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 Islander ImmunogenicityLactation healthcare providers prepared to manage anaphylaxis.first 3 months were 66% and 69% for the group trea PatientsIn this trial, the percentages of pated with tients with any flare for the and 5 identified as Othe1r;4 2 w8 ewree rAes iHains,p 5an wice roerNLaattiinvoe.HCaowmamiiaonn/Other PAs with all theraacific IslanderImmunogenicityRisk Summary Lactation should be pre-treated with antihistamines and corticosteroids. peutic proteins, there is a potential for KRYSTEXXA co-administered with methotrexafirst 3 months were 66% and 69% for the group treate and the groupted withved incidence of antibodpeutic proteins,y positivitythere is a potential for It is not known whether this drug is excreted in human milk.Risk Summary Anaphylaxis may occur with anshould be pre-treay infusion, incted with antihistamines and corticosteroids.luding a first infusion, co-morbid conditions amanodn g5tihdee netnifiroeldle ads p Oatthieenrt;s 2 i8n cwluedreed Hispanic or immunogenicityLatino. Common.The obserAs with all theraand 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 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 dyipseeratseen 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 unknotreated with KR , treated with KRYSTEXXA alone, respectivelyte, unless the c Therefore, KRYSTEXXA should not be used when breastfeeding wn the percentages of patients with antreated with KRy flare for the subsequent 3 YSTEXXA co-administered with methotrexadiabete,tes (18%) and depgreassstrioone s(o1p6h%a)g. ePaal trieenfltusx w diitshe aasne e (G2F2R%), obesityhandling, (20%), t timing of sample collection,ype 2 concomitant medications, risk to the newborn/infant.Patients should be closely monitored for an adelayed type hypersensitivity reactions happropriate period ofve also been reported. assay sensitivity and specificity and assay methodology, sampleunless the clear benefit to the mother can overcome the unknown time for anaphylaxis after administraPatients should be ction of KRlosely monitored for an aYSTEXXA. Patientsppropriate period ofthe percentages of patients with an 8% y flare for the subsequent 3 40 mL/min/1.73 m wdeiraeb eexteclsu d(1e8d% from) an dt hdise ptrreiasl.sion (16%). Patientsand underlying disease. with an eGFRhandling, timing of sample collection, risk to the newborn/infant.month increments of treatment were 27% during Month 6,For these reasons, the comparison ofconcomitant medications, KRYSTEXXA (pegloticase) injection, for intravenous use time for anaphylaxis after administraphylaxis and tion of KRYSTEXXA.during Month 9 and 9% during Month 12. Patientsmonth increments of trea In the group treatment were 27% during Month 6,ted 8%40 mL/min/1.73 m were excluded from this the incidence of antibodies to pegloticase with the incidence ofPediatric UsePediatric Useshould be informed of the symptoms and signs of ana trial. and underlying disease. For these reasons, the comparison of KRYSTEXXA(pegloticase) injection, for intravenous use 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 the the incidence of antibodies to pegloticase with the incidence of The safety and effectiveness of KRYSTEXXA in pediatric patientsinstructed to seek immediate medical care should anaphylaxiswith KRYSTEXXA alone, the percentages of patients with any flaredreactionantibodies to other products may be misleading.Brief Summary - Please see the KRYSTEXXA package insertinstructed to seek immediate medical care should anaphylaxisorrete.T haed vmeorssetduring theantibodies to other products may be misleading. ctiveisnheesds. of KRYSTEXXA in pediatric patients with KRYSTEXXA alone, the percentages of patients with any flare methotrexate pre-treatmTehnetmpeorsito cdos mwmaso ngloyu rte flpa less than 18 years of agTeh hea svaef entoytabnede ne fefestablfor 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% duringent periods was gout flIn a 52-week,are. The mos randomized,t double-blind trial which evaluatedless 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 advemreseth roetarecxtiaotnes p trhea-tt roecactmurred in5% infor Full Prescribing Information. The risk of anaphylaxis is higher in patients whose uric acid levelMonth 12. Month 12. either treatment group dcuorminmg othnelyKreRpYoSrTtEedX XaAd vceor-saed rminister ed in5% inGeriatric UseGeriatric Use eactionse dthat occKRurrYSTEXXA co-administered with methotrexaIn a 52-week, randomized,te compared todouble-blind trial which evaluated WARNING:ANAPHYLAXIS and INFUSION REACTIONS, with methotrexate or KReYitShTeErX tXreAa atmloennetpgerroiuopdar tely 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 withdueri npgro tvhidee KdR iYnSTEXXA KRco-YSTEXXA alone,administered approximaKRYSTEXXA co-administered with methotrexate compared toOf the total number of patients treated with KRYSTEXXA 8 mg WARNING:ANAPHYLAXIS and INFUSION REACTIONS,levels above 6 mg/dL are obserincreases to above 6 mg/dL, 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 ved. 