Major interaction on record — check this product against your medications before combining. Based on 14 of 40 ingredients. Check your meds →
Dietary supplement

Shotgun 5X Watermelon Ingredients & Drug Interactions

by VPX

Shotgun 5X Watermelon label
See full label image
Powder Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 9, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Shotgun 5X Watermelon 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

Shotgun 5X Watermelon is a dietary supplement by VPX with 40 active ingredients. Its ingredients are commonly taken for morning sickness in pregnancy, premenstrual syndrome (pms), preventing or treating b6 deficiency.Based on those ingredients, 880 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Caffeine Anhydrous, L-Arginine, Vitamin B6. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Shotgun 5X Watermelon by VPX

Ask about any prescription or over-the-counter medication and we check it for interactions with Shotgun 5X Watermelon by VPX — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
Prefer a human? Send your question to our licensed pharmacists — free, answered by email within 24 hours.

HelloPharmacist Scorecard of Shotgun 5X Watermelon by VPX

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 Sep 10, 2026

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

Most active ingredients don't disclose an individual amount — you can't tell how much of each you're getting.

Why this rating?
  • The label discloses an exact amount for 4 of its 39 active ingredients.
  • “Protein Hydrolysate Matrix” is a proprietary blend — the label gives one combined amount (3.50 Gram(s)) without saying how much of each component you get.
  • “Proprietary Branched Chain Ethyl Ester Amino Acid Matrix” is a proprietary blend — the label gives one combined amount (6.16 Gram(s)) without saying how much of each component you get.
  • “Power, Speed, Strength and Endurance Matrix” is a proprietary blend — the label gives one combined amount (3.17 Gram(s)) without saying how much of each component you get.

Shotgun 5X Watermelon is a 39-ingredient pre-workout powder centered on branched-chain amino acids (BCAAs: leucine, isoleucine, valine), creatine, and supporting amino acids meant to boost athletic performance. The active ingredients include three forms of creatine (monohydrate, gluconate, magnesium chelate) for muscle strength; whey protein isolate and hydrolysate for protein; L-arginine, L-citrulline malate, and their derivatives for vasodilation and blood flow; beta-alanine (and beta-alanine ethyl ester) for muscle endurance; caffeine anhydrous for energy and alertness; L-tyrosine for focus; and micronutrients like vitamin B6, sodium, and calcium.

Inactive ingredients include malic acid, sucralose (sweetener), citric acid, natural and artificial flavors, and glycine.

Does it work?

Strong 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
Strong

Clinical evidence supports at least one of this product's ingredients for its stated purpose.

Why this rating?
  • The label markets this product for: increases muscle gene proteins and athletic performance.
  • We looked for evidence on: Athletic performance, Cerebral creatine deficiency syndromes, muscle strength, muscle hypertrophy, exercise performance.
  • The strongest evidence on file: Caffeine is rated "Likely Effective" for Athletic performance (Natural Medicines).
  • Also on file: Whey Protein is rated "Possibly Effective" for Athletic performance.
  • Also on file: Creatine is rated "Possibly Effective" for Athletic performance, Muscle strength, Cerebral creatine deficiency syndromes.

Evidence for this product's individual ingredients shows mixed support. Creatine is rated possibly effective for muscle strength and athletic performance, and L-arginine and L-citrulline are rated possibly effective for athletic performance.

Beta-alanine is rated possibly effective for athletic performance and physical performance. Caffeine is rated likely effective for mental alertness and athletic performance.

Whey protein is rated possibly effective for athletic performance. L-tyrosine is rated possibly effective for cognitive function and memory, though not for athletic performance (rated possibly ineffective).

Vitamin B6 is rated effective for certain medical conditions like sideroblastic anemia but lacks a specific sports-performance rating in our data. Sodium and calcium have effectiveness ratings for various medical uses, not athletic performance per se.

Overall, the product combines ingredients with established and preliminary support for muscle and athletic goals, though you should check the individual ingredient evidence for what matters to you.

The evidence, ingredient by ingredient Vitamin B6 Sodium Calcium Whey Protein Casein Peptides L-arginine Histidine Beta-alanine

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 12 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 active ingredients here are generally well tolerated at standard doses in healthy adults. Creatine is well tolerated but can cause water retention, muscle cramps, and dehydration; those with kidney disease should be cautious.

Beta-alanine commonly causes harmless tingling (paresthesia) and flushing of the skin, starting on the scalp within 20 minutes and lasting about an hour—this is dose-dependent and often mild at lower amounts. Caffeine at moderate amounts is generally safe but can cause anxiety, insomnia, tremor, and headache; high doses carry rare risk of stroke.

Whey protein is generally well tolerated but can trigger or worsen acne in some people, especially teens and young adults; a small number of users have reported bloating, cramps, nausea, or diarrhea. L-arginine and L-tyrosine are generally well tolerated orally but can cause headache, nausea, and GI upset.

