Major interaction on record — check this product against your medications before combining. Based on 12 of 17 ingredients. Check your meds →
Dietary supplement

Wrath Ingredients & Drug Interactions

by Chaotic-Labz

Wrath label
See full label image
Other (e.g. Tea Bag) 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 Wrath 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

Wrath is a dietary supplement by Chaotic-Labz with 17 active ingredients. Its ingredients are commonly taken for mental alertness and reducing fatigue, improving athletic performance, headache and migraine relief.Based on those ingredients, 1,628 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Green Tea extract, 11-hydroxyyohimbine, Citrus aurantium 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 Wrath by Chaotic-Labz

Ask about any prescription or over-the-counter medication and we check it for interactions with Wrath by Chaotic-Labz — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Wrath by Chaotic-Labz

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

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 0 of its 17 active ingredients.
  • “Wrath's Xtreme (Thermo-Lipolytic) Proprietary Blend” is a proprietary blend — the label gives one combined amount (1,596 mg) without saying how much of each component you get.

Wrath contains 17 ingredients, 8 of which are active compounds aimed at stimulation and thermogenesis (fat-burning). The main ones are caffeine anhydrous for alertness and energy, plus a cluster of lesser-studied stimulants: bitter orange extract (which contains synephrine, an adrenaline-like compound), isopropylnorsynephrine HCl (a synthetic beta-agonist), 1,3-DMAA (methylhexamine), alpha-yohimbine (rauwolscine), and N-methyl-phenylethylamine.

The product also includes green tea extract (which itself contains caffeine), raspberry ketone extract, capsicum (cayenne pepper), lemon extract, and several citrus extracts. The remaining ingredients are inactive fillers and binders like dextrose, microcrystalline cellulose, and magnesium stearate.

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: weight loss and metabolic boost.
  • We looked for evidence on: Athletic performance, Fatigue, thermogenesis, appetite suppression, calorie burning.
  • The strongest evidence on file: Caffeine is rated "Likely Effective" for Athletic performance (Natural Medicines).
  • Also on file: Yohimbe is rated "Insufficient Reliable Evidence To Rate" for Athletic performance, Fatigue.
  • Also on file: Cocoa is rated "Insufficient Reliable Evidence To Rate" for Athletic performance, Chronic fatigue syndrome (CFS).

Caffeine is effective for neonatal apnea and postoperative headache, and is likely effective for mental alertness and athletic performance. For the other active ingredients — bitter orange, isopropylnorsynephrine, alpha-yohimbine, 1,3-DMAA, N-methyl-phenylethylamine, raspberry ketone, and lemon extract — the evidence we hold is insufficient to rate their effectiveness for obesity, athletic performance, depression, or other claimed purposes.

Green tea extract shows likely effectiveness for human papillomavirus conditions and possibly effective for ovarian cancer and high cholesterol. The product's other citrus extracts lack established effectiveness data in our sources.

The evidence, ingredient by ingredient Caffeine Cocoa Phenethylamine (pea) Bitter Orange Isopropylnorsynephrine Raspberry Ketone Rauwolscine 1,3-dmaa

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 12 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 12 of 12.
  • General safety write-ups exist for 12 of 12.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Caffeine in moderate amounts is generally well tolerated, but high doses carry risks: anxiety, insomnia, tremors, nausea, and rarely, stroke. The more concerning ingredients are poorly studied stimulants.

Bitter orange can raise blood pressure and heart rate, especially combined with caffeine, and has rare reports of heart attack, QT prolongation, stroke, and seizure. Isopropylnorsynephrine is regarded as unsafe and has been tied to hypertension, palpitations, respiratory distress, and when combined with other stimulants or intense exercise, stroke and cardiac arrest.

1,3-DMAA is banned in supplements in many countries due to serious cardiovascular harm including cardiac arrest, atrial fibrillation, myocardial infarction, and life-threatening lactic acidosis. Alpha-yohimbine is a potent, poorly studied stimulant; a related compound (yohimbine) has caused loss of consciousness, paralysis, and seizures.

Raspberry ketone resembles a stimulant and has case reports of heart palpitations, tachycardia, elevated blood pressure, and coronary spasm. Capsicum commonly causes burning sensations and gastrointestinal upset.

Side effects, ingredient by ingredient Caffeine Cocoa Phenethylamine (pea) Bitter Orange Isopropylnorsynephrine Raspberry Ketone Rauwolscine 1,3-dmaa

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?
  • 12 of the 12 matched ingredients can interact with medications — Lemon, Yohimbe, Cocoa, Capsicum, Green Tea, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; seizure medications; diabetes medications; heart-rhythm medications; lithium.
  • For scale: 1,629 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.

Stop and check before using if you take monoamine oxidase inhibitors (MAOIs) — risk of dangerous blood pressure spike. Major caution with nadolol or atorvastatin (green tea will reduce their levels).

Check with your pharmacist if you're on antidepressants, other stimulants, blood thinners (including warfarin), blood pressure drugs, antidiabetes drugs, sedatives, antipsychotics, seizure medications, or any drug metabolized by the CYP2D6 or CYP3A4 enzyme pathways. No interactions are documented for theobromine, beta-phenylethylamine, R-beta-methylphenylethylamine, citrus natsudaidai, citrus junos, or tananka extract, as we hold no data for these.

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.

Wrath is a high-stimulant product designed for energy and thermogenesis, built on ingredients with substantial drug interaction risk and limited long-term human safety data. If you take any prescription medications — especially antidepressants, blood pressure drugs, blood thinners, diabetes drugs, sedatives, or antipsychotics — do not start this product without talking to your pharmacist or doctor first.

Even without medications, this combination of potent, poorly studied stimulants carries cardiovascular risk.

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

Assessment coverage: 12 of 17 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jan 23, 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 Wrath, straight from the product label.

