Pegvaliase is a medication used in the treatment of phenylketonuria (PKU), a genetic disorder that causes a buildup of the amino acid phenylalanine in the body. Phenylalanine is found in many foods containing protein and is normally broken down by the enzyme phenylalanine hydroxylase (PAH). However, individuals with PKU have a deficiency in this enzyme, leading to the accumulation of phenylalanine, which can be toxic to the brain and nervous system.

Pegvaliase works by acting as a substitute for the missing enzyme, phenylalanine hydroxylase. It is a PEGylated form of the enzyme phenylalanine ammonia lyase (PAL), which is derived from a bacterium called Pseudomonas fluorescens. This enzyme helps break down phenylalanine into other substances that the body can eliminate, reducing the levels of phenylalanine in the blood.

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:

• Pegvaliase is a medicine for a condition called phenylketonuria (PKU), where the body can't break down an amino acid called phenylalanine.
• It's given as a shot under the skin every day.
• People with PKU need to follow a low-protein diet.
• Before starting pegvaliase, doctors check how much phenylalanine is in the blood.
• Some patients might need to take antihistamines or fever medicine before their injection to prevent allergic reactions.
• Doctors may also adjust the dose or diet to keep phenylalanine levels safe.
• Everyone getting pegvaliase should have an epinephrine auto-injector in case of severe allergic reactions.

Pegvaliase (Palynziq) dose in the treatment of Phenylketonuria:

• In the treatment of Phenylketonuria (PKU) with Pegvaliase given as a SubQ (subcutaneous) injection, the dosing starts with an induction phase of 2.5 mg once weekly for 4 weeks.
• After this, there's a titration phase where the dose is gradually increased: 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, and finally, 10 mg once daily for 1 week.
• The maintenance phase starts after induction and titration, with a dose of 20 mg once daily for at least 24 weeks.
• If there's not enough improvement, the dose may be increased to 40 mg once daily.
• However, if there's still no response after 16 weeks on 40 mg once daily, treatment should be stopped.
• The goal is to use the lowest effective dose that the patient can tolerate, with the maximum dose being 40 mg per 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 high levels of phenylalanine in pregnant women can lead to serious problems for the baby, including miscarriage, birth defects like microcephaly and major heart problems, and issues with growth and future learning abilities.
• It's crucial for women with phenylketonuria (PKU) to control their phenylalanine levels during pregnancy and for three months before trying to get pregnant to lower the risk of these problems.
• Right now, doctors recommend controlling phenylalanine levels through diet.
• We don't have enough information about using pegvaliase, a medication for PKU, during pregnancy.
• If a woman is exposed to pegvaliase during pregnancy or within a month after stopping the medication, it's important for healthcare providers to keep track of her and the baby's health through a special program.
• If you need more information or assistance, you can call 866-906-6100.

Pegvaliase use during breastfeeding:

• The presence of pegvaliase in breast milk is uncertain, and using pegvaliase may affect the amount of phenylalanine in breast milk.
• The decision whether to breastfeed while receiving pegvaliase therapy should weigh the potential risk of the baby being exposed to the medication against the benefits of breastfeeding for the baby and the benefits of treatment for the mother.
• Before breastfeeding, it's important to consider the baby's phenylalanine levels.

Dose adjustment in renal disease:

• According to the manufacturer's labeling, there are no specific dosage adjustments recommended for pegvaliase in individuals with renal impairment.
• This means that the standard dosing regimen outlined in the prescribing information should be followed regardless of the patient's kidney function.

Dose adjustment in liver disease:

• According to the manufacturer's labeling, there are no specific dosage adjustments recommended for pegvaliase in individuals with hepatic (liver) impairment.
• This means that the standard dosing regimen outlined in the prescribing information should be followed regardless of the patient's liver function.

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):

• According to the manufacturer's labeling, there are no specific contraindications listed for pegvaliase.
• This means that there are no absolute reasons stated in the labeling that would prohibit the use of pegvaliase in certain individuals.

