Staying Cool Ingredients & Drug Interactions
by Eu Natural
What is this page for?
First and foremost: checking Staying Cool against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.
Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy
Staying Cool is a dietary supplement by Eu Natural with 22 active ingredients. Its ingredients are commonly taken for morning sickness in pregnancy, premenstrual syndrome (pms), preventing or treating b6 deficiency.Based on those ingredients, 1,666 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are KSM-66, St. John's Wort Extract, BioPerine Nutrient Enhancer. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.
Check Your Meds Against Staying Cool by Eu Natural
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AI summaries are generated from our interaction database for education only — always confirm with your pharmacist. How we use AI
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HelloPharmacist Scorecard of Staying Cool by Eu Natural
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.
What’s inside
Partial disclosure
Staying Cool contains 22 active ingredients spanning vitamins (B6, B12, D, E, niacin, riboflavin, thiamine, folate), minerals (selenium, zinc, manganese, boron), herbal extracts (ashwagandha, black cohosh, hops, magnolia bark, St. John's Wort, kudzu root), and a plant-based blend (shatavari root extract) plus black pepper extract to enhance nutrient absorption.
The product also contains two inactive ingredients—cellulose and rice extract—which function as fillers and binders.
Does it work?
Moderate evidence
The evidence backing these ingredients is mixed. Vitamin B6, thiamine, riboflavin, vitamin B12, and selenium have solid evidence for treating their respective deficiency states.
Niacin is likely effective for pellagra and possibly effective for certain types of cholesterol problems. Vitamin D is effective for rickets and related bone disorders.
Vitamin E is effective for vitamin E deficiency. Ashwagandha rates as possibly effective for anxiety, stress, and insomnia.
Black cohosh is possibly effective for menopausal hot flashes. For many others—including boron, manganese, pantothenic acid, hops, magnolia bark, St.
John's Wort for depression (rated likely effective), and kudzu—the evidence is either insufficient or not established in our data. Chaste Tree extract and folate effectiveness data are not on file.
How safe is it?
Well-documented data
Most of these ingredients are generally well tolerated at normal doses, but several carry cautions. Vitamin B6 is safe at standard amounts but can cause nerve damage (sensory neuropathy) at high doses over time, especially above 1,000 mg daily.
Selenium is safe in small amounts but becomes toxic at high doses and has been linked to increased skin cancer risk in some studies. Vitamin D is safe at recommended doses but excessive intake causes toxicity with high blood calcium.
Niacin commonly causes flushing and can damage the liver at high doses. Vitamin E at high doses increases bleeding risk.
St. John's Wort causes photosensitivity (increased sun sensitivity) and can trigger mood changes including mania in susceptible people.
Black cohosh, ashwagandha, and kudzu carry rare but serious liver concerns. Ashwagandha, black cohosh, and magnolia bark lack adequate pregnancy safety data.
Boron is not recommended in pregnancy or while breastfeeding due to limited safety information.
Meds to double-check
Major interaction found
Before taking this product, double-check your medications against these drug types, worst first: if you take digoxin or other heart rhythm drugs, cancer medications, or anti-rejection drugs like tacrolimus, the St. John's Wort can significantly reduce their effectiveness.
Blood pressure medications may have additive lowering effects from vitamin B6, niacin, and ashwagandha. Blood thinners (warfarin, clopidogrel) and antiplatelet drugs interact with vitamin E, selenium, magnolia, kudzu, and aspirin-like agents.
Seizure medications (phenytoin, phenobarbital, mephenytoin) are reduced by St. John's Wort and vitamin B6 at high doses, and increased by black pepper.
Certain antibiotics (tetracyclines, quinolones, cephalexin) have reduced absorption with zinc and manganese. Diabetes medications may need adjustment if ashwagandha lowers blood sugar.
Statins (atorvastatin) interact with vitamin D, black pepper, and niacin. Check your specific prescriptions with the tool below.
The bottom line
Scorecard at a glancePartially disclosed formula with some supporting evidence for its stated purpose. Major medication interactions have been identified, and safety information is well characterized.
This is a complex multi-ingredient supplement that anyone on prescription medications—especially blood thinners, heart rhythm drugs, seizure medications, diabetes drugs, or antidepressants—should discuss with their pharmacist or doctor before taking. The product works best as a targeted formula when you know which ingredients address your specific needs and have confirmed no conflicts with your health and medications.
If you're pregnant, breastfeeding, or have liver disease, talk with your provider first, as several ingredients carry cautions in these situations.
Educational only — not medical advice; always confirm with your pharmacist. Our editorial policy · How we use AI
Assessment coverage: 21 of 22 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Nov 22, 2024.
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
General information
Key facts about Staying Cool, straight from the product label.
| Brand | Eu Natural |
|---|---|
| Barcode (UPC) | 855244008097 |
| Net contents | 60 Vegetarian Capsule(s) |
| Market status | On market |
| Date entered into DSLD | Nov 22, 2024 |
| DSLD ID | 321864 |
| Product type | Botanical With Nutrients |
| Supplement form | Capsule |
| Dietary claims / uses | Nutrient, All Other, Structure/Function |
| Intended target group(s) | Adult Female (18 - 50 Years), Menopause, Seniors/Mature (>50 Years) - Women ONLY, Gluten Free |
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 Staying Cool by Eu Natural, sourced from the NIH Dietary Supplement Label Database.
