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.

Renal Dose Adjustments

No adjustment recommended

Liver Dose Adjustments

No adjustment recommended

Dose Adjustments

PREMEDICATION:

• Consider premedication with an H1-receptor antagonist, H2-receptor antagonist, and/or antipyretic prior to administration based upon individual patient tolerability

FOR READMINISTRATION FOLLOWING ANAPHYLAXIS:

• If the decision is made to readminister this drug after an anaphylaxis episode
• Administer the first dose under the supervision of a healthcare provider equipped to manage anaphylaxis and closely observe the patient for at least 60 minutes following the dosing
• Subsequent dose titration should be based on patient tolerability and therapeutic response

Phenylalanine Concentration Below 30 micromol/L:

• If during therapy, blood phenylalanine concentrations drops below 30 micromol/L, dose reduction and/or dietary protein and phenylalanine intake should be modified to maintain blood phenylalanine concentrations within a clinically acceptable range

Blood Level Monitoring:

• Obtain a baseline blood phenylalanine concentration
• Measure blood phenylalanine concentrations every 4 weeks until a maintenance dose is established
• After a maintenance dose is established, periodic blood phenylalanine concentrations should be obtained to assess blood phenylalanine control

Diet:

• Monitor dietary protein and phenylalanine intake throughout therapy; dietary intake may need to be adjusted based on blood phenylalanine concentrations

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for Palynziq. It includes element to assure safe use and an implementation system. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNING: RISK OF ANAPHYLAXIS

• Anaphylaxis has been reported after administration of this drug and may occur at any time during treatment.
• Administer initial dose under the supervision of a healthcare provider equipped to manage anaphylaxis, and closely observe patients for at least 60 minutes following injection. Prior to self-injection, confirm patient competency with self-administration, and patient and observer (if applicable) ability to recognize signs and symptoms of anaphylaxis and administer auto-injectable epinephrine, if needed.
• Consider having an adult observer for patients who may need assistance in recognizing and managing anaphylaxis during treatment. If an adult observer is needed, the observer should be present during and for at least 60 minutes after administration, should be able to administer auto-injectable epinephrine, and call for emergency medical support.
• Prescribe auto-injectable epinephrine to all patients. Prior to the first dose, instruct patient and observer (if applicable) to recognize the signs and symptoms of anaphylaxis, how to properly administer auto-injectable epinephrine, and to seek immediate medical care upon its use. Instruct patients to carry auto-injectable epinephrine with them at all times during treatment.
• Consider the risks and benefits of readministering this drug following an episode of anaphylaxis. If the decision is made to readminister, the first dose should be readministered under the supervision of a healthcare provider equipped to manage anaphylaxis and the patient should be closely observed for at least 60 minutes following this dose.
• Because of the risk of anaphylaxis, this drug is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the Palynziq REM.

CONTRAINDICATIONS: None

Safety and efficacy have not been established in patients younger than 18 years.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

• Initial administration and/or readministration after an anaphylaxis episode should occur under the supervision of a healthcare provider equipped to manage anaphylaxis; closely observe patient for at least 60 minutes following injection
• Administer subcutaneously into front middle of thighs or into abdomen (at least 2 inches away from navel); may also be administered by a caregiver to the top of buttocks or back of upper arm
• Do not inject into moles, scars, birthmarks, bruises, rashes, or areas where the skin is hard, tender, red, damaged, burned, inflamed, or tattooed
• Patients should receive instruction on self-administration of this drug and auto-injectable epinephrine; disposal of used syringes should be reviewed
• Patients should be instructed not to share syringes due to risk of blood borne infections

Missed dose: If a dose is missed, take next dose as scheduled; do not take 2 doses to make-up for the missed dose

Storage requirements:

• Prior to use: Store in refrigerator 36F to 46F (2C to 8C) in original carton to protect from light; do not freeze or shake
• In use: May store in original carton at room temperature 68F to 77F (20C to 25C) for up to 30 days; do not return product to the refrigerator

General:

• Treatment should be managed by a healthcare provider experienced in the management of phenylketonuria (PKU).
• For hypersensitivity reactions, consider premedication with an H1-receptor antagonist, H2-receptor antagonist, and/or antipyretic.
• Ensure injectable epinephrine is available and ready to be administered at all times during therapy; patients who experience anaphylaxis should seek immediate medical care, discontinue therapy, and resume treatment only at the instruction of a healthcare provider.

Monitoring:

• Monitor injection sites for redness, swelling, or tenderness
• Monitor for anaphylaxis and hypersensitivity reactions
• Obtain baseline phenylalanine concentration; measure blood phenylalanine concentrations every 4 weeks until a maintenance dose is established
• After a maintenance dose is established, periodic blood phenylalanine concentrations should be obtained to assess blood phenylalanine control
• Monitor dietary protein and phenylalanine intake

Patient advice:

• Read the US FDA-approved patient labeling (Medication Guide and Instructions for Use).
• Patients should receive proper instruction for self-administration of this drug and auto-injectable epinephrine; patients should be instructed to carry auto-injectable epinephrine with them at all times during therapy.
• Patients should understand the need to adhere to dietary protein and phenylalanine intake and how to adjust if needed.
• Female patients of reproductive potential should speak to their healthcare provider if they pregnant or are planning to become pregnant.

Frequently asked questions

• What is Palynziq used to treat?