Brand Chaotic-Labz
Barcode (UPC) 283333505583
Net contents 90 Caplet(s)
Market status On market
Date entered into DSLD Jan 23, 2015
DSLD ID 41142
Product type Other Combinations
Supplement form Other (e.g. Tea Bag)
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (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 Wrath by Chaotic-Labz, 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 Caplet(s)
Maximum serving Sizes:
3 Caplet(s)
Servings per container
30
UPC/BARCODE
283333505583
IngredientAmount% DV
Caffeine Anhydrous0 NP--
Theobromine0 NP--
Beta-Phenylethylamine0 NP--
N-Methyl-Phenylethylamine0 NP--
Citrus aurantium extract0 NP--
Isopropylnorsynephrine HCl0 NP--
Raspberry Ketone extract0 NP--
Alpha-Yohimbine0 NP--
Methylhexamine HCl0 NP--
R-Beta-Methylphenylethylamine0 NP--
Wrath's Xtreme (Thermo-Lipolytic) Proprietary Blend1596 mg--
Green Tea extract0 NP--
11-hydroxyyohimbine0 NP--
Capsicum Annuum fruit extract0 NP--
Citrus Natsudaidai Hayata extract0 NP--
Citrus Junos Sieb extract0 NP--
Citrus limonium extract0 NP--
Tananka extract0 NP--

Other ingredients: Dextrose, Microcrystalline Cellulose, Sodium Starch Glycolate, Dicalcium Phosphate, Hydroxypropyl Methylcellulose, Stearic Acid, Magnesium Stearate, Silica

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.
Suggested/Recommended/Usage/Directions

SUGGESTED USE: As a Dietary Supplement take one (1) caplet in the morning for the first two (2) days to access your personal tolerance level and needs. Once tolerance level has been established take 1-3 caplets in the morning daily or as needed for desired fat loss.

Precautions

Do not take Wrath after 3pm as it may cause restless sleep. DO NOT EXCEED THREE (3) CAPLETS DAILY.

WARNING *WARNING *WARNING *WARNING *WARNING DO NOT USE IF PREGNANT OR NURSING.

Not intended for use by those with a medical condition.

Consult a physician or licensed qualified health care professional before using this product if you have a family history of any medical condition, including but not limited to thyroid disease, heart problems, high blood pressure, diabetes, depression or other psychiatric conditions, glaucoma, photosensitivity, hypertensive crisis, hemophilia, difficulty urination, prostate enlargement, seizure disorder, kidney problems, liver disease, pancreas disorders, peptic ulcers, or if you are contemplating becoming pregnant, or if you are using a monoamine oxidase inhibitor (MAOI), anti-platelet/anti-cooagulant drugs, theophyline, estrogen, acetaminophen, blood pressure lowering drugs, tricyclic antidepressants, beta-blocking drugs, thyroid drugs, sedatives or any other dietary supplement, prescription drug, or over-the-counter drug containing ephedrine, pseudoephedrine, or phenylpropanolamine (ingredients found in various allergy, cough, cold, or weight control products).

Exceeding recommended dosage may cause adverse effects, including but not limited to restlessness, insomnia, gastrointestinal disorders, heart attack, or stroke. Discontinue use and call a physician or licensed qualified health care professional immediately if you experience rapid heartbeat, dizziness, severe headache, shortness of breath or other similar symptoms.

KEEP OUT OF REACH OF CHILDREN.

General Statements

- HELPS TO INCREASE BODY’S CORE TEMPERATURE THROUGHOUT DAY - HELPS TO DECREASE THE BODY’S ABILITY TO CONVERT CALORIES TO FAT - HELPS TO INCREASE THE AMOUNT OF BASE CALORIES BURNED PER DAY - HELPS TO SUPPRESS THE BODY’S NATURAL HUNGER LEVELS - HELPS TO IMPROVE MOOD AND ENERGY LEVELS THROUGHOUT DAY

KILL THE COMPETITION

ELECTRIFY YOUR FAT

FDA Disclaimer Statement

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

Storage

Keep container tightly closed in a cool, dry and dark place.

FDA Statement of Identity

DIETARY SUPPLEMENT

Seals/Symbols

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CHAOTIC LABZ XTREME SPORTS NUTRITION

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See for yourself

Wrath by Chaotic-Labz label

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

Wrath 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 Wrath by Chaotic-Labz

These are the 17 active ingredients this product is made of. Select any to open its full monograph.

Serving size3 Caplet(s) Dosage formOther (e.g. Tea Bag) Servings per container30 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.

Wrath's Xtreme (Thermo-Lipolytic) Proprietary Blend

1596 mg per serving

Other (inactive) ingredients: Dextrose, Microcrystalline Cellulose, Sodium Starch Glycolate, Dicalcium Phosphate, Hydroxypropyl Methylcellulose, Stearic Acid, Magnesium Stearate, Silica. These complete the product’s ingredient list but are not active constituents.

Interaction report

Wrath by Chaotic-Labz Drug Interactions

Want to check YOUR meds against Wrath?

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
1,628Drugs
23 Major 1,597 Moderate 8 Minor

Ingredients driving the most interactions

Green Tea extract 1,293
11-hydroxyyohimbine 1,125
Citrus aurantium extract 957
Alpha-Yohimbine 677
Theobromine 661

Individual Drug Interactions

The ingredients in Wrath interact with 1,628 drugs. Click any drug to see the details.

12 of the 17 ingredients in Wrath interact with drugs. Each result below shows which ingredient is responsible. Green Tea extract 11-hydroxyyohimbine Citrus aurantium extract Alpha-Yohimbine Theobromine Caffeine Anhydrous Isopropylnorsynephrine HCl Methylhexamine HCl Capsicum Annuum fruit extract N-Methyl-Phenylethylamine Raspberry Ketone extract Citrus limonium extract

Each ingredient & the kinds of drugs it affects

For each ingredient in Wrath 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.

Green Tea extract58 drug types · 1,293 drugs

Atorvastatin (Lipitor)

Green tea extract seems to reduce the levels and clinical effects of atorvastatin.
In healthy humans, taking green tea extract 300 mg or 600 mg along with atorvastatin reduces plasma levels of atorvastatin by approximately 24%. The elimination of atorvastatin is not affected. Atorvastatin is a substrate of organic anion-transporting polypeptides (OATPs). Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs. Some OATPs are expressed in the small intestine and are responsible for the uptake of drugs and other compounds, which may have resulted in reduced plasma levels of atorvastatin. It is not clear if drinking green tea alters the absorption of atorvastatin.

