Why Drug Interactions Matter With Amphetamine/Dextroamphetamine XR

Taking Amphetamine/Dextroamphetamine XR alongside certain other medications, supplements, or even foods can change how the drug works in your body — sometimes in dangerous ways. Some combinations can make the medication too strong, others can make it less effective, and a few can trigger life-threatening reactions.

This guide covers the most important interactions you should know about, so you can have an informed conversation with your doctor and pharmacist.

How Drug Interactions Work

Drug interactions happen in a few different ways:

• Increased effect: Another substance makes Amphetamine/Dextroamphetamine XR stronger or last longer, raising the risk of side effects.
• Decreased effect: Another substance reduces the medication's effectiveness, meaning your ADHD symptoms may not be well-controlled.
• New risks: The combination creates a new danger that neither drug would cause on its own (like serotonin syndrome).

Medications That Interact With Amphetamine/Dextroamphetamine XR

MAO Inhibitors — Do Not Combine (Contraindicated)

This is the most dangerous interaction. MAO inhibitors (MAOIs) combined with amphetamine can cause a hypertensive crisis — a sudden, severe spike in blood pressure that can be life-threatening.

You should not take Amphetamine/Dextroamphetamine XR if you've used an MAOI in the past 14 days. Common MAOIs include:

• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Isocarboxazid (Marplan)
• Selegiline (Emsam) at higher doses
• Linezolid (Zyvox) — an antibiotic that also has MAOI activity

Serotonergic Medications — Risk of Serotonin Syndrome

Taking Amphetamine/Dextroamphetamine XR with drugs that increase serotonin can cause serotonin syndrome, a potentially life-threatening condition. Symptoms include agitation, confusion, rapid heartbeat, high fever, muscle rigidity, and loss of coordination.

Medications that raise this risk include:

• SSRIs: Fluoxetine (Prozac), Sertraline (Zoloft), Escitalopram (Lexapro), Paroxetine (Paxil)
• SNRIs: Venlafaxine (Effexor), Duloxetine (Cymbalta)
• Triptans: Sumatriptan (Imitrex), Rizatriptan (Maxalt) — used for migraines
• Tramadol (Ultram) — a pain medication
• Lithium
• St. John's Wort — an herbal supplement

Many people with ADHD also take an SSRI or SNRI for anxiety or depression. This combination isn't automatically dangerous, but it does require careful monitoring by your doctor. Never start or stop a serotonergic medication without talking to your provider first.

CYP2D6 Inhibitors — Increased Amphetamine Levels

Some medications slow down the liver enzyme (CYP2D6) that helps break down amphetamine. This can increase amphetamine levels in your blood, making side effects more likely. Examples:

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

Blood Pressure Medications

Amphetamine/Dextroamphetamine XR can raise blood pressure. If you take antihypertensive medications (blood pressure drugs), the stimulant may reduce their effectiveness. Your doctor may need to adjust your blood pressure medication or monitor you more closely.

Tricyclic Antidepressants

Drugs like amitriptyline, nortriptyline, and imipramine can enhance the effects of amphetamine. This combination may increase heart rate and blood pressure beyond what either drug would cause alone.

Alkalinizing and Acidifying Agents

This is a less obvious but important interaction:

• Alkalinizing agents (like sodium bicarbonate or antacids) increase amphetamine absorption and slow its elimination, potentially making the medication too strong.
• Acidifying agents (like ammonium chloride or high-dose vitamin C) decrease amphetamine levels by speeding up elimination through the kidneys.

Supplements and Over-the-Counter Drugs to Watch

• Vitamin C (ascorbic acid): High doses can reduce how well Amphetamine/Dextroamphetamine XR works by acidifying your urine and speeding up elimination.
• St. John's Wort: Increases serotonin — risk of serotonin syndrome when combined with amphetamine.
• Antacids (Tums, Rolaids): Can increase amphetamine absorption. Avoid taking them at the same time as your medication.
• Decongestants (pseudoephedrine): Both are stimulants and can compound cardiovascular effects like increased heart rate and blood pressure.
• Caffeine: While not a dangerous interaction, caffeine combined with amphetamine can increase jitteriness, anxiety, and heart rate.

Food and Drink Interactions

• Orange juice and citrus fruits: Acidic drinks can reduce the absorption and effectiveness of Amphetamine/Dextroamphetamine XR. Avoid drinking large amounts of orange juice within an hour of taking your medication.
• Vitamin C-fortified foods: Same effect as citrus — high vitamin C content can lower medication levels.
• Alcohol: Not a direct pharmacological interaction, but alcohol impairs judgment and can mask the stimulant's effects. The combination can also increase cardiovascular strain.
• High-fat meals: May delay absorption slightly but don't reduce overall effectiveness.

What to Tell Your Doctor

Before starting Amphetamine/Dextroamphetamine XR, give your doctor a complete list of everything you take, including:

• All prescription medications
• Over-the-counter drugs (pain relievers, cold medicine, antacids)
• Herbal supplements (especially St. John's Wort)
• Vitamins (especially vitamin C)
• Recreational substances

Also tell your doctor if you:

• Have been prescribed an MAOI in the past 14 days
• Take any medication for depression, anxiety, or migraines
• Take blood pressure medication
• Use any stimulants (including high caffeine intake)

Your pharmacist is another great resource. When filling your prescription, they'll check for interactions automatically — but only if they know about everything you're taking.

Final Thoughts

Amphetamine/Dextroamphetamine XR is safe and effective when used properly, but it does interact with a number of common medications, supplements, and foods. The most critical things to avoid are MAO inhibitors (never combine) and unmonitored use with serotonergic drugs.

When in doubt, tell your doctor and pharmacist about everything you take. It's always better to ask than to guess.

If you're currently taking Amphetamine/Dextroamphetamine XR and having trouble finding it in stock, Medfinder can help you locate a pharmacy near you.