Pegvaliase: Pediatric drug information

(For additional information see "Pegvaliase: Drug information" and see "Pegvaliase: Patient drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)

ALERT: US Boxed Warning

Anaphylaxis

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 Palynziq REMS.

Brand Names: US

Palynziq

Brand Names: Canada

Palynziq

Therapeutic Category

Phenylalanine Ammonia Lyase Enzyme;
Phenylalanine Ammonia Lyase, Recombinant

Dosing: Pediatric

Note: Due to risk of hypersensitivity, all patients should be prescribed an epinephrine autoinjector. Consider premedication with antihistamines (ie, H₁-antagonist, H₂-antagonist), and/or antipyretic to prevent hypersensitivity reactions (based on patient tolerability). Administer initial dose or first dose following anaphylaxis under the supervision of a health care provider equipped to manage anaphylaxis, and closely observe patients for ≥60 minutes following injection.

Phenylketonuria

Phenylketonuria (PKU): Limited data available:

Note: Should only be administered under the supervision of a qualified health care provider experienced in the management of PKU. Measure baseline blood phenylalanine concentration prior to initiation. Dose should be individualized to maintain a serum phenylalanine concentration ≤600 micromol/L, taking into consideration patient tolerability and dietary protein intake. Reduce dose or modify diet to avoid serum phenylalanine concentrations <30 micromol/L.

Induction and Titration: Adolescents ≥16 years: SubQ: Pegvaliase should be titrated in a stepwise manner as per the following table based on tolerability and dietary protein intake; additional time may be needed at each step.

	Dose	Typical Duration
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 4 times weekly	1 week
	10 mg once daily	1 week then transition to maintenance dosing

Maintenance: Individualize dose to achieve a serum phenylalanine concentration ≤600 micromol/L, taking patient tolerance and daily protein intake into consideration; use lowest effective and tolerated dose.

Adolescents ≥16 years: SubQ: 20 mg once daily; if after 24 weeks response not achieved (ie, control of blood phenylalanine concentrations), may further increase dose to 40 mg once daily; if after 16 weeks response not achieved may consider further dose increase to 60 mg once daily. Discontinue therapy if a response has not been achieved after administering 60 mg once daily for 16 weeks. Maximum daily dose: 60 mg/day.

Dosing: Kidney Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Adult

(For additional information see "Pegvaliase: Drug information")

Note: Due to risk of hypersensitivity, prescribe an epinephrine auto-injector to all patients. Administer initial dose or first dose following anaphylaxis under the supervision of a health care provider equipped to manage anaphylaxis, and closely observe patients for ≥60 minutes following injection. Consider premedication with antihistamines (H₁antagonist, H₂antagonist) and/or antipyretic to prevent hypersensitivity reactions (based on patient tolerability).

Phenylketonuria

Phenylketonuria:

Induction and titration: SUBQ:

Note: Measure baseline blood phenylalanine concentration prior to initiation. Additional time may be required prior to each dosage escalation based on patient tolerability.

**Pegvaliase Induction and Titration Dosing**
	SUBQ dose	Typical duration
Induction	2.5 mg once weekly	4 weeks
Titration (after 4-week induction)	2.5 mg twice weekly	1 week
	10 mg once weekly	1 week
	10 mg twice weekly	1 week
	10 mg 4 times weekly	1 week
	10 mg once daily	1 week, then transition to maintenance dosing

Maintenance (after induction and titration): SUBQ: 20 mg once daily for at least 24 weeks. Individualize dose to the lowest effective and tolerated dose to achieve response (blood phenylalanine concentration ≤600 micromole/L), taking daily protein intake into consideration. May increase to 40 mg once daily if a response 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. Maximum dose: 60 mg/day.

Dosage adjustment:

Reduce dose and/or modify diet to avoid serum phenylalanine concentrations <30 micromole/L.

Temporary reduction (reducing the dose 1 or 2 steps back in the dosing regimen) is recommended to prevent further events in patients experiencing a hypersensitivity reaction during the titration phase (Ref).

Discontinuation of therapy: If an adequate response has not been achieved after administering 60 mg once daily for 16 weeks of continuous treatment, discontinue therapy.

Dosing: Kidney Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Dosing: Hepatic Impairment: Adult

There are no dosage adjustments provided in the manufacturer's labeling.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Incidence ranges include induction, titration, and maintenance dosing.

