Vyvanse Drug Interactions: What to Avoid and What to Tell Your Doctor

If you take Vyvanse (lisdexamfetamine dimesylate), it's important to know which medications, supplements, and foods can interact with it. Some interactions are dangerous; others may reduce how well Vyvanse works. This guide covers the key interactions you need to know about.

How Drug Interactions Work

A drug interaction happens when one substance changes how another substance works in your body. This can happen in several ways:

• Increased effects: Two drugs that affect the same brain chemicals can amplify each other's effects, potentially to dangerous levels.
• Decreased effectiveness: Some substances can speed up or slow down how your body processes a drug, making it less effective or more potent.
• New side effects: Combining certain medications can trigger side effects that neither drug causes alone.

Vyvanse is converted to dextroamphetamine in the body, which affects dopamine, norepinephrine, and serotonin pathways. This means it can interact with many medications that also affect these neurotransmitter systems.

Medications That Interact with Vyvanse

Major Interactions (Avoid)

These combinations are dangerous and should be avoided:

• MAOIs (monoamine oxidase inhibitors): Drugs like phenelzine (Nardil), tranylcypromine (Parnate), isocarboxazid (Marplan), and selegiline (Emsam). Do not take Vyvanse if you have taken an MAOI within the past 14 days. This combination can cause a hypertensive crisis—a dangerous, potentially fatal spike in blood pressure.
• Other amphetamine-based stimulants: Taking Vyvanse with Adderall or other amphetamine products doubles the stimulant load and increases the risk of cardiovascular events and overdose.

Moderate Interactions (Use Caution)

These combinations may require dose adjustments or monitoring:

• SSRIs and SNRIs: Antidepressants like sertraline (Zoloft), fluoxetine (Prozac), escitalopram (Lexapro), venlafaxine (Effexor), and duloxetine (Cymbalta). When combined with Vyvanse, these can increase the risk of serotonin syndrome—a potentially life-threatening condition. Many patients safely take both, but your doctor should monitor for symptoms like agitation, rapid heart rate, muscle rigidity, and fever.
• Tricyclic antidepressants: Drugs like amitriptyline and nortriptyline. Amphetamines can enhance the effects of tricyclics, and vice versa. Monitor for increased side effects.
• Blood pressure medications (antihypertensives): Vyvanse can raise blood pressure, potentially counteracting antihypertensive medications. Your doctor may need to adjust your blood pressure medication dose.
• CYP2D6 inhibitors: Drugs like paroxetine (Paxil) and quinidine can slow the metabolism of amphetamines, potentially increasing Vyvanse's effects and side effects.
• Acidifying agents: Medications and substances that lower urinary pH (such as ammonium chloride or large doses of vitamin C) can increase renal excretion of amphetamines, making Vyvanse less effective.
• Alkalinizing agents: Substances that raise urinary pH (such as sodium bicarbonate or antacids) can decrease renal excretion, potentially increasing amphetamine levels and side effects.
• Proton pump inhibitors (PPIs): Omeprazole (Prilosec), esomeprazole (Nexium), and other PPIs may affect the absorption of Vyvanse, though the clinical significance is generally mild.

Always consult your doctor or pharmacist before starting any new medication while taking Vyvanse.

Supplements and Over-the-Counter Drugs to Watch Out For

• St. John's Wort: This herbal supplement affects serotonin levels and can increase the risk of serotonin syndrome when combined with Vyvanse.
• Vitamin C (high doses): Large doses of vitamin C acidify urine and can reduce Vyvanse's effectiveness. Avoid taking large vitamin C supplements close to your Vyvanse dose.
• Decongestants (pseudoephedrine, phenylephrine): Found in many cold and allergy medications, these stimulants can add to Vyvanse's cardiovascular effects (increased heart rate and blood pressure).
• Melatonin: Generally considered safe to take with Vyvanse and may help with stimulant-related insomnia. However, discuss with your doctor first.

Food and Drink Interactions

• Alcohol: Avoid alcohol while taking Vyvanse. Alcohol can mask the stimulant effects of Vyvanse, leading to overconsumption of either substance. It also increases the risk of cardiovascular side effects and impaired judgment.
• Caffeine: Caffeine is a stimulant, and combining it with Vyvanse can amplify side effects like increased heart rate, anxiety, and insomnia. You don't have to eliminate caffeine entirely, but be mindful of your intake.
• Acidic foods and drinks: Highly acidic foods and beverages (orange juice, citrus fruits, sodas) consumed close to dosing time may reduce Vyvanse absorption. Take Vyvanse with water or neutral foods.
• Food timing: Vyvanse can be taken with or without food. Taking it with breakfast may help reduce nausea and is a good way to build the habit of morning dosing.

What to Tell Your Doctor

Before starting Vyvanse, make sure your doctor knows about:

• All medications you take — prescription, over-the-counter, and herbal supplements
• Any MAOIs you've taken in the past 14 days
• Your complete medical history — especially heart problems, high blood pressure, mental health conditions, thyroid issues, and any history of substance abuse
• Allergies — particularly to amphetamine products
• Pregnancy or breastfeeding status
• Any new symptoms after starting Vyvanse — especially rapid heartbeat, agitation, confusion, or fever, which could indicate an interaction

Final Thoughts

Drug interactions with Vyvanse are manageable when you and your healthcare team are aware of them. The most critical rule: never take Vyvanse with MAOIs. For everything else, communication with your doctor and pharmacist is key.

Your pharmacist is an excellent resource for checking interactions whenever you start a new medication. Don't hesitate to ask them.

For more about Vyvanse, see our guides on Vyvanse side effects, what Vyvanse is and how it's used, and how Vyvanse works. If you're having trouble finding Vyvanse at your pharmacy, Medfinder can help you check availability without calling around.