b'B:16"T:15.75"S:14.75"B:22"B:22"T:20.75"T:20.75"S:20.25"S:20.25"healthcare providers prepared to manage anaphylaxis. PatientsIn this trial, the percentages of patients with any flare for the14 were Asian, 5 were Native Hawaiian/Other Pacific IslanderImmunogenicityLactation healthcare providers prepared to manage anaphylaxis.first 3 months were 66% and 69% for the group trea ImmunogenicityRisk SummaryLactation should be pre-treated with antihistamines and corticosteroids.PatientsIn this trial, the percentages of pated with tients with any flare for the and 5 identified as Othe1r;4 2 w8 ewree rAes Hiains,p 5an wice roerNLaattiinvoe.HCaowmamiiaonn/ Other PAs with all theraacific Islanderpeutic proteins, there is a potential for first 3 months were 66% and 69% for the group treated with Anaphylaxis may occur with anshould be pre-treay infusion, incted with antihistamines and corticosteroids.luding a first infusion,KRYSTEXXA co-administered with methotrexate and the groupco-morbid conditions amanodn g5tihdee netnifiroeldle ads p Oatthieenrt;s 2 i8n cwluedree dHispanic or immunogenicityLatino. Common.The obserAs with all theraved incidence of antibodpeutic proteins,y positivitythere is a potential for It is not known whether this drug is excreted in human milk.Risk Summary and generally manifests within 2 hours of the infusion. treated with KRYSTEXXA alone,KRYSTEXXA co-administered with methotrexate and the groupTherefore, It is not known whether this drug is excreted in human milk. Anaphylaxis may occur with an Hoy infusion,wever, including a first infusion,respectively. In the grouphypertension (63%), ostceoo-amrthorribtiids(c2o5n%di)t,i ohnysp earmlipoindge mthieae(2n4ro%ll)e, d patiein an assay is highly dependent on several factors incnts includedimmunogenicity. The observed incidence of antibodludingy positivityKRYSTEXXA should not be used when breastfeeding treated with KR ,treated with KRYSTEXXA alone, respectivelyte,unless the c Therefore, KRYSTEXXA should not be used when breastfeeding wn delayed type hypersensitivity reactions haand generally manifests within 2 hours of the infusion.ve also been reported. HoweverYSTEXXA co-administered with methotrexa . In the group gastroesophageal refluxh dyipseeratesen s(i2o2n% (6),3 o%b)e, soitsyt e(2oa0r%th)r, ittyisp (e2 25 %), hypeassay sensitivity and specificity and assay methodologrlipidemia (24%),in an assay is highly dependent on several factors incy, sampleluding lear benefit to the mother can overcome the unknoPatients should be closely monitored for an adelayed type hypersensitivity reactions happropriate period ofve also been reported. treated with KRy flare for the subsequent 3), obesityhandling, (20%), t timing of sample collection, concomitant medications,unless the clear benefit to the mother can overcome the unknown the percentages of patients with an YSTEXXA co-administered with methotrexadiabete,tes(18%) and depgreassstrioone s(o1p6h%a)g. ePaalt rieenfltusx w diitshe aasne e (G2F2R%ype 2assay sensitivity and specificity and assay methodology, sample risk to the newborn/infant.Patients should be ction of KRlosely monitored for an appropriate period ofthe percentages of patients with an 8% y flare for the subsequent 3 40 mL/min/1.73 m wedriaeb eexteclsu (d1e8d% fr)o amn dt hdise ptrreiasls. ion (16%). Patientsand underlying disease. handling, timing of sample collection, risk to the newborn/infant.time for anaphylaxis after administra YSTEXXA. Patientsmonth increments of treatment were 27% during Month 6,with an eGFR For these reasons, the comparison ofconcomitant medications, KRYSTEXXA (pegloticase) injection, for intravenous use time for anaphylaxis after administration of KRYSTEXXA. Patientsmonth increments of treatment were 27% during Month 6, 8%trial. Pediatric Use KRYSTEXXA (pegloticase) injection, for intravenous useshould be informed of the symptoms and signs of anaphylaxis andduring Month 9 and 9% during Month 12. In the group treated40 mL/min/1.73 m were excluded from this the incidence of antibodies to pegloticase with the incidence ofPediatric Use and underlying disease. For these reasons, the comparison of should be informed of the symptoms and signs of anaphylaxis andduring Month 9 and 9% during Month 12. In the group treated The most commonly reported adverse reaction during thethe incidence of antibodies to pegloticase with the incidence of The safety and effectiveness of KRYSTEXXA in pediatric patients instructed to seek immediate medical care should anaphylaxiswith KRYSTEXXA alone, the percentages of patients with any flare during the Brief Summary - Please see the KRYSTEXXA package insertinstructed to seek immediate medical care should anaphylaxishe most commaso ngloyu rte flpaorrete. dT haed vmeorssetreactionantibodies to other products may be misleading. less than 18 years of agTeh hea svaef entoytabnede ne fefesctatibvleisnheesds.of KRYSTEXXA in pediatric patients with KRYSTEXXA alone, the percentages of patients with any flare methotrexate pre-treatmTent periods w antibodies to other products may be misleading.for Full Prescribing Information.Brief Summary - Please see the KRYSTEXXA package insert occur after discharge from the healthcare setting. were 14% during Month 6, 9% during Month 9 and 21% duringiods was gout flare. The mostless than 18 years of age have not been established. occur after discharge from the healthcare setting. were 14% during Month 6, 9% during Month 9 and 21% during commonly reported advmeresteh roetarecxtiaotnes p trhea-tt roecactmurerendtpine r 5% inIn a 52-week, randomized, double-blind trial which evaluated for Full Prescribing Information. The risk of anaphylaxis is higher in patients whose uric acid levelMonth 12. Month 12. poSrte ed in5% inGeriatric UseGeriatric Use either treatment group dcuorminmg othnelyKreRY TEdX XaAd vceor-saed mreiancistitoenrse dt hat occKRurrYSTEXXA co-administered with methotrexaIn a 52-week, randomized,te compared todouble-blind trial which evaluated WARNING: ANAPHYLAXIS and INFUSION REACTIONS,increases to above 6 mg/dL, administeredtely 26% of patients had pre- Of the total number of patients treated with KRYSTEXXA 8 mg increases to above 6 mg/dL,The risk of ana particularly when 2 consecutive phylaxis is higher in patients whose uric acid level During pre-marketing, 24-week controlled clinical trials withwith methotrexate or KReYitShTeErX tXreAa atmloennetpgerroiuopddaurer inpgro tvhidee KdR iYnSTEXXA KRco-YSTEXXA alone, approximaKRYSTEXXA co-administered with methotrexate compared toOf the total number of patients treated with KRYSTEXXA 8 mg G6PD DEFICIENCY ASSOCIA YSIS andved. Monitor serum uric acid levelsparticularly when 2 consecutive KRYSTEXXA alone, the frequencies of gout flares were high in all During pre-marketing, 24-week controlled clinical trials with Table 