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.G6PD DEFICIENCY ASSOCIATED HEMOLYSIS andlevels above 6 mg/dL are obser Table 1. every 2 weeks in the controlled studies, 34% (29 of 85) were 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 to ved. Monitor serum uric acid levels treatment groups, but more so with KRKRYSTEXXA alone,YSTEXXA trea the frequencies of gout flares were high in all tment duringin titer from baseline or who were negaexisting antibodies to pegloticase.tive at baseline andPatients with an increase65 years of age and older and 12% (10 of 85) were 75 years of METHEMOGLOBINEMIA prior to infusions and discontinue treatment if levels increase totreatment groups, but more so with KRYSTEXXA treatment during Table 1.Adverse Reactions Occurring in 5% or More ofage and older. No overall differences in safety or effectiveness METHEMOGLOBINEMIA above 6 mg/dL. Because of the possibility that concomitant use ofthe first 3 months of treatment, and decreased in the subsequenttive at baseline and 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 ain titer from baseline or who were negat one or more postwere observed between older and younger paage and older. No overall differences in safety or effectiveness tients, but greater See full prescribing information for complete boxed warning. 3 months of treatment. the first 3 months of treatment, and decreased in the subsequent y flarePatients in Either the KRYSTEXXA Co-administered withdeveloped an anti-pegloticase response at one or more posttients, but greaterAnaphylaxis and infusion reactions have been reportedoral urate-lowering therapy and KRYSTEXXA may potentially bluntThe percentages of patients with an Patients in Either the KRYSTEXXA Co-administered with dose time points was 30% and 51%, for the KRYSTEXXA co- were observed between older and younger pa No doseAnaphylaxis and infusion reactions have been reportedThe percentages of patients with anMethotrexate or KRy flareYSTEXXA Alone Treatment Period dose time points was 30% and 51%, for the KRYSTEXXA co-sensitivity of some older individuals cannot be ruled out.the rise of serum uric acid levels,oral urate-lo it is recommended thawering therapy and KRt before YSTEXXA may potentially blunt for the first 3 months were 74%,3 months of trea 81%, and 51%,tment.for KRYSTEXXA 8 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 Periodadministered with methotrexate and KRYSTEXXA alone treatmentsensitivity of some older individuals cannot be ruled out. No dose 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 methotrexate and KRYSTEXXA alone treatment adjustment is needed for patients 65 years of age and older. Anaphylaxis may occur with anto occur during and after administration of KRstarting KRYSTEXXA.YSTEXXA patients discontinue oral ura groups, respectively. Patients with higher antibody titers wereadjustment is needed for patients 65 years of age and older.y infusion, including a first infusion, and generally manifests within 2 hoursrespectively mg every 2 weeks, KRYSTEXXA 8 mg every 4 weeks, and placebo, y titers wereAnaphylaxis may occur with any infusion,medica including a tions and not institute therastarting KRpy with oral uraYSTEXXA patients discontinue oral urate-loweringte-lowering .The percentages of patients with any flare for theKRYSTEXXA more likely to have faster cgroups,learance and lo respectivelywer efficac. Patients with higher antibody. Renal Impairment medications and not institute therapy with oral urasubsequent 3 months were 41%,te-loweringrespectively 57%,.The percenta AdversewithKRYSTEXXA KRYSTEXXA more likely to have faster clearance and lower efficacNo dose adjustment is required for pay. Renal Impairment first infusion, and generally manifests within 2 hours and 67%, for KRges of paYSTEXXA tients with any flare for theKRYSTEXXA tients with renal impairment.of the infusion. However, delayed hypersensitivityagents while taking KRYSTEXXA. Alone During pre-marketing 24-week controlled clinical trials with agents while taking KRYSTEXXA. 8 mg every 2 weeks, KRsubsequent 3 months were 41%, 57%, and 67%, for KRYSTEXXAMethotrexate withAlone During pre-marketing 24-week controlled clinical trials with In a 52-week, randomized,No dose adjustment is required for pa double-blind trial which evaluated tients with renal impairment. reactions have also been reported.of the infusion. However, delayed hypersensitivity Infusion Reactions YSTEXXA 8 mg every 4 weeks, andReaction Adverse (N=49) KRYSTEXXA alone, anti-pegloticase antibodies developed in 92%In a 52-week, randomized, double-blind trial which evaluated 8 mg every 2 weeks, KRYSTEXXA 8 mg every 4 weeks, andMethotrexatereactions have also been reported. Infusion Reactions placebo, respectively. Patients received gout flare prophylaxis with(N=96) n (%) (N=49) YSTEXXA alone,y 2 weeks, anti-pegloticase antibodies developed in 92% KRYSTEXXA co-administered with methotrexate compared toKRYSTEXXA should be administered in healthcareIn a 52-week, controlled trial which evaluated KRYSTEXXA placebo, respectively. Patients received gout flare prophylaxis withReaction (N=96) KRYSTEXXA everand 28%KRYSTEXXA co-administered with methotrexate compared to of patients treated with KR KRYSTEXXA should be administered in healthcaren (%) n (%) KRYSTEXXA alone, 85% of patients had chronic kidney disease settings and by healthcare providers prepared tod triRaYl SwThEicXhX Aevaluated KRYSTEXXAcolchicine and/or nonsteroidal anti-inflammatory drugs (NSAIDs)n (%) for placebo. of patients treated with KRYSTEXXA every 2 weeks, and 28%KRYSTEXXA alone, 85% of patients had chronic kidney disease co-administered with mIent hao 5tr2e-xwateee cko, mcopnatrreodlle to K colchicine and/or nonsteroidal anti-inflammatory drugs (NSAIDs)Anti-PEG antibodies were also detected in 42% of settings and by healthcare providers prepared tobased on estimated glomerular filtration rate (eGFR) of40 to manage anaphylaxis and infusion reactions. ctoio-nasd]m, pinaitsietenrtesd w weirtehpmree-thtroetaretexda twe icthompared tstarting ao KRYSTEXXAt least one week before receiving KRYSTEXXA. Gout flare64(67%) 35 (71%) for placebo. High anti-pegloticase antibod based on estimated glomerular filtration rate (eGFR) of40 toalone [see Adverse Reac starting at least one week before receiving KRYSTEXXA. patients treated with