Vitamin B6 is safe at normal and recommended doses, but high chronic doses (over 1000 mg daily total or cumulative doses of 1000+ grams) can cause nerve damage (sensory neuropathy), though this can occur at lower doses too. Sodium and calcium are essential nutrients but high intakes carry risks (high blood pressure, kidney strain, bone effects, and cancer risk in population studies).

Side effects, ingredient by ingredient Vitamin B6 Sodium Calcium Whey Protein Casein Peptides L-arginine Histidine Beta-alanine

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?
  • 11 of the 14 matched ingredients can interact with medications — Calcium, Barley, Whey Protein, Potassium, L-arginine, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 880 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 Shotgun 5X Watermelon, double-check with your doctor or pharmacist if you take HIV medications (especially dolutegravir, elvitegravir, raltegravir—Major severity with calcium), blood pressure medications (antihypertensives, ACE inhibitors, ARBs—interactions from vitamin B6, sodium, L-arginine, L-citrulline), Parkinson medication (levodopa—Major severity from whey protein), ephedrine (Major severity from caffeine), heart/blood vessel drugs (sildenafil, diltiazem, sotalol, isoproterenol—Moderate from L-arginine and L-citrulline), blood thinners (anticoagulant/antiplatelet drugs—Moderate from L-arginine), diabetes drugs (antidiabetes medications—Moderate from L-arginine), thyroid medication (levothyroxine—Moderate from calcium; thyroid hormone—Moderate from L-tyrosine), antibiotic or anti-seizure medications (quinolones, tetracyclines, phenytoin, phenobarbital, carbamazepine), or lithium. No interactions are documented for the ingredients we could not check.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFormula with limited ingredient disclosure with clinical evidence supporting its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

This is a pre-workout powder built for athletes and active people aiming to boost strength, endurance, and focus. If you're taking any blood pressure medications, diabetes drugs, HIV antiretrovirals, heart medications, thyroid pills, blood thinners, or Parkinson medication, you need to check your exact drug list with your doctor or pharmacist before using it—several ingredients here can reduce those medications' effectiveness or cause dangerous blood pressure drops.

People with kidney disease should be cautious with creatine. Expect harmless tingling and skin flushing from beta-alanine, and possible acne or GI upset from whey.

Talk it over with your own healthcare provider before you start, especially if you take any prescription drugs.

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

Assessment coverage: 21 of 39 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Mar 25, 2015.

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 Shotgun 5X Watermelon, straight from the product label.

Brand VPX
Barcode (UPC) 610764860941
Net contents 1.26 lb; 574 Gram(s)
Market status On market
Date entered into DSLD Mar 25, 2015
DSLD ID 42145
Product type Other Combinations
Supplement form Powder
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten Free
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 Shotgun 5X Watermelon by VPX, 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:
20.5 Gram(s)
Maximum serving Sizes:
20.5 Gram(s)
Servings per container
28
UPC/BARCODE
610764860941
IngredientAmount% DV
Calories56 {Calories}--
Vitamin B6100 mcg5%
Sodium33 mg1%
Calcium11 mg1%
Whey Protein Isolate0 NP--
L-Leucine Ethyl Ester Hydrochloride0 NP--
L-Isoleucine Ethyl Ester Hydrochloride0 NP--
L-Valine Ethyl Ester Hydrochloride0 NP--
L-Leucine0 NP--
L-Arginine0 NP--
L-Isoleucine0 NP--
Creatine Monohydrate0 NP--
L-Tyrosine0 NP--
L-Valine0 NP--
L-Histidine0 NP--
Caffeine Anhydrous0 NP--
Beta-Alanine0 NP--
Whey Protein hydrolysate0 NP--
Folate40 mcg10%
L-Citrulline Malate0 NP--
Protein14 Gram(s)28%
L-Arginine Ethyl Ester Dihydrochloride0 NP--
L-Alanyl-L-Glutamine0 NP--
Creatine Gluconate0 NP--
Beta-Alanine Ethyl Ester Hydrochloride0 NP--
Guanidinopropionic Acid0 NP--
Creatine Magnesium Chelate0 NP--
L-2-aminopentanoic Acid0 NP--
Barley0 NP--
Gamma-Butyrobetaine HCl0 NP--
Protein Hydrolysate Matrix3.5 Gram(s)--
Casein Protein hydrolysate0 NP--
Proprietary Branched Chain Ethyl Ester Amino Acid Matrix6.16 Gram(s)--
Creatine Taurinate0 NP--
COP0 NP--
Di-Na Creatine Phosphate Tetrahydrate0 NP--
MTB Pump0 NP--
Bis Picolinato Oxo Vanadium0 NP--
Power, Speed, Strength and Endurance Matrix3.17 Gram(s)--
KIC0 NP--
Redline Energy & Meltdown Fat Burning Technology240 mg--
Monosodium Phosphate Anhydrous0 NP--
Trisodium Phosphate Dodecahydrate0 NP--
Di-L-Arginine-L-Malate0 NP--
Gamma-Butyrobetaine Ethyl Ester Chloride0 NP--
Proprietary Muscle Volumizing, NO2, Insulinotrophic and Glutamine Matrix4.88 Gram(s)--

