{"id":1829,"date":"2022-08-11T11:34:28","date_gmt":"2022-08-11T11:34:28","guid":{"rendered":"https:\/\/palynziqhcp-dev-001.azurewebsites.net\/en-us\/palynziq\/?page_id=1829"},"modified":"2024-06-12T14:06:36","modified_gmt":"2024-06-12T14:06:36","slug":"side-effects-and-safety-profile","status":"publish","type":"page","link":"https:\/\/hcp.biomarin.com\/en-us\/palynziq\/side-effects-and-safety-profile\/","title":{"rendered":"Safety Profile"},"content":{"rendered":"
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Safety Profile\n<\/h1>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n <\/div>\n\n
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Recognizing how the immune system responds to PALYNZIQ is critical to understanding the safety, dosing, and efficacy<\/h2>\n

As with all therapeutic proteins, there is potential for immunogenicity1<\/sup><\/p>\n <\/div>\n\n

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Non\u2013IgE-mediated anaphylaxis was observed in PALYNZIQ clinical trials1,a<\/sup><\/h3>\n <\/div>\n\n
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\n\t\t\t \"Non\u2013IgE-mediated\t\t\t<\/div>\n\t\t\t
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Anaphylaxis has been reported after administration of PALYNZIQ and may occur at any time during treatment1<\/sup><\/h3>\n
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  • Most episodes occurred within 1 hour after injection (81%; 34 of 42 episodes), though delayed episodes also occurred up to 48 hours after administration of PALYNZIQ1<\/sup><\/li>\n
  • Most episodes occurred within 1 year of dosing (69%; 29 of 42 episodes), but cases also occurred after 1 year of dosing and up to 1604 days (4.4 years) of total follow-up1<\/sup><\/li>\n
  • 48% of anaphylaxis episodes (20 of 42 episodes) were managed with administration of auto-injectable epinephrine1<\/sup><\/li>\n
  • Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis1<\/sup><\/li>\n<\/ul>\n

    a <\/sup>27 of 29 patients who had anaphylaxis were tested for anti\u2013pegvaliase-pqpz IgE antibodies, which recognize the PEGylated protein product. Of those 27 patients, 26 tested negative. The one patient who screened positive for anti\u2013pegvaliase-pqpz IgE had insufficient sample to confirm IgE positivity. This patient tested negative for anti\u2013pegvaliase-pqpz IgE at routine visits before and after the anaphylaxis episode.1<\/sup><\/small><\/p>\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n

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    Learn about different types of hypersensitivity\n<\/h2>\n\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t
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    Type I vs Type III hypersensitivity<\/h2>\n <\/div>\n\n
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    \n\t\t\t \"Type\t\t\t<\/div>\n\t\t\t
    \n\t\t\t \"Type\t\t\t<\/div>\n <\/div>\n <\/figure>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n
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    In the clinical trials, the majority of adverse reactions were mild to moderate in severity1,2<\/sup><\/h3>\n <\/div>\n\n
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    \n\t\t\t \"Most\t\t\t<\/div>\n\t\t\t
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    • 15% of patients (44 of 285) discontinued treatment due to an adverse event1<\/sup><\/li>\n
    • The most common adverse reactions leading to discontinuation were hypersensitivity reactions (6%), including anaphylaxis (3%), angioedema (1%), arthralgia (4%), generalized skin reactions lasting at least 14 days (2%), and ISRs (1%)1<\/sup><\/li>\n<\/ul>\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n
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      View adverse reactions by exposure-adjusted rate\n<\/h2>\n\t\t\t\t\t\t\t\t\t<\/div>\n\t\t\t\t
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      The exposure-adjusted rate of adverse reactions was highest during induction and titration, and generally decreased in the maintenance phase1<\/sup><\/h3>\n <\/div>\n\n
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      \n\t\t\t \"Adverse\t\t\t<\/div>\n\t\t\t
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      c<\/sup>\u00a0Hypersensitivity, including anaphylaxis.<\/small><\/p>\n

