Major interaction on record — check this product against your medications before combining. Based on 14 of 15 ingredients. Check your meds →
Dietary supplement

Active-Male Brain Awake MAX3 + Nitric Oxide Booster Ingredients & Drug Interactions

by Irwin Naturals

Active-Male Brain Awake MAX3 + Nitric Oxide Booster label
See full label image
Softgel Capsule Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 23, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Active-Male Brain Awake MAX3 + Nitric Oxide Booster against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.

Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy

The interaction bottom line Most serious interaction: Major

Active-Male Brain Awake MAX3 + Nitric Oxide Booster is a dietary supplement by Irwin Naturals with 15 active ingredients. Its ingredients are commonly taken for morning sickness in pregnancy, premenstrual syndrome (pms), preventing or treating b6 deficiency.Based on those ingredients, 1,738 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Ginkgo biloba Leaf Extract, BioPerine, Ginger Rhizome Extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Active-Male Brain Awake MAX3 + Nitric Oxide Booster by Irwin Naturals

Ask about any prescription or over-the-counter medication and we check it for interactions with Active-Male Brain Awake MAX3 + Nitric Oxide Booster by Irwin Naturals — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Active-Male Brain Awake MAX3 + Nitric Oxide Booster by Irwin Naturals

Our pharmacy team’s full take, with four database checks built into the cards below — a summary of what is known, not a grade of the product itself.

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Jul 11, 2026

What’s inside

Partial disclosure
Ingredient Transparency · database check
Partial

Most active ingredients list an amount, but at least one is hidden in a blend or missing.

Why this rating?
  • The label discloses an exact amount for 12 of its 14 active ingredients.
  • “BioPerine Complex” is a proprietary blend — the label gives one combined amount (3 mg) without saying how much of each component you get.
  • “InnovaTea” is listed as a grouped ingredient — the label gives one combined amount (24 mg) without saying how much of each component you get.

This product contains 14 active ingredients. Vitamin B6 supports nerve health and is used for certain anemias and deficiency states.

L-citrulline is an amino acid that converts to arginine in your body and may support circulation. Vitamin D supports bone health and calcium absorption.

Vitamin B12 is essential for nerve and blood cell function. Ginger rhizome extract is used traditionally for nausea and inflammation.

Ginkgo biloba leaf extract is intended to support cognitive function and circulation. Phosphatidylserine is a phospholipid thought to support brain cell health.

BioPerine (black pepper extract) is included to enhance absorption of other ingredients. Acetyl-L-carnitine supports cellular energy and cognition.

Caffeine provides mental alertness and focus. Theanine (AlphaWave L-Theanine) is an amino acid that may promote calm focus.

Fish oil supplies omega-3 fatty acids for brain and heart health. Gotu kola and holy basil are herbal extracts traditionally used for stress and mental clarity.

The remaining ingredients are inactive fillers and capsule materials.

Does it work?

Moderate evidence
Evidence for Intended Use · database check
By FDA rules, dietary supplements can’t claim to treat, cure, or prevent disease — so labels speak in careful marketing language. We discern each product’s intended use from its name, label claims, and label statements, then grade the clinical evidence for that use. How these ratings are computed
Moderate

Some clinical evidence supports this product's ingredients for its stated purpose, but it isn't conclusive.

Why this rating?
  • The label markets this product for: focus, mental clarity and brain health support.
  • We looked for evidence on: Age-related cognitive decline, Attention, Anxiety, cognitive function, mental performance, brain fog.
  • The strongest evidence on file: Ginkgo is rated "Possibly Effective" for Anxiety (Natural Medicines).
  • Also on file: Acetyl-l-carnitine is rated "Possibly Effective" for Age-related cognitive decline.
  • Also on file: Phosphatidylserine is rated "Possibly Effective" for Age-related cognitive decline.

The evidence for what this product does is mixed. Vitamin B6 is effective for certain rare anemias and proven deficiency but only possibly effective for pregnancy nausea.

L-citrulline is possibly effective for athletic performance but insufficient evidence exists for heart disease or diabetes. Vitamin D is effective for specific bone and mineral disorders.

Vitamin B12 is effective for deficiency and certain neurological conditions. Ginger is possibly effective for pregnancy-related nausea and menstrual discomfort, but possibly ineffective for exercise soreness.

Ginkgo, phosphatidylserine, and acetyl-L-carnitine are each possibly effective for age-related cognitive decline and Alzheimer disease, though the evidence is modest. Caffeine is effective for mental alertness and athletic performance.

Theanine is possibly effective for cognitive function. Fish oil is effective for high triglycerides and possibly effective for heart failure.

The evidence for gotu kola, holy basil, and other uses is insufficient or shows possible ineffectiveness. Overall, this product is framed as a brain and nitric oxide booster, but the strongest evidence applies mainly to specific medical deficiencies rather than to enhancement in healthy people.

The evidence, ingredient by ingredient Vitamin B6 L-citrulline Vitamin D Vitamin B12 Ginger Black Pepper Ginkgo Phosphatidylserine

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

Adverse-effect, pregnancy, and general safety data are on file for most of these ingredients.

Why this rating?
  • We hold adverse-effect (side-effect) data for 14 of the 14 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 14 of 14.
  • General safety write-ups exist for 14 of 14.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most of these ingredients are generally well tolerated at typical doses. However, several safety concerns merit attention.

Vitamin B6 at high doses over time can damage nerves (sensory neuropathy), particularly with daily doses exceeding 1,000 mg or cumulative doses of 1,000 grams or more. L-citrulline and vitamin D are generally safe at recommended amounts, but L-citrulline has not been long-term studied, and vitamin D toxicity can occur with very high doses, causing calcium buildup in blood and tissues.

Ginkgo increases bleeding risk and may cause heart arrhythmias; it's not safe in pregnancy or while breastfeeding. Ginger at doses above 5 grams daily increases side effects and has rarely caused small bowel blockage.

Black pepper is safe in food amounts but concentrated supplements warrant caution. Caffeine can cause anxiety, insomnia, tremor, and at high doses, heart arrhythmia and stroke.

Acetyl-L-carnitine is generally tolerated short-term but long-term safety is unclear. Phosphatidylserine, theanine, gotu kola, and holy basil all lack sufficient pregnancy and breastfeeding safety data, so they should be avoided during these periods unless your doctor advises otherwise.

Fish oil at very high doses (over 3 grams daily) may suppress immune function and increase stroke risk.

Side effects, ingredient by ingredient Vitamin B6 L-citrulline Vitamin D Vitamin B12 Ginger Black Pepper Ginkgo Phosphatidylserine

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

At least one ingredient has a documented Major-severity interaction. Check your medications for a personalized result.

Why this rating?
  • 14 of the 14 matched ingredients can interact with medications — Ginkgo, Gotu Kola, Black Pepper, Acetyl-l-carnitine, Vitamin B12, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; seizure medications; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,739 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking this, double-check your medications against these drug types. Most critical: seizure medications (phenytoin, phenobarbital), blood thinners and antiplatelet drugs (warfarin, others), blood pressure medications, heart rhythm drugs (verapamil, diltiazem, digoxin, amiodarone), diabetes medications, statins, and any stimulants.

If you take ephedrine or any sympathomimetic, the caffeine here poses a Major risk. Also check with your pharmacist if you're on HIV drugs, immunosuppressants, thyroid hormone, antidepressants, anti-anxiety meds, or barbiturates.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glancePartially disclosed formula with some supporting evidence for its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

If you take any prescription medications—especially blood pressure drugs, blood thinners, seizure medications, statins, diabetes drugs, heart medications, or antidepressants—check each one against this product using the tool below before you start. The caffeine-ephedrine and ginkgo-talinolol interactions are serious.

This product is not intended to replace medical treatment. Talk to your pharmacist about whether the ingredients and doses match your health needs and medication list.

Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI

Assessment coverage: 14 of 14 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Mar 25, 2025.

This Scorecard evaluates available label information, ingredient evidence, and known medication-safety considerations. It does not independently verify product identity, purity, potency, contamination, or manufacturing quality. How these ratings are computed

At a glance

General information

Key facts about Active-Male Brain Awake MAX3 + Nitric Oxide Booster, straight from the product label.

Brand Irwin Naturals
Barcode (UPC) 840081402870
Net contents 60 Liquid Soft-Gel(s)
Market status On market
Date entered into DSLD Mar 25, 2025
DSLD ID 323275
Product type Other Combinations
Supplement form Softgel Capsule
Dietary claims / uses Nutrient, All Other, Structure/Function
Intended target group(s) Women (not pregnant or lactating), Adult Male (18-50 Years)
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Active-Male Brain Awake MAX3 + Nitric Oxide Booster by Irwin Naturals, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
3 Liquid Softgel(s)
Maximum serving Sizes:
3 Liquid Softgel(s)
Servings per container
20
UPC/BARCODE
840081402870
IngredientAmount% DV
Calories30 Calorie(s)--
Total Carbohydrates1 Gram(s)1%
Vitamin B65 mg294%
L-Citrulline750 mg--
Vitamin D1.4 mcg7%
Cholesterol20 mg7%
Total Fat2 Gram(s)2%
Vitamin B12108 mcg4500%
Protein3 Gram(s)--
BioPerine Complex3 mg--
Ginger Rhizome Extract0 NP--
Ginkgo biloba Leaf Extract60 mg--
Phosphatidylserine2.5 mg--
BioPerine0 NP--
Acetyl-L-Carnitine225 mg--
Caffeine23.52 mg--
AlphaWave L-Theanine45 mg--
Fish Oil1323 mg--
Gotu Kola herb extract12.5 mg--
Holy Basil Herb Extract100 mg--
InnovaTea24 mg--

Other ingredients: Gelatin, Water, Purified, Glycerin, Annatto, Beeswax, Mannitol, Sunflower Lecithin, Medium Chain Triglyceride Oil, Maltodextrin, Soy Lecithin, Titanium Dioxide, Silicon Dioxide

Tap any ingredient to jump to its full detail below.

