Medically reviewed by Drugs.com. Last updated on July 25, 2020.
(peg VAL i ase)
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Prefilled Syringe, Subcutaneous [preservative free]:
Palynziq: pegvaliase-pqpz 20 mg/mL (1 mL); pegvaliase-pqpz 10 mg/0.5 mL (0.5 mL); pegvaliase-pqpz 2.5 mg/0.5 mL (0.5 mL)
Brand Names: U.S.
- Phenylalanine Ammonia Lyase Enzyme
- Phenylalanine Ammonia Lyase, Recombinant
A PEGylated phenylalanine ammonia lyase (PAL) enzyme that converts phenylalanine to ammonia and trans-cinnamic acid, thereby reducing blood phenylalanine concentrations.
Tmax: ~8 hours
Vd: 20 mg/dose: 1.8 to 241 L; 40 mg/dose: 3.1 to 49.5 L
Via catabolic pathways and degrades into small peptides and amino acids
20 mg/dose: 14 to 132 hours; 40 mg/dose: 14 to 127 hours
Use: Labeled Indications
Phenylketonuria (PKU): To reduce blood phenylalanine concentrations in adult patients with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations >600 micromol/L on existing management.
There are no contraindications listed in the manufacturer's labeling.
Note: Prescribe an epinephrine auto-injector to all patients. Measure baseline blood phenylalanine concentration prior to initiation. Consider premedication with antihistamines (H1-antagonist, H2-antagonist) and/or antipyretic to prevent hypersensitivity reactions (based on patient tolerability). Reduce dose or modify diet to avoid serum phenylalanine concentrations <30 micromol/L.
Phenylketonuria (PKU): SubQ:
Induction: 2.5 mg once weekly for 4 weeks
Titration (after 4-week induction): 2.5 mg twice weekly for 1 week, then 10 mg once weekly for 1 week, then 10 mg twice weekly for 1 week, then 10 mg 4 times/week for 1 week, then 10 mg once daily for 1 week. Additional time may be required prior to each dosage escalation based on patient tolerability.
Maintenance (after induction and titration): 20 mg once daily for at least 24 weeks. Individualize dose to achieve blood phenylalanine concentration ≤600 micromol/L, taking patient tolerance and daily protein intake into consideration. May increase to 40 mg once daily if a response (blood phenylalanine concentration 600 micromol/L or less) has not been achieved after administering 20 mg once daily for 24 weeks. May consider further increase to 60 mg once daily if a response has not been achieved after administering 40 mg once daily continuously for at least 16 weeks without achieving blood phenylalanine control. Discontinue therapy if an adequate response has not been achieved after administering 60 mg once daily for 16 weeks of continuous treatment. Use lowest effective and tolerated dose. Maximum dose: 60 mg/day.
Refer to adult dosing.
SubQ administration: Administer subcutaneously in the front middle thighs or the abdomen (at least 2 inches away from navel) if self-injecting; if a caregiver is administering the injection, the back of the upper arms and the top of the buttocks may also be used. Rotate injection sites; if more than 1 injection is needed for a single dose, administer the second injection at least 2 inches away from the first injection site; second site may be on the same or a different body part as the first injection. Perform initial administration or readministration (after anaphylaxis) under close observation by a health care provider for ≥60 minutes following injection.
Dietary protein and phenylalanine intake may need to be adjusted based on blood phenylalanine concentrations.
Store in refrigerator at 2°C to 8°C (36°F to 46°F) in original carton to protect from light; do not freeze or shake.
If needed, product may be stored in original carton at room temperature at 20°C to 25°C (68°F to 77°F) for up to 30 days. Do not return the product to the refrigerator once stored at room temperature. Discard after 30 days at room temperature or after the expiration date, whichever comes first.
MedroxyPROGESTERone: May enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Monitor therapy
PEGylated Drug Products: May enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Monitor therapy
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.
Incidence ranges include induction, titration, and maintenance dosing.
Central nervous system: Headache (35% to 50%), fatigue (13% to 22%), anxiety (5% to 18%), dizziness (16% to 17%)
Dermatologic: Skin changes (21% to 44%), pruritus (20% to 24%), alopecia (5% to 17%)
Gastrointestinal: Nausea (18% to 26%), vomiting (13% to 26%), abdominal pain (14% to 25%), diarrhea (9% to 22%)
Hematologic & oncologic: Change in serum protein (below LLN: complement factor C3 8% to 84%; complement factor C4 48% to 62%), C-reactive protein increased (64% to 68%), hypophenylalaninemia (16% to 61%)
Hypersensitivity: Anaphylaxis (9% to 84%), hypersensitivity reaction (53% to 69%)
Immunologic: Antibody development (100%; neutralizing antibodies to PAL enzyme activity: 88%)
Local: Injection site reaction (72% to 88%)
Neuromuscular & skeletal: Arthralgia (61% to 83%), increased creatine phosphokinase (18% to 43%)
Respiratory: Oropharyngeal pain (13% to 23%), cough (9% to 22%), nasal congestion (4% to 18%)
1% to 10%:
Hypersensitivity: Angioedema (8%), serum sickness (2%)
Neuromuscular & skeletal: Joint stiffness (8%), joint swelling (8%), musculoskeletal disease (7%)
ALERT: U.S. Boxed WarningAnaphylaxis
Anaphylaxis has been reported after administration of pegvaliase and may occur at any time during treatment. Administer the initial dose of pegvaliase under the supervision of a health care provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient competency with self-administration, and patient’s and observer’s (if applicable) ability to recognize signs and symptoms of anaphylaxis and administer auto-injectable epinephrine, if needed. Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during pegvaliase treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after pegvaliase administration, should be able to administer auto-injectable epinephrine, and call for emergency medical support upon its use. Prescribe auto-injectable epinephrine to all patients treated with pegvaliase. Prior to the first dose, instruct the patient and observer (if applicable) how to recognize the signs and symptoms of anaphylaxis, how to properly administer auto-injectable epinephrine, and to seek immediate medical care upon its use. Instruct patients to carry auto-injectable epinephrine with them at all times during treatment with pegvaliase. Consider the risks and benefits of readministering pegvaliase following an episode of anaphylaxis. If the decision is made to readminister pegvaliase, readminister the first dose under the supervision of a health care provider equipped to manage anaphylaxis and closely observe the patient for at least 60 minutes following the dose. Because of the risk of anaphylaxis, pegvaliase is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the pegvaliase REMS
Concerns related to adverse effects:
• Hypersensitivity reactions: [US Boxed Warning]: Anaphylaxis has been reported and may occur at any time during treatment; administer initial dose under the supervision of a health care provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient competency with self-administration; prescribe auto-injectable epinephrine to all patients treated with pegvaliase and instruct patients to carry auto-injectable epinephrine with them at all times during treatment. Symptoms of anaphylaxis include syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/tightness, tachycardia, angioedema, throat tightness, skin flushing, rash, urticaria, pruritus, and GI symptoms; delayed episodes of anaphylaxis occurred up to 48 hours after administration (most episodes occurred within first year; some cases reported after 2 years). Hypersensitivity reactions (other than anaphylaxis) have been also been reported; dose adjustment or temporary drug interruption may be considered. Consider premedication prior to administration.
