ILARIS
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ILARIS (ILARIS).
Monoclonal antibody that binds to interleukin-1 beta (IL-1β), blocking its interaction with the IL-1 receptor, thereby inhibiting IL-1β-mediated inflammatory responses.
| Metabolism | No information on metabolism; canakinumab is a monoclonal antibody expected to be degraded into small peptides and amino acids via general protein catabolism. |
| Excretion | Canakinumab is degraded into small peptides and amino acids via general protein catabolic pathways. No significant renal or biliary excretion of intact drug. Elimination occurs through proteolytic degradation. |
| Half-life | 26.9 days (range 22.1–33.2 days) in patients with cryopyrin-associated periodic syndromes, supporting monthly subcutaneous dosing. |
| Protein binding | Approximately 95% bound to serum albumin (high affinity, non-saturable binding). |
| Volume of Distribution | 6.0 L (approx. 0.086 L/kg for a 70 kg adult), indicating distribution primarily in the vascular space with limited extravascular penetration. |
| Bioavailability | Subcutaneous: Approximately 68% (absolute bioavailability) with peak concentrations achieved at 2–7 days post-dose. |
| Onset of Action | Subcutaneous: Clinical response (e.g., resolution of fever and rash) observed within 24–48 hours after a single dose. |
| Duration of Action | Subcutaneous: Duration of clinical effect is approximately 8 weeks, corresponding to the dosing interval of every 4 weeks. |
150 mg subcutaneously every 8 weeks for CAPS; 300 mg subcutaneously every 4 weeks for TRAPS, HIDS/MKD, and FMF; 300 mg subcutaneously every 4 weeks for Still's disease (adult and pediatric ≥2 years); 4 mg/kg (max 300 mg) subcutaneously every 4 weeks for gout flares.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment recommended for mild to moderate renal impairment (CrCl ≥30 mL/min). Not studied in severe renal impairment (CrCl <30 mL/min) or end-stage renal disease; use with caution. |
| Liver impairment | No dose adjustment recommended for mild hepatic impairment (Child-Pugh A). Not studied in moderate to severe hepatic impairment (Child-Pugh B or C). |
| Pediatric use | CAPS: weight ≥7.5 kg, 2 mg/kg (max 150 mg) every 8 weeks; Still's disease: weight ≥7.5 kg, 4 mg/kg (max 300 mg) every 4 weeks; TRAPS, HIDS/MKD, FMF: weight ≥40 kg, 150 mg every 4 weeks; gout flares: not indicated in pediatric patients. |
| Geriatric use | No specific dose adjustment required; use with caution due to higher incidence of infections and reduced renal function. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ILARIS (ILARIS).
| Breastfeeding | Canakinumab is a large protein molecule (IgG1) expected to be present in breast milk in small amounts, but systemic absorption by the infant is likely minimal due to gastrointestinal degradation. No M/P ratio reported. Limited human data. Weigh benefit of breastfeeding against potential risk to infant. |
| Teratogenic Risk | ILARIS (canakinumab) is an IgG1 monoclonal antibody. IgG antibodies cross the placenta increasingly as pregnancy progresses, with the highest transfer in the third trimester. No adequate and well-controlled studies in pregnant women. In animal reproduction studies, no evidence of fetal harm was observed at doses up to 30 times the maximum human dose. However, human data are insufficient to determine teratogenic risk. Recommend avoiding use in pregnancy unless potential benefit outweighs risk. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Known hypersensitivity to canakinumab or any of its excipients"]
| Precautions | ["Increased risk of serious infections due to IL-1 blockade; do not start during active infection","Hypersensitivity reactions including anaphylaxis","Neutropenia (monitor absolute neutrophil count prior to initiation)","Live vaccines should not be given concurrently with canakinumab","May interfere with immune response to vaccines"] |
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| Fetal Monitoring | Monitor for signs of infection (fever, neutropenia) in mother and infant due to immunosuppression. Monitor pregnancy outcome for potential adverse effects. For infants exposed in utero, monitor for immunologic effects, including response to vaccines (avoid live vaccines for 16 weeks after last maternal dose). |
| Fertility Effects | No specific human data on fertility effects. Animal studies showed no impairment of fertility. Theoretical risk due to modulation of IL-1beta may affect implantation and maintenance of pregnancy, but clinical significance unknown. |