>10%:

Dermatologic: Alopecia (5% to 19%), pruritus (20% to 27%), skin changes (21% to 47%)

Gastrointestinal: Abdominal pain (14% to 30%), diarrhea (9% to 27%), nausea (18% to 31%), vomiting (13% to 30%)

Hematologic & oncologic: Change in serum protein (below LLN: complement factor C3 [68% to 84%]; complement factor C4 [49% to 62%]), C-reactive protein increased (64% to 71%), hypophenylalaninemia (16% to 65%)

Hypersensitivity: Hypersensitivity reaction (54% to 72%)

Immunologic: Antibody development (100%; neutralizing antibodies to PAL enzyme activity: 89%)

Local: Injection site reaction (72% to 88%)

Nervous system: Anxiety (5% to 21%), dizziness (16% to 21%), fatigue (13% to 24%), headache (36% to 56%)

Neuromuscular & skeletal: Arthralgia (68% to 86%; severe arthralgia: 4%), increased creatine phosphokinase in blood specimen (18% to 48%)

Respiratory: Cough (9% to 30%), nasal congestion (4% to 27%), oropharyngeal pain (13% to 29%)

1% to 10%:

Hypersensitivity: Anaphylaxis (10%), angioedema (8%), serum sickness (2%)

Neuromuscular & skeletal: Joint stiffness (8%), joint swelling (8%), muscle rigidity (7%)

Contraindications

There are no contraindications listed in the manufacturer's US labeling.

Canadian labeling: Previous severe hypersensitivity (eg, severe serum sickness, severe angioedema, severe anaphylactic reactions) or a recurrence of a mild to moderate anaphylactic reaction to pegvaliase or any component of the formulation; history of anaphylactic reaction to products containing polyethylene glycol (PEG) or any other products containing PEGylated ingredients.

Warnings/Precautions

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. Signs and 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 also been reported, including angioedema, injection site reactions, and arthralgias; dose adjustment or temporary drug interruption may be considered. Consider premedication prior to administration. Patients with a history of anaphylaxis or severe allergic reactions to PEGylated drugs should be assessed by an allergist/immunologist prior to starting pegvaliase (Caballero 2021; Hausmann 2019).

• 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.

Dosage Forms: US

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)

Generic Equivalent Available: US

Pricing: US

Solution Prefilled Syringe (Palynziq Subcutaneous)

2.5 mg/0.5 mL (per 0.5 mL): $738.00

10 mg/0.5 mL (per 0.5 mL): $738.00

20 mg/mL (per mL): $738.00

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Prefilled Syringe, Subcutaneous:

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)

Administration: Pediatric

Note: Consider premedication with antihistamines (ie, H₁-antagonist, H₂-antagonist) and/or an antipyretic to prevent hypersensitivity reactions (based on patient tolerability). Perform initial administration or readministration (after anaphylaxis) under close observation by a health care provider for ≥60 minutes following injection.

Parenteral: SubQ: Allow sealed tray containing prefilled syringe to sit at room temperature for ≥30 minutes before injecting. Administer subcutaneously. If self-injecting, administer in the front middle thigh or the abdomen at least 2 inches (5 cm) away from navel; if a caregiver is administering, the back of the upper arms or 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; the second site may be on the same or a different body part as the first injection. Avoid injection sites that have moles, scars, birthmarks, bruises, tattoos, or rashes or areas where the skin is hard, tender, red, damaged, burned, or inflamed.

Missed dose: If a dose is missed, it should be skipped, and the next dose administered as scheduled.

Administration: Adult

Perform initial administration or readministration (after anaphylaxis) under close observation by a health care provider for ≥60 minutes following injection. Consider the use of an observer to be present during and for at least 60 minutes after each administration when patient is self-injecting, at least for the first several months of treatment (ie, first 6 months) (Ref).

SUBQ administration: Administer SUBQ in the front middle of thighs or the abdomen (at least 2 inches [5 cm] 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 (5 cm) away from the first injection site; second site may be on the same or a different body part as the first injection. Pegvaliase should not be injected into moles, birthmarks, bruises, rashes, or areas where the skin is hard, tender, red, damaged, burned, inflamed, or tattooed.

Storage/Stability

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.

Medication Guide and/or Vaccine Information Statement (VIS)

An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:

Palynziq: https://www.accessdata.fda.gov/drugsatfda_docs/label/2018/761079s000lbl.pdf#page=23

Use

Reduction of blood phenylalanine concentrations in patients with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations >600 micromol/L on existing management (FDA approved in adults).

