ZELAPAR
Clinical safety rating: caution
Comprehensive clinical and safety monograph for ZELAPAR (ZELAPAR).
Selective and irreversible inhibitor of monoamine oxidase B (MAO-B), which increases dopamine levels in the striatum by blocking its metabolism.
| Metabolism | Primarily hepatic via CYP1A2 and CYP2C19; also metabolized by flavin-containing monooxygenase (FMO). |
| Excretion | Renal: 70-80% as metabolites (10% as unchanged drug in bile/feces); biliary/fecal: 20-30%. |
| Half-life | Terminal elimination half-life: 2-4 hours (selegiline); due to irreversible MAO-B inhibition, clinical effect persists for 24-72 hours after single dose. |
| Protein binding | 90-94% bound to plasma proteins (primarily albumin and alpha-1-acid glycoprotein). |
| Volume of Distribution | Approximately 1.2 L/kg (extensive tissue distribution). |
| Bioavailability | Oral (orally disintegrating tablet): 70-80% (presystemic metabolism reduced compared to conventional tablets). |
| Onset of Action | Orally disintegrating tablet: 0.5-1 hour for subjective improvement; objective effects (MAO-B inhibition) within 1 hour. |
| Duration of Action | 24-72 hours based on MAO-B inhibition (irreversible binding); clinical benefit may persist for 1-2 days after discontinuation. |
| Molecular Weight | 187.28 |
1.25 mg sublingually once daily in the morning; may increase to 2.5 mg once daily if needed.
| Dosage form | TABLET, ORALLY DISINTEGRATING |
| Renal impairment | No dose adjustment required for mild to moderate renal impairment. Not recommended in severe renal impairment (CrCl <30 mL/min) due to lack of data. |
| Liver impairment | No dose adjustment required for mild hepatic impairment (Child-Pugh A). Not recommended in moderate to severe hepatic impairment (Child-Pugh B or C) due to lack of data. |
| Pediatric use | Not approved for use in pediatric patients; safety and efficacy not established. |
| Geriatric use | No specific dose adjustment recommended; monitor for increased risk of adverse effects such as hallucinations, orthostatic hypotension, and drowsiness. |
| 1st trimester | Selegiline is contraindicated in the first trimester due to potential teratogenic effects observed in animal studies and lack of human data. |
| 2nd trimester | Use caution; limited human data but potential risks from monoamine oxidase inhibition may affect fetal development. Only use if benefit outweighs risk. |
| 3rd trimester | Use caution; risk of hypertensive crisis during labor and potential neonatal effects (e.g., irritability) due to MAO inhibition. Avoid if possible near term. |
Clinical note
Comprehensive clinical and safety monograph for ZELAPAR (ZELAPAR).
| Placental transfer | Selegiline crosses the placenta. Animal studies show transfer and fetal exposure. Human data limited. |
| Breastfeeding | Selegiline is excreted into breast milk in small amounts. Due to potential for serious adverse reactions in the nursing infant (e.g., hypertensive crisis, monoamine oxidase inhibition effects), breastfeeding is not recommended during therapy. |
■ FDA Black Box Warning
None.
| Common Effects | Dizziness Dryness in mouth Blurred vision Nausea Sleepiness Weakness Nervousness |
| Serious Effects |
Concurrent use of other MAOIs (including linezolid, methylene blue)Concurrent use of SSRIs, SNRIs, tricyclic antidepressants, or other serotonergic drugs (risk of serotonin syndrome)Concurrent use of sympathomimetics (e.g., amphetamines, ephedrine)PheochromocytomaSevere hepatic impairmentHistory of hypersensitivity to selegiline
| Precautions | Risk of hypertensive crisis with tyramine-rich foods or certain medications due to MAO-A inhibition at high doses, May cause serotonin syndrome if co-administered with serotonergic drugs, Avoid use with opioids (e.g., meperidine) or other MAO inhibitors |
| Food/Dietary | At therapeutic doses (5 mg or less), tyramine restriction is not generally required, but at higher doses (10 mg/day), avoid tyramine-rich foods such as aged cheeses, cured meats, sauerkraut, soy sauce, beer, red wine, and yeast extracts to prevent hypertensive crisis. Avoid tyramine within 48 hours after discontinuation of higher doses. |
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| Lactation Rating | L5 - Contraindicated |
| Teratogenic Risk | ZELAPAR (selegiline transdermal system) is classified as FDA Pregnancy Category C. Animal studies have shown fetal toxicity at doses higher than human therapeutic doses. There are no adequate and well-controlled studies in pregnant women. In the first trimester, there is a potential risk of neural tube defects due to inhibition of monoamine oxidase, though human data are lacking. Second and third trimester risks include possible intrauterine growth restriction and placental vasoconstriction from amphetamine metabolites. Use only if potential benefit justifies potential risk to fetus. |
| Fetal Monitoring | Monitor maternal blood pressure for hypertensive crises due to tyramine interaction. Fetal monitoring includes ultrasound for growth restriction in the second and third trimesters. Consider fetal echocardiography if prolonged use in pregnancy. |
| Fertility Effects | In animal studies, selegiline did not impair fertility. In humans, there are no data on fertility effects. However, hyperprolactinemia may occur due to dopamine modulation, potentially affecting ovulation. |
| Clinical Pearls | ZELAPAR (selegiline orally disintegrating tablet) is a selective MAO-B inhibitor used for Parkinson's disease. Avoid concomitant use with meperidine, tramadol, methadone, propoxyphene, and St. John's wort due to risk of serotonin syndrome. Discontinue 14 days before elective surgery if general anesthesia with opioids is planned. Monitor for hypotension and dyskinesias. Use with caution in patients with a history of peptic ulcer disease. |
| Patient Advice | Do not chew or swallow the tablet; place on tongue and allow to dissolve. · Take in the morning with or without food. · Avoid foods high in tyramine (e.g., aged cheeses, cured meats, fermented products) unless on a low tyramine diet, as high doses may cause hypertensive crisis. · Inform all healthcare providers you are taking ZELAPAR, especially before any surgery or receiving opioids. · Do not stop taking abruptly; consult your doctor for discontinuation. · Report any signs of serotonin syndrome: agitation, hallucinations, rapid heart rate, fever, muscle stiffness, or coordination problems. |