Other ingredients: Natural & Artificial flavors, Malic Acid, Sucralean brand Sucralose, Citric Acid Anhydrous, Glycine

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.
General Statements

{Bar graph} INCREASES IN MUSCLE GENE PROTEINS WITH SHOTGUN(R) 5X(TM) Muscle Myo-D Increases 515.00% Muclse MRF-4 Increases 400.40% Muscle Myf5 Increases 179.60% Muscle Myogenin Increases 152.80% Myfibrillar Protein Increases 167.20%

ORIGINAL SHOTGUN PREWORKOUT

BACKED BY 3 UNIVERSITY STUDIES NATURAL & ARTIFICIAL FLAVORS

{American flag} Made in USA from Domestic & Imported Ingredients in VPX State of the Art Facilities

Not a significant source of fat, calories from fat, saturated fat, trans fat, cholesterol, carbohydrates, dietary fiber, sugars, vitamin A, vitamin C, iron and potassium.

Calories per gram: Fat 9 - Carbohydrate 4 - Protein 4

* When combined with resistance exercise and a sensible diet.

ALL RIGHTS RESERVED.

{Bar graph} SHOTGUN(R) 5X(TM) UNIVERSITY PROVEN TO INCREASE MUSCLE DNA BY 1800% SHOTGUN(R) 5X(TM) - 1,800% Placebo

Precautions

WARNING: Do not use this product if you are pregnant or nursing or have a medical condition.

Not recommended for use by individual under 18 years of age.

This product contains caffeine and should not be used with any other caffeine and/or stimulant containing products. Too much caffeine may cause nervousness, irritability, sleeplessness, and occasionally, rapid heartbeat. One serving of SHOTGUN(R) 5X(TM) provides caffeine equivalent to less than two cups of coffee.

This product is intended for use by healthy individuals only.

KEEP OUT OF REACH OF CHILDREN.

Do not use SHOTGUN(R) 5X(TM) with REDLINE(R) or any other products containing caffeine or other stimulants.

CONTAINS: Milk

WARNING: Too much caffeine may cause nervousness, irritability, sleeplessness, and occasionally, rapid heartbeat.

Not recommended for use by children under 18 years of age.

Use only as a dietary supplement. Do not use for weight reduction.

Do not purchase if safety seal is broken or missing.

Formula

This product contains caffeine and should not be used with any other caffeine and/or stimulant containing products.

One serving of SHOTGUN(R) 5X(TM) provides caffeine equivalent to less than two cups of coffee.

CONTAINS: Milk

One serving of SHOTGUN(R) 5X(TM) provides caffeine equivalent to less than two cups of coffee.

Brand IP Statement(s)

Muscle energetic compounds within SHOTGUN(R) 5X (TM) may cause a tingling sensation in lips and skin.

Unlike other Supplements which may require several scoops, SHOTGUN(R) 5X(TM) is extremely powerful and requires only one scoop. The SHOTGUN(R) 5X(TM), FAST 5(M), and NO-SYNTHESIZE(R) supplement strategy represents the most advanced and latest muscle growth and athletic performance strategy.

LIVE POWERFULLY(TM)

IGNITE MUSCLE GENES 5X(TM)

(C)2014

UNLIMITED GROWTH POTENTIAL University proven to Alter Muscle at the Genetic Level. SHOTGUN(R) 5X(TM) Activates Satellite Cell Proliferation to Promote the Birth of New Muscle. SHOTGUN(R) 5X(TM) generated the most ground-breaking University research in the history of Muscle Science.

Formulation

Contains no Niacin.

CONTAINS NO FRUIT JUICE

Suggested/Recommended/Usage/Directions

Drink an additional one half (1/2) ounce of water for each pound of body weight.

RECOMMENDED USE: Do not use SHOTGUN(R) 5X(TM) with REDLINE(R) or any other products containing caffeine or other stimulants. Mix one scoop of SHOTGUN(R) 5X(TM) with 8 to 10 ounces of water or your favorite beverage. Drink SHOTGUN(R) 5X(TM) prior to any type of athletic event or resistance training. For enhanced results consume FAST 5(TM) during and NO-SYNTHESIZE(R) after training. Unlike other Supplements which may require several scoops, SHOTGUN(R) 5X(TM) is extremely powerful and requires only one scoop.

Seals/Symbols

SUCRALEAN ZERO CALORIE SWEETENER

PeptoPro(R)

COP(R) Creatinol-O-Phosphate Patent No. 8,372,821

VPX(R)

VITAL PHARMACEUTICALS GMP

GLUTEN FREE GF

{NON} GMO

FDA Statement of Identity

DIETARY SUPPLEMENT

Storage

STORE AT 15(0)C to 25(0)C (59(0)F to 77(0)F).

FDA Disclaimer Statement

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

General

V001

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

See for yourself

Shotgun 5X Watermelon by VPX label

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

Shotgun 5X Watermelon 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 Shotgun 5X Watermelon by VPX

These are the 40 active ingredients this product is made of. Select any to open its full monograph.