1. with methotrexate or KRYSTEXXA alone period existing antibodies to pegloticase.are provided inKRYSTEXXA alone, Patients with an increaseapproximately 26% of patients had pre-every 2 weeks in the controlled studies, 34% (29 of 85) were WARNING:TED HEMOL ANAPHYLAXIS and INFUSION REACTIONS,levels above 6 mg/dL are obserlevels above 6 mg/dL are observed. Monitor serum uric acid levelsKRYSTEXXA alone, the frequencies of gout flares were high in allTable 1. every 2 weeks in the controlled studies, 34% (29 of 85) werePatients with an increase 65 years of age and older and 12% (10 of 85) were 75 years of G6PD DEFICIENCY ASSOCIATED HEMOLprior to infusions and discontinue treaYSIS andtment if levels increase totreatment groups, but more so with KRYSTEXXA treatment duringin titer from baseline or who were negaexisting antibodies to pegloticase.tive at baseline and65 years of age and older and 12% (10 of 85) were 75 years of METHEMOGLOBINEMIA age and older. No overall differences in safety or effectiveness METHEMOGLOBINEMIA prior to infusions and discontinue treatment if levels increase to the first 3 months of treatreatment,tment groups, and decreased in the subsequentbut more so with KRYSTEXXA treatment during Table 1. Adverse Reactions Occurring in 5% or More ofin titer from baseline or who were negative at baseline andage and older. No overall differences in safety or effectiveness See full prescribing information for complete boxed warning. above 6 mg/dL. Because of the possibility that concomitant use ofTable 1. Adverse Reactions Occurring in 5% or More of developed an anti-pegloticase response at one or more post See full prescribing information for complete boxed warning. the first 3 months of treatment, and decreased in the subsequent Patients in Either the KRYSTEXXA Co-administered withdeveloped an anti-pegloticase response at one or more post were observed between older and younger patients, but greater oral urate-lowering theraabove 6 mg/dL.py and KRYSTEXXA may potentially bluntBecause of the possibility that concomitant use of 3 months of treatment. The percentages of patients with any flareAnaphylaxis and infusion reactions have been reported oral urate-lowering therapy and KRYSTEXXA may potentially blunt3 months of treatment. The percentages of patients with anMethotrexate or KRy flarePatients in Either the KRYSTEXXA Co-administered with dose time points was 30% and 51%, for the KRYSTEXXA co- were observed between older and younger patients, but greaterAnaphylaxis and infusion reactions have been reportedit is recommended that beforefor the first 3 months were 74%, 81%, and 51%, for KRYSTEXXA 8YSTEXXA Alone Treatment Period dose time points was 30% and 51%, for the KRYSTEXXA co-sensitivity of some older individuals cannot be ruled out. No dose No dose the rise of serum uric acid levels, te and KRYSTEXXA alone treatment to occur during and after administration of KRYSTEXXA.for the first 3 months were 74%, 81%, and 51%, for KRYSTEXXA 8Methotrexate or KRYSTEXXA Alone Treatment Padministered with methotrexaeriodto occur during and after administration of KR the rise of serum uric acid levels,te-loweringit is recommended thamg every 2 weeks,t before KRYSTEXXA 8 mg every 4 weeks, and placebo,administered with methotrexay titers were te and KRYSTEXXA alone treatment adjustment is needed for pasensitivity of some older individuals cannot be ruled out.tients 65 years of age and older. Anaphylaxis may occur with any infusion, including a starting KRYSTEXXA.YSTEXXA patients discontinue oral ura groups, respectively. Patients with higher antibod adjustment is needed for patients 65 years of age and older.YSTEXXA patients discontinue oral urate-lowering . The percentages of patients with any flare for the mg every 2 weeks, KRYSTEXXA 8 mg every 4 weeks, and placebo,more likely to have faster cgroups,learance and lo respectivelywer efficacy. Anaphylaxis may occur with an starting KRpy with oral urate-loweringrespectively KRYSTEXXA . Patients with higher antibodRenal Impairment y titers were first infusion, and generally manifests within 2 hoursy infusion,medica including a tions and not institute theraand generally manifests within 2 hours agents while taking KRmedications and not institute therapy with oral urasubsequent 3 months were 41%,te-loweringrespectively 57%,. The percenta and 67%, for KRges of paYSTEXXA tients with any flare for thewithKRYSTEXXA KRYSTEXXA more likely to have faster clearance and lower efficacNo dose adjustment is required for pay. Renal Impairment KRYSTEXXA tients with renal impairment. of the infusion. Howeverfirst infusion,, delayed hypersensitivityYSTEXXA. 8 mg every 2 weeks, KRsubsequent 3 months were 41%, Adverse Methotrexate AlonewithDuring pre-marketing 24-week controlled clinical trials withIn a 52-week, randomized,No dose adjustment is required for paagents while taking KRYSTEXXA. YSTEXXA 8 mg every 4 weeks, and57%, and 67%, for KRYSTEXXA double-blind trial which evaluated tients with renal impairment. of the infusion. However, delayed hypersensitivity Infusion Reactions Reaction Adverse (N=49) Alone During pre-marketing 24-week controlled clinical trials withIn a 52-week, randomized, double-blind trial which evaluated reactions have also been reported. 8 mg every 2 weeks, KRYSTEXXA 8 mg every 4 weeks, andKRYSTEXXA alone, anti-pegloticase antibodies developed in 92% (N=96) Methotrexate KRYSTEXXA alone, anti-pegloticase antibodies developed in 92% reactions have also been reported. Infusion Reactions placebo, respectively. Patients received gout flare prophylaxis withReaction n (%) (N=49) KRYSTEXXA co-administered with methotrexate compared toKRYSTEXXA should be administered in healthcare In a 52-week, controlled trial which evaluated KRYSTEXXARYSTEXXAplacebo, respectively. Patients received gout flare prophylaxis withn (%) (N=96) of patients treated with KRYSTEXXA every 2 weeks, and 28%KRYSTEXXA co-administered with methotrexate compared toKRYSTEXXA should be administered in healthcare rial which evaluated Kcolchicine and/or nonsteroidal anti-inflammatory drugs (NSAIDs)n (%) of patients treated with KRYSTEXXA every 2 weeks,KRYSTEXXA alone, and 28% 85% of patients had chronic kidney diseasesettings and by healthcare providers prepared to co-administered with mIent hao 5tr2e-xwateee ck,o mcopnatrreoldle tdotKRYSTEXXAcolchicine and/or nonsteroidal anti-inflammatory drugs (NSAIDs)n (%) for placebo. Anti-PEG antibodies were also detected in 42% ofKRYSTEXXA alone, 85% of patients had chronic kidney disease settings and by healthcare providers prepared to co-administered with methotrexate compared to KRYSTEXXA starting at least one week before receiving KRYSTEXXA. based on estimated glomerular filtration rate (eGFR) of40 tomanage anaphylaxis and infusion reactions.alone [see Adverse Reactions], patients were pre-treated withstarting at least one week before receiving KRYSTEXXA. 