Likelihood Likely Evidence B
Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Green tea contains caffeine. 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
Nadolol (Corgard)

Green tea seems to reduce the levels and clinical effects of nadolol.
Preliminary clinical research shows that green tea consumption reduces plasma concentrations of nadolol. Compared to a control group, both peak levels and total drug exposure (AUC) of nadolol were reduced by approximately 85% in subjects who drank green tea daily for two weeks. Drinking green tea with nadolol also significantly reduced nadolol's systolic blood pressure lowering effect. Other clinical research shows that a single dose of green tea can affect plasma nadolol levels for at least one hour. Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is involved in the uptake of nadolol in the intestine The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea.

Likelihood Likely Evidence B
5-Fluorouracil

Theoretically, high doses of green tea might increase the effects and side effects of 5-fluorouracil.
Animal research shows that taking green tea in amounts equivalent to about 6 cups daily in humans for 4 weeks prior to receiving a single injection of 5-fluorouracil increases the maximum plasma levels of 5-fluorouracil by about 2.5-fold and the area under the curve by 425%.

Likelihood Possible Evidence D
Adenosine (Adenocard)

Theoretically, green tea might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Green tea contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, caffeine doesn't 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, green tea may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Conflicting reports exist regarding the effect of green tea on bleeding risk when used with anticoagulant or antiplatelet drugs; however, most evidence suggests that drinking green tea in moderate amounts is unlikely to cause a significant interaction. Green tea contains small amounts of vitamin K, approximately 7 mcg per cup. Some case reports have associated the antagonism of warfarin with the vitamin K content of green tea. However, these reports are rare, and very large doses of green tea (about 8-16 cups daily) appear to be needed to cause these effects. Furthermore, the catechins and caffeine in green tea are reported to have antiplatelet activity.

Likelihood Unlikely Evidence D
Beta-Adrenergic Agonists

Green tea contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists.

Likelihood Probable Evidence D
Bortezomib (Velcade)

Theoretically, green tea might interfere with the effects of bortezomib.
In vitro research shows that green tea polyphenols, such as epigallocatechin gallate (EGCG), interact with bortezomib and block its proteasome inhibitory action. This prevents the induction of cell death in multiple myeloma or glioblastoma cancer cell lines. Advise patients taking bortezomib, not to take green tea.

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

Theoretically, green tea might reduce the effects of carbamazepine and increase the risk for convulsions.
Green tea contains caffeine. 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
Celiprolol (Celicard)

Theoretically, green tea might reduce the levels and clinical effects of celiprolol.
In a small human study, taking green tea daily for 4 days appears to decrease blood and urine levels of celiprolol by at least 98%. This interaction is possibly due to the inhibition of organic anion transporting polypeptide (OATP). Green tea catechins have been shown to inhibit organic anion transporting polypeptides (OATP), one of which, OATP1A2, is found in the intestine The interaction is thought to be due primarily to the epigallocatechin gallate (EGCG) content of green tea.

Likelihood Possible Evidence D
Cimetidine (Tagamet)

Theoretically, concomitant use might increase the effects and adverse effects of caffeine in green tea.
Green tea contains caffeine. Cimetidine can reduce caffeine clearance by 31% to 42%.

Likelihood Likely Evidence B
Clozapine (Clozaril)

Theoretically, green tea might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Animal research suggests that, although green tea extract does not affect the elimination of clozapine, it delays the time to reach peak concentration and reduces the peak plasma levels. Also, concomitant administration of green tea and clozapine might theoretically cause acute exacerbation of psychotic symptoms due to the caffeine in green tea. Caffeine can increase the effects and toxicity of clozapine. Caffeine doses of 400-1000 mg daily inhibit clozapine metabolism. Clozapine is metabolized by cytochrome P450 1A2 (CYP1A2). Researchers speculate that caffeine might inhibit CYP1A2. However, there is no reliable evidence that caffeine affects CYP1A2. There is also speculation that genetic factors might make some patients be more sensitive to the interaction between clozapine and caffeine.

Likelihood Possible Evidence B
Contraceptive Drugs

Theoretically, concomitant use might increase the effects and adverse effects of caffeine found in green tea.
Green tea contains caffeine. Oral contraceptives can decrease caffeine clearance by 40% to 65%.

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

Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Green tea contains caffeine. Caffeine is metabolized by cytochrome P450 1A2 (CYP1A2),. Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from green tea and increase caffeine levels.

Likelihood Possible Evidence D
Dipyridamole (Persantine)

Theoretically, green tea might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Green tea contains caffeine. Caffeine might inhibit 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 might increase the risk of adverse effects from caffeine.
In human research, disulfiram decreases the clearance and increases the half-life of caffeine.

Likelihood Probable Evidence B
Diuretic Drugs

Theoretically, using green tea with diuretic drugs might increase the risk of hypokalemia.
Green tea contains caffeine. In excessive amounts, caffeine 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.
Green tea contains caffeine. Estrogen inhibits caffeine metabolism.

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

Theoretically, green tea might reduce the effects of ethosuximide and increase the risk for convulsions.
Green tea contains caffeine. 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, green tea might reduce the effects of felbamate and increase the risk for convulsions.
Green tea contains caffeine. 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
Fexofenadine (Allegra)

Green tea can decrease blood levels of fexofenadine.
Clinical research shows that green tea can significantly decrease blood levels and excretion of fexofenadine. Taking green tea extract with a dose of fexofenadine decreased bioavailability of fexofenadine by about 30%. In vitro, green tea inhibits the cellular accumulation of fexofenadine by inhibiting the organic anion transporting polypeptide (OATP) drug transporter. Research shows that two of the major catechins found in green tea, epicatechin gallate (ECG) and epigallocatechin gallate (EGCG), inhibit OATPs, specifically OATP1A2, OATP1B1, and OATP2B1. In addition, green tea has been shown to reduce the absorption of some drugs that are OATP substrates.

Likelihood Probable Evidence B
Flutamide (Eulexin)

Theoretically, green tea might increase the levels and adverse effects of flutamide.
Green tea contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide. Theoretically, concomitant use of caffeine and flutamide might increase serum concentrations of flutamide and increase the risk adverse effects.

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Hepatotoxic Drugs

Theoretically, concomitant use might have additive adverse hepatotoxic effects.
Green tea extract supplements have been linked to several cases of hepatotoxicity and might have additive hepatotoxic effects with other drugs..

