Emsam Drug Interactions: What to Avoid and What to Tell Your Doctor

Emsam (selegiline transdermal system) has more clinically significant drug interactions than most antidepressants. Because it is a monoamine oxidase inhibitor (MAOI), combining it with many common medications can cause serious or life-threatening reactions. Understanding these interactions is essential for anyone starting or currently using Emsam.

This guide covers the most important drug interactions with Emsam, organized by risk level, and explains what to tell every healthcare provider who treats you.

Why Emsam Has So Many Drug Interactions

Emsam inhibits MAO enzymes that play a key role in breaking down neurotransmitters and many drugs in the body. When MAO is inhibited, levels of serotonin, norepinephrine, and dopamine rise. Adding other drugs that also affect these systems can cause these neurotransmitters to reach dangerously high levels — triggering either serotonin syndrome or hypertensive crises.

Also, because Emsam inhibition is irreversible, these interaction risks continue for up to 14 days after you remove the last patch.

CONTRAINDICATED: Never Use These With Emsam

The following combinations are strictly contraindicated — meaning they must never be used together, and a required washout period is mandatory before switching:

SSRIs (Selective Serotonin Reuptake Inhibitors) — Fluoxetine (Prozac), sertraline (Zoloft), escitalopram (Lexapro), citalopram (Celexa), paroxetine (Paxil). Risk: serotonin syndrome. Must wait at least 2 weeks after stopping SSRIs before starting Emsam (5 weeks after stopping fluoxetine due to its long half-life). Must wait 2 weeks after stopping Emsam before starting an SSRI.

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors) — Venlafaxine (Effexor), duloxetine (Cymbalta), desvenlafaxine (Pristiq). Risk: serotonin syndrome. Same washout requirements as SSRIs.

TCAs (Tricyclic Antidepressants) — Amitriptyline (Elavil), nortriptyline (Pamelor), clomipramine, imipramine. Risk: serotonin syndrome. Same 2-week washout required.

Bupropion (Wellbutrin, Zyban) — Risk: hypertensive reactions due to additive dopaminergic and noradrenergic effects. Contraindicated. Wait 2 weeks after stopping Emsam before starting bupropion.

Other MAOIs — Phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan). Risk: additive MAO inhibition with potentially fatal consequences. Contraindicated. Wait 14 days between any two MAOIs.

Carbamazepine (Tegretol) — Uniquely dangerous: carbamazepine paradoxically increases selegiline blood levels approximately 2-fold, raising the risk of hypertensive crisis at any dose. Strictly contraindicated with Emsam.

Opioids — especially meperidine (Demerol), tramadol (Ultram), and methadone — Risk: serotonin syndrome or opioid toxicity. These are contraindicated. If urgent pain management is needed, only non-serotonergic opioids (such as morphine or hydromorphone) can be considered with extreme caution. Discuss with your doctor.

Stimulants/amphetamines — Adderall (amphetamine/dextroamphetamine), Ritalin (methylphenidate), Vyvanse (lisdexamfetamine). Risk: acute hypertensive episode. Contraindicated.

Dextromethorphan (DXM) — Found in many OTC cough syrups (Robitussin DM, NyQuil, DayQuil). Risk: serotonin syndrome. Avoid all cough products containing DXM while on Emsam.

Mirtazapine (Remeron) — Risk: serotonin syndrome. Contraindicated.

Buspirone (Buspar) — Risk: acute hypertensive episode. Contraindicated.

Use With Caution (Monitor Carefully)

The following are not strictly contraindicated but require medical monitoring due to potential blood pressure effects:

Sympathomimetic drugs — OTC decongestants containing pseudoephedrine (Sudafed), phenylephrine, or phenylpropanolamine can raise blood pressure when combined with Emsam. Avoid or monitor BP closely.

Adrenergic agents (bronchodilators) — Inhaled beta-agonists like albuterol may have exaggerated cardiovascular effects. Use with monitoring.

Food Interactions With Emsam

At the lowest dose (6 mg/24hr), no dietary tyramine restrictions are required. At 9 mg/24hr and 12 mg/24hr, avoid:

Aged cheeses (cheddar, parmesan, blue cheese, brie)

Cured or fermented meats (salami, pepperoni, prosciutto, beef jerky)

Tap beer, red wine, and alcohol-free beer

Fermented soy products (soy sauce, miso, tofu in large amounts)

Overripe fruit, sauerkraut, and fava/broad beans

Herbal Supplements to Avoid

St. John's Wort — Serotonin syndrome risk. Do not use with Emsam.

Ginseng — May have additive monoaminergic effects. Discuss with your doctor.

Drugs That Are Safe With Emsam

Not everything interacts with Emsam. The following common medications do NOT require dose adjustment and are generally considered safe to use with Emsam based on pharmacokinetic studies: alprazolam (Xanax), ibuprofen, levothyroxine (Synthroid), olanzapine (Zyprexa), risperidone (Risperdal), warfarin (Coumadin).

What to Tell Every Healthcare Provider

Tell every doctor, dentist, ER provider, and pharmacist that you are using Emsam. This includes telling your anesthesiologist before any surgery — the patch must be removed at least 10 days before planned surgery. Never take a new OTC or prescription medication without first checking with your pharmacist or prescriber for Emsam interactions. For a full overview of Emsam side effects, see: Emsam Side Effects: What to Expect.