ZILRETTA
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZILRETTA (ZILRETTA).
Corticosteroid receptor agonist; suppresses inflammation by inhibiting multiple inflammatory cytokines (e.g., IL-1, IL-6, TNF-alpha), phospholipase A2, and prostaglandin synthesis; administered as a long-acting intra-articular injection.
| Metabolism | Hepatic via CYP3A4 (major); also metabolized by CYP3A5; triamcinolone acetonide is the active moiety released from the microsphere formulation. |
| Excretion | Primarily hepatic metabolism; <5% excreted unchanged in urine, negligible biliary/fecal elimination. |
| Half-life | Triamcinolone acetonide: terminal half-life approximately 4.3 hours (immediate-release portion) and 41 hours (extended-release, due to slow dissolution); clinical suppression of cortisol for up to 6 weeks. |
| Protein binding | Approximately 68% bound to albumin and corticosteroid-binding globulin. |
| Volume of Distribution | Apparent Vd approximately 1.4 L/kg; indicates extensive tissue distribution. |
| Bioavailability | Intra-articular: 100% (local administration); systemic absorption is gradual and sustained due to microsphere formulation. |
| Onset of Action | Within 2–4 weeks after intra-articular injection; pain relief may begin earlier in some patients. |
| Duration of Action | Up to 12 weeks for pain relief; single dose provides sustained benefit for 3–6 months; maximal effect at 4–6 weeks. |
60 mg intra-articular injection once per knee; second dose not recommended within 12 months
| Dosage form | FOR SUSPENSION, EXTENDED RELEASE |
| Renal impairment | No dose adjustment required for renal impairment; not studied in end-stage renal disease |
| Liver impairment | No specific dose adjustment; use caution in severe hepatic impairment (Child-Pugh C) |
| Pediatric use | Not approved for use in pediatric patients (<18 years); safety and efficacy not established |
| Geriatric use | No specific dose adjustment; monitor for increased risk of infection, fracture, and cardiovascular events in elderly |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZILRETTA (ZILRETTA).
| Breastfeeding | Triamcinolone acetonide is excreted in human breast milk. The milk-to-plasma ratio is unknown. Extended-release formulation may result in sustained levels. Consider risk-benefit; alternatives may be preferred due to potential for infant growth suppression and adrenal suppression. |
| Teratogenic Risk | Corticosteroids, including ZILRETTA (triamcinolone acetonide extended-release injectable suspension), are associated with increased risk of cleft palate and intrauterine growth restriction when administered during the first trimester. Second and third trimester exposure may increase risk of preterm labor, low birth weight, and adrenal suppression in the neonate. The extended-release formulation may lead to prolonged fetal exposure. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to triamcinolone acetonide or any component of the formulation","Active infection (e.g., septic arthritis)","Uncontrolled diabetes mellitus","Coagulopathy or bleeding disorder (relative)","Pregnancy (category C; avoid use)"]
| Precautions | ["Do not administer intravenously, epidurally, intrathecally, or by any non-intra-articular route","Risk of joint infection","Risk of corticosteroid-related systemic effects (e.g., adrenal suppression, Cushing's syndrome)","Not for repeated use in the same joint","Risk of anaphylaxis","Use with caution in patients with diabetes (may increase blood glucose)","Avoid in patients with active infection or unstable joint"] |
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| Fetal Monitoring | Monitor maternal blood glucose, blood pressure, and signs of infection. For fetal surveillance, consider serial growth ultrasounds due to risk of intrauterine growth restriction. Neonatal assessment for adrenal suppression is recommended after delivery if prolonged maternal use. |
| Fertility Effects | Corticosteroids may cause menstrual irregularities and reversible suppression of ovulation. No permanent fertility impairment reported; however, extended-release formulation's prolonged exposure may transiently reduce fertility. |