Likelihood Unlikely Evidence D
Imatinib (Gleevec)

Theoretically, green tea might reduce the levels and clinical effects of imatinib.
In animal research, a single dose of green tea extract reduces the area under the curve (AUC) of imatinib by up to approximately 64% and its main metabolite N-desmethyl imatinib by up to approximately 81%. This interaction has not been shown in humans. The mechanism of action is unclear but may involve multiple pathways.

Likelihood Possible Evidence D
Green Tea extract full monograph & all 58 interactions

11-hydroxyyohimbine13 drug types · 1,125 drugs

Monoamine Oxidase Inhibitors (Maois)

Concomitant use of MAOIs with yohimbe can result in additive effects.
Yohimbine, a constituent of yohimbe, has MAO inhibitory effects. At high doses, yohimbine is a non-selective inhibitor of MAO.

Likelihood Likely Evidence D
Antihypertensive Drugs

Theoretically, yohimbe might reduce the effects of antihypertensive drugs.
Yohimbine, a constituent of yohimbe, is an alpha-2 adrenoceptor antagonist and has been reported to increase blood pressure in clinical research. Theoretically, concomitant use of yohimbe and antihypertensive drugs can interfere with blood pressure control.

Likelihood Probable Evidence D
Clonidine (Catapres)

Theoretically, yohimbe might precipitate clonidine withdrawal.
Chronic clonidine use can downregulate alpha-2 adrenoreceptors. Animal research and one human case report suggest that concomitant administration of yohimbine, an alpha-2 adrenoceptor antagonist, may precipitate clonidine withdrawal and lead to sympathomimetic toxicity, including hypertensive crisis.

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

CYP2D6 inhibitors may increase the levels and adverse effects of yohimbine, a constituent of yohimbe.
In vitro and clinical research shows that the yohimbe bark constituent, yohimbine, is metabolized by CYP2D6 isoenzymes. Paroxetine, a cytochrome P450 (CYP) 2D6 inhibitor, increases the maximum serum concentration of yohimbine and reduces the clearance of yohimbine compared to yohimbine alone in patients who are extensive CYP2D6 metabolizers..

Likelihood Probable Evidence B
Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, yohimbe might increase the levels and adverse effects of CYP2D6 substrates.
In vitro research suggests that yohimbine, a constituent of yohimbe bark, inhibits CYP2D6 enzyme activity.

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

Theoretically, CYP3A4 inhibitors might increase the levels and adverse effects of yohimbine, a constituent of yohimbe bark.
In vitro and clinical research shows that the yohimbe bark constituent, yohimbine, is metabolized by CYP3A4 enzymes. Theoretically, drugs that inhibit CYP3A4 might increase the levels and adverse effects of yohimbine.

Likelihood Possible Evidence D
Paroxetine (Paxil)

Paroxetine decreases the clearance of yohimbine and may increase its effects.
Paroxetine, a cytochrome P450 (CYP) 2D6 inhibitor, increases the maximum serum concentration of yohimbine by about 350% and reduces the clearance of yohimbine by about 80% compared to yohimbine alone in patients who are extensive CYP2D6 metabolizers. No significant changes in pharmacokinetic parameters of yohimbine were observed with coadministration of paroxetine in patients who are poor CYP2D6 metabolizers.

Likelihood Probable Evidence B
Phenothiazines

Theoretically, using yohimbine with phenothiazines might have additive effects.
Yohimbine, a constituent of yohimbe, has alpha-2 adrenergic antagonist effects. Theoretically, combining it with phenothiazines can cause additive alpha-2 adrenergic antagonism.

Likelihood Possible Evidence D
Stimulant Drugs

Theoretically, taking yohimbe with stimulant drugs can have additive effects.
Yohimbine, a constituent of yohimbe, has sympathomimetic effects and increases blood pressure in a dose-dependent manner. Theoretically, taking yohimbe with stimulant drugs can have additive stimulant and hypertensive effects.

Likelihood Possible Evidence D
Tricyclic Antidepressants (Tcas)

Theoretically, taking yohimbe with TCAs can increase adverse effects.
A small clinical study in patients taking TCAs for at least 4 weeks shows that receiving doses of intravenous yohimbine 2.5-20 mg daily for up to 7 days precipitates severe anxiety, agitation, and tremor. The effects of yohimbe bark itself are unclear; oral yohimbe bark contains 0.6% to 1.38% yohimbine, but it is unclear how much is absorbed.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, combining yohimbe bark with antiplatelet or anticoagulant drugs might have additive effects; however, this has not been reported in clinical research.
Research in healthy adults shows that taking yohimbine, a constituent of yohimbe bark, in doses of 8 mg or more, seems to inhibit platelet aggregation in vitro by binding to the alpha-2 adrenoceptor. The effects of yohimbe bark itself are unclear; yohimbe bark contains 0.6% to 1.38% yohimbine, but it is unclear how much is absorbed.

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

Theoretically, yohimbe might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that yohimbe extract induces CYP1A2 enzymes.

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

Theoretically, yohimbe might decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that yohimbe extract induces CYP3A4 enzymes.

Likelihood Possible Evidence D
11-hydroxyyohimbine full monograph & interactions

Citrus aurantium extract13 drug types · 957 drugs

Midazolam (Versed)

Bitter orange might increase blood levels of midazolam.
One small clinical study shows that bitter orange juice can increase midazolam levels, likely through inhibition of cytochrome P450 3A4 (CYP3A4). Theoretically, bitter orange might increase the risk of midazolam-related adverse effects.

Likelihood Probable Evidence B
Monoamine Oxidase Inhibitors (Maois)

Theoretically, taking MAOIs with synephrine-containing bitter orange preparations might increase the hypertensive effects of synephrine, potentially leading to hypertensive crisis.
Bitter orange contains tyramine, octopamine, and synephrine, which are MAO substrates.

Likelihood Probable Evidence D
Antidiabetes Drugs

Theoretically, bitter orange might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Some clinical research shows that drinking a tea containing bitter orange and Indian snakeroot reduces fasting and postprandial glucose levels in patients with type 2 diabetes who are using antidiabetes drugs. However, it is unclear if these effects are due to bitter orange, Indian snakeroot, or the combination. An animal study also shows that p-synephrine in combination with gliclazide , a sulfonylurea, causes an additional 20% to 44% decrease in glucose levels when compared with gliclazide alone.