Serving size20.5 Gram(s) Dosage formPowder Servings per container28 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
100 mcg 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

Sodium

Interacts with
205 drugs
33 mg per serving

Sodium is an essential mineral and electrolyte your body needs to balance fluids, support nerves, and help muscles work. Most people in modern diets g...

Sodium monograph & interactions

Calcium

Interacts with
168 drugs
11 mg per serving

Calcium is an essential mineral your body needs for strong bones, nerve signaling, and muscle function, and supplements can help fill gaps when diet f...

Calcium monograph & interactions

Folate

40 mcg per serving Form: Folic Acid

Protein

14 Gram(s) per serving

Protein Hydrolysate Matrix

3.5 Gram(s) per serving Form: BCAA Peptide, EAA's, Glutamine Peptides

Proprietary Branched Chain Ethyl Ester Amino Acid Matrix

6.16 Gram(s) per serving
  • › L-Leucine Ethyl Ester Hydrochloride
  • › L-Isoleucine Ethyl Ester Hydrochloride
  • › L-Valine Ethyl Ester Hydrochloride
  • › L-Leucine
  • › L-Arginine
  • › L-Isoleucine
  • › L-Valine
  • › L-Arginine Ethyl Ester Dihydrochloride
  • › L-Alanyl-L-Glutamine
  • › L-2-aminopentanoic Acid

Power, Speed, Strength and Endurance Matrix

3.17 Gram(s) per serving

Redline Energy & Meltdown Fat Burning Technology

240 mg per serving

Proprietary Muscle Volumizing, NO2, Insulinotrophic and Glutamine Matrix

4.88 Gram(s) per serving

Other (inactive) ingredients: Natural & Artificial flavors, Malic Acid, Sucralean brand Sucralose, Citric Acid Anhydrous, Glycine. These complete the product’s ingredient list but are not active constituents.

Interaction report

Shotgun 5X Watermelon by VPX Drug Interactions

Want to check YOUR meds against Shotgun 5X Watermelon?

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
880Drugs
20 Major 776 Moderate 84 Minor

Ingredients driving the most interactions

Caffeine Anhydrous 655
L-Arginine 403
Vitamin B6 210
Sodium 205
L-Citrulline Malate 178

Individual Drug Interactions

The ingredients in Shotgun 5X Watermelon interact with 880 drugs. Click any drug to see the details.

11 of the 40 ingredients in Shotgun 5X Watermelon interact with drugs. Each result below shows which ingredient is responsible. Caffeine Anhydrous L-Arginine Vitamin B6 Sodium L-Citrulline Malate Casein Protein hydrolysate Calcium Trisodium Phosphate Dodecahydrate Whey Protein Isolate L-Tyrosine Barley

Each ingredient & the kinds of drugs it affects

For each ingredient in Shotgun 5X Watermelon 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.

Caffeine Anhydrous41 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 Anhydrous full monograph & all 41 interactions

L-Arginine9 drug types · 403 drugs

Ace Inhibitors (Aceis)

Theoretically, concomitant use of L-arginine and ACE inhibitors may increase the risk for hypotension and hyperkalemia.
Combining L-arginine with some antihypertensive drugs, especially ACE inhibitors, seems to have additive vasodilating and blood pressure-lowering effects. Furthermore, ACE inhibitors can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients. Theoretically, concomitant use of ACE inhibitors with L-arginine may increases the risk of hyperkalemia.

Likelihood Probable Evidence D
Angiotensin Receptor Blockers (Arbs)

Theoretically, concomitant use of L-arginine and ARBs may increase the risk of hypotension and hyperkalemia.
L-arginine increases nitric oxide, which causes vasodilation. Combining L-arginine with ARBs seems to increase L-arginine-induced vasodilation. Furthermore, ARBs can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients. Theoretically, concomitant use of ARBs with L-arginine may increases the risk of hyperkalemia.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, concomitant use of L-arginine with anticoagulant and antiplatelet drugs might have additive effects and increase the risk of bleeding.
Preliminary research suggests that L-arginine infusions reduce platelet aggregation in humans. The clinical significance of this effect is unclear.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, concomitant use of L-arginine might have additive effects with antidiabetes drugs.
Preliminary clinical research shows that L-arginine decreases blood glucose levels in patients with type 2 diabetes.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, concomitant use of L-arginine and antihypertensive drugs may increase the risk of hypotension.
L-arginine increases nitric oxide, which causes vasodilation. Clinical evidence shows that L-arginine can reduce blood pressure in some individuals with hypertension. Furthermore, combining L-arginine with some antihypertensive drugs seems to have additive vasodilating and blood pressure-lowering effects.

Likelihood Probable Evidence D
Isoproterenol (Isuprel)

Theoretically, concurrent use of isoproterenol and L-arginine might result in additive effects and hypotension.
Preliminary clinical evidence suggests that L-arginine enhances isoproterenol-induced vasodilation in patients with essential hypertension or a family history of essential hypertension.

