warnings and cautions
5 WARNINGS AND PRECAUTIONS Intra-articular Use Only : Do not administer ZILRETTA by epidural, intrathecal, intravenous, intraocular, intramuscular, intradermal, or subcutaneous routes. ( 5.1 ) Serious Neurologic Adverse Reactions with Epidural and Intrathecal Administration : Serious neurologic events have been reported following epidural or intrathecal corticosteroid administration. Corticosteroids are not approved for this use. ( 5.2 ) Hypersensitivity Reactions : Serious reactions have been reported with triamcinolone acetonide injection. Institute appropriate care upon occurrence of an anaphylactic reaction. ( 5.3 ) Joint Infection and Damage : May cause joint pain accompanied by joint swelling. If this occurs, conduct appropriate evaluation to exclude septic arthritis and institute appropriate antimicrobial therapy if septic arthritis is confirmed. ( 5.4 ) 5.1 Warnings and Precautions Specific for ZILRETTA ZILRETTA has not been evaluated and should not be administered by the following routes: Epidural Intrathecal Intravenous Intraocular Intramuscular Intradermal Subcutaneous [see Warnings and Precautions (5.2) ]. 5.2 Serious Neurologic Adverse Reactions with Epidural and Intrathecal Administration Serious neurologic events, some resulting in death, have been reported with epidural injection of corticosteroids. Specific events reported include, but are not limited to, spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke [see Adverse Reactions (6) ] . These serious neurologic events have been reported with and without use of fluoroscopy. Reports of serious medical events have been associated with the intrathecal route of corticosteroid administration [see Adverse Reactions (6) ] . The safety and effectiveness of epidural and intrathecal administration of corticosteroids have not been established, and corticosteroids are not approved for this use. In particular, the formulation of ZILRETTA should not be considered safe to use for epidural or intrathecal administration. 5.3 Hypersensitivity Reactions Rare instances of anaphylaxis have occurred in patients with hypersensitivity to corticosteroids. Cases of serious anaphylaxis, including death, have been reported in individuals receiving triamcinolone acetonide injection, regardless of the route of administration [see Adverse Reactions (6) ] . Institute appropriate care upon occurrence of an anaphylactic reaction. 5.4 Joint Infection and Damage Intra-articular injection of corticosteroid may be complicated by joint infection. A marked increase in pain accompanied by local swelling, further restriction of joint motion, fever, and malaise are suggestive of septic arthritis. If this complication occurs and a diagnosis of septic arthritis is confirmed, institute appropriate antimicrobial therapy [see Adverse Reactions (6) ] . Avoid injection of a corticosteroid into an infected site. Local injection of a corticosteroid into a previously infected joint is not usually recommended. Examine any joint fluid present to exclude a septic process. Corticosteroid injection into unstable joints is generally not recommended. Intra-articular injection may result in damage to joint tissues. 5.5 Increased Risk of Infections Intra-articularly injected corticosteroids are systemically absorbed. Patients who are on corticosteroids are more susceptible to infections than are healthy individuals. There may be decreased resistance and inability to localize infection when corticosteroids are used. Infection with any pathogen (viral, bacterial, fungal, protozoan, or helminthic) in any location of the body may be associated with the use of corticosteroids alone or in combination with other immunosuppressive agents. These infections may be mild to severe. With increasing doses of corticosteroids, the rate of occurrence of infectious complications increases. Corticosteroids may also mask some signs of current infection. Advise patients to inform their health care provider if they develop fever or other signs or symptoms of infection. Advise patients who have not been vaccinated to avoid exposure to chicken pox or measles. Instruct patients to contact their health care provider immediately if they are exposed [see Patient Counseling Information (17) ] . 5.6 Alterations in Endocrine Function Corticosteroids can produce reversible hypothalamic-pituitary-adrenal axis suppression, with the potential for adrenal insufficiency after withdrawal of treatment, which may persist for months. In situations of stress during that period (as in trauma, surgery, or illness), institute corticosteroid replacement therapy. Metabolic clearance of corticosteroids is decreased in hypothyroid patients and increased in hyperthyroid patients. 5.7 Cardiovascular Effects Corticosteroids can cause elevations of blood pressure, salt and water retention, and increased excretion of potassium. These effects are less likely to occur with synthetic derivatives. Monitor patients with congestive heart failure or hypertension for signs of edema, weight gain, and imbalance in serum electrolytes. Dietary salt restriction and potassium supplementation may be necessary. 5.8 Renal Effects Corticosteroids can cause salt and water retention, and increased excretion of potassium. These effects are less likely to occur with synthetic derivatives. All corticosteroids increase calcium excretion. Monitor patients with renal insufficiency for signs of edema, weight gain, and imbalance in serum electrolytes. Dietary salt restriction and potassium supplementation may be necessary. 5.9 Increased Intraocular Pressure Corticosteroid use may be associated with development or exacerbation of increased intraocular pressure. Monitor patients with elevated intraocular pressure for potential treatment adjustment. 5.10 Gastrointestinal Perforation Corticosteroid administration is associated with increased risk of gastrointestinal perforation in patients with certain GI disorders such as active or latent peptic ulcers, diverticulosis, diverticulitis, ulcerative colitis and in patients with fresh intestinal anastomoses. 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.