Systemic exposure/diabetes study

ZILRETTA decreased peak systemic exposure¹

Results based on a pharmacokinetic study evaluating concentration of TA in plasma following a single intra-articular injection of ZILRETTA^® (triamcinolone acetonide extended-release injectable suspension) (n=60) or TAcs (n=18)²
- TA plasma concentrations are shown for blood samples collected periodically over
  24 hours¹
ZILRETTA reduced peak systemic exposure to TA compared with TAcs (1144 pg/mL vs 21,062 pg/mL)^3*

Based on C_max levels following a single intra-articular injection of ZILRETTA and TAcs.

TAcs=triamcinolone acetonide crystalline suspension.

Minimal increase in blood glucose levels vs TAcs in patients with controlled type 2 diabetes³

Results based on a pharmacodynamic study evaluating a single injection of ZILRETTA or TAcs in patients with orally controlled Type 2 diabetes; primary endpoint was the change in average blood glucose 72 hours pre-injection compared with 72 hours post-injection³
ZILRETTA demonstrated a statistically significantly smaller LS mean change (14.7 mg/dL vs 33.9 mg/dL; P=0.0452)³
- ZILRETTA: Average glucose values were 155.2 mg/dL pre-injection and 163.4 mg/dL
  (range: 89.8 mg/dL to 298.8 mg/dL) post-injection^1,3
- TAcs: Average glucose values were 161.7 mg/dL pre-injection and 198.8 mg/dL
  (range: 135.1 mg/dL to 315.8 mg/dL) post-injection^1,3
Corticosteroids may increase blood glucose concentrations; effects on blood glucose can vary widely from patient to patient and may differ from the results seen in this study

The clinical relevance of this plasma exposure and blood glucose information is unknown

LS=least squares.

Indication and Important Safety Information

Indication

ZILRETTA^® (triamcinolone acetonide extended-release injectable suspension) is indicated as an intra-articular injection for the management of osteoarthritis pain of the knee.

Limitation of Use: The efficacy and safety of repeat administration of ZILRETTA have not been demonstrated.

Contraindication

ZILRETTA is contraindicated in patients who are hypersensitive to triamcinolone acetonide, corticosteroids, or any components of the product.

Warnings and Precautions

Intra-articular Use Only: ZILRETTA has not been evaluated and should not be administered by epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous routes. Serious events have been reported with epidural and intrathecal administration of corticosteroids and none are approved for this use. ZILRETTA should not be considered safe for epidural or intrathecal administration.
Hypersensitivity Reactions: Rare instances of anaphylaxis, including serious cases, have occurred in patients with hypersensitivity to corticosteroids.
Joint Infection and Damage: A marked increase in pain accompanied by local swelling, restriction of joint motion, fever, and malaise are suggestive of septic arthritis. Examine joint fluid to exclude a septic process. If diagnosis is confirmed, institute appropriate antimicrobial therapy. Avoid injecting corticosteroids into a previously infected or unstable joint. Intra-articular administration may result in damage to joint tissues.
Increased Risk of Infections: Infection with any pathogen in any location of the body may be associated with corticosteroid use. Corticosteroids may increase the susceptibility to new infection and decrease resistance and the ability to localize infection.
Alterations in Endocrine Function: Corticosteroids can produce reversible hypothalamic-pituitary-adrenal axis suppression, with potential for adrenal insufficiency after withdrawal of treatment, which may persist for months. In situations of stress during that period, institute corticosteroid replacement therapy.
Cardiovascular and Renal Effects: Corticosteroids can cause blood pressure elevation, salt and water retention, and increased potassium excretion. Monitor patients with congestive heart failure, hypertension, and renal insufficiency for edema, weight gain, and electrolyte imbalance. Dietary salt restriction and potassium supplementation may be needed.
Increased Intraocular Pressure: Corticosteroid use may be associated with increased intraocular pressure. Monitor patients with elevated intraocular pressure for potential treatment adjustment.
Gastrointestinal Perforation: Corticosteroid administration may increase risk of gastrointestinal perforation in patients with certain GI disorders and fresh intestinal anastomoses. Avoid corticosteroids in these patients.
Alterations in Bone Density: Corticosteroids decrease bone formation and increase bone resorption. Special consideration should be given to patients with or at increased risk of osteoporosis prior to treatment.
Behavior and Mood Disturbances: Corticosteroids may cause adverse psychiatric reactions. Prior to treatment, special consideration should be given to patients with previous or current emotional instability or psychiatric illness. Advise patients to immediately report any behavior or mood disturbances.

Adverse Reactions

The most commonly reported adverse reactions (incidence ≥1%) in clinical studies included sinusitis, cough, and contusions.

Please see full Prescribing Information.

Systemic exposure/diabetes study

ZILRETTA decreased peak systemic exposure1

Minimal increase in blood glucose levels vs TAcs in patients with controlled type 2 diabetes3

ZILRETTA decreased peak systemic exposure¹

Minimal increase in blood glucose levels vs TAcs in patients with controlled type 2 diabetes³