Pegvaliase (Palynziq) is a recombinant pegylated enzyme that converts phenylalanine to ammonia and trans-cinnamic acid.

Indications of Pegvaliase (Palynziq):

• Phenylketonuria (PKU):

  • It is effective in reducing blood phenylalanine concentrations in adult patients with phenylketonuria who have uncontrolled blood phenylalanine concentrations >600 micromol/L on existing management.

Pegvaliase (Palynziq) dose in adults:

Note:

• Phenylalanine levels should be checked before starting therapy.
• An epinephrine auto-injector should be given to all patients.
• In order to prevent hypersensitivity reactions, premedication with antihistamines (H-1 antagonist, H-2 antagonist) and/or antipyretic is necessary.
• Dose reduction or diet modification is needed to avoid serum phenylalanine concentrations <30 micromol/L.

Pegvaliase (Palynziq) dose in the treatment of Phenylketonuria:

• Induction:

  • 2.5 mg SubQ once weekly for 4 weeks.

• Titration (after 4-week induction):

  • 2.5 mg  SubQ 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 a 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 S/C once daily for at least 24 weeks.
  • May increase to 40 mg once daily if a response (20% reduction from baseline in blood phenylalanine or blood phenylalanine concentration 600 micromol/L or less) has not been achieved after administering 20 mg once daily for 24 weeks.
  • If a response is not achieved after giving 40 mg once daily for 16 weeks, therapy should be stopped.
  • The lowest effective and tolerated dose should be used.

• Maximum dose:

  • 40 mg/day.

Pegvaliase (Palynziq) use in children:

The safety and efficacy of the drug in children has not been established.

Pregnancy Risk Category: N (not defined)

• Uncontrolled maternal phenylalanine levels can lead to adverse pregnancy outcomes.
• To minimize the chance of adverse fetal outcomes, maternal phenylalanine levels should be controlled throughout pregnancy and 3 months prior to pregnancy.
• Current recommendations for dietary control are:
• There are limited data available on the use of pegvaliase during pregnancy.
• The risk of miscarriage, birth defects,microcephaly, cardiac malformations, intrauterine growth retardation, and future intellectual disability is significantly increased with phenylalanine concentrations >600 micro mols/L (10 mg/dL).
• Pegvaliase-exposed women should be enrolled by their health care providers during pregnancy, or within one month of the last dose of the pregnancy surveillance program.

Pegvaliase use during breastfeeding:

• The excretion of pegvaliase in breast milk is not known.
• It is possible that milk concentrations of phenylalanine could be affected.
• According to the manufacturer the decision to breastfeed during therapy is based on the risks/benefits of breastfeeding to the infant and the benefits to the mother.
• Before breastfeeding, it is important to check the infant's phenylalanine level.

Dose adjustment in renal disease:

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

Dose adjustment in liver disease:

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

Common Side Effects of Pegvaliase (Palynziq):

• Central Nervous System:

  • Headache
  • Fatigue
  • Anxiety
  • Dizziness

• Dermatologic:

  • Skin Changes
  • Pruritus
  • Alopecia

• Gastrointestinal:

  • Nausea
  • Vomiting
  • Abdominal Pain
  • Diarrhea

• Hematologic & Oncologic:

  • Change In Serum Protein
  • C-Reactive Protein Increased
  • Hypophenylalaninemia

• Hypersensitivity:

  • Anaphylaxis
  • Hypersensitivity Reaction

• Immunologic:

  • Antibody Development

• Local:

  • Injection Site Reaction

• Neuromuscular & Skeletal:

  • Arthralgia
  • Increased Creatine Phosphokinase

• Respiratory:

  • Oropharyngeal Pain
  • Cough
  • Nasal Congestion

Less Common Side Effects Of Pegvaliase (Palynziq):

• Hypersensitivity:

  • Angioedema
  • Serum Sickness

• Neuromuscular & Skeletal:

  • Joint Stiffness
  • Joint Swelling
  • Musculoskeletal Disease

Contraindications to Pegvaliase (Palynziq):

The manufacturer's labeling does not list any contraindications.

Warnings and precautions

• Hypersensitivity reactions: [US Boxed Warning]

  • Pegvaliase is notorious for causing anaphylaxis presenting with syncope, hypotension, hypoxia, dyspnea, wheezing, chest discomfort/tightness, tachycardia, angioedema, throat tightness, skin flushing, rash, urticaria, pruritus, and GI symptoms.
  • Anaphylaxis can be delayed for up to 48 hours following administration. Most episodes occur within the first year, but some cases are reported after two years.
  • Anaphylaxis may occur at any moment during treatment.
  • Therefore, supervision by a healthcare provider who is trained to manage anaphylaxis for the initial dose is necessary.
  • Close monitoring is required for one hour after injection.
  • It is important to evaluate the patient's self-management skills.
  • auto-injectable epinephrine should be given to all patients treated with pegvaliase and instruct patients to carry auto-injectable epinephrine with them at all times during treatment.
  • Other hypersensitivity reactions may occur, which can require dose adjustment or withdrawal temporaire therapy.
  • Before treatment, it is important to premedication.

Pegvalias: Drug Interaction

Monitoring parameters:

• Blood phenylalanine concentration before starting therapy, every 4 weeks until maintenance is achieved, then frequently 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).
• Serum phenylalanine concentrations should be maintained between 120 and 360 micromol/L for 3 months before and during pregnancy.

How to administer Pegvaliase (Palynziq)?

• In the case of self-administration, Pegvaliase should be injected subcutaneously in the front middle thighs or the abdomen (at least 2 inches away from navel).
• In the case of administration by another person, it should be injected subcutaneously on the back of the upper arms or the top of the buttocks.
• Rotate injection sites. If a single dose required more than 1 injection, the second injection should be given 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.
• Close monitoring is required for initial administration or re-administration (after anaphylaxis) by a health care provider for ≥60 minutes following injection.

Mechanism of action of Pegvaliase (Palynziq):

Pegvaliase, a recombinant PEGylated Phenylalanine Ammonia Lyase (PAL), reduces blood levels of phenylalanine by converting it to ammonia or trans-cinnamic acids.

Absorption:

• Time: 8 hours

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.

International Brands of Pegvaliase:

• Palynziq

Palynziq Price in the US:

The cost of each prefilled syringe of Palynziq:

• 2.5 mg/0.5 mL: $612.00
• 10 mg/0.5 mL: $612.00
• 20 mg/mL: $612.00

Pegvaliase Brand Names in Pakistan:

No Brands Available in Pakistan.