cid sequence. The hevy nd light chin vrible regions tht form the humn C5 binding site consist of humn frmework regions grfted to murine complementrity-determining regions. (rvulizumb-cwvz) injection is sterile, cler to trnslucent, slight whitish color, preservtive-free solution for intrvenous use. Ech single-dose vil contins 300 mg rvulizumb-cwvz t concentrtion of 10 mg/ml with ph of 7.0. Ech ml lso contins polysorbte 80 (0.2 mg) (vegetble origin), sodium chloride (8.77 mg), sodium phosphte dibsic (1.78 mg), sodium phosphte monobsic (0.46 mg), nd Wter for Injection, USP. 12 CLINICAL PHARMACOLOGY 12.1 Mechnism of Action Rvulizumb-cwvz is terminl complement inhibitor tht specificlly binds to the complement protein C5 with high ffinity, thereby inhibiting its clevge to C5 (the proinflmmtory nphyltoxin) nd C5b (the inititing subunit of the terminl complement complex [C5b-9]) nd preventing the genertion of the terminl complement complex C5b9. inhibits terminl complement-medited intrvsculr hemolysis in ptients with PNH. 12.2 Phrmcodynmics Immedite nd complete inhibition of serum free C5 (concentrtion of less thn 0.5 mcg/ml) ws observed by the end of the first infusion nd sustined throughout the entire 26-week tretment period in ll ptients, both complement-inhibitor nïve nd previously treted with eculizumb. The extent nd durtion of the phrmcodynmic response in ptients with PNH were exposure dependent for. Free C5 levels of <0.5 mcg/ml were correlted with mximl intrvsculr hemolysis control nd complete terminl complement inhibition. Complete terminl complement inhibition following initition of tretment led to normliztion of serum LDH by week 4 in complement-inhibitor nïve ptients, nd mintined LDH normliztion in ptients previously treted with eculizumb [see Clinicl Studies (14)]. 12.3 Phrmcokinetics Rvulizumb-cwvz phrmcokinetics increse proportionlly over dose rnge of 200 to 5400 mg. Rvulizumb-cwvz C mx nd C trough prmeters re presented in Tble 5. Tble 5: Men ± SD (%CV) Phrmcokinetic Prmeters of in Ptients with PNH who re Complement Inhibitor-Nïve nd Ptients Previously Treted with C mx (mcg/ml) C trough (mcg/ml) N Complement Inhibitor-Nïve N Previously Treted with LD 125 771 ± 166 (21.5) 95 843 ± 204 (24.1) MD 124 1379 ± 276 (20.0) 95 1386 ± 268 (19.4) LD 125 391 ± 137 (35.0) 96 405 ± 121 (29.9) MD 124 473 ± 158 (33.4) 95 501 ± 143 (28.6) Elimintion The men (SD) terminl elimintion hlf-life nd clernce of rvulizumb-cwvz in ptients with PNH re 49.7 (8.9) dys nd 0.08 (0.022) L/dy respectively. Specific Popultions No cliniclly significnt differences in the phrmcokinetics of rvulizumb-cwvz were observed bsed on sex, ge (18 to 83 yers), rce, heptic impirment, or mild to mode renl impirment (egfr 30 to 89 ml/ min/1.73 m 2, estimted by MDRD). The effect of severe renl impirment (egfr 15 to 29 ml/min/1.73 m 2, estimted by MDRD) on rvulizumb-cwvz phrmcokinetics is unknown. Body weight ws significnt covrite on the phrmcokinetics of rvulizumb-cwvz. 13 NONCLINICAL TOXICOLOGY 13.1 Crcinogenesis, Mutgenesis, Impirment of Fertility Long-term niml crcinogenicity studies of rvulizumb-cwvz hve not been conducted. Genotoxicity studies hve not been conducted with rvulizumb-cwvz. Effects of rvulizumb-cwvz upon fertility hve not been studied in nimls. Intrvenous injections of mle nd femle mice with murine nti-c5 ntibody t up to 0.8-2.2 times the equivlent of the clinicl dose of hd no dverse effects on mting or fertility. 14 CLINICAL STUDIES The sfety nd efficcy of in ptients with PNH ws ssessed in two open-lbel, rndomized, ctivecontrolled, non-inferiority Phse 3 studies: PNH Study 301 nd PNH Study 302. Study 301 enrolled ptients with PNH who were complement inhibitor nïve nd hd ctive hemolysis. Study 302 enrolled ptients with PNH who were cliniclly stble fter hving been treted with eculizumb for t lest the pst 6 months. In both studies, ws dosed intrvenously in ccordnce with the weight-bsed dosing described in Section 2.1 (4 infusions of over 26 weeks) bove. ws dministered on Dys 1, 8, 15, nd 22, followed by mintennce tretment with 900 mg of eculizumb on Dy 29 nd every 2 weeks (q2w) therefter for totl of 26 weeks of tretment, ccording to the pproved dosing regimen of eculizumb which ws the stndrd-of-cre for PNH t the time of studies. Ptients were vccinted ginst meningococcl infection prior to or t the time of inititing tretment with or eculizumb, or received prophylctic tretment with pproprite ntibiotics until 2 weeks fter vccintion. Prophylctic tretment with pproprite ntibiotics beyond 2 weeks fter vccintion ws t the discretion of the provider. 