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      • The exposure-adjusted rate represents the number of episodes divided by person-years (the number of patients multiplied by the years patients were exposed to treatment)<\/small>\n
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        • It is calculated by taking the number of events divided by the number of person-years (the number of patients multiplied by the number of years they were exposed to the treatment)<\/small><\/li>\n<\/ul>\n <\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n
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          Rates of the 3 most common adverse reactions decreased from induction\/titration to maintenance,d<\/sup> despite increasing dose1,6<\/sup><\/h3>\n <\/div>\n\n
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          \n\t\t\t \"Comparison\t\t\t<\/div>\n\t\t\t
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          <\/p>\n

          c<\/sup>Hypersensitivity, including anaphylaxis.
          \nd<\/sup>Maintenance phase defined as when subjects reached stable dose for 8 weeks.
          \ne<\/sup>Hypersensitivity, including anaphylaxis.
          \nf<\/sup>Maintenance, all doses includes patients on placebo and PALYNZIQ doses <20 mg.<\/small><\/p>\n<\/figcaption>\n <\/figure>\n <\/div>\n <\/div>\n<\/div>\n\n

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          The types and rate of adverse reactions reported during the maintenance phase were similar in patients who received 20 mg, 40 mg, and 60 mg once daily.1<\/sup><\/h4>\n\t\t\t\t\t\t \t\t\t\t\t <\/div>\n\t\t\t\t\t <\/div>\n\t\t\t\t<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n
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          • The exposure-adjusted rate of anaphylaxis was highest during induction and titration phases (0.25 episodes\/person-years) and decreased in the maintenance phase (0.05 episodes\/person-years)<\/li>\n
          • The frequency of hypersensitivity reactions with PALYNZIQ is highest early in treatment when the immune response is most reactive, but may occur at any time during treatment1<\/sup><\/li>\n
          • Later in treatment, the immune response stabilizes1,3<\/sup><\/li>\n
          • The exposure-adjusted rate represents the number of episodes divided by person-years (the number of patients multiplied by the years patients were exposed to treatment)\n
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            • It is calculated by taking the number of events divided by the number of person-years (the number of patients multiplied by the number of years they were exposed to the treatment)<\/li>\n<\/ul>\n<\/li>\n<\/ul>\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n
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              In clinical trials, adverse reactions were managed with medication, dose reduction, interruption, and discontinuation1<\/sup><\/h2>\n <\/div>\n <\/div>\n <\/div>\n<\/div>\n\n
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              \n \"Medicine <\/div>\n <\/figure>\n <\/div>\n
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              Premedication1<\/sup>\n<\/h3>\n

              Premedication may be considered, based on individual patient tolerability, prior to each dose of PALYNZIQ. Most frequently administered H1- and H2-receptor antagonists and antipyretics during PRISM-2 g,h,i,j<\/sup><\/p>\n

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              • ranitidine hydrochloridej<\/sup><\/li>\n
              • ibuprofen<\/li>\n
              • fexofenadine hydrochloride<\/li>\n
              • cetirizine hydrochloride<\/li>\n
              • diphenhydramine hydrochloride<\/li>\n
              • loratadine<\/li>\n
              • acetaminophen<\/li>\n
              • naproxen sodium<\/li>\n<\/ul>\n <\/div>\n<\/div>\n\n
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                \n \"Anaphylaxis <\/div>\n <\/figure>\n <\/div>\n
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                Anaphylaxis1<\/sup><\/span>\n<\/h3>\n
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                • Medication<\/strong>: managed with autoinjectable epinephrine, corticosteroids, antihistamines, and\/or oxygen<\/li>\n
                • Dose reduction<\/strong>: 9.5%<\/li>\n
                • Interruption<\/strong>: 35.7% of patients<\/li>\n
                • Discontinuation<\/strong>: 21.4% of patients<\/li>\n<\/ul>\n <\/div>\n<\/div>\n\n
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                  \n \"Arthralgia <\/div>\n <\/figure>\n <\/div>\n
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                  Arthralgia1<\/sup>\n<\/h3>\n
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                  • Medication<\/strong>: managed with nonsteroidal anti-inflammatory drugs, glucocorticoids, and acetaminophen<\/li>\n
                  • Dose reduction<\/strong>: 3.8% of patients<\/li>\n
                  • Interruption<\/strong>: 3.6% of patients<\/li>\n
                  • Discontinuation<\/strong>: 0.6% of patients<\/li>\n<\/ul>\n <\/div>\n<\/div>\n\n
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                    \n \"Injection <\/div>\n <\/figure>\n <\/div>\n
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                    Injection site reactions1<\/sup>\n<\/h3>\n
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                    • Medication<\/strong>: treated with topical antihistamine, corticosteroids<\/li>\n
                    • Dose reduction<\/strong>: 0.4% of patients<\/li>\n
                    • Interruption<\/strong>: 0.3% of patients<\/li>\n
                    • Discontinuation<\/strong>: 0.1% of patients<\/li>\n<\/ul>\n <\/div>\n<\/div>\n\n
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                      g<\/sup>Patients (n=215) may have been prescribed premedications in combination, and\/or may have switched between different premedication regimens during the study period.
                      \n<\/small>h<\/sup>The rates of use of these medications in this population only partially reflects their use as premedications; these medications may also have been used to treat other conditions, such as seasonal allergies, headaches, etc.
                      \n<\/small>i<\/sup>During PRISM-2, premedication was administered 2-3 hours prior to PALYNZIQ.
                      \n<\/small>j<\/sup>Please note: the FDA has advised a voluntary recall of ranitidine made by many manufacturers, due to concerns over purity. Consider substituting a different H2 blocker.<\/small><\/p>\n <\/div>\n<\/div>\n\t\t\t<\/div>\n\t\t<\/div>\n\t<\/div>\n<\/div>\n\n

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                      References:\n<\/h4>\n\t\t\t\t\t\t
                        \n
                      1. PALYNZIQ [package insert]. Novato, CA: BioMarin Pharmaceutical Inc; 2020. \n<\/span><\/li>\n
                      2. Thomas J, Levy H, Amato S, et al<\/em>, for the PRISM investigators. Pegvaliase for the treatment of phenylketonuria: results of a long-term phase 3 clinical trial program (PRISM). Mol Genet Metab<\/em>. 2018;124(1):27-38. \n<\/span><\/li>\n
                      3. Gupta S, Lau K, Harding CO, et al<\/em>. Association of immune response with efficacy and safety outcomes in adults with phenylketonuria administered pegvaliase in phase 3 clinical trials. EBioMedicine<\/em>. 2018;37:366-373. \n<\/span><\/li>\n
                      4. Monta\u00f1ez MI, Mayorga C, Bogas G, et al<\/em>. Epidemiology, mechanisms, and diagnosis of drug-induced anaphylaxis. Front Immunol<\/em>. 2017;8:1-10. \n<\/span><\/li>\n
                      5. Hausmann O, Daha M, Longo N, et al<\/em>. Pegvaliase: immunological profile and recommendations for the clinical management of hypersensitivity reactions in patients with phenylketonuria treated with this enzyme substitution therapy. Mol Genet Metab<\/em>. 2019;128(1-2):84-91. doi:10.1016\/j.ymgme.2019.05.006. \n<\/span><\/li>\n
                      6. Data on file, BioMarin Pharmaceutical Inc; 2017.\n<\/span><\/li>\n <\/ol>\n\t\t\t\t\t<\/div>\n\t<\/div>\n<\/div>\n\n","protected":false},"excerpt":{"rendered":"","protected":false},"author":2,"featured_media":0,"parent":0,"menu_order":0,"comment_status":"closed","ping_status":"closed","template":"","meta":{"_acf_changed":false,"inline_featured_image":false,"footnotes":""},"acf":[],"yoast_head":"\nSafety Profile | Palynziq HCP<\/title>\n<meta name=\"description\" content=\"Recognizing how the immune system responds to PALYNZIQ is critical to understanding the safety, dosing, and efficacy.\" \/>\n<meta name=\"robots\" content=\"index, follow, max-snippet:-1, max-image-preview:large, max-video-preview:-1\" \/>\n<link rel=\"canonical\" href=\"https:\/\/hcp.biomarin.com\/en-us\/palynziq\/side-effects-and-safety-profile\/\" \/>\n<meta property=\"og:locale\" content=\"en_US\" \/>\n<meta property=\"og:type\" content=\"article\" \/>\n<meta property=\"og:title\" content=\"Safety Profile | 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