Label statements
These statements are the manufacturer’s wording, reproduced from the product label — the label is saying it, not HelloPharmacist. We don’t verify or endorse them.
Formula

Active-Male Brain Awake MAX3 + Nitric Oxide Booster works fast to help promote focus, mental clarity and is specially formulated with a Nitric Oxide Booster to help optimize performance. The Nitric Oxide Boost comes in the form of L-Citrulline, an amino acid that converts to L-arginine in the body. L-Arginine can then be converted to Nitric Oxide. Nitric Oxide helps blood vessels relax and dilate, allowing for increased blood flow throughout the body. This formula also features Ginkgo extract, one of the best botanicals for the brain. Ginkgo extract can improve cognitive function and enhance memory in healthy individuals, as well as support overall blood flow to the brain. Patented BioPerine - Our special BioPerine Complex enhances the bioavailability, absorption and potency of many nutrients.

Formulation

Active-Male Brain Awake MAX3 + Nitric Oxide Booster can be used daily or as needed to support brain health and to help optimize performance and productivity. Delivering powerful brain-boosters and supportive ingredients that calm and nourish the central nervous system, this product helps to promote focus and mental clarity, while improving information retention and increasing feelings of energy. What makes us different: Liquid Soft-Gels - The nutrients in these easy-to-swallow liquid soft-gels are released fast. Other forms of delivery can contain binders and fillers that may cause stomach upset and offer no traditional value. Advanced Liquid Soft-Gels provide an optimum delivery system. Quality assurance - Irwin Naturals is committed to providing the highest quality products for your health. We employ compliance testing to ensure purity and potency.

Promotes focus & mental clarity The power of MAX3 1. Patented BioPerine Absorption 2. Fast-acting liquid soft-gels 3. Highly-specialized beneficial oils

No preservatives added.

General Statements

Global responsibility - Over the years we have donated to organizations that support the environment and the health of children.

Questions: Contact consumer affairs Weekdays 8:00 AM to 5:00 PM (PST) 100+ highly specialized products: www.IrwinNaturals.com

Full Disclosure Ingredient Panel

FDA Disclaimer Statement

These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.

Seals/Symbols

Pass Quality Tested Guaranteed

Precautions

Usage warnings: Do not use if safety seal is broken. This product contains an ingredient that may affect blood sugar. It is recommended to limit additional caffeine intake while taking this product. Individuals with low blood pressure should not take this product. Do not exceed recommended daily intake.

Check with your doctor before using this product and engaging in activity, if you are using medication, including anti-coagulants (blood thinners), or have any medical conditions, including heart disease or high/low blood pressure. Do not use if you may become pregnant, are pregnant or nursing.

Not intended for use by persons under 18. Keep out of reach of children.

Contains: Fish (anchovy, sardine), soy, tree nuts (coconut, palm kernel)

Storage

Store in a cool, dry place.

FDA Statement of Identity

Dietary Supplement

Suggested/Recommended/Usage/Directions

Directions: (Adults) Take three (3) liquid soft gels twice daily with a meal and a full glass (8oz) of water. If caffeine keeps you up at night, do not take this product in the evening since it contains natural caffeine.

Brand IP Statement(s)

BioPerine is a registered trademark of Sabinsa Corporation. Alphawave is a registered trademark ingredient from Ethical Naturals, Inc. InnovaTea is a registered trademark of NutriScience Innovations, LLC.

Is this label outdated? Report a formula or label change and our pharmacy team will review it.

See for yourself

Active-Male Brain Awake MAX3 + Nitric Oxide Booster by Irwin Naturals label

The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.

Active-Male Brain Awake MAX3 + Nitric Oxide Booster label

Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.

View the full label (PDF)
What’s inside

The Ingredients in Active-Male Brain Awake MAX3 + Nitric Oxide Booster by Irwin Naturals

These are the 15 active ingredients this product is made of. Select any to open its full monograph.

Serving size3 Liquid Softgel(s) Dosage formSoftgel Capsule Servings per container20 Amounts shown are per serving.

Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.

Vitamin B6

Interacts with
210 drugs
5 mg per serving Form: Pyridoxine Hydrochloride

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is b...

Vitamin B6 monograph & interactions

L-Citrulline

Interacts with
178 drugs
750 mg per serving

L-citrulline is an amino acid that the body turns into L-arginine to help make nitric oxide, which relaxes blood vessels and may improve blood flow. I...

L-Citrulline monograph & interactions

Vitamin D

Interacts with
715 drugs
1.4 mcg per serving

Vitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people,...

Vitamin D monograph & interactions

Vitamin B12

Interacts with
20 drugs
108 mcg per serving Form: Methylcobalamin

Vitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very h...

Vitamin B12 monograph & interactions

Protein

3 Gram(s) per serving

BioPerine Complex

3 mg per serving

Ginkgo biloba Leaf Extract

Interacts with
1,266 drugs
60 mg per serving

Ginkgo is one of the world's most popular herbal supplements, mostly taken to support memory and circulation. The evidence for these uses is mixed and...

Ginkgo biloba Leaf Extract monograph & interactions

Phosphatidylserine

Interacts with
219 drugs
2.5 mg per serving

Phosphatidylserine is a natural fat-like compound found in cell membranes, especially in the brain, and it is sold mainly to support memory and thinki...

Phosphatidylserine monograph & interactions

Acetyl-L-Carnitine

Interacts with
203 drugs
225 mg per serving Form: Acetyl-L-Carnitine Hydrochloride

Acetyl-L-carnitine is a form of the amino acid carnitine that the body uses to help produce energy in cells. It is most studied for nerve pain and mem...

Acetyl-L-Carnitine monograph & interactions

AlphaWave L-Theanine

Interacts with
565 drugs
45 mg per serving

Theanine (usually L-theanine) is an amino acid found naturally in tea leaves that many people take to feel calmer and less stressed without strong dro...

AlphaWave L-Theanine monograph & interactions

Fish Oil

Interacts with
327 drugs
1323 mg per serving Form: Anchovy, Sardine

Fish oil provides omega-3 fatty acids (EPA and DHA) that are best known for lowering high triglyceride levels. The evidence for other heart and health...

Fish Oil monograph & interactions

Gotu Kola herb extract

Interacts with
579 drugs
12.5 mg per serving

Gotu kola is a traditional Ayurvedic and Asian herb that people use for wound healing, circulation, skin problems, and as a calming or memory-supporti...

Gotu Kola herb extract monograph & interactions

Holy Basil Herb Extract

Interacts with
212 drugs
100 mg per serving Form: Ocimum tenuiflorum Herb Extract

Holy basil (tulsi) is a traditional Ayurvedic herb most often used today for stress and general wellness, but the human evidence is mostly small and p...

Holy Basil Herb Extract monograph & interactions

InnovaTea

24 mg per serving Form: Tea Extract, Natural

Other (inactive) ingredients: Gelatin, Water, Purified, Glycerin, Annatto, Beeswax, Mannitol, Sunflower Lecithin, Medium Chain Triglyceride Oil, Maltodextrin, Soy Lecithin, Titanium Dioxide, Silicon Dioxide. These complete the product’s ingredient list but are not active constituents.

Interaction report

Active-Male Brain Awake MAX3 + Nitric Oxide Booster by Irwin Naturals Drug Interactions

Want to check YOUR meds against Active-Male Brain Awake MAX3 + Nitric Oxide Booster?

Ask about interactions with your drugs in plain English — “Can I take it with lisinopril?” — and we find you the answer in seconds, ingredient by ingredient.

 Go to the checker
1,738Drugs
9 Major 1,716 Moderate 13 Minor

Ingredients driving the most interactions

Ginkgo biloba Leaf Extract 1,266
BioPerine 1,019
Ginger Rhizome Extract 1,007
Vitamin D 715
Caffeine 655

Individual Drug Interactions

The ingredients in Active-Male Brain Awake MAX3 + Nitric Oxide Booster interact with 1,738 drugs. Click any drug to see the details.

14 of the 15 ingredients in Active-Male Brain Awake MAX3 + Nitric Oxide Booster interact with drugs. Each result below shows which ingredient is responsible. Ginkgo biloba Leaf Extract BioPerine Ginger Rhizome Extract Vitamin D Caffeine Gotu Kola herb extract AlphaWave L-Theanine Fish Oil Phosphatidylserine Holy Basil Herb Extract Vitamin B6 Acetyl-L-Carnitine L-Citrulline Vitamin B12

Each ingredient & the kinds of drugs it affects

For each ingredient in Active-Male Brain Awake MAX3 + Nitric Oxide Booster with known interactions, here are the types of medications they can affect. Open any type for the detail — or search your exact drug in the checker above.

