Major interaction on record — check this product against your medications before combining. Based on 17 of 18 ingredients. Check your meds →
Dietary supplement

Maximum Energy Blend Ingredients & Drug Interactions

by Uptime

Tablet Or Pill Category: Other Combinations
Most serious interaction: Major
The interaction bottom line Most serious interaction: Major

Maximum Energy Blend is a dietary supplement by Uptime with 18 active ingredients. Its ingredients are commonly taken for bone health and osteoporosis prevention, dietary calcium deficiency, heartburn relief (calcium carbonate antacids).Based on those ingredients, 1,675 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Green Tea extract, Eleuthero, Schisandra. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Maximum Energy Blend by Uptime

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

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 7 of its 18 active ingredients.
  • “Uptime Power Base (Combination)” is listed as a grouped ingredient — the label gives one combined amount (270 mg) without saying how much of each component you get.

Maximum Energy Blend contains 18 active ingredients formulated to support energy and vitality. The lineup includes mineral and vitamin-like compounds (calcium, zinc, magnesium), traditional botanical extracts (cayenne, schisandra, astragalus, eleuthero, guarana extract, kola nut extract, green tea extract, reishi mushroom, noni), herbal preparations (Korean ginseng, royal jelly), amino acid metabolites (5-HTP), coenzyme Q10, lutein, and caffeine.

The tablet is also made up of several inactive ingredients—cellulose, stearic acid, silicon dioxide, croscarmellose sodium, magnesium stearate, and ethyl cellulose—which serve as binders and flow agents. These actives are chosen for their roles in energy metabolism, antioxidant support, immune function, and mental alertness, though evidence for many of these uses varies.

Caffeine and guarana extract directly stimulate the central nervous system, while minerals like magnesium and zinc participate in hundreds of enzymatic reactions throughout the body.

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: increase energy and provide nutrition.
  • We looked for evidence on: Athletic performance, fatigue, mental focus, endurance.
  • The strongest evidence on file: Caffeine is rated "Likely Effective" for Athletic performance (Natural Medicines).
  • Also on file: Coenzyme Q10 is rated "Possibly Ineffective" for Chemotherapy-related fatigue.
  • Also on file: Magnesium is rated "Possibly Ineffective" for Athletic performance.

Effectiveness data in our files varies widely across the ingredients. Calcium is effective for kidney failure, dyspepsia, hypocalcemia, and hyperkalemia, and likely effective for osteoporosis.

Zinc is effective for zinc deficiency and likely effective for Wilson disease. Magnesium is effective for dyspepsia, constipation, and hypomagnesemia.

Caffeine is effective for neonatal apnea and postoperative headache, and likely effective for mental alertness and athletic performance. Green tea extract is likely effective for human papillomavirus (HPV) and possibly effective for ovarian cancer and high cholesterol.

Other ingredients show mixed or limited evidence. Cayenne is likely effective for nerve pain conditions (postherpetic neuralgia and diabetic neuropathy) and possibly effective for cluster headache, back pain, and nausea after surgery.

Lutein is possibly effective for age-related macular degeneration and cataracts. Coenzyme Q10 is likely effective for CoQ10 deficiency and possibly effective for fibromyalgia, migraine, heart failure, and diabetic nerve pain.

For schisandra, astragalus, eleuthero, guarana, kola nut, royal jelly, reishi mushroom, 5-HTP, and noni, the evidence we hold is either insufficient to rate or shows these ingredients as possibly ineffective for the conditions tested. Talk with your doctor or pharmacist about whether any of these actives match your personal health goals.

The evidence, ingredient by ingredient Calcium Zinc Lutein 5-htp Coenzyme Q10 Royal Jelly Magnesium Capsicum

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 17 of the 17 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 17 of 17.
  • General safety write-ups exist for 17 of 17.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients in this blend are generally well tolerated when used as directed, though several carry important cautions. Calcium, zinc, magnesium, and caffeine are safe in recommended amounts but can cause problems at high doses—particularly calcium and zinc, which at very high intakes have been linked to concerns about prostate cancer risk and copper deficiency respectively.

Caffeine is possibly unsafe in pregnancy and may pass into breast milk. Cayenne, 5-HTP, astragalus, eleuthero, royal jelly, and reishi mushroom should be avoided in pregnancy and breastfeeding due to insufficient safety data or theoretical uterine stimulation.

Schisandra, green tea extract, and guarana extract are similarly not well studied for these life stages. Lutein and coenzyme Q10 have limited pregnancy/lactation data on file.

Royal jelly poses a particular risk: it can trigger serious allergic reactions—including anaphylaxis—in people with a history of asthma or atopy. Common mild side effects from individual ingredients include digestive upset (calcium, magnesium, cayenne, 5-HTP), caffeine-related jitteriness and sleep disruption, and headache (various ingredients).

Side effects, ingredient by ingredient Calcium Zinc Lutein 5-htp Coenzyme Q10 Royal Jelly Magnesium Capsicum

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?
  • 16 of the 17 matched ingredients can interact with medications — Schisandra, Royal Jelly, Noni, Calcium, 5-htp, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,676 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.

Check with your doctor or pharmacist before taking this product if you use ephedrine or related stimulants (major risk of serious heart, stroke, and seizure complications with the caffeine and guarana in this blend), HIV integrase inhibitors like dolutegravir or elvitegravir (calcium reduces their levels), the antibiotic ceftriaxone (calcium can cause dangerous organ damage), levodopa/carbidopa for Parkinson's disease (magnesium cuts absorption), blood thinners like warfarin (multiple ingredients may interfere), blood pressure medications (several ingredients can lower pressure further), antiseizure drugs like phenytoin or carbamazepine (caffeine-containing ingredients may reduce their effects), diabetes medications (several ingredients may lower blood sugar), antibiotics including quinolones and tetracyclines (zinc and magnesium interfere with absorption), thyroid hormone levothyroxine (calcium reduces absorption), or heart medications including digoxin, diltiazem, or nadolol. No interactions are documented for Korean ginseng, but we hold no monograph for it either.

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 broad-spectrum energy blend may appeal to people looking to support alertness, antioxidant defense, and general vitality—especially those already aware of the individual ingredients. However, the sheer number of actives and their interactions with medications make this product one to clear with your own doctor or pharmacist before starting, particularly if you take any prescription drugs, blood thinners, heart or blood pressure medications, antiseizure drugs, diabetes medications, or thyroid hormones.

If you have asthma or a history of allergies, royal jelly in this formula warrants extra caution. Pregnant or breastfeeding individuals should discuss this product's safety with their healthcare provider before use.

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

Assessment coverage: 17 of 18 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Feb 23, 2018.

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 Maximum Energy Blend, straight from the product label.

Brand Uptime
Barcode (UPC) 025713918282
Net contents 60 Tablet(s)
Market status On market
Date entered into DSLD Feb 23, 2018
DSLD ID 82699
Product type Other Combinations
Supplement form Tablet Or Pill
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Vegetarian, Adult (18 - 50 Years), Sugar 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 Maximum Energy Blend by Uptime, 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:
1 Tablet(s)
Maximum serving Sizes:
1 Tablet(s)
Servings per container
60
UPC/BARCODE
025713918282
IngredientAmount% DV
Calcium150 mg15%
Cayenne0 NP--
Schisandra0 NP--
Zinc5 mg33.3%
Caffeine0 NP--
Lutein25 mcg--
5-HTP0.5 mg--
Astragalus0 NP--
Coenzyme Q100.5 mg--
Green Tea extract0 NP--
Royal Jelly1 mg--
Magnesium50 mg12.5%
Eleuthero0 NP--
Korean Ginseng0 NP--
Guarana extract0 NP--
Kola Nut extract0 NP--
Uptime Power Base (Combination)270 mg--
Noni0 NP--
Reishi Mushroom0 NP--

Other ingredients: Cellulose, Stearic Acid, Silicon Dioxide, Croscarmellose Sodium, Magnesium Stearate, Ethyl Cellulose

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

UPTIME Maximum Energy Blend is a unique superfood supplement designed to help increase energy and provide nutrition.

Fast + Balanced + Lasting New look | Trusted since 1985

Energy to excel

Mental ~ Physical

Formula

The tablets are formulated with ginseng, guarana coenzyme Q10, herbs, minerals and nutrients to help give you a heightened boost during intense work, exercise or play.

Coenzyme Q10 Guarana Ginseng

Suggested/Recommended/Usage/Directions

Recommended Use: Take one tablet for moderate energy. Take 3 tablets for maximum energy. Do not exceed 3 tablets per day.

Try UPTIME Energy drinks!

Precautions

Do not exceed 3 tablets per day.

Do not take if you are pregnant, nursing or under 12 years of age. If you are taking medication and/or have a medical condition, consult your doctor before use.

Do not take if you are pregnant, nursing or under 12 years of age. If you are taking medication and/or have a medical condition, consult your doctor before use. Keep out of reach of children.

FDA Disclaimer Statement

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

Storage

Store in a cool, dry place that is protected from light.

FDA Statement of Identity

Energy Supplement

Formulation

0 calories 0 Sugar

Vegetarian approved

See for yourself

Maximum Energy Blend by Uptime label

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

What’s inside

The Ingredients in Maximum Energy Blend by Uptime

These are the 18 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Tablet(s) Dosage formTablet Or Pill Servings per container60 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.

