Avoid corticosteroids in these patients because signs of peritoneal irritation following gastrointestinal perforation may be minimal or absent. 

5.11 Alterations in Bone Density 

Corticosteroids decrease bone formation and increase bone resorption through their effect on calcium regulation and inhibition of osteoblast function. 

Special consideration should be given to patients with or at increased risk of osteoporosis (e.g., postmenopausal women) before initiating corticosteroid therapy. 

5.12 Behavioral and Mood Disturbances 

Corticosteroid use may be associated with new or aggravated adverse psychiatric reactions ranging from euphoria, insomnia, mood swings, and personality changes to severe depression and frank psychotic manifestations. 

Special consideration should be given to patients with previous or current emotional instability or psychiatric illness before initiating corticosteroid therapy. Advise patients and/or caregivers to immediately report any new or worsening behavior or mood disturbances to their health care provider. 

6 ADVERSE REACTIONS

The following serious adverse reactions are described elsewhere in the labeling. 

Serious Neurologic Adverse Reactions with Epidural and Intrathecal Administration [ see Warnings and Precautions ( 5.2) ] 

Hypersensitivity Reactions [ see Warnings and Precautions ( 5.3) ] 

Joint Infection and Damage [ see Warnings and Precautions ( 5.4) ] 

Increased Risk of Infections [ see Warnings and Precautions ( 5.5) ] 

Alterations in Endocrine Function [ see Warnings and Precautions ( 5.6) ] 

Cardiovascular Effects [ see Warnings and Precautions ( 5.7) ] 

Renal Effects [ see Warnings and Precautions ( 5.8) ] 

Increased Intraocular Pressure [ see Warnings and Precautions ( 5.9) ] 

Gastrointestinal Perforation [ see Warnings and Precautions ( 5.10) ] 

Alternations in Bone Density [ see Warnings and Precautions ( 5.11) ] 

Behavioral and Mood Disturbances [ see Warnings and Precautions ( 5.12) ] 

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. 

The data below reflect exposure to a single 32 mg intra-articular injection of ZILRETTA in clinical studies in patients with moderate to severe pain due to osteoarthritis of the knee. Clinical studies included randomized, double-blind, parallel-group, placebo and/or active-controlled, and pharmacokinetic/pharmacodynamic studies with follow-up ranging from 6-24 weeks. A total of 424 patients received ZILRETTA and 262 received placebo. Treatment emergent adverse reactions reported by greater than or equal to 1% of patients in the ZILRETTA arms are summarized below ( Table 1 and 2). 

Overall, the incidence and nature of adverse reactions was similar to that observed with placebo.