Pegvaliase is used to lower phenylalanine blood levels in adults with phenylketonuria (PKU) not controlled with other treatment.

Pegvaliase is available only from a certified pharmacy under a special program.

Pegvaliase may also be used for purposes not listed in this medication guide.

Pegvaliase can cause a serious allergic reaction. Your first dose will be given in a medical setting.

Get emergency medical help if you have signs of an allergic reaction such as hives, itching, dizziness, wheezing, trouble breathing, or swelling in your face or throat. Your doctor may prescribe an epinephrine injection kit to keep with you at all times.

Follow all directions on your prescription label and read all medication guides or instruction sheets. Your doctor may occasionally change your dose. Use the medicine exactly as directed.

Pegvaliase is injected under the skin. You may be given other medications to help prevent serious side effects or an allergic reaction.

You will receive your first dose in a medical setting to make sure you do not have an allergic reaction.

Read and follow all Instructions for Use. Ask your doctor or pharmacist if you need help.

Prepare an injection only when you are ready to give it. Call your pharmacist if the medicine looks cloudy, has changed colors, or has particles in it.

Do not shake the prefilled syringe or you may ruin the medicine.

Your healthcare provider will show you where to inject pegvaliase. Do not inject into the same place two times in a row.

You may need to have someone with you for at least 1 hour after you inject this medicine at home, to watch you for signs of an allergic reaction and give the epinephrine injection if needed.

Read the Warning Card about allergic reactions and learn what symptoms to watch for. Keep the card with you at all times.

You will need frequent medical tests.

You will need to follow a special diet. Follow all instructions of your doctor or dietitian. Learn about the foods you should eat or avoid.

Store this medicine in the refrigerator, do not freeze.

You may store the medicine for up to 30 days at room temperature in its original container, protected from light. Do not put the medicine back into the refrigerator. Throw away any unused medicine after 30 days or after the expiration date on the label has passed.

Throw away a prefilled syringe after one use, even if there is still medicine left inside.

Do not reuse a needle or syringe. Place them in a puncture-proof "sharps" container and dispose of it following state or local laws. Keep out of the reach of children and pets.

Usual Adult Dose for Phenylketonuria:

INDUCTION: 2.5 mg subcutaneously once a week for 4 weeks
-Titrate in a step-wise manner as tolerated over at least 5 weeks (described below); additional time may be required prior to each dose escalation based on tolerability
RECOMMENDED TITRATION SCHEDULE:
Week 1: 2.5 mg subcutaneously twice a week
Week 2: 10 mg subcutaneously once a week
Week 3: 10 mg subcutaneously twice a week
Week 4: 10 mg subcutaneously four times a week
Week 5: 10 mg subcutaneously once a day
Week 6: 20 mg subcutaneously once a day
-After at least 24 weeks at 20 mg/day, may consider increasing dose to 40 mg/day for patients unable to achieve blood phenylalanine control
-After at least 16 weeks at 40 mg/day, may consider increasing dose to 60 mg/day for patients unable to achieve blood phenylalanine control
MAINTENANCE DOSE: 20 to 60 mg subcutaneously once a day; maintenance dose should be individualized to achieve blood phenylalanine control (blood phenylalanine concentrations less than or equal to 600 micromol/L)
MAXIMUM DOSE:
-If, after 16 weeks at 60 mg/day, patient has not achieved an adequate response, therapy should be discontinued

Comments:
-Administer initial dose under the supervision of a healthcare provider; treatment should be managed by a healthcare provider experienced in the management of PKU.
-Obtain baseline blood phenylalanine concentration; assess tolerability, blood phenylalanine concentrations, and dietary protein and phenylalanine intake throughout treatment.
-Therapeutic response may not be achieved until titration to an effective maintenance dose is achieved; individualize dose, use lowest effective and tolerated dose.

Use: To reduce blood phenylalanine concentrations in patients with phenylketonuria (PKU) who have uncontrolled blood phenylalanine concentrations greater than 600 micromol/L on existing management.

Pegvaliase can cause a serious allergic reaction. Your doctor may prescribe an epinephrine injection kit to use in case you have a severe allergic reaction. Keep this injection kit with you at all times.

Tell your doctor if you think you might be unable to give yourself an emergency epinephrine injection.

Follow your doctor's instructions about using pegvaliase if you are pregnant. Controlling your phenylalanine levels is very important during pregnancy. Your name may be listed on a pregnancy registry to track the effects of pegvaliase on the baby.

Ask a doctor if it is safe to breastfeed while using this medicine.

Not approved for use by anyone younger than 18 years old.

Skip the missed dose and use your next dose at the regular time. Do not use two doses at one time.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Avoid injecting into skin that is red, bruised, hard, tender, injured, or irritated. Do not inject pegvaliase into skin areas with moles, scars, birthmarks, or tattoos.

Stop the pegvaliase injection and get emergency medical help if you have signs of an allergic reaction:

• hives, rash, itching;

• confusion, dizziness, feeling like you might pass out;

• nausea, vomiting, diarrhea;

• loss of bladder or bowel control;

• fast heartbeats;

• wheezing, chest tightness, difficult breathing;

• flushing (warmth, redness, or tingly feeling); or

• swelling of your face, lips, tongue, or throat.

Common side effects of pegvaliase may include:

• cough, stuffy nose;

• mouth and throat pain;

• dizziness;

• anxiety;

• low phenylalanine blood levels;

• a spreading skin reaction (itching, redness, rash) that could last at least 14 days;

• headache, joint pain;

• nausea, vomiting, stomach pain, diarrhea;

• tiredness; or

• pain, tenderness, bruising, redness, itching, or swelling where the injection was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Other drugs may affect pegvaliase, including prescription and over-the-counter medicines, vitamins, and herbal products. Tell your doctor about all other medicines you use.