Calcium

Interacts with
168 drugs
150 mg per serving Form: Calcium Carbonate

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

Zinc

Interacts with
67 drugs
5 mg per serving Form: Zinc Oxide

Zinc is an essential mineral that your body needs for immune function, wound healing, taste, and smell. Most people get enough from food, but suppleme...

Zinc monograph & interactions

Lutein

No known
interactions
25 mcg per serving

Lutein is a plant-based antioxidant pigment that concentrates in the eye, and the best evidence suggests it (often combined with zeaxanthin) may help...

Lutein monograph & interactions

5-HTP

Interacts with
398 drugs
0.5 mg per serving

5-HTP is a compound your body uses to make serotonin, and people take it as a supplement hoping to improve mood, sleep, and headaches. Some early rese...

5-HTP monograph & interactions

Coenzyme Q10

Interacts with
198 drugs
0.5 mg per serving

CoQ10 is a vitamin-like substance your body makes naturally that helps cells produce energy and acts as an antioxidant. It is generally well tolerated...

Coenzyme Q10 monograph & interactions

Royal Jelly

Interacts with
174 drugs
1 mg per serving

Royal jelly is a nutrient-rich substance made by worker bees to feed the queen bee. People take it for menopause symptoms, energy, skin, and immune su...

Royal Jelly monograph & interactions

Magnesium

Interacts with
295 drugs
50 mg per serving Form: Magnesium Oxide

Magnesium is an essential mineral your body needs for muscles, nerves, blood pressure, and many other functions, and supplements are useful for preven...

Magnesium monograph & interactions

Uptime Power Base (Combination)

270 mg per serving

Other (inactive) ingredients: Cellulose, Stearic Acid, Silicon Dioxide, Croscarmellose Sodium, Magnesium Stearate, Ethyl Cellulose. These complete the product’s ingredient list but are not active constituents.

Interaction report

Maximum Energy Blend by Uptime Drug Interactions

Want to check YOUR meds against Maximum Energy Blend?

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
1,675Drugs
26 Major 1,630 Moderate 19 Minor

Ingredients driving the most interactions

Eleuthero 1,140
Caffeine 655

Each ingredient & the kinds of drugs it affects

For each ingredient in Maximum Energy Blend 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

Eleuthero10 drug types · 1,140 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research shows that a constituent of eleuthero, dihydroxybenzoic acid, appears to inhibit platelet aggregation. Concomitant use with anticoagulant or antiplatelet drugs might increase the risk of bleeding. This effect has not been reported in humans.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, eleuthero might have additive effects when used with antidiabetes drugs.
Animal research suggests that certain constituents of eleuthero have hypoglycemic activity in both healthy and diabetic animals. A small study in adults with type 2 diabetes also shows that taking eleuthero for 3 months can lower blood glucose levels. However, one very small study in healthy individuals shows that taking powdered eleuthero 3 grams, 40 minutes prior to a 75-gram oral glucose tolerance test, significantly increases postprandial blood glucose levels when compared with placebo. These contradictory findings might be due to patient-specific variability and variability in active ingredient ratios.

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.
In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2. This effect has not been reported in humans.

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2C9.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9. This effect has not been reported in humans.

Likelihood Possible Evidence D
Digoxin (Lanoxin)

Eleuthero might increase serum digoxin levels and increase the risk of side effects.
In one case report, a 74-year-old male who was stabilized on digoxin presented with an elevated serum digoxin level after starting an eleuthero supplement, without symptoms of toxicity. After stopping the supplement, serum digoxin levels returned to normal. It is not clear whether this was due to a pharmacokinetic interaction or to interference with the digoxin assay. Although the product was found to be free of digoxin and digitoxin, it was not tested for other contaminants.

Likelihood Unlikely Evidence D
Immunosuppressants

Theoretically, eleuthero might interfere with immunosuppressive drugs because of its immunostimulant activity.
Animal and in vitro research shows that eleuthero extracts have immunomodulatory effects, including increasing cellular and humoral activity.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, eleuthero might increase levels of P-glycoprotein substrates.
In vitro research suggests that eleuthero can inhibit the multi-drug transporter protein, P-glycoprotein. However, it is too soon to tell if this is clinically important. This interaction has not been reported in humans.

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2D6. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP2D6 drug metabolism.

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

Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.
In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP3A4. However, research in healthy human volunteers has found that taking eleuthero 485 mg twice daily for 14 days does not inhibit CYP3A4 drug metabolism.

Likelihood Unlikely Evidence B
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Theoretically, eleuthero might decrease levels of drugs metabolized by OATP.
In vitro research suggests that eleuthero inhibits OATP2B1, which might reduce the bioavailability of oral drugs that are substrates of OATP2B1. Due to the weak inhibitory effect identified in this study, this interaction is not likely to be clinically significant.

Likelihood Possible Evidence D

Schisandra12 drug types · 803 drugs

Cyclophosphamide

Theoretically, schisandra might increase the levels and clinical effects of cyclophosphamide.
In vitro research shows that schisandra increases the concentration of cyclophosphamide, likely through inhibition of cytochrome P450 3A4. After multiple doses of the schisandra constituents schisandrin A and schisantherin A, the maximum concentration of cyclophosphamide was increased by 7% and 75%, respectively, while the overall exposure to cyclophosphamide was increased by 29% and 301%, respectively.

Likelihood Probable Evidence D
Cyclosporine (Neoral, Sandimmune)

Schisandra can increase the levels and clinical effects of cyclosporine.
A small observational study in children with aplastic anemia found that taking schisandra with cyclosporine increased cyclosporine trough levels by 93% without increasing the risk of adverse events. However, the dose of cyclosporine was reduced in 9% of children to maintain appropriate cyclosporine blood concentrations.

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

Theoretically, schisandra might increase the levels and clinical effects of CYP2C19 substrates.
In vitro research shows that schisandra inhibits CYP2C19, and animal research shows that schisandra increases the concentration of voriconazole, a CYP2C19 substrate. Theoretically, schisandra may also inhibit the metabolism of other CYP2C19 substrates. This effect has not been reported in humans.

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

Theoretically, schisandra might decrease the levels and clinical effects of CYP2C9 substrates.
In vitro and animal research suggests that schisandra induces CYP2C9 enzymes. This effect has not been reported in humans.

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

Schisandra can increase the levels and clinical effects of drugs metabolized by CYP3A4.
Most clinical and laboratory research shows that schisandra, administered either as a single dose or up to twice daily for 14 days, inhibits CYP3A4 and increases the concentration of CYP3A4 substrates such as cyclophosphamide, midazolam, tacrolimus, and talinolol. Although one in vitro and animal study shows that schisandra may induce CYP3A4 metabolism, this effect appears to be overpowered by schisandra's CYP3A4 inhibitory activity and has not been reported in humans.

Likelihood Probable Evidence D
Midazolam (Versed)

Schisandra can increase the levels and clinical effects of midazolam.
A small pharmacokinetic study in healthy adults shows that taking schisandra extract (Hezheng Pharmaceutical Co.) containing deoxyschizandrin 33.75 mg twice daily for 8 days and a single dose of midazolam 15 mg on day 8 increases the overall exposure to midazolam by about 119%, increases the peak plasma level of midazolam by 86%, and decreases midazolam clearance by about 52%. This effect has been attributed to inhibition of CYP3A4 by schisandra.

Likelihood Probable Evidence B
P-Glycoprotein Substrates

Schisandra might increase the levels and clinical effects of P-glycoprotein substrates.
In vitro research shows that schisandra extracts and constituents such as schisandrin B inhibit P-glycoprotein mediated efflux in intestinal cells and in P-glycoprotein over-expressing cell lines. Additionally, a small clinical study shows that schisandra increases the peak concentration and overall exposure to talinolol, a P-glycoprotein probe substrate. Theoretically, schisandra might inhibit the efflux of other P-glycoprotein substrates.

Likelihood Possible Evidence D
Sirolimus (Rapamune)

Schisandra can increase the levels and clinical effects of sirolimus.
A small pharmacokinetic study in healthy volunteers shows that taking 3 capsules of schisandra (Hezheng Pharmaceutical Company) containing a total of 33.75 mg deoxyschizandrin twice daily for 13 days and then taking a single dose of sirolimus 2 mg increases the overall exposure and peak level of sirolimus by two-fold. This effect is thought to be due to inhibition of cytochrome P450 3A4 by schisandra, as well as possible inhibition of the P-glycoprotein drug transporter.

Likelihood Probable Evidence B
Tacrolimus (Prograf)

Schisandra can increase the levels and clinical effects of tacrolimus.
Clinical research in healthy children and adults, transplant patients, and patients with nephrotic syndrome and various rheumatic immunologic disorders shows that taking schisandra with tacrolimus increases tacrolimus peak levels by 183% to 268%, prolongs or delays time to peak tacrolimus concentrations, increases overall exposure to tacrolimus by 126% to 343%, and decreases tacrolimus clearance by 19% to 73%. This effect is thought to be due to inhibition of P-glycoprotein drug transporter and CYP3A4 and CYP3A5 by schisandra. Some clinical and observational studies suggest that schisandra increases tacrolimus levels similarly in both expressors and non-expressors of CYP3A5, while other studies suggest it does so to a greater degree in CYP3A5 expressors than non-expressors. Animal research suggests that the greatest increase in tacrolimus levels occurs when schisandra is taken either concomitantly or up to 2 hours before tacrolimus, and clinical and observational research in humans suggests that schisandra may increase whole blood levels of tacrolimus and decrease clearance of tacrolimus in a dose-dependent manner.