Supplement Facts
| Ingredient | Amount | % DV |
|---|---|---|
| Vitamin B6 | 8.5 mg | 500% |
| Pantothenic Acid | 5 mg | 100% |
| Thiamine | 12 mg | 1000% |
| Riboflavin | 13 mg | 1000% |
| Selenium | 55 mcg | 100% |
| Vitamin D | 2000 IU | 250% |
| Niacin | 8 mg | 50% |
| Vitamin E | 30 mg | 200% |
| Vitamin B12 | 12 mcg | 500% |
| Zinc | 11 mg | 100% |
| Manganese | 2.3 mg | 100% |
| KSM-66 | 0 NP | -- |
| Shatavari root extract | 0 NP | -- |
| Boron | 0 NP | -- |
| Black Cohosh Root Extract | 0 NP | -- |
| Chaste Tree extract | 0 NP | -- |
| Hops Flower Extract | 0 NP | -- |
| Magnolia bark extract | 0 NP | -- |
| St. John's Wort Extract | 0 NP | -- |
| Folate | 1000 mcg | 250% |
| Pueraria mirifica root extract | 0 NP | -- |
| Staying Cool Menopause Complex | 1 Gram(s) | -- |
| BioPerine Nutrient Enhancer | 0 NP | -- |
Other ingredients: Cellulose, Rice extract
Tap any ingredient to jump to its full detail below.
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
Plant-powered multi-blend for "Eu" (you)!
Share your story #EuNatural #BeYou
Suggested/Recommended/Usage/Directions
Suggested use 1 capsule twice daily with a meal and 8 oz. H2O For best results, use for at least eight weeks.
Precautions
Do not exceed two capsules per day.
Caution: Keep out of reach of children.
If you are pregnant, nursing, or taking any prescription medicine, consult your physician before taking this product.
Gluten & wheat free, KSM-66 contains a milk-derivative
Formula
Taken to promote healthy menopause, STAYING COOL provides essential vitamins, miners, and herbal extracts to support your daily and nightly wellness.
Vitex & black cohosh
FDA Disclaimer Statement
These statements have not been evaluated by the Food and Drug Administration. This product is not intended to diagnose, treat, cure or prevent any disease.
Seals/Symbols
CGMP Certified Blended in the USA
Formulation
Hot flashes Menopause relief
Zero fillers, zero binders, zero artificial ingredients Gluten & wheat free, KSM-66 contains a milk-derivative
FDA Statement of Identity
Dietary Supplement
Is this label outdated? Report a formula or label change and our pharmacy team will review it.
Staying Cool by Eu Natural label
The label scan from the NIH Dietary Supplement Label Database. Tap to enlarge.
Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.
View the full label (PDF)The Ingredients in Staying Cool by Eu Natural
These are the 22 active ingredients this product is made of. Select any to open its full monograph.
Serving size1 Vegetarian Capsule(s) Dosage formCapsule Servings per container30 Amounts shown are per serving.
Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.
Vitamin B6
Interacts with210 drugs
Vitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is b...
Vitamin B6 monograph & interactionsPantothenic Acid
No knowninteractions
Pantothenic acid is vitamin B5, an essential nutrient your body uses to turn food into energy. True deficiency is very rare because it is found in nea...
Pantothenic Acid monograph & interactionsThiamine
Interacts with3 drugs
Thiamine (vitamin B1) is an essential nutrient your body needs to turn food into energy and to keep your nerves and heart healthy. Most people get eno...
Thiamine monograph & interactionsRiboflavin
Interacts with20 drugs
Riboflavin (vitamin B2) is an essential nutrient your body needs to turn food into energy and to keep skin, eyes, and nerves healthy. It is generally...
Riboflavin monograph & interactionsSelenium
Interacts with321 drugs
Selenium is an essential trace mineral your body needs in small amounts for thyroid function, antioxidant defense, and immune health. Most people who...
Selenium monograph & interactionsVitamin D
Interacts with715 drugs
Vitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people,...
Vitamin D monograph & interactionsNiacin
Interacts with727 drugs
Niacin (vitamin B3) is an essential nutrient your body needs for energy and metabolism, and deficiency is uncommon in most developed countries. Prescr...
Niacin monograph & interactionsVitamin E
Interacts with764 drugs
Vitamin E is an essential fat-soluble vitamin and antioxidant that most people get in adequate amounts from a normal diet. Supplements can help correc...
Vitamin E monograph & interactionsVitamin B12
Interacts with20 drugs
Vitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very h...
Vitamin B12 monograph & interactionsZinc
Interacts with67 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 suppleme...
Zinc monograph & interactionsManganese
Interacts with83 drugs
Manganese is an essential trace mineral your body needs in small amounts for bone formation, metabolism, and antioxidant defense, and most people get...
Manganese monograph & interactionsFolate
Staying Cool Menopause Complex
Other (inactive) ingredients: Cellulose, Rice extract. These complete the product’s ingredient list but are not active constituents.
Staying Cool by Eu Natural Drug Interactions
HelloPharmacist Interaction Report
Staying Cool by Eu Natural is a 22-ingredient supplement with documented interactions affecting a substantial number of medications.
The most serious interaction comes from St. John's Wort extract, which significantly reduces the effectiveness of digoxin (a heart rhythm medication) and several other drugs by speeding up how your liver breaks them down — this is a Major severity concern that warrants close attention if you take any heart, cancer, or anti-rejection medications.
Read the full breakdown — every affected drug type, severity by severity
Several other ingredients carry Moderate interactions with common drug categories. Vitamin D can increase calcium levels dangerously when combined with thiazide diuretics or certain heart rhythm drugs.