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

MedroxyPROGESTERone: May enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor therapy

PEGylated Drug Products: May enhance the adverse/toxic effect of Pegvaliase. Specifically, the risk of anaphylaxis or hypersensitivity reactions may be increased. Risk C: Monitor therapy

Dietary Considerations

Dietary protein and phenylalanine intake may need to be adjusted based on blood phenylalanine concentrations.

Reproductive Considerations

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).

Pregnancy Considerations

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 micromole/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 micromole/L (6 mg/dL) are achieved prior to conception (ACOG 802 2020; Vockley 2014). Maternal plasma concentrations of PHE 120 to 360 micromole/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).

Monitoring Parameters

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).

Reference Range

General blood phenylalanine goal range: 120 to 360 micromol/L (ACMG [Vockley 2014]); with pegvaliase therapy, the manufacturer recommends a target of 30 to <600 micromol/L.

Mechanism of Action

A PEGylated phenylalanine ammonia lyase (PAL) enzyme that converts phenylalanine to ammonia and trans-cinnamic acid, thereby reducing blood phenylalanine concentrations.

Pharmacokinetics (Adult Data Unless Noted)

Absorption: T_max: ~8 hours

Distribution: V_d: 20 mg/dose: 1.8 to 241 L; 40 mg/dose: 3.1 to 49.5 L

Metabolism: Via catabolic pathways and degrades into small peptides and amino acids.

Half-life elimination: 20 mg/dose: 14 to 132 hours; 40 mg/dose: 14 to 127 hours

Brand Names: International

International Brand Names by Country

For country code abbreviations (show table)

(AT) Austria: Palynziq;
(DE) Germany: Palynziq;
(IE) Ireland: Palynziq;
(IT) Italy: Palynziq;
(PR) Puerto Rico: Palynziq;
(SA) Saudi Arabia: Palynziq;
(SI) Slovenia: Palynziq

American College of Obstetricians and Gynecologists (ACOG). Management of women with phenylalanine hydroxylase deficiency (phenylketonuria): ACOG Committee opinion, number 802. Obstet Gynecol. 2020;135(4):e167-e170. doi:10.1097/AOG.0000000000003768 [PubMed 32217978]
Caballero ML, Krantz MS, Quirce S, Phillips EJ, Stone CA Jr. Hidden dangers: recognizing excipients as potential causes of drug and vaccine hypersensitivity reactions. J Allergy Clin Immunol Pract. 2021;9(8):2968-2982. doi:10.1016/j.jaip.2021.03.002 [PubMed 33737254]
Hausmann O, Daha M, Longo N, et al. 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. 2019;128(1-2):84-91. doi:10.1016/j.ymgme.2019.05.006 [PubMed 31375398]
Longo N, Dimmock D, Levy H, et al. Evidence- and consensus-based recommendations for the use of pegvaliase in adults with phenylketonuria. Genet Med. 2019;21(8):1851-1867. doi:10.1038/s41436-018-0403-z [PubMed 30546086]
Palynziq (pegvaliase-pqpz) [prescribing information]. Novato, CA: BioMarin Pharmaceutical Inc; November 2020.
Palynziq (pegvaliase) [EMA summary of product characteristics]. Shanbally, Ringaskiddy, Ireland: BioMarin International Limited; received July 2023.
Palynziq (pegvaliase) [product monograph]. Toronto, Ontario, Canada: BioMarin Pharmaceutical (Canada) Inc; April 2023.
Rohr F, Kritzer A, Harding CO, Viau K, Levy HL. Discontinuation of pegvaliase therapy during maternal PKU pregnancy and postnatal breastfeeding: a case report. Mol Genet Metab Rep. 2020;22:100555. doi:10.1016/j.ymgmr.2019.100555 [PubMed 31956506]
van Wegberg AMJ, MacDonald A, Ahring K, et al. The complete European guidelines on phenylketonuria: diagnosis and treatment. Orphanet J Rare Dis. 2017;12(1):162. doi:10.1186/s13023-017-0685-2
Vockley J, Andersson HC, Antshel KM, et al; American College of Medical Genetics and Genomics Therapeutics Committee. Phenylalanine hydroxylase deficiency: diagnosis and management guideline. Genet Med. 2014;16(2):188-200. doi: 10.1038/gim.2013.157. [PubMed 24385074]

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Pegvaliase: Pediatric drug information