Ginkgo biloba Leaf Extract23 drug types · 1,266 drugs

Talinolol

Taking ginkgo with talinolol seems to increase blood levels of talinolol.
There is some evidence that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of talinolol by 36% in healthy male individuals. However, single doses of ginkgo do not seem to affect talinolol pharmacokinetics.

Likelihood Probable Evidence B
Alprazolam (Xanax)

Theoretically, ginkgo might decrease the levels and clinical effects of alprazolam.
In clinical research, ginkgo extract (Ginkgold) 120 mg twice daily seems to decrease alprazolam levels by about 17%. However, ginkgo does not appear to decrease the elimination half-life of alprazolam. This suggests that ginkgo is more likely to decrease absorption of alprazolam rather than induce hepatic metabolism of alprazolam.

Likelihood Probable Evidence B
Anticoagulant/Antiplatelet Drugs

Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin. Theoretically, ginkgo might increase the risk of bleeding if used with other anticoagulant or antiplatelet drugs.
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. Several case reports have documented serious bleeding events in patients taking ginkgo. However, population and clinical studies have produced mixed results. Some evidence shows that short-term use of ginkgo leaf does not significantly reduce platelet aggregation and blood clotting. A study in healthy males who took a specific ginkgo leaf extract (EGb 761) 160 mg twice daily for 7 days found no change in prothrombin time. An analysis of a large medical record database suggests that ginkgo increases the risk of a bleeding adverse event by 38% when taken concurrently with warfarin. It has been suggested that ginkgo has to be taken for at least 2-3 weeks to have a significant effect on platelet aggregation. However, a meta-analysis of 18 studies using standardized ginkgo extracts, 80-480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT. In addition, a single dose of ginkgo plus clopidogrel or ticlopidine does not seem to significantly increase bleeding time or platelet aggregation. Also, taking ginkgo leaf extract daily for 8 days in conjunction with rivaroxaban does not affect anti-factor Xa activity; however, this study did not evaluate bleeding time.

Likelihood Possible Evidence A
Anticonvulsants

Theoretically, ginkgo might reduce the effectiveness of anticonvulsants.
Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves. Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity. However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, taking ginkgo with antidiabetes drugs might alter the response to antidiabetes drugs.
Ginkgo leaf extract seems to alter insulin secretion and metabolism, and might affect blood glucose levels in people with type 2 diabetes. The effect of ginkgo seems to differ depending on the insulin and treatment status of the patient. In diet-controlled diabetes patients with hyperinsulinemia, taking ginkgo does not seem to significantly affect insulin or blood glucose levels. In patients with hyperinsulinemia who are treated with oral hypoglycemic agents, taking ginkgo seems to decrease insulin levels and increase blood glucose following an oral glucose tolerance test. Researchers speculate that this could be due to ginkgo-enhanced hepatic metabolism of insulin. In patients with pancreatic exhaustion, taking ginkgo seems to stimulate pancreatic beta-cells, resulting in increased insulin and C-peptide levels, but with no significant change in blood glucose levels in response to an oral glucose tolerance test.

Likelihood Possible Evidence B
Atorvastatin (Lipitor)

Theoretically, ginkgo might decrease the levels and clinical effects of atorvastatin.
In humans, intake of ginkgo extract appears to increase atorvastatin clearance, reducing the area under the curve of atorvastatin by 10% to 14% and the maximum concentration by 29%. However, this interaction does not appear to affect cholesterol synthesis and absorption. Further, a model in rats with hyperlipidemia suggests that administering ginkgo extract does not impact blood levels of atorvastatin and leads to lower total cholesterol, low-density lipoprotein cholesterol, and triglycerides when compared with rats given atorvastatin alone.

Likelihood Probable Evidence B
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, ginkgo might increase levels of drugs metabolized by CYP1A2.
Laboratory research suggests that ginkgo leaf extract can mildly inhibit CYP1A2 enzymes. However, clinical research suggests ginkgo might not affect CYP1A2. Until more is known, use ginkgo cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Possible Evidence B
Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP2C19.
Some clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce CYP2C19 enzymes and potentially decrease levels of drugs metabolized by these enzymes. However, other clinical research shows that taking ginkgo 120 mg twice daily for 12 days has no effect on levels of drugs metabolized by CYP2C19.

Likelihood Probable Evidence B
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, ginkgo might increase levels of drugs metabolized by CYP2C9.
In vitro, a specific standardized extract of ginkgo leaf (EGb 761) inhibits CYP2C9 activity . The terpenoid (ginkgolides) and flavonoid (quercetin, kaempferol, etc.) constituents seem to be responsible for this effect. Most ginkgo extracts contain some amount of these constituents. Therefore, other ginkgo leaf extracts might also inhibit the CYP2C9 enzyme. However, clinical research suggests that ginkgo might not have a significant effect on CYP2C9 in humans. Ginkgo does not seem to significantly affect the pharmacokinetics of CYP2C9 substrates diclofenac or tolbutamide.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, ginkgo might decrease levels of drugs metabolized by CYP3A4.
There is conflicting evidence about whether ginkgo induces or inhibits CYP3A4. Ginkgo does not appear to affect hepatic CYP3A4. However, it is not known if ginkgo affects intestinal CYP3A4. Preliminary clinical research suggests that taking ginkgo does not significantly affect levels of donepezil, lopinavir, or ritonavir, which are all CYP3A4 substrates. Other clinical research also suggests ginkgo does not significantly affect CYP3A4 activity. However, there are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4).

Likelihood Possible Evidence B
Efavirenz (Sustiva)

Theoretically, ginkgo might decrease the levels and clinical effects of efavirenz.
There are two case reports of decreased efavirenz concentrations and increased viral load in patients taking ginkgo. In one case, an HIV-positive male experienced over a 50% decrease in efavirenz levels over the course of 14 months while taking ginkgo extract. HIV-1 RNA copies also increased substantially, from less than 50 to more than 1500. It is suspected that terpenoids from the ginkgo extract reduced drug levels by inducing cytochrome P450 3A4 (CYP3A4). In another case report, a patient stable on antiviral therapy including efavirenz for 10 years, had an increase in viral load from <50 copies/mL to 1350 copies/mL after 2 months of taking a combination of supplements including ginkgo. After stopping ginkgo, the viral load was again controlled with the same antiviral therapy regimen.

Likelihood Possible Evidence D
Ibuprofen (Advil, Others)

Theoretically, ginkgo might increase the risk of bleeding when used with ibuprofen.
Ginkgo might have antiplatelet effects and has been associated with several case reports of spontaneous bleeding. In one case, a 71-year-old male had taken a specific ginkgo extract (Gingium, Biocur) 40 mg twice daily for 2.5 years. About 4 weeks after starting ibuprofen 600 mg daily he experienced a fatal intracerebral hemorrhage. However, the antiplatelet effects of ginkgo have been questioned. A meta-analysis and other studies have not found a significant antiplatelet effect with standardized ginkgo extracts, 80 mg to 480 mg taken daily for up to 32 weeks.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, taking ginkgo with P-glycoprotein substrates might increase the levels and adverse effects of these substrates.
A small clinical study in healthy volunteers shows that using ginkgo leaf extract 120 mg orally three times daily for 14 days can increase levels of the P-glycoprotein substrate, talinolol, by 36% in healthy male individuals. However, single doses of ginkgo do not have the same effect.

Likelihood Possible Evidence B
Risperidone (Risperdal)

Theoretically, taking ginkgo with risperidone might increase the levels and adverse effects of risperidone.
A single case of priapism has been reported for a 26-year-old male with schizophrenia who used risperidone 3 mg daily along with ginkgo extract 160 mg daily. Risperidone is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4. CYP3A4 activity might be affected by ginkgo. Theoretically, ginkgo may inhibit the metabolism of risperidone and increase the risk of adverse effects.

Likelihood Possible Evidence D
Rosiglitazone (Avandia)

Theoretically, ginkgo might decrease the levels and clinical effects of rosiglitazone.
Animal research shows that ginkgo leaf extract orally 100 or 200 mg/kg daily for 10 days alters the pharmacodynamics of rosiglitazone in a dose-dependent manner. The 100 mg/kg and 200 mg/kg doses reduce the area under the concentration time curve (AUC) of rosiglitazone by 39% and 52%, respectively, and the half-life by 28% and 39%, respectively. It is hypothesized that these changes may be due to induction of cytochrome P450 2C8 by ginkgo.

Likelihood Possible Evidence D
Seizure Threshold Lowering Drugs

Theoretically, taking ginkgo with drugs that lower the seizure threshold might increase the risk for convulsions.
Ginkgo seeds contain ginkgotoxin. Large amounts of ginkgotoxin can cause neurotoxicity and seizure. Ginkgotoxin is present in much larger amounts in ginkgo seeds than leaves. Ginkgo leaf extract contains trace amounts of ginkgotoxin. The amount of ginkgotoxin in ginkgo leaf and leaf extract seems unlikely to cause toxicity. However, there are anecdotal reports of seizure occurring after use of ginkgo leaf both in patients without a history of seizure disorder and in those with previously well-controlled epilepsy.