KRYSTEXXA.Anti-PEG antibodies were also detected in 42% of y manage anaphylaxis and infusion reactions. Gout flare64 (67%) 35 (71%) patients treated with KRYSTEXXA. High anti-pegloticase antibody 90 mL/min/1.73 m at baseline. In the pre-marketing 24-weekPre-medicate with antihistamines and corticosteroidsstandardized infusion reaalcotnioen [ speroep AhdyvlaexrsiseaRneda cwteiornes d],i spcaotnietnintus ewdere prGout flares may occur after initiae-treated with tion of KRYSTEXXA.An increasetiter was associated with a failure to maintain pegloticase-induced 90 mL/min/1.73 m at baseline. In the pre-marketing 24-weekPre-medicate with antihistamines and corticosteroidsGout flares may occur after initiation of KRYSTEXXA.An increase13(14%) 5(10%) titer was associated with a failure to maintain pegloticase-induced controlled clinical trials with KRYSTEXXA alone, a total of 32% and closely monitor for anaphylaxis for an appropriated iizfe sde rinufmus uiornicraecaicdt iloenv eplrsophylaxis and in gout flares is frequently obserwere discontinued ved upon initiation of anti- Arthralgia normalization of uric acid.The impact of anti-PEG antibodies oncontrolled clinical trials with KRYSTEXXA alone, a total of 32% from treatment with KRYsStaTnEdXaXrAand closely monitor for anaphylaxis for an appropriatein gout flares is frequently observed upon initiation of anti- Arthralgia 13 (14%) 5 (10%)period of time after administration of KRYSTEXXA. from atrt e2a tcmonesnet cwuittihv eK vRiYsiStsT EaXftXeArtifh eserum uric ahyperuricemic theracid levels py, due to changing serum uric acid levelsnormalization of uric acid.peuticsThe impact of anti-PEG antibodies on (27 of 85) of patients treated with KRYSTEXXA 8 mg every 2 increased to above 6 mg/dLpatients responses to other PEG-containing thera (27 of 85) of patients treated with KRYSTEXXA 8 mg every 2 period of time after administration of KRYSTEXXA. sits after the 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 infusioninitiation of KRYSTEXXA itnhcerreaapsye dto t ore adbuocvee t h6e m rigs/kd Lo fa itn 2fu csioonnsecutive viresulting in mobilization of urate from tissue deposits.py, due to changing serum uric acid levelsGout flareis unknown. weeks had a creatinine clearance of 62.5 mL/min. No overallMonitor serum uric acid levels prior to each infusionisk of infusion COVID-19 9(9%) 3 (6%) is unknown. differences in efficacy were observed.reactions. Infusion reactiinon w resulting in mobilization of uratory drug (NSAID) te from tissue deposits. Gout flare and discontinue treatment if levels increase to above 6itisa tioenr eo fr eKpRoYrSteTdE XinX 4A% th oefr appayt ieton trseduce the rprophylaxis with a non-steroidal anti-inflamma differences in efficacy were observed.and discontinue treatment if levels increase to above 6% of patients Nausea 5( 5%) 6(12%) There was a higher incidence of infusion reactions in patients in the KRYSTEXXA co-adrmeaicntisiotnerse. dIn wfuisthio mn e 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 6rethaocttrioenxas twe egrreo urepported in 4or colchicine is recommended starting at least 1 week beforeNausea 5( 5%) 6 (12%) OVERDOSAGEmg/dL, particularly when 2 consecutive levels above 6RYST YSTEXXA theraor colchicine is recommended starting at least 1 week before5(5%) 2 (4%) with high anti-pegloticase antibody titer: 53% (16 of 30) in theOVERDOSAGE ve been reported.mg/dL are observed. XXithAKcoR-YaSdTmEiXnXisAt earleodn ewith methoinitiatrexation of KRte group py and lasting at least 6 months, Fatigue with high anti-pegloticase antibody titer: 53% (16 of 30) in the No reports of overdosage with KRYSTEXXA ha compared to 31% of patiine nthtsetKreatedE wmg/dL are observed.y prior tocompared to 31% of Rpeaaticetniotsn str]e. aInte bdo twhith KRYSunless medically contraindicaTEXXA alone initiation of KR Fatigue 5 (5%) KRYSTEXXA every 2 weeks group compared to 6% in patientsNo reports of overdosage with KRYSTEXXA have been reported.Screen patients at risk for G6PD deficienc experienced infusion reactions [see Adverseted or not toleraYSTEXXA therated. KRYSTEXXA py and lasting at least 6 months, 2 (4%) KRYSTEXXA ever The maximum dose that has been administered as a single who had undetectable or low antibody titers.y 2 weeks group compared to 6% in patients starting KRYSTEXXA.Screen patients at risk for G6PD deficiency prior toe actions]. In both unless medically contraindicated or not toleraTheted. KRYSTEXXA4 (4%)a 15 (31%) a who had undetectable or low antibody titers. The maximum dose that has been administered as a single Hemolysis and treatment groups, the maxjopreirtyie onfc eindf uinsifounsi orena rcetaiocntiso oncsc [usreree dA davterse Redoes not need to be discontinued because of a gout flare. Infusion reaction intravenous dose is 12 mg as uricase protein. Patients suspected starting KRYSTEXXA. Hemolysis and treatment groups, the majority of infusion reactions occurred at does 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 methemoglobinemiahave been reported withthe first or second KRYSTEXXA infusion and during the time of gout flare should be managed concurrently as appropriate for thePostmarketing Experienceof receiving an overdose should be monitored, and general methemoglobinemiahave been reported withPain in extremity 1 (1%) 3 (6%) Postmarketing Experiencesupportive measures should be initiaof receiving an overdose should be monitored,ted as no specific antidote and general KRYSTEXXA in patients with G6PD deficiency. the first or second eKaRcYtSioTnEsX wXAe rien fsuimsioilna rand durindividual paing the timetientof [see Dosagout flare should be mana Pain in extremity 1 (1%) The following adverse reactions have been identified during