Dextroamphetamine XR Drug Interactions: What to Avoid and What to Tell Your Doctor

Drug Interactions You Need to Know About

Dextroamphetamine XR can interact with a range of other medications, supplements, and even certain foods. Some interactions are dangerous. Others may make the medication less effective or increase side effects.

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

How Drug Interactions Work

A drug interaction happens when another substance changes how a medication works in your body. With dextroamphetamine XR, interactions can:

• Increase the drug's effects — leading to higher risk of side effects like rapid heartbeat, high blood pressure, or anxiety
• Decrease the drug's effects — making it less effective at controlling your symptoms
• Create a dangerous new effect — like serotonin syndrome or a hypertensive crisis

Major Drug Interactions (Avoid or Use with Extreme Caution)

MAO Inhibitors — Contraindicated

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

MAO inhibitors include:

• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Isocarboxazid (Marplan)
• Selegiline (Emsam, Zelapar) — especially at higher doses
• Linezolid (Zyvox) — an antibiotic that also has MAOI activity
• Methylene blue (used in certain medical procedures)

Rule: You must stop an MAOI at least 14 days before starting dextroamphetamine XR, and vice versa.

Serotonergic Drugs — Risk of Serotonin Syndrome

Combining dextroamphetamine XR with drugs that increase serotonin can cause serotonin syndrome — a potentially life-threatening condition with symptoms including agitation, confusion, rapid heartbeat, high fever, muscle twitching, and loss of coordination.

Medications that increase serotonin risk include:

• SSRIs: fluoxetine (Prozac), sertraline (Zoloft), paroxetine (Paxil), escitalopram (Lexapro), citalopram (Celexa)
• SNRIs: venlafaxine (Effexor), duloxetine (Cymbalta), desvenlafaxine (Pristiq)
• Triptans: sumatriptan (Imitrex), rizatriptan (Maxalt) — used for migraines
• Opioids: fentanyl, tramadol (Ultram), meperidine (Demerol)
• Other: St. John's Wort, lithium, buspirone (Buspar)

Many people with ADHD also take antidepressants. This combination isn't always avoidable, but it requires careful monitoring by your doctor.

CYP2D6 Inhibitors — Increased Amphetamine Levels

Some medications slow down the liver enzyme (CYP2D6) that helps break down amphetamines. This can increase dextroamphetamine levels in your blood, raising the risk of side effects.

Common CYP2D6 inhibitors:

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

Moderate Drug Interactions

Blood Pressure Medications

Dextroamphetamine XR can raise blood pressure, which may reduce the effectiveness of antihypertensive medications like lisinopril, amlodipine, metoprolol, or losartan. Your doctor may need to adjust your blood pressure medication if you're starting a stimulant.

Urinary Alkalinizing Agents

Substances that make your urine more alkaline — like sodium bicarbonate (baking soda) or certain antacids — can increase amphetamine levels by slowing how quickly your kidneys clear the drug. This can intensify both the effects and side effects.

Urinary Acidifying Agents

Conversely, substances that make your urine more acidic — like ascorbic acid (vitamin C) — decrease amphetamine levels by speeding up clearance through the kidneys.

Tricyclic Antidepressants (TCAs)

Dextroamphetamine can increase blood levels of TCAs like amitriptyline (Elavil), nortriptyline (Pamelor), and imipramine (Tofranil). This combination requires monitoring for TCA side effects.

Proton Pump Inhibitors and Antacids

Medications like omeprazole (Prilosec), esomeprazole (Nexium), and aluminum/magnesium antacids (Maalox, Mylanta) can increase the absorption of dextroamphetamine by raising stomach pH. This may lead to stronger effects than expected.

Supplements and OTC Medications to Watch

• Vitamin C (ascorbic acid): Can reduce dextroamphetamine effectiveness. Avoid large doses or supplements within a few hours of your medication.
• St. John's Wort: Increases serotonin and can contribute to serotonin syndrome risk.
• Antihistamines (Benadryl, Zyrtec, etc.): Dextroamphetamine may reduce their sedative effects, which matters if you're relying on them for sleep.
• Decongestants (pseudoephedrine, phenylephrine): Both stimulants and decongestants can raise blood pressure and heart rate. Using them together may amplify these effects.
• Caffeine: Not technically a drug interaction, but caffeine adds to the stimulant effects and can worsen insomnia, anxiety, and rapid heartbeat.

Food and Drink Interactions

• Acidic juices (orange juice, grapefruit juice): Decrease absorption of dextroamphetamine. Avoid within 1 hour of dosing.
• Vitamin C-rich foods in large amounts: Same effect as vitamin C supplements — can reduce effectiveness.
• Alkaline foods: May slightly increase absorption, though this is rarely clinically significant with normal diets.
• Alcohol: Should be avoided. Alcohol is a depressant that can mask stimulant effects and increase the risk of cardiovascular side effects. It also impairs judgment about how much medication effect you're feeling.

What to Tell Your Doctor

Before starting dextroamphetamine XR, give your doctor a complete list of:

• All prescription medications you take
• Over-the-counter medications (including cold medicines, antacids, and pain relievers)
• Vitamins and supplements (especially vitamin C and St. John's Wort)
• Herbal products
• Any recreational substances

Also tell your doctor if you've taken an MAO inhibitor in the past 14 days, if you have high blood pressure, or if you take medication for depression or anxiety.

When you pick up a new medication from the pharmacy, always ask your pharmacist to check for interactions with dextroamphetamine XR.

Final Thoughts

Dextroamphetamine XR is generally safe when taken as prescribed, but it does interact with a number of common medications and supplements. The most critical interactions to know are MAO inhibitors (absolutely avoid) and serotonergic drugs (monitor carefully).

Stay informed and communicate openly with your healthcare team. For more about this medication, see our guides on side effects and uses and dosage. If you're having trouble finding it at your pharmacy, try Medfinder.