Likelihood Possible Evidence D
Simvastatin (Zocor)

Theoretically, ginkgo might decrease the levels and clinical effects of simvastatin.
Clinical research shows that taking ginkgo extract can reduce the area under the curve and maximum concentration of simvastatin by 32% to 39%. However, ginkgo extract does not seem to affect the cholesterol-lowering ability of simvastatin.

Likelihood Probable Evidence B
Sofosbuvir (Sovaldi)

Theoretically, ginkgo might increase the levels and clinical effects of sofosbuvir.
Animal research in rats shows that giving a ginkgo extract 25 mg/kg orally daily for 14 days increases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 11%, increases the half-life by 60%, and increases the plasma concentration at 4 hours by 38%. This interaction appears to be related to the inhibition of intestinal P-glycoprotein by ginkgo.

Likelihood Possible Evidence D
Tacrolimus (Prograf)

Theoretically, ginkgo might increase the blood levels of tacrolimus.
In vitro evidence suggests that certain biflavonoids in ginkgo leaves (i.e. amentoflavone, ginkgetin, bilobetin) may inhibit the metabolism of tacrolimus by up to 50%. This interaction appears to be time-dependent and due to inhibition of cytochrome P450 (CYP) 3A4 by these bioflavonoids. In rats given tacrolimus 1 mg/kg orally, amentoflavone was shown to increase the area under the concentration time curve (AUC) of tacrolimus by 3.8-fold.

Likelihood Possible Evidence D
Trazodone (Desyrel)

Theoretically, ginkgo might increase the levels and clinical effects of trazodone.
In a case report, an Alzheimer patient taking trazodone 20 mg twice daily and ginkgo leaf extract 80 mg twice daily for four doses became comatose. The coma was reversed by administration of flumazenil (Romazicon). Coma might have been induced by excessive GABA-ergic activity. Ginkgo flavonoids are thought to have GABA-ergic activity and act directly on benzodiazepine receptors. Ginkgo might also increase metabolism of trazodone to active GABA-ergic metabolites, possibly by inducing cytochrome P450 3A4 (CYP3A4) metabolism.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Ginkgo has been shown to increase the risk of bleeding in some people when taken with warfarin.
Several pharmacodynamic studies suggest that ginkgo inhibits platelet aggregation. It is thought that the ginkgo constituent, ginkgolide B, displaces platelet-activating factor (PAF) from its binding sites, decreasing blood coagulation. Several case reports have documented serious bleeding events in patients taking ginkgo. Information from a medical database suggests that when taken concurrently with warfarin, ginkgo increases the risk of a bleeding adverse event by 38%. There is also some evidence that ginkgo leaf extract can inhibit cytochrome P450 2C9, an enzyme that metabolizes warfarin. This could result in increased warfarin levels. However, population and clinical research has produced mixed results. Clinical research in healthy people suggests that ginkgo has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin. A meta-analysis of 18 studies using standardized ginkgo extracts, 80 mg to 480 mg daily for up to 32 weeks, did not find a significant effect on platelet aggregation, fibrinogen concentration, or PT/aPTT. There is also some preliminary clinical research that suggests ginkgo might not significantly increase the effects of warfarin in patients that have a stable INR.

Likelihood Possible Evidence B
Nifedipine (Procardia)

Theoretically, taking ginkgo with oral, but not intravenous, nifedipine might increase levels and adverse effects of nifedipine.
Animal research and some clinical evidence suggests that taking ginkgo leaf extract orally in combination with oral nifedipine might increase nifedipine levels and cause increased side effects, such as headaches, dizziness, and hot flushes. However, taking ginkgo orally does not seem to affect the pharmacokinetics of intravenous nifedipine.

Likelihood Possible Evidence B
Omeprazole (Prilosec)

Theoretically, taking ginkgo with omeprazole might decrease the levels and clinical effects of omeprazole.
Clinical research shows that a specific ginkgo leaf extract (Remembrance, Herbs Product LTD) 140 mg twice daily can induce cytochrome P450 (CYP) 2C19 enzymes and decrease levels of omeprazole by about 27% to 42%.

Likelihood Possible Evidence B
Ginkgo biloba Leaf Extract full monograph & interactions

BioPerine17 drug types · 1,019 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, black pepper might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit platelet aggregation. This has not been reported in humans.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, black pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal research shows that piperine, a constituent of black pepper, can reduce blood glucose levels. Monitor blood glucose levels closely. Dose adjustments might be necessary.

Likelihood Possible Evidence D
Atorvastatin (Lipitor)

Theoretically, black pepper might increase blood levels of atorvastatin.
Animal research shows that taking piperine, a constituent of black pepper, 35 mg/kg can increase the maximum serum concentration of atorvastatin three-fold. This has not been reported in humans.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, black pepper might increase the effects and side effects of cyclosporine.
In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine. This has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.
In vitro research suggests that some constituents of black pepper inhibit CYP2D6. This has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
In vitro research and pharmacokinetic simulation data suggest that piperine, a constituent of black pepper, as well as the pepper fruit seem to inhibit CYP3A4. This has not been reported in humans.

Likelihood Possible Evidence D
Lithium

Theoretically, black pepper might increase blood levels of lithium due to its diuretic effects. The dose of lithium might need to be reduced.
Black pepper is thought to have diuretic properties.

Likelihood Probable Evidence D
Nevirapine (Viramune)

Black pepper might increase blood levels of nevirapine.
Clinical research shows that piperine, a constituent of black pepper, increases the plasma concentration of nevirapine. However, no adverse effects were observed in this study.

Likelihood Probable Evidence D
P-Glycoprotein Substrates

Theoretically, black pepper might increase levels of P-glycoprotein substrates.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit P-glycoprotein.

Likelihood Possible Evidence D
Pentobarbital (Nembutal)

Theoretically, black pepper might increase the sedative effects of pentobarbital.
Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

Black pepper might increase blood levels of phenytoin.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption, slow elimination, and increase levels of phenytoin. Taking a single dose of black pepper 1 gram along with phenytoin seems to double the serum concentration of phenytoin. Consuming a soup with black pepper providing piperine 44 mg/200 mL of soup along with phenytoin also seems to increase phenytoin levels when compared with consuming the same soup without black pepper.

Likelihood Possible Evidence B
Propranolol (Inderal)

Black pepper might increase blood levels of propranolol.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol.

Likelihood Possible Evidence B
Rifampin (Rifadin)

Black pepper might increase blood levels of rifampin.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and serum levels of rifampin.

Likelihood Possible Evidence B
Theophylline

Black pepper might increase blood levels of theophylline.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of theophylline.

Likelihood Possible Evidence D
Amoxicillin (Amoxil, Trimox)

Theoretically, black pepper might increase the effects and side effects of amoxicillin.
Animal research shows that taking piperine, a constituent of black pepper, with amoxicillin increases plasma levels of amoxicillin. This has not been reported in humans.

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

Theoretically, black pepper might increase blood levels of carbamazepine, potentially increasing the effects and side effects of carbamazepine.
One clinical study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that taking a single 20 mg dose of purified piperine, a constituent of black pepper, increases carbamazepine levels. Piperine may increase carbamazepine absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or inhibiting cytochrome P450 3A4 (CYP3A4) in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects. In vitro research also shows that piperine can increase carbamazepine levels by 11% in a time-dependent manner.

Likelihood Possible Evidence B
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, black pepper might decrease levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that black pepper induces CYP1A2. This has not been reported in humans.

Likelihood Possible Evidence D
BioPerine full monograph & interactions

Ginger Rhizome Extract14 drug types · 1,007 drugs

Anticoagulant/Antiplatelet Drugs

Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation. However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials. Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.
Animal and human research suggests that ginger might increase insulin levels and/or decrease blood glucose levels.

Likelihood Possible Evidence D
Cytochrome P450 3A4 (Cyp3A4) Substrates

Ginger might increase or decrease the levels of CYP3A4 substrates.
In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity. Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration.
Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Losartan (Cozaar)

Theoretically, ginger might increase levels of losartan and the risk of hypotension.
In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan. It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.

Likelihood Possible Evidence D
Nifedipine (Procardia)

Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.
Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone.

Likelihood Possible Evidence B
P-Glycoprotein Substrates

Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.
In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates. Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration.

Likelihood Possible Evidence D
Phenprocoumon (Marcoumar, Others)

Ginger might increase the risk of bleeding with phenprocoumon.
Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Ginger might increase the risk of bleeding with warfarin.
Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation. In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin. In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen. A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months. However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin. Until more is known, monitor INRs closely in patients taking large amounts of ginger.

Likelihood Possible Evidence B
Calcium Channel Blockers

Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.
Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects. Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone.

Likelihood Unlikely Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.
In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time.

Likelihood Possible Evidence D
Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, ginger might increase the levels of CYP1A2 substrates.
In vitro research shows that ginger inhibits CYP1A2 activity. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2B6 (Cyp2B6) Substrates

Theoretically, ginger might increase the levels of CYP2B6 substrates.
In vitro research shows that ginger inhibits CYP2B6 activity. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2C9 (Cyp2C9) Substrates

Theoretically, ginger might increase the levels of CYP2C9 substrates.
In vitro research shows that ginger inhibits CYP2C9 activity. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Metronidazole (Flagyl)

Theoretically, ginger might increase levels of metronidazole.
In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced.

