selegiline EMSAM
Class: MAOIFDA Indications: MDD, Parkinson's Disease
Off-Label Use: Panic Disorder, Social Anxiety, Alzheimers Disease
Prescribing
Forms: 5mg tablet; 6, 9, 12mg patchDose Range: 30-60 mg/day
Starting: 2.5-5 mg bid, titrate slowly to 30-60 mg daily in divided doses;
EMSAM: 6 mg/day, titrate gradually up to 12 mg/day as needed
Stopping: Generally no need to taper
Precautions
Contraindications: all known antidepressants, including St. John's Wort and other MAOIs; certain pain medications: meperidine, methadone, Darvon (caution advised with Ultram); the triptans Imitrex and Maxalt; dextromethorphan; SudafedEMSAM contraindicated with high-tyramine foods at doses ≥9 mg/day;
oral selegiline contraindicated with high-tyramine foods at doses ≥ roughly 20 mg/day
Side Effects: application site reaction (transdermal patch), headache, diarrhea, insomnia, weight gain
Pharmacodynamics
1° MOA: Selective irreversible monoamine oxidase B inhibitor2° MOA: 2° may inhibit NET and DAT
Target: MAO-B (inhibitor of)
Pharmacokinetics
t½: 10° TMAX: 1°Substrate of: 1A2, 2B6, 3A4
Inhibits: ∅ ; Induces: ∅
Active Metabolites: R(–)-methamphetamine, R(–)-amphetamine, N-desmethylselegiline
DDIs
- - When taken with serotonergic medications (especially SSRIs), all doses of EMSAM can cause serotonin syndrome, with tremor, rigidity, fever, tachycardia, confusion ∴ don't start selegiline into 5-half lives of any stopped antidepressant, and wait ~2 weeks after stopping selegiline before starting any antidepressant
Misc
- - oral formulation doesn't exhibit antidepressant activity until doses roughly ≥20-30mg/day (as its MAO-A inhibition really kicks in), and these doses confer a risk of tyramine-provoked hypertensive crises
- - transdermal form (EMSAM) delivers the drug directly into systemic circulation, hitting the brain in high doses with antidepressant effects while avoiding first-pass through the liver and thus ↓ risk of tyramine reactions
- - oral selegiline loses its MOA-B selectivity at doses roughly ≥20 mg/day (subtherapeutic for depression) whereas the EMSAM doesn't begin to lose its MOA-B selectivity until doses ≥9 mg/day which is above the recommened starting dose for depression (6mg/day)
- - EMSAM's t½ is 18-25°
- - bioavailability of oral formulation is ↑'d 3 to 4 fold when taken with food
Special Populations
Category C—Two cases of exposure to selegiline during human pregnancy have been located, and only one them involved exposure throughout gestation. Although there is no indication of physical teratogenicity in animal studies or the two human cases, selegiline did result in significant neurochanges in rats when combined with another monoamine oxidase (MAO) inhibitor. Until additional human data are available, the use of selegiline during pregnancy should be avoided if possible.
Except for the one case above (breastfeeding for 3 days), no reports have described the use of selegiline during human lactation. The low molecular weight suggests that excretion into breast milk will occur. The effect of this exposure on a nursing infant is unknown. Because of significant neurotoxicity observed in animals, the safest course is to avoid selegiline during nursing until data are available.
The recommended dose for elderly patients (≥65) is 6mg/24°
No dose adjustment necessary
No dose adjustment necessary