Selegiline: uses, dosing, side effects & brands

The following adverse reactions are discussed in more detail in the Warnings and Precautions section of labeling: • Risk for Hypertension [see Warnings and Precautions (5.1) ] • Risk of Serotonin Syndrome [see Warnings and Precautions (5.2) ] • Falling Asleep During Activities of Daily Living and Somnolence [see Warnings and Precautions (5.3) ] • Hypotension/Orthostatic Hypotension [see Warnings and Precautions (5.4) ] • Dyskinesia [see Warnings and Precautions (5.5) ] • Hallucinations/Psychotic-Like Behavior [see Warnings and Precautions (5.6) ] • Impulse Control/Compulsive Behaviors [see Warnings and Precautions (5.7) ] • Withdrawal Emergent Hyperpyrexia and Confusion [see Warnings and Precautions (5.8) ] • Irritation of the Buccal Mucosa [see Warnings and Precautions (5.9) ] • Risk for Patients with Phenylketonuria [see Warnings and Precautions (5.10) ] The most common adverse reactions (incidence at least 3% greater than on placebo) are constipation, skin disorders, vomiting, dizziness, dyskinesia, insomnia, dyspnea, myalgia, and rash (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Bausch Health US, LLC at 1-800-321-4576 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, the incidence of adverse reactions (number of unique patients experiencing an adverse reaction per…

ZELAPAR is contraindicated in patients with: • Concomitant use of opioid drugs (e.g., meperidine, tramadol, or methadone). 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 (5.2) ] . • Concomitant use of other drugs in the monoamine oxidase inhibitor (MAOI) class or other drugs that are potent inhibitors of monoamine oxidase, including linezolid), because of an increased risk for hypertensive crisis [see Warnings and Precautions (5.1)]. At least 14 days should elapse between discontinuation of ZELAPAR and initiation of treatment with any MAO inhibitor. • Concomitant use of St. John’s wort or cyclobenzaprine (a tricyclic muscle relaxant). • Concomitant use of dextromethorphan, because of reported episodes of psychosis or bizarre behavior. ZELAPAR is contraindicated in patients using the following drugs: opioid drugs (e.g., meperidine, tramadol, methadone), MAO inhibitors including selective MAO-B inhibitors, dextromethorphan, St. John’s wort, and cyclobenzaprine ( 4 )

7.1 Opioid Drugs Because serious, sometimes fatal reactions have been precipitated with concomitant use of opioid drugs (e.g., meperidine and its derivatives, methadone, or tramadol) and MAOIs, including selective MAO-B inhibitors, concomitant use of these drugs with ZELAPAR is contraindicated [see Contraindications ( 4 ) and Warnings and Precautions ( 5.2 )] . At least 14 days should elapse between discontinuation of ZELAPAR and initiation of treatment with these drugs. 7.2 Dextromethorphan The combination of MAO inhibitors and dextromethorphan has been reported to cause brief episodes of psychosis or bizarre behavior. Therefore, in view of ZELAPAR’s MAO inhibitory activity, dextromethorphan should not be used concomitantly with ZELAPAR [see Contraindications (4) ] . 7.3 MAO Inhibitors ZELAPAR is contraindicated for concomitant use with other drugs in the MAOI class or other drugs that are potent inhibitors of monoamine oxidase (including linezolid, an oxazolidinone antibacterial, which also has reversible nonselective MAO inhibition activity) because of the increased risk for hypertensive crisis [see Contraindications (4) and Warnings and Precautions (5.1 )] . At least 14 days should elapse between discontinuation of ZELAPAR and initiation of treatment with other MAOIs. 7.4 Sympathomimetic Medications Uncontrolled hypertension, including hypertensive crisis, has been reported when taking the recommended dose of swallowed selegiline and a sympathomimetic medication (ephedrine). 7.5 Tyramine/Selegiline Interaction The enzyme, monoamine oxidase (MAO) (primarily type A), in the gastrointestinal tract and liver provides protection from ingested amines (e.g., tyramine) that, if absorbed, have the capacity to cause uncontrolled hypertension (tyramine reaction). If MAO is inhibited in the gastrointestinal tract and liver, ingestion of exogenous amines contained in some foods such as fermented cheese, herring, or over-the-counter cough/cold medicines may be absorbed systemically causing release of norepinephrine and a rise in systemic blood pressure with the potential for uncontrolled hypertension. Selective MAO-B inhibitors lose their selectivity for MAO-B when taken in doses higher than recommended . Non-selective MAO-A inhibitors or MAO-B inhibitors in higher than recommended doses may result in MAO-A inhibition in the gastrointestinal tract and liver. Results of a tyramine challenge study indicate that ZELAPAR is relatively selective for MAO-B at the recommended dose. In most cases, there is no need for dietary tyramine restriction in patients prescribed ZELAPAR [see Clinical Pharmacology (12.2) ] at the recommended dose. Because the selectivity for inhibiting MAO-B diminishes as the dose of ZELAPAR is increased above the recommended daily dose, patients should not take more than 2.5 mg of ZELAPAR daily. Reports of hypertensive reactions have occurred in patients who ingested tyramine-containing consumables (i.e., food or drink) while receiving swallowed selegiline at the recommended dose (a dose believed to be relatively selective for MAO-B). Hypertensive crisis has also been reported with ZELAPAR use that was not above the recommended dosing. Uncontrolled hypertension has been reported when taking the recommended dose of swallowed selegiline and a sympathomimetic medication (ephedrine). 7.6 Tricyclic Antidepressants and Selective Serotonin Reuptake Inhibitors Severe toxicity has also been reported in patients receiving the combination of tricyclic antidepressants and swallowed selegiline, or selective serotonin reuptake inhibitors and swallowed selegiline [see Warnings and Precautions (5.2) ] . 7.7 Drugs that Induce CYP450 Adequate studies have not been done investigating the effect of CYP3A4 inducers on selegiline. Drugs that induce CYP3A4 (e.g., phenytoin, carbamazepine, nafcillin, phenobarbital, and rifampin) should be used with caution. 7.8 Dopaminergic Antagonists It is possible that dopamine antagonists, such as antipsychotics or metoclopramide, could diminish the effectiveness of ZELAPAR.