14.1 Study in Complement-Inhibitor Nïve Ptients with PNH The Complement-Inhibitor Nïve Study [ALXN1210-PNH-301; NCT02946463] ws 26-week, multicenter, open-lbel, rndomized, ctive-controlled, non-inferiority Phse 3 study conducted in 246 ptients nïve to complement inhibitor tretment prior to study entry. Ptients with PNH with flow cytometric confirmtion of t lest 5% PNH cells were rndomized 1:1 to either or eculizumb. The men totl PNH grnulocyte clone size ws 85%, the men totl PNH monocyte clone size ws 88%, nd the men totl PNH RBC clone size ws 39%. Ninety-eight percent of ptients hd documented PNH-ssocited condition dignosed prior to enrollment on the tril: nemi (85%), hemoglobinuri (63%), history of plstic nemi (32%), history of renl filure (12%), myelodysplstic syndrome (5%), pregnncy (3%), nd other (16%). Mjor bseline chrcteristics were blnced between tretment groups. Tble 6: Bseline Chrcteristics in the Complement-Inhibitor Nïve Study Prmeter Age (yers) t first infusion in study Sttistics Men (SD) Min, mx (N 125) 44.8 (15.2) 18, 83 (N 121) 46.2 (16.2) 18, 86 Sex Mle 65 (52.0) 69 (57.0) Rce Asin White Blck or Africn Americn Americn Indin or Alsk Ntive Other Not reported Pre-tretment LDH levels (U/L) Units of prbc/whole blood trnsfused within 12 months prior to first dose Antithrombotic gents used within 28 dys prior to first dose Medin Min, mx Medin Min, mx 72 (57.6) 43 (34.4) 2 ( 1.6) 1 ( 0.8) 4 ( 3.2) 3 ( 2.4) 1513.5 (378.0, 3759.5) 6.0 (1, 44) 57 (47.1) 51 (42.1) 4 ( 3.3) 1 ( 0.8) 4 ( 3.3) 4 ( 3.3) 1445.0 (423.5, 3139.5) 6.0 (1, 32) 22 (17.6) 22 (18.2) Ptients with history of MAVE b 17 (13.6) 25 (20.7) Ptients with history of thrombosis 17 (13.6) 20 (16.5) Ptients with concomitnt nticogulnt tretment 23 (18.4) 28 (23.1) Other s specified on cse report form included thrombocytopeni, chronic kidney disese, nd pncytopeni, s well s number of other conditions. b MAVE mjor dverse vsculr event Efficcy ws estblished bsed upon trnsfusion voidnce nd hemolysis s directly mesured by normliztion of LDH levels. Trnsfusion voidnce ws defined s ptients who did not receive trnsfusion nd not meet the protocol specified guidelines for trnsfusion from bseline up to Dy 183. Supportive efficcy dt included the percent chnge from bseline in LDH levels, the proportion of ptients with brekthrough hemolysis defined s t lest one new or worsening symptom or sign of intrvsculr hemolysis in the presence of elevted LDH 2 ULN, fter prior LDH reduction to < 1.5 ULN on therpy nd the proportion of ptients with stbilized hemoglobin. LD Loding Dose; MD Mintennce Dose Distribution The men (SD) volume of distribution t stedy stte ws 5.34 (0.92) L. 3
Non-inferiority of to eculizumb ws demonstd cross endpoints in the complement inhibitor nïve tretment popultion described in the tble below. Tble 7: Efficcy Results in the Complement-Inhibitor Nïve Study Trnsfusion voidnce (N125) (N121) Sttistic for Comprison 73.6% 66.1% Difference in Tretment Effect (95% CI) 6.8 (-4.66, 18.14) LDH normliztion 53.6% 49.4% Odds rtio 1.19 (0.80, 1.77) LDH percent chnge -76.84% -76.02% Difference in % chnge from bseline Brekthrough hemolysis Hemoglobin stbiliztion 4.0% 10.7% Difference in 68.0% 64.5% Difference in -0.83 (-5.21, 3.56) -6.7 (-14.21, 0.18) 2.9 (-8.80, 14.64) Note: LDH lctte dehydrogense; CI confidence intervl For the trnsfusion voidnce endpoint, tretment differences (95% CIs) re bsed on estimted differences in percent with 95% CI. For the lctte dehydrogense normliztion endpoint, the djusted prevlence within ech tretment is displyed. There ws no observble difference in ftigue between nd eculizumb fter 26 weeks of tretment compred to bseline s mesured by the FACIT-ftigue instrument. Ptient-reported ftigue my be n underor over-estimtion, becuse ptients were not blinded to tretment ssignment. 