Niacin interacts with blood pressure medications, cholesterol drugs, diabetes medications, and gout treatments. Selenium affects blood thinners and immune-suppressing drugs.
Ashwagandha (KSM-66) may potentiate sedatives, lower blood pressure additively, reduce diabetes medication effectiveness, and interfere with thyroid hormone. Zinc reduces absorption of several antibiotics and HIV medications.
Black Pepper (BioPerine) raises levels of phenytoin, rifampin, nevirapine, and other drugs. Vitamin E increases bleeding risk with blood thinners.
Vitamin B6 at high doses may reduce seizure medication levels. Black Cohosh and Magnolia bark both interact with multiple drug categories including serotonergic medications and blood thinners.
We could not check Chaste Tree extract or Folate — no interaction data are on file for these ingredients. Altogether, these interactions span 1,639 individual medications.
Before you start this product, run your exact medications through the search tool on this page. The breadth of interactions here means almost anyone on a prescription should verify first.
Check your own medications below · Editorial policy · How we use AI
Want to check YOUR meds against Staying Cool?
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 checkerIngredients driving the most interactions
Individual Drug Interactions
The ingredients in Staying Cool interact with 1,666 drugs. Click any drug to see the details.
19 of the 22 ingredients in Staying Cool interact with drugs. Each result below shows which ingredient is responsible. KSM-66 St. John's Wort Extract BioPerine Nutrient Enhancer Hops Flower Extract Vitamin E Niacin Vitamin D Black Cohosh Root Extract Pueraria mirifica root extract Magnolia bark extract Selenium Vitamin B6 Chaste Tree extract Manganese Shatavari root extract Zinc Riboflavin Vitamin B12 Thiamine
BrincidofovirTembexa
How Brincidofovir interacts with Staying Cool — through 1 ingredient. Tap an ingredient for the detail:
Black Cohosh Root ExtractOrganic Anion-transporting Polypeptide Substrates (oatp) Minor
Interaction Summary
Black cohosh may inhibit one form of OATP, OATP2B1, which could reduce the bioavailability and clinical effects of OATP2B1 substrates.
Read the full Black Cohosh Root Extract + Brincidofovir interactionCiprofloxacin, HydrocortisoneCipro HC Otic
How Ciprofloxacin, Hydrocortisone interacts with Staying Cool — through 1 ingredient. Tap an ingredient for the detail:
Black Cohosh Root ExtractOrganic Anion-transporting Polypeptide Substrates (oatp) Minor
Interaction Summary
Black cohosh may inhibit one form of OATP, OATP2B1, which could reduce the bioavailability and clinical effects of OATP2B1 substrates.
Read the full Black Cohosh Root Extract + Ciprofloxacin, Hydrocortisone interactionSulfadiazine, TrimethoprimCoptin
How Sulfadiazine, Trimethoprim interacts with Staying Cool — through 1 ingredient. Tap an ingredient for the detail:
ThiamineTrimethoprim (proloprim) Minor
Interaction Summary
Trimethoprim might increase blood levels of thiamine.
Read the full Thiamine + Sulfadiazine, Trimethoprim interactionTrimethoprimProloprim, Trimpex
How Trimethoprim interacts with Staying Cool — through 1 ingredient. Tap an ingredient for the detail:
ThiamineTrimethoprim (proloprim) Minor
Interaction Summary
Trimethoprim might increase blood levels of thiamine.
Read the full Thiamine + Trimethoprim interactionEach ingredient & the kinds of drugs it affects
For each ingredient in Staying Cool 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.
KSM-66
Antidiabetes Drugs
Theoretically, taking ashwagandha with antidiabetes drugs might increase the risk of hypoglycemia.
There is preliminary clinical evidence suggesting that ashwagandha might lower blood glucose levels. Theoretically, ashwagandha might have additive effects when used with antidiabetes drugs and increase the risk of hypoglycemia.
Antihypertensive Drugs
Theoretically, taking ashwagandha with antihypertensive drugs might increase the risk of hypotension.
Animal research suggests that ashwagandha might lower systolic and diastolic blood pressure. Theoretically, ashwagandha might have additive effects when used with antihypertensive drugs and increase the risk of hypotension.
Benzodiazepines
Theoretically, taking ashwagandha might increase the sedative effects of benzodiazepines.
There is preliminary evidence that ashwagandha might have an additive effect with diazepam (Valium) and clonazepam (Klonopin). This may also occur with other benzodiazepines.
Cns Depressants
Theoretically, taking ashwagandha might increase the sedative effects of CNS depressants.
Ashwagandha seems to have sedative effects. Theoretically, this may potentiate the effects of barbiturates, other sedatives, and anxiolytics.
Hepatotoxic Drugs
Theoretically, taking ashwagandha with hepatotoxic drugs might increase the risk of liver damage.
Ashwagandha has been linked to cases of acute hepatitis, liver failure, hepatic encephalopathy, autoimmune hepatitis, the need for liver transplantation, and death due to liver failure.
Immunosuppressants
Theoretically, taking ashwagandha might decrease the effects of immunosuppressants.
Ashwagandha has demonstrated immunostimulant effects in humans. Animal research has shown that ashwagandha can attenuate the immunosuppression caused by cyclophosphamide.
Thyroid Hormone
Ashwagandha might increase the effects and adverse effects of thyroid hormone.