Likelihood Probable Evidence B
Talinolol

Schisandra can increase the levels and clinical effects of talinolol.
A small pharmacokinetic study in healthy volunteers shows that taking schisandra extract 300 mg twice daily for 14 days with a single dose of talinolol 100 mg on day 14 increases the peak talinolol level by 51% and the overall exposure to talinolol by 47%. This effect is thought to be due to the possible inhibition of cytochrome P450 3A4 and P-glycoprotein by schisandra. tly.

Likelihood Probable Evidence B
Voriconazole (Vfend)

Theoretically, schisandra might increase the levels and clinical effects of voriconazole.
Animal research shows that oral schisandra given daily for 1 or 14 days increases levels of intravenously administered voriconazole, a cytochrome P450 (CYP) 2C19 substrate. This effect is thought to be due to inhibition of CYP2C19 by schisandra. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, schisandra might decrease the levels and clinical effects of warfarin.
Animal research suggests that oral schisandra extract, given daily for 6 days, reduces levels of intravenously administered warfarin. This effect might be due to the induction of cytochrome P450 (CYP) 2C9 metabolism by schisandra. However, this interaction has not been reported in humans.

Likelihood Possible Evidence D

Caffeine41 drug types · 655 drugs

Ephedrine

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

Likelihood Probable Evidence D
Adenosine (Adenocard)

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

Likelihood Possible Evidence B
Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

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

Likelihood Probable Evidence D
Carbamazepine (Tegretol)

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

Likelihood Possible Evidence D
Cimetidine (Tagamet)

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

Likelihood Likely Evidence B
Clozapine (Clozaril)

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

Likelihood Possible Evidence B
Dipyridamole (Persantine)

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

Likelihood Probable Evidence B
Disulfiram (Antabuse)

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

Likelihood Probable Evidence B
Diuretic Drugs

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

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

Likelihood Possible Evidence D
Felbamate (Felbatol)

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

Likelihood Possible Evidence D
Flutamide (Eulexin)

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

Likelihood Probable Evidence D
Fluvoxamine (Luvox)

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

Likelihood Probable Evidence D
Lithium

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

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

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

Likelihood Possible Evidence D
Nicotine

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

Likelihood Probable Evidence B
Pentobarbital (Nembutal)

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

Likelihood Possible Evidence B
Phenobarbital (Luminal)

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

Likelihood Possible Evidence D
Phenylpropanolamine

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

Likelihood Probable Evidence B
Phenytoin (Dilantin)

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

Likelihood Possible Evidence D
Pioglitazone (Actos)

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

Likelihood Possible Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Riluzole (Rilutek)

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

Likelihood Possible Evidence D

Guarana extract41 drug types · 655 drugs

Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Guarana contains caffeine. 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, guarana might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Guarana 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 (Persantine) than adenosine-induced stress testing.

Likelihood Possible Evidence B
Anticoagulant/Antiplatelet Drugs

Theoretically, guarana may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research suggests that guarana extract can inhibit platelet aggregation. This effect may be due to the caffeine in guarana, which is also reported to have antiplatelet activity. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Beta-Adrenergic Agonists

Theoretically, concomitant use might increase the clinical effects of beta-adrenergic agonists.
Guarana contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase cardiac inotropic effects of beta-agonists.

Likelihood Probable Evidence D
Carbamazepine (Tegretol)

Theoretically, guarana 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 given to animals 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 two-fold in healthy individuals.

Likelihood Possible Evidence D
Cimetidine (Tagamet)

Theoretically, concomitant use might increase the effects and adverse effects of caffeine in guarana.
Guarana contains caffeine. Cimetidine decreases the rate of caffeine clearance by 31% to 42%.

Likelihood Likely Evidence B
Clozapine (Clozaril)

Theoretically, guarana might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Guarana contains caffeine. Caffeine can 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). 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 more sensitive to the interaction between clozapine and caffeine.

Likelihood Possible Evidence B
Dipyridamole (Persantine)

Theoretically, guarana might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Guarana 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 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 D
Diuretic Drugs

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

Theoretically, guarana might reduce the effects of ethosuximide and increase the risk for convulsions.
Guarana contains caffeine. Animal research shows that caffeine 92.4 mg/kg can decrease the anticonvulsant activity of ethosuximide. This effect has not been observed in humans.

Likelihood Possible Evidence D
Felbamate (Felbatol)

Theoretically, guarana might reduce the effects of felbamate and increase the risk for convulsions.
Guarana contains caffeine. Animal research shows that a high dose of caffeine 161.7 mg/kg can decreases the anticonvulsant activity of felbamate. This effect has not been observed in humans.

Likelihood Possible Evidence D
Flutamide (Eulexin)

Theoretically, guarana might increase the levels and adverse effects of flutamide.
Guarana contains caffeine. In vitro evidence shows 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.
Guarana contains caffeine. Fluvoxamine reduces caffeine metabolism.

Likelihood Probable Evidence D
Lithium

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

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Guarana contains caffeine. Caffeine has been shown to inhibit 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.
Guarana 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 D
Pentobarbital (Nembutal)

Theoretically, guarana might decrease the effects of pentobarbital.
Guarana contains caffeine. In vivo evidence suggests that caffeine can negate the hypnotic effects of pentobarbital in humans. However, animal research suggests that guarana does not alter the hypnotic effect of pentobarbital.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

Theoretically, guarana might reduce the effects of phenobarbital and increase the risk for convulsions.
Guarana contains caffeine. Animal research shows 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.
Guarana 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, guarana might reduce the effects of phenytoin and increase the risk for convulsions.
Guarana contains caffeine. Animal research shows 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, guarana might increase the levels and clinical effects of pioglitazone.
Guarana contains caffeine. 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
Riluzole (Rilutek)

Theoretically, concomitant use might increase the levels and adverse effects of both caffeine and riluzole.
Guarana contains caffeine. 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
Stimulant Drugs

Theoretically, concomitant use might increase stimulant adverse effects.
Guarana contains caffeine. Due to the central nervous system (CNS) stimulant effects of caffeine, concomitant use with stimulant drugs can increase the risk of adverse effects.

Likelihood Possible Evidence D

Kola Nut extract41 drug types · 655 drugs

Adenosine (Adenocard)

Theoretically, cola nut might decrease the vasodilatory effects of adenosine and interfere with its use prior to stress testing.
Cola nut 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 (including cola nut) 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
Alcohol (Ethanol)

Theoretically, alcohol might increase the levels and adverse effects of the caffeine in cola nut.
Cola nut contains caffeine. Concomitant use of alcohol and caffeine can increase caffeine serum concentrations and the risk of caffeine adverse effects. Alcohol reduces caffeine metabolism.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, cola nut may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Cola nut contains caffeine. Caffeine is reported to have antiplatelet activity. This interaction has not been reported in humans.

Likelihood Unlikely Evidence D
Beta-Adrenergic Agonists

Theoretically, the caffeine in cola nut might increase the clinical effects of beta-adrenergic agonists.
Cola nut contains caffeine. Theoretically, concomitant use of large amounts of caffeine might increase the cardiac inotropic effects of beta-agonists.

Likelihood Probable Evidence D
Carbamazepine (Tegretol)

Theoretically, cola nut might reduce the effects of carbamazepine and increase the risk for convulsions.
Cola nut 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
Clozapine (Clozaril)

Theoretically, cola nut might increase the levels and adverse effects of clozapine and acutely exacerbate psychotic symptoms.
Cola nut contains caffeine. 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 more sensitive to the interaction between clozapine and caffeine.

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

Theoretically, CYP1A2 inhibitors might increase the levels and adverse effects of the caffeine in cola nut.
Cola nut contains caffeine. Caffeine is metabolized by CYP1A2,.

Likelihood Possible Evidence D
Dipyridamole (Persantine)

Theoretically, cola nut might decrease the vasodilatory effects of dipyridamole and interfere with its use prior to stress testing.
Cola nut contains caffeine. Caffeine may inhibit dipyridamole-induced vasodilation. It is recommended that methylxanthines and methylxanthine-containing products, such as cola nut, be stopped 24 hours prior to pharmacological stress tests. Methylxanthines appear more likely to interfere with dipyridamole than with adenosine-induced stress testing.

Likelihood Probable Evidence B
Disulfiram (Antabuse)

Theoretically, disulfiram might increase the levels and adverse effects of the caffeine in cola nut.
Cola nut contains caffeine. In human research, disulfiram decreases the rate of caffeine clearance.

Likelihood Probable Evidence D
Diuretic Drugs

Theoretically, using cola nut with diuretic drugs might increase the risk of hypokalemia.
Cola nut contains caffeine. In excessive amounts, caffeine can reduce potassium levels due to stimulation of the sodium-potassium pump. Certain diuretics can also lower potassium levels.

Likelihood Possible Evidence D
Ephedrine

Theoretically, concomitant use might increase the risk for stimulant adverse effects.
Cola nut 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 the caffeine in cola nut.
Cola nut contains caffeine. Estrogen inhibits caffeine metabolism.

Likelihood Probable Evidence B
Ethosuximide (Zarontin)

Theoretically, cola nut might reduce the effects of ethosuximide and increase the risk for convulsions.
Cola nut 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, cola nut might reduce the effects of felbamate and increase the risk for convulsions.
Cola nut 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
Flutamide (Eulexin)

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

Likelihood Possible Evidence D
Fluvoxamine (Luvox)

Theoretically, fluvoxamine might increase the levels and adverse effects of the caffeine in cola nut.
Cola nut contains caffeine. Fluvoxamine reduces caffeine metabolism.

