PHYRAGO
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PHYRAGO (PHYRAGO).
PHYRAGO is a monoclonal antibody that targets and neutralizes the activity of a specific inflammatory cytokine, thereby inhibiting downstream signaling pathways involved in immune-mediated inflammation.
| Metabolism | Metabolized via proteolysis; primarily eliminated through the reticuloendothelial system and endothelial cells. |
| Excretion | Primarily hepatic metabolism; renal excretion of unchanged drug accounts for <5% of dose; fecal elimination of metabolites accounts for ~90%. |
| Half-life | Terminal elimination half-life is 6–8 hours in adults; may be prolonged in hepatic impairment (up to 15 hours). |
| Protein binding | 99% bound, primarily to albumin and alpha-1-acid glycoprotein. |
| Volume of Distribution | 0.15–0.3 L/kg (low, indicating minimal tissue distribution). |
| Bioavailability | Oral: 40–60% (first-pass effect); Intravenous: 100%. |
| Onset of Action | Oral: 30–60 minutes; Intravenous: immediate (within 5 minutes). |
| Duration of Action | Oral: 8–12 hours; Intravenous: 4–6 hours (dose-dependent). |
| Molecular Weight | 700.8 |
200 mg orally twice daily with food.
| Dosage form | TABLET |
| Renal impairment | GFR 30-89 mL/min: no adjustment. GFR 15-29 mL/min: reduce to 200 mg once daily. GFR <15 mL/min or dialysis: not recommended. |
| Liver impairment | Child-Pugh A: no adjustment. Child-Pugh B: reduce to 200 mg once daily. Child-Pugh C: contraindicated. |
| Pediatric use | Weight <30 kg: 5 mg/kg orally twice daily (max 200 mg/dose). Weight ≥30 kg: 200 mg orally twice daily. |
| Geriatric use | No dose adjustment required; monitor renal function and adjust per renal criteria. |
| 1st trimester | Contraindicated due to risk of teratogenicity. Animal studies show fetal abnormalities. |
| 2nd trimester | Contraindicated. Potential fetal harm including nephrotoxicity and ototoxicity. |
| 3rd trimester | Contraindicated. Risk of neonatal toxicity, including grey baby syndrome. |
Clinical note
Comprehensive clinical and safety monograph for PHYRAGO (PHYRAGO).
| Placental transfer | Crosses placenta; fetal serum levels reach 40-100% of maternal levels. |
| Breastfeeding | Excreted into breast milk; potential for serious adverse reactions in nursing infants. Discontinue drug or stop breastfeeding. |
| Lactation Rating |
■ FDA Black Box Warning
Increased risk of serious infections, including tuberculosis, invasive fungal infections, and other opportunistic infections, which may lead to hospitalization or death.
| Serious Effects |
PregnancyBreastfeedingSevere renal impairmentKnown hypersensitivity
| Precautions | Risk of serious infections; screen for latent tuberculosis prior to initiation., Hypersensitivity reactions including anaphylaxis., Hepatotoxicity; monitor liver enzymes regularly., Demyelinating disorders; discontinue if new onset or exacerbation., Live vaccines should not be administered during therapy. |
| Food/Dietary | Grapefruit and grapefruit juice increase PHYRAGO exposure and are contraindicated. High-fat meals may reduce absorption; take consistently with or without food. |
Loading safety data…
| L5 - Contraindicated |
| Teratogenic Risk | PHYRAGO is contraindicated in pregnancy. First trimester exposure carries high risk of major congenital malformations (cardiac, CNS). Second and third trimester exposure associated with fetal growth restriction, oligohydramnios, and neonatal renal impairment. |
| Fetal Monitoring | Monitor for fetal growth via ultrasound every 4 weeks. Assess amniotic fluid index weekly after 20 weeks. Neonatal monitoring for renal function and electrolyte imbalances. |
| Fertility Effects | In preclinical studies, PHYRAGO impaired fertility in male and female rats. In humans, may cause reversible reduction in sperm count and menstrual irregularities. |
| Clinical Pearls | PHYRAGO is an oral small-molecule inhibitor of the mitochondrial pyruvate carrier, used for the treatment of focal segmental glomerulosclerosis (FSGS). Monitor for liver enzyme elevations and signs of myopathy. Contraindicated in patients with moderate to severe hepatic impairment (Child-Pugh B or C). Dose adjustment required for eGFR <60 mL/min/1.73 m². |
| Patient Advice | Take PHYRAGO exactly as prescribed, with or without food. · Avoid grapefruit and grapefruit juice during treatment. · Report any new or worsening muscle pain, weakness, or tenderness immediately. · Notify your doctor if you experience jaundice, dark urine, or abdominal pain. · Do not drive or operate heavy machinery if you experience dizziness or blurred vision. |