Palynziq

2 DOSAGE AND ADMINISTRATION Obtain baseline blood Phe concentration before initiating treatment. ( 2.1 ) Consider premedication for hypersensitivity reactions. ( 2.1 , 5.1 , 5.3 ) The recommended initial dosage for PALYNZIQ is 2.5 mg subcutaneously once weekly for 4 weeks. ( 2.2 ) See the Full Prescribing Information for titration, maintenance, discontinuation, and dose reduction. ( 2.2 ) See Full Prescribing Information for dosage and administration modifications due to anaphylaxis. ( 2.3 ) Obtain blood Phe concentrations every 4 weeks until a maintenance dosage is established. ( 2.4 ) Periodically monitor blood Phe concentrations during maintenance therapy and monitor dietary protein and phenylalanine intake throughout treatment. ( 2.4 ) Rotate injection sites. If more than one injection is needed for a single dose, the injection sites should be at least 2 inches away from each other. ( 2.5 ) 2.1 Important Recommendation Prior to PALYNZIQ Treatment Treatment with PALYNZIQ should be managed by a healthcare provider experienced in the management of PKU. Obtain baseline blood phenylalanine concentration before initiating treatment. Consider premedication with an H 1 -receptor antagonist, H 2 -receptor antagonist, and/or antipyretic based upon individual patient tolerability [see Warnings and Precautions (5.1 , 5.3) ] . 2.2 Recommended Dosage and Administration Induction The recommended initial induction dosage for PALYNZIQ is 2.5 mg subcutaneously once weekly for 4 weeks. Administer the initial dose under the supervision of a healthcare provider [see Dosage and Administration (2.5) ]. Titration Titrate the PALYNZIQ dosage in a step-wise manner, based on tolerability, over at least 5 weeks, to achieve a dosage of 20 mg subcutaneously once daily according to Table 1. Maintenance Therapeutic response may not be achieved until the patient is titrated to an effective maintenance dosage of PALYNZIQ. Use the lowest effective and tolerated dosage of PALYNZIQ. Assess patient tolerability, blood phenylalanine concentrations, and dietary protein and phenylalanine intake throughout treatment. Individualize the maintenance dosage to achieve blood phenylalanine control (blood phenylalanine concentrations less than or equal to 600 micromol/L), taking into account patient tolerability to PALYNZIQ and dietary protein and phenylalanine intake (see Table 1 ). Maintain the PALYNZIQ dosage at 20 mg once daily for at least 24 weeks. Consider increasing the PALYNZIQ dosage to 40 mg once daily in patients who have been on 20 mg once daily continuously for at least 24 weeks without achieving blood phenylalanine control. Consider increasing the PALYNZIQ dosage to a maximum of 60 mg once daily in patients who have been on 40 mg once daily continuously for at least 16 weeks without achieving blood phenylalanine control. Discontinuation Discontinue PALYNZIQ in patients who have not achieved an adequate response after 16 weeks of continuous treatment with the maximum dosage of 60 mg once daily [see Clinical Studies (14) ]. Table 1: Recommended Dosing Regimen Treatment PALYNZIQ Dosage Duration Additional time may be required prior to each dosage escalation based on patient tolerability. Induction 2.5 mg once weekly 4 weeks Titration 2.5 mg twice weekly 1 week 10 mg once weekly 1 week 10 mg twice weekly 1 week 10 mg four times per week 1 week 10 mg once daily 1 week Maintenance Individualize treatment to the lowest effective and tolerated dosage. Consider increasing to 40 mg once daily in patients who have not achieved a response with 20 mg once daily continuous treatment for at least 24 weeks. Consider increasing to a maximum of 60 mg once daily in patients who have not achieved a response with 40 mg once daily continuous treatment for at least 16 weeks [see Clinical Studies (14) ]. 20 mg once daily 24 weeks 40 mg once daily 16 weeks Maximum Discontinue PALYNZIQ in patients who have not achieved an adequate response after 16 weeks of continuous treatment at the maximum dosage of 60 mg once daily. 60 mg once daily 16 weeks Dose Reduction During titration and maintenance of PALYNZIQ treatment, patients may experience blood phenylalanine concentrations below 30 micromol/L. For blood phenylalanine concentrations below 30 micromol/L, the dosage of PALYNZIQ may be reduced and/or dietary protein and phenylalanine intake may be modified to maintain blood phenylalanine concentrations within a clinically acceptable range and above 30 micromol/L [see Warning and Precaution (5.5) ] . Missed Dose If a dose is missed, instruct patients to take their next dose as scheduled and to not take two doses of PALYNZIQ to make up for the missed dose. 2.3 Dosage and Administration Modifications Due to Anaphylaxis If the decision is made to readminister PALYNZIQ after an anaphylaxis episode, administer the first dose following the anaphylaxis episode 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 dose titration should be based on patient tolerability and therapeutic response [see Warnings and Precautions (5.1) ] . 2.4 Blood Phenylalanine Monitoring and Diet After initiating treatment with PALYNZIQ, obtain blood phenylalanine concentrations every 4 weeks until a maintenance dosage is established. After a maintenance dosage is established, periodic blood phenylalanine monitoring is recommended to assess blood phenylalanine control. Frequent blood Phe monitoring is recommended in the pediatric population. Monitor patients' dietary protein and phenylalanine intake throughout treatment with PALYNZIQ and counsel them on how to adjust their dietary protein and phenylalanine intake, as needed, based on blood phenylalanine concentrations. 2.5 Administration Instructions Each prefilled syringe of PALYNZIQ is intended for use as a single subcutaneous injection. Inspect PALYNZIQ visually for particulate matter and discoloration prior to administration. PALYNZIQ is a clear to slightly opalescent, colorless to pale yellow solution. Discard if discolored, cloudy, or if particulate matter is present. Prior to first dose of PALYNZIQ, prescribe epinephrine, and 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. Perform initial administration(s) and/or readministration after an anaphylaxis episode under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection [see Warnings and Precautions (5.1) ] . Prior to self-injection, confirm patient competency with self-administration using aseptic technique. Discard after use. 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 each PALYNZIQ administration, should be able to administer epinephrine, and call for emergency medical support upon its use [see Warnings and Precautions (5.1) ] . The recommended injection sites for PALYNZIQ are: the front middle of thighs and the abdomen at least 2 inches (five centimeters) away from the navel. If a caregiver is giving the injection, the top of the buttocks and the back of the upper arms are also appropriate injection sites. Do not inject PALYNZIQ into moles, scars, birthmarks, bruises, rashes, or areas where the skin is hard, tender, red, damaged, burned, inflamed, or tattooed. Check the injection site for redness, swelling, or tenderness. Rotate sites for subcutaneous injections of PALYNZIQ. If more than one injection is needed for a single dose of PALYNZIQ, the injection sites should be at least 2 inches away from each other. The second injection site can be on the same part of the body or a different part of the body.

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1 INDICATIONS AND USAGE PALYNZIQ is indicated to reduce blood phenylalanine concentrations in adult and pediatric patients 12 years of age and older with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management.