Likelihood Probable Evidence D
Potassium-Sparing Diuretics

Theoretically concomitant use of potassium-sparing diuretics with L-arginine may increases the risk of hyperkalemia.
Potassium-sparing diuretics can increase potassium levels. Use of L-arginine has been associated with hyperkalemia in some patients.

Likelihood Possible Evidence D
Sildenafil (Viagra)

Theoretically, concurrent use of sildenafil and L-arginine might increase the risk for hypotension.
In vivo, concurrent use of L-arginine and sildenafil has resulted in increased vasodilation. Theoretically, concurrent use 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
Testosterone

Theoretically, concomitant use of L-arginine and testosterone might have additive effects.
In clinical research, L-arginine increases the level of testosterone in male patients with erectile dysfunction. The clinical significance of this finding is unclear.

Likelihood Possible Evidence D
L-Arginine 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

Sodium7 drug types · 205 drugs

Antihypertensive Drugs

Theoretically, a high intake of dietary sodium might reduce the effectiveness of antihypertensive drugs.
High intake of dietary sodium can increase systolic and diastolic blood pressure. Also, high intake of sodium may necessitate increased use of antihypertensive medications to achieve blood pressure control in some patients, such as those with chronic kidney disease.

Likelihood Probable Evidence A
Corticosteroids

Concomitant use of mineralocorticoids and some glucocorticoids with sodium supplements might increase the risk of hypernatremia.
Mineralocorticoids and some glucocorticoids (corticosteroids) cause sodium retention. This effect is dose-related and depends on mineralocorticoid potency. It is most common with hydrocortisone, cortisone, and fludrocortisone, followed by prednisone and prednisolone.

Likelihood Possible Evidence D
Didanosine (Videx)

Concomitant use of didanosine with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia.
Didanosine formulations contain a significant amount of sodium.

Likelihood Probable Evidence C
Lithium

Altering dietary intake of sodium might alter the levels and clinical effects of lithium.
High sodium intake can reduce plasma concentrations of lithium by increasing lithium excretion. Reducing sodium intake can significantly increase plasma concentrations of lithium and cause lithium toxicity in patients being treated with lithium carbonate. Stabilizing sodium intake is shown to reduce the percentage of patients with lithium level fluctuations above 0.8 mEq/L. Patients taking lithium should avoid significant alterations in their dietary intake of sodium.

Likelihood Probable Evidence B
Sodium Phosphates

Theoretically, concomitant use of sodium phosphate with sodium supplements might increase the risk of hypernatremia.
Use of high doses (> 45 mL in 24 hours) of sodium phosphate, such as those used for bowel cleansing before surgery, can lead to serious electrolyte disturbances, including hypernatremia. The risk of hypernatremia is highest in the elderly and people with other risk factors for electrolyte disturbances.

Likelihood Possible Evidence D
Sodium-Containing Drugs

Concomitant use of sodium-containing drugs with additional sodium from dietary or supplemental sources may increase the risk of hypernatremia and long-term sodium-related complications.
The Chronic Disease Risk Reduction (CDRR) intake level of 2.3 grams of sodium daily indicates the intake at which it is believed that chronic disease risk increases for the apparently healthy population. Some medications contain high quantities of sodium. When used in conjunction with sodium supplements or high-sodium diets, the CDRR may be exceeded. Additionally, concomitant use may increase the risk for hypernatremia; this risk is highest in the elderly and people with other risk factors for electrolyte disturbances.

Likelihood Possible Evidence D
Tolvaptan (Samsca)

Theoretically, concomitant use of tolvaptan with sodium might increase the risk of hypernatremia.
Tolvaptan is a vasopressin receptor 2 antagonist that is used to increase sodium levels in patients with hyponatremia. Patients taking tolvaptan should use caution with the use of sodium salts such as sodium chloride.

Likelihood Probable Evidence C
Sodium full monograph & interactions

L-Citrulline Malate2 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 Malate full monograph & interactions

Casein Protein hydrolysate1 drug type · 172 drugs

Antihypertensive Drugs

Theoretically, combining these casein peptides with antihypertensive drugs might increase the risk of hypotension.
Clinical research shows that some casein peptides, including the lactotripeptides isoleucine-proline-proline (IPP) and valine-proline-proline (VPP), can modestly reduce blood pressure in patients with hypertension.

Likelihood Probable Evidence B
Casein Protein hydrolysate full monograph & interactions

Calcium18 drug types · 168 drugs

Ceftriaxone (Rocephin)

Co-administration of intravenous calcium and ceftriaxone can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys.
Avoid administering intravenous calcium in any form, such as parenteral nutrition or Lactated Ringers, within 48 hours of intravenous ceftriaxone. Case reports in neonates show that administering intravenous ceftriaxone and calcium can result in precipitation of a ceftriaxone-calcium salt in the lungs and kidneys. In several cases, neonates have died as a result of this interaction. So far there are no reports in adults; however, there is still concern that this interaction might occur in adults.