64 (67%) 35 (71%) for placebo. High anti-pegloticase antibodGout flarepatients treated with KRYSTEXXA.Anti-PEG antibodies were also detected in 42% of y manage anaphylaxis and infusion reactions., e-treated withGout flare64 (67%) 35 (71%) 90 mL/min/1.73 m at baseline.based on estima In the pre-marketing 24-week ted glomerular filtration rate (eGFR) of40 to Pre-medicate with antihistamines and corticosteroids tn re prGout flares may occur after initiation of KRYSTEXXA. An increasepatients treated with KRYSTEXXA. High anti-pegloticase antibody 90 mL/min/1.73 m at baseline. In the pre-marketing 24-week standardized infusion reaalcotnioen [ speroep AhdyvlaexrsiseaRneda cwteiornes d]i spcao ietnintus ewdetiter was associated with a failure to maintain pegloticase-inducedPre-medicate with antihistamines and corticosteroids were discontinuedGout flares may occur after initia Arthralgia 13 (14%) 5 (10%) controlled clinical trials with KRYSTEXXA alone, a total of 32%and closely monitor for anaphylaxis for an appropriatestandarAd iizfe sde rinufmus uiornicraecaicdt iloenv eplsrophylaxis and in gout flares is frequently observed upon initiation of anti-tion of KRYSTEXXA. An increasenormalization of uric acid.titer was associa The impact of anti-PEG antibodies on ted with a failure to maintain pegloticase-inducedcontrolled clinical trials with KRYSTEXXA alone, a total of 32% from treatment with KRYSTEXXand closely monitor for anaphylaxis for an appropriateRYSTEXXA if serum uric acid levelsin gout flares is frequently observed upon initiation of anti- Arthralgia 13 (14%) 5 (10%) normalization of uric acid. The impact of anti-PEG antibodies on (27 of 85) of patients treated with KRYSTEXXA 8 mg every 2 period of time after administration of KRYSTEXXA.increased to above 6 mgfr/odmLattr e2a tcmonesnet cwuittihve K visits after thehyperuricemic therapy, due to changing serum uric acid levelspatients responses to other PEG-containing therapeutics (27 of 85) of patients treated with KRYSTEXXA 8 mg every 2 period of time after administration of KRYSTEXXA.hyperuricemic thera COVID-19 9 (9%) 3 (6%) patients responses to other PEG-containing theraweeks had a creapeutics tinine clearance of 62.5 mL/min. No overallMonitor serum uric acid levels prior to each infusion g/d Lo fa itn 2fu csioonns ecutive viresulting in mobilizasits after thetion of urate from tissue deposits.py, due to changing serum uric acid levelsGout flare(9%) is unknown. weeks had a creatinine clearance of 62.5 mL/min. No overall initiation of KRYSTEXXA itnhcerreaapsye dto t ore adbuocvee t h6e m riskCOVID-19 9 3 (6%) Monitor serum uric acid levels prior to each infusion i is unknown. differences in efficacy were observed.and discontinue treatment if levels increase to above 6reactions. Infusion reactinointisa twioenr eo fr eKpRoYrSteTdE XinX 4A% th oefr appayt ieton trse duce the rprophylaxis with a non-steroidal anti-inflammaisk of infusionresulting in mobilization of uratory drug (NSAID) te from tissue deposits. Gout flaredifferences in efficacy were observed.and discontinue treatment if levels increase to above 6% of patientsNausea 5( 5%) 6 (12%) There was a higher incidence of infusion reactions in patients in the KRYSTEXXA co-adrmeaicntisiotenrse. dIn wfuisthio mn erethaocttrioenxas twe egrreou prophylaxis with a non-steroidal anti-inflammatory drug (NSAID)There was a higher incidence of infusion reactions in patients mg/dL, particularly when 2 consecutive levels above 6 repported in 4or colchicine is recommended starting at least 1 week beforeNausea 5( 5%) 6 (12%) OVERDOSAGE mg/dL, particularly when 2 consecutive levels above 6t least 1 week beforewith high anti-pegloticase antibody titer: 53% (16 of 30) in theOVERDOSAGE ve been reported. mg/dL are observed.A co-administerleodn ewith methoinitiatrexation of KRte group YSTEXXA theraor colchicine is recommended starting apy and lasting at least 6 months,Fatigue 5 (5%) 2 (4%) with high anti-pegloticase antibody titer: 53% (16 of 30) in the No reports of overdosage with KRYSTEXXA ha compared to 31% of patiine nthtsetKreRaYtSeTdE wXXith KRYSTEXXA amg/dL are observed.y prior to comiopnasr [esde eto A 3d1v%ers oefRpeaaticetniotsn str]e. aInte bdo twhi th KRYSunless medically contraindicaTEXXA aloneinitiation of KR Fatigue 5 (5%) 2 (4%) No reports of overdosage with KRYSTEXXA have been reported.Screen patients at risk for G6PD deficienc experienced infusion react ted or not toleraYSTEXXA therated. KRYSTEXXA py and lasting at least 6 months,KRYSTEXXA every 2 weeks group compared to 6% in patientsThe maximum dose that has been administered as a single who had undetectable or loKRYSTEXXA everw antibody titers.y 2 weeks group compared to 6% in patients Infusion reaction a intravenous dose is 12 mg as uricase protein. Patients suspectedScreen patients at risk for G6PD deficiency prior toee Adverse Reactions]. In bothunless medically contraindicated or not tolerated. KRYSTEXXA4 (4%)a 15 (31%) The maximum dose that has been administered as a single starting KRYSTEXXA. Hemolysis and treatment groups, the meaxjopreitryie onfc eindf uinsfiouns iorena rcetaiocntiso oncs c[usrred atdoes not need to be discontinued because of a gout flare. Thewho had undetectable or low antibody titers.starting KRYSTEXXA. He molysis and treatment groups, the majority of infusion reactions occurred atdoes not need to be discontinued because of a gout flare. TheInfusion reaction 4 (4%) 15 (31%) intravenous dose is 12 mg as uricase protein. Patients suspected methemoglobinemia have been reported withgout flare should be managed concurrently as appropriate for thePostmarketing Experienceof receiving an overdose should be monitored, and general the fir st or second KRYSTEXXA infusion and during the time ofPain in extremity 1 (1%) 3 (6%) Postmarketing Experienceof receiving an overdose should be monitored, and general methemoglobinemia have been reported withte for the KRYSTEXXA in patients with G6PD deficiency. the firsste o irn sfuescioonnd r eKaRcYtSioTnEsX wXAe rien fsuismioilna rand durindividual pa [see Dosagout flare should be mana Pain in extremity 1 (1%) The following adverse reactions have been identified duringsupportive measures should be initiated as no specific antidote infusion. Manifestations of the ing the timetientofge and Administration].ged concurrently as appropria 3 (6%)KRYSTEXXA in patients with G6PD deficiency. individual patient [see Dosage and Administration]. postapproval use of KRYSTEXXA.The follo Because these reactions are wing adverse reactions have been identified during has been identified. supportive measures should be initiated as no specific antidote KRYSTEXXA is contraindicated in patients with G6PDto that observed in the pinrefu-msioanrk. eMtianng