infusion. Manifestations of these infusion r ge and Administration].ged concurrently as appropriate for the3 (6%)KRYSTEXXA in patients with G6PD deficiency. individual patient [see Dosage and Administration]. The following adverse reactions have been identified duringsupportive measures should be initiated as no specific antidote KRYSTEXXA is contraindicated in patients with G6PDinfu-msioanrk. eMtianngi fterisatalst.ions of these infusion reactions were similar postapproval use of KRYSTEXXA. Because these reactions arehas been identified.to that observed in the preKRYSTEXXA is contraindicated in patients with G6PDto that observed in the pre-marketing trials. Congestive Heart FailureHypertension 1 (1%) 3 (6%) postapproval use of KR has been identified.reported voluntarily from a population of uncertain size,YSTEXXA. it is notBecause these reactions are deficiency. During pre-marketing 24-week controlled clinical trials withCongestive Heart FailureHypertension 1 (1%) 3 (6%) PATIENT COUNSELING INFORMATIONdeficiency. KRYSTEXXA has not been formally studied in patients withtion of uncertain size, it is not During pre-marketing 24-week controlled cwinglinical trials withKRYSTEXXA has not been formally studied in patients with0 4 (8%) always possible to reliably estimareported voluntarily from a populate their frequency or establishPATIENT COUNSELING INFORMATION KRYSTEXXA alone, KRYSTEXXA was not discontinued follo congestive heart failure, but some patients in the pre-marketing, VomitingVomiting0 4 (8%) always possible to reliably estimate their frequency or establishAdvise the patient to read the FDA-approved patient labeling INDICATIONS AND USAGE KRYSTEXXA alone, KRYSTEXXA was not discontinued followingcongestive heart failure, but some pation of tients in the pre-marketing, a causal relationship. 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 exacerbaKRYSTEXXA INDICATIONS AND USAGEInfusion24-week controlled c a Included one case of anaphylaxis (Medication Guide). (pegloticase) is indicated for the treatment ofreactions were reported in 26% of pa2 consecutive serum uric acid levels above 6 mg/dL. Two cases of congestive heart failure linical trials experienced exacerbation ofa Included one case of anaphylaxis General disorders and administration site conditions: asthenia, tients treated withcongestive heart failure.chronic gout in adult patients refractorKRYSTEXXA(pegloticase) is indica tment ofreactions were reported in 26% of patients treated withmalaise, peripheral swelling Anaphylaxis and Infusion Reactionsy to conventional therated for the treapy. KRYSTEXXA ALONE General disorders and administration site conditions: asthenia, KRYSTEXXA 8 mg every 2 weeks, and 41% of patients treatedcongestive heart failure.tients receiving Two cases of congestive heart failureAnaphylaxis and Infusion Reactions exacerbation occurred during the trials in pachronic gout in adult patients refractory to conventional therapy. KRYSTEXXA 8 mg every 2 weeks, and 41% of patients treatedKRYSTEXXA ALONE malaise, peripheral swellingAnaphylaxis and infusion reactions can occur at any infusion exacerbation occurred during the trials in patients receiving The data described below reflect exposure to KRYSTEXXA inGout refractory to conventional therapy occurs in patients whowith KRYSTEXXA 8 mg every 4 weeks, compared to 5% oftreatment with KRYSTEXXA 8 mg every 2 weeks. No caseswhile on therapy. Counsel pa Anaphylaxis and infusion reactions can occur at any infusion treatment with KRYSTEXXA 8 mg every 2 weeks. No cases patients with chronic goTuht er edfaratactdoerys ctroi bceodn vbeenlotiwon raelfl tehcetr aepxpyosure to KDRRYUG INTERACTIONSSTEXXA intients on the importance of Gout refractory to conventional therapy occurs in papatientstients whotreated with placebo.with KRTheseYSTEXXA 8 mg ever infusion reactions occurredy 4 weeks, compared to 5% ofDRUG INTERACTIONS while on therapy. Counsel patients on the importance of have failed to normalize serum uric acid and whose signs and inwere reported in placebo-treated patients. Four subjects hadctory to conventional therapy Methotrexate adhering to any prescribed medications to help prevent or have failed to normalize serum uric acid and whose signs andpatients treated with placebo. intraThesevenousinfusion reactionsexacerba occurredtions of pre-existing congestive heart failure whileinwere reported in placebo-treated patients. Four subjects had in two replicate randompizaetdie, nptlsa cweibtho -cchornotnriocl legodu, td oreufbrale- Methotrexate adhering to any prescribed medications to help prevent or symptoms are inadequately controlled with xanthine oxidasepatients being pre-treated with an oral antihistamine, y 2 weeks has been studied in patientslessen the severity of these reactions.symptoms are inadequately controlled with xanthine oxidasepatients being pre-treated with an oral antihistamine, intravenousd, plwacitehbo-controlleKRd, dYSTEXXA 8 mg everouble- YSTEXXA 8 mg every 2 weeks has been studied in paexacerbations of pre-existing congestive heart failure while blind 24-week clinical trinia ltsw: o8 5re ppalitcieantets r awnedroem trizeeated inhibitors at the maximum medically appropriate dose or forcorticosteroid and/or acetaminophen.This pre-treatment mayreceiving KRYSTEXXA 8 mg every 2 weeks during the open-labelcal trials: 85 patients were twith chronic gout refractorreated withKRy to conventional therapy takinglessen the severity of these reactions.phylaxis, Educate patients tients on the signs and symptoms of anainhibitors at the maximum medically appropriate dose or forcorticosteroid and/or acetaminophen.This pre-treatment mayreceiving KRYSTEXXA 8 mg every 2 weeks during the open-label KRYSTEXXA 8 mg everyb 2li nwde 2e4ks-w; 8e4e kp actliineints were treated with with chronic gout refractory to conventional therapy takingEducate 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-administrationincluding wheezing, peri-oral or lingual edema, hemodynamic whom these drugs are contraindicated. have blunted or obscured symptoms or signs of infusion reactionsextension study. KRYSTEXXA 8 mg every 4 weeks; and 43 patients were treated concomitant oral methotrexate 15 mg weekly. Co-administrationincluding wheezing, peri-oral or lingual edema, hemodynamic and therefore the reported frequency may be an underestimate. 