Likelihood Probable Evidence D
Dolutegravir (Tivicay)

Calcium seems to reduce levels of dolutegravir.
Advise patients to take dolutegravir either 2 hours before or 6 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium carbonate 1200 mg concomitantly with dolutegravir 50 mg reduces plasma levels of dolutegravir by almost 40%. Calcium appears to decrease levels of dolutegravir through chelation.

Likelihood Probable Evidence B
Elvitegravir (Vitekta)

Calcium seems to reduce levels of elvitegravir.
Advise patients to take elvitegravir either 2 hours before or 2 hours after taking calcium supplements. Pharmacokinetic research suggests that taking calcium along with elvitegravir can reduce blood levels of elvitegravir through chelation.

Likelihood Probable Evidence B
Aluminum

Calcium citrate might increase aluminum absorption and toxicity. Other types of calcium do not increase aluminum absorption.
Calcium citrate can increase the absorption of aluminum when taken with aluminum hydroxide. The increase in aluminum levels may become toxic, particularly in individuals with kidney disease. However, the effect of calcium citrate on aluminum absorption is due to the citrate anion rather than calcium cation. Calcium acetate does not appear to increase aluminum absorption.

Likelihood Possible Evidence B
Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Calcium might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption when taken in a fasting state.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide and calcium can be taken together if taken with food. However, if taken on an empty stomach, bictegravir/emtricitabine/tenofovir alafenamide should not be taken with, or 2 hours after, calcium containing products.

Likelihood Probable Evidence D
Bisphosphonates

Calcium reduces the absorption of bisphosphonates.
Advise patients to take bisphosphonates at least 30 minutes before calcium, but preferably at a different time of day. Calcium supplements decrease absorption of bisphosphonates.

Likelihood Probable Evidence C
Calcipotriene (Dovonex)

Taking calcipotriene with calcium might increase 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 calcium supplements might increase the risk of hypercalcemia.

Likelihood Possible Evidence B
Digoxin (Lanoxin)

Using intravenous calcium with digoxin might increase the risk of fatal cardiac arrhythmias.
Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. However, one retrospective analysis of clinical data suggests that intravenous calcium does not increase the risk of dysrhythmias or mortality in patients receiving digoxin.

Likelihood Possible Evidence B
Diltiazem (Cardizem, Others)

Theoretically, calcium may reduce the therapeutic effects of diltiazem.
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically, calcium might increase this risk of hypercalcemia and reduce the effectiveness of diltiazem.

Likelihood Probable Evidence D
Levothyroxine (Synthroid, Others)

Calcium seems to reduce the absorption and effectiveness of levothyroxine.
Advise patients to take levothyroxine and calcium supplements at least 4 hours apart. Calcium reduces levothyroxine absorption, probably by forming insoluble complexes. Calcium carbonate supplements reduce effectiveness of levothyroxine in patients with hypothyroidism.

Likelihood Probable Evidence B
Lithium

Theoretically, concomitant use of calcium and lithium may increase this risk of hypercalcemia.
Clinical research suggests that long-term use of lithium may cause hypercalcemia in 10% to 60% of patients. Theoretically, concomitant use of lithium and calcium supplements may further increase this risk.

Likelihood Possible Evidence B
Quinolone Antibiotics

Calcium seems to reduce the absorption of quinolone antibiotics.
Advise patients to take oral quinolones at least 2 hours before or 4-6 hours after calcium supplements or calcium-fortified foods. Taking calcium at the same time as oral quinolones can reduce quinolone absorption. Calcium binds to quinolones in the gut.

Likelihood Probable Evidence B
Raltegravir (Isentress)

Calcium may reduce levels of raltegravir.
Pharmacokinetic research shows that taking a single dose of calcium carbonate 3000 mg along with raltegravir 400 mg twice daily modestly decreases the mean area under the curve of raltegravir, but the decrease does not necessitate a dose adjustment of raltegravir. However, a case of elevated HIV-1 RNA levels and documented resistance to raltegravir has been reported for a patient taking calcium carbonate 1 gram three times daily plus vitamin D3 (cholecalciferol) 400 IU three times daily in combination with raltegravir 400 mg twice daily for 11 months. It is thought that calcium reduced raltegravir levels by chelation, leading to treatment failure.

Likelihood Possible Evidence B
Sotalol (Betapace)

Calcium seems to reduce the absorption of sotalol.
Advise patients to separate doses by at least 2 hours before or 4-6 hours after calcium. Calcium appears to reduce the absorption of sotalol, probably by forming insoluble complexes.

Likelihood Possible Evidence B
Tetracycline Antibiotics

Calcium seems to reduce the absorption of tetracycline antibiotics.
Advise patients to take oral tetracyclines at least 2 hours before, or 4-6 hours after calcium supplements. Taking calcium at the same time as oral tetracyclines can reduce tetracycline absorption. Calcium binds to tetracyclines in the gut.

Likelihood Probable Evidence C
Thiazide Diuretics

Taking calcium along with thiazides might increase the risk of hypercalcemia and renal failure.
Thiazides reduce calcium excretion by the kidneys. Using thiazides along with moderately large amounts of calcium carbonate increases the risk of milk-alkali syndrome (hypercalcemia, metabolic alkalosis, renal failure). Patients may need to have their serum calcium levels and/or parathyroid function monitored regularly.

