General

**REMS Drug**

Pronunciation:
peg-val-i-ase

Trade Name(s)

• Palynziq

Ther. Class.

none assigned

Pharm. Class.

enzymes

Indications

Treatment of phenylketonuria in adult patients who have uncontrolled blood phenylalanine concentrations >600 micromol/L on existing therapy.

Action

As a phenylalanine ammonia lyase enzyme, it acts as a replacement for phenylalanine hydroxylase (as enzyme that is deficient in patients with phenylketonuria), and converts phenylalanine to ammonia and  trans -cinnamic acid.

Therapeutic Effect(s):

Reduction in blood phenylalanine concentrations.

Pharmacokinetics

Absorption: Unknown.

Distribution: Well distributed to tissues.

Metabolism and Excretion: Metabolized via catabolic pathways into small peptides and amino acids; excretion pathway(s) unknown.

Half-life: 14–132 hr.

TIME/ACTION PROFILE (plasma concentrations)

Contraindication/Precautions

Contraindicated in:

• OB:   Pregnancy.

Use Cautiously in:

• Lactation:  Use while breastfeeding only if potential maternal benefit justifies potential risk to infant;
• Pedi:   Safety and effectiveness not established in children.

Adverse Reactions/Side Effects

Derm: alopecia, pruritus, rash

EENT: nasal congestion, oropharyngeal pain

GI: abdominal pain, diarrhea, nausea, vomiting

Local: injection site reactions

MS: ↑ CK, arthralgia

Neuro: anxiety, dizziness, fatigue, headache

Resp: cough

Misc: HYPERSENSITIVITY REACTIONS (including anaphylaxis and angioedema), serum sickness

* CAPITALS indicate life-threatening.
Underline indicate most frequent.

Interactions

Drug-Drug

Use with other  PEGylated products  may ↑ risk of anaphylaxis.

Route/Dosage

SUBQ (Adults): Induction phase: 2.5 mg once weekly for 4 wk; then proceed to titration phase;  Titration phase: 2.5 mg twice weekly for 1 wk, then 10 mg once weekly for 1 wk, then 10 mg twice weekly for 1 wk, then 10 mg 4 times weekly for 1 wk, then 10 mg once daily for 1 wk; then proceed to maintenance phase;  Maintenance phase: 20 mg once daily for ≥24 wk; may consider ↑ to 40 mg once daily if adequate response (blood phenylalanine concentration ≤600 micromol/L) has not been achieved after patient receives 20 mg once daily for ≥24 wk. May consider ↑ to 60 mg once daily if adequate response (blood phenylalanine concentration ≤600 micromol/L) has not been achieved after patient receives 40 mg once daily for ≥16 wk. Discontinue therapy if adequate response (blood phenylalanine concentration ≤600 micromol/L) has not been achieved after patient receives 60 mg once daily for ≥16 wk.

Availability

Solution for injection (prefilled syringes): 2.5 mg/0.5 mL, 10 mg/0.5 mL, 20 mg/mL

Assessment

• Monitor for signs and symptoms of anaphylaxis (syncope; hypotension; hypoxia; dyspnea; wheezing; chest discomfort/tightness; tachycardia; swelling of face, lips, eyes, and tongue; throat tightness; flushing; rash; urticaria; pruritus; vomiting; nausea; diarrhea) during and for ≥60 min after 1st injection.  If anaphylaxis occurs,  treat with epinephrine, corticosteroids, antihistamines, and oxygen. If readministering pegvaliase, premedicate with H₁ –receptor antagonist, H₂  receptor antagonist, and antipyretic. Consider the risks and benefits of readministering pegvaliase following an episode of anaphylaxis. If the decision is made to readminister pegvaliase, readminister the 1st dose under the supervision of a health care provider equipped to manage anaphylaxis and closely observe the patient for at ≥60 min after the dose.
• Monitor daily intake of protein and phenylalanine during therapy.

Lab Test Considerations:

Obtain baseline blood phenylalanine concentration before starting therapy. During initial therapy, monitor phenylalanine levels every 4 wk until maintenance dose established. Then monitor blood phenylalanine levels periodically during therapy. Monitor blood phenylalanine levels in breastfeeding women treated with pegvaliase.

Implementation

• Administer 1st dose under supervision of a health care provider. Prior to allowing patients to self-inject subsequent doses, confirm that patient is able to self-administer, recognize signs and symptoms of anaphylaxis, and administer autoinjectable epinephrine, if needed. Prescribe autoinjectable epinephrine to all patients. If patient needs an adult observer to assist with injection, observer should be present during and for ≥60 min after administration.
• Premedicate with H₁ –receptor antagonist, H₂ –receptor antagonist, and an antipyretic for hypersensitivity reactions.
•  REMS: Palynziq is only available through  Palynziq REMS. Prescribers must be trained and certified and must prescribe autoinjectable epinephrine. Pharmacies must be certified. Patients must be educated about risk of anaphylaxis and have autoinjectable epinephrine with them at all times. Information is available at www.PALYNZIQREMS.com or by telephone 1-855-758-REMS (1-855-758-7367).
• SUBQ Pinch skin and inject at 45–90° angle in front middle of thighs and abdomen at least 2 inches away from navel. If a caregiver is giving injection, top of buttocks and back of upper arms may also be used for injection. Rotate injection sites. Do not inject into moles, scars, birthmarks, bruises, rashes, or areas where skin is hard, tender, red, damaged, burned, inflamed, or tattooed. Check injection site for redness, swelling, or tenderness. Solution is clear to slightly opalescent, colorless to pale yellow; do not inject solutions that are cloudy, discolored, or contain particulate matter. Store in refrigerator in original carton to protect from light; do not freeze. Stable for up to 30 days at room temperature; do not return to refrigerator if stored at room temperature.

Patient/Family Teaching

•  REMS: Instruct patient in correct technique for injection, storage, and disposal of equipment. Omit missed doses and administer next dose a scheduled; do not double doses. Explain purpose and requirements of REMS program to patient and caregiver. Advise patient to read  Medication Guide  before starting therapy and with each Rx refill in case of changes.
• Advise patient to monitor dietary protein and phenylalanine intake and counsel patient on how to adjust dietary intake of protein and phenylalanine based on phenylalanine blood levels.
• Inform patient and caregiver on risk of anaphylaxis. Instruct patient to carry autoinjectable epinephrine with them at all times. Instruct patient and caregiver on how to recognize signs and symptoms of anaphylaxis (fainting; dizziness or light-headedness; sudden confusion; trouble breathing or wheezing; chest discomfort or chest tightness; fast heart rate; swelling of your face, lips, eyes, or tongue; throat tightness; flushed skin; rash; itching; raised bumps on skin; nausea; vomiting or diarrhea; losing control of urine or stools), how to properly administer autoinjectable epinephrine, and to seek immediate medical care upon its use.
• Instruct patient to notify health care provider of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care provider before taking other Rx, OTC, herbal products.
• Rep:  Advise women of reproductive potential to notify health care provider if pregnancy is planned or suspected or if breastfeeding. If pegvaliase is administered during pregnancy, or if patient becomes pregnant while receiving pegvaliase or within 1 mo after last dose, report pegvaliase exposure to pregnancy surveillance program by calling 1-866-906-6100.

Evaluation/Desired Outcomes

20% reduction from baseline in blood phenylalanine concentration or blood phenylalanine concentration ≤600 micromol/L. Discontinue pegvaliase in patients not responding after 16 wk at 40 mg daily.