Likelihood Possible Evidence B
Caffeine

Bitter orange might increase blood pressure and heart rate when taken with caffeine.
Small clinical studies show that taking bitter orange in combination with caffeine can increase blood pressure and heart rate in otherwise healthy normotensive adults. Theoretically, this might increase the risk of serious cardiovascular adverse effects.

Likelihood Possible Evidence B
Colchicine

Bitter orange might affect colchicine levels.
Colchicine is a substrate of P-glycoprotein and cytochrome P450 3A4 (CYP3A4). Bitter orange has been reported to inhibit CYP3A4 and increase levels of CYP3A4 substrates. However, one small clinical study in healthy adults shows that drinking bitter orange juice 240 mL twice daily for 4 days and taking a single dose of colchicine 0.6 mg on the 4th day decreases colchicine peak serum levels by 24%, time to peak serum level by 1 hour, and overall exposure to colchicine by 20%. The clinical significance of this finding is unclear.

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

Bitter orange might increase levels of drugs metabolized by CYP3A4.
Small clinical studies suggest that single or multiple doses of freshly squeezed bitter orange juice 200-240 mL can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects. However, the extent of the effect of bitter orange on CYP3A4-mediated drug interactions is unknown. Some evidence suggests that bitter orange selectively inhibits intestinal CYP3A4, but not hepatic CYP3A4. Its effect on P-glycoprotein, which strongly overlaps with CYP3A4 interactions, is unclear. One small clinical study shows that drinking 8 ounces of freshly squeezed bitter orange juice has no effect on cyclosporine, which seems to be more dependent on hepatic CYP3A4 and P-glycoprotein than intestinal CYP3A4.

Likelihood Possible Evidence B
Dextromethorphan (Robitussin Dm, Others)

Bitter orange might increase blood levels of dextromethorphan.
One small clinical study shows that bitter orange juice increases dextromethorphan levels, likely through cytochrome P450 3A4 (CYP3A4) inhibition. Theoretically, bitter orange might increase the risk for dextromethorphan-related adverse effects.

Likelihood Possible Evidence B
Felodipine (Plendil)

Bitter orange might increase blood levels of felodipine.
One small clinical study shows that bitter orange juice increases felodipine levels, likely through cytochrome P450 3A4 (CYP3A4) inhibition. Theoretically, bitter orange might increase the risk for felodipine-related adverse effects.

Likelihood Probable Evidence B
Indinavir (Crixivan)

Bitter orange might increase blood levels of indinavir.
One small clinical study shows that bitter orange juice slightly increases indinavir levels, but this effect is likely to be clinically insignificant. Bitter orange selectively inhibits intestinal cytochrome P450 3A4 (CYP3A4); however, the metabolism of indinavir seems to be more dependent on hepatic CYP3A4. The effect of bitter orange on other protease inhibitors has not been studied.

Likelihood Possible Evidence B
Qt Interval-Prolonging Drugs

Theoretically, bitter orange might have an additive effect when combined with drugs that prolong the QT interval, potentially increasing the risk of ventricular arrhythmias.
One case report suggests that taking bitter orange in combination with other stimulants such as caffeine might prolong the QT interval in some patients.

Likelihood Possible Evidence D
Sildenafil (Viagra)

Bitter orange juice might increase blood levels of sildenafil.
A small clinical study in healthy adult males shows that drinking freshly squeezed bitter orange juice 250 mL daily for 3 days and taking a single dose of sildenafil 50 mg on the 3rd day increases the peak plasma concentration of sildenafil by 18% and the overall exposure to sildenafil by 44%. Theoretically, this may be due to inhibition of cytochrome P450 3A4 by bitter orange.

Likelihood Probable Evidence B
Stimulant Drugs

Theoretically, bitter orange might increase the risk of hypertension and adverse cardiovascular effects when taken with stimulant drugs.
Bitter orange appears to have stimulant effects.

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

Theoretically, bitter orange might increase levels of drug metabolized by CYP2D6.
In vitro research shows that octopamine, a constituent of bitter orange, weakly inhibits CYP2D6 enzymes. This effect has not been reported in humans.

Likelihood Possible Evidence D
Citrus aurantium extract full monograph & interactions

Alpha-Yohimbine6 drug types · 677 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, rauwolscine may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Rauwolscine is structurally related to yohimbine. In vitro research shows that yohimbine inhibits platelet aggregation.

Likelihood Possible Evidence D
Calcium Channel Blockers

Theoretically, rauwolscine may have additive coronary vasodilatory effects if used with calcium channel blockers.
In vitro, rauwolscine inhibits calcium influx in aortic smooth muscle cells.

Likelihood Possible Evidence D
Clonidine (Catapres)

Theoretically, rauwolscine may inhibit the effects of clonidine.
In animal research, rauwolscine antagonized the effects of clonidine.

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

Theoretically, rauwolscine might increase levels of drugs metabolized by CYP2D6.
Rauwolscine is structurally related to yohimbine. In vitro research shows that yohimbine inhibits CYP2D6 enzyme activity.

Likelihood Possible Evidence D
Seizure Threshold Lowering Drugs

Theoretically, taking rauwolscine with seizure threshold lowering drugs might increase the risk of adverse convulsant effects.
In animal research, intraperitoneal rauwolscine lowered the seizure threshold level of the drug metrazol.

Likelihood Possible Evidence D
Stimulant Drugs

Theoretically, taking rauwolscine with stimulant drugs might increase the risk of adverse stimulant effects.
Rauwolscine has demonstrated stimulant effects in animal research.

Likelihood Possible Evidence D
Alpha-Yohimbine full monograph & interactions

Theobromine37 drug types · 661 drugs

Ace Inhibitors (Aceis)

Theoretically, taking cocoa with ACEIs might increase the risk of adverse effects.
Human research shows that dark chocolate can inhibit ACE. Additionally, prolonged angioedema in an elderly patient on an ACE inhibitor was precipitated with intake of diabetic chocolate.

Likelihood Possible Evidence D
Adenosine (Adenocard)

Theoretically, cocoa might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Cocoa contains caffeine. Caffeine is a competitive inhibitor of adenosine at the cellular level. However, 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 than adenosine-induced stress testing.

