Drug Interactions between Enlon-Plus and tizanidine

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: The sedative effect of tizanidine may be potentiated by concomitant use of other agents with central nervous system (CNS) depressant effects. In addition, tizanidine and many of these agents (e.g., alcohol, anxiolytics, sedatives, hypnotics, antidepressants, antipsychotics, opioids, muscle relaxants) also can exhibit hypotensive effects, which may be additive during coadministration and may increase the risk of symptomatic hypotension and orthostasis, particularly during initiation of therapy or dose escalation. Tizanidine itself is a central alpha-2 adrenergic agonist. Pharmacologic studies have found tizanidine to possess between 1/10 to 1/50 of the potency of clonidine, a structurally similar agent, in lowering blood pressure. In a single-dose study where blood pressure was monitored closely after dosing, two-thirds of patients treated with an 8 mg dose had a 20% reduction in either the diastolic or systolic blood pressure. The reduction was seen within 1 hour after dosing, peaked 2 to 3 hours after dosing, and was associated at times with bradycardia, orthostatic hypotension, lightheadedness, dizziness, and rarely, syncope. The hypotensive effect of tizanidine is dose-related and has been measured following single doses of 2 mg or more.

MANAGEMENT: Caution is advised and more gradual dose titration may be appropriate when tizanidine is used with other substances that can cause CNS depression and/or hypotension, particularly in elderly or debilitated patients. Ambulatory patients should be counseled to avoid hazardous activities requiring complete mental alertness and motor coordination until they know how these agents affect them, and to avoid rising abruptly from a sitting or recumbent position. Patients should contact their physician if they experience dizziness, lightheadedness, syncope, orthostasis, or excessive CNS effects that interfere with their normal activities.