"Using data from over 18,000 patients, scientists have identified more than two dozen genetic risk factors involved in Parkinson's disease, including six that had not been previously reported. The study, published in Nature Genetics, was partially"...
No specific information is available about clinically significant overdoses with swallowed selegiline or ZELAPAR. 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 ZELAPAR is achieved only at doses in the range recommended for the treatment of Parkinson's 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 non-selective MAO inhibitors [e.g., tranylcypromine (PARNATE®), isocarboxazid (MARPLAN®), and phenelzine (NARDIL®)]. 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 reaction.
Overdose With Non-Selective MAO Inhibitors
NOTE: The following description of presenting symptoms and clinical course is based upon overdose descriptions of nonselective MAO inhibitors and does not include information from patients who have overdosed on oral selegiline or ZELAPAR.
Characteristically, signs and symptoms of non-selective MAO inhibitor 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 MAO inhibitor 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.
Treatment Or Management Of Overdose
Treatment of overdose with non-selective MAO inhibitors 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.
Support respiration, 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.
ZELAPAR is contraindicated in patients using meperidine, tramadol, methadone, or propoxyphene. Serotonin syndrome, a potentially serious condition, which can result in death, has been reported with concomitant use of meperidine (e.g., Demerol and other trade names). At least 14 days should elapse between discontinuation of ZELAPAR and initiation of treatment with these medications [see WARNINGS AND PRECAUTIONS].
ZELAPAR is contraindicated in patients on any other MAO inhibitor (selective or nonselective), because of an increased risk for hypertensive crisis. At least 14 days should elapse between discontinuation of ZELAPAR and initiation of treatment with any MAO inhibitor.
ZELAPAR is contraindicated in patients using St. John's wort, or cyclobenzaprine (a tricyclic muscle relaxant).
Last reviewed on RxList: 9/29/2014
This monograph has been modified to include the generic and brand name in many instances.
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