i ftersiatalst.ions of these infusion reactions were similar KRYSTEXXA is contraindicated in patients with G6PDto that observed in the pre-marketing trials. Congestive Heart FailureHypertension 1 (1%) 3 (6%) postapproval use of KRYSTEXXA. Because these reactions arehas been identified.deficiency.During pre-marketing 24-week controlled clinical trials withCongestive Heart FailureHypertension 1 (1%) 3 (6%) PATIENT COUNSELING INFORMATION reported voluntarily from a population of uncertain size, it is not deficiency.KRYSTEXXA has not been formally studied in patients withreported voluntarily from a population of uncertain size, it is not During pre-marketing 24-week controlled clinical trials withKRYSTEXXA has not been formally studied in patients with0 4 (8%) always possible to reliably estimate their frequency or establish PATIENT COUNSELING INFORMATION KRYSTEXXA alone, KRYSTEXXA was not discontinued followingcongestive heart failure, but some patients in the pre-marketing,VomitingAdvise the patient to read the FDA-approved patient labeling Vomiting0 4 (8%) always possible to reliably estimate their frequency or establishINDICATIONS AND USAGE KRYSTEXXA alone, KRYSTEXXA was not discontinued followingcongestive heart failure, but some patients in the pre-marketing,a causal relationship. (Medication Guide). Advise the patient to read the FDA-approved patient labeling 2 consecutive serum uric acid levels above 6 mg/dL. Infusion24-week controlled clinical trials experienced exacerbation of KRYSTEXXA INDICATIONS AND USAGEInfusion24-week controlled c a Included one case of anaphylaxis a causal relationship. (Medication Guide). tients treated withcongestive heart failure. Two cases of congestive heart failure linical trials experienced exacerbation of(pegloticase) is indicated for the treatment ofreactions were reported in 26% of pa2 consecutive serum uric acid levels above 6 mg/dL. a Included one case of anaphylaxis General disorders and administration site conditions: asthenia, KRYSTEXXA(pegloticase) is indica tment ofreactions were reported in 26% of patients treated withcongestive heart failure. Two cases of congestive heart failure KRYSTEXXA ALONE malaise, peripheral swelling Anaphylaxis and Infusion Reactions chronic gout in adult patients refractory to conventional therated for the treapy.General disorders and administration site conditions: asthenia, KRYSTEXXA 8 mg every 2 weeks, and 41% of patients treatedexacerbation occurred during the trials in patients receivingmalaise, peripheral swellingAna Anaphylaxis and Infusion Reactionschronic gout in adult patients refractory to conventional therapy.KRYSTEXXA ALONE phylaxis and infusion reactions can occur at any infusiony 2 weeks, and 41% of patients treatedexacerbation occurred during the trials in patients receiving The data described below reflect exposure to KRYSTEXXA in Gout refractory to conventional therapy occurs in patients whowith KRYSTEXXA 8 mg everKRYSTEXXA 8 mg every 4 weeks, compared to 5% oftreatment with KRYSTEXXA 8 mg every 2 weeks. No cases Anaphylaxis and infusion reactions can occur at any infusionwith KRYSTEXXA 8 mg every 4 weeks, compared to 5% of data described below reflect exposure to KDRRYUG INTERACTIONSSTEXXA inwhile on therapy. Counsel patients on the importance of Gout refractory to conventional therapy occurs in patients whotreatment with KRYSTEXXA 8 mg every 2 weeks. No cases patients with chronic goTuht erefractory to conventional therapywhile on therapy. Counsel patients on the importance of have failed to normalize serum uric acid and whose signs andpatients treated with placebo. These infusion reactions occurred inwere reported in placebo-treated patients. Four subjects hadDRUG INTERACTIONS adhering to any prescribed medications to help prevent or patients treated with placebo. These infusion reactions occurred inhronic gout refractory to convenMethotrexatetional therapy have failed to normalize serum uric acid and whose signs andwere reported in placebo-treated patients. Four subjects had in two replicate randompizaetdie, nptlsa cweibtho -ccontrolled, double- adhering to any prescribed medications to help prevent or symptoms are inadequately controlled with xanthine oxidasepatients being pre-treated with an oral antihistamine, intravenousexacerbations of pre-existing congestive heart failure whileMethotrexate lessen the severity of these reactions.symptoms are inadequately controlled with xanthine oxidasepatients being pre-treated with an oral antihistamine, intravenous ltsw: o8 5re ppalitcieantets r awnedroem trizeeadte, dp lwacitehb o-controlleKRd, dYSTEXXA 8 mg everouble- y 2 weeks has been studied in patientslessen the severity of these reactions.exacerbations of pre-existing congestive heart failure while blind 24-week clinical triniainhibitors at the maximum medically appropriate dose or forcorticosteroid and/or acetaminophen. This pre-treatment mayreceiving KRYSTEXXA 8 mg every 2 weeks during the open-label85 patients were twith chronic gout refractor YSTEXXA 8 mg every 2 weeks has been studied in patients reated withKRy to conventional therapy taking Educate patients on the signs and symptoms of anaphylaxis, receiving KRYSTEXXA 8 mg every 2 weeks during the open-label KRYSTEXXA 8 mg everyb 2li nwde 2e4ks-w; 8e4e kp actliineinctaslwtreiarles :t reated with inhibitors at the maximum medically appropriate dose or forcorticosteroid and/or acetaminophen. This pre-treatment maywith chronic gout refractory to conventional therapy taking Educate patients on the signs and symptoms of anaphylaxis,S:14.5" T:15" B:15.25" T:15" S:9.75" T:10.75" B:11"whom these drugs are contraindicated. have blunted or obscured symptoms or signs of infusion reactionsextension study. KRYSTEXXA 8 mg every 2 weeks; 84 patients wconcomitant oral methotrexaere treated withte 15 mg weekly. Co-administration whom these drugs are contraindicated. and therefore the reported frequenchave blunted or obscured symptoms or signs of infusion reactionsextension study. KRYSTEXXA 8 mg every 4 weeks; and 43 patients were treatedincluding wheezing, peri-oral or lingual edema, hemodynamic y may be an underestimate.concomitant oral methotrexate 15 mg weekly. Co-administrationincluding wheezing, S:14.5" B:15.25"Limitations of Use: and therefore the reported frequency may be an underestimaExercise caution when using KRte.YSTEXXA in patients who haveKRYSTEXXA 8 mg every 4 weeks; and 43 patieof methotrexants were treatte with KRedYSTEXXA may increase pegloticaseinstability, and rash or urticaria, nausea or vomiting. peri-oral or lingual edema, hemodynamic with placebo. These patients were between the ages of 23 and Exercise caution when using KRYSTEXXA in patients who havelac of methotrexate with KRYSTEXXA may increase pegloticaseinstability, and rash or urticaria, nausea or vomiting.KRYSTEXXA is not recommended for the treaLimitations of Use: tment ofManifestations of these reactions included urticaria (frequency ofcongestive heart failure and monitor patients closely following89 years (average 55 yewairtsh);p 173e pbaot. iTehnetss ew peareti emnatsle w aenrde3b9e tween theconcentra ages of 2tion compared to KR3 andYSTEXXA alone.Educate patients on the most common signs and symptoms ofManifestations of these reactions included urticaria (frequency ofcongestive heart failure and monitor patients closely followingconcentration compared to KRYSTEXXA alone. Educate patients on the most common signs and symptoms ofasymptomatic hyperuricemia.KRYSTEXXA is not recommended for the treatment of 10.6%), dyspnea (frequency of 7.1%), chest discomfort (frequencywere female; and 143 pa an infusion reaction, inc luding urticaria (skin rash), erythema infusion. infusion. 