phenelzine NARDIL
Class: MAOIFDA Indications: Depressed Patients Characterized As "atypical," "nonendogenous," Or "neurotic"
Off-Label Use: Treatment-resistant Depression, Treatment-resistant Panic Disorder, Bulimia Nervosa
Prescribing
Forms: 15mg tabletDose Range: 30-90 mg/day
Starting: 45 mg/day in 3 divided doses; increase to 60-90 mg/day; after desired therapeutic effect is achieved lower dose as far as possible
Once dosing is stabilized, some patients may tolerate qd or bid dosing rather than tid.
Stopping: Generally no need to taper, as the drug wears off slowly over 2-3 weeks.
Monitoring: Monitor blood pressure and BMI. Hepatic function should be monitored periodically in patients receiving high doses.
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; Sudafedhigh-tyramine foods
Serious Side Effects: Hypertensive crisis (especially when MAOIs are used with certain tyramine-containing foods or prohibited drugs), induction of mania, seizures, hepatotoxicity
Contraindicated in patients with congestive heart failure or hypertension.
Side Effects: sedation/somnolence, dizziness, weight gain, tremor, weakness/asthenia, insomnia, visual changes, hyperhidrosis, xerostomia, increased appetite, weight gain, sexual dysfunction, orthostatic hypotension
Pharmacodynamics
1° MOA: Non-selective irreversible monoamine oxidase inhibitor2° MOA: One of phenelzine's 2° metabolites, PEH, inhibits GABA-T, which ↑'s GABA levels (in brain and body). Another 2° metabolite is the stimulant, phenethylamine, which ↑'s presynaptic DA & NE release.
Target: MAO-A, MAO-B
Pharmacokinetics
t½: 11.6° TMAX: 2-3°Substrate of: Oxidation
Inhibits: ∅ ; Induces: ∅
Active Metabolites: PEH , phenethylamine
DDIs
- - Do not coadminister with any serotonergic medications (especially SSRIs, SNRIs, TCAs), which can cause serotonin syndrome
- - Don't start phenelzine into 5-half lives of any stopped antidepressant, and wait ~2 weeks after stopping selegiline before starting any antidepressant. Do not use patient is taking meperidine, any sympathomimetic agent or guanethidine, non-subcutaneous sumatriptan, tramadol, chlorpheniramine, methamphetamine, methadone, mrompheniramine, St. John's wort, amphetamine, fentanyl, dextromethorphan, or another MAOI.
- - Use with caution with coprescribed noradrenergic agents, e.g. phenylephrine, phentermine, pseudoephedrine, local anesthetics containing vasoconstrictors, NDRIs, modafinil, tapentadol, armodafinil.
Misc
- - foods to generally avoid, as they are usually high in tyramine content: dry sausage, pickled herring, liver, broad bean pods, sauerkraut, cheese, yogurt, alcoholic beverages, nonalcoholic beer and wine, chocolate, caffeine, meat, and fish
- - Great resource → Avoiding High-tyramine Foods Made Easy
Special Populations
Category C—The human pregnancy experience is too limited to assess the embryo-fetal risk. It is not known if phenelzine crosses the human placenta. The molecular weight of the sulfate form (about 234) and elimination half-life suggest that exposure of the embryo-fetus should be expected. The Collaborative Perinatal Project monitored 21 mother-child pairs exposed to MAO inhibitors during the 1st trimester, 3 of which were exposed to phenelzine. Three of the 21 infants had malformations (RR 2.26). Details of the three cases with phenelzine exposure were not specified.
No reports describing the use of phenelzine during breastfeeding have been located. Its molecular weight and moderately long t½ suggest that it will be excreted into breast milk.
Initial dose 7.5 mg/day; increase every few days by 7.5-15 mg/day
Elderly patients may have greater sensitivity to adverse effects.
No dose adjustment necessary
No dose adjustment necessary. The serum aminotransferase elevations that occur on phenelzine therapy are usually self-limited and mild and do not require dose modification or discontinuation of therapy.