Likelihood Possible Evidence D
Ginger Rhizome Extract full monograph & interactions

Vitamin D8 drug types · 715 drugs

Aluminum

Vitamin D might increase aluminum absorption and toxicity, but this has only been reported in people with renal failure.
The protein that transports calcium across the intestinal wall can also bind and transport aluminum. This protein is stimulated by vitamin D, which may therefore increase aluminum absorption. This mechanism may contribute to increased aluminum levels and toxicity in people with renal failure, when they take vitamin D and aluminum-containing phosphate binders chronically.

Likelihood Probable Evidence B
Atorvastatin (Lipitor)

Vitamin D might reduce absorption of atorvastatin.
A small, low-quality clinical study shows that taking vitamin D reduces levels of atorvastatin and its active metabolites by up to 55%. However, while atorvastatin levels decreased, total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels did not substantially change. Atorvastatin is metabolized in the gut by CYP3A4 enzymes, and researchers theorized that vitamin D might induce CYP3A4, causing reduced levels of atorvastatin. However, this proposed mechanism was not specifically studied.

Likelihood Probable Evidence B
Calcipotriene (Dovonex)

Taking calcipotriene with vitamin D increases the risk for hypercalcemia.
Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia. Theoretically, combining calcipotriene with vitamin D supplements might increase the risk of hypercalcemia.

Likelihood Probable Evidence D
Digoxin (Lanoxin)

Theoretically, hypercalcemia induced by high-dose vitamin D can increase the risk of arrhythmia from digoxin.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and digoxin concurrently.

Likelihood Possible Evidence D
Diltiazem (Cardizem, Others)

Theoretically, hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of diltiazem for arrhythmia.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically this could also occur with diltiazem. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and diltiazem concurrently.

Likelihood Probable Evidence B
Thiazide Diuretics

Theoretically, taking thiazide diuretics and high-dose vitamin D can increase the risk of hypercalcemia.
Thiazide diuretics decrease urinary calcium excretion, which could lead to hypercalcemia if vitamin D supplements are taken concurrently. This has been reported in people being treated with vitamin D for hypoparathyroidism, and also in elderly people with normal parathyroid function who were taking a thiazide, vitamin D, and calcium-containing antacids daily.

Likelihood Probable Evidence D
Verapamil (Calan, Others)

Hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of verapamil for arrhythmia.
Hypercalcemia due to high doses of vitamin D can reduce the effectiveness of verapamil in atrial fibrillation. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and verapamil concurrently.

Likelihood Probable Evidence B
Cytochrome P450 3A4 (Cyp3A4) Substrates

Vitamin D might induce CYP3A4 enzymes and reduce the bioavailability of CYP3A4 substrates.
There is some concern that vitamin D might induce CYP3A4. In vitro research suggests that vitamin D induces CYP3A4 transcription. Additionally, observational research has found that increased UV light exposure and serum vitamin D levels are associated with decreased serum levels of CYP3A4 substrates such as tacrolimus and sirolimus, while no association between UV light exposure or vitamin D levels and levels of mycophenolic acid, a non-CYP3A4 substrate, was found. A small, low-quality clinical study shows that taking vitamin D reduces levels of the CYP3A4 substrate atorvastatin and its active metabolites by up to 55%; however, the clinical effects of atorvastatin were not reduced. While researchers theorized that vitamin D might induce CYP3A4, this proposed mechanism was not specifically studied.

Likelihood Possible Evidence D
Vitamin D full monograph & interactions

Caffeine41 drug types · 655 drugs

Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Use of ephedrine with caffeine can increase the risk of stimulatory adverse effects. There is evidence that using ephedrine with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction, stroke, seizures, and death.

Likelihood Probable Evidence D
Adenosine (Adenocard)

Theoretically, caffeine might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Some evidence shows that caffeine is a competitive inhibitor of adenosine and can reduce the vasodilatory effects of adenosine in humans. However, other research shows that caffeine does not seem to affect supplemental adenosine because high interstitial levels of adenosine overcome the antagonistic effects of caffeine. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. However, methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing.

Likelihood Possible Evidence B
Anticoagulant/Antiplatelet Drugs

Theoretically, caffeine may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Caffeine is reported to have antiplatelet activity. Theoretically, it might increase the risk of bleeding when used concomitantly with these agents; however, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

Theoretically, large amounts of caffeine might increase the cardiac inotropic effects of beta-agonists.

Likelihood Probable Evidence D
Carbamazepine (Tegretol)

Theoretically, caffeine might reduce the effects of carbamazepine and increase the risk for convulsions.
Animal research suggests that taking caffeine can lower the anticonvulsant effects of carbamazepine and can induce seizures when taken in doses above 400 mg/kg. Human research has shown that taking caffeine 300 mg in three divided doses along with carbamazepine 200 mg reduces the bioavailability of carbamazepine by 32% and prolongs the plasma half-life of carbamazepine 2-fold in healthy individuals.

Likelihood Possible Evidence D
Cimetidine (Tagamet)

Theoretically, cimetidine might increase the levels and adverse effects of caffeine.
Cimetidine decreases the rate of caffeine clearance by 31% to 42%.

Likelihood Likely Evidence B
Clozapine (Clozaril)

Caffeine might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Caffeine might increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg per day inhibit clozapine metabolism. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Although researchers speculate that caffeine might inhibit CYP1A2, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients more sensitive to an interaction between clozapine and caffeine. In one case report, severe, life-threatening clozapine toxicity and multiorgan system failure occurred in a patient with schizophrenia stabilized on clozapine who consumed caffeine 600 mg daily.

Likelihood Possible Evidence B
Dipyridamole (Persantine)

Theoretically, caffeine might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Caffeine inhibits dipyridamole-induced vasodilation. It is recommended that methylxanthines and methylxanthine-containing products be stopped 24 hours prior to pharmacological stress tests. Methylxanthines appear more likely to interfere with dipyridamole (Persantine) than adenosine-induced stress testing.

Likelihood Probable Evidence B
Disulfiram (Antabuse)

Theoretically, disulfiram use might increase the levels and adverse effects of caffeine.
Disulfiram decreases the rate of caffeine clearance.

Likelihood Probable Evidence B
Diuretic Drugs

Theoretically, using caffeine with diuretic drugs might increase the risk of hypokalemia.
Caffeine, especially in excessive amounts, can reduce potassium levels due to stimulation of the sodium-potassium pump. Diuretics can also cause lower potassium levels.

Likelihood Possible Evidence D
Estrogens

Theoretically, estrogens might increase the levels and adverse effects of caffeine.
Estrogen inhibits caffeine metabolism.

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

Theoretically, caffeine might reduce the effects of ethosuximide and increase the risk for convulsions.
Animal research suggests that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Felbamate (Felbatol)

Theoretically, caffeine might reduce the effects of felbamate and increase the risk for convulsions.
Animal research suggests that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Flutamide (Eulexin)

Theoretically, caffeine might increase the levels and adverse effects of flutamide.
In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide. However, this effect has not been reported in humans.

Likelihood Probable Evidence D
Fluvoxamine (Luvox)

Theoretically, fluvoxamine might increase the levels and adverse effects of caffeine.
Fluvoxamine reduces caffeine metabolism.

Likelihood Probable Evidence D
Lithium

Abrupt caffeine withdrawal might increase the levels and adverse effects of lithium.
Caffeine has diuretic activity. When abruptly discontinued, caffeine may alter the clearance of lithium. There are two case reports of lithium tremor that worsened upon abrupt coffee withdrawal and 6 case reports of elevated serum lithium levels after reducing or eliminating caffeine intake. In one case, a male with schizoaffective disorder stabilized on lithium had an elevated lithium level after reducing his caffeine intake by 87%. At a later date, he increased his caffeine intake by 6-fold, resulting in a subtherapeutic lithium level and a recurrence of psychiatric symptoms.

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Caffeine has been shown to inhibit monoamine oxidase (MAO) A and B in laboratory studies. Concomitant intake of large amounts of caffeine with MAOIs might precipitate a hypertensive crisis. In a case report, a patient that consumed 10-12 cups of caffeinated coffee and took the MAOI tranylcypromine presented with severe hypertension. Hypertension was resolved after the patient switched to drinking decaffeinated coffee.

Likelihood Possible Evidence D
Nicotine

Theoretically, concomitant use might increase the risk of hypertension.
Concomitant use of caffeine and nicotine has been shown to have additive cardiovascular effects, including increased heart rate and blood pressure. Blood pressure was increased by 10.8/12.4 mmHg when the agents were used concomitantly.

Likelihood Probable Evidence B
Pentobarbital (Nembutal)

Theoretically, caffeine might decrease the effects of pentobarbital.
Caffeine might negate the hypnotic effects of pentobarbital.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

Theoretically, caffeine might reduce the effects of phenobarbital and increase the risk for convulsions.
Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital. However, the exact mechanism of this interaction is unclear.

Likelihood Possible Evidence D
Phenylpropanolamine

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of caffeine.
Concomitant use of phenylpropanolamine and caffeine might cause an additive increase in blood pressure. Phenylpropanolamine also seems to increase caffeine serum levels.