14.2 Study in -Experienced Ptients with PNH The study in eculizumb-experienced ptients [ALXN1210-PNH-302; NCT03056040] ws 26-week, multicenter, open-lbel, rndomized, ctive-controlled, non-inferiority Phse 3 study conducted in 195 ptients with PNH who were cliniclly stble fter hving been treted with eculizumb for t lest the pst 6 months. Ptients who demonstd cliniclly stble disese fter being treted with eculizumb for t lest the prior 6 months were rndomized 1:1 to either continue eculizumb or to switch to. The men totl PNH grnulocyte clone size ws 83%, the men totl PNH monocyte clone size ws 86%, nd the men totl PNH RBC clone size ws 60%. Ninety five percent of ptients hd documented PNH-ssocited condition dignosed prior to enrollment on the tril: nemi (67%), hemturi or hemoglobinuri (49%), history of plstic nemi (37%), history of renl filure (9%), myelodysplstic syndrome (5%), pregnncy compliction (7%), nd other (14%). Mjor bseline chrcteristics were blnced between the two tretment groups. Tble 8: Bseline Chrcteristics in -Experienced Ptients with PNH Prmeter Sttistics (N 97) Age (yers) t first infusion in study Rce White Asin Blck or Africn Americn Other Not reported Unknown Multiple Sex Mle Pre-tretment LDH levels (U/L) Units of prbc/whole blood trnsfused within 12 months prior to first dose Antithrombotic gents used within 28 dys prior to first dose Men (SD) Min, mx Medin Min, mx Medin Min, mx 46.6 (14.41) 18, 79 50 (51.5) 23 (23.7) 5 (5.2) 2 (2.1) 13 (13.4) 3 (3.1) 1 (1.0) (N 98) 48.8 (13.97) 23, 77 61 (62.2) 19 (19.4) 3 (3.1) 1 (1.0) 13 (13.3) 1 (1.0) 0 50 (51.5) 48 (49.0) 224.0 135.0, 383.5 4.0 (1, 32) 234.0 100.0, 365.5 2.5 (2, 15) 20 (20.6) 13 (13.3) Ptients with history of MAVE 28 (28.9) 22 (22.4) Ptients with history of thrombosis Ptients with concomitnt nticogulnt tretment 27 (27.8) 21 (21.4) 22 (22.7) 16 (16.3) MAVE mjor dverse vsculr event Efficcy ws estblished bsed on hemolysis s mesured by LDH percent chnge from bseline to Dy 183 nd supportive efficcy dt ws trnsfusion voidnce, proportion of ptients with stbilized hemoglobin, nd the proportion of ptients with brekthrough hemolysis through Dy 183. Non-inferiority of to eculizumb ws demonstd cross endpoints in the ptients with PNH previously treted with eculizumb described in the tble below. Tble 9: Efficcy Results in the -Experienced Ptients with PNH - Experienced Study 16 HOW SUPPLIED/STORAGE AND HANDLING (rvulizumb-cwvz) injection is cler to trnslucent, slight whitish color preservtive-free, solution supplied s one 300 mg/30 ml (10 mg/ml) single-dose vil per crton. NDC 25682-022-01. Store vils refriged t 2 C 8 C (36 F 46 F) in the originl crton to protect from light. Do not freeze. Do not shke. Refer to Dosge nd Administrtion (2.3) for informtion on the stbility nd storge of diluted solutions of. 17 PATIENT COUNSELING INFORMATION Advise the ptient to red FDA-pproved ptient lbeling (Mediction Guide). Meningococcl Infection Advise ptients of the risk of meningococcl infection/sepsis. Inform ptients tht they re required to receive meningococcl vccintion t lest 2 weeks prior to receiving the first dose of, if they hve not previously been vccinted. They re required to be revccinted ccording to current medicl guidelines for meningococcl vccines use while on therpy. Inform ptients tht vccintion my not prevent meningococcl infection. Inform ptients bout the signs nd symptoms of meningococcl infection/sepsis, nd strongly dvise ptients to seek immedite medicl ttention if these signs or symptoms occur. These signs nd symptoms re s follows: hedche with nuse or vomiting hedche nd fever hedche with stiff neck or stiff bck fever fever nd rsh confusion muscle ches with flu-like symptoms eyes sensitive to light Inform ptients tht they will be given n Ptient Sfety Crd tht they should crry with them t ll times. This crd describes symptoms which, if