KINERET
Clinical safety rating: caution
Comprehensive clinical and safety monograph for KINERET (KINERET).
Recombinant human interleukin-1 receptor antagonist (IL-1Ra) that competitively inhibits IL-1 binding to IL-1 type I receptor, blocking IL-1-mediated inflammatory signaling.
| Metabolism | Metabolized by renal catabolism; no known involvement of CYP450 enzymes or other specific hepatic pathways. |
| Excretion | Primarily renal; approximately 78% of administered dose is excreted unchanged in the urine over 24 hours. Minimal biliary/fecal elimination (less than 1%). |
| Half-life | Terminal elimination half-life is 108 minutes (1.8 hours) in patients with normal renal function. This short half-life necessitates daily subcutaneous dosing to maintain therapeutic interleukin-1 receptor blockade. |
| Protein binding | Approximately 95% bound to plasma proteins, primarily albumin. |
| Volume of Distribution | Volume of distribution is 0.18 L/kg (approximately 12.6 L in a 70 kg adult), indicating limited distribution primarily within the vascular and extracellular fluid spaces. |
| Bioavailability | Subcutaneous: 95-100% bioavailable. Not administered intravenously clinically; absolute bioavailability from subcutaneous injection is nearly complete due to minimal presystemic metabolism. |
| Onset of Action | Subcutaneous: Clinical improvement (reduction in joint swelling and pain) is noted within 1 to 3 days after first dose in patients with rheumatoid arthritis and cryopyrin-associated periodic syndromes. |
| Duration of Action | Duration of action is approximately 24 hours based on sustained suppression of interleukin-1-mediated inflammatory markers (e.g., CRP, IL-6). Dosing is therefore required once daily; missed doses may lead to rapid recurrence of symptoms. |
100 mg subcutaneously once daily.
| Dosage form | VIAL |
| Renal impairment | CrCl 30-50 mL/min: 100 mg every other day; CrCl <30 mL/min or ESRD on dialysis: 100 mg every 3 days. |
| Liver impairment | No dosage adjustment required for mild to moderate hepatic impairment. Not studied in severe hepatic impairment. |
| Pediatric use | Weight ≥50 kg: 100 mg subcutaneously once daily; Weight <50 kg: 2 mg/kg subcutaneously once daily, maximum 100 mg. |
| Geriatric use | No specific dose adjustment; monitor renal function as age-related decline may necessitate renal adjustment. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for KINERET (KINERET).
| Breastfeeding | Unknown if excreted in human milk. Caution is advised. M/P ratio not reported. |
| Teratogenic Risk | FDA Pregnancy Category B. Animal studies have not demonstrated fetal risk, but no adequate human studies in pregnant women. Use only if clearly needed. |
| Fetal Monitoring | Monitor maternal complete blood count (CBC) and renal function periodically. No specific fetal monitoring required. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Hypersensitivity to E. coli-derived proteins, anakinra, or any product component","Active infections"]
| Precautions | ["Serious infections, including bacterial, fungal, viral, and opportunistic infections, have been reported; do not initiate in patients with active infections; consider risks versus benefits in patients with history of recurrent or chronic infections.","Hypersensitivity reactions including anaphylaxis have occurred; discontinue if severe reaction develops.","Immunosuppression: Use with tumor necrosis factor (TNF) blocking agents may increase risk of serious infections; concomitant use is not recommended.","Malignancies: Lymphoma and other malignancies have been observed with anakinra, though a causal relationship is uncertain.","Neutropenia: Monitor neutrophil counts, especially during first months of therapy; use with caution in patients with pre-existing neutropenia."] |
Loading safety data…
| Fertility Effects | No evidence of impaired fertility from animal studies. Human data not available. |