Concomitant use of ashwagandha with thyroid hormones may cause additive therapeutic and adverse effects. Preliminary clinical research and animal studies suggest that ashwagandha boosts thyroid hormone synthesis and secretion. In one clinical study, ashwagandha increased triiodothyronine (T3) and thyroxine (T4) levels by 41.5% and 19.6%, respectively, and reduced serum TSH levels by 17.4% from baseline in adults with subclinical hypothyroidism.
Cytochrome P450 1A2 (Cyp1A2) Substrates
Theoretically, ashwagandha might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that ashwagandha extract induces CYP1A2 enzymes.
Cytochrome P450 3A4 (Cyp3A4) Substrates
Theoretically, ashwagandha might decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that ashwagandha extract induces CYP3A4 enzymes.
Serotonergic Drugs
Some animal studies have reported that ashwagandha can enhance serotonergic transmission by altering certain serotonin (5-HT) receptors. However, there is no evidence to suggest that ashwagandha increases the risk of serotonin-related effects, and there have been no published case reports of serotonin syndrome when combined with other serotonergic drugs. Nevertheless, due to the lack of extensive studies on the matter and the fact that ashwagandha appears to affect serotonergic pathways, it would be prudent to exercise caution when combining it with drugs that affect serotonin. [References: - Effects of Withania somnifera (Ashwaga ndha) on Stress and the Stress-Related Neuropsychiatric Disorders Anxiety, Depression, and Insomnia. Curr Neuropharmacol. 2021 Sep 14; 19: 1468–1495. - A Prospective, Randomized Double-Blind, Placebo-Controlled Study of Safety and Efficacy of a High-Concentration Full-Spectrum Extract of Ashwagandha Root in Reducing Stress and Anxiety in Adults. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3573577/]
St. John's Wort Extract
Alprazolam (Xanax)
St. John's wort increases the clearance of alprazolam and decreases its effects.
Alprazolam, which is used as a probe for cytochrome P450 3A4 (CYP3A4) activity, has a two-fold increase in clearance when given with St. John's wort. St. John's wort reduces the half-life of alprazolam from 12.4 hours to 6 hours.
Contraceptive Drugs
St. John's wort increases the clearance of contraceptive drugs and reduces their clinical effects.
Females taking St. John's wort and oral contraceptives concurrently should use an additional or alternative form of birth control. St. John's wort can decrease norethindrone and ethinyl estradiol levels by 13% to 15%, resulting in breakthrough bleeding, irregular menstrual bleeding, or unplanned pregnancy. Bleeding irregularities usually occur within a week of starting St. John's wort and regular cycles usually return when St. John's wort is discontinued. Unplanned pregnancy has occurred with concurrent use of oral contraceptives and St. John's wort extract. St. John's wort is thought to induce the cytochrome P450 1A2 (CYP1A2), 2C9 (CYP2C9), and 3A4 (CYP3A4) enzymes, which are responsible for metabolism of progestins and estrogens in contraceptives.
Cyclosporine (Neoral, Sandimmune)
St. John's wort reduces the levels and clinical effects of cyclosporine.
Concomitant use can decrease plasma cyclosporine levels by 30% to 70%. Using St. John's wort with cyclosporine in patients with heart, kidney, or liver transplants can cause subtherapeutic cyclosporine levels and acute transplant rejection. This interaction has occurred with a St. John's wort extract standardized to 0.3% hypericin and dosed at 300-600 mg per day. Withdrawal of St. John's wort can result in a 64% increase in cyclosporine levels. St. John's wort induces cytochrome P450 3A4 (CYP3A4) and the multi-drug transporter, P-glycoprotein/MDR-1, which increases cyclosporine clearance.
Cytochrome P450 3A4 (Cyp3A4) Substrates
St. John's wort increases the metabolism and reduces the levels of CYP3A4 substrates.
St. John's wort induces CYP3A4 enzymes and increases metabolism of CYP3A4 substrates. Clinically significant interactions have been reported with St. John's wort products containing hyperforin 1 mg or more.
Digoxin (Lanoxin)
St. John's wort reduces the levels and clinical effects of digoxin.
St. John's wort can reduce the bioavailability, serum levels, and therapeutic effects of digoxin. Taking an extract of St. John's wort 900 mg, containing hyperforin 7.5 mg or more, daily for 10-14 days, can reduce serum digoxin levels by 25% in healthy people. St. John's wort is thought to affect the multidrug transporter, P-glycoprotein, which mediates the absorption and elimination of digoxin and other drugs. St. John's wort products providing less than 7.5 mg of hyperforin daily do not appear to affect digoxin levels.
Docetaxel (Taxotere)
St. John's wort reduces the levels and clinical effects of docetaxel.
Clinical research shows that taking a specific St. John's wort product (Hyperiplant, VSM) 300 mg three times daily for 14 days increases docetaxel clearance by about 14%, resulting in decreased plasma concentrations of docetaxel in cancer patients. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort.
Imatinib (Gleevec)
St. John's wort reduces the levels and clinical effects of imatinib.
Taking St. John's wort 900 mg daily for 2 weeks reduces the bioavailability and half-life of a single dose of imatinib and decreases its serum levels by 30% in healthy volunteers. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort, which increases clearance of imatinib.
Irinotecan (Camptosar)
St. John's wort reduces the levels and clinical effects of irinotecan.
St. John's wort 900 mg daily for 18 days decreases serum levels of irinotecan by at least 50%. Clearance of the active metabolite of irinotecan, SN-38, is also increased, resulting in a 42% decrease in the area under the concentration-time curve. This is thought to be due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort.