Warnings and precautions

Hypersensitivity reactions: [US Boxed Warning]

• Pegvaliase comes with a boxed warning about the risk of hypersensitivity reactions, including anaphylaxis, which can occur at any time during treatment.
• The first dose should be administered under the supervision of a healthcare provider equipped to manage anaphylaxis, with patients closely observed for at least 60 minutes after injection.
• Patients should be trained in self-administration before self-injection, and they should carry auto-injectable epinephrine at all times during treatment.
• Symptoms of anaphylaxis may include fainting, low blood pressure, difficulty breathing, wheezing, chest discomfort, fast heart rate, swelling, skin rash, itching, or gastrointestinal symptoms.
• Delayed episodes of anaphylaxis have been reported, even up to 48 hours after administration.
• Other hypersensitivity reactions may also occur, and dose adjustments or temporary interruption of treatment may be considered.

Pegvaliase: Drug Interaction

Monitoring parameters:

Monitoring Blood Phenylalanine Concentration

• Before Starting Treatment:
  • Blood phenylalanine concentration should be measured.
• During Treatment Initiation:
  • Check blood phenylalanine concentration every 4 weeks until maintenance is reached.
• Throughout Treatment:
  • Continue periodic monitoring of blood phenylalanine concentration to ensure it remains within the target range.

Signs and Symptoms of Anaphylaxis/Hypersensitivity

• Initial Dose:
  • Monitor for signs and symptoms of anaphylaxis/hypersensitivity for at least 60 minutes after the first dose.
• Reinitiation of Therapy:
  • Repeat monitoring for signs and symptoms of anaphylaxis/hypersensitivity upon restarting treatment, especially after a previous episode of anaphylaxis.

Maintaining Serum Phenylalanine Concentrations during Pregnancy

• Before Conception and During Pregnancy:
  • Ensure serum phenylalanine concentrations are maintained between 120 and 360 micromol/L for at least 3 months prior to conception and throughout pregnancy to reduce the risk of adverse fetal events.

How to administer Pegvaliase (Palynziq)?

SubQ Administration Guidelines

• Injection Sites:
  • For self-administration: Inject into the front middle thighs or the abdomen, keeping at least 2 inches away from the navel.
  • For caregiver administration: Back of the upper arms and top of the buttocks may also be used.
• Rotation of Injection Sites:
  • Rotate injection sites to prevent irritation or discomfort.
  • If multiple injections are needed for a single dose, administer the second injection at least 2 inches away from the first site. The second site can be on the same or a different body part as the first injection.
• Close Observation:
  • Initial administration or re-administration (after anaphylaxis) should be done under close observation by a healthcare provider for at least 60 minutes following injection to monitor for any adverse reactions.

Mechanism of action of Pegvaliase (Palynziq):

• Pegvaliase is a type of enzyme called PEGylated phenylalanine ammonia lyase (PAL).
• This enzyme works by converting phenylalanine, an amino acid found in protein-containing foods, into ammonia and trans-cinnamic acid.
• By doing this, pegvaliase helps to reduce the levels of phenylalanine in the blood.
• This is important for people with phenylketonuria (PKU), a genetic disorder where the body cannot break down phenylalanine properly, leading to high levels in the blood.
• By lowering phenylalanine levels, pegvaliase helps to manage PKU and prevent associated health problems.

Absorption:

• Time to Peak Concentration (T): Approximately 8 hours.

Distribution:

• Volume of Distribution (V):
  • For a dose of 20 mg: Ranges from 1.8 to 241 liters.
  • For a dose of 40 mg: Ranges from 3.1 to 49.5 liters.

Metabolism:

• Metabolized via catabolic pathways.
• Degradation leads to the formation of small peptides and amino acids.

Elimination:

• Half-life:
  • For a dose of 20 mg: Half-life ranges from 14 to 132 hours.
  • For a dose of 40 mg: Half-life ranges from 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.