ELDEPRYL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ELDEPRYL (ELDEPRYL).

How it works

Selective irreversible inhibitor of monoamine oxidase B (MAO-B), which increases levels of dopamine in the brain.

What the body does with it

Metabolism	Hepatic via cytochrome P450 enzymes (CYP2B6, CYP2C9, CYP3A4) and flavin-containing monooxygenase; metabolites include N-desmethylselegiline, L-amphetamine, and L-methamphetamine.
Excretion	Renal excretion of metabolites (approximately 45% as methamphetamine and amphetamine metabolites, 10–15% as conjugated metabolites, <5% unchanged). Biliary/fecal elimination accounts for <10%.
Half-life	Terminal elimination half-life is 0.5–1.5 hours for the parent drug; however, metabolites (amphetamine and methamphetamine) have half-lives of 10–30 hours, contributing to prolonged pharmacological effects.
Protein binding	Approximately 94–98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Vd is approximately 1.5–2.5 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral: 5–10% due to extensive first-pass metabolism. Transdermal: approximately 75%.
Onset of Action	Oral: approximately 0.5–1 hour. Transdermal: 2–4 hours.
Duration of Action	Oral: 12–24 hours due to active metabolites. Transdermal: 24 hours per patch application.

Classification & Brands

Action Class	MAO-B Inhibitors
Brand Substitutes	Selgin 10mg Tablet

Dosing & administration

5 mg orally twice daily (morning and noon) for Parkinson's disease; 10 mg orally once daily or 5 mg orally twice daily for major depressive disorder as adjunct to SSRIs.

Dosage form	CAPSULE
Renal impairment	No specific guidelines; use with caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation of metabolites.
Liver impairment	Contraindicated in patients with severe hepatic impairment (Child-Pugh class C); reduce dose by 50% in moderate impairment (Child-Pugh class B), no adjustment needed for mild (Child-Pugh class A).
Pediatric use	Safety and efficacy not established in pediatric patients; no recommended dosing available.
Geriatric use	Initiate at lower doses (e.g., 5 mg once daily) and titrate slowly due to increased risk of orthostatic hypotension and drug interactions; monitor for cognitive side effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ELDEPRYL (ELDEPRYL).

Breastfeeding	Selegiline and its metabolites are excreted in breast milk. M/P ratio unknown. Due to potential for serious adverse effects in nursing infants (e.g., hypertensive crisis, serotonin syndrome), breastfeeding is not recommended during therapy.
Teratogenic Risk	FDA Pregnancy Category C. Selegiline crosses the placenta. First trimester: Limited human data; animal studies show increased fetal resorptions and skeletal anomalies at high doses. Second/third trimester: No well-controlled studies; risk of fetal monoamine oxidase inhibition. Potential risks include preterm labor and fetal growth restriction due to vasoactive metabolites.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with other MAOIs or selective serotonin reuptake inhibitors (SSRIs)","Concomitant use with meperidine or other opioids","Pheochromocytoma","Severe hepatic or renal impairment"]

Clinical Precautions

Precautions

["Risk of hypertensive crisis when used with tyramine-rich foods or non-selective MAOIs","May cause serotonin syndrome when combined with other serotonergic drugs","Concomitant use with opioids (e.g., meperidine) contraindicated","Caution in patients with history of peptic ulcer or hypertension"]

Clinical Tips & Counseling

Drug interactions

Loading safety data…

ELDEPRYL

Clinical safety rating: caution

Comprehensive clinical and safety monograph for ELDEPRYL (ELDEPRYL).

How it works

Selective irreversible inhibitor of monoamine oxidase B (MAO-B), which increases levels of dopamine in the brain.

What the body does with it

Metabolism	Hepatic via cytochrome P450 enzymes (CYP2B6, CYP2C9, CYP3A4) and flavin-containing monooxygenase; metabolites include N-desmethylselegiline, L-amphetamine, and L-methamphetamine.
Excretion	Renal excretion of metabolites (approximately 45% as methamphetamine and amphetamine metabolites, 10–15% as conjugated metabolites, <5% unchanged). Biliary/fecal elimination accounts for <10%.
Half-life	Terminal elimination half-life is 0.5–1.5 hours for the parent drug; however, metabolites (amphetamine and methamphetamine) have half-lives of 10–30 hours, contributing to prolonged pharmacological effects.
Protein binding	Approximately 94–98% bound to plasma proteins, primarily albumin and alpha-1-acid glycoprotein.
Volume of Distribution	Vd is approximately 1.5–2.5 L/kg, indicating extensive tissue distribution.
Bioavailability	Oral: 5–10% due to extensive first-pass metabolism. Transdermal: approximately 75%.
Onset of Action	Oral: approximately 0.5–1 hour. Transdermal: 2–4 hours.
Duration of Action	Oral: 12–24 hours due to active metabolites. Transdermal: 24 hours per patch application.

Classification & Brands

Action Class	MAO-B Inhibitors
Brand Substitutes	Selgin 10mg Tablet

Dosing & administration

5 mg orally twice daily (morning and noon) for Parkinson's disease; 10 mg orally once daily or 5 mg orally twice daily for major depressive disorder as adjunct to SSRIs.

Dosage form	CAPSULE
Renal impairment	No specific guidelines; use with caution in severe renal impairment (CrCl <30 mL/min) due to potential accumulation of metabolites.
Liver impairment	Contraindicated in patients with severe hepatic impairment (Child-Pugh class C); reduce dose by 50% in moderate impairment (Child-Pugh class B), no adjustment needed for mild (Child-Pugh class A).
Pediatric use	Safety and efficacy not established in pediatric patients; no recommended dosing available.
Geriatric use	Initiate at lower doses (e.g., 5 mg once daily) and titrate slowly due to increased risk of orthostatic hypotension and drug interactions; monitor for cognitive side effects.

Use during pregnancy

1st trimester	Consult provider
2nd trimester	Consult provider
3rd trimester	Consult provider

Clinical note

Comprehensive clinical and safety monograph for ELDEPRYL (ELDEPRYL).

Breastfeeding	Selegiline and its metabolites are excreted in breast milk. M/P ratio unknown. Due to potential for serious adverse effects in nursing infants (e.g., hypertensive crisis, serotonin syndrome), breastfeeding is not recommended during therapy.
Teratogenic Risk	FDA Pregnancy Category C. Selegiline crosses the placenta. First trimester: Limited human data; animal studies show increased fetal resorptions and skeletal anomalies at high doses. Second/third trimester: No well-controlled studies; risk of fetal monoamine oxidase inhibition. Potential risks include preterm labor and fetal growth restriction due to vasoactive metabolites.

Warnings & precautions

■ FDA Black Box Warning

None.

Side Effect Profile

Serious Effects

Absolute Contraindications

["Concomitant use with other MAOIs or selective serotonin reuptake inhibitors (SSRIs)","Concomitant use with meperidine or other opioids","Pheochromocytoma","Severe hepatic or renal impairment"]