Why Drug Interactions Matter With Dexedrine

If you take Dexedrine (Dextroamphetamine), understanding drug interactions isn't optional — it's essential for your safety. Dexedrine interacts with a wide range of medications, supplements, and even common foods. Some of these interactions are dangerous enough to be life-threatening.

This guide covers the major and moderate interactions you need to know about, plus what to tell your doctor before starting Dexedrine.

How Drug Interactions Work

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

• Increase Dexedrine's effects — making side effects worse or creating dangerous toxicity
• Decrease Dexedrine's effects — making it less effective for treating your ADHD or narcolepsy
• Create new risks — like serotonin syndrome or dangerously high blood pressure

Interactions can happen with prescription medications, over-the-counter drugs, supplements, and food. That's why your doctor and pharmacist need a complete picture of everything you take.

Major Drug Interactions (Avoid or Use Extreme Caution)

MAOIs — Contraindicated

Monoamine oxidase inhibitors (MAOIs) are the most dangerous interaction with Dexedrine. Combining them can cause a hypertensive crisis — a sudden, life-threatening spike in blood pressure. Dexedrine is absolutely contraindicated within 14 days of taking an MAOI.

MAOIs include:

• Phenelzine (Nardil)
• Tranylcypromine (Parnate)
• Isocarboxazid (Marplan)
• Selegiline (Emsam) — at higher doses
• Linezolid (Zyvox) — an antibiotic with MAOI properties

Serotonergic Medications — Risk of Serotonin Syndrome

Taking Dexedrine with drugs that increase serotonin levels can cause serotonin syndrome — a potentially fatal condition. Symptoms include agitation, rapid heart rate, high body temperature, muscle twitching, diarrhea, and in severe cases, seizures and organ failure.

Medications that increase serotonin risk when combined with Dexedrine:

• SSRIs: Fluoxetine (Prozac), Sertraline (Zoloft), Escitalopram (Lexapro), Paroxetine (Paxil), Citalopram (Celexa)
• SNRIs: Venlafaxine (Effexor), Duloxetine (Cymbalta)
• Tricyclic antidepressants: Amitriptyline (Elavil), Nortriptyline (Pamelor)
• Triptans: Sumatriptan (Imitrex), Rizatriptan (Maxalt)
• Others: Lithium, Tramadol (Ultram), Fentanyl, Buspirone (Buspar)

Important note: Many ADHD patients also take an SSRI or SNRI for anxiety or depression. This combination is common and can be safe under careful medical supervision — but it requires monitoring. Don't stop any medication without talking to your doctor.

CYP2D6 Inhibitors — Increased Dexedrine Levels

Some medications block the liver enzyme (CYP2D6) that breaks down Dextroamphetamine, causing higher drug levels and increased side effects. These include:

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

Moderate Drug Interactions

Blood Pressure Medications

Dexedrine can raise blood pressure, which may reduce the effectiveness of antihypertensive medications. If you take blood pressure medicine, your doctor may need to adjust your dose. Common medications affected include:

• Lisinopril (Zestril, Prinivil)
• Amlodipine (Norvasc)
• Losartan (Cozaar)
• Metoprolol (Lopressor)

Antipsychotics

Antipsychotics like Haloperidol (Haldol) and Chlorpromazine (Thorazine) may reduce the stimulant effect of Dexedrine. Conversely, Dexedrine may counteract the effects of these medications. Your prescriber should weigh the benefits and risks carefully.

Seizure Medications

Phenytoin (Dilantin) and Phenobarbital may have altered blood levels when taken with Dexedrine. If you take anti-seizure medication, your doctor should monitor your levels.

Alkalinizing and Acidifying Agents

• Alkalinizing agents like sodium bicarbonate (baking soda), antacids, and some medications increase the absorption of Dexedrine, potentially making it stronger
• Acidifying agents like ascorbic acid (Vitamin C) decrease absorption, potentially making Dexedrine less effective

Proton Pump Inhibitors (PPIs)

Medications like Omeprazole (Prilosec) and Esomeprazole (Nexium) may increase Dexedrine absorption by making the stomach less acidic.

Supplements and OTC Medications to Watch

• Vitamin C (Ascorbic Acid): Can reduce Dexedrine absorption and effectiveness. Avoid large doses or take them at a different time.
• St. John's Wort: Increases serotonin and can contribute to serotonin syndrome. Do not take with Dexedrine.
• Melatonin: Generally considered safe but may interact with Dexedrine's effects on sleep. Discuss with your doctor.
• Decongestants (Pseudoephedrine, Phenylephrine): Both are stimulants that can add to Dexedrine's cardiovascular effects — increased heart rate and blood pressure.
• Antihistamines: Dexedrine may counteract the sedating effects of medications like Diphenhydramine (Benadryl).

Food and Drink Interactions

Acidic Foods and Drinks

Orange juice, grapefruit juice, lemonade, soda, and other acidic beverages can reduce how well Dexedrine is absorbed in your stomach. For best results, avoid acidic foods and drinks for about an hour before and after your dose.

Alkaline Foods

On the flip side, alkaline foods can increase absorption. This usually isn't a problem, but it's worth knowing.

Caffeine

Caffeine is a stimulant, and combining it with Dexedrine can increase side effects like jitteriness, rapid heart rate, anxiety, and insomnia. Most doctors recommend limiting caffeine intake while taking Dexedrine.

Alcohol

While not a direct pharmacological interaction, alcohol can impair judgment and mask the effects of stimulants. This can lead to dangerous overconsumption of alcohol. Many doctors advise caution or avoidance.

What to Tell Your Doctor

Before starting Dexedrine, give your doctor a complete list of:

• All prescription medications you take
• All over-the-counter medications (including cold medicine, antacids, and pain relievers)
• All supplements and vitamins
• Any herbal products (especially St. John's Wort)
• Your caffeine habits
• Any recreational substances

Also tell your doctor about any past reactions to medications, and whether you have a history of heart problems, high blood pressure, glaucoma, thyroid disorders, or mental health conditions.

If another doctor prescribes you a new medication while you're on Dexedrine, make sure they know you're taking a stimulant. Pharmacists are also a great resource — they check for interactions automatically, but only if they know everything you're taking.

Final Thoughts

Dexedrine interacts with more medications than most people realize. The good news is that most interactions are manageable with proper monitoring and dose adjustments. The key is transparency — tell your healthcare team everything you take, and don't start or stop any medication without checking first.

For more on how Dexedrine works in your body, see our mechanism of action guide. And if you're having trouble finding Dexedrine at the pharmacy, Medfinder can help you locate it near you.