No specific information is available about clinically significant overdoses with swallowed selegiline or ZELAPARÃ?. However, experience gained during development of the 5 mg swallowed dosage form reveals that some individuals exposed to doses of 600 mg of d,l-selegiline suffered severe hypotension and psychomotor agitation.

Since the selective inhibition of MAO-B by ZELAPARÃ? is achieved only at doses in the range recommended for the treatment of Parkinsons disease (e.g., 2.5 mg/day), overdoses are likely to cause significant inhibition of both MAO-A and MAO-B. Consequently, the signs and symptoms of overdose may resemble those observed with marketed nonselective MAO inhibitors [e.g., tranylcypromine (PARNATE^Ã?), isocarboxazide (MARPLAN^Ã?), and phenelzine (NARDIL^Ã?)]. For this reason, in cases of overdose with selegiline, dietary tyramine restriction should be observed for several weeks to avoid the risk of a hypertensive/cheese reaction.

NOTE: This section is provided for reference; it does not describe events that have actually been observed with oral selegiline or ZELAPARÃ? in overdose.

Characteristically, signs and symptoms of non-selective MAOI overdose may not appear immediately. Delays of up to 12 hours between ingestion of drug and the appearance of signs may occur. Importantly, the peak intensity of the syndrome may not be reached for upwards of a day following the overdose. Death has been reported following overdosage. Therefore, immediate hospitalization, with continuous patient observation and monitoring for a period of at least two days following the ingestion of such drugs in overdose, is strongly recommended.

The clinical picture of MAOI overdose varies considerably; its severity may be a function of the amount of drug consumed. The central nervous and cardiovascular systems are prominently involved.

Signs and symptoms of overdosage may include, alone or in combination, any of the following: drowsiness, dizziness, faintness, irritability, hyperactivity, agitation, severe headache, hallucinations, trismus, opisthotonos, convulsions, and coma; rapid and irregular pulse, hypertension, hypotension and vascular collapse; precordial pain, respiratory depression and failure, hyperpyrexia, diaphoresis, and cool, clammy skin.

NOTE: Because there is no recorded experience with swallowed selegiline or ZELAPARÃ? overdose, the following suggestions are offered based upon the assumption that such overdoses may be modeled by non-selective MAOI poisoning. In any case, up-to-date information about the treatment of overdose can often be obtained from a certified Regional Poison Control Center. Telephone numbers of certified Poison Control Centers are listed in the Physicians Desk Reference (PDR).

Treatment of overdose with non-selective MAOIs is symptomatic and supportive. Induction of emesis or gastric lavage with instillation of charcoal slurry may be helpful in early poisoning, provided the airway has been protected against aspiration. Signs and symptoms of central nervous system stimulation, including convulsions, should be treated with diazepam, given slowly intravenously. Phenothiazine derivatives and central nervous system stimulants should be avoided. Hypotension and vascular collapse should be treated with intravenous fluids and, if necessary, blood pressure titration with an intravenous infusion of a dilute pressor agent. It should be noted that adrenergic agents may produce a markedly increased pressor response.

Respiration should be supported by appropriate measures, including management of the airway, use of supplemental oxygen, and mechanical ventilatory assistance, as required.

Body temperature should be monitored closely. Intensive management of hyperpyrexia may be required. Maintenance of fluid and electrolyte balance is essential.

ZELAPARÃ? is contraindicated in patients with a known hypersensitivity to any formulation of selegiline or any of the inactive ingredients of ZELAPARÃ?.

Meperidine and Other Analgesics: ZELAPARÃ? is contraindicated for use with meperidine. Serious reactions have been precipitated with concomitant use of meperidine (e.g., Demerol and other tradenames) and MAO inhibitors including selective MAO-B inhibitors. These reactions have been characterized by coma, severe hypertension or hypotension, severe respiratory depression, convulsions, malignant hyperpyrexia, excitation, peripheral vascular collapse and death. At least 14 days should elapse between discontinuation of ZELAPARÃ? and initiation of treatment with meperidine. (See PRECAUTIONS-DRUG INTERACTIONS.)

For similar reasons, ZELAPARÃ? should not be administered with the analgesic agents tramadol, methadone, and propoxyphene.

Dextromethorphan: ZELAPARÃ? should not be used with the antitussive agent dextromethorphan. The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior.

MAO inhibitors: ZELAPARÃ? should not be administered along with other selegiline products (e.g., Eldepryl and other tradenames) because of the increased risk of nonselective MAO inhibition that may lead to a hypertensive crisis. At least 14 days should elapse between discontinuation of ZELAPARÃ? and initiation of treatment with other selegiline products.

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