Likelihood Possible Evidence B
Alcohol (Ethanol)

Theoretically, concomitant use might increase levels and adverse effects of caffeine.
Cocoa contains caffeine. Alcohol reduces caffeine metabolism. Concomitant use of alcohol can increase caffeine serum concentrations and the risk of caffeine adverse effects.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, cocoa may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Clinical research shows that intake of cocoa can inhibit platelet adhesion, aggregation, and activity and increase aspirin-induced bleeding time. For patients on dual antiplatelet therapy, cocoa may enhance the inhibitory effect of clopidogrel, but not aspirin, on platelet aggregation.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, taking cocoa with antihypertensive drugs might increase the risk of hypotension.
Clinical research shows that cocoa can modestly decrease blood pressure in hypertensive and normotensive patients.

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

Theoretically, large amounts of cocoa might increase the cardiac inotropic effects of beta-agonists.
Cocoa contains caffeine. Theoretically, large amounts of caffeine might increase cardiac inotropic effects of beta-agonists. A case of atrial fibrillation associated with consumption of large quantities of chocolate in a patient with chronic albuterol inhalation abuse has also been reported.

Likelihood Probable Evidence D
Cytochrome P450 1A2 (Cyp1A2) Inhibitors

Theoretically, concomitant use might increase the levels and adverse effects of caffeine.
Cocoa contains caffeine. Caffeine is metabolized by cytochrome P450 1A2 (CYP1A2),. Theoretically, drugs that inhibit CYP1A2 may decrease the clearance rate of caffeine from cocoa and increase caffeine levels.

Likelihood Possible Evidence D
Dipyridamole (Persantine)

Theoretically, cocoa might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Cocoa contains caffeine. Caffeine may inhibit 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 than adenosine-induced stress testing.

Likelihood Probable Evidence B
Disulfiram (Antabuse)

Theoretically, disulfiram might increase the risk of adverse effects from caffeine.
Cocoa contains caffeine. In human research, disulfiram decreases the rate of caffeine clearance.

Likelihood Probable Evidence B
Diuretic Drugs

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

Likelihood Possible Evidence D
Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Cocoa contains caffeine. 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 Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Flutamide (Eulexin)

Theoretically, cocoa might increase the levels and adverse effects of flutamide.
Cocoa contains caffeine. In vitro evidence suggests that caffeine can inhibit the metabolism of flutamide.

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Lithium

Theoretically, abrupt cocoa withdrawal might increase the levels and adverse effects of lithium.
Cocoa contains caffeine. There are two case reports of lithium tremor that worsened upon abrupt coffee withdrawal.

Likelihood Possible Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Cocoa contains caffeine. Large amounts of caffeine with MAOIs might precipitate a hypertensive crisis.

Likelihood Possible Evidence D
Nicotine

Theoretically, concomitant use might increase the risk of hypertension.
Cocoa contains caffeine. 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, cocoa might decrease the effects of pentobarbital.
Cocoa contains caffeine. Caffeine might negate the hypnotic effects of pentobarbital.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

Theoretically, cocoa might reduce the effects of phenobarbital and increase the risk for convulsions.
Cocoa contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital. 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.
Cocoa contains 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, cocoa might reduce the effects of phenytoin and increase the risk for convulsions.
Cocoa contains caffeine. 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
Quinolone Antibiotics

Theoretically, quinolone antibiotics might increase the levels and adverse effects of caffeine.
Cocoa contains caffeine. Quinolones (also referred to as fluoroquinolones) decrease caffeine clearance.

Likelihood Probable Evidence B
Riluzole (Rilutek)

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

Likelihood Possible Evidence D
Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.
Cocoa contains caffeine. Concomitant use might increase the risk of stimulant adverse effects.

Likelihood Probable Evidence C
Theophylline

Theoretically, cocoa might increase the levels and adverse effects of theophylline.
Cocoa contains caffeine. Large amounts of caffeine might inhibit theophylline metabolism. Caffeine decreases theophylline clearance 23% to 29%.

Likelihood Probable Evidence B
Theobromine full monograph & all 37 interactions

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

Isopropylnorsynephrine HCl2 drug types · 344 drugs

Antihypertensive Drugs

Theoretically, isopropylnorsynephrine might decrease the effects of antihypertensive drugs.
In vitro research shows that isopropylnorsynephrine is a highly selective, direct-acting beta-adrenergic receptor agonist with positive chronotropic effects, and hypertension has been reported in patients taking combination products containing isopropylnorsynephrine and other stimulants.

Likelihood Possible Evidence D
Stimulant Drugs

Theoretically, taking isopropylnorsynephrine with stimulant drugs might have additive effects and increase the risk of adverse cardiovascular effects.
Isopropylnorsynephrine is an investigational beta-agonist and a derivative of synephrine and octopamine, which are stimulant constituents of bitter orange. In vitro research shows that isopropylnorsynephrine is a highly selective, direct-acting beta-adrenergic receptor agonist with positive chronotropic effects. Theoretically, isopropylnorsynephrine may also have stimulant effects.

Likelihood Possible Evidence D
Isopropylnorsynephrine HCl full monograph & interactions

Methylhexamine HCl2 drug types · 321 drugs

Cytochrome P450 2D6 (Cyp2D6) Substrates

1,3-DMAA strongly inhibits cytochrome P450 2D6 (CYP2D6) enzymes in vitro. Theoretically, 1,3-DMAA can increase levels of CYP2D6 substrates. Some of drugs that are CYP2D6 substrates include amitriptyline (Elavil), clozapine (Clozaril), codeine, desipramine (Norpramin), donepezil (Aricept), fentanyl (Duragesic), flecainide (Tambocor), fluoxetine (Prozac), meperidine (Demerol), methadone (Dolophine), metoprolol (Lopressor, Toprol XL), olanzapine (Zyprexa), ondansetron (Zofran), tramadol (Ultram), trazodone (Desyrel), and others.