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 havewith placebo. ; and 43 patieof methotrexants were treatte with KRedYSTEXXA may increase pegloticaseinstability, and rash or urticaria, nausea or vomiting.These patKieRnYtsS TwEeXrXeA b e8t mwege env tehreya4g wese eokf s23 andExercise caution when using KRYSTEXXA in patients who haveof 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 followingth placebaot. iTehnetss ew peareti emnatsle w aenrde3b9etween theconcentra ages of 2tion compared to KR3 andYSTEXXA alone.Educate patients on the most common signs and symptoms of 89 years (average 55 yewairs); 173 pManifestations 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 of asymptomatic hyperuricemia.KRYSTEXXA is not recommended for the treatment of 10.6%), dyspnea (frequency of 7.1%), chest discomfort (frequencywere female; and 143 painfusion. infusion. 89ti eynetasr sw (earvee Wrahgiete 5/C5a yuecaarssi)a; n1, 7237pwaetireents werePEGylated products male and 39an infusion reaction, including urticaria (skin rash), erythema an infusion reaction, including urticaria (skin rash), erythema asymptomatic hyperuricemia. 10.6%), dyspnea (frequency of 7.1%), chest discomfort (frequencyale; and 143 patients were White/Caucasian, 27 werePEGylated products (redness of the skin), dyspnea (difficulty breathing), flushing,of 9.5%), chest pain (frequency of 9.5%), erythema (frequencyBlack/African American,w 2e4r ew feerme Hispanic/Latino and 18 were Because anti-pegloticase antibodies appear to bind to the PEG(redness of the skin), dyspnea (difficulty breathing), flushing, CONTRAINDICATIONS of 9.5%), and pruritus (frequency of 9.5%).These manifestationsRe-treatment with KRYSTEXXA H Because anti-pegloticase antibodies appear to bind to the PEG chest discomfort, chest pain, and rash.CONTRAINDICATIONS of 9.5%), chest pain (frequency of 9.5%), erythema (frequencyRe-treatment with KRYSTEXXApeanic/Latino and 18 were No controlled trial data are available on the safety and efficacy all other ethnicities. ComBmlaconk/ cAofr-imcaonr bAimd ecroincdaniti,o 2n4swameroengi sth portion of the drug, there may be potential for binding withchest discomfort, chest pain, and rash.KRYSTEXXA is contraindicated in: These manifestationsall other ethnicities. Common co-morbid conditions among theportion of the drug, there may be potential for binding withAdvise patients to seek medical care immediately if they KRYSTEXXA is contraindicated in: overlap with the symptoms of anaof 9.5%), and pruritus (frequencphylaxis, but in a given y of 9.5%). No controlled trial data are available on the safety and efficacy 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 KRYSTEXXA after stopping treatment for enrolled patients included hypertension (72%), dyslipidemialonger than 4 weeks. Duoeftroe -tthreea itmmmenutn owgitehn iKcRitYyS oTfE KXRXYAS aTfEteXrX Ast,opping treat(m49e%nt) ,f ocrhronic kidney deisneraosllee d(2 p8a%ti)e, ndtisa binectleusd e(2d4 h%y)p, ecroteronna patients responses to other PEG-containing therapeuticsexperience any symptoms of an allergic reaction during or atPatients with glucose-6-phosphate dehydrogenase (G6PD)patient did not occur together to satisfy the clinical criteria forsiorny (72%), dyslipidemiaother PEGylated products. The impact of anti-PEG antibodies on experience any symptoms of an allergic reaction during or at patient did not occur together to satisfy the clinical criteria for deficiency [see Warnings and Precautions] Patients with glucose-6-phosphate dehydrogenase (G6PD) diagnosing anaphylaxis. Infusion reactions are thought to resultis unknown. patients responses to other PEG-containing theraanpeutics y time after the infusion of KRYSTEXXA [see Warnings and nger than 4 weeks. Due to trhisek i mofmunogenicity of KaRrtYeSryT EdXisXeAa,se (18%), ar(r4h9y%th)m, ciah r(o1n6i%c ), and cardiac failure/leftkidney disease (28%), diabetes (24%), coronary deficiency [see Warnings and Precautions] diagnosing anaphylaxis. Infusion reactions are thought to result patients receiving re-trelaotment may be at increasedis unknown. Precautions, Adverse Reactions]any time after the infusion of KRYSTEXXA [see Warnings andPatients with history of serious hypersensitivity reactions, from release of various mediators, such as cytokines. Infusionts rec.eTihveinrgef roer-et,r peaattmienetnstrmecaeyi vbien gat increasedv reisnktr iocfular dysfunction (a1r2te%ry). disease (18%), arrhythmia (16%), and cardiac failure/leftPrecautions, Adverse Reactions]from release of various mediators, such as cytokines. Infusion anaphylaxis and infusionp arteieanctions n reactions.Therefore, patients receiving ventricular dysfunction (12%). USE IN SPECIFIC POPULATIONSAdvise patients to discontinue any oral urate-lowering agents including anaphylaxis, to KR Patients with historYSTEXXA or any of its componentsy of serious hypersensitivity reactions,reactions occurred at any time during a course of treatmentre-treatment after a druagn-afrpehey ilnatxeisrv aanl dsh inofuulds iobe monitored During the pre-marketing