Drug Interactions between bupivacaine / dexamethasone / epinephrine and neostigmine

MONITOR: Concomitant use of acetylcholinesterase inhibitors and corticosteroids or adrenocorticotropic agents may result in severe muscle weakness in patients with myasthenia gravis. The mechanism of the interaction is unknown. It has been suggested that corticosteroids at high doses have a direct effect on neuromuscular transmission. Marked deterioration in muscle strength has been reported in patients with myasthenia gravis shortly after the initiation of corticosteroid therapy, particularly when high dosages were used. The use of cortisone appears to be associated with the highest rate of myasthenia gravis exacerbation, with an intermediate rate for prednisone and the lowest rate for methylprednisolone. In most cases, the decline in muscular function was relatively refractory to acetylcholinesterase inhibitors. However, clinical improvement generally occurs during prolonged corticosteroid therapy when administered properly.

MANAGEMENT: Caution and monitoring for muscle weakness is recommended with the use of corticosteroids or adrenocorticotropic agents in combination with acetylcholinesterase inhibitors in the treatment of patients with myasthenia gravis. Prednisone or prednisolone are often considered part of the standard treatment for this condition. Recommendations in the medical literature have advised that corticosteroid therapy should be instituted at relatively low dosages and in a controlled setting in patients with myasthenia gravis. Respiratory support should be available, and the dosage should be increased stepwise as tolerated. Dose reductions of the acetylcholinesterase inhibitor may be required as symptoms improve, which often may be delayed and gradual. However, according to some manufacturers of the corticosteroids dexamethasone and triamcinolone, anticholinesterase agents should be discontinued at least 24 hours before initiating corticosteroid therapy in patients with myasthenia gravis. Other management recommendations in the medical literature suggest avoiding the use of corticosteroids at high doses; however, if high doses are required, consider pre-treatment with intravenous immunoglobulin or plasmapheresis. Local protocols and/or the manufacturer's product labeling should be consulted for specific guidance.