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. |
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 | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for ZELAPAR (ZELAPAR).
| Breastfeeding | Selegiline and its metabolites are excreted in human breast milk. M/P ratio is unknown. Due to the risk of amphetamine-like effects (e.g., irritability, poor feeding) and potential for adverse effects on the infant's developing nervous system, breastfeeding is not recommended during therapy. |
| 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. |
■ FDA Black Box Warning
None.
| Common Effects | Dizziness Dryness in mouth Blurred vision Nausea Sleepiness Weakness Nervousness |
| Serious Effects |
["Concurrent use of other MAO inhibitors (including linezolid)","Concurrent use of selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), or other serotonergic drugs","Pheochromocytoma"]
| 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"] |
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| 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. |