89ti eynetasr sw (earvee Wrahgiete 5/C5a yuecaarssi)a; n1, 7237pwaetireen ts werePEGylated products male and 39an infusion reaction, including urticaria (skin rash), erythema asymptomatic hyperuricemia. of 9.5%), chest pain (frequenc10.6%),y of 9.5%), dyspnea (frequenc erythema (frequency of 7.1%),ychest discomfort (frequencywere female; and 143 patients were White/Caucasian, 27 werePEGylated products (redness of the skin), dyspnea (difficulty breathing), flushing, CONTRAINDICATIONS Re-treatment with KRYSTEXXABlack/African American, 24 were Hispanic/Latino and 18 wereBecause anti-pegloticase antibodies appear to bind to the PEG(redness of the skin), dyspnea (difficulty breathing), flushing, of 9.5%), chest pain (frequency of 9.5%), erythema (frequencyBlack/African American, 24 were Hispanic/Latino and 18 wereBecause anti-pegloticase antibodies appear to bind to the PEG chest discomfort, chest pain, and rash.CONTRAINDICATIONS of 9.5%), and pruritus (frequency of 9.5%). These manifestationsRe-treatment with KRYSTEXXAall other ethnicities. Common co-morbid conditions among theportion of the drug, there may be potential for binding withchest discomfort, chest pain, and rash.KRYSTEXXA is contraindicated in: of 9.5%), and pruritus (frequency of 9.5%). These manifestations No controlled trial data are available on the safety and efficacy KRYSTEXXA is contraindicated in: overlap with the symptoms of anaphylaxis, but in a givenall othpeerr teetnhsniiocnit i(e7s2. %Co),m dmysolinp icdoe-mmiao rbid conditions among theportion of the drug, there may be potential for binding withAdvise patients to seek medical care immediately if they No conXtAro alleftde rt rsiatol pdpaitnag a trree aatvmaeilnatb lfeo ro n the safety anedn reoflfilecda cpya tients included hy other PEGylated products. The impact of anti-PEG antibodies on Advise patients to seek medical care immediately if they overlap with the symptoms of anaphylaxis, but in a given of re-treatment with KRYSTEXPatients with glucose-6-phosphate dehydrogenase (G6PD)patient did not occur together to satisfy the clinical criteria forlonger than 4 weeks. Duoefrtoe -tthreea itmmmenutn owgitehn iKcRitYyS oTfE KXRXYAS aTfEteXrX Ast,opping treat(m49e%nt) ,f ocrh ronic kidney deisneraosllee d(2 p8a%ti)e, ndtisa binectleusd e(2d4 h%y)p, coerteronnsaiorny(72%), dyslipidemiaother PEGylated products. The impact of anti-PEG antibodies on experience any symptoms of an allergic reaction during or att patients responses to other PEG-containing therapeuticspatient did not occur together to satisfy the clinical criteria for(49%), chronic kidney disease (28%), diabetes (24%), coronarypatients responses to other PEG-containing theraanpeutics y time after the infusion of KRexperience anYSTEXXA y symptoms of an allergic reaction during or adeficiency [see Warnings and Precautions]Patients with glucose-6-phosphate dehydrogenase (G6PD) diagnosing anaphylaxis. Infusion reactions are thought to resultlonger than 4 weeks. Due to the immunogenicity of KRYSTEXXA,is unknown. [see Warnings and patients receiving re-treatment may be at increased risk ofartery disease (18%), arrhythmia (16%), and cardiac failure/left deficiency [see Warnings and Precautions] from release of various mediadiagnosing anators, such as cphylaxis.ytokines. Infusion reactions are thought to resultInfusionlar dysfunction (a1r2te%ry). disease (18%), arrhythmia (16%), and cardiac failure/leftis unknown. Precautions, Adverse Reactions]any time after the infusion of KRYSTEXXA [see Warnings and Patients with history of serious hypersensitivity reactions,anaphylaxis and infusionp arteieancttiso nresc. eTihveinrge froer-et,r peaattmienetnstrmecaeyi vbien ga t increasedv reisnktr oicfu anaphylaxis and infusion reactions. Therefore, patients receivingventricular dysfunction (12%). USE IN SPECIFIC POPULATIONSAdvise patients to discontinue anPrecautions,y oral ura Adversete-lo Reactions]wering agents Patients with history of serious hypersensitivity reactions, reactions occurred at anfrom release of various mediay time during a course of treatment tors, such as cytokines. Infusion including anaphylaxis, to KRYSTEXXA or any of its components reactions occurred at any time during a course of treare-treatment tment after a drug-free interval should be monitoredDuring the pre-marketing placebo-controlled clinical trials, thePregnancyUSE IN SPECIFIC POPULATIONSAdvise patients to discontinue any oral uray oral urate-te-lowering agentsincluding anaphylaxis, to KRYSTEXXA or any of its componentswith approximately 3% occurring with the first infusion, andnt after a drug-free interval should be monitoredntrolled clinical trials, thePregnancybefore starting on KRYSTEXXA and not to take anrea-ctrteioantms]e. During the pre-marketing placebdo -icnoRisk Summary before starting on KRYSTEXXA and not to take any oral urate- with approximately 3% occurring with the first infusion,carefully and[see Adverse Re most commonly reported adverse reactions that occurreWARNINGS AND PRECAUTIONS approximately 91% occurred during the time of infusion. carefully [see Adverse Reactions]. most commonly reported adverse reactions that occurred inRisk Summary lowering agents while on KRYSTEXXA.WARNINGS AND PRECAUTIONS approximately 91% occurred during the time of infusion.ADVERSE REACTIONS greater than or equal to 5% of patients treated with KRYSTEXXAThere are no adequate and well-controlled studies of KRYSTEXXAlowering agents while on KRYSTEXXA.AnaphylaxisKRYSTEXXA should be administered in a healthcare setting byADVERSE REACTIONS ter tha innToar belqeu 2a.l to 5% of patients treated with KRYSTEXXAThere are no adequate and well-controlled studies of KRGlucose-6-phosphate dehydrogenase (G6PD) DeficiencYSTEXXAy In a 52-week controlled trial, which evaluated KRYSTEXXAKRYSTEXXA should be administered in a healthcare setting by8 mg every 2 weeks areg rperaovided in pregnant women. Based on animal