Likelihood Probable Evidence B
Phenytoin (Dilantin)

Theoretically, caffeine might reduce the effects of phenytoin and increase the risk for convulsions.
Animal research suggests that caffeine can decrease the anticonvulsant activity of phenytoin. The effect does not seem to be related to the seizure threshold-lowering effects of caffeine. However, the exact mechanism of this interaction is unclear.

Likelihood Possible Evidence D
Pioglitazone (Actos)

Theoretically, caffeine might increase the levels and clinical effects of pioglitazone.
Animal research suggests that caffeine can modestly increase the maximum concentration, area under the curve, and half-life of pioglitazone, and also reduce its clearance. This increased the antidiabetic effects of pioglitazone. However, the exact mechanism of this interaction is unclear.

Likelihood Possible Evidence D
Quinolone Antibiotics

Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
Quinolones (also called fluoroquinolones) can decrease caffeine clearance by inhibiting cytochrome P450 1A2 (CYP1A2) enzyme.

Likelihood Probable Evidence B
Riluzole (Rilutek)

Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Caffeine and riluzole are both metabolized by cytochrome P450 1A2 (CYP1A2), and concomitant use might reduce the metabolism of one or both agents.

Likelihood Possible Evidence D
Caffeine full monograph & all 41 interactions

Gotu Kola herb extract2 drug types · 579 drugs

Cns Depressants

Theoretically, taking gotu kola might increase the sedative effects of CNS depressants.
In vitro research suggests that gotu kola may have sedative effects via binding of GABA receptors.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, taking gotu kola with hepatotoxic drugs might have additive adverse effects.
There are at least four case reports of hepatotoxicity associated with the use of gotu kola. However, more information is needed to determine if gotu kola was the causative factor in these cases.

Likelihood Possible Evidence D
Gotu Kola herb extract full monograph & interactions

AlphaWave L-Theanine3 drug types · 565 drugs

Antihypertensive Drugs

Theanine might lower blood pressure, potentiating the effects of antihypertensive drugs.
Animal research shows that theanine can lower blood pressure in spontaneously hypertensive animals. Theoretically, concomitant use of theanine and antihypertensive drugs might potentiate the antihypertensive activity.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, theanine might have additive sedative effects when used in conjunction with CNS depressants. However, it is unclear if this concern is clinically relevant.
Theoretically, theanine may compete with glutamate and/or increase plasma gamma-aminobutyric acid (GABA) levels, which could cause CNS depression. In one clinical study, some subjects taking oral theanine reported drowsiness.

Likelihood Unlikely Evidence D
Serotonergic Drugs

Clinical studies regarding the effects of L-theanine on serotonin levels are conflicting. Some studies suggest it can increase serotonin levels in the brain while others report that it may decrease them. Nevertheless, there have been no reports of l-theanine being a causative agent in serotonergic-related side effects or serotonin syndrome.

Likelihood Unlikely Evidence C
AlphaWave L-Theanine full monograph & interactions

Fish Oil9 drug types · 327 drugs

Antihypertensive Drugs

Theoretically, taking fish oil with antihypertensive drugs might increase the risk of hypotension.
Clinical evidence indicates that fish oils can modestly lower blood pressure and might have additive effects in patients treated with antihypertensives.

Likelihood Probable Evidence B
Contraceptive Drugs

Theoretically, taking fish oil with contraceptive drugs might decrease the triglyceride-lowering effects of fish oil.
There is some evidence that contraceptive drugs might interfere with the triglyceride lowering effects of fish oils.

Likelihood Probable Evidence B
Cyclosporine (Neoral, Sandimmune)

Taking fish oil with cyclosporine might increase levels and adverse effects of cyclosporine.
In kidney transplant recipients on a general immunosuppressive regimen, taking omega-3 fatty acids daily seems to increase peak blood levels of cyclosporine when compared with placebo. This increase was as much as 20% after one month. However, the area under the curve was not significantly affected.

Likelihood Probable Evidence B
Orlistat (Xenical, Alli)

Theoretically, taking fish oil with orlistat might decrease the absorption of fish oil fatty acids.
Orlistat binds lipase in the gastrointestinal tract and reduces fat absorption. Theoretically, taking fish oil with orlistat might decrease absorption of fish oil fatty acids. To avoid this potential interaction, recommend separating administration of orlistat and fish oil by at least 2 hours.

Likelihood Probable Evidence D
Sirolimus (Rapamune)

Taking fish oil with sirolimus might increase levels and adverse effects of sirolimus.
Pharmacokinetic research shows that omega-3 fatty acids increase exposure to sirolimus in kidney transplant patients on a calcineurin inhibitor-free immunosuppressive regimen. A 25% dose reduction in sirolimus was required to keep patients within the expected trough-concentration window. Researchers hypothesize that this may be due to inhibition of cytochrome P450 3A4 (CYP3A4) by fish oil, although this has not been confirmed in clinical research.

Likelihood Probable Evidence B
Tacrolimus (Prograf)

Taking fish oil with tacrolimus might increase levels and adverse effects of tacrolimus.
In a small group of patients, taking fish oil 2.6 grams (Omacor) daily for 4 weeks increased the 8-hour area under the curve of tacrolimus by 25% when compared with baseline. Peak levels were increased by approximately 22%. Researchers hypothesize that this may be due either to an increase in bioavailability or to inhibition of cytochrome P450 3A4 (CYP3A4) by fish oil, although this has not been confirmed in clinical research.

Likelihood Probable Evidence B
Anticoagulant/Antiplatelet Drugs

Fish oil may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, evidence is conflicting.
While fish oil may not be a potent inhibitor of platelet function, high doses of fish oil might have antiplatelet effects. Theoretically, concomitant use of fish oil with anticoagulant or antiplatelet drugs may increase the risk of bleeding. However, the most rigorous research shows that short-term doses of fish oil 10 grams daily or long-term doses of 1.5 grams daily for up to 52 weeks does not increase the risk of bleeding or affect coagulation parameters in chronically ill and vulnerable patients. Other controlled research shows that fish oil does not affect platelet function or increase the risk of bleeding. Some research even suggests that perioperative fish oil use decreases bleeding risk. Some research suggests fish oil does not have additive antiplatelet effects when combined with aspirin, but other clinical evidence suggests that adding fish oil to low-dose aspirin treatment increases antiplatelet effects in patients who are aspirin-resistant. Also, some clinical research seems to show that fish oil has additive antiplatelet effects when used with aspirin and clopidogrel compared to aspirin and clopidogrel alone.

Likelihood Unlikely Evidence B
Platinum Agents

Theoretically, taking fish oil with platinum agents can cause resistance to platinum agents, potentially decreasing their effectiveness.
Platinum-induced fatty acids (PIFAs) are fatty acids secreted from human and mouse stem cells when exposed to platinum-based chemotherapy. Animal research suggests that PIFAs cause resistance to chemotherapy by stimulating lysophospholipid production in the spleen, which interferes with the DNA damage caused by certain chemotherapy drugs. One PIFA, known as 16:4(n-3), has been found in both raw fish and some commercially available fish oil products. Mackerel and herring have high PIFA concentrations, while salmon and tuna have low PIFA concentrations. Levels of PIFA in commercial fish oil products ranged from 0.2- 5.7 microMol. Animal research shows that PIFA-containing fish oil products cause resistance to cisplatin, fluorouracil, irinotecan, and oxaliplatin. It is unclear if all commercially available fish oil products contain PIFAs. Additionally, it is argued that levels of PIFA found in some fish oil products are too low to be of clinical concern. Furthermore, a lack of chemotherapy resistance in countries with high fish intake, such as Greenland, Japan, and Norway, suggest that this interaction may not be clinically significant.

Likelihood Unlikely Evidence D
Warfarin (Coumadin)

Fish oil may have antiplatelet effects and might increase the risk of bleeding if used with warfarin.
Fish oil has antiplatelet effects at high doses. Case reports show elevated INR in patients taking warfarin and fish oil 1-2 grams daily. However, some clinical research shows that taking fish oil 3-6 grams daily does not significantly increase INR in patients taking warfarin.

Likelihood Unlikely Evidence B
Fish Oil full monograph & interactions

Phosphatidylserine2 drug types · 219 drugs

Anticholinergic Drugs

Theoretically, phosphatidylserine might decrease the effectiveness anticholinergic drugs.
Phosphatidylserine is thought to increase acetylcholine levels, which could theoretically interfere with the activity of anticholinergic agents.

Likelihood Possible Evidence B
Cholinergic Drugs

Theoretically, phosphatidylserine might have additive effects with cholinergic drugs.
Phosphatidylserine is thought to increase acetylcholine levels, which could theoretically lead to additive cholinergic effects when used with cholinergic drugs.

Likelihood Possible Evidence B
Phosphatidylserine full monograph & interactions

Holy Basil Herb Extract3 drug types · 212 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, holy basil seed oil might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
Animal research shows that holy basil seed oil can prolong bleeding time, possibly due to inhibition of platelet aggregation. However, it is not known if this occurs in humans.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, holy basil might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Small clinical studies show that taking holy basil can decrease fasting blood glucose and other measures of glycemic control in patients with type 2 diabetes.

