Drug Interactions between crizotinib and Enlon-Plus

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.

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GENERALLY AVOID: Crizotinib can cause bradycardia and may have additive effects with other drugs that also slow the heart rate. Bradycardia with a heart rate less than 50 beats per minute occurred in 10% to 14% of patients treated with crizotinib in two clinical studies.

MANAGEMENT: Concomitant use of crizotinib with other agents known to cause bradycardia such as beta-blockers, calcium channel blockers, cholinesterase inhibitors, clonidine, and digoxin should generally be avoided whenever possible. Otherwise, heart rate and blood pressure should be monitored closely. If Grade 2 or 3 symptomatic bradycardia occurs, crizotinib should be withheld, the use of concomitant medications re-evaluated, and the dosage of crizotinib adjusted accordingly. Crizotinib should be permanently discontinued for Grade 4 bradycardia. In patients who develop Grade 4 bradycardia associated with concomitant medications known to cause bradycardia or hypotension, crizotinib should be withheld until Grade 1 or less, and if concomitant medications can be discontinued, crizotinib may be restarted at 250 mg once daily with frequent monitoring.

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