Likelihood Probable Evidence D
Lithium

Theoretically, abrupt cola nut withdrawal might increase the levels and adverse effects of lithium.
Cola nut contains caffeine. Abrupt caffeine withdrawal can increase serum lithium levels. There are two case reports of lithium tremor that worsened upon abrupt coffee withdrawal.

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, concomitant use might increase the risk of a hypertensive crisis.
Cola nut contains caffeine. 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.
Cola nut 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 D
Pentobarbital (Nembutal)

Theoretically, cola nut might decrease the effects of pentobarbital.
Cola nut contains caffeine. Theoretically, caffeine might negate the hypnotic effects of pentobarbital.

Likelihood Possible Evidence B
Phenobarbital (Luminal)

Theoretically, cola nut might reduce the effects of phenobarbital and increase the risk for convulsions.
Cola nut contains caffeine. Animal research suggests that caffeine can decrease the anticonvulsant activity of phenobarbital. However, this effect has not been reported in humans.

Likelihood Possible Evidence D
Phenylpropanolamine

Theoretically, phenylpropanolamine might increase the risk of hypertension, as well as the levels and adverse effects of the caffeine in cola nut.
Cola nut 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, cola nut might reduce the effects of phenytoin and increase the risk for convulsions.
Cola nut 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
Pioglitazone (Actos)

Theoretically, cola nut might increase the levels and clinical effects of pioglitazone.
Cola nut contains caffeine. 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 the caffeine in cola nut.
Cola nut contains caffeine. Quinolones (also called fluoroquinolones) can decrease caffeine clearance by inhibiting cytochrome P450 1A2 (CYP1A2).

Likelihood Probable Evidence B

Noni8 drug types · 542 drugs

Ace Inhibitors (Aceis)

Theoretically, combining noni and ACE inhibitors might increase the risk of hyperkalemia.
Noni juice contains significant amounts of potassium, about 6 mEq/100 mL juice. This may increase the risk for hyperkalemia when used in conjunction with ACE inhibitors, which can also increase potassium levels.

Likelihood Possible Evidence D
Angiotensin Receptor Blockers (Arbs)

Theoretically, combining noni and ARBs might increase the risk of hyperkalemia.
Noni juice contains significant amounts of potassium, about 6 mEq/100 mL juice. This may increase the risk for hyperkalemia when used in conjunction with ARBs, which can also increase potassium levels.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, noni may increase the risk of hypotension when used in combination with antihypertensive drugs.
Preliminary clinical research suggests that drinking noni juice can reduce blood pressure in individuals with hypertension.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, taking noni with hepatotoxic drugs might increase the risk of liver damage.
There is concern that noni might cause hepatotoxicity in some patients. Advise patients against combining noni with potentially hepatotoxic drugs.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

Theoretically, taking noni fruit juice concomitantly with phenytoin may lower phenytoin levels and increase the risk of seizures.
In one case report, an adult taking phenytoin for partial seizures experienced low serum phenytoin levels while taking noni juice 90-200 mL daily. Serum phenytoin levels increased after decreasing noni juice consumption; similarly, serum phenytoin levels decreased after increasing noni juice consumption. Some researchers believe noni juice may induce cytochrome P450 2C9 enzymes, which would decrease phenytoin levels, but this has not been well studied. Patients may need additional monitoring when starting or stopping noni juice supplementation.

Likelihood Possible Evidence D
Potassium-Sparing Diuretics

Theoretically, combing noni and a potassium-sparing diuretic might increase the risk of hyperkalemia.
Noni juice contains significant amounts of potassium, about 6 mEq/100 mL juice. This may increase the risk for hyperkalemia when used in conjunction with potassium-sparing diuretics, which can also increase potassium levels.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, taking noni juice concomitantly with warfarin might decrease the effectiveness of warfarin.
In one case, a 41-year-old patient stabilized on warfarin had a decreased international normalized ratio (INR) following consumption of a specific commercial noni juice product (Noni juice 4 Everything). While the patient was still taking noni juice, an increase in warfarin dose did not produce an increase in INR. However, it should be noted that this particular product contained extracts and derivatives from more than 115 components, many of which contained vitamin K. Furthermore, vitamin K was listed as a separate ingredient of the product, suggesting that the product was possibly fortified with vitamin K. It has not been verified that noni fruit alone contains a significant amount of vitamin K or interacts with warfarin.

Likelihood Possible Evidence D
Ranitidine (Zantac)

Taking noni fruit with ranitidine might increase the levels and clinical effects of ranitidine.
Clinical evidence shows that taking an aqueous extract of noni fruit 30 minutes prior to taking a single oral dose of ranitidine can increase the rate of absorption and plasma concentration of ranitidine.

Likelihood Possible Evidence B

5-HTP3 drug types · 398 drugs

Carbidopa (Lodosyn)

Combining 5-HTP and carbidopa can increase the risk of serotonergic side effects.
Carbidopa is sometimes used with 5-HTP to minimize peripheral 5-HTP metabolism and boost the amount that reaches the brain. However, this combination might also increase the risk of some side effects including hypomania, restlessness, rapid speech, anxiety, insomnia, and aggressiveness. Combining carbidopa and 5-HTP might also increase the risk of scleroderma-like skin changes due to elevated serotonin levels.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, concomitant use of 5-HTP with medications that cause sedation might have additive effects.
In clinical trials, 5-HTP has been associated with drowsiness and somnolence.

Likelihood Possible Evidence D
Serotonergic Drugs

Combining serotonergic drugs with 5-HTP might cause additive serotonergic effects.
5-HTP can increase serotonin levels and cause serotonergic effects. Theoretically, combining serotonergic drugs with 5-HTP might increase the risk of serotonergic side effects, including serotonin syndrome and cerebral vasoconstrictive disorders. However, serotonin syndrome with 5-HTP has not yet been reported in humans. Monitor patients for signs of serotonin syndrome and other serotonergic side effects if using 5-HTP with serotonergic drugs.

Likelihood Possible Evidence D

Reishi Mushroom3 drug types · 375 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, high doses of reishi mushroom might increase the risk of bleeding.
A dose of 1.5 grams daily of reishi mushroom does not seem to decrease platelet aggregation, but a higher dose of 3 grams daily does.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, reishi mushroom might have additive effects with antidiabetes drugs.
Animal research suggests that reishi mushroom decreases blood sugar. However, in patients with type 2 diabetes, taking reishi mushroom does not reduce fasting glucose levels, and its effects on glycated hemoglobin are inconsistent.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, concurrent use of reishi mushroom with antihypertensive drugs might increase the risk of hypotension.
Reishi mushroom has shown hypotensive activity in animal research. Clinical evidence suggests that reishi mushroom reduces blood pressure in some, but not all, patients with hypertension.

Likelihood Possible Evidence D

Magnesium15 drug types · 295 drugs

Levodopa/Carbidopa (Sinemet)

Magnesium can reduce the bioavailability of levodopa/carbidopa.
Clinical research in healthy volunteers shows that taking magnesium oxide 1000 mg with levodopa 100 mg/carbidopa 10 mg reduces the area under the curve (AUC) of levodopa by 35% and of carbidopa by 81%. In vitro and animal research shows that magnesium produces an alkaline environment in the digestive tract, which might lead to degradation and reduced bioavailability of levodopa/carbidopa.

Likelihood Probable Evidence B
Aminoglycoside Antibiotics

Concomitant use of aminoglycoside antibiotics and magnesium can increase the risk for neuromuscular weakness.
Both aminoglycosides and magnesium reduce presynaptic acetylcholine release, which can lead to neuromuscular blockade and possible paralysis. This is most likely to occur with high doses of magnesium given intravenously.

Likelihood Possible Evidence D
Antacids

Use of acid reducers may reduce the laxative effect of magnesium oxide.
A retrospective analysis shows that, in the presence of H2 receptor antagonists (H2RAs) or proton pump inhibitors (PPIs), a higher dose of magnesium oxide is needed for a laxative effect. This may also occur with antacids. Under acidic conditions, magnesium oxide is converted to magnesium chloride and then to magnesium bicarbonate, which has an osmotic laxative effect. By reducing acidity, antacids may reduce the conversion of magnesium oxide to the active bicarbonate salt.

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

Magnesium might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide should be taken at least 2 hours before or 6 hours after magnesium containing products.

Likelihood Probable Evidence D
Bisphosphonates

Magnesium can decrease absorption of bisphosphonates.
Cations, including magnesium, can decrease bisphosphonate absorption. Advise patients to separate doses of magnesium and these drugs by at least 2 hours.

Likelihood Probable Evidence B
Calcium Channel Blockers

Magnesium can have additive effects with calcium channel blockers, although evidence is conflicting.
Magnesium inhibits calcium entry into smooth muscle cells and may therefore have additive effects with calcium channel blockers. Severe hypotension and neuromuscular blockades may occur when nifedipine is used with intravenous magnesium, although some contradictory evidence suggests that concurrent use of magnesium with nifedipine does not increase the risk of neuromuscular weakness. High doses of magnesium could theoretically have additive effects with other calcium channel blockers.

Likelihood Possible Evidence D
Digoxin

Magnesium salts may reduce absorption of digoxin.
Clinical evidence suggests that treatment with oral magnesium hydroxide or magnesium trisilicate reduces absorption of digoxin from the intestines. This may reduce the blood levels of digoxin and decrease its therapeutic effects.