Mephenytoin (Mesantoin)
St. John's wort reduces the levels and clinical effects of mephenytoin.
Preliminary clinical research in healthy males shows that taking St. John's wort for 14 days induces cytochrome P450 2C19 (CYP2C19) and significantly increases metabolism of mephenytoin (Mesantoin). In people with wild-type 2C19, metabolism was almost 4-fold greater in subjects who received St. John's wort compared to placebo. In contrast, patients with 2C19*2/*2 and *2/*3 genotypes did not demonstrate a similar increase in metabolism.
Non-Nucleoside Reverse Transcriptase Inhibitors (Nnrtis)
St. John's wort decreases the levels and clinical effects of NNRTIs.
St. John's wort increases the oral clearance of nevirapine (Viramune) by 35%. Subtherapeutic concentrations are associated with therapeutic failure, development of viral resistance, and development of drug class resistance. St. John's wort induces intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and intestinal P-glycoprotein/MDR-1, a drug transporter.
Omeprazole (Prilosec)
St. John's wort decreases the levels and clinical effects of omeprazole.
Taking St. John's wort, 300 mg orally three times daily for 14 days, reduces serum concentrations of omeprazole by inducing its metabolism via cytochrome P450 (CYP) 2C19 and 3A4. The reduction of omeprazole serum levels is dependent on CYP2C19 genotype, with reductions up to 50% in extensive metabolizers and 38% in poor metabolizers.
Oxycodone (Oxycontin)
St. John's wort decreases the levels and clinical effects of oxycodone.
St. John's wort can increase oxycodone metabolism by inducing cytochrome P450 3A4 (CYP3A4), reducing plasma levels and analgesic activity.
P-Glycoprotein Substrates
St. John's wort decreases the levels and clinical effects of P-glycoprotein substrates.
St. John's wort induces P-glycoprotein. P-glycoprotein is a carrier mechanism responsible for transporting drugs and other substances across cell membranes. When P-glycoprotein is induced in the gastrointestinal (GI) tract, it can prevent the absorption of some medications. In addition, induction of p-glycoprotein can decrease entry of drugs into the central nervous system (CNS) and decrease access to other sites of action.
Phenobarbital (Luminal)
St. John's wort decreases the levels and clinical effects of phenobarbital.
St. John's wort may increase the metabolism of phenobarbital. Plasma concentrations of phenobarbital should be monitored carefully. The dose of phenobarbital may need to be increased when St. John's wort is started and decreased when it is stopped.
Phenprocoumon (Marcoumar, Others)
St. John's wort decreases the levels and clinical effects of phenprocoumon.
St. John's wort appears to increase the metabolism of phenprocoumon (an anticoagulant that is not available in the US) by increasing the activity of the cytochrome P450 2C9 (CYP2C9) enzyme. This may result in decreases in the anticoagulant effect and international normalized ratio (INR).
Phenytoin (Dilantin)
St. John's wort decreases the levels and clinical effects of phenytoin.
St. John's wort may increase the metabolism of phenytoin. Plasma concentrations of phenytoin should be monitored closely. The dose of phenytoin may need to be increased when St. John's wort is started and decreased when it is stopped.
Protease Inhibitors (Pis)
St. John's wort reduces the levels and clinical effects of PIs.
In healthy volunteers, St. John's wort can reduce the plasma concentrations of indinavir (Crixivan) by inducing cytochrome P450 3A4 (CYP3A4). This might result in treatment failure and viral resistance. St. John's wort also induces P-glycoprotein, which can result in decreased intracellular protease inhibitor concentrations and increased elimination.
Rivaroxaban (Xarelto)
St. John's wort decreases the levels and clinical effects of rivaroxaban.
A small pharmacokinetic study in healthy volunteers shows that taking a single dose of rivaroxaban 20 mg after using a specific St. John's wort extract (Jarsin, Vifor SA) 450 mg orally twice daily for 14 days reduces the bioavailability of rivaroxaban by 24% and reduces rivaroxaban's therapeutic inhibition of factor Xa by 20%.
Tacrolimus (Prograf)
St. John's wort decreases the levels and clinical effects of tacrolimus.
Taking a St. John's wort extract (Jarsin) 600 mg daily significantly decreases tacrolimus serum levels. Dose increases of 60% may be required to maintain therapeutic tacrolimus levels in patients taking St. John's wort. St. John's wort is thought to lower tacrolimus levels by inducing cytochrome P450 3A4 (CYP3A4) enzymes. A small clinical study in healthy adults also shows that taking St. John's wort 300 mg three times daily for 10 days decreases the total systemic exposure to tacrolimus by 27% and 33% after taking a single 5 mg dose of immediate-release or prolonged-release tacrolimus, respectively.
Warfarin (Coumadin)
St. John's wort decreases the levels and clinical effects of warfarin.
Taking St. John's wort significantly increases clearance of warfarin, including both its R- and S-isomers. This is likely due to induction of cytochrome P450 (CYP) 1A2 and CYP3A4. St. John's wort can also significantly decrease International Normalized Ratio (INR) in people taking warfarin. In addition, taking warfarin at the same time as St. John's wort might reduce warfarin bioavailability. When a dried extract is mixed with warfarin in an aqueous medium, up to 30% of warfarin is bound to particles, reducing its absorption.
Aminolevulinic Acid
St. John's wort might have additive phototoxic effects with aminolevulinic acid.
Concomitant use with St. John's wort extract may cause synergistic phototoxicity. Delta-aminolevulinic acid can cause a burning erythematous rash and severe swelling of the face, neck, and hands when taken with St. John's wort.
