**REMS Drug**
Pronunciation:
peg-val-i-ase
Trade Name(s)
Ther. Class.
none assigned
Pharm. Class.
enzymes
Treatment of phenylketonuria (PKU) in adult patients who have uncontrolled blood phenylalanine concentrations >600 micromol/L on existing therapy.
As a phenylalanine ammonia lyase enzyme, it acts as a replacement for phenylalanine hydroxylase (as enzyme that is deficient in patients with PKU), and converts phenylalanine to ammonia and trans -cinnamic acid.
Therapeutic Effect(s):
Reduction in blood phenylalanine concentrations.
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)
ROUTE | ONSET | PEAK | DURATION |
---|---|---|---|
SUBQ | unknown | 8 hr | unknown |
Contraindicated in:
Use Cautiously in:
Derm: alopecia, pruritus, rash
EENT: nasal congestion, oropharyngeal pain
GI: abdominal pain, diarrhea, nausea, vomiting
Local: injection site reactions
MS: ↑ creatine kinase, arthralgia
Neuro: anxiety, dizziness, headache
Resp: cough
Misc: fatigue, HYPERSENSITIVITY REACTIONS (including anaphylaxis and angioedema), serum sickness
* CAPITALS indicate life-threatening.
Underline indicate most frequent.
Drug-Drug
Use with other PEGylated products may ↑ risk of anaphylaxis.
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.
Solution for injection (prefilled syringes): 2.5 mg/0.5 mL, 10 mg/0.5 mL, 20 mg/mL
Monitor for signs and symptoms of anaphylaxis (syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/chest tightness, tachycardia, swelling of face, lips, eyes, tongue, throat tightness, flushing, rash, urticaria, pruritus, vomiting, nausea, diarrhea) during and for at least 60 min after first injection. Treat with epinephrine, corticosteroids, antihistamines and oxygen. If readministering pegvaliase, premedicate with H1 –receptor antagonist, H2 receptor antagonist, and antipyretic. Observe patient for at least 60 min after injection.
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.
Inform patient and caregiver on risk of anaphylaxis. Instruct patient to carry auto-injectable epinephrine with them at all times. Instruct patient and caregiver on how to recognize signs and symptoms of anaphylaxis (fainting, dizziness or lightheadedness, 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 auto-injectable epinephrine, and to seek immediate medical care upon its use.
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.