Likelihood Possible Evidence B
Potassium-Sparing Diuretics

Potassium-sparing diuretics decrease excretion of magnesium, possibly increasing magnesium levels.
Potassium-sparing diuretics also have magnesium-sparing properties, which can counteract the magnesium losses associated with loop and thiazide diuretics. Theoretically, increased magnesium levels could result from concomitant use of potassium-sparing diuretics and magnesium supplements.

Likelihood Probable Evidence D
Quinolone Antibiotics

Magnesium decreases absorption of quinolones.
Magnesium can form insoluble complexes with quinolones and decrease their absorption. Advise patients to take these drugs at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

Likelihood Probable Evidence D
Skeletal Muscle Relaxants

Parenteral magnesium alters the pharmacokinetics of skeletal muscle relaxants, increasing their effects and accelerating the onset of effect.
Parenteral magnesium shortens the time to onset of skeletal muscle relaxants by about 1 minute and prolongs the duration of action by about 2 minutes. Magnesium potentiates the effects of skeletal muscle relaxants by decreasing calcium-mediated release of acetylcholine from presynaptic nerve terminals, reducing postsynaptic sensitivity to acetylcholine, and having a direct effect on the membrane potential of myocytes. Magnesium also has vasodilatory actions and increases cardiac output, allowing a greater amount of muscle relaxant to reach the motor end plate. A clinical study found that low-dose rocuronium (0.45 mg/kg), when given after administration of magnesium 30 mg/kg over 10 minutes, has an accelerated onset of effect, which matches the onset of effect seen with a full-dose rocuronium regimen (0.6 mg/kg). In another clinical study, onset times for rocuronium doses of 0.3, 0.6, and 1.2 mg/kg were 86, 76, and 50 seconds, respectively, when given alone, but were reduced to 66, 44, and 38 seconds, respectively, when the doses were given after a 15-minute infusion of magnesium sulfate 60 mg/kg. Giving intraoperative intravenous magnesium sulfate, 50 mg/kg loading dose followed by 15 mg/kg/hour, reduces the onset time of rocuronium, enhances its clinical effects, reduces the dose of intraoperative opiates, and prolongs the spontaneous recovery time. It does not affect the activity of subsequently administered neostigmine.

Likelihood Probable Evidence A
Sulfonylureas

Magnesium increases the systemic absorption of sulfonylureas, increasing their effects and side effects.
Clinical research shows that administration of magnesium hydroxide with glyburide increases glyburide absorption, increases maximal insulin response by 35-fold, and increases the risk of hypoglycemia, when compared with glyburide alone. A similar interaction occurs between magnesium hydroxide and glipizide. The mechanism of this effect appears to be related to the elevation of gastrointestinal pH by magnesium-based antacids, increasing solubility and enhancing absorption of sulfonylureas.

Likelihood Probable Evidence B
Tetracycline Antibiotics

Magnesium decreases absorption of tetracyclines.
Magnesium can form insoluble complexes with tetracyclines in the gut and decrease their absorption and antibacterial activity. Advise patients to take these drugs 1 hour before or 2 hours after magnesium supplements.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, magnesium may have antiplatelet effects, but the evidence is conflicting.
In vitro evidence shows that magnesium sulfate inhibits platelet aggregation, even at low concentrations. Some preliminary clinical evidence shows that infusion of magnesium sulfate increases bleeding time by 48% and reduces platelet activity. However, other clinical research shows that magnesium does not affect platelet aggregation, although inhibition of platelet-dependent thrombosis can occur.

Likelihood Unlikely Evidence B
Gabapentin (Neurontin)

Gabapentin absorption can be decreased by magnesium.
Clinical research shows that giving magnesium oxide orally along with gabapentin decreases the maximum plasma concentration of gabapentin by 33%, time to maximum concentration by 36%, and area under the curve by 43%. Advise patients to take gabapentin at least 2 hours before, or 4 to 6 hours after, magnesium supplements.

Likelihood Unlikely Evidence B
Sevelamer (Renagel, Renvela)

Sevelamer may increase serum magnesium levels.
In patients on hemodialysis, sevelamer use was associated with a 0.28 mg/dL increase in serum magnesium. The mechanism of this interaction remains unclear.

Likelihood Possible Evidence B

Cayenne6 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

Astragalus4 drug types · 208 drugs

Antidiabetes Drugs

Theoretically, taking astragalus with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research in humans shows that astragalus might have hypoglycemic effects. Theoretically, taking astragalus, especially in combination with other hypoglycemic agents, might increase the risk of hypoglycemia.

Likelihood Probable Evidence A
Cyclophosphamide

Theoretically, astragalus might interfere with cyclophosphamide therapy.
Evidence regarding the effect of astragalus on immunosuppression caused by cyclophosphamide is conflicting. Some animal research suggests that astragalus reverses cyclophosphamide-induced immunosuppression. However, other animal research shows no effect.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, astragalus might interfere with immunosuppressive therapy.
Astragalus seems to stimulate immune function. Theoretically, taking astragalus might decrease the effects of immunosuppressive therapy.

Likelihood Possible Evidence D
Lithium

Theoretically, astragalus might increase levels and adverse effects of lithium.
Animal research suggests that astragalus has diuretic properties. Theoretically, due to this diuretic effect, astragalus might reduce excretion and increase levels of lithium.

Likelihood Probable Evidence D

Coenzyme Q103 drug types · 198 drugs

Alkylating Agents

Coenzyme Q10 has antioxidant effects. Theoretically, this may reduce the activity of chemotherapy drugs that generate free radicals.
Theoretically, antioxidants such as coenzyme Q10 might protect tumor cells from chemotherapeutic agents that work by inducing oxidative stress, such as alkylating agents (e.g., cyclophosphamide) and radiation therapy. The clinical importance of this interaction is unknown.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Coenzyme Q10 is chemically similar to menaquinone and might have vitamin K-like procoagulant effects, which could decrease the effects of warfarin.
Concomitant use of coenzyme Q10 and warfarin might reduce the anticoagulant effects of warfarin. Four cases of decreased warfarin efficacy thought to be due to coenzyme Q10 have been reported. However, there is some preliminary clinical research that suggests coenzyme Q10 might not significantly decrease the effects of warfarin in patients who have a stable INR.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, coenzyme Q10 might have additive effects with antihypertensive drugs.
Some clinical research shows that coenzyme Q10 can significantly lower blood pressure, although other studies have shown conflicting results.

Likelihood Possible Evidence B

Royal Jelly2 drug types · 174 drugs

Antihypertensive Drugs

Theoretically, royal jelly might increase the risk of hypotension when taken with antihypertensive drugs.
Animal research suggests that royal jelly might lower blood pressure.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Royal jelly might increase the risk of bleeding when taken with warfarin.
In one case, an 87-year-old male who was previously stabilized on warfarin developed hematuria and was found to have an INR of 7.29 after taking a royal jelly supplement for one week.

Likelihood Possible Evidence D

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

Zinc10 drug types · 67 drugs

Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Theoretically, zinc might decrease levels of bictegravir/emtricitabine/tenofovir alafenamide by reducing its absorption.
Advise patients that bictegravir/emtricitabine/tenofovir alafenamide should be taken at least 2 hours before or 6 hours after zinc containing products.

Likelihood Probable Evidence D
Cephalexin (Keflex)

Zinc might decrease cephalexin levels by chelating with cephalexin in the gut and preventing its absorption.
A pharmacokinetic study shows that zinc sulfate 250 mg taken concomitantly with cephalexin 500 mg decreases peak levels of cephalexin by 31% and reduces the exposure to cephalexin by 27%. Also, taking zinc sulfate 3 hours before cephalexin decreases peak levels of cephalexin by 11% and reduces the exposure to cephalexin by 18%. By decreasing cephalexin levels, zinc might increase the risk of treatment failure. This effect does not occur when zinc is taken 3 hours after the cephalexin dose. To avoid an interaction, advise patients take zinc sulfate 3 hours after taking cephalexin.

Likelihood Probable Evidence B
Cisplatin (Platinol-Aq)

Theoretically, zinc might interfere with the therapeutic effects of cisplatin.
Animal research suggests that zinc stimulates tumor cell production of the protein metallothionein, which binds and inactivates cisplatin. It is not known whether zinc supplements or high dietary zinc intake can cause clinically significant interference with cisplatin therapy. Cisplatin might also increase zinc excretion.

Likelihood Possible Evidence D
Integrase Inhibitors

Theoretically, taking zinc along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Zinc is a divalent cation. Pharmacokinetic studies have shown that other divalent cations such as calcium and iron can decrease blood levels of the integrase inhibitor dolutegravir through chelation.

Likelihood Possible Evidence D
Penicillamine (Cuprimine, Depen)

Zinc might reduce the levels and clinical effects of penicillamine.
By forming an insoluble complex with penicillamine, zinc interferes with penicillamine absorption and activity. Zinc supplements reduce the efficacy of low-dose penicillamine (0.5-1 gram/day), but do not seem to affect higher doses (1-2.75 gram/day), provided dosing times are separated. Advise patients to take zinc and penicillamine at least 2 hours apart.

Likelihood Probable Evidence B
Quinolone Antibiotics

Zinc can decrease the levels and clinical effects of quinolones antibiotics.
Quinolones form complexes with zinc in the gastrointestinal tract, reducing absorption of both the quinolone and zinc if taken at the same time. Advise patients to take these drugs at least 2 hours before, or 4-6 hours after, zinc supplements.

