Physical and Chemical Compatibility of Extended-Release Triamcinolone Acetonide (TA-ER) with Common Local Anesthetics

Abstract

IntroductionIntra-articular (IA) corticosteroids are used extensively for the treatment of patients with knee osteoarthritis pain. In clinical practice, local anesthetics are frequently combined with corticosteroids prior to IA injection to provide rapid-onset analgesia. From this common practice there is no evidence to suggest that the addition of local anesthetics to corticosteroid preparations, including triamcinolone acetonide (TA), alters the physical properties or efficacy of the corticosteroid. Triamcinolone acetonide extended-release (TA-ER, formerly FX006) is a novel, microsphere-based TA formulation that demonstrated analgesic efficacy in phase 2 and 3 randomized controlled trials.MethodsThe current study assessed the compatibility of TA-ER and lidocaine, ropivacaine, and/or bupivacaine in vitro. The TA-ER and local anesthetic mixtures were assayed for changes in syringeability, pH, particle size, percentage free drug, purity, and appearance compared with TA-ER alone.ResultsBy these measures, the combination of local anesthetics with TA-ER did not negatively impact the chemical or physical properties of TA-ER when compared to TA-ER controls.ConclusionThese results demonstrate that lidocaine, bupivacaine, and ropivacaine are physically and chemically compatible with TA-ER, suggesting that local anesthetic solutions can be added to TA-ER preparations in clinical practice without adversely affecting TA-ER in vitro product characteristics.FundingFlexion Therapeutics, Inc.

Pharmacological and clinical implications of local anaesthetic mixtures: a narrative review

“…Triamcinolone acetone, betamethasone and methylprednisolone are all particulate steroids. Triamcinolone acetone is compatible with lidocaine, bupivacaine and ropivacaine [95] but the presence of human serum may alter this [96]. Betamethasone results in local anaesthetic precipitation when combined with bupivacaine or ropivacaine but not lidocaine [97].…”

Effect of triamcinolone in regional anesthesia for fast-track knee replacement. Case series

“…This product is approved for interscalene brachial plexus block, transversus abdominis plane block, and surgical infiltration, but it is expensive. Regional anesthesia techniques are evolving to facilitate early ambulation after this kind of surgeries [4]. Although the physical and chemical compatibility of triamcinolone with common local anesthetics has been described [5], it is usually reserved just for chronic pain management procedures like chronic musculoskeletal injections [6].…”

Magnesium Sulfate Combined with a Levobupivacaine Periarticular Cocktail for Analgesia in the Early Postoperative Period after Total Knee Arthroplasty

“…Exclusion criteria: (1) Revision TKA, simultaneous bilateral TKA, or staged bilateral TKA 4 ; (2) patients with local or systemic infection, severe diseases of the heart, lung, liver, kidney, or nervous system, hypermagnesemia, severe coagulation dysfunction, history of chronic pain diseases with long-term use of analgesics, history of long-term use of calcium channel blockers, and allergic history to magnesium sulfate or amide local anesthetics; (3) All 60 surgeries were performed by the same surgical team and same experienced chief surgeon. All patients were under spinal anesthesia, and none of the selected patients had preemptive analgesia.…”

“…Currently, "periarticular cocktail" formulations mostly consist of amide local anesthetics combined with glucocorticoids. 3 Levobupivacaine has advantages of low cardiotoxicity, a long duration and a wide safety range, and this drug has gradually become a new type of long-acting amide local anesthetic that is widely used in clinical practice. However, there are still few studies on magnesium sulfate injection as a "periarticular cocktail" for injection around the knee joint.…”