Bupropion (Wellbutrin)
St. John's wort might reduce the levels and effects of bupropion.
Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20%. This effect is attributed to the induction of cytochrome P450 2B6 (CYP2B6) by St. John's wort.
Clopidogrel (Plavix)
St. John's wort might increase the levels and effects of clopidogrel.
Taking St. John's wort with clopidogrel seems to increase the activity of clopidogrel. In clopidogrel non-responders, taking St. John's wort seems to induce metabolism of clopidogrel to its active metabolite by cytochrome P450 enzymes 3A4 and 2C19. This leads to increased antiplatelet activity. Theoretically, this might lead to an increased risk of bleeding in clopidogrel responders.
Clozapine (Clozaril)
St. John's wort might decrease the levels and clinical effects of clozapine.
A case report describes a female with schizophrenia controlled on clozapine who had a return of symptoms when she started taking St. John's wort. The plasma concentration of clozapine was reduced, likely because its clearance was increased due to induction of the cytochrome P450 enzymes 3A4, 1A2, 2C9, and 2C19 by St. John's wort.
Cytochrome P450 1A2 (Cyp1A2) Substrates
St. John's wort may increase the metabolism and reduce the levels of CYP1A2 substrates.
Clinical and in vitro research shows that St. John's wort induces CYP1A2, but to a lesser extent than CYP3A4.
BioPerine Nutrient Enhancer
Anticoagulant/Antiplatelet Drugs
Theoretically, black pepper might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit platelet aggregation. This has not been reported in humans.
Antidiabetes Drugs
Theoretically, black pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal research shows that piperine, a constituent of black pepper, can reduce blood glucose levels. Monitor blood glucose levels closely. Dose adjustments might be necessary.
Atorvastatin (Lipitor)
Theoretically, black pepper might increase blood levels of atorvastatin.
Animal research shows that taking piperine, a constituent of black pepper, 35 mg/kg can increase the maximum serum concentration of atorvastatin three-fold. This has not been reported in humans.
Cyclosporine (Neoral, Sandimmune)
Theoretically, black pepper might increase the effects and side effects of cyclosporine.
In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine. This has not been reported in humans.
Cytochrome P450 2D6 (Cyp2D6) Substrates
Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.
In vitro research suggests that some constituents of black pepper inhibit CYP2D6. This has not been reported in humans.
Cytochrome P450 3A4 (Cyp3A4) Substrates
Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
In vitro research and pharmacokinetic simulation data suggest that piperine, a constituent of black pepper, as well as the pepper fruit seem to inhibit CYP3A4. This has not been reported in humans.
Lithium
Theoretically, black pepper might increase blood levels of lithium due to its diuretic effects. The dose of lithium might need to be reduced.
Black pepper is thought to have diuretic properties.
Nevirapine (Viramune)
Black pepper might increase blood levels of nevirapine.
Clinical research shows that piperine, a constituent of black pepper, increases the plasma concentration of nevirapine. However, no adverse effects were observed in this study.
P-Glycoprotein Substrates
Theoretically, black pepper might increase levels of P-glycoprotein substrates.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit P-glycoprotein.
Pentobarbital (Nembutal)
Theoretically, black pepper might increase the sedative effects of pentobarbital.
Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time.
Phenytoin (Dilantin)
Black pepper might increase blood levels of phenytoin.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption, slow elimination, and increase levels of phenytoin. Taking a single dose of black pepper 1 gram along with phenytoin seems to double the serum concentration of phenytoin. Consuming a soup with black pepper providing piperine 44 mg/200 mL of soup along with phenytoin also seems to increase phenytoin levels when compared with consuming the same soup without black pepper.
Propranolol (Inderal)
Black pepper might increase blood levels of propranolol.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol.
Rifampin (Rifadin)
Black pepper might increase blood levels of rifampin.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and serum levels of rifampin.
Theophylline
Black pepper might increase blood levels of theophylline.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of theophylline.
Amoxicillin (Amoxil, Trimox)
Theoretically, black pepper might increase the effects and side effects of amoxicillin.
Animal research shows that taking piperine, a constituent of black pepper, with amoxicillin increases plasma levels of amoxicillin. This has not been reported in humans.
Carbamazepine (Tegretol)
Theoretically, black pepper might increase blood levels of carbamazepine, potentially increasing the effects and side effects of carbamazepine.
One clinical study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that taking a single 20 mg dose of purified piperine, a constituent of black pepper, increases carbamazepine levels. Piperine may increase carbamazepine absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or inhibiting cytochrome P450 3A4 (CYP3A4) in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects. In vitro research also shows that piperine can increase carbamazepine levels by 11% in a time-dependent manner.
Cytochrome P450 1A2 (Cyp1A2) Substrates
Theoretically, black pepper might decrease levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that black pepper induces CYP1A2. This has not been reported in humans.
Hops Flower Extract
Cns Depressants
Theoretically, concomitant use of hops with sedative drugs might cause additive sedation.
Some animal research shows that hops has sedative effects.
Estrogens
Theoretically, concomitant use of large amounts of hops might interfere with hormone replacement therapy due to competition for estrogen receptors.
In vitro research suggests that certain hops constituents can competitively bind to estrogen receptors. However, most hops extracts contain very small amounts of these constituents.
Cytochrome P450 1A2 (Cyp1A2) Substrates
Hops extract does not seem to affect the metabolism of CYP1A2 substrates.
