Neurologic/Psychiatric: Convulsions, depression, emotional instability, euphoria, headache, increased intracranial pressure with papilledema (pseudotumor cerebri) usually following discontinuation of treatment, insomnia, mood swings, neuritis, neuropathy, paresthesia, personality changes, psychiatric disorders [see Warnings and Precautions ( 5.12)] , vertigo. Arachnoiditis, meningitis, paraparesis/paraplegia, and sensory disturbances have occurred after intrathecal administration. Spinal cord infarction, paraplegia, quadriplegia, cortical blindness, and stroke (including brainstem) have been reported after epidural administration of corticosteroids [see Warnings and Precautions ( 5.2)] . 

Ophthalmic: Exophthalmos, glaucoma, increased intraocular pressure [see Warnings and Precautions ( 5.9)] , posterior subcapsular cataracts, rare instances of blindness associated with periocular injections. 

Other: Abnormal fat deposits, decreased resistance to infection, hiccups, increased or decreased motility and number of spermatozoa, malaise, moon face, weight gain.  

7 DRUG INTERACTIONS

No drug-drug interaction studies have been conducted with ZILRETTA. Table 3 contains drug interactions associated with systemic corticosteroids. 

Table 3: Drug Interactions Associated with Systemic Corticosteroids  

Aminoglutethimide  Aminoglutethimide may lead to a loss of corticosteroid-induced adrenal suppression.  

Amphotericin B injection and potassium-depleting agents  When corticosteroids are administered concomitantly with potassium-depleting agents (i.e., amphotericin B, diuretics), observe patients closely for development of hypokalemia. There have been cases reported in which concomitant use of amphotericin B and hydrocortisone was followed by cardiac enlargement and congestive heart failure.  

Antibiotics  Macrolide antibiotics have been reported to cause a significant decrease in corticosteroid clearance.  

Anticholinesterases  Concomitant use of anticholinesterase agents and corticosteroids may produce severe weakness in patients with myasthenia gravis. If possible, withdraw anticholinesterase agents at least 24 hours before initiating corticosteroid therapy.  

Anticoagulants, oral  Coadministration of corticosteroids and warfarin usually results in inhibition of response to warfarin, although there have been some conflicting reports. Therefore, monitor coagulation indices frequently to maintain the desired anticoagulant effect.  

Antidiabetics  Because corticosteroids may increase blood glucose concentrations, dosage adjustments of antidiabetic agents may be required.  

Antitubercular drugs  Serum concentrations of isoniazid may be decreased.  

CYP 3A4 inducers 

(e.g., barbiturates, phenytoin, carbamazepine, and rifampin) 

 Drugs which induce hepatic microsomal drug metabolizing enzyme activity may enhance metabolism of corticosteroids and require that the dosage of corticosteroid be increased.  

CYP 3A4 inhibitors