Armodafinil Drug Interactions You Should Know About

Armodafinil (brand name Nuvigil) is generally well-tolerated, but it interacts with several common medications in ways that can reduce their effectiveness or increase the risk of side effects. Some of these interactions are serious enough that they could affect your health if not properly managed.

This guide covers the most important Armodafinil drug interactions — including prescription medications, over-the-counter drugs, supplements, and food — so you know what to watch for and what to tell your doctor.

How Drug Interactions Work with Armodafinil

Most of Armodafinil's drug interactions happen because of how it's processed by your liver. Armodafinil affects two important liver enzymes:

• CYP3A4 — Armodafinil induces (speeds up) this enzyme. Medications that are broken down by CYP3A4 may be cleared from your body faster than normal, making them less effective.
• CYP2C19 — Armodafinil inhibits (slows down) this enzyme. Medications that are processed by CYP2C19 may build up in your body to higher-than-expected levels, increasing the risk of side effects.

This two-way effect — speeding up some enzymes while slowing down others — is what makes Armodafinil's interaction profile unique and important to understand.

Major Drug Interactions

These interactions are the most clinically significant. If you take any of these medications, your doctor needs to know before you start Armodafinil:

Hormonal Contraceptives

This is one of the most important interactions. Armodafinil induces CYP3A4, which speeds up the breakdown of hormones in birth control. This can reduce the effectiveness of:

• Birth control pills (oral contraceptives)
• Patches (Xulane)
• Vaginal rings (NuvaRing)
• Hormonal implants (Nexplanon)

What to do: Use an alternative or additional method of contraception (such as condoms or a copper IUD) while taking Armodafinil and for one month after stopping it. Talk to your doctor about your options.

Cyclosporine (Neoral, Sandimmune)

Armodafinil's CYP3A4 induction can significantly reduce Cyclosporine blood levels. Cyclosporine is an immunosuppressant used after organ transplants and for autoimmune conditions. Reduced levels could lead to organ rejection or disease flare-ups.

What to do: If you take Cyclosporine, your doctor will need to monitor your blood levels closely and may need to adjust your dose.

Midazolam (Versed) and Triazolam (Halcion)

These are benzodiazepines that are broken down by CYP3A4. Armodafinil can reduce their levels, making them less effective. This is particularly important if Midazolam is being used for procedural sedation.

Warfarin (Coumadin)

Armodafinil may alter how Warfarin is metabolized. Because Warfarin is a blood thinner with a narrow therapeutic range, even small changes in metabolism can increase the risk of bleeding or blood clots.

What to do: Your doctor should monitor your INR (blood clotting time) more frequently when starting or stopping Armodafinil.

Phenytoin (Dilantin)

Phenytoin is an anti-seizure medication processed by CYP2C19. Because Armodafinil inhibits CYP2C19, Phenytoin levels may increase, raising the risk of toxicity (dizziness, double vision, unsteadiness).

What to do: Your doctor should monitor Phenytoin blood levels if you start Armodafinil.

Omeprazole (Prilosec) and Other CYP2C19 Substrates

Armodafinil's inhibition of CYP2C19 can increase levels of Omeprazole and other drugs processed by this enzyme. While this interaction is usually less dangerous than the ones above, it's worth noting — especially if you take higher doses of Omeprazole.

Carbamazepine (Tegretol)

This anti-seizure medication is both a CYP3A4 inducer and a CYP3A4 substrate. Taking it with Armodafinil can create a mutual interaction where both drugs reduce each other's levels. Your doctor may need to adjust doses of both medications.

Moderate Drug Interactions

These interactions are less likely to cause serious harm but should still be on your radar:

• Diazepam (Valium) — Processed by CYP2C19; Armodafinil may increase levels, leading to increased sedation.
• Propranolol (Inderal) — A blood pressure medication processed by CYP2C19; levels may increase with Armodafinil.
• Clomipramine (Anafranil) — A tricyclic antidepressant; levels may increase.
• MAO inhibitors (Phenelzine, Tranylcypromine) — Use with caution due to potential for unpredictable interactions.

Supplements and OTC Medications to Watch

Some over-the-counter products can interact with Armodafinil or worsen its side effects:

• Caffeine — Not technically a drug interaction, but caffeine and Armodafinil are both stimulating. Combining them can increase anxiety, jitteriness, insomnia, and heart palpitations. If you use Armodafinil, consider reducing your caffeine intake.
• St. John's Wort — This herbal supplement is a potent CYP3A4 inducer. Taking it with Armodafinil could create unpredictable changes in drug metabolism.
• Melatonin — Not a direct interaction, but taking melatonin to counteract Armodafinil-related insomnia should be discussed with your doctor to make sure the timing and dosing make sense.
• Antihistamines (Diphenhydramine/Benadryl, Cetirizine/Zyrtec) — These cause drowsiness, which can counteract Armodafinil's wakefulness effects. Consider non-sedating alternatives if you need allergy relief.

Food and Drink Interactions

Food

Taking Armodafinil with food delays absorption (it takes longer to reach peak levels) but doesn't significantly reduce the total amount absorbed. You can take it with or without food.

Grapefruit and Grapefruit Juice

Grapefruit inhibits CYP3A4, which could increase Armodafinil levels in your body. While this interaction is generally mild, it's worth being aware of if you consume large amounts of grapefruit regularly.

Alcohol

Alcohol can worsen CNS side effects of Armodafinil, including dizziness and impaired judgment. It can also counteract the medication's wakefulness-promoting effects. It's best to limit alcohol while taking Armodafinil.

What to Tell Your Doctor

Before starting Armodafinil, make sure your doctor has a complete picture of everything you take. Specifically, tell them about:

1. All prescription medications — especially blood thinners, anti-seizure drugs, immunosuppressants, birth control, and psychiatric medications.
2. Over-the-counter medications — including pain relievers, antihistamines, and stomach acid reducers like Omeprazole.
3. Supplements and herbal products — including St. John's Wort, caffeine pills, and melatonin.
4. Your caffeine habits — how much coffee, tea, or energy drinks you consume daily.
5. Alcohol use — how often and how much you drink.

If you start any new medication while already taking Armodafinil, let both your prescriber and pharmacist know so they can check for interactions.

Final Thoughts

Armodafinil is a safe and effective medication when used properly, but its effects on liver enzymes (CYP3A4 and CYP2C19) mean it can interact with a wide range of other drugs. The most critical interactions involve hormonal birth control, blood thinners like Warfarin, immunosuppressants like Cyclosporine, and anti-seizure medications.

The simplest way to stay safe: keep your doctor and pharmacist informed about everything you take. For more information about Armodafinil, read our guides on side effects, uses and dosage, and how it works.