placebo-controlled clinical trials, the PregnancyUSE IN SPECIFIC POPULATIONSAdvise patients to discontinue any oral urate-lowering agents reactions occurred at any time during a course of treatment including anaphylaxis, to KRYSTEXXA or any of its componentswith approximately 3% occurring with the first infusion, andDuring the pre-marketing placebo-controlled clinical trials, thePregnancybefore starting on KRYSTEXXA and not to take any oral urate- with approximately 3% occurring with the first infusion, and carefully [see Adverse R reea-ctrteioantms].ent after a drug-free interval should be monitored Risk Summary lowering agents while on KRbefore starting on KRYSTEXXA. YSTEXXA and not to take any oral urate- WARNINGS AND PRECAUTIONS approximately 91% occurred during the time of infusion. carefully [see Adverse Reactions]. most commonly reported adverse reactions that occurred inWARNINGS AND PRECAUTIONS approximately 91% occurred during the time of infusion.ADVERSE REACTIONS monly reported athd vKeRrYseS TreEaXcXtAions that occurred inRisk Summary lowering agents while on KRYSTEXXA.greater than or equal tom 5%os to cf opmatients treated wi There are no adequate and well-controlled studies of KRYSTEXXA AnaphylaxisKRYSTEXXA should be administered in a healthcare setting byADVERSE REACTIONS thannToar belqeu 2a.l to 5% of patients treated with KRYSTEXXAThere are no adequate and well-controlled studies of KRGlucose-6-phosphate dehydrogenase (G6PD) DeficiencYSTEXXAy The following serious adverse reactions are discussed in greater8 mg every 2 weeks areg rperaovteidr ed i in pregnant women. Based on animal reproduction studies, no Anaphylaxishealthcare providers prepared to manaKRYSTEXXA should be administered in a healthcare setting byThe 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 In a 52-week controlled trial, which evaluated KRYSTEXXAge infusion reactions.In a 52-week controlled trial, which evaluated KRYSTEXXAhealthcare providers prepared to manage infusion reactions.detail in other sections of the label: structural abnormalities were observed when pegloticase wasInform patients not to take KRYSTEXXA if they have a condition co-administered with methotrexate compared to KRYSTEXXAPatients should be pre-treated with antihistamines andTable 2.Adverse Reactions Occurring in 5% or More ofstructural abnormalities were obserts and ved when pegloticase wasInform paPatients should be pre-treated with antihistamines andAnaphylaxis [see Warnings and Precautions]detail in other sections of the label: administered by subcutaneous injection to pregnant ra known as G6PD deficiency. Explain to patients not to take KRtients that G6PD YSTEXXA if they have a condition alone, patients were pre-treaco-administered with methotrexated with standardized infusion te compared to KRcorticosteroids.YSTEXXA KRYSTEXXA should be infused slowly over no lessTable 2. Adverse Reactions Occurring in 5% or More ofadministered by subcutaneous injection to pregnant rats andknown as G6PD deficiency. Explain to patients that G6PD Patients Treated with KRYSTEXXA Compared to Placeboalone, patients were pre-treated with standardized infusioncorticosteroids. KRYSTEXXA should be infused slo the infusion Infusion Reactions [seeWAnaarnings and Precautions]phylaxis [see Warnings and Precautions] Patients Treated with KRYSTEXXA Compared to Placeborabbits during the period of organogenesis at doses up to 50deficiency is more frequently found in individuals of African,reaction prophylaxis and were discontinued from treatmentthan 120 minutes. In the event of an infusion reaction, wly over no less Infusion Reactions [see Warnings and Precautions] rabbits during the period of organogenesis at doses up to 50deficiency is more frequently found in individuals of African, with KRYSTEXXA if serum uric acid levels increased to above 6than 120 minutes. In the event of an infusion reaction, G6PD Deficiency Associated Hemolysis and Methemoglobinemiaand 75 times, respectively, the maximum recommended humanMediterranean, or Southern Asian ancestry and that they may be reaction prophylaxis and were discontinued from treashould be slotmentwed, or stopped and restarted at a slower rate.the infusion G6PD Deficiency Associated Hemolysis and Methemoglobinemiaand 75 times, respectively, the maximum recommended humanMediterranean, or Southern Asian ancestry and that they may be mg/dL at 2 consecutive visits after the initiawith KRYSTEXXA if serum uric acid levels increased to above 6 tion of KRYSTEXXAshould be slowed, or stopped and restarted at a slower ra[see Warnings and Precautions] KRYSTEXXA Placebo dose (MRHD). Decreases in mean fetal and pup body weightstested to determine if they have 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 acidte. [see Warnings and Precautions] Adverse8 mg every 2KRYSTEXXA Placebo dose (MRHD). Decreases in mean fetal and pup body weightstested to determine if they have G6PD deficiency, unless already were observed at approximately 50 and 75 times the MRHD,therapy to reduce the risk of anaphylaxis. One patient randomized Gout Flares [see Warnings and Precautions] (N=43) known [see Warnings and Precautions, Contraindications].therapy 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] Reaction Adverse 8 mg every 2respectively [see Data]. 