Likelihood Probable Evidence B
Ritonavir (Norvir)

Zinc modestly reduces levels of ritonavir.
Clinical research shows that zinc might reduce serum ritonavir levels by chelating with ritonavir in the gut and preventing its absorption. In patients with HIV, ritonavir is taken with atazanavir to prevent the metabolism and increase the effects of atazanavir. A pharmacokinetic study shows that, in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate (Solvazinc tablets) 125 mg as a single dose or as multiple daily doses for 2 weeks reduces plasma levels of ritonavir by about 16%. However, atazanavir levels still remains high enough to prevent HIV virus replication. Therefore, the decrease in ritonavir levels is not likely to be clinically significant.

Likelihood Probable Evidence B
Tetracycline Antibiotics

Zinc might reduce levels of tetracycline antibiotics.
Tetracyclines form complexes with zinc in the gastrointestinal tract, which can reduce absorption of both the tetracycline and zinc when taken at the same time. Taking zinc sulfate 200 mg with tetracycline reduces absorption of the antibiotic by 30% to 40%. Demeclocycline and minocycline cause a similar interaction. However, doxycycline does not seem to interact significantly with zinc. Advise patients to take tetracyclines at least 2 hours before, or 4-6 hours after, zinc supplements to avoid any interactions.

Likelihood Probable Evidence B
Amiloride (Midamor)

Amiloride can modestly reduce zinc excretion and increase zinc levels.
Clinical research shows that amiloride can reduce urinary zinc excretion, especially at doses of 10 mg per day or more. This zinc-sparing effect can help to counteract zinc losses caused by thiazide diuretics, but it is unlikely to cause zinc toxicity at usual amiloride doses. The other potassium-sparing diuretics, spironolactone (Aldactone) and triamterene (Dyrenium), do not seem to have a zinc-sparing effect.

Likelihood Probable Evidence B
Atazanavir (Reyataz)

Zinc modestly reduces levels of atazanavir, although this effect does not seem to be clinically significant.
Clinical research shows that zinc might decrease serum atazanavir levels by chelating with atazanavir in the gut and preventing its absorption. Although a single dose of zinc sulfate (Solvazinc tablets) 125 mg orally does not affect atazanavir concentrations in patients being treated with atazanavir/ritonavir, co-administration of zinc sulfate 125 mg daily for 2 weeks reduces plasma levels of atazanavir by about 22% in these patients. However, despite this decrease, atazanavir levels still remain at high enough concentrations for the prevention of HIV virus replication.

Likelihood Probable Evidence B
The maker

Brand information

Manufacturer and brand details for Maximum Energy Blend, from the product label.

Uptime

Name
Uptime Energy, Inc.
Street Address
P.O. Box 90659
City
Santa Barbara
State
CA
ZipCode
93190-0659
Phone Number
1.800.441.5656
Web Address
www.uptime.energy
Pharmacist Counseling Corner

Maximum Energy Blend by Uptime: Common Questions

Does Maximum Energy Blend by Uptime interact with any medications?
Yes. Based on its ingredients, Maximum Energy Blend has a known interaction with 1,675 medications, including 26 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Maximum Energy Blend contains 18 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 or breastfeeding?
Several ingredients—schisandra, 5-HTP, astragalus, eleuthero, royal jelly, and reishi mushroom—should be avoided in pregnancy or breastfeeding because there isn't enough safety data or they may stimulate the uterus. Others like calcium, zinc, magnesium, caffeine, and lutein have limited or mixed data on file. Talk with your doctor or pharmacist about whether this blend is right for you at this life stage, and never stop or start it without their input.
What causes the energy boost—is it just the caffeine?
Caffeine is the primary direct stimulant, coming from the caffeine ingredient itself plus guarana extract and kola nut extract, which also contain caffeine. Green tea extract adds more caffeine and antioxidants. Other ingredients like schisandra, eleuthero, and astragalus are traditional 'adaptogens' meant to support energy and stamina, though our data shows insufficient evidence for most of these claims. The mineral and coenzyme ingredients support energy metabolism at the cellular level.
Are there any fillers or other ingredients I should know about?
Yes. Beyond the 18 active ingredients, the tablet contains cellulose, stearic acid, silicon dioxide, croscarmellose sodium, magnesium stearate, and ethyl cellulose—these are standard binders, anti-caking agents, and capsule materials that help the tablet hold together and flow smoothly during manufacturing.
Can I take this if I have high blood pressure?
Multiple ingredients in this blend—including green tea extract, noni, reishi mushroom, and coenzyme Q10—can theoretically lower blood pressure further. If you already take blood pressure medication, this could push your levels too low. Check with your own doctor or pharmacist before starting.
Is this product safe for people with asthma or allergies?
Royal jelly in this formula is a concern: it can trigger serious allergic reactions—including anaphylaxis—in people with a history of asthma or atopy (atopic dermatitis, eczema, allergic rhinitis). If you have either of these conditions, talk with your doctor or pharmacist before using this product.
What should I do if I'm already taking multiple supplements?
Since this blend has 18 active ingredients, you risk taking too much of some nutrients (like calcium, zinc, or magnesium) if you're using other supplements. Use the medication checker on this page to verify any overlaps, and discuss your full supplement list with your doctor or pharmacist to confirm the total doses are safe.

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.

Maximum Energy Blend label
Go deeper

The Full Monographs Behind Maximum Energy Blend’s Ingredients

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

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

Zinc

Interacts with 67 drugs

Zinc is an essential mineral that your body needs for immune function, wound healing, taste, and smell. Most people get enough from food, but supplements can help correct or prevent a defici...

Read the full Zinc monograph →
Herb & supplement monograph

Lutein

Lutein is a plant-based antioxidant pigment that concentrates in the eye, and the best evidence suggests it (often combined with zeaxanthin) may help slow progression of age-related macular...

Read the full Lutein monograph →
Herb & supplement monograph

5-htp

Interacts with 398 drugs

5-HTP is a compound your body uses to make serotonin, and people take it as a supplement hoping to improve mood, sleep, and headaches. Some early research is promising, but the overall evide...

Read the full 5-htp monograph →
Herb & supplement monograph

Coenzyme Q10

Interacts with 198 drugs

CoQ10 is a vitamin-like substance your body makes naturally that helps cells produce energy and acts as an antioxidant. It is generally well tolerated and is most studied for heart condition...

Read the full Coenzyme Q10 monograph →
Herb & supplement monograph

Royal Jelly

Interacts with 174 drugs

Royal jelly is a nutrient-rich substance made by worker bees to feed the queen bee. People take it for menopause symptoms, energy, skin, and immune support, but solid human evidence is limit...

Read the full Royal Jelly monograph →
Herb & supplement monograph

Magnesium

Interacts with 295 drugs

Magnesium is an essential mineral your body needs for muscles, nerves, blood pressure, and many other functions, and supplements are useful for preventing or correcting deficiency. Some othe...

Read the full Magnesium 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

Schisandra

Interacts with 803 drugs

Schisandra is a traditional Chinese medicine berry used as an adaptogen for stress, fatigue, and liver support. Human evidence is limited and most claims are not well proven, but it appears...

Read the full Schisandra 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

Astragalus

Interacts with 208 drugs

Astragalus is a root used for centuries in traditional Chinese medicine, mainly to support the immune system and help the body cope with stress. While early studies are interesting, strong h...

Read the full Astragalus 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

Eleuthero

Interacts with 1,140 drugs

Eleuthero is an herb traditionally used as an 'adaptogen' to fight fatigue, boost energy, and help the body handle stress. The scientific evidence behind these uses is limited and mixed, so...

Read the full Eleuthero monograph →
Herb & supplement monograph

Guarana

Interacts with 655 drugs

Guarana is an Amazonian seed that is naturally high in caffeine, which explains most of its stimulant and energy effects. While it may give a short-term boost in alertness and reduce fatigue...

Read the full Guarana monograph →
Herb & supplement monograph

Cola Nut

Interacts with 655 drugs

Cola nut is a caffeine-containing seed from West Africa used mainly as a natural stimulant for energy and alertness. Most of its effects come from caffeine, and strong human evidence for spe...

Read the full Cola Nut monograph →
Herb & supplement monograph

Noni

Interacts with 542 drugs

Noni is a tropical fruit used widely in folk medicine and sold mostly as a juice or supplement, but solid human evidence for its many claimed benefits is limited. While moderate juice intake...

Read the full Noni monograph →
Herb & supplement monograph

Reishi Mushroom

Interacts with 375 drugs

Reishi is a traditional Asian mushroom widely used to support the immune system and overall wellness. Human evidence for most of its claimed benefits is limited or low-quality, so it should...

Read the full Reishi Mushroom monograph →
Sources

Sources & How We Checked

Maximum Energy Blend'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 1,231 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.