Likelihood Possible Evidence B
Pentobarbital (Nembutal)

Theoretically, holy basil seed oil might increase the sedative effects of pentobarbital.
Animal research shows that holy basil seed oil increases pentobarbitone-induced sleeping time. However, it is not known if this occurs in humans or if this applies to other barbiturates or sedatives.

Likelihood Possible Evidence D
Holy Basil Herb Extract full monograph & interactions

Vitamin B65 drug types · 210 drugs

Amiodarone (Cordarone)

Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
Despite initial case reports suggesting that pyridoxine may have a protective effect against amiodarone-induced photosensitivity, preliminary clinical research suggests that pyridoxine may actually exacerbate this adverse effect.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure. Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenobarbital, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenobarbital to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenytoin, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenytoin to avoid high doses of vitamin B6.

Likelihood Possible Evidence D
Levodopa

Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people.

Likelihood Unlikely Evidence D
Vitamin B6 full monograph & interactions

Acetyl-L-Carnitine4 drug types · 203 drugs

Acenocoumarol (Sintrom)

Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of acenocoumarol.
L-carnitine, the parent compound of acetyl-L-carnitine, might enhance the anticoagulant effects of acenocoumarol, an oral anticoagulant that is similar to warfarin, but shorter-acting. There are at least two case reports of INR elevation when L-carnitine was taken with acenocoumarol. In one case, a 33-year-old male with a previously stable INR had an elevated INR of 4.65 after L-carnitine was started and continued for 10 weeks. INR normalized after discontinuation of the L-carnitine-containing product. It is unclear if such an interaction would also occur with acetyl-L-carnitine.

Likelihood Possible Evidence D
Serotonergic Drugs

Theoretically, acetyl-L-carnitine might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders, when taken with serotonergic drugs.
Animal research shows that acetyl-L-carnitine can increase levels of serotonin in the brain.

Likelihood Possible Evidence D
Thyroid Hormone

Theoretically, acetyl-L-carnitine might decrease the effectiveness of thyroid hormone replacement.
L-carnitine appears to act as a peripheral thyroid hormone antagonist by inhibiting entry of thyroid hormone into the nucleus of cells. Taking L-carnitine also seems to diminish some of the symptoms of hyperthyroidism. It is unclear if such an interaction would occur with acetyl-L-carnitine.

Likelihood Probable Evidence B
Warfarin (Coumadin)

Theoretically, acetyl-L-carnitine might increase the anticoagulant effects of warfarin.
L-carnitine, the parent compound of acetyl-L-carnitine, might increase the anticoagulant effects of acenocoumarol, a shorter-acting oral anticoagulant similar to warfarin. There is not enough information to know whether this interaction occurs with acetyl-L-carnitine and warfarin.

Likelihood Possible Evidence D
Acetyl-L-Carnitine full monograph & interactions

L-Citrulline2 drug types · 178 drugs

Antihypertensive Drugs

Theoretically, concomitant use of L-citrulline with antihypertensive drugs might have additive effects and increase the chance of hypotension.
L-citrulline is converted to L-arginine, which can increase nitric oxide and cause vasodilation. However, a meta-analysis of 5 small clinical studies suggests that taking L-citrulline 3-6 grams daily for 1-8 weeks does not lower blood pressure when compared with control.

Likelihood Possible Evidence B
Phosphodiesterase-5 Inhibitors

Theoretically, concurrent use of phosphodiesterase-5 (PDE-5) inhibitors and L-citrulline might result in additive vasodilation.
L-citrulline is converted to L-arginine, which can increase nitric oxide and cause vasodilation. Theoretically, taking L-arginine with PDE-5 inhibitors might have additive vasodilatory and hypotensive effects. However, in studies evaluating the combined use of L-arginine and sildenafil for erectile dysfunction, hypotension was not reported.

Likelihood Possible Evidence D
L-Citrulline full monograph & interactions

Vitamin B121 drug type · 20 drugs

Metformin (Glucophage)

Metformin, a common medication used to manage type 2 diabetes, has been associated with lower vitamin B12 levels in some individuals. Prolonged use of metformin can interfere with the absorption of B12 in the digestive system, potentially leading to a deficiency in this essential vitamin.

Likelihood Possible Evidence A
Vitamin B12 full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Active-Male Brain Awake MAX3 + Nitric Oxide Booster, from the product label.

Irwin Naturals

See all Irwin Naturals products
Name
Irwin Naturals
Street Address
5310 Beethoven Street
City
Los Angeles
State
CA
ZipCode
90066
Phone Number
1-800-297-3273
Web Address
www.IrwinNaturals.com
Pharmacist Counseling Corner

Active-Male Brain Awake MAX3 + Nitric Oxide Booster by Irwin Naturals: Common Questions

Does Active-Male Brain Awake MAX3 + Nitric Oxide Booster by Irwin Naturals interact with any medications?
Yes. Based on its ingredients, Active-Male Brain Awake MAX3 + Nitric Oxide Booster has a known interaction with 1,738 medications, including 9 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Active-Male Brain Awake MAX3 + Nitric Oxide Booster contains 15 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Is this safe to take during pregnancy?
Several ingredients lack sufficient safety data in pregnancy: ginkgo, phosphatidylserine, theanine, gotu kola, and holy basil are all best avoided. L-citrulline also advises against use. Vitamin B6 and ginger are sometimes used for morning sickness but only under a doctor's supervision. Talk with your OB or pharmacist before taking any new supplement during pregnancy.
Does this actually boost nitric oxide?
L-citrulline is converted to arginine in the body and does increase nitric oxide, which dilates blood vessels. However, the clinical evidence for real improvements in circulation or sexual function at the dose in this product is limited. The evidence for 'brain awake' effects from the cognitive ingredients is also modest—mostly showing possible benefits rather than proven ones.
What are the most common side effects?
Caffeine may cause anxiety, insomnia, jitteriness, headache, or nausea. Ginger and fish oil commonly cause heartburn or stomach upset. Ginkgo may cause dizziness or mild gastrointestinal discomfort. Vitamin B6, phosphatidylserine, and acetyl-L-carnitine can each cause headache or nausea. Most people tolerate the ingredients without problems, but side effects depend on individual sensitivity and the dose.
Can I take this with my blood pressure medication?
No, not without checking first. L-citrulline, vitamin B6, vitamin D, theanine, and fish oil all theoretically lower blood pressure, so taking them together with your medication could cause your pressure to drop too far. Your pharmacist can review your specific drug and dose to advise whether it's safe.
Is there caffeine in this, and how much?
Yes, this product contains caffeine as listed in the active ingredients. The product facts provided do not specify the exact dose per capsule, so check the label. If you're sensitive to caffeine or take other stimulants, this is important to know.
Does this interfere with blood thinners like warfarin?
Yes, potentially. Ginkgo, ginger, acetyl-L-carnitine, and fish oil at high doses all carry documented risks of increasing bleeding when combined with warfarin or other anticoagulants. If you take a blood thinner, do not start this product without talking to your pharmacist or doctor.

Written and reviewed by the HelloPharmacist editorial staff. Our editorial policy

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Active-Male Brain Awake MAX3 + Nitric Oxide Booster label
Go deeper

The Full Monographs Behind Active-Male Brain Awake MAX3 + Nitric Oxide Booster’s Ingredients

Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.

Herb & supplement monograph

Vitamin B6

Interacts with 210 drugs

Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is best known for helping with pregnancy-rel...

Read the full Vitamin B6 monograph → Herb & supplement monograph

L-citrulline

Interacts with 178 drugs

L-citrulline is an amino acid that the body turns into L-arginine to help make nitric oxide, which relaxes blood vessels and may improve blood flow. It is popular for exercise performance an...

Read the full L-citrulline monograph → Herb & supplement monograph

Vitamin D

Interacts with 715 drugs

Vitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people, especially those with low sun exposure,...

Read the full Vitamin D monograph → Herb & supplement monograph

Vitamin B12

Interacts with 20 drugs

Vitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very helpful for people who are deficient — su...

Read the full Vitamin B12 monograph → Herb & supplement monograph

Ginger

Interacts with 1,007 drugs

Ginger is a widely used culinary spice with a long history in traditional medicine, and it has the strongest evidence for helping with nausea and vomiting, including from motion sickness, pr...

Read the full Ginger monograph → Herb & supplement monograph

Black Pepper

Interacts with 1,019 drugs

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to help the body absorb other ingredients (li...

Read the full Black Pepper monograph → Herb & supplement monograph

Ginkgo

Interacts with 1,266 drugs

Ginkgo is one of the world's most popular herbal supplements, mostly taken to support memory and circulation. The evidence for these uses is mixed and generally weak, and it is not proven to...

Read the full Ginkgo monograph → Herb & supplement monograph

Phosphatidylserine

Interacts with 219 drugs

Phosphatidylserine is a natural fat-like compound found in cell membranes, especially in the brain, and it is sold mainly to support memory and thinking. Some research suggests possible bene...

Read the full Phosphatidylserine monograph → Herb & supplement monograph

Acetyl-l-carnitine

Interacts with 203 drugs

Acetyl-L-carnitine is a form of the amino acid carnitine that the body uses to help produce energy in cells. It is most studied for nerve pain and memory-related conditions, though the evide...