Likelihood Probable Evidence C
Verapamil (Calan, Others)

Theoretically, calcium may reduce the therapeutic effects of verapamil.
Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically, use of calcium supplements may increase this risk of hypercalcemia and reduce the effectiveness of verapamil.

Likelihood Probable Evidence D
Calcium Channel Blockers

Intravenous calcium may decrease the effects of calcium channel blockers; oral calcium is unlikely to have this effect.
Intravenous calcium is used to decrease the effects of calcium channel blockers in the management of overdose. Intravenous calcium gluconate has been used before intravenous verapamil (Isoptin) to prevent or reduce the hypotensive effects without affecting the antiarrhythmic effects. But there is no evidence that dietary or supplemental calcium when taken orally interacts with calcium channel blockers.

Likelihood Unlikely Evidence D
Calcium full monograph & interactions

Trisodium Phosphate Dodecahydrate3 drug types · 62 drugs

Ace Inhibitors (Aceis)

Using ACEIs with high doses of potassium increases the risk of hyperkalemia.
ACEIs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion. Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia. However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels.

Likelihood Likely Evidence C
Angiotensin Receptor Blockers (Arbs)

Using ARBs with high doses of potassium increases the risk of hyperkalemia.
ARBs block the actions of the renin-angiotensin-aldosterone system and reduce potassium excretion. Concomitant use of these drugs with potassium supplements increases the risk of hyperkalemia. However, concomitant use of these drugs with moderate dietary potassium intake (about 3775-5200 mg daily) does not increase serum potassium levels.

Likelihood Likely Evidence C
Potassium-Sparing Diuretics

Concomitant use increases the risk of hyperkalemia.
Using potassium-sparing diuretics with potassium supplements increases the risk of hyperkalemia.

Likelihood Likely Evidence C
Trisodium Phosphate Dodecahydrate full monograph & interactions

Whey Protein Isolate4 drug types · 53 drugs

Levodopa

Theoretically, whey protein might decrease levodopa absorption.
Small clinical studies show that concomitant ingestion of protein or high doses of leucine or isoleucine (100 mg/kg) and levodopa can exacerbate tremor, rigidity, and the "on-off" syndrome in patients with Parkinson disease.

Likelihood Probable Evidence D
Bisphosphonates

Theoretically, whey protein might reduce the absorption of bisphosphonates.
Whey protein contains minerals such as calcium that bind bisphosphonates in the gut. Advise patients to take bisphosphonates at least 30 minutes before whey protein, but preferably at a different time of day.

Likelihood Probable Evidence D
Quinolone Antibiotics

Theoretically, whey protein might decrease quinolone absorption.
Whey protein contains minerals, such as calcium, that can bind to quinolones in the gut. To avoid this interaction, advise patients to take oral quinolones at least 2 hours before or 4-6 hours after whey protein.

Likelihood Probable Evidence D
Tetracycline Antibiotics

Theoretically, whey protein might decrease tetracycline absorption.
Whey protein contains minerals, such as calcium, that bind to tetracyclines in the gut. To avoid this interaction, advise patients to take oral tetracyclines at least 2 hours before or 4-6 hours after whey protein.

Likelihood Probable Evidence D
Whey Protein Isolate full monograph & interactions

L-Tyrosine2 drug types · 21 drugs

Levodopa

Theoretically, tyrosine might decrease the effectiveness of levodopa.
Tyrosine and levodopa compete for absorption in the proximal duodenum by the large neutral amino acid (LNAA) transport system. Advise patients to separate doses of tyrosine and levodopa by at least 2 hours.

Likelihood Probable Evidence D
Thyroid Hormone

Theoretically, tyrosine might have additive effects with thyroid hormone medications.
Tyrosine is a precursor to thyroxine and might increase levels of thyroid hormones.

Likelihood Probable Evidence D
L-Tyrosine full monograph & interactions

Barley1 drug type · 1 drug

Triclabendazole (Egaten)

Theoretically, barley might decrease the clinical effects of triclabendazole.
Animal research suggests that a diet supplemented with barley can reduce the bioavailability of triclabendazole when taken concomitantly. This effect has not been shown in humans.

Likelihood Possible Evidence D
Barley full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Shotgun 5X Watermelon, from the product label.