In vitro research suggests that flavonoid constituents of hops inhibit CYP1A2 enzyme activity. However, a pharmacokinetic study in healthy postmenopausal patients shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, does not affect levels of caffeine, a CYP1A2 probe substrate.
Cytochrome P450 3A4 (Cyp3A4) Substrates
Theoretically, hops extract might alter metabolism of CYP3A4 substrates; however, this effect may not be clinically significant.
Animal research suggests that specific constituents of hops, called lupulones, can induce hepatic CYP3A4 enzyme activity. However, a pharmacokinetic study in healthy postmenopausal patients with normal metabolism shows that taking a standardized extract of spent hops containing prenylated phenols, as 59.5 mg twice daily for 2 weeks, decreases the concentration of alprazolam, a CYP3A4 probe substrate, by 7.6%. This reduction is unlikely to be clinically relevant.
Vitamin E
Alkylating Agents
Theoretically, antioxidant effects of vitamin E might reduce the effectiveness of alkylating agents.
There's concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.
Anticoagulant/Antiplatelet Drugs
Concomitant use of vitamin E and anticoagulant or antiplatelet agents might increase the risk of bleeding.
Vitamin E seems to inhibit of platelet aggregation and antagonize the effects of vitamin K-dependent clotting factors. These effects appear to be dose-dependent, and are probably only likely to be clinically significant with doses of at least 800 units daily. Mixed tocopherols, such as those found in food, might have a greater antiplatelet effect than alpha-tocopherol. RRR alpha-tocopherol (natural vitamin E) 1000 IU daily antagonizes vitamin K-dependent clotting factors. Advise patients to avoid high doses of vitamin E, especially in people with low vitamin K intake or other risk factors for bleeding.
Antitumor Antibiotics
Theoretically, antioxidant effects of vitamin E might reduce the effectiveness of antitumor antibiotics.
There's concern that antioxidants could reduce the activity of antitumor antibiotic drugs such as doxorubicin, which generate free radicals. However, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that might interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin E have on chemotherapy involving antitumor antibiotics. Advise patients to consult their oncologist before using vitamin E supplements, especially in high doses.
Cyclosporine (Neoral, Sandimmune)
A specific form of vitamin E might increase absorption and levels of cyclosporine.
There is some evidence that one specific formulation of vitamin E (D-alpha-tocopheryl-polyethylene glycol-1000 succinate, TPGS, tocophersolan, Liqui-E) might increase absorption of cyclosporine. This vitamin E formulation forms micelles which seems to increase absorption of cyclosporine by 40% to 72% in some patients. However, this interaction is unlikely to occur with the usual forms of vitamin E.
Cytochrome P450 3A4 (Cyp3A4) Substrates
Theoretically, vitamin E might induce metabolism of CYP3A4, possibly reducing the levels CYP3A4 substrates.
Vitamin E appears to bind with the nuclear receptor, pregnane X receptor (PXR), which results in increased expression of CYP3A4. Although the clinical significance of this is not known, use caution when considering concomitant use of vitamin E and other drugs affected by these enzymes.
Selumetinib (Koselugo)
Taking selumetinib with vitamin E can result in a total daily dose of vitamin E that exceeds safe limits and therefore might increase the risk of bleeding.
Selumetinib contains 48-54 IU vitamin E per capsule. The increased risk of bleeding with vitamin E appears to be dose-dependent. Be cautious when using selumetinib in combination with supplemental vitamin E, especially in patients at higher risk of bleed, such as those with chronic conditions and those taking antiplatelet drugs.
Warfarin (Coumadin)
Using vitamin E with warfarin might increase the risk of bleeding.
Due to interference with production of vitamin K-dependent clotting factors, use of more than 400 IU of vitamin E daily with warfarin might increase prothrombin time (PT), INR, and the risk of bleeding,. At a dose of 1000 IU per day, vitamin E can antagonize vitamin K-dependent clotting factors even in people not taking warfarin. Limited clinical evidence suggests that doses up to 1200 IU daily may be used safely by patients taking warfarin, but this may not be applicable in all patient populations.
Niacin
Vitamin E might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
A combination of niacin and simvastatin (Zocor) effectively raises high-density lipoprotein (HDL) cholesterol levels in people with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50%. Vitamin E alone combined with a statin does not seem to decrease HDL levels. It is not known whether the adverse effect on HDL is due to one of the other antioxidants or to the combination. It also is not known whether it will occur in other patient populations.
Niacin
Alcohol (Ethanol)
Concomitant use of alcohol and niacin might increase the risk of flushing and hepatotoxicity.
Alcohol can exacerbate the flushing and pruritus associated with niacin. Large doses of niacin might also exacerbate liver dysfunction associated with chronic alcohol use. A case report describes delirium and lactic acidosis in a patient taking niacin 3 grams daily who ingested 1 liter of wine. Advise patients to avoid large amounts of alcohol while taking niacin.
Allopurinol (Zyloprim)
Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as allopurinol.
Large doses of niacin can reduce urinary excretion of uric acid, potentially resulting in hyperuricemia. Doses of uricosurics such as allopurinol might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.
Anticoagulant/Antiplatelet Drugs
Theoretically, niacin may have additive effects when used with anticoagulant or antiplatelet drugs.
Several cases of clotting factor synthesis deficiency and coagulopathy have been reported in patients taking sustained-release niacin. Also, thrombocytopenia has been reported in patients treated with niacin or niacin plus lovastatin.