reproduction studies, no Anaphylaxishealthcare providers prepared to manage infusion reactions.The following serious adverse reactions are discussed in greater8 mg every 2 weeks are provided in Table 2. in pregnant women. Based on animal reproduction studies, noGlucose-6-phosphate dehydrogenase (G6PD) Deficiency YSTEXXAdetail in other sections of the label:The following serious adverse reactions are discussed in greaterstructural abnormalities were observed when pegloticase wasInform patients not to take KRYSTEXXA if they have a condition co-administered with methotrexaIn a 52-week controlled trial,te compared to KRYSTEXXAwhich evaluated KRPatients should be pre-treated with antihistamines anddetail in other sections of the label: Table 2. Adverse Reactions Occurring in 5% or More ofstructural abnormalities were observed when pegloticase wasInform patients not to take KRYSTEXXA if they have a condition healthcare providers prepared to manage infusion reactions. co-administered with methotrexate compared to KRYSTEXXA Anaphylaxis [see Warnings and Precautions] administered by subcutaneous injection to pregnant rats andknown as G6PD deficiency. Explain to patients that G6PD alone, patients were pre-treated with standardized infusionPatients should be pre-treawly over no less ted with antihistamines and Anaphylaxis [see Warnings and Precautions] Table 2. Adverse Reactions Occurring in 5% or More oftients that G6PD corticosteroids. KRYSTEXXA should be infused slo Patients Treated with KRYSTEXXA Compared to Placeboalone, patients were pre-treated with standardized infusioncorticosteroids. KRYSTEXXA should be infused slo Infusion Reactions wly over no less[see Warnings and Precautions] Patients Treated with KRYSTEXXA Compared to Placeborabbits during the period of organogenesis aadministered by subcutaneous injection to pregnant rat doses up to 50known as G6PD deficiency. Explain to paAfrican, reaction prophylaxis and were discontinued from treatmentthan 120 minutes. In the event of an infusion reaction, the infusion[see Warnings and Precautions] and 75 times, respectively, the maximum recommended humandeficiencts and y is more frequently found in individuals ofAfrican, reaction prophylaxis and were discontinued from treatmentthan 120 minutes. In the event of an infusion reaction, G6PD Deficiency Associa Infusion Reactionsrabbits during the period of organogenesis at doses up to 50 Mediterranean, or Southern deficiencAsian ancestry is more frequently found in individuals of y and that they may be ted Hemolysis and Methemoglobinemia with KRYSTEXXA if serum uric acid levels increased to above 6should be slowed, or stopped and restarted at a slower rate.the infusiony Associated Hemolysis and Methemoglobinemiaand 75 times, respectively, the maximum recommended humany and that they may be with KRYSTEXXA if serum uric acid levels increased to above 6[see Warnings and Precautions] G6PD DeficiencKRYSTEXXA Placebo dose (MRHD). Decreases in mean fetal and pup body weightstested to determine if they haMediterranean,ve G6PD deficienc or Southern y, unless alreadAsian ancestry mg/dL at 2 consecutive visits after the initiation of KRYSTEXXAshould be slowed, or stopped and restarted at a slower rate. KRYSTEXXA ve G6PD deficiency, unless already mg/dL at 2 consecutive visits after the initiation of KRThe risk of infusion reaction is higher in paYSTEXXAtients whose uric acid Gout Flares [see Warnings and Precautions][see Warnings and Precautions] Adverse 8 mg every 2(N=43) were observed at approximadose (MRHD).tely 50 and 75 times the MRHD, Decreases in mean fetal and pup bodknown y weights [see Warnings and Precautions,tested to determine if they ha Contraindications].Placebotherapy to reduce the risk of anaphylaxis. One patient randomizedThe risk of infusion reaction is higher in patients whose uric acid Gout Flares [see Warnings and Precautions] Adverse 8 mg every 2(N=43) were observed at approximately 50 and 75 times the MRHD,known [see Warnings and Precautions, Contraindications].level increases to above 6 mg/dL, particularly when 2 consecutive Congestive Heart Failure [see Warnings and Precautions] Reaction weeks (N=85) n (%) respectively [see Data].therapy to reduce the risk of anaphylaxis. One patient randomizeda weeks (N=85) respectively [see Data]. Gout Flares to the group treated with KRYSTEXXA co-administered withlevel increases to above 6 mg/dL, particularly when 2 consecutive Congestive Heart Failure [see Warnings and Precautions] Reaction a n (%)to the group treated with KRYSTEXXA co-administered with levels above 6 mg/dL are observed. Monitor serum uric acid levelsn (%) n (%) All pregnancies have a background risk of birth defect, lossGout Flares methotrexate (1%) experienced anaphylaxis during the firstClinical Trials Experience Explain to patients that gout flares may initially increase when levels above 6 mg/dL are observed. Monitor serum uric acid levelsClinical Trials Experience All pregnancies have a background risk of birth defect, lossExplain to patients that gout flares may initially increase when infusion and no patients experienced anamethotrexate (1%) experienced anaphylaxis in the group phylaxis during the first prior to infusions and discontinue treatment if levels increase toBecause clinical studies are conducted under widely varying andGout flare65 (77%) 35 (81%) or other adverse outcomes. In the US general population, thestarting treatment with KRYSTEXXA, and that medications to treated with KRYSTEXXA aloneinfusion and no pa [see Adverse Reactions]tients experienced ana. phylaxis in the groupprior to infusions and discontinue treatment if levels increase toBecasues ree acclitnioicna lr astteusd ioebss aerrev ecdo nind ucclitneidca ul nder widely varying andGout flare65 (77%) 35 (81%) or other adverse outcomes. In the US general populagetion, thestarting treatment with KRYSTEXXA, and that medications to above 6 mg/dL. Because of the possibility that concomitant use ofestimated background risk of major birth defects and miscarria help reduce flares may need to be taken regularly for the first above 6 mg/dL. Because of the possibility that concomitant use of controlled conditions, advertreated with KRYSTEXXA alone [see Adverse Reactions]oral urate-lo. wering therapy and KRYSTEXXA may potentially bluntverse rea cthtieo n rates observed in clinical22 (26%) 2 (5%) estimated background risk of major birth defects and miscarriafew months after KRgehelp reduce flares may need to be taken regularly for the first studies of a drug cannotc obnet rdoirlleecdt lcyo cnodmitpioanrse,d a tdo rates in Infusion reactionin clinical recognized pregnancies is 2% to 4% and 15% toYSTEXXA is started [see Warnings and During pre-marketing clinical trials with KRYSTEXXA alone,oral urate-lowering therapy and KRt before YSTEXXA may potentially