SILIQ
Clinical safety rating: caution
Comprehensive clinical and safety monograph for SILIQ (SILIQ).
Interleukin-17A antagonist; binds to and neutralizes IL-17A, preventing its interaction with the IL-17 receptor and reducing pro-inflammatory cytokine release.
| Metabolism | Metabolized via non-CYP450 pathways; degradation into small peptides and amino acids. |
| Excretion | Primarily degraded into small peptides and amino acids via general protein catabolism; no significant renal or biliary elimination of intact drug. |
| Half-life | Approximately 22-23 days (range 20-26 days) with steady-state reached by 16-20 weeks after monthly dosing. |
| Protein binding | Approximately 90% bound, primarily to albumin; minor binding to alpha-1-acid glycoprotein. |
| Volume of Distribution | Approximately 6.2 L (0.089 L/kg for 70 kg individual), indicating limited distribution into tissues, consistent with a monoclonal antibody confined primarily to vascular and interstitial spaces. |
| Bioavailability | Subcutaneous: Approximately 75% (range 55-90%) relative to intravenous administration. |
| Onset of Action | Subcutaneous administration: Clinical improvement in psoriasis symptoms observed as early as 4 weeks after first dose. |
| Duration of Action | Following a single subcutaneous dose, pharmacodynamic effects (e.g., reduction in IL-17A levels) may persist for several months; due to long half-life, therapeutic effect is maintained for at least 12 weeks after last dose. |
Subcutaneous injection: 210 mg (two 105 mg injections) every 4 weeks after a single 420 mg loading dose (four 105 mg injections) on day 0.
| Dosage form | INJECTABLE |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not studied in severe renal impairment (eGFR <15 mL/min/1.73m²) or ESRD. |
| Liver impairment | No dose adjustment required for mild (Child-Pugh A) or moderate (Child-Pugh B) hepatic impairment. Not studied in severe (Child-Pugh C) hepatic impairment. |
| Pediatric use | Safety and efficacy not established in pediatric patients below 18 years of age. |
| Geriatric use | No specific dose adjustment required. No overall differences in safety or efficacy observed between elderly (≥65 years) and younger adults. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for SILIQ (SILIQ).
| Breastfeeding | It is unknown whether brodalumab is excreted in human milk. However, brodalumab is a human monoclonal antibody, and human IgG is excreted in breast milk. The M/P ratio is not known. Due to the potential for adverse reactions in nursing infants from brodalumab, breastfeeding is not recommended during treatment and for at least 5 half-lives (approximately 5 weeks) after the last dose. |
| Teratogenic Risk | SILIQ (brodalumab) is a human monoclonal IgG2 antibody. Based on its mechanism of action (IL-17RA blockade) and animal studies, there is a potential risk of fetal harm. In animal reproduction studies, administration of brodalumab to pregnant monkeys throughout organogenesis resulted in increased incidence of abortions and fetal loss at doses 50 times the human exposure (AUC). There are no adequate and well-controlled studies in pregnant women. Therefore, SILIQ should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. First trimester: unknown risk; second and third trimesters: IgG antibodies can cross the placenta, with increasing transfer as pregnancy progresses; potential for fetal immune suppression and altered immune response. |
■ FDA Black Box Warning
None.
| Serious Effects |
["Previous serious hypersensitivity reaction to secukinumab"]
| Precautions | ["Increased risk of infections, including serious infections","Hypersensitivity reactions","Inflammatory bowel disease exacerbation"] |
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| Fetal Monitoring | Monitor for signs of infection in the mother. No specific fetal monitoring is recommended beyond standard prenatal care. Consider monitoring infant for potential immune-mediated effects if exposure occurs in utero. |
| Fertility Effects | No clinical data on fertility effects in humans. In animal studies, no adverse effects on male or female fertility were observed in monkeys at doses up to 150 mg/kg (approximately 66 times the human exposure by AUC). |