Antidiabetes Drugs
Niacin can increase blood glucose levels and may diminish the effects of antidiabetes drugs.
Niacin impairs glucose tolerance in a dose-dependent manner, probably by causing or aggravating insulin resistance and increasing hepatic production of glucose. In diabetes patients, niacin 4.5 grams daily for 5 weeks can increase plasma glucose by an average of 16% and glycated hemoglobin (HbA1c) by 21%. However, lower doses of 1.5 grams daily or less appear to have minimal effects on blood glucose. In some patients, glucose levels increase when niacin is started, but then return to baseline when a stable dose is reached. Up to 35% of patients with diabetes may need adjustments in hypoglycemic therapy when niacin is added.
Antihypertensive Drugs
Theoretically, niacin may increase the risk of hypotension when used with antihypertensive drugs.
The vasodilating effects of niacin can cause hypotension. Furthermore, some clinical evidence suggests that a one-hour infusion of niacin can reduce systolic, diastolic, and mean blood pressure in hypertensive patients. This effect is not observed in normotensive patients.
Bile Acid Sequestrants
Bile acid sequestrants can bind niacin and decrease absorption. Separate administration by 4-6 hours to avoid an interaction.
In vitro studies show that colestipol (Colestid) binds about 98% of available niacin and cholestyramine (Questran) binds 10% to 30%.
Gemfibrozil (Lopid)
Theoretically, concomitant use of niacin and gemfibrozil might increase the risk of myopathy in some patients.
A case of myopathy from concomitant use of niacin and gemfibrozil has been reported. Niacin alone has also been associated with cases of myopathy. Using gemfibrozil with niacin might further increase the risk of developing myopathy.
Hepatotoxic Drugs
Theoretically, concomitant use of niacin and hepatotoxic drugs might increase the risk of hepatotoxicity.
Niacin has been associated with cases of liver toxicity, especially when used in pharmacologic doses. Sustained-release niacin preparations appear to be associated with a higher risk of hepatotoxicity than immediate-release niacin.
Hmg-Coa Reductase Inhibitors ("Statins")
Theoretically, concomitant use of niacin and statins might increase the risk of myopathy and rhabdomyolysis in some patients.
Some case reports have raised concerns that niacin might increase the risk of myopathy and rhabdomyolysis when combined with statins. However, a significantly increased risk of myopathy has not been demonstrated in clinical trials, including those using an FDA-approved combination of lovastatin and niacin (Advicor).
Probenecid (Benemid)
Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as probenecid.
Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia. Doses of uricosurics such as probenecid might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.
Sulfinpyrazone (Anturane)
Theoretically, niacin might antagonize the therapeutic effects of uricosurics such as sulfinpyrazone.
Large doses of niacin reduce urinary excretion of uric acid, potentially causing hyperuricemia. Doses of uricosurics such as sulfinpyrazone might need to be increased to maintain control of gout in patients who start taking niacin. People who have frequent attacks of gout despite uricosuric therapy should avoid niacin.
Thyroid Hormone
Theoretically, niacin might antagonize the therapeutic effects of thyroid hormones.
Clinical research and case reports suggests that taking niacin can reduce serum levels of thyroxine-binding globulin by up to 25% and moderately reduce levels of thyroxine (T4). Patients taking thyroid hormone for hypothyroidism might need dose adjustments when using niacin.
Transdermal Nicotine (Nicoderm)
Theoretically, concomitant use of niacin and transdermal nicotine might increase the risk of flushing and dizziness.
Niacin and nicotine can both cause flushing and dizziness.
Warfarin (Coumadin)
There is limited evidence that niacin may increase the anticoagulant effects of warfarin.
In a case report, a patient on warfarin developed an elevated international normalized ratio (INR) of 3.9 after taking niacin for two weeks. The patient's INR was previously stable, ranging between 2 and 3 in recent months, and no other medication changes were identified. The elevated INR returned to therapeutic range within 4 days following the discontinuation of niacin.
Aspirin
Large doses of aspirin might alter the clearance of niacin.
Aspirin is often used with niacin to reduce niacin-induced flushing. Doses of 80-975 mg aspirin have been used, but 325 mg appears to be optimal. Aspirin also seems to reduce the clearance of niacin by competing for glycine conjugation. Taking aspirin 1 gram seems to reduce niacin clearance by 45%. This is probably a dose-related effect and not clinically significant with the more common aspirin dose of 325 mg.
Vitamin D
Aluminum
Vitamin D might increase aluminum absorption and toxicity, but this has only been reported in people with renal failure.
The protein that transports calcium across the intestinal wall can also bind and transport aluminum. This protein is stimulated by vitamin D, which may therefore increase aluminum absorption. This mechanism may contribute to increased aluminum levels and toxicity in people with renal failure, when they take vitamin D and aluminum-containing phosphate binders chronically.
Atorvastatin (Lipitor)
Vitamin D might reduce absorption of atorvastatin.
A small, low-quality clinical study shows that taking vitamin D reduces levels of atorvastatin and its active metabolites by up to 55%. However, while atorvastatin levels decreased, total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels did not substantially change. Atorvastatin is metabolized in the gut by CYP3A4 enzymes, and researchers theorized that vitamin D might induce CYP3A4, causing reduced levels of atorvastatin. However, this proposed mechanism was not specifically studied.
Calcipotriene (Dovonex)
Taking calcipotriene with vitamin D increases the risk for hypercalcemia.
Calcipotriene is a vitamin D analog used topically for psoriasis. It can be absorbed in sufficient amounts to cause systemic effects, including