PLEGRIDY
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PLEGRIDY (PLEGRIDY).
Peginterferon beta-1a is a pegylated form of interferon beta-1a that binds to interferon type I receptors, leading to expression of anti-inflammatory and immunomodulatory proteins, reducing inflammatory activity in multiple sclerosis.
| Metabolism | Peginterferon beta-1a is thought to be degraded via proteolysis; specific enzymes not identified. |
| Excretion | Plegridy is cleared primarily through catabolism. No specific excretion data available; it is not expected to be excreted renally or fecally as an intact protein. |
| Half-life | The terminal elimination half-life is approximately 78 hours (range 55–113 hours) after subcutaneous administration, supporting the every-14-day dosing interval. |
| Protein binding | Plegridy binds to serum proteins; specific binding proteins and percentage bound not fully characterized, but pegylation and Fc fusion likely result in high binding (estimated >90%). |
| Volume of Distribution | The volume of distribution is approximately 8.7 L (Vz after SC dosing) in healthy subjects, indicating distribution primarily in the extracellular space and limited tissue penetration. In L/kg (assuming 70 kg): ~0.12 L/kg. |
| Bioavailability | Subcutaneous bioavailability is approximately 60%. |
| Onset of Action | The onset of action is gradual; clinical effects are observed within 12 weeks of therapy initiation. Pharmacodynamic markers (e.g., neopterin and MxA) show increases within 24–48 hours. |
| Duration of Action | The duration of action corresponds to the dosing interval (every 14 days). Clinical effect is maintained with regular dosing; no acute tolerance develops. |
Subcutaneous injection: 125 mcg every 14 days. Initial titration: 125 mcg subcutaneously on day 1, then 125 mcg on day 15, then 125 mcg every 14 days thereafter.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (CrCl < 30 mL/min) or ESRD. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | Safety and efficacy in pediatric patients (< 18 years) have not been established. |
| Geriatric use | No specific dose adjustment recommended, but elderly patients may have decreased renal function; monitor for adverse effects. Clinical studies did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PLEGRIDY (PLEGRIDY).
| Breastfeeding | It is unknown if peginterferon beta-1a is excreted in human milk. M/P ratio not available. Precautions: because many drugs are excreted in human milk, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of the drug to the mother. |
| Teratogenic Risk | Peginterferon beta-1a (Plegridy) is not teratogenic in animal studies at doses up to 30 times the human dose. In pregnant women, limited data show no increased risk of major birth defects, but the drug should be used only if clearly needed. First trimester: no evidence of teratogenicity. Second and third trimesters: no specific risks identified, but interferon exposure may be associated with increased risk of spontaneous abortion. |
■ FDA Black Box Warning
None
| Serious Effects |
["Patients with a history of hypersensitivity to interferon beta or peginterferon beta-1a or any of the product components"]
| Precautions | ["Hepatotoxicity (monitor liver function tests)","Depression and suicide risk","Injection site reactions including necrosis","Allergic reactions including anaphylaxis","Seizures","Cardiomyopathy and congestive heart failure","Thrombotic microangiopathy","Pulmonary arterial hypertension"] |
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| Fetal Monitoring | Monitor for signs of depression, suicidal ideation, and hepatic injury. Complete blood count and liver function tests should be monitored periodically. Fetal monitoring: consider ultrasound assessment if concerns arise; no specific fetal monitoring required beyond standard obstetric care. |
| Fertility Effects | In animal studies, peginterferon beta-1a did not affect fertility in female rats at doses up to 50 mcg/kg. Human data are lacking; potential immunosuppressive effects might theoretically impact fertility, but no significant effects reported. |