Source: Health Products and Food Branch (CA) Revision Year: 2020
Trispan contains the synthetic long-acting glucocorticoid, triamcinolone hexacetonide, as a sterile aqueous suspension. It has a prolonged anti-inflammatory action.
The product is a microcrystalline water suspension with a depot effect. Trispan is a relatively water insoluble derivative of triamcinolone acetonide (0.0002% at 25°C in water). It is not rapidly removed from the site of injection after intra-articular administration, nor is it rapidly metabolized in situ.
Trispan is a synthetic glucocorticoid with pronounced anti-inflammatory activity. TAH, the tbutylacetic acid ester of triamcinolone acetonide, is almost insoluble in water and therefore dissolution/dispersion in the tissue at the injection site is generally slow, taking a few weeks to several months. Esterification at C21 of the steroid ring prevents glucocorticoid activity, but once in solution the t-butylacetic acid ester group is hydrolysed to release the active antiinflammatory moiety, triamcinolone acetonide. TAH forms a depot in/around the affected joint, resulting in extremely low systemic levels, although systemic absorption is almost complete.
The anti-inflammatory potency of triamcinolone on a milligram by milligram comparison is approximately five times that of hydrocortisone. Triamcinolone has practically no mineralocorticoid effect, therefore no sodium retention occurs.
The hexacetonide ester is almost insoluble in water, so dissolution is slow and the effect in the tissue of the injection site lasts for a long time, from a few weeks to several months. Generally, the onset of effect after Trispan administration occurs after 24 hours and normally lasts for 4 to 6 weeks.
Triamcinolone hexacetonide is hydrolysed by human serum in vitro (43% hydrolysed after 24 hours), but following intra-articular injection the substance does not disperse in situ.
Published studies and current therapeutic guidelines on the treatment of Juvenile Idiopathic Arthritis (JIA) indicate efficacy and safety of Trispan in children and adolescents with this condition.
Based on conventional studies of safety pharmacology and repeat dose toxicology studies, no unexpected hazards have been identified. The median lethal dose in mice after 7, 14 and 21 days was in excess of 4000 mg/kg, 2000 mg/kg and 1000 mg/kg respectively following subcutaneous administration. The median lethal dose in rats after 7 and 14 days was 419 mg/kg and 21 mg/kg, following subcutaneous administration.
Sub-acute and chronic toxicity studies in animals did not produce any findings that could be attributed to the drug, other than those which are associated with the pharmacologic activities of steroids, (decreased body weight gain, the reduction in resistance to infection, hematologic abnormalities, effects on adrenals, thymus, etc.).
Long-term studies in animals have not been performed to evaluate carcinogenic potential.
There was no evidence of a potential for genetic and chromosome mutations when tested in limited studies performed in bacterial and mammalian cells.
Corticosteroids have been shown to reduce fertility when administered to rats.
Triamcinolone hexacetonide is a potent teratogen in many animals. Cleft palate has been reported in mice, rats, rabbits, and hampsters at doses equivalent to the human dose. CNS anomalies and cranial malformations have been observed in monkeys following gestational exposure. To date however, no signs of teratogenicity of corticosteroids have been observed in humans.
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