Calcium 62 references
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  3. Thys-Jacobs S, Ceccarelli S, Bierman A, et al. Calcium supplementation in premenstrual syndrome: a randomized crossover trial. J Gen Intern Med 1989;4:183-9. PubMed
  4. Maton PN, Burton ME. Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use. Drugs 1999;57:855-70.
  5. Clemens JD, Feinstein AR. Calcium carbonate and constipation: a historical review of medical mythopoeia. Gastroenterology 1977;72:957-61. DOI
  6. Saunders D, Sillery J, Chapman R. Effect of calcium carbonate and aluminum hydroxide on human intestinal function. Dig Dis Sci 1988;33:409-13. PubMed
  7. Friedman PA, Bushinsky DA. Diuretic effects on calcium metabolism. Semin Nephrol 1999;19:551-6.
  8. Koo WK, Walters JC, Esterlitz J, et al. Maternal calcium supplementation and fetal bone mineralization. Obstet Gynecol 1999;94:577-82. DOI
  9. Raman L, Rajalakshmi K, Krishnamachari KAVR, et al. Effect of calcium supplementation to undernourished mothers during pregnancy on the bone density of the neonates. Am J Clin Nutr 1978; 31:466-9. DOI
  10. Murry JJ, Healy MD. Drug-mineral interactions: a new responsibility for the hospital dietician. J Am Diet Assoc 1991;91:66-73.
  11. Chan JM, Giovannucci E, Andersson SO, et al. Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer. Cancer Causes Control 1998;9:559-66.
  12. Butner LE, Fulco PP, Feldman G, et al. Calcium carbonate-induced hypothyroidism. Ann Intern Med 2000:132:595. PubMed
  13. Schneyer CR. Calcium carbonate and reduction of levothyroxine efficacy. JAMA 1998;279:750. PubMed
  14. Moser LR, Smythe MA, Tisdale JE. The use of calcium salts in the prevention and management of verapamil-induced hypotension. Ann Pharmacother 2000;34:622-9. PubMed
  15. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA 2000;283:2822-5. PubMed
  16. Kahela P, Anttila M, Tikkanen R, Sundquist H. Effect of food, food constituents and fluid volume on the bioavailability of sotalol. Acta Pharmacol Toxicol (Copenh) 1979;44:7-12.. PubMed
  17. Pletz MW, Petzold P, Allen A, et al. Effect of calcium carbonate on bioavailability of orally administered gemifloxacin. Antimicrob Agents Chemother 2003;47:2158-60.. PubMed
  18. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  19. Decktor DL, Robinson M, Maton PN, et al. Effects of aluminum/magnesium hydroxide and calcium carbonate on esophageal and gastric pH in subjects with heartburn. Am J Ther 1995;2:546-52. PubMed
  20. Simoneau G. Absence of rebound effect with calcium carbonate. Eur J Drug Metab Pharmacokinet 1996;21:351-7. PubMed
  21. Peters ML, Leonard M, Licata AA. Role of alendronate and risedronate in preventing and treating osteoporosis. Cleve Clin J Med 2001;68:945-51. PubMed
  22. Bourke JF, Mumford R, Whittaker P, et al. The effects of topical calcipotriol on systemic calcium homeostasis in patients with chronic plaque psoriasis. J Am Acad Dermatol 1997;37:929-34.
  23. Gueguen L, Pointillart A. The bioavailability of dietary calcium. J Am Coll Nutr 2000;19:119s-136s. PubMed
  24. Vella A, Gerber TC, Hayes DL, Reeder GS. Digoxin, hypercalcaemia, and cardiac conduction. Postgrad Med J 1999;75:554-6. PubMed
  25. Bania TC, Blaufeux B, Hughes S, et al. Calcium and digoxin vs. calcium alone for severe verapamil toxicity. Acad Emerg Med 2000;7:1089-96. PubMed
  26. Tseng M, Breslow RA, Graubard BI, Ziegler RG. Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort. Am J Clin Nutr 2005;81:1147-54. PubMed
  27. Weingarten MA, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev 2004;(1):CD003548. PubMed
  28. Tavani A, Bertuccio P, Bosetti C, et al. Dietary intake of calcium, vitamin D, phosphorus and the risk of prostate cancer. Eur Urol 2005;48:27-33. PubMed
  29. Giovannucci E, Liu Y, Stampfer MJ, Willett WC. A prospective study of calcium intake and incident and fatal prostate cancer. Cancer Epidemiol Biomarkers Prev 2006;15:203-10. PubMed
  30. Rocephin (ceftriaxone) and calcium interaction. Pharmacist's Letter / Prescriber's Letter 2007;23(10):231005.
  31. Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomised control trial. BMJ 2008;336:262-6.
  32. Bolland MJ, Avenell A, Baron JA, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691. PubMed
  33. Calcium supplementation and vascular events. Pharmacist's Letter / Prescriber's Letter 2008;24(3):240306.
  34. Dietary reference intakes for calcium and vitamin D. Institute of Medicine, November 30, 2010. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Repo
  35. Coburn JW, Mischel MG, Goodman WG, et al. Calcium citrate markedly enhances aluminum absorption from aluminum hydroxide. Am J Kidney Dis. 1991;17(6):708-11. PubMed
  36. Bradley JS, Wassel RT, Lee L, et al. Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events. Pediatrics. 2009;123(4):e609-13. PubMed
  37. Kays MB, Overholser BR, Mueller BA, et al. Effects of sevelamer hydrochloride and calcium acetate on the oral bioavailability of ciprofloxacin. Am J Kidney Dis. 2003;42(6):1253-9. PubMed
  38. Neuhofel, A. L., Wilton, J. H., Victory, J. M., Hejmanowsk, L. G., and Amsden, G. W. Lack of bioequivalence of ciprofloxacin when administered with calcium-fortified orange juice: a new twist on an old interaction. J Clin Pharmacol. 2002;42(4):461-466. DOI
  39. Dickinson, H. O., Nicolson, D. J., Cook, J. V., Campbell, F., Beyer, F. R., Ford, G. A., and Mason, J. Calcium supplementation for the management of primary hypertension in adults. Cochrane.Database.Syst.Rev. 2006;(2):CD004639. PubMed
  40. Jones, B. J. and Twomey, P. J. Requesting patterns for serum calcium concentration in patients on long-term lithium therapy. Int J Clin Pract. 2009;63(1):170-172. PubMed
  41. Levine, M., Nikkanen, H., and Pallin, D. J. The effects of intravenous calcium in patients with digoxin toxicity. J Emerg.Med. 2011;40(1):41-46. PubMed
  42. Castelo-Branco, C., Ciria-Recasens, M., Cancelo-Hidalgo, M. J., Palacios, S., Haya-Palazuelos, J., Carbonell-Abello, J., Blanch-Rubio, J., Martinez-Zapata, M. J., Manasanch, J., and Perez-Edo, L. Efficacy of ossein-hydroxyapatite complex compared with ca
  43. Li K, Kaaks R, Linseisen J, Rohrmann S. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation i
  44. Chung M, Tang AM, Fu Z. Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis. Ann Intern Med. 2016 Oct 25. PubMed
  45. Nolan CR, Califano JR, Butzin CA. Influence of calcium acetate or calcium citrate on intestinal aluminum absorption. Kidney Int. 1990;38(5):937-41. PubMed
  46. Lewis JR, Radavelli-Bagatini S, Rejnmark L, et al. The effects of calcium supplementation on verified coronary heart disease hospitalization and death in postmenopausal women: a collaborative meta-analysis of randomized controlled trials. J Bone Miner Res PubMed
  47. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  48. Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SL. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. JAMA. 2017 Mar 28;317(12):1234-1243. PubMed
  49. Grove ML, Cook D. Calcium and heart attacks. Doesn't apply to most calcium prescriptions. BMJ. 2010;341:c5003. PubMed
  50. Insentress [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2014.
  51. Roberts JL, Kiser JJ, Hindman JT, Meditz AL. Virologic failure with a raltegravir-containing antiretroviral regimen and concomitant calcium administration. Pharmacotherapy 2011;31(10):298e-302e. DOI
  52. Vitekta [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2014.
  53. Storan ER, O'Gorman SM, Murphy A, Laing M. Case Report of Calciphylaxis Secondary to Calcium and Vitamin D<sub>3</sub> Supplementation. J Cutan Med Surg. 2017;21(2):162-163. DOI
  54. Jenkins DJA, Spence JD, Giovannucci EL, et al. Supplemental vitamins and minerals for CVD prevention and treatment. J Am Coll Cardiol 2018;71(22):2570-84. PubMed
  55. Borkenhagen JF, Connor EL, Stafstrom CE. Neonatal hypocalcemic seizures due to excessive maternal calcium ingestion. Pediatr Neurol 2013;48(6):469-71. PubMed
  56. WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization; 2016 (http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/ anc-positive-pregnancy-experience/en/).
  57. Aune D, Navarro Rosenblatt DA, Chan DS, et al. Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies. Am J Clin Nutr. 2015;101(1):87-117. PubMed
  58. Lan T, Park Y, Colditz GA, et al. Adolescent dairy product and calcium intake in relation to later prostate cancer risk and mortality in the NIH-AARP Diet and Health Study. Cancer Causes Control. 2020;31(10):891-904. PubMed
  59. Zhang Y, Li Y, Liu J, et al. Association of Vitamin D or Calcium Supplementation with Cardiovascular Outcomes and Mortality: A Meta-Analysis with Trial Sequential Analysis. J Nutr Health Aging 2021;25(2):263-270. PubMed
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  61. Hetaimish B. Neonatal Calcinosis Cutis After Treatment of Hypocalcemia with Calcium Gluconate: A Report of 2 Cases. Am J Case Rep 2024;25:e943397. PubMed
  62. US Food and Drug Administration (FDA). Biktarvy Prescribing Information. October 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210251Orig1s020lbl.pdf. Accessed July 16, 2025.