experienced, should prompt the ptient to immeditely seek medicl evlution. Other Infections Counsel ptients of the incresed risk of infections, prticulrly those due to encpsulted bcteri, especilly Neisseri species. Advise ptients of the need for vccintion ginst meningococcl infections ccording to current medicl guidelines. Counsel ptients bout gonorrhe prevention nd dvise regulr testing for ptients t risk. Advise ptients to report ny new signs nd symptoms of infection. Discontinution Inform ptients with PNH tht they my develop hemolysis due to PNH when is discontinued nd tht they will be monitored by their helthcre professionl for t lest 16 weeks following discontinution. Inform ptients who discontinue to keep the Ptient Sfety Crd with them for eight months fter the lst dose, becuse the incresed risk of meningococcl infection persists for severl weeks following discontinution of. Infusion rections Advise ptients tht dministrtion of my result in infusion rections. Mnufctured by: Alexion Phrmceuticls, Inc. 121 Seport Boulevrd Boston, MA 02210 USA US License Number 1743 This product, or its use, my be covered by one or more US ptents, including US Ptent No. 9,371,377; 9,079,949 nd 9,663,574 in ddition to others including ptents pending. is trdemrk of Alexion Phrmceuticls, Inc. 2018 Alexion Phrmceuticls, Inc. n 97 n 98 Sttistic for Comprison LDH Percent chnge -0.82% 8.4% Difference in % chnge from bseline Brekthrough hemolysis 0% 5.1% Difference in Trnsfusion voidnce 87.6% 82.7% Difference in Hemoglobin Stbiliztion 76.3% 75.5% Difference in Tretment Effect (95% CI) 9.2 (-0.42, 18.8) 5.1 (-8.9, 19.0) 5.5 (-4.3, 15.7) 1.4 (-10.4, 13.3) Note: CI confidence intervl There ws no observble difference in ftigue between nd eculizumb fter 26 weeks of tretment compred to bseline s mesured by the FACIT-ftigue instrument. Ptient-reported ftigue my be n underor over-estimtion, becuse ptients were not blinded to tretment ssignment. 4
MEDICATION GUIDE (ul-toe-meer -is) (rvulizumb-cwvz) injection, for intrvenous use Wht is the most importnt informtion I should know bout? is medicine tht ffects your immune system. cn lower the bility of your immune system to fight infections. increses your chnce of getting serious nd lifethretening meningococcl infections. Meningococcl infections my quickly become life-thretening nd cuse deth if not recognized nd treted erly. 1. You must receive meningococcl vccines t lest 2 weeks before your first dose of if you hve not lredy hd this vccine. 2. If your doctor decided tht urgent tretment with is needed, you should receive meningococcl vccintion s soon s possible. 3. If you hve not been vccinted nd therpy must be initited immeditely, you should lso receive 2 weeks of ntibiotics with your vccintions. 4. If you hd meningococcl vccine in the pst, you might need dditionl vccintion before strting. Your doctor will decide if you need dditionl meningococcl vccintion. 5. Meningococcl vccines reduce the risk of meningococcl infection but do not prevent ll meningococcl infections. Cll your doctor or get emergency medicl cre right wy if you get ny of these signs nd symptoms of meningococcl infection: hedche with nuse or vomiting hedche nd fever hedche with stiff neck or stiff bck fever fever nd rsh confusion muscle ches with flu-like symptoms eyes sensitive to light Your doctor will give you Ptient Sfety Crd bout the risk of meningococcl infection. Crry it with you t ll times during tretment nd for 8 months fter your lst dose. Your risk of meningococcl infection my continue for severl months fter your lst dose of. It is importnt to show this crd to ny doctor or nurse who trets you. This will help them dignose nd tret you quickly. is only vilble through progrm clled the REMS. Before you cn receive, your doctor must: enroll in the REMS progrm counsel you bout the risk of meningococcl infection give you informtion bout the symptoms of meningococcl infection give you Ptient Sfety Crd bout your risk of meningococcl infection, s discussed bove mke sure tht you re vccinted with meningococcl vccine Ultomiris my lso increse