Likelihood Possible Evidence D
Stimulant Drugs

1,3-DMAA is thought to have stimulant effects. There is concern that taking 1,3-DMAA with stimulant drugs might increase the risk of adverse cardiovascular effects. Some preliminary research shows that taking 1,3-DMAA 50 mg daily in combination with caffeine 250 mg daily does not increase respiratory rate, blood pressure, or other cardiovascular outcomes compared to taking caffeine alone in healthy men. However, a number of cardiovascular side effects have been reported for patients taking 1,3-DMAA in combination with other stimulants including caffeine. Theoretically, combining 1,3-DMAA with stimulant drugs might increase the risk of adverse cardiovascular effects. Some stimulant drugs include amphetamine, caffeine, diethylpropion (Tenuate), methylphenidate, phentermine (Ionamin), pseudoephedrine (Sudafed, others), and many others.

Likelihood Possible Evidence D
Methylhexamine HCl full monograph & interactions

Capsicum Annuum fruit extract6 drug types · 239 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, capsicum may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro research shows that capsicum might increase the effects of antiplatelet drugs. Also, population research shows that capsicum is associated with an increased risk of self-reported bleeding in patients taking warfarin. However, clinical research shows that taking a single dose of capsaicin (Asian Herbex Ltd.), the active ingredient in capsicum, 400-800 mcg orally in combination with aspirin 500 mg does not decrease platelet aggregation when compared with taking aspirin 500 mg alone. Also, there was no notable effect on measures of platelet aggregation with capsaicin. It is unclear whether capsaicin must be used in more than a single dose to affect platelet aggregation.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking capsicum with antidiabetes drugs might increase the risk of hypoglycemia.
Preliminary clinical research shows that consuming capsicum 5 grams along with a glucose drink attenuates the rise in plasma glucose after 30 minutes by 21%, decreases the 2-hour postprandial area under the curve of plasma glucose by 11%, and increases the 2-hour postprandial area under the curve of plasma insulin by 58% in healthy individuals when compared with placebo. Other clinical research shows that taking capsicum 5 mg daily for 28 days significantly reduces postprandial blood glucose and insulin levels, but not fasting blood glucose and insulin levels, in patients with gestational diabetes.

Likelihood Possible Evidence B
Aspirin

Theoretically, taking capsicum with aspirin might reduce the bioavailability of aspirin.
Animal research shows that acute or chronic intake of capsicum pepper reduces oral aspirin bioavailability. This has not been shown in humans.

Likelihood Possible Evidence D
Theophylline

Theoretically, taking capsicum with theophylline might increase the levels and adverse effects of theophylline.
In animal research, oral administration of capsicum reduced excretion of theophylline. However, capsicum does not seem to affect the pharmacokinetics of theophylline when administered intravenously.

Likelihood Possible Evidence D
Ace Inhibitors (Aceis)

Theoretically, using topical capsaicin may increase the risk of ACE inhibitor-induced cough.
There is one case report of a topically applied capsaicin cream contributing to the cough reflex in a patient using an ACEI. However, it is unclear if this interaction is clinically significant.

Likelihood Unlikely Evidence D
Ciprofloxacin (Cipro)

Theoretically, taking capsicum with ciprofloxacin might increase levels and adverse effects of ciprofloxacin.
Animal research shows that concomitant use of capsaicin, the active constituent of capsicum, and ciprofloxacin increases the bioavailability of ciprofloxacin by up to 70%.

Likelihood Possible Evidence D
Capsicum Annuum fruit extract full monograph & interactions

N-Methyl-Phenylethylamine2 drug types · 187 drugs

Monoamine Oxidase Inhibitors (Maois)

Theoretically, taking phenethylamine concomitantly with MAOIs may increase adverse effects.
In humans, phenethylamine is oxidized by MAO-B to form the inactive metabolite phenylacetic acid. Animal research shows that administering an MAOI prior to phenethylamine increases the amphetamine-like effects of phenethylamine. However, low-quality clinical research has used phenethylamine with selegiline, an MAOI, with apparent safety.

Likelihood Possible Evidence D
Serotonergic Drugs

Theoretically, combining serotonergic drugs with phenethylamine might increase the risk of serotonergic adverse effects.
Animal research shows that phenethylamine increases levels of serotonin, norepinephrine, and dopamine. Theoretically, combining serotonergic drugs with phenethylamine might increase the risk of additive serotonergic adverse effects, including serotonin syndrome and cerebral vasoconstrictive disorders. However, low-quality clinical research has used phenethylamine with selegiline, a monoamine oxidase inhibitor (MAOI), with apparent safety.

Likelihood Possible Evidence D
N-Methyl-Phenylethylamine full monograph & interactions

Raspberry Ketone extract2 drug types · 174 drugs

Stimulant Drugs

Theoretically, raspberry ketone might increase the risk of adverse cardiovascular effects with stimulant drugs.
Structurally, raspberry ketone resembles synephrine, a known stimulant agent. Heart palpitations, elevated blood pressure, coronary vasospasm, pulseless electrical activity arrest, and resistant polymorphic ventricular tachycardia have been reported in patients taking raspberry ketone.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, raspberry ketone might increase warfarin dose requirements.
In one case report, a patient taking warfarin 55 mg per week had a decrease in INR over a period of one month while taking raspberry ketone 250 mg daily. A warfarin dose increase to 70 mg per week was necessary to maintain a therapeutic INR while taking raspberry ketone. The mechanism for this potential interaction is not known.

Likelihood Possible Evidence D
Raspberry Ketone extract full monograph & interactions

Citrus limonium extract1 drug type · 1 drug

Itraconazole (Sporanox)

Theoretically, taking itraconazole capsules or tablets with a beverage containing lemon might increase the levels and clinical effects of itraconazole.
In one case report, dissolving itraconazole tablets in a small amount of specific beverages containing lemon prior to administration increased the level of itraconazole in a lung transplant patient. In this case, the increased bioavailability was desirable and was likely due to improved tablet dissolution in the acidic beverage.

Likelihood Possible Evidence D
Citrus limonium extract full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Wrath, from the product label.

