XIFYRM
Clinical safety rating: caution
Comprehensive clinical and safety monograph for XIFYRM (XIFYRM).
XIFYRM is a monoclonal antibody that targets and neutralizes interleukin-36 (IL-36), thereby inhibiting the inflammatory signaling cascade involved in pustular psoriasis.
| Metabolism | XIFYRM is a monoclonal antibody; metabolism is expected to involve degradation into small peptides and amino acids via general protein catabolism. |
| Excretion | Renal: 70% unchanged; Fecal: 20%; Biliary: <10% |
| Half-life | Terminal elimination half-life: 15 hours; prolonged in renal impairment (creatinine clearance <30 mL/min) to 30 hours |
| Protein binding | 93% bound to serum albumin; also binds to alpha-1-acid glycoprotein |
| Volume of Distribution | 1.2 L/kg; indicates extensive tissue distribution, exceeding total body water |
| Bioavailability | Oral: 85% (range 80-90%); Subcutaneous: 100%; Intravenous: 100% |
| Onset of Action | Oral: 30-60 minutes; Intravenous: 5-10 minutes |
| Duration of Action | Oral: 12-24 hours; Intravenous: 6-12 hours; due to sustained-release formulation for oral route |
500 mg orally twice daily with food.
| Dosage form | SOLUTION |
| Renal impairment | GFR 30-89 mL/min: 500 mg twice daily. GFR 15-29 mL/min: 500 mg once daily. GFR <15 mL/min or dialysis: 500 mg every 48 hours. |
| Liver impairment | Child-Pugh A: No adjustment. Child-Pugh B: Reduce dose to 250 mg twice daily. Child-Pugh C: Not recommended. |
| Pediatric use | For patients >12 years and >=40 kg: 500 mg twice daily. For patients 6-12 years (20-39 kg): 250 mg twice daily. For patients <6 years: Not established. |
| Geriatric use | No specific dose adjustment based on age alone; monitor renal function and adjust per renal criteria. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for XIFYRM (XIFYRM).
| Breastfeeding | No data on excretion in human milk. Due to potential for serious adverse reactions in nursing infants, breastfeeding is contraindicated during therapy and for 30 days after last dose. M/P ratio: unknown. |
| Teratogenic Risk | XIFYRM is contraindicated in pregnancy. First trimester: High risk of major congenital malformations including craniofacial defects, neural tube defects, and cardiac anomalies. Second and third trimesters: Risk of spontaneous abortion, intrauterine growth restriction, and oligohydramnios. Embryo-fetal toxicity is dose-dependent. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to XIFYRM or any of its excipients","Active serious infection"]
| Precautions | ["Increased risk of infections due to immunomodulation","Hypersensitivity reactions including anaphylaxis","Potential for reactivation of tuberculosis or other latent infections","Avoid live vaccines during treatment"] |
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| Fetal Monitoring |
| Monitor pregnancy status prior to initiation and monthly during therapy. If pregnancy occurs, discontinue immediately. Perform ultrasound to assess fetal anatomy and amniotic fluid volume. Monitor maternal renal function, liver function, and electrolytes monthly. |
| Fertility Effects | XIFYRM impairs fertility in females by disrupting ovarian function and causing anovulation. In males, it reduces spermatogenesis and sperm motility. Fertility impairment is reversible upon discontinuation but may persist for several months. |