the risk of other types of serious infections. People who tke my hve n incresed risk of getting infections cused by Streptococcus pneumonie nd Hemophilus influenze. Certin people my lso hve n incresed risk of gonorrhe infection. Tlk to your helthcre provider to find out if you re t risk for gonorrhe infection, bout gonorrhe prevention, nd regulr testing. Cll your helthcre provider right wy if you hve ny new signs or symptoms of infection. Wht is? is prescription medicine clled monoclonl ntibody. is used to tret dults with disese clled Proxysml Nocturnl Hemoglobinuri (PNH). It is not known if is sfe nd effective in children. Who should not receive? Do not strt if you hve meningococcl infection. Before you receive, tell your doctor bout ll of your medicl conditions, including if you: hve n infection or fever re pregnnt or pln to become pregnnt. It is not known if will hrm your unborn bby. re brestfeeding or pln to brestfeed. It is not known if psses into your brest milk. You should not brest feed during tretment nd for 8 months fter your finl dose of. Tell your doctor bout ll the medicines you tke, including prescription nd over-the-counter medicines, vitmins, nd herbl supplements. nd other medicines cn ffect ech other cusing side effects. Know the medictions you tke nd the vccines you receive. Keep list of them to show your doctor nd phrmcist when you get new medicine. How should I receive? is given through vein by intrvenous (I.V.) infusion usully over bout 2 hours. You will usully receive: strting dose of s n infusion by your doctor, nd then 2 weeks lter, you will strt to receive n infusion of every 8 weeks. If you re chnging tretment from SOLIRIS to, you should receive your strting dose of 2 weeks fter your lst dose of SOLIRIS. After ech infusion, you should be monitored for t lest 1 hour for llergic rections. See Wht re the possible side effects of? If you stop receiving, your doctor will need to monitor you closely for t lest 16 weeks fter you stop. Stopping my cuse brekdown of your red blood cells due to PNH. Symptoms or problems tht cn hppen due to red blood cell brekdown include: drop in the number of your blood clots red blood cell count shortness of breth tiredness trouble swllowing blood in your urine erectile dysfunction (ED) stomch-re (bdomen) pin in mles If you miss n infusion, cll your doctor right wy. Wht re the possible side effects of? cn cuse serious side effects including: See Wht is the most importnt informtion I should know bout? Infusion rections. Infusion rections my hppen during your infusion. Symptoms of n infusion rection with my include lower bck pin, pin with the infusion, or feeling fint. Tell your doctor or nurse right wy if you develop these symptoms, or ny other symptoms during your infusion tht my men you re hving serious infusion rection, including: chest pin trouble brething or shortness of breth swelling of your fce, tongue, or throt feel fint or pss out Your doctor will tret your symptoms s needed. The most common side effects of re upper respirtory infection nd hedche. 5
Tell your doctor bout ny side effect tht bothers you or tht does not go wy. These re not ll the possible side effects of. For more informtion, sk your doctor or phrmcist. Cll your doctor for medicl dvice bout side effects. You my report side effects to FDA t 1-800-FDA-1088. Generl informtion bout the sfe nd effective use of. Medicines re sometimes prescribed for purposes other thn those listed in Mediction Guide. You cn sk your phrmcist or doctor for informtion bout tht is written for helth professionls. Wht re the ingredients in? Active ingredient: rvulizumb-cwvz Inctive ingredients: polysorbte 80 (vegetble origin), sodium chloride, sodium phosphte dibsic, sodium phosphte monobsic, nd Wter for Injection Mnufctured by Alexion Phrmceuticls, Inc., 121 Seport Boulevrd, Boston, MA 02210 USA. U.S. License Number 1743 For more informtion, go to www..com or Cll: 1-888-765-4747 This Mediction Guide hs been pproved by the U.S. Food nd Drug Administrtion Issued: 12/2018 2018 Alexion Phrmceuticls, Inc. Printed in USA 6