Chaotic-Labz

See all Chaotic-Labz products
Web Address
www.chaoticlabz.com
Pharmacist Counseling Corner

Wrath by Chaotic-Labz: Common Questions

Does Wrath by Chaotic-Labz interact with any medications?
Yes. Based on its ingredients, Wrath has a known interaction with 1,628 medications, including 23 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Wrath contains 17 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 if I'm pregnant?
No. Bitter orange and isopropylnorsynephrine carry safety ratings advising against use in pregnancy due to stimulant effects and lack of safety data. Caffeine poses pregnancy risks at high doses — your doctor can advise on safe limits. 1,3-DMAA is unsafe in pregnancy. Most other active ingredients lack adequate pregnancy safety data. Talk with your doctor before considering this product.
Can I take this while breastfeeding?
Safety data is not established for most ingredients in this product while breastfeeding. Caffeine does pass into breast milk in small amounts — moderate intake is often considered acceptable, but high doses can affect the baby. Bitter orange, isopropylnorsynephrine, 1,3-DMAA, alpha-yohimbine, and raspberry ketone all have insufficient or negative breastfeeding safety information. Talk with your pharmacist or doctor for personalized guidance.
What are the most common side effects from caffeine in here?
Anxiety, insomnia, jitteriness, tremors, nausea, diarrhea, and restlessness. Rare but serious effects include stroke. Combined with the other stimulants in this product, cardiovascular side effects like elevated heart rate and blood pressure are a real concern.
Why is 1,3-DMAA in this product if it's banned?
1,3-DMAA (methylhexamine) was banned by the FDA in 2013 due to serious cardiovascular harm. However, some supplement makers still source and sell it. The ingredient carries risk of cardiac arrest, heart attack, stroke, and life-threatening complications, especially when combined with other stimulants like those in this formula.
Will this help me lose weight or boost my athletic performance?
Caffeine is likely effective for athletic performance. Bitter orange, isopropylnorsynephrine, alpha-yohimbine, 1,3-DMAA, and raspberry ketone all lack sufficient reliable evidence to support weight loss or athletic benefit — we cannot say they work based on the data we hold. Green tea extract does have some evidence for weight-related effects, but it's limited.
What's the difference between the stimulants in here?
Caffeine works by blocking adenosine (a sleepiness signal). Bitter orange's synephrine mimics adrenaline. Isopropylnorsynephrine is a synthetic beta-agonist (adrenaline-receptor activator). Alpha-yohimbine and 1,3-DMAA are potent, poorly studied compounds that increase norepinephrine and dopamine. All together, they stack stimulation with compounded cardiovascular risk.

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

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Label information is sourced from the NIH Dietary Supplement Label Database and reflects the product version on file; always read your actual product label. This page is for education only and is not a substitute for professional medical advice. Confirm with your pharmacist or doctor before combining supplements and medications.

Wrath label
Go deeper

The Full Monographs Behind Wrath’s Ingredients

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

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

Cocoa

Interacts with 661 drugs

Cocoa is rich in plant compounds called flavanols that may modestly support blood vessel function and blood pressure, but most chocolate products are high in sugar, fat, and calories, which...

Read the full Cocoa monograph → Herb & supplement monograph

Phenethylamine (pea)

Interacts with 187 drugs

Phenethylamine (PEA) is a natural compound made in the body and found in foods like chocolate; supplements are marketed for mood, focus, and energy. Reliable human research on the supplement...

Read the full Phenethylamine (pea) monograph → Herb & supplement monograph

Bitter Orange

Interacts with 957 drugs

Bitter orange is a citrus fruit whose extracts contain synephrine, a mild stimulant often added to weight-loss and energy supplements. Evidence that it works for weight loss or performance i...

Read the full Bitter Orange monograph → Herb & supplement monograph

Isopropylnorsynephrine

Interacts with 344 drugs

Isopropylnorsynephrine is a synthetic stimulant chemically related to synephrine, marketed mainly in weight-loss and pre-workout supplements. It has very little human safety or effectiveness...

Read the full Isopropylnorsynephrine monograph → Herb & supplement monograph

Raspberry Ketone

Interacts with 174 drugs

Raspberry ketone is a natural aroma compound found in red raspberries that is heavily marketed for weight loss, but there is no good human evidence that it helps people lose weight. Most cla...

Read the full Raspberry Ketone monograph → Herb & supplement monograph

Rauwolscine

Interacts with 677 drugs

Rauwolscine (alpha-yohimbine) is a stimulant alkaloid closely related to yohimbine that is marketed mainly in fat-burning and pre-workout supplements. Human evidence for its benefits is very...

Read the full Rauwolscine monograph → Herb & supplement monograph

1,3-dmaa

Interacts with 321 drugs

DMAA (1,3-dimethylamylamine) is a synthetic stimulant that was sold in pre-workout and weight-loss supplements but has been linked to serious harm, including high blood pressure, heart probl...

Read the full 1,3-dmaa monograph → Herb & supplement monograph

Green Tea

Interacts with 1,293 drugs

Green tea is a popular beverage rich in antioxidants called catechins, and drinking it in normal amounts is considered safe for most people. Concentrated green tea extracts are a different s...

Read the full Green Tea monograph → Herb & supplement monograph

Yohimbe

Interacts with 1,125 drugs

Yohimbe is a West African tree bark that contains yohimbine, a compound mainly promoted for erectile dysfunction and as an aphrodisiac. A prescription form of yohimbine has some evidence for...

Read the full Yohimbe monograph → Herb & supplement monograph

Capsicum

Interacts with 239 drugs

Capsicum (chili pepper) contains capsaicin, which is best known and best studied as a topical treatment for certain types of pain. Topical capsaicin products are supported by reasonable evid...

Read the full Capsicum monograph → Herb & supplement monograph

Lemon

Interacts with 1 drug

Lemon is a common citrus fruit that is a good source of vitamin C and citric acid, and it is widely used in food, drinks, and home remedies. While it can support hydration and a healthy diet...

Read the full Lemon monograph →
Sources

Sources & How We Checked

Wrath'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 843 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.

Caffeine 236 references
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See these in context on the Cocoa monograph →

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See these in context on the Green Tea monograph →

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See these in context on the Capsicum monograph →

Lemon 2 references
  1. Ruggenenti P, Caruso MR, Cortinovis M, et al. Fresh lemon juice supplementation for the prevention of recurrent stones in calcium oxalate nephrolithiasis: A pragmatic, prospective, randomised, open, blinded endpoint (PROBE) trial. EClinicalMedicine 2021;4 PubMed
  2. Umemura K, Katada Y, Nakagawa S, et al. Improved absorption of itraconazole tablet by co-administration with lemon beverages in a lung transplant recipient: A case report. J Infect Chemother 2022;28(8):1203-1207. PubMed

See these in context on the Lemon monograph →

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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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