Read the full Acetyl-l-carnitine monograph → Herb & supplement monograph

Theanine

Interacts with 565 drugs

Theanine (usually L-theanine) is an amino acid found naturally in tea leaves that many people take to feel calmer and less stressed without strong drowsiness. Early research suggests it may...

Read the full Theanine monograph → Herb & supplement monograph

Fish Oil

Interacts with 327 drugs

Fish oil provides omega-3 fatty acids (EPA and DHA) that are best known for lowering high triglyceride levels. The evidence for other heart and health benefits is mixed, and it is generally...

Read the full Fish Oil monograph → Herb & supplement monograph

Gotu Kola

Interacts with 579 drugs

Gotu kola is a traditional Ayurvedic and Asian herb that people use for wound healing, circulation, skin problems, and as a calming or memory-supporting herb. Some early studies suggest poss...

Read the full Gotu Kola monograph → Herb & supplement monograph

Holy Basil

Interacts with 212 drugs

Holy basil (tulsi) is a traditional Ayurvedic herb most often used today for stress and general wellness, but the human evidence is mostly small and preliminary. It is generally well tolerat...

Read the full Holy Basil monograph → Herb & supplement monograph

Caffeine

Interacts with 655 drugs

Caffeine is a natural stimulant found in coffee, tea, and many other plants and products. In moderate amounts it can boost alertness and reduce tiredness for most healthy adults, but too muc...

Read the full Caffeine monograph →
Sources

Sources & How We Checked

Active-Male Brain Awake MAX3 + Nitric Oxide Booster's label data comes from the NIH Dietary Supplement Label Database; the ingredient interaction data is from the Natural Medicines database, reviewed by our pharmacists.

Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.

The 742 references behind this product’s interaction data

Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.

Vitamin B6 32 references
  1. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Geerling BJ, Dagnelie PC, Badart-Smook A, et al. Diet as a risk factor for the development of ulcerative colitis. Am J Gastroenterol 2000;95:1008-13. PubMed
  4. South M. Neonatal seizures after pyridoxine use -- reply. Lancet 1999;354:2083. PubMed
  5. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  6. Baxter P, Aicardi J. Neonatal seizures after pyridoxine use. Lancet 1999;354:2082-3. PubMed
  7. Bendich A, Cohen M. Vitamin B6 safety issues. Ann N Y Acad Sci 1990;585:321-30.
  8. Schaumburg H, Kaplan J, Windebank A. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983;309:445-8. PubMed
  9. Gordon N. Pyridoxine dependency: an update. Dev Med Child Neurol 1997;39:63-5. PubMed
  10. Lewis PJ. Pain in the hand and wrist. Pyridoxine supplements may help patients with carpal tunnel syndrome. BMJ 1995;310:1534. PubMed
  11. Kaufman G. Pyridoxine against amiodarone-induced photosensitivity (letter). Lancet 1984;1:51-2. PubMed
  12. Mulrow JP, Mulrow CD, McKenna WJ. Pyridoxine and amiodarone-induced photosensitivity. Ann Intern Med 1985;103:68-9. PubMed
  13. Kawada A, Kashima A, Shiraishi H, et al. Pyridoxine-induced photosensitivity and hypophosphatasia. Dermatology 2000;201:356-60.. PubMed
  14. Vasile A, Goldberg R, Kornberg B. Pyridoxine toxicity: report of a case. J Am Osteopath Assoc 1984;83:790-1. DOI
  15. Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256. DOI
  16. Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15:484-5..
  17. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 2007;90:15-20.
  18. Hatzitolios, A., Iliadis, F., Katsiki, N., and Baltatzi, M. Is the anti-hypertensive effect of dietary supplements via aldehydes reduction evidence based? A systematic review. Clin Exp.Hypertens. 2008;30(7):628-639. PubMed
  19. Vasdev, S., Ford, C. A., Parai, S., Longerich, L., and Gadag, V. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Mol.Cell Biochem. 1999;200(1-2):155-162.
  20. de, Vogel S., Dindore, V., van, Engeland M., Goldbohm, R. A., van den Brandt, P. A., and Weijenberg, M. P. Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 2008;138(12):2372-2378. PubMed
  21. Hagen, I., Nesheim, B. I., and Tuntland, T. No effect of vitamin B-6 against premenstrual tension. A controlled clinical study. Acta Obstet.Gynecol.Scand. 1985;64(8):667-670. PubMed
  22. Aybak, M., Sermet, A., Ayyildiz, M. O., and Karakilcik, A. Z. Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension. Arzneimittelforschung. 1995;45(12):1271-1273.
  23. Lal, K. J., Dakshinamurti, K., and Thliveris, J. The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension. J Hypertens. 1996;14(3):355-363. PubMed
  24. Lauritzen CH, Reuter HD, Repges R, Bohnert K, and Schmidt U. Treatment of premenstrual tension syndrome with Vitex agnus castus. Controlled, double-blind study versus pyridoxine. Phytomed 1997;4(3):183-189. PubMed
  25. Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: A randomized trial. Am J Med 2013;126(2):141-9. PubMed
  26. Hankey GJ, Eikelboom JW, Yi Q, et al. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: Results of a randomized placebo-controlled trial. Stroke 2012;43(6):1572-7. PubMed
  27. Hoyer-Kuhn H, Kohbrok S, Volland R, Franklin J, Hero B, Beck BB, Hoppe B. Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice. Clin J Am Soc Nephrol. 2014 Mar;9(3):468-77. PubMed
  28. Mahmoud A, Tabassum S, Al Enazi S, et al. Amelioration of levetiracetam-induced behavioral side effects by pyridoxine. A randomized double blind controlled study. Pediatr Neurol 2021;119:15-21. PubMed
  29. Gupta M, Gallante B, Bamberger JN, et al. Prospective randomized evaluation of idiopathic hyperoxaluria treatments. J Endourol 2021;35(12):1844-1851. PubMed
  30. Li H, Chen M, Liang S, et al. Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement. Clin Nutr 2021;40(4):2293-2300. PubMed
  31. Tanigawa J, Nabatame S, Tominaga K, et al. High-dose pyridoxine treatment for inherited glycosylphosphatidylinositol deficiency. Brain Dev 2021;43(6):680-687. PubMed
  32. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed

See these in context on the Vitamin B6 monograph →

L-citrulline 8 references
  1. Cheng JW, Balwin SN. L-arginine in the management of cardiovascular diseases. Ann Pharmacother 2001;35:755-64. PubMed
  2. Schwedhelm E, Maas R, Freese R, et al. Pharmacokinetic and pharmacodynamic properties of oral L-citrulline and L-arginine: impact on nitric oxide metabolism. Br J Clin Pharmacol 2008;65:51-9. PubMed
  3. Romero MJ, Platt DH, Caldwell RB, Caldwell RW. Therapeutic use of citrulline in cardiovascular disease. Cardiovasc Drug Rev 2006;24:275-90. PubMed
  4. Balderas-Munoz K, Castillo-Martínez L, Orea-Tejeda A, et al. Improvement of ventricular function in systolic heart failure patients with oral L-citrulline supplementation. Cardiol J 2012;19:612-7. PubMed
  5. Sharif Kashani B, Tahmaseb Pour P, Malekmohammad M, et al. Oral l-citrulline malate in patients with idiopathic pulmonary arterial hypertension and Eisenmenger Syndrome: a clinical trial. J Cardiol 2014;64:231-5. PubMed
  6. Pérez-Guisado J, Jakeman PM. Citrulline malate enhances athletic anaerobic performance and relieves muscle soreness. J Strength Cond Res 2010;24:1215-22. PubMed
  7. Mirenayat MS, Moradi S, Mohammadi H, Rouhani MH. Effect of L-citrulline supplementation on blood pressure: a systematic review and meta-analysis of clinical trials. Curr Hypertens Rep. 2018;20(11):98. PubMed
  8. Xu Z, Liu C, Liu S, Zhou Z. Comparison of efficacy and safety of daily oral L-arginine and PDE5Is alone or combination in treating erectile dysfunction: A systematic review and meta-analysis of randomised controlled trials. Andrologia. 2021:e14007. PubMed

See these in context on the L-citrulline monograph →

Vitamin D 26 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999.
  3. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med 2001;345:66-7. PubMed
  4. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  5. Demontis R, Leflon A, Fournier A, et al. 1 alpha(OH) vitamin D3 increases plasma aluminum in hemodialyzed patients taking AI(OH)3. Clin Nephrol 1986;26:146-9.
  6. Crowe M, Wollner L, Griffiths RA. Hypercalcemia following vitamin D and thiazide therapy in the elderly. Practitioner 1984;228:312-3.
  7. Parfitt AM. Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism. Ann Intern Med 1972;77:557-63. PubMed
  8. Thiazide diuretics and the risk of osteoporosis. Pharmacist's Letter/Prescriber's Letter 2003;19(11):191105.
  9. Moon J. The role of vitamin D in toxic metal absorption. J Am Coll Nutr 1994;13:559-64.
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Ginger 64 references
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Ginkgo 97 references
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See these in context on the Acetyl-l-carnitine monograph →

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Gotu Kola 18 references
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Holy Basil 8 references
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DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

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