• REMS program: [US Boxed Warning]: Because of the risk of anaphylaxis, pegvaliase is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Palynziq REMS. Prescribers and pharmacies must be certified with the program and prescribers must prescribe auto-injectable epinephrine. Patients must enroll in the program, be educated about the risk of anaphylaxis, and carry auto-injectable epinephrine at all times during treatment. Further information is available at www.PALYNZIQREMS.com or at 1-855-758-7367.
Blood phenylalanine concentration prior to initiation, every 4 weeks until maintenance is achieved, then periodically throughout treatment; signs and symptoms of anaphylaxis/hypersensitivity for ≥60 minutes after initial dose or upon reinitiation of therapy (after a previous episode of anaphylaxis). Maintain serum phenylalanine concentrations between 120 and 360 micromol/L for 3 months prior to conception and during pregnancy.
Family planning is recommended for females with phenylalanine hydroxylase deficiency (ACOG 802 2020). Phenylalanine concentrations should be normalized 3 months prior to conception (ACOG 802 2020; Vockley 2014). Women planning a pregnancy should discontinue pegvaliase and allow for a 4-week washout period prior to conception (Longo 2019). In one case report, pegvalaise was discontinued over a period of 10 weeks to allow dietary transition and decrease maternal adverse events; conception occurred 4 weeks after pegvaliase was fully discontinued (Rohr 2020).
Pegvaliase is not contraindicated in males planning to father a child (Longo 2019).
Information related to the use of pegvaliase in pregnant women is limited.
Uncontrolled maternal phenylalanine concentrations are associated with adverse pregnancy outcomes. Phenylalanine (PHE) concentrations >600 micromol/L (10 mg/dL) may increase the risk of miscarriage, birth defects (including microcephaly and major cardiac malformations), intrauterine growth retardation, and future intellectual disability. Pregnancy outcomes are comparable to the general population when appropriate maternal PHE concentrations are maintained (van Wegberg 2017). Fetal development is optimal when maternal PHE concentrations <360 micromol/L (6 mg/dL) are achieved prior to conception (ACOG 802 2020; Vockley 2014). Maternal plasma concentrations of PHE 120 to 360 micromol/L (2 to 6 mg/dL) are recommended throughout pregnancy (ACOG 802 2020).
Pegvaliase is not currently recommended for use during pregnancy. Treatments other than pegvaliase are currently recommended for the treatment of phenylketonuria in pregnant women (Longo 2019; Vockley 2014).
Data collection to monitor pregnancy and infant outcomes following exposure to pegvaliase is ongoing. Health care providers are encouraged to enroll women exposed to pegvaliase during pregnancy or within 1 month following the last dose to the pregnancy surveillance program (866-906-6100).
What is this drug used for?
• It is used to treat phenylketonuria (PKU).
All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:
• Joint pain
• Abdominal pain
• Mouth pain
• Sore throat
• Loss of strength and energy
• Hair loss
• Stuffy nose
WARNING/CAUTION: Even though it may be rare, some people may have very bad and sometimes deadly side effects when taking a drug. Tell your doctor or get medical help right away if you have any of the following signs or symptoms that may be related to a very bad side effect:
• Chest pain
• Passing out
• Fast heartbeat
• Leaking of urine
• Leaking of stool
• Skin rash
• Facial swelling
• Chest tightness
• Throat tightness
• Trouble breathing
• Severe nausea
• Skin reaction
• Severe injection site irritation
• Signs of an allergic reaction, like rash; hives; itching; red, swollen, blistered, or peeling skin with or without fever; wheezing; tightness in the chest or throat; trouble breathing, swallowing, or talking; unusual hoarseness; or swelling of the mouth, face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a limited summary of general information about the medicine's uses from the patient education leaflet and is not intended to be comprehensive. This limited summary does NOT include all information available about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not intended to provide medical advice, diagnosis or treatment and does not replace information you receive from the healthcare provider. For a more detailed summary of information about the risks and benefits of using this medicine, please speak with your healthcare provider and review the entire patient education leaflet.
Frequently asked questions
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More about pegvaliase
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- Drug class: miscellaneous metabolic agents
Other brands: Palynziq