PALYNZIQ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PALYNZIQ (PALYNZIQ).
PALYNZIQ (pegvaliase-pqpz) is a recombinant phenylalanine ammonia lyase conjugated to polyethylene glycol. It converts phenylalanine to trans-cinnamic acid and ammonia, reducing blood phenylalanine levels in patients with phenylketonuria.
| Metabolism | Pegvaliase is a PEGylated recombinant phenylalanine ammonia lyase that degrades phenylalanine via conversion to trans-cinnamic acid and ammonia. It is not metabolized by cytochrome P450 enzymes; the PEG moiety undergoes non-enzymatic hydrolysis. |
| Excretion | Renal (predominantly as intact pegylated enzyme); less than 5% fecal. No active metabolites. |
| Half-life | Approximately 60–80 hours (terminal half-life); supports weekly dosing regimen. |
| Protein binding | Not significantly bound to plasma proteins (<5%). |
| Volume of Distribution | Approximately 0.3–0.5 L/kg; indicates distribution primarily within extracellular fluid and plasma. |
| Bioavailability | Subcutaneous: Approximately 100% (pegylated recombinant enzyme; absorption complete from injection site). |
| Onset of Action | Subcutaneous: Clinical reduction in plasma phenylalanine observed within 1–2 weeks; maximal effect by 4–6 weeks. |
| Duration of Action | Subcutaneous: Duration of action approximately 7 days, consistent with weekly dosing; sustained suppression of phenylalanine levels with continued administration. |
2.4 mg subcutaneously once daily.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required based on GFR; drug is not renally cleared. |
| Liver impairment | No dose adjustment recommended; pharmacokinetics not studied in hepatic impairment. |
| Pediatric use | 1.0 mg subcutaneously once daily for patients weighing <7 kg; 1.6 mg subcutaneously once daily for 7-12 kg; 2.4 mg subcutaneously once daily for >12 kg. |
| Geriatric use | No specific dose adjustment; clinical studies did not include sufficient patients aged ≥65 to determine different response. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PALYNZIQ (PALYNZIQ).
| Breastfeeding | No data on presence in human milk; M/P ratio unknown. Effects on breastfed infant and milk production not established. Weigh benefits of breastfeeding against potential risk. |
| Teratogenic Risk | Insufficient human data; animal studies show no teratogenic effects at exposures up to 12 times the human dose. First trimester: no known structural anomalies. Second/third trimester: no known adverse fetal effects. |
| Fetal Monitoring |
■ FDA Black Box Warning
WARNING: ANAPHYLAXIS Anaphylaxis has been reported in some patients during and after treatment with PALYNZIQ. Because of the risk of anaphylaxis, PALYNZIQ is available only through a Risk Evaluation and Mitigation Strategy (REMS) program. Patients should be observed for an appropriate period of time after administration of PALYNZIQ and should be counseled on the symptoms of anaphylaxis.
| Serious Effects |
["History of anaphylaxis with pegvaliase-pqpz or any of its excipients."]
| Precautions | ["Anaphylaxis: Risk of serious hypersensitivity reactions; patients must be monitored and have access to appropriate medical support.","Hypersensitivity reactions (including arthralgia, injection site reactions, rash, urticaria) are common and may require dose adjustment or discontinuation.","Serum sickness-like reactions: Delayed hypersensitivity reactions may occur.","Angioedema: Can occur and require prompt management.","Concomitant use with other allergy medications may increase risk of severe hypersensitivity reactions."] |
Loading safety data…
| Monitor maternal serum phenylalanine levels weekly and adjust diet to maintain levels 60-120 μmol/L. Fetal ultrasound for growth and anatomy. Postnatal monitoring of infant phenylalanine levels. |
| Fertility Effects | No known effects on fertility in animal studies. Human data insufficient. |