The following serious adverse reactions are discussed in greater detail in other sections of the label: Anaphylaxis [see Warnings and Precautions (5.1) ] Infusion Reactions [see Warnings and Precautions (5.2) ] G6PD Deficiency Associated Hemolysis and Methemoglobinemia [see Warnings and Precautions (5.3) ] Gout Flares [see Warnings and Precautions (5.4) ] Congestive Heart Failure [see Warnings and Precautions (5.5) ] Co-administration with methotrexate: The most common adverse reactions (≥ 5% of patients) are gout flares, arthralgia, COVID-19, nausea and fatigue.
( 6.1 ) KRYSTEXXA alone: The most common adverse reactions (≥ 5% of patients) are gout flares, infusion reactions, nausea, contusion or ecchymosis, nasopharyngitis, constipation, chest pain, anaphylaxis and vomiting. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Amgen Inc. at 1-800-77-AMGEN (1-800-772-6436) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1Clinical Trials Experience
Because clinical studies are conducted under widely varying and controlled conditions, adverse reaction rates observed in clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug, and may not predict the rates observed in a broader patient population in clinical practice. Co-administration with Methotrexate A 52-week, randomized, double-blind trial was conducted in adult subjects with chronic gout refractory to conventional therapy to evaluate administration of KRYSTEXXA 8 mg every 2 weeks co-administered with weekly administration of oral methotrexate 15 mg, compared to KRYSTEXXA alone.
In this trial, subjects who were able to tolerate two weeks on methotrexate 15 mg were then randomized to receive four additional weeks on either methotrexate 15 mg or matching placebo prior to initiating KRYSTEXXA therapy. A total of 152 subjects were randomized, and of these, 145 subjects completed the 4-week methotrexate run-in period and received KRYSTEXXA (96 subjects received KRYSTEXXA co-administered with methotrexate and 49 received KRYSTEXXA plus placebo) during the treatment period.
All subjects received pre-treatment with an oral antihistamine, intravenous corticosteroid and acetaminophen. These subjects were between the ages of 24 and 83 years (average 55 years); 135 subjects were male and 17 and were female; 105 subjects were White/Caucasian, 22 were Black/African American, 14 were Asian, 5 were Native Hawaiian/Other Pacific Islander and 5 identified as Other; 28 were Hispanic or Latino. Common co-morbid conditions among the enrolled subjects included hypertension (63%), osteoarthritis (25%), hyperlipidemia (24%), gastroesophageal reflux disease (22%), obesity (20%), type 2 diabetes (18%) and depression (16%).
Subjects with an eGFR < 40 mL/min/1.73 m 2 were excluded from this trial. The most commonly reported adverse reaction during the methotrexate pre-treatment periods was gout flare. The most commonly reported adverse reactions that occurred in ≥ 5% in either treatment group during the KRYSTEXXA co-administered with methotrexate or KRYSTEXXA alone period are provided in Table 1. Table 1. Adverse Reactions Occurring in 5% or More of Subjects in Either the KRYSTEXXA Co-administered with Methotrexate or KRYSTEXXA Alone Treatment Period Adverse Reaction KRYSTEXXA with Methotrexate (N = 96) n (%) KRYSTEXXA Alone (N = 49) n (%) Gout flare 64 (67%) 35 (71%) Arthralgia 13 (14%) 5 (10%) COVID-19 9 (9%) 3 (6%) Nausea 5 (5%) 6 (12%) Fatigue 5 (5%) 2 (4%) Infusion reaction 4 (4%) Included one case of anaphylaxis. 15 (31%) Pain in extremity 1 (1%) 3 (6%) Hypertension 1 (1%) 3 (6%) Vomiting 0 4 (8%) KRYSTEXXA ALONE The data described below reflect exposure to KRYSTEXXA in subjects with chronic gout refractory to conventional therapy in two replicate randomized, placebo-controlled, double-blind 24-week clinical trials: 85 subjects were treated with KRYSTEXXA 8 mg every 2 weeks; 84 subjects were treated with KRYSTEXXA 8 mg every 4 weeks; and 43 subjects were treated with placebo.
These subjects were between the ages of 23 and 89 years (average 55 years); 173 subjects were male and 39 were female; and 143 patients were White/Caucasian, 27 were Black/African American, 24 were Hispanic/Latino and 18 were all other ethnicities. Common co-morbid conditions among the enrolled subjects included hypertension (72%), dyslipidemia (49%), chronic kidney disease (28%), diabetes (24%), coronary artery disease (18%), arrhythmia (16%), and cardiac failure/left ventricular dysfunction (12%).
During the pre-marketing placebo-controlled clinical trials, the most commonly reported adverse reactions that occurred in greater than or equal to 5% of subjects treated with KRYSTEXXA 8 mg every 2 weeks are provided in Table 2. Table 2. Adverse Reactions Occurring in 5% or More of Subjects Treated with KRYSTEXXA Compared to Placebo Adverse Reaction KRYSTEXXA 8 mg every 2 weeks Placebo (N = 85) n If the same subject in a given group had more than one occurrence in the same preferred term event category, the subject was counted only once.
(%) (N = 43) n (%) Gout flare 65 (77%) 35 (81%) Infusion reaction 22 (26%) 2 (5%) Nausea 10 (12%) 1 (2%) Contusion Most did not occur on the day of infusion and could be related to other factors (e.g., concomitant medications relevant to contusion or ecchymosis, insulin dependent diabetes mellitus). or Ecchymosis 9 (11%) 2 (5%) Nasopharyngitis 6 (7%) 1 (2%) Constipation 5 (6%) 2 (5%) Chest Pain 5 (6%) 1 (2%) Anaphylaxis 4 (5%) 0 (0%) Vomiting 4 (5%) 1 (2%)