VPX

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Web Address
VPXSPORTS.COM
Pharmacist Counseling Corner

Shotgun 5X Watermelon by VPX: Common Questions

Does Shotgun 5X Watermelon by VPX interact with any medications?
Yes. Based on its ingredients, Shotgun 5X Watermelon has a known interaction with 880 medications, including 20 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Shotgun 5X Watermelon contains 40 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.
Does this have a lot of caffeine?
The product facts don't list the exact caffeine dose per serving, so you'll need to check the label or contact the manufacturer. Caffeine anhydrous is included, and at moderate amounts it boosts mental alertness and athletic performance, but high intakes can cause anxiety, tremor, insomnia, and headache.
Can I use this if I'm pregnant or nursing?
Safety data during pregnancy and breastfeeding is limited or missing for most ingredients in this product. Creatine, beta-alanine, and L-citrulline are rated as lacking enough safety information, so they're best avoided unless your doctor advises otherwise. Vitamin B6 is rated likely safe in pregnancy at normal amounts, and caffeine is rated possibly safe at limited intake. Talk with your doctor or pharmacist about what's safe for your situation.
Will this product help me build muscle?
Creatine and whey protein are rated possibly effective for muscle strength and athletic performance. L-arginine, L-citrulline, and beta-alanine are also rated possibly effective for athletic performance. The evidence suggests these ingredients can support muscle work and recovery, but results depend on your training, diet, and consistency.
What's the harmless tingling feeling I might get?
That's paresthesia from beta-alanine, a common and harmless side effect. It typically starts on the scalp within 20 minutes of taking the dose, spreads across the body, and lasts about an hour. It's dose-dependent—lower doses cause milder or no tingling. Discontinuing the product will stop it.
Is this safe if I have kidney problems?
Creatine is present in this product in three forms, and while it's generally well tolerated in healthy adults, people with kidney disease should be cautious. Case reports have raised concerns about kidney injury with creatine use. Check with your doctor or pharmacist before using this product if you have any kidney issues.
Can this product cause acne?
Whey protein in this product has been associated with acne development or worsening, especially in teenagers and young adults. Multiple case reports show that stopping whey protein typically clears the acne, and some people who didn't respond to acne treatments while using whey became responsive after stopping it. If you're prone to acne, monitor your skin carefully.

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

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Shotgun 5X Watermelon label
Go deeper

The Full Monographs Behind Shotgun 5X Watermelon’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

Sodium

Interacts with 205 drugs

Sodium is an essential mineral and electrolyte your body needs to balance fluids, support nerves, and help muscles work. Most people in modern diets get more than enough—often too much—from...

Read the full Sodium monograph → Herb & supplement monograph

Calcium

Interacts with 168 drugs

Calcium is an essential mineral your body needs for strong bones, nerve signaling, and muscle function, and supplements can help fill gaps when diet falls short. Most people do best getting...

Read the full Calcium monograph → Herb & supplement monograph

Whey Protein

Interacts with 53 drugs

Whey protein is a high-quality, complete protein made from cow's milk that can help people meet protein needs and support muscle growth when combined with exercise. It is generally safe for...

Read the full Whey Protein monograph → Herb & supplement monograph

Casein Peptides

Interacts with 172 drugs

Casein peptides are small protein fragments made from milk casein, often studied for mild blood pressure support and relaxation. The evidence is limited and mostly modest, so they should not...

Read the full Casein Peptides monograph → Herb & supplement monograph

L-arginine

Interacts with 403 drugs

L-arginine is an amino acid that the body uses to make nitric oxide, a substance that helps blood vessels relax and widen. It is popularly used for blood pressure, erectile dysfunction, and...

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

Histidine

Histidine is an essential amino acid your body needs to build proteins and to make compounds like histamine and carnosine. Most people get enough from a normal diet, and good-quality researc...

Read the full Histidine monograph → Herb & supplement monograph

Beta-alanine

Beta-alanine is an amino acid taken mostly by athletes to raise muscle carnosine, which may help buffer acid and reduce fatigue during short, high-intensity exercise. The evidence is moderat...

Read the full Beta-alanine monograph → Herb & supplement monograph

Creatine

Creatine is one of the most studied sports supplements, with solid evidence that it can boost strength and performance during short, high-intensity activities like weightlifting and sprintin...

Read the full Creatine monograph → Herb & supplement monograph

Potassium

Interacts with 62 drugs

Potassium is an essential mineral your body needs for nerve signals, muscle function, and a steady heartbeat, and most people get enough from a balanced diet rich in fruits and vegetables. P...

Read the full Potassium monograph → Herb & supplement monograph

Tyrosine

Interacts with 21 drugs

L-tyrosine is an amino acid your body uses to make brain chemicals like dopamine and norepinephrine. Some studies suggest it may help mental performance during short-term stress, sleep loss,...

Read the full Tyrosine 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 → Herb & supplement monograph

Barley

Interacts with 1 drug

Barley is a nutritious whole grain that is a good source of soluble fiber called beta-glucan, which has solid evidence for modestly lowering LDL ('bad') cholesterol when eaten regularly. It...

Read the full Barley 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 →
Sources

Sources & How We Checked

Shotgun 5X Watermelon'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 604 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..
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Sodium 38 references
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Calcium 62 references
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Whey Protein 25 references
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L-arginine 66 references
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Beta-alanine 13 references
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L-citrulline 8 references
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Barley 15 references
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Casein Peptides 4 references
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Potassium 12 references
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Parts of this content are provided by the Therapeutic Research Center, LLC.

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.

© 2021 Therapeutic Research Center, LLC

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