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] weeks (N=85) n (%) (N=43)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 weeks (N=85) n (%) respectively [see Data]. Gout Flaresto the group treated with KRYSTEXXA co-administered with levels above 6 mg/dL are observed. Monitor serum uric acid levelsna (%) na (%) 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 (77%) 35 (81%) or other adverse outcomes.All pregnancies ha In the US general populave a background risk of birth defect,tion, thet 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 and Gout flare65 starting trea loss tment with KRExplain to paYSTEXXA, and thatients that medications to prior to infusions and discontinue treatment if levels increase to above 6 mg/dL. Because of the possibility that concomitant use ofcontrolled conditions, adBveecrasues ree acclitnioicna lr astteusd obs estimated background risk of major birth defects and miscarria help reduce flares may need to be taken regularly for the first treated with KRYSTEXXA aloneinfusion and no pa [see Adverse Reactions]tients experienced ana. phylaxis in the groupabove 6 mg/dL. Because of the possibility that concomitant use ofies aerrev ecdo nind ucclitneidca ulnder widely varying and Gout flare65 (77%) 35 (81%) or other adverse outcomes. In the US general populagetion, thestarting treatment with KRYSTEXXA, and that medications to treated with KRYSTEXXA alone [see Adverse Reactions]oral urate-lo. wering therapy and KRYSTEXXA may potentially bluntrse rea cthtieon rates observed in clinical 22(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 tdov erates 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 KRYSTEXXA may potentially bluntInfusion reaction22 (26%) 2 (5%) in clinical recognized pregnancies is 2% to 4% and 15% to few months after KRYSTEXXA is started [see Warnings and the rise of serum uric acid levels, it is recommended that before During pre-marketing clinical trials with KRYSTEXXA alone, the rise of serum uric acid levels, it is recommended tha studriuegs ,o afn addmruagycnaont nporte dbiec td tirheec rtlayt ecsompared to rates in the 20%, respectively. Precautions, Adverse Reactions].Advise patients that they should KRYSTEXXA was not discontinued following 2 consecutive serumstarting KRYSTEXXA patients discontinue oral urate-loweringclinical st before tudies of another d Nausea 10(12%) 1 (2%) 20%, respectively.clinical studies of another drug, and may not predict the ratesKRYSTEXXA was not discontinued following 2 consecutive serumYSTEXXA patients discontinue oral uraobserved in a broader patient population in clinical practice. Nausea 10 (12%) 1 (2%) Precautions, Adverseve a flare. Reactions]. Advise patients that they should medications and not institute thera not stop KRYSTEXXA therapy if they hauric acid levels above 6 mg/dL.Anaphylaxis was reported with astarting KRpy with oral urate-loweringte-loweringobserved in a broader patient population in clinical practice. Datanot stop KRYSTEXXA therapy if they have a flare. frequency of 6.5% (8/123) of pauric acid levels above 6 mg/dL.tients treated with KRYSTEXXA Anaphylaxis was reported with amedications and not institute therapy with oral uraCo-administration with Methotrexatete-loweringContusionbor 9( 11%) 2(5%) Animal Data DataManufactured by:agents while taking KRYSTEXXA. btients treated with KRYSTEXXAagents while taking KRYSTEXXA. Co-administration with Methotrexate b Contusion or 9( 11%) 2 (5%) Animal DataHorizon 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 dosingA 52-week, randomized, double-blind trial was conducted in Ecchymosis In 2 separate embryo-fetal developmental studies, pregnant regimen.There were no cases of anaevery 2 weeks and 4.8% (6/126) for the ever G6PD Deficiency Associated Hemolysis andadult patients with chroAni c5 2g-owuet erekf, rraacntodroym tioz ecdo,n dvoeunbtiloen-abllind trial was conducted in Ecchymosisb In 2 separate embryo-fetal developmental studies,Dublin, pregnantIrelandHorizon Therapeutics Ireland DAC phylaxis in patientsy 4-week dosingG6PD Deficiency Associated Hemolysis andrats and rabbits received pegloticase during the period of receiving placebo. regimen. Methemoglobinemiaouterevferrayctory to conventional 6(7%) 1 (2%) organogenesis at doses up to arats and rabbits received pegloticase during the period ofDublin, Ireland There were no cases of anaphylaxis in patientstherapy to evaluate admaidniuslttr apatiotine notfsKwRiYthS TcEhXroXnAic 8 g mg Nasopharyngitis pproximately 50 and 75 times Anaphylaxis generally occurred withinMethemoglobinemia 2 hours after treatment. receiving placebo.Anaphylaxis generally occurred within Life threatening hemolytic reactions and methemoglobinemia h ewraitphy w toe eekvlayl uaadtme iandismtriantiisotnra otfio onr aolf KRYSTEXXA 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-administeretd the maximum recommended human dose (MRHD), US License Number 2022 Life threatening hemolytic reactions and methemoglobinemia Distributed by:2 hours after treatment. have been reported with KRYSTEXXA in patients with glucose- Constipation 5 (6%) 2 (5%) (on a mg/m basis at mathe maximum recommended human dose (MRHD), respectively have been reported with KRYSTEXXA in patients with glucose-methotrexate 15 mg, co2m wpaereekdstcoo K-aRdYmSTinEiXstXeAr eadlo wneit.h I nw etheiks lytr iaadl,ministration of oral 5 (6%) 2 (5%) ternal doses up to 40 and 30 mg/kg Diagnostic criteria of anaphylaxis were skin or mucosal tissue6-phosphate dehydrogenase (G6PD) deficiency. Because STEXXA alone. In this trial, Constipation twice 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,Distributed by: Inc.Diagnostic criteria of anaphylaxis were skin or mucosal tissuepatients who were able mtoe ttohloetrraetxea ttwe o1 5w meegk,s c oonm mpaertehdo ttroe xKaRtYe Horizon Therapeutics USA, Inc.involvement, and, either airway compromise, and/or reducedehydrogenase (G6PD) deficiency. Because ChestPain 5 (6%) 1 (2%)No evidence of of the risk of hemolysis a6n-dp hmoespthheamteo dglobinemia, do not otrexate Deerfield, IL 60015involvement, and, either airway compromise, and/or