Drug Interactions between corticorelin and Prevduo

GENERALLY AVOID: Anticholinergic agents and other agents with significant anticholinergic activity (e.g., clozapine, class IA antiarrhythmics especially disopyramide) may antagonize the effects of cholinergic skeletal muscle stimulants (e.g., ambenonium, edrophonium, guanidine, neostigmine, pyridostigmine). Although this interaction may be desirable in some situations, such as when atropine is used to treat excessive muscarinic side effects and cholinergic crisis induced by anticholinesterase overdose, unintentional or indiscriminate use of anticholinergic agents in the treatment of myasthenia gravis may exacerbate symptoms. In addition, such use may mask the less serious, gastrointestinal signs of cholinergic overdose and lead to inadvertent induction of cholinergic crisis, which can produce respiratory paralysis and death.

MANAGEMENT: Agents with potent anticholinergic activity should preferably be avoided in patients receiving cholinergic skeletal muscle stimulants. If concurrent use is necessary, patients treated for myasthenia gravis should be monitored for potential exacerbation of symptoms. Caution is advised not only because anticholinergic agents may mask the signs of a cholinergic overdose, but also because increasing muscle weakness associated with disease aggravation may be difficult to distinguish from that due to cholinergic crisis.

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.