bluntInfusion reaction22 (26%) 2 (5%) YSTEXXA is started [see Warnings and the rise of serum uric acid levels, it is recommended thaDuring pre-marketing clinical trials with KRYSTEXXA alone,studies of a drug cannote dbiec td tirheec rtlayt ecso mpared to rates in the20%, respectively. in clinical recognized pregnancies is 2% to 4% and 15% to Precautions,Adverse Reactions]few months after KR. Advise patients that they should KRYSTEXXA was not discontinued following 2 consecutive serumthe rise of serum uric acid levels, it is recommended thaclinical st before tudies of another drug, and may not pr Nausea10 (12%) 1 (2%) 20%, respectively. Precautions, Reactions]. Advise patients that they should starting KRYSTEXXA patients discontinue oral urate-loweringe ratesKRYSTEXXA was not discontinued following 2 consecutive serumte-loweringlinicta lp sotpuudliaetsio onfiann coltinhiecra dl rpurga,c taincde. may not predict th Nausea 10 (12%) 1 (2%) not stop KRYSTEXXA therapy if they ha Adverseve a flare. observed in a broader pcatienuric acid levels above 6 mg/dL. Anaphylaxis was reported with amedications and not institute therastarting KRpy with oral uraYSTEXXA patients discontinue oral urate-loweringobserved in a broader patient population in clinical practice. Datanot stop KRYSTEXXA therapy if they have a flare. b Animal DataDataManufactured by: frequency of 6.5% (8/123) of pauric acid levels above 6 mg/dL.tients treated with KRYSTEXXAAnaphylaxis was reported with a agents while taking KRYSTEXXA.medications and not institute therapy with oral uraCo-administration with Methotrexatete-loweringContusion or 9( 11%) b 2 (5%) Animal Data agents while taking KRYSTEXXA. Co-administration with Methotrexate b Contusion or 9( 11%) 2 (5%) Horizon Therapeutics Ireland DAC Manufactured by: every 2 weeks and 4.8% (6/126) for the everfrequency of 6.5% (8/123) of pay 4-week dosing tients treated with KRYSTEXXAA 52-week, randomized, double-blind trial was conducted inEcchymosis In 2 separate embryo-fetal developmental studies, pregnant G6PD Deficiency Associated Hemolysis andEcchymosisb rats and rabbits received pegloticase during the period ofHorizon Therapeutics Ireland DAC regimen. There were no cases of anaevery 2 weeks and 4.8% (6/126) for the everphylaxis in patients y 4-week dosingG6PD Deficiency Associated Hemolysis andmizedo,n dvoeunbtiloen-abll ind trial was conducted inIn 2 separate embryo-fetal developmental studies,Dublin, pregnantIreland Methemoglobinemiaadult patients with chronAi c5 2g-owuet erekf,r raacntodroy to c organogenesis at doses up to arats and rabbits received pegloticase during the period ofDublin, Ireland regimen. There were no cases of anaphylaxis in patients lt ptaiotine notfsKwRiYthS TchErXoXnAic 8 g mougterevferrayctory to conventional6 (7%) 1 (2%) pproximately 50 and 75 times receiving placebo. Anaphylaxis generally occurred withinMethemoglobinemiatherapy to evaluate admaidnuistra Nasopharyngitis2 hours after treatment. receiving placebo. Anaphylaxis generally occurred within Life threat ening hemolytic reactions and methemoglobinemia toe eekvlayl uaadtme iandismtriantiisotnra otifo onr aolfKRYSTEXXA 8 mg every Nasopharyngitis 6 (7%) 1 (2%) organogenesis at doses up to a respectively pproximately 50 and 75 times US License Number 2022 2 weeks co-administeretdh ewraitphy w the maximum recommended human dose (MRHD), US License Number 2022 Life threatening hemolytic reactions and methemoglobinemia 2 hours after treatment. have been reported with KRYSTEXXA in patients with glucose-with weekly administration of oral5 (6%) 2 (5%) the maximum recommended human dose (MRHD),Distributed by: respectivelymethotrexate 15 mg, co2m wpaereekdstcoo K-aRdYmSTinEiXstXeAre adlone. In this trial,Constipation (on a mg/m basis at maternal doses up to 40 and 30 mg/kgDistributed by: Diagnostic criteria of anaphylaxis were skin or mucosal tissue6-phosphate dehydrogenhaasvee(bGe6ePnD r)e dpeofirtceiedn wcyit. hB KecRaYuSsTeE XXA in patients with glucose- methotrexate 15 mg, compared to KRYSTEXXA alone. In this trial,Constipation 5 (6%) 2 (5%)involvement, and, either airway compromise,Diagnostic criteria of ana and/or reduced phylaxis were skin or mucosal tissue of the risk of hemolysis and methemoglobinemia, do patients who were able to tolerate two weeks on methotrexatetwice weekly, in rats and rabbits,(on a mg/m basis a respectively).t ma No evidence of ternal doses up to 40 and 30 mg/kg Horizon Therapeutics USA, Inc.6-phosphate dehydrogenasen(Got6 PD) deficiency. Bpaetcieanutssewho were able to tolerate two weeks on methotrexateChest Pain 5 (6%) 1 (2%) twice weekly, in rats and rabbits, respectively). No evidence of Deerfield, IL 60015 Horizon Therapeutics USA, Inc.blood pressure with or without associainvolvement, and,ted symptoms, either airway compromise, and a and/or reduced15 mg were then randomized to receive four additional weeks onur additional weeks onChest Pain 5 (6%) structural abnormalities was observed in rats or rabbits. However, However,Deerfield, IL 60015of the risk of hemolysis and methemoglobinemia, do not1 (2%)administer KRYSTEXXA to patients with G6PD deficiency [see15gmorgmwaetrceh itnhge np lraacnedboom pizrieodrttoorineictieaivtien gfodecreases in mean fetal and pup bodstructural abnormalities was obsery weights were observed ved in rats or rabbits.KRYSTEXXA and the HORIZON logo are trademarks owned bytemporal relationship to KRblood pressure with or without associa either methotrexate 15 m Anaphylaxis 4 (5%) 0 (0%) KRYSTEXXA and the HORIZON logo are trademarks owned byYSTEXXA or placebo injection with no ted symptoms,Contra and a indications]. Screeand mpaintiiesntets at risk for G6PD deficiency r KRYSTEXXA to patients with G6PD deficiency [seeeither methotrexate 15 mg or momaticzheidn,g placebo prior to initiatingAnaphylaxis 4 (5%) 0 (0%) decreases in mean fetal and pup bodts and rabbits,y weights were obseror licensed to Horizon.ved KRYSTEXXA therapy. A total of 152 subjects were rand at approximately 50 and 75 times the MRHD in raother identifiable cause. Manifestatemporal relations inctionship to KRluded wheezing,YSTEXXA or placebo injection with noperi- Contraindications]. Screen pfa Atiefrnictsa na,trisk for G6PD deficiencyKRYSTEXXA therapy. A total of 152 subjects were randomized,at approximately 50 and 75 times the MRHD in rats and rabbits,or licensed to Horizon.prior to starting KRYSTEXXA. For example, patients o and of fA tfhriecsaen,,145 subjects completed the 4-week methotrexateVomiting4 (5%) 1 (2%) respectively (on a mg/m basis at maternal doses up to 40 and 30 2022 Horizon Therapeutics plc L-KRY-US-00018 7/22oral or lingual edema, or hemodother identifiable cause.ynamic instability Manifesta, with or without tions included wheezing, peri-Mediterranean (including Spriooru tthoe srtna rEtuinrgo