Pegvaliase

Pegvaliase is an enzyme used to reduce blood phenylalanine concentrations in adults with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations of more than 600 micromol/L on existing management.

• Pegvaliase is available under the following different brand names: Palynziq, pegylated phenylalanine ammonia-lyase (PAL), pegvaliase-pqpz

Common side effects of Pegvaliase include:

• injection site reactions
• joint pain
• hypersensitivity reactions
• headache
• generalized skin reactions lasting at least 14 days
• itching
• nausea
• abdominal pain
• sore throat and mouth
• vomiting
• cough
• diarrhea
• fatigue
• dizziness
• anxiety
• hair loss
• stuffy nose

Serious side effects of Pegvaliase include:

• hives
• difficulty breathing
• swelling of the face, lips, tongue, or throat
• rash
• itching
• confusion
• dizziness
• lightheadedness
• nausea
• vomiting
• diarrhea
• loss of bladder or bowel control
• fast heartbeats
• wheezing
• chest tightness
• trouble breathing
• flushing (warmth, redness, or tingly feeling)

Rare side effects of Pegvaliase include:

• none

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors;
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights;
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult dosage

Injectable solution, single-dose prefilled syringe

• 2.5 mg/0.5 mL
• 10 mg/0.5 mL
• 20 mg/mL

Phenylketonuria

Adult dosage

• Induction
  • Initial dose: 2.5 mg SC once weekly for 4 weeks
• Titration
  • Based on tolerability, titrate the dose in a stepwise manner over at least 5 weeks, to achieve a dosage of 20 mg SC once a day
  • Weekly titration schedule
  • Week 1: 2.5 mg twice weekly
  • Week 2: 10 mg once weekly
  • Week 3: 10 mg twice weekly
  • Week 4: 10 mg 4 times a week
  • Week 5: 10 mg once daily
  • Additional time may be needed for dose escalation depending on tolerability
• Maintenance
  • Therapeutic response may not be achieved until a patient is titrated to an effective maintenance dosage
  • Use the lowest effective and tolerated dose
  • Assess patient tolerability, blood phenylalanine concentrations, and dietary protein and phenylalanine intake throughout treatment
  • Individualize maintenance dosage to achieve blood phenylalanine control (blood phenylalanine concentrations less than 600 micromol/L)
  • Maintain at 20 mg SC once a day for at least 24 weeks; consider increasing to 40 mg/day in patients who have been maintained continuously on 20 mg once a day for at least 24 weeks without achieving blood phenylalanine control
  • Consider increasing to a maximum of 60 mg/day in those who have been on 40 mg/day for at least 16 weeks without achieving blood phenylalanine control
• Discontinuation
  • Discontinue in patients who have not achieved a response after 16 weeks of continuous treatment with a maximum dosage of 60 mg/day

Dosage Considerations – Should be Given as Follows:

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Pegvaliase has severe interactions with no other drugs
• Pegvaliase has serious interactions with no other drugs
• Pegvaliase has moderate interactions with the following drugs:
  • certolizumab pegol
  • Factor IX, recombinant
  • griseofulvin
  • methoxy polyethylene glycol/epoetin beta
  • pegademase
  • pegaptanib
  • pegaspargase
  • pegfilgrastim
  • peginterferon alfa 2a
  • peginterferon alfa 2b
  • peginterferon beta-1a
  • polyethylene
  • pegvisomant
  • polyethylene glycol & electrolytes
  • polyethylene glycol 400/propylene glycol ophthalmic
  • polyethylene glycol/electrolytes/sodium ascorbate/ascorbic acid
  • sodium sulfate/potassium chloride/magnesium sulfate/polyethylene glycol
• Pegvaliase has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• None

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Pegvaliase?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Pegvaliase?”

Cautions

• In clinical trials with induction/titration/maintenance dosing, 26 (9%) of 285 patients experienced a total of 37 anaphylaxis episodes
• Management of hypersensitivity reactions should be based on the severity of the reaction, recurrence of the reaction, and clinical judgment of the healthcare provider, and may include dosage adjustment, temporary drug interruption, or treatment with antihistamines, antipyretics, and/or corticosteroids
• REMS program
  • Treatment is available only through a restricted program under Palynziq REMS, because of the risk of anaphylaxis
  • Hypersensitivity reactions, other than anaphylaxis, reported
  • Requirements of the REMS program
  • Prescribers must be certified with the program by enrolling in the program and completing training
  • Prescribers must prescribe auto-injectable epinephrine
  • Pharmacies must be certified with the program and must dispense only to patients who are authorized to receive treatment
  • Patients must enroll in the program and be educated about the risk of anaphylaxis by a certified prescriber to ensure they understand the risks and benefits of treatment
  • Patients must have auto-injectable epinephrine available at all times
  • Further information, including a list of qualified pharmacies, is available at www.PALYNZIQREMS.com or by telephone at 1-855-758-REMS (1-855-758-7367)
• Drug interactions overview
  • Most patients treated with pegvaliase develop anti-polyethylene glycol (PEG) IgM and IgG antibodies
  • Risk of coadministration with different PEGylated products is unknown; however, there is a case report of anaphylaxis following a medroxyprogesterone acetate injectable suspension that contained PEG 3350
  • Carefully read all drug labels, including OTC drugs to check contents for PEG

Pregnancy and Lactation

• Based on findings in studies of pregnant animals without PKU, pegvaliase-pqpz may cause fetal harm when administered to a pregnant woman
• Limited available data on pegvaliase-pqpz use in pregnant women are insufficient to inform a drug-associated risk of adverse developmental outcomes
• Risks to the fetus associated with poorly controlled phenylalanine concentrations in women with PKU during pregnancy include increased risk for miscarriage, major birth defects (eg, microcephaly, major cardiac malformations), intrauterine fetal growth restriction, and future intellectual disability with low IQ; therefore, closely phenylalanine concentrations in women with PKU during pregnancy
• Advise pregnant women of the potential risks to the fetus
• Disease-associated maternal and/or embryo-fetal risk
• Uncontrolled blood phenylalanine concentrations before and during pregnancy are associated with an increased risk of adverse pregnancy outcomes and fetal adverse effects; to reduce the risk of hyperphenylalaninemia-induced fetal adverse effects, blood phenylalanine concentrations should be maintained between 120–360 micromol/L during pregnancy and during the 3 months before conception
• Dose adjustments during pregnancy and the postpartum period
• Phenylalanine concentrations below 30 micromol/L in pregnant women with PKU may be associated with adverse fetal outcomes; monitor blood phenylalanine concentrations during pregnancy and adjust the dose or modify dietary protein and phenylalanine intake to avoid blood phenylalanine concentrations below 30 micromol/L
• Lactation
  • There are no data on the presence of pegvaliase-pqpz in human milk, the effects on the breastfed infant, or milk production
  • A prenatal/postnatal study in rats showed that pegvaliase-pqpz is present in rat milk and that administration of this drug during lactation decreased pup weight and survival