reducedhemolysis and methemoglobinemia, do not olearla wtee tewkosowneeks on meth Chest Pain 5 (6%) structural abnormalities was obsertwice weeklyved in ra, in rats and rabbits,ts or rabbits. Ho respectively).wever, Deerfield, IL 60015blood pressure with or without associated symptoms, and aadminister KRYSTEXXA toofptahteie rnistkswofi th G6PD deficiency [see 15 mg were then randompaiztieedn ttsowrehcoe iwvee rfeo uarb aled tdoit iton 1 (2%)However, 15 mgmwaetrceh itnhge np lraacnedboom pizrieodrttoorineicteiaitvien gfour additional weeks on decreases 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 by temporal relationship to KRblood pressure with or without associa either methotrexate 15 mg or 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 mpaintiiesntetsrKaRt YriSsk for G6PD deficiencyTEXXA to patients with G6PD deficiency [seeKRYSTEXXA therapy. ethotrexate 15e rme gr aonrd momaticzheidn,g placebo prior to initiating Anaphylaxis 4 (5%) 0 (0%) decreases in mean fetal and pup bodts and rabbits,y weights were obseror licensed to Horizon.vedpatients at risk for G6PD deficiency A teoittahle orfm152 subjects w at approximately 50 and 75 times the MRHD in raother identifiable cause. Manifestatemporal relations inctionship to KRluded wheezing,YSTEXXA or placebo injection with noperi- prior to starting KRYSTEXCXoAn.t rFaoinr deixcaamtiopnles,] .p Sactireenetns of African, KRYSTEXXA therapy.A total oeft h15ot2r esxuabtjeects were randomized, 4 (5%) 1 (2%) respectively (on a mg/m basis aat approximat mately 50 and 75 times the MRHD in raternal doses up to 40 and 30ts and rabbits, Therapeutics plc L-KRor licensed to Horizon.Y-US-00018 7/22prior to starting pKeRaYnS aTnEdX XMAi.d Fdoler example, patients of African,and of these, 145 subjects completed the 4-week m VomitingVomiting4 (5%) 1 (2%)2022 Horizon 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 Southern Euro and of these, 145 subjects completed the 4-week methotrexate respectively (on a mg/m basis at maternal doses up to 40 and 30 oral or lingual edema, or hemodynamic instability, with or withoutM run-in period and received KRYSTEXXA (96 subjects received a received mg/kg every other day, in rats and rabbits, respectively).respectively).rash or urticaria, nausea or vomiting. Cases occurred in patientsEastern), and Southern Asieadni taenrrcaensetrayn a (rinec alut dinincgre Saosuedth reirsnk European and Middle If the same subject in a given group had more than oneNo effects on mean fetal bodmg/kg every weights were obsery other day, in raved ats and rabbits,t rash or urticaria, nausea or vomiting. Cases occurred in patientsrurne-din w piethri omde athnodt rreexcaetiev eadn dK R4Y9S rTeEcXeXivAe d(96 subjectsabeing pre-treated with one or more doses of an oral antihistamine, for G6PD deficiency. Eastern), and Southern Asian ancestry are at incKreRaYsSeTdE riskXXA co-administe If the same subject in a given group had more than oneNo effects on mean fetal body weights were observed at KRYSTEXXA co-administered with methotrexate and 49 receivedbeing pre-treated with one or more doses of an oral antihistamine, for G6PD deficiency. KRYSTEXXA plus placebo) during the treatment period.All occurrence in the same preferred term event category, theapproximately 10 and 25 times the MRHD in rats and rabbits,an intravenous corticosteroid and/or acetaminophen.This pre- All occurrence in the same preferred term event category, the an intravenous corticosteroid and/or acetaminophen.Gout FlaresThis pre- KRYSTEXXA hp launsoprlaalc aenbtoih) idsutarimngin teh,e treatment periodsubject was counted only once approximat mately 10 and 25 times the MRHD in rats and rabbits, patients received pre-treatment wit respectively (on a mg/m basis a ternal doses up to 10 mg/kg treatment may have blunted or obscured symptoms or signsGout Flares pa taienndt sa creectaemiveindo pphree-nt.reTahtemsee npta wtiiethnt asn 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 bMost did not occur on the day of infusion and could be related to of anaphylaxis and therefore the reported frequency may beThese patients b Most did not occur on the day of infusion and could be related totwice weekly in both species).of anaphylaxis and therefore the reported frequencKRYSTEXXA co-administered with methotrexay may beIn a 52-week, randomized,te compared todouble-blind trial which evaluawere betweted en the ages ionft r2a4v eannodu s8 3c oyretiacross (atevreoirda gaen d5 5a cyeetaarms)i;nophen. other factors (e.g., concomitant medications relevant to contusion an underestimate. KRYSTEXXA co-administered with methotrexate compared towere between the ages of 24 and 83 years (average 55 years); other factors (e.g., concomitant medications relevant to contusion an underestimate. KRYSTEXXA alone, patients were administered gout flare prophylaxis 135 patients were male and 17 and were female; 105 patientsor 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 administered gouwt eflraer eW phroitpeh/Cylaauxicsasian, 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 BY F:7.875"11760971 KXX Brief Summary PREPARED BY M1411760971 KXX Brief Summary M14Job info Images FontsSpecial InstructionsDate: Job info Helvetica Neue LT Std (57 Condensed, 57 Con-FontsNone Special Instructions7-15-2022 3:53 PM KXX_Logo_Pos_BLACK.ai (44.72%; 70KB)ImagesKXX_Logo_Pos_BLACK.ai densed Oblique), (44.72%; 70KB)Helvetica Neue (Condensed Helvetica Neue LT Std (57 Condensed, 57 Con- None 5/14/24 11:00 AM12131058_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 BY 9.875" w x 14.5" hTrim/Flat 10.375" w x 15" h 10.375" w x 15" hLive/Safety 9.875" w x 14.5" h 12131058vc#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 _'