Why Amphetamine Drug Interactions Matter

If you take Amphetamine for ADHD or narcolepsy, knowing which medications, supplements, and foods can interact with it is essential for your safety. Some interactions can reduce how well your medication works. Others can cause dangerous side effects.

This guide covers the most important Amphetamine drug interactions — what to avoid, what to watch for, and what to tell your doctor.

How Drug Interactions Work

A drug interaction happens when another substance changes how a medication works in your body. With Amphetamine, interactions can happen in several ways:

• Another drug increases Amphetamine levels in your body, raising the risk of side effects
• Another drug decreases Amphetamine levels, making it less effective
• Amphetamine changes how another drug works, making it stronger or weaker
• Two drugs affect the same brain chemicals, causing a combined effect that can be dangerous

Major Drug Interactions (Avoid These)

The following interactions are considered serious. In some cases, these combinations are contraindicated — meaning they should never be used together.

MAO Inhibitors (MAOIs)

This is the most dangerous interaction. Taking Amphetamine with an MAO inhibitor — or within 14 days of stopping one — can cause a hypertensive crisis (a sudden, severe spike in blood pressure that can be life-threatening).

MAOIs include:

• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Isocarboxazid (Marplan)
• Selegiline (Emsam) — the patch form used for depression
• Linezolid (Zyvox) — an antibiotic that also has MAOI activity

Rule: Do not take Amphetamine if you've used an MAOI within the past 14 days.

Serotonergic Medications

Combining Amphetamine with drugs that increase serotonin can lead to serotonin syndrome, a potentially life-threatening condition. Symptoms include agitation, high fever, rapid heartbeat, muscle rigidity, and diarrhea.

Medications to be cautious with include:

• SSRIs: Fluoxetine (Prozac), Sertraline (Zoloft), Escitalopram (Lexapro), Paroxetine (Paxil), Citalopram (Celexa)
• SNRIs: Venlafaxine (Effexor), Duloxetine (Cymbalta), Desvenlafaxine (Pristiq)
• Triptans: Sumatriptan (Imitrex), Rizatriptan (Maxalt) — used for migraines
• Others: Tramadol (Ultram), St. John's Wort, Lithium

Many people take an SSRI and Amphetamine together for co-occurring ADHD and depression or anxiety. This can be done safely under close medical supervision, but you should know the warning signs of serotonin syndrome.

CYP2D6 Inhibitors

Some medications slow down the liver enzyme (CYP2D6) that breaks down Amphetamine. This can increase Amphetamine levels in your blood, raising the risk of side effects. These include:

• Fluoxetine (Prozac)
• Paroxetine (Paxil)
• Quinidine
• Bupropion (Wellbutrin)

Moderate Drug Interactions

These interactions are less immediately dangerous but can still affect your treatment. Your doctor should be aware of them.

Antihypertensives (Blood Pressure Medications)

Amphetamine can raise blood pressure and heart rate, which may reduce the effectiveness of blood pressure medications. If you take medications like Lisinopril, Amlodipine, Metoprolol, or Losartan, your doctor may need to adjust your doses.

Anticonvulsants

Medications like Phenytoin (Dilantin) and Phenobarbital may have their absorption affected by Amphetamine. Your doctor should monitor anticonvulsant levels if you're taking both.

Proton Pump Inhibitors (PPIs)

PPIs like Omeprazole (Prilosec) and Esomeprazole (Nexium) can change stomach acidity, which may alter how extended-release Amphetamine formulations are absorbed.

Tricyclic Antidepressants (TCAs)

Amphetamine can enhance the effects of TCAs like Amitriptyline, Nortriptyline (Pamelor), and Imipramine (Tofranil). This combination may increase the risk of cardiovascular side effects.

Lithium

Lithium may reduce the stimulant effects of Amphetamine. If you take both, your doctor should monitor your response closely.

Supplements and Over-the-Counter Medications to Watch

It's not just prescription drugs you need to worry about. Several common supplements and OTC products can interact with Amphetamine:

• Vitamin C (ascorbic acid) — High doses of vitamin C can increase the acidity of your urine, which speeds up the elimination of Amphetamine from your body. This can make the medication less effective.
• Antacids (Tums, sodium bicarbonate) — These alkalinize your urine, which slows Amphetamine elimination and can increase its effects and side effects.
• Decongestants containing pseudoephedrine or phenylephrine — These are stimulants themselves and can amplify the cardiovascular effects of Amphetamine (increased heart rate and blood pressure).
• St. John's Wort — Increases serotonin levels and may raise the risk of serotonin syndrome when combined with Amphetamine.
• Caffeine supplements — Can increase jitteriness, insomnia, and heart rate when combined with Amphetamine.

Food and Drink Interactions

What you eat and drink can affect how Amphetamine works:

• Acidic foods and drinks — Orange juice, grapefruit juice, tomato-based foods, and sodas can decrease Amphetamine absorption and effectiveness. Avoid consuming large amounts of these around the time you take your medication.
• Alkaline foods — Foods that reduce stomach acidity may increase Amphetamine absorption.
• Caffeine — Coffee, tea, and energy drinks can worsen side effects like anxiety, insomnia, and increased heart rate. While moderate caffeine intake is usually fine, be mindful of the combined stimulant effect.
• Alcohol — Alcohol can mask the effects of Amphetamine and increase the risk of cardiovascular side effects. It's generally recommended to limit or avoid alcohol while taking stimulant medications.

What to Tell Your Doctor

Before starting Amphetamine — or at any appointment — make sure your doctor knows about:

• All prescription medications you take, including those prescribed by other doctors
• Over-the-counter medications, including pain relievers, cold medicines, and antacids
• Supplements and vitamins, especially vitamin C, St. John's Wort, and any herbal products
• Caffeine intake — how many cups of coffee, tea, or energy drinks you consume daily
• Any recent medication changes — especially if you've recently stopped or started a new medication

Keep an updated medication list on your phone or in your wallet. This makes it easy to share with any healthcare provider, pharmacist, or emergency room doctor.

Final Thoughts

Amphetamine is a safe and effective medication when used as prescribed, but it does interact with a significant number of other drugs, supplements, and foods. The most dangerous interactions involve MAO inhibitors and serotonergic medications. The most common — and often overlooked — involve everyday things like vitamin C, antacids, and caffeine.

The best way to stay safe is to keep your doctor and pharmacist informed about everything you take. If you experience unusual symptoms after starting a new medication or supplement, contact your doctor right away.

For more information, read our guides on Amphetamine side effects and what Amphetamine is. If you're having trouble finding your medication, use Medfinder to check pharmacy availability near you.