pKeRaYnS aTnEdX XMAi.d Fdolerexample, patients o and of these, 145 subjects completed the 4-week methotrexateVomiting4 (5%) 1 (2%) respectively (on a mg/m basis at maternal doses up to 40 and 30 2022 Horizon Therapeutics plc L-KRY-US-00018 7/22oral or lingual edema, or hemodynamic instability, with or withoutmg/kg every other day, in rats and rabbits, respectively).rash or urticaria, nausea or vomiting. Cases occurred in patientsMediterranean (inclut dinincgre Saosuetdh reirsnkE uropean and Middlerun-in period and received KRYSTEXXA (96 subjects receivedaIf the same subject in a given group had more than onemg/kg every other day, in rats and rabbits, respectively).Eastern), and Southern Asian ancestry are a run-in period and received KRYSTEXXA (96 subjects received KRYSTEXXA co-administered with methotrexate and 49 receiveda No effects on mean fetal body weights were observed at rash or urticaria, nausea or vomiting. Cases occurred in patientsEastern), and Southern Asian ancestry are at increased risk If the same subject in a given group had more than oneved at being pre-treated with one or more doses of an oral antihistamine,for G6PD deficiency. K tegory, theapproximately 10 and 25 times the MRHD in raNo effects on mean fetal bodts and rabbits,y weights were obser being pre-treated with one or more doses of an oral antihistamine,for G6PD deficiency. KRYSTEXXA plus placeboR) YdSurTiEnXgX tAh ec otr-eaadtmmiennist tpeererido dw. iAthllmethotrexate and 4occurrence in the same preferred term event ca9 received an intravenous corticosteroid and/or acetaminophen. This pre-an intravenous corticosteroid and/or acetaminophen.Gout Flares This pre- KRYSTEXXA p launsoprlaalc aenbtoih) idsutarimngin teh, e treatment periodsubject was counted only once Alloccurrence in the same preferred term event carespectively (on a mg/m basis ategory, theapproximat mately 10 and 25 times the MRHD in rats and rabbits, patients received pre-treatment with ternal doses up to 10 mg/kg treatment may have blunted or obscured symptoms or signs Gout Flares patientsa creectaemiveindo pphree-ntr. eTahtemsee npt awtiiethn tas n oral antihistamine,subject was counted only once. twice weekly in both species).respectively (on a mg/m basis at maternal doses up to 10 mg/kg treatment may have blunted or obscured symptoms or signs In a 52-week,randomized, double-blind trial which evaluatedintravenous corticosteroid andb Most did not occur on the day of infusion and could be related to of anaphylaxis and therefore the reported frequency may be ophen. These patientsb Most did not occur on the day of infusion and could be related totwice weekly in both species).were betweted en the ages ionft r2a4v eannodu s8 3c oyretiacrs (averof anaphylaxis and therefore the reported frequencKRYSTEXXA co-administered with methotrexay may be In a 52-week, randomized,te compared todouble-blind trial which evaluaosteroida gaen d5 5a cyeetaarms)i;nother factors (e.g., concomitant medications relevant to contusion an underestimate. an underestimate. KRYSTEXXA alone, patientKRs wYSTEXXA co-administered with methotrexate compared to were between the ages of 24 antients d 83 years (average 55 years);other factors (e.g., concomitant medications relevant to contusion ere administered gout flare prophylaxis135 patients were male and 17 and were female; 105 pa or ecchymosis, insulin dependent diabetes mellitus).KRYSTEXXA should be administered in a healthcare setting bysimilar to that in the pre-marketing,KRYSTEXXAplacebo-controlled trials.alone, patients were admin istered gouwt eflraer eW phroitpeh/Cylaauxicsa sian, 135 pa22 wertients were male and 17 and were female; 105 pae Black/African American,tientsor ecchymosis, insulin dependent diabetes mellitus).KRYSTEXXA should be administered in a healthcare setting bysimilar to that in the pre-marketing, placebo-controlled trials.were White/Caucasian, 22 were Black/African American, FS:9.875" FS:9.875"FS:9.875" FS:9.875"F:10.375" F:10.375"F:10.375" F:10.375"F:7.875" PREPARED BYF:7.875"11760971 KXX Brief Summary PREPARED BYM1411760971 KXX Brief Summary M14Job info Images FontsSpecial InstructionsDate: 7-15-2022 3:53 PMJob info KXX_Logo_Pos_BLACK.ai (44.72%; 70KB)Images Helvetica Neue LT Std (57 Condensed, 57 ConFonts- None Special InstructionsKXX_Logo_Pos_BLACK.ai densed Oblique), (44.72%; 70KB)Helvetica Neue Helvetica Neue LT Std (Condensed(57 Condensed, 57 Con- None12131058_KRY_VA_Nonpersonal_Journal_Ad_M3FR.indd 2 Client: HORIZON THERAPEUTICSDate: 7-15-2022 3:53 PM Bold) densed Oblique), Helvetica Neue (Condensed5/14/24 11:00 AMProduct: KRYSTEXXA Client: HORIZON THERAPEUTICSClient Code: L-KRY-US-00018 Product: KRYSTEXXA Bold) Additional InformationWF Issue # 8675238 Client Code: L-KRY-US-00018 Bleed Size: 22w x 15.25h Additional InformationReleasing as: PDF X1a WF Issue # 8675238 Bleed Size: 22w x 15.25hFinal Size: Trim Size: 20.75w x 15hReleasing as: PDF X1aFinishing: Magazine Final Size: Trim Size: 20.75w x 15hGutter: and Live: 0.5" Finishing: Magazine Inks Additional Comments for SizingColors: 1C Gutter: and Live: 0.5"Black Inks Live: 20.25"w x 14.5"h Additional Comments for SizingColors: 1CBlack Live: 20.25"w x 14.5"hTeamProducer: Lisa Farley TeamAD: Jamie Gardner Producer: Lisa FarleyAE: Katie Pastellides AD: Jamie Gardner Scale: 1"= 1"QC: NA AE: Katie Pastellides Scale: 1"= 1"Production: Eddie Coln QC: NA Bleed 11.625" w x 15.25" h 11.625" w x 15.25" hProduction: Eddie Coln Trim/Flat 10.375" w x 15" hBleed 10.375" w x 15" h 11.625" w x 15.25" h11.625" w x 15.25" hDigital Artist: Hank Encizo Digital Artist: Hank Encizo PREPARED BY9.875" w x 14.5" hTrim/Flat 9.875" w x 14.5" h10.375" w x 15" hLive/Safety 10.375" w x 15" h12131058vc#12149549 PrePress:Horizon:Krystexxa:11760971:11760971_2022_KXX_Brief_Summary_M14.indd Live/Safety 9.875" w x 14.5" h 9.875" w x 14.5" hM3FR_ _ Path:KRY VA Nonpersonal Ads: Journal AdsPath: PrePress:Horizon:Krystexxa:11760971:11760971_2022_KXX_Brief_Summary_M14.inddJob info _ _ Images FontsSpecial InstructionsDate: 5-14-2024 11:00 AM L-KRY-US-00018 KRYSTEXXA HCP Brief Sum- None Please rename file: P-KRY-US-01260 04/24Client: Horizon mary_July 2022.pdf (67.48%; 151KB)Product: KrystexxaClient Code:P-KRY-US-01260 Additional InformationWF Issue # None NoneReleasing as: PDFx1AFinal Size: 15.75 (w) x 10.75 (h) - InchesFinishing: NoneGutter: None Inks Additional Comments for SizingColors: 4/0: 4/c processCyan, Magenta, Yellow, Black NoneTeamProducer: Tiffany ChangAD: Sara LeslieAE: Cristin Parise Scale: 1"= 1"QC: LW Bleed 16" w x 11" h 16" w x 11" hProduction: Steve Bertuzzi Trim/Flat 15.75" w x 10.75" h 15.75" w x 10.75" hDigital Artist: Agosto, Victor (NYC-SRX) Live/Safety 14.75" w x 9.75" h 14.75" w x 9.75" h Path: PrePress:Horizon:Krystexxa:12131058:12131058_KRY_VA_Nonpersonal_Journal_Ad_M3FR.inddPDFX1A _'