See these in context on the Calcium monograph →

Capsicum 89 references
  1. Covington TR, et al. Handbook of Nonprescription Drugs. 11th ed. Washington, DC: American Pharmaceutical Association, 1996.
  2. Cooper RL, Cooper MM. Red pepper-induced dermatitis in breast-fed infants. Dermatol 1996;93:61-2. PubMed
  3. Millqvist E. Cough provocation with capsaicin is an objective way to test sensory hyperreactivity in patients with asthma-like symptoms. Allergy 2000;55:546-50. DOI
  4. Locock RA. Capsicum. Can Pharm J 1985;118:517-9.
  5. Mason L, Moore RA, Derry S, et al. Systematic review of topical capsaicin for the treatment of chronic pain. BMJ 2004;328:991. PubMed
  6. Schmulson MJ, Valdovinos MA, Milke P. Chili pepper and rectal hyperalgesia in irritable bowel syndrome. Am J Gastroenterol 2003;98:1214-5. PubMed
  7. Surh YJ, Lee SS. Capsaicin in hot chili pepper: carcinogen, co-carcinogen or anticarcinogen? Food Chem Toxicol 1996;34:313-6. PubMed
  8. Bouraoui A, Brazier JL, Zouaghi H, Rousseau M. Theophylline pharmacokinetics and metabolism in rabbits following single and repeated administration of Capsicum fruit. Eur J Drug Metab Pharmacokinet 1995;20:173-8.
  9. Hogaboam CM, Wallace JL. Inhibition of platelet aggregation by capsaicin. An effect unrelated to actions on sensory afferent neurons. Eur J Pharmacol 1991;202:129-31. PubMed
  10. Wang JP, Hsu MF, Teng CM. Antiplatelet effect of capsaicin. Thromb Res 1984;36:497-507. PubMed
  11. Williams SR, Clark RF, Dunford JV. Contact dermatitis associated with capsaicin: Hunan hand syndrome. Ann Emerg Med 1995;25:713-5. PubMed
  12. Zollman TM, Bragg RM, Harrison DA. Clinical effects of oleoresin capsicum (pepper spray) on the human cornea and conjunctiva. Ophthalmology 2000;107:2186-9. PubMed
  13. Bortolotti M, Coccia G, Grossi G, Miglioli M. The treatment of functional dyspepsia with red pepper. Aliment Pharmacol Ther 2002;16:1075-82. PubMed
  14. Hakas JF Jr. Topical capsaicin induces cough in patient receiving ACE inhibitor. Ann Allergy 1990;65:322-3.
  15. Rapoport AM, Bigal ME, Tepper SJ, Sheftell FD. Intranasal medications for the treatment of migraine and cluster headache. CNS Drugs 2004;18:671-85. PubMed
  16. Stjarne P, Rinder J, Heden-Blomquist E, et al. Capsaicin desensitization of the nasal mucosa reduces symptoms upon allergen challenge in patients with allergic rhinitis. Acta Otolaryngol 1998;118:235-9. PubMed
  17. Levy RL. Intranasal capsaicin for acute abortive treatment of migraine without aura. Headache 1995;35:277.
  18. Fusco BM, Marabini S, Maggi CA, et al. Preventative effect of repeated nasal applications of capsaicin in cluster headache. Pain 1994;59:321-5. PubMed
  19. Sicuteri F, Fusco BM, Marabini S, et al. Beneficial effect of capsaicin application to the nasal mucosa in cluster headache. Clin J Pain 1989;5:49-53. PubMed
  20. Marabini S, Ciabatti PG, Polli G, et al. Beneficial effects of intranasal applications of capsaicin in patients with vasomotor rhinitis. Eur Arch Otorhinolaryngol 1991;248:191-4. PubMed
  21. Frerick H, Keitel W, Kuhn U, et al. Topical treatment of chronic low back pain with a capsicum plaster. Pain 2003;106:59-64. PubMed
  22. Keitel W, Frerick H, Kuhn U, et al. Capsicum pain plaster in chronic non-specific low back pain. Arzneimittelforschung 2001;51:896-903. PubMed
  23. Shalansky S, Lynd L, Richardson K, et al. Risk of warfarin-related bleeding events and supratherapeutic international normalized ratios associated with complementary and alternative medicine: a longitudinal analysis. Pharmacotherapy. 2007;27:1237-47. PubMed
  24. Sumano-López H, Gutiérrez-Olvera L, Aguilera-Jiménez R, et al. Administration of ciprofloxacin and capsaicin in rats to achieve higher maximal serum concentrations. Arzneimittelforschung. 2007;57(5):286-90. PubMed
  25. Wanwimolruk S, Nyika S, Kepple M, et al. Effects of capsaicin on the pharmacokinetics of antipyrine, theophylline and quinine in rats. J Pharm Pharmacol. 1993;45(7):618-21. PubMed
  26. Cruz L, Castañeda-Hernández G, Navarrete A. Ingestion of chilli pepper (Capsicum annuum) reduces salicylate bioavailability after oral asprin administration in the rat. Can J Physiol Pharmacol.
  27. Rodriguez-Stanley, S., Collings, K. L., Robinson, M., Owen, W., and Miner, P. B., Jr. The effects of capsaicin on reflux, gastric emptying and dyspepsia. Aliment.Pharmacol.Ther. 2000;14(1):129-134. PubMed
  28. Brown, L., Takeuchi, D., and Challoner, K. Corneal abrasions associated with pepper spray exposure. Am.J.Emerg.Med. 2000;18(3):271-272. PubMed
  29. Vesaluoma, M., Muller, L., Gallar, J., Lambiase, A., Moilanen, J., Hack, T., Belmonte, C., and Tervo, T. Effects of oleoresin capsicum pepper spray on human corneal morphology and sensitivity. Invest Ophthalmol.Vis.Sci. 2000;41(8):2138-2147.
  30. Stam, C., Bonnet, M. S., and van Haselen, R. A. The efficacy and safety of a homeopathic gel in the treatment of acute low back pain: a multi-centre, randomised, double-blind comparative clinical trial. Br Homeopath J 2001;90(1):21-28. PubMed
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  32. Fett, D. D. Botanical briefs: Capsicum peppers. Cutis 2003;72(1):21-23.
  33. McCarthy, G. M. and McCarty, D. J. Effect of topical capsaicin in the therapy of painful osteoarthritis of the hands. J.Rheumatol. 1992;19(4):604-607.
  34. Chaiyata, P., Puttadechakum, S., and Komindr, S. Effect of chili pepper (Capsicum frutescens) ingestion on plasma glucose response and metabolic rate in Thai women. J.Med.Assoc.Thai. 2003;86(9):854-860.
  35. Petruzzi, M., Lauritano, D., De Benedittis, M., Baldoni, M., and Serpico, R. Systemic capsaicin for burning mouth syndrome: short-term results of a pilot study. J.Oral Pathol.Med. 2004;33(2):111-114. PubMed
  36. Misra, M. N., Pullani, A. J., and Mohamed, Z. U. Prevention of PONV by acustimulation with capsicum plaster is comparable to ondansetron after middle ear surgery: [La prevention des NVPO par acustimulation avec un emplatre de Capsicum est comparable a ce PubMed
  37. Milke, P., Diaz, A., Valdovinos, M. A., and Moran, S. Gastroesophageal reflux in healthy subjects induced by two different species of chilli (Capsicum annum). Dig.Dis. 2006;24(1-2):184-188.
  38. de Jong, N. W., van der Steen, J. J., Smeekens, C. C., Blacquiere, T., Mulder, P. G., van Wijk, R. G., and de Groot, H. Honeybee interference as a novel aid to reduce pollen exposure and nasal symptoms among greenhouse workers allergic to sweet bell pepp
  39. Final report on the safety assessment of capsicum annuum extract, capsicum annuum fruit extract, capsicum annuum resin, capsicum annuum fruit powder, capsicum frutescens fruit, capsicum frutescens fruit extract, capsicum frutescens resin, and capsaicin.
  40. Tandan, R., Lewis, G. A., Krusinski, P. B., Badger, G. B., and Fries, T. J. Topical capsaicin in painful diabetic neuropathy. Controlled study with long-term follow-up. Diabetes Care 1992;15(1):8-14. PubMed
  41. Gupta, P. J. Red hot chilli consumption is harmful in patients operated for anal fissure - a randomized, double-blind, controlled study. Dig.Surg. 2007;24(5):354-357. PubMed
  42. Patane, S., Marte, F., Di Bella, G., Cerrito, M., and Coglitore, S. Capsaicin, arterial hypertensive crisis and acute myocardial infarction associated with high levels of thyroid stimulating hormone. Int.J Cardiol. 5-1-2009;134(1):130-132. PubMed
  43. Gupta, P. J. Consumption of red-hot chili pepper increases symptoms in patients with acute anal fissures. A prospective, randomized, placebo-controlled, double blind, crossover trial. Arq Gastroenterol. 2008;45(2):124-127. PubMed
  44. Gupta, P. J. Consumption of red-hot chili pepper increases symptoms in patients with acute anal fissures. Ann.Ital.Chir 2008;79(5):347-351.
  45. Patane, S., Marte, F., La Rosa, F. C., and La, Rocca R. Capsaicin and arterial hypertensive crisis. Int J Cardiol. 10-8-2010;144(2):e26-e27. PubMed
  46. Chaiyasit, K., Khovidhunkit, W., and Wittayalertpanya, S. Pharmacokinetic and the effect of capsaicin in Capsicum frutescens on decreasing plasma glucose level. J Med.Assoc.Thai. 2009;92(1):108-113.
  47. Blanc, P., Liu, D., Juarez, C., and Boushey, H. A. Cough in hot pepper workers. Chest 1991;99(1):27-32. PubMed
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Cola Nut 157 references
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DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

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