Triamcinolone hexacetonide is a synthetic corticosteroid belonging to the glucocorticoid class, primarily used for its potent anti-inflammatory and immunosuppressive effects. It was developed in the mid-20th century as part of efforts to create corticosteroid derivatives with enhanced duration of action and reduced systemic side effects compared to earlier steroids like hydrocortisone and prednisone. Triamcinolone hexacetonide is particularly known for its long-acting effect when administered via intra-articular or intramuscular injection, making it effective in treating chronic inflammatory conditions such as arthritis, tendinitis, and other musculoskeletal disorders in both humans and animals. The chemical modification of triamcinolone into a hexacetonide ester increases its lipid solubility, extending its local activity and reducing systemic absorption, which helped establish its use in clinical practice during the 1960s and 1970s.
BRAND NAMES
Aristospan: This is a commonly cited brand name, particularly for the injectable suspension used to treat joint inflammation, arthritis, and certain skin disorders.
Hexatrione is a brand name for an injectable triamcinolone hexacetonide suspension manufactured by Ethypharm Laboratories. The FDA also notes that it was used in the U.S. as an alternative during a shortage of Aristospan, another triamcinolone hexacetonide product.
Trispan: This is the DIN name listed for triamcinolone hexacetonide in Canada, according to the Drug and Health Product Register.
MECHANISM OF ACTION
Triamcinolone hexacetonide is a potent glucocorticoid that exerts its anti-inflammatory and immunosuppressive effects by modulating gene expression. It binds to cytoplasmic glucocorticoid receptors, forming a complex that moves into the nucleus to regulate transcription of target genes. This results in upregulation of anti-inflammatory proteins, such as lipocortin-1, which inhibits phospholipase A2 and reduces the production of prostaglandins and leukotrienes, and suppression of pro-inflammatory genes, lowering levels of cytokines, chemokines, and adhesion molecules. It also has immunosuppressive effects, decreasing lymphocyte proliferation and suppressing immune cell activation. The hexacetonide ester prolongs tissue retention, allowing sustained local anti-inflammatory action with minimal systemic absorption, making it highly effective for chronic joint and musculoskeletal inflammation.
PHARMACOKINETICS
Absorption
Triamcinolone hexacetonide is slowly absorbed from injection sites due to its poor water solubility and hexacetonide ester, allowing prolonged local action with minimal systemic exposure. Peak plasma levels are low, reducing systemic side effects.
Distribution
Triamcinolone hexacetonide has a moderate volume of distribution, concentrating mainly in inflamed tissues and synovial fluid, with prolonged local retention due to its lipophilic hexacetonide ester.
Metabolism
Triamcinolone hexacetonide is metabolized in the liver via the CYP3A4 enzyme system, generating active metabolites including triamcinolone acetonide and 6β-hydroxy-triamcinolone acetonide. Following intra-articular injection, it is absorbed slowly and primarily excreted through the kidneys and feces.
Excretion
Triamcinolone hexacetonide is primarily eliminated through the liver and kidneys. Like other systemic corticosteroids, it is initially metabolized in the liver before being excreted from the body.
PHARMACODYNAMICS
Triamcinolone hexacetonide is a long-acting glucocorticoid that decreases inflammation and suppresses immune responses by modulating gene expression. Its hexacetonide ester allows prolonged local action, effectively decreasing pain, swelling, and tissue inflammation with minimal systemic effects.
ADMINISTRATION
Triamcinolone hexacetonide is a synthetic corticosteroid mainly given by injection for its strong and long-lasting anti-inflammatory effects and is not intended for intravenous use. The administration method depends on the condition being treated, but it is typically injected into or around a joint or directly into a skin lesion.
DOSAGE AND STRENGTH
Triamcinolone hexacetonide is available in injectable formulations, typically 10 mg/mL or 20 mg/mL vials for intra-articular or soft tissue administration. The dosage varies depending on the species, age, body weight, and specific condition being treated.
Humans (intra-articular for joints): 10–40 mg per joint, depending on joint size and severity of inflammation, usually once every 4–6 weeks.
Animals (veterinary use): Dose is species-specific; for example, 0.5–2 mg/kg body weight is common for intra-articular or soft tissue injections.
FOOD INTERACTIONS
Triamcinolone hexacetonide is primarily administered by injection, so it has minimal direct interactions with food. However, systemic effects of corticosteroids can be influenced by diet: a high-sodium intake may worsen fluid retention, a low-potassium diet can increase the risk of hypokalemia, and alcohol or foods that affect liver metabolism may alter drug metabolism. While these dietary factors do not significantly affect its local anti-inflammatory action, they should be considered when systemic absorption occurs.
DRUG INTERACTIONS
Triamcinolone hexacetonide may interact with other drugs: NSAIDs can increase gastrointestinal irritation, anticoagulants may have altered effects, and potassium-wasting diuretics can elevate the risk of hypokalemia. It can reduce the effectiveness of hypoglycemic agents and live vaccines due to immunosuppression. Drugs that affect CYP3A4 may alter its metabolism, so careful monitoring and dose adjustments are recommended.
CONTRAINDICATIONS
Triamcinolone hexacetonide is contraindicated in individuals with hypersensitivity to corticosteroids, active infections, or septic joints, and should be avoided around the time of live vaccinations. It should be used cautiously in conditions such as uncontrolled diabetes, hypertension, osteoporosis, or peptic ulcers, and only under medical supervision during pregnancy or lactation.
SIDE EFFECTS
Common side effects:
Local injection site reactions.
Fluid retention and weight gain
Increased appetite
Mood and behavior changes, including agitation, anxiety, insomnia, or depression
Headache
Increased sweating
Bruising
Adrenal gland suppression
Cushing's syndrome
High blood sugar
Eye problems
Cardiovascular issues
Musculoskeletal effects
Gastrointestinal problems
Allergic reactions
OVERDOSE
Weight gain and fluid retention.
Metabolic and hormonal changes.
Cardiovascular issues.
Neurological and psychological effects.
Musculoskeletal effects.
Gastrointestinal problems.
Skin issues.
Increased infection risk.
TOXICITY
Triamcinolone hexacetonide has low systemic toxicity at recommended doses, but overdose or frequent high-dose use can cause HPA axis suppression, hyperglycemia, musculoskeletal effects, gastrointestinal irritation, and increased infection risk. Repeated local injections may also lead to tissue atrophy or joint damage.
