Drug Interactions between amikacin and Prevduo

MONITOR: Aminoglycosides may antagonize the effects of anticholinesterase agents such as neostigmine and pyridostigmine. The interaction has been established between aminoglycosides and depolarizing and nondepolarizing muscle relaxants and is also predicted to occur with anticholinesterase agents. Anticholinesterase agents inhibit cholinesterase activity and lead to prolonged and intensified muscarinic and nicotinic effects of acetylcholine. Aminoglycosides appear to decrease the sensitivity of postsynaptic membrane to acetylcholine. They also possess neuromuscular blocking activity, which may interfere with neuromuscular transmission by inhibiting the release of acetylcholine at neuromuscular junctions by interfering with calcium influx. This effect on neuromuscular transmission may be particularly significant in patients with myasthenia gravis.

MANAGEMENT: Caution and close monitoring for the efficacy of the anticholinesterase agent is recommended if it is to be used concomitantly with aminoglycosides, particularly in patients with myasthenia gravis. Concomitant use in these patients should be avoided if possible. If coadministration is considered necessary, the dose of the anticholinesterase agent may need to be increased.

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.