Regulatory Decision Summary for Triamcinolone Hexacetonide Injectable Suspension

Triamcinolone hexacetonide (TAH) is a synthetic glucocorticoid hormone which is almost insoluble in water, and dissolution/dispersion in the tissue at the injection site is slow, taking weeks to several months. Esterification of the steroid ring also prevents glucocorticoid activity; once in solution the ester group is hydrolysed to release the active anti-inflammatory moiety, triamcinolone acetonide. Thus, the ester produces a more sustained local effect than the active steroid, forming a depot in/around the affected joint, and producing extremely low systemic levels, despite almost complete systemic absorption. Injected TAH produces a local anti-inflammatory effect beginning around 24 hours after administration and normally lasting for 4 to 6 weeks.

TAH is indicated as an intra-articular injection or infiltration in the treatment of subacute and chronic inflammatory joint diseases and inflammatory conditions involving the joint anatomy, including arthritis, tendonitis and bursitis.  The target population is adults and adolescents, except for the juvenile idiopathic arthritis indication, which includes children 3 years and older.

In accordance with the Health Canada Drug Submissions Relying on Third-Party Data guidance, the efficacy and safety data supporting this submission are derived from the literature, comprising current clinical practice guidelines, systematic reviews and product labels from foreign jurisdictions, including the European Medicines Agency (EMA) Summary of Product Characteristics and the United States Food and Drug Administration (FDA) Prescribing Information. The approved clinical indications and dosing recommendations for Triamcinolone Hexacetonide Injectable Suspension 20 mg/mL correspond to those of the reference medicinal product for the EMA approval, Lederspan 20 mg/mL suspension for injection, and pharmaceutical comparability to the reference product has been established. The results of an adequate and current literature search have been provided to support the safe and effective use for the indication for the treatment of Juvenile Idiopathic Arthritis; the published studies showed statistical and clinical superiority of TAH over the comparator, triamcinolone acetonide, for a number of clinically important outcomes. The safety profile of corticosteroids (local and systemic), in adults and children, is well described and appropriately reflected in the Product Monograph.

TAH is a well-known active substance, with an approximately forty year history of use in Canada, so uncertainties regarding the safety and efficacy of the drug are minimal. Health Canada considers that the benefit-harm-uncertainty profile of Triamcinolone Hexacetonide Injectable Suspension is favorable, when used for the approved indications (rheumatoid arthritis, juvenile idiopathic arthritis (JIA), osteoarthritis, post-traumatic arthritis, synovitis, tendinitis, bursitis, and epicondylitis), and according to the information in the Product Monograph.