palynziq

Important safety information

Hypersensitivity Reactions, Other than Anaphylaxis : Management should be based on the severity of the reaction, recurrence, and clinical judgement. ( 5.3 ) Injection Site Infections : Serious injection site infections, including abscess, cellulitis, necrosis, and ulcer have been reported. Instruct patients to contact their healthcare provider if signs or symptoms of an infection develop, persist, or worsen. ( 5.4 ) Hypophenylalaninemia : Some PKU patients treated with PALYNZIQ have experienced hypophenylalaninemia; monitor blood Phe levels periodically during treatment. ( 5.5 ) 5.1 Anaphylaxis In PALYNZIQ Studies 1, 2, and 3 with an induction/titration/maintenance dosage regimen, 10% (29/285) of PALYNZIQ-treated patients experienced a total of 42 anaphylaxis episodes [see Adverse Reactions (6.1) and Clinical Pharmacology (12.6) ]. The exposure-adjusted rate of anaphylaxis was highest during the induction and titration phases (0.25 episodes/person-years; 5% of PALYNZIQ-treated patients with at least one episode) and decreased in the maintenance phase (0.05 episodes/person-years; 7% of PALYNZIQ-treated patients with at least one episode). Signs and symptoms of anaphylaxis reported in PALYNZIQ-treated patients included syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/chest tightness, tachycardia, angioedema (swelling of face, lips, eyes, tongue), throat tightness, skin flushing, rash, urticaria, pruritus, and gastrointestinal symptoms (vomiting, nausea, diarrhea). Anaphylaxis occurred within 1 hour after injection in 81% of PALYNZIQ-treated patients (34/42 episodes); however, delayed episodes also occurred up to 48 hours after PALYNZIQ administration. Anaphylaxis occurred within the first year of dosing in 69% of PALYNZIQ-treated patients (29/42 episodes), but cases also occurred after one year of dosing and up to 1,604 days (4.4 years) into treatment. Management of anaphylaxis in PALYNZIQ-treated patients included: administration of epinephrine (48%; 20/42 episodes), corticosteroids (55%; 23/42 episodes), antihistamines (57%; 24/42 episodes), and/or oxygen (5%; 2/42 episodes). In these trials, 72% (21/29) of patients who experienced anaphylaxis were rechallenged with PALYNZIQ and 29% (6/21) of patients who were rechallenged had recurrence of anaphylaxis. All anaphylaxis episodes resolved without sequelae. In Study 4, conducted in patients who were 12 to less than 18 years of age [see Clinical Trials (14) ], premedication was administered to all patients. A single episode of anaphylaxis, was reported in 11% (4/36) of PALYNZIQ-treated patients with symptoms similar to those reported in the adult clinical trials. All 4 patients were managed with administration of epinephrine. Treatment with PALYNZIQ was discontinued in two patients and the other two patients were rechallenged with PALYNZIQ without recurrence of anaphylaxis. Steps to Take to Prevent, Mitigate, Monitor for, and Manage Anaphylaxis Prior to PALYNZIQ administration, consider premedication with an H 1 -receptor antagonist, H 2 -receptor antagonist, and/or antipyretic based upon individual patient tolerability. Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during PALYNZIQ treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after PALYNZIQ administration, should be able to administer epinephrine, and call for emergency medical support upon its use. Anaphylaxis requires immediate treatment with epinephrine. Prescribe epinephrine to all PALYNZIQ-treated patients while considering the risks associated with epinephrine use (refer to the epinephrine prescribing information for complete information). Instruct patients to carry epinephrine with them at all times during PALYNZIQ treatment. Prior to the first PALYNZIQ dose, instruct the patient and observer (if applicable) on how to recognize the signs and symptoms of anaphylaxis, how to properly administer epinephrine, and to seek immediate medical care upon its use. Consider the risks and benefits of readministering PALYNZIQ following an episode of anaphylaxis. If the decision is made to readminister PALYNZIQ, administer the first dose under the supervision of a healthcare provider equipped to manage anaphylaxis and closely observe the patient for at least 60 minutes following the dose. Subsequent PALYNZIQ dose titration should be based on patient tolerability and therapeutic response. PALYNZIQ is available only through a restricted program under a REMS [see Warnings and Precautions (5.2) ]. 5.2 PALYNZIQ REMS PALYNZIQ is available only through a restricted program under a REMS called the PALYNZIQ REMS because of the risk of anaphylaxis [see Warnings and Precautions (5.1) ]. Notable requirements of the PALYNZIQ REMS include the following: Prescribers must be certified with the program by enrolling in the program and completing training. Prescribers must prescribe epinephrine with PALYNZIQ. Pharmacies must be certified with the program and must dispense only to patients who are authorized to receive PALYNZIQ. Patients must enroll in the program and be educated about the risk of anaphylaxis by a certified prescriber to ensure they understand the risks and benefits of treatment with PALYNZIQ. Patients must have epinephrine available at all times while taking PALYNZIQ. Further information, including a list of qualified pharmacies, is available at www.PALYNZIQREMS.com or by telephone 1-855-758-REMS (1-855-758-7367). 5.3 Other Hypersensitivity Reactions In Studies 1, 2, and 3 of PALYNZIQ with induction/titration/maintenance dosage regimen, hypersensitivity reactions, other than anaphylaxis [see Warnings and Precautions (5.1) , Adverse Reactions (6.1) , and Immunogenicity (12.6) ], have been reported in 72% (204/285) PALYNZIQ-treated patients. The exposure adjusted rate of other hypersensitivity reactions was highest during the induction and titration phases (4.3 episodes/person-year; 50% of PALYNZIQ-treated patients with at least one adverse reaction) and decreased in the maintenance phase (1.3 episodes/person-year; 61% of PALYNZIQ-treated patients with at least one adverse reaction). Hypersensitivity reactions generally occurred more frequently in PALYNZIQ-treated patients with higher anti-pegvaliase-pqpz antibody titers [see Clinical Pharmacology (12.6) ]. In Study 4, hypersensitivity reactions other than anaphylaxis were reported in 33% (12/36) of PALYNZIQ-treated patients who were 12 to less than 18 years of age. The exposure adjusted rate of other hypersensitivity reactions during the induction and titration phases was 1 episodes/person-year; 3/36 (8%) of PALYNZIQ-treated patients had at least one adverse reaction. The exposure adjusted rate of other hypersensitivity reactions during the maintenance phase was 1.4 episodes/person-year; 11/34 (32%) of PALYNZIQ-treated patients had at least one adverse reaction. Prior to PALYNZIQ administration, consider premedication with an H 1 -receptor antagonist, H 2 -receptor antagonist, and/or antipyretic based upon individual patient tolerability [see Dosage and Administration (2.1) ] . Management of hypersensitivity reactions should be based on the severity of the reaction, recurrence of the reaction, and the clinical judgement of the healthcare provider, and may include dosage adjustment, temporary drug interruption, or treatment with antihistamines, antipyretics, and/or corticosteroids. 5.4 Injection Site Infections Serious injection site infections including abscess, cellulitis, necrosis, and ulcer have been reported with PALYNZIQ in clinical trials and in the postmarketing setting. Some cases required hospitalization, surgical debridement, intravenous antibiotics, and discontinuation of PALYNZIQ. Provide proper training to patients and/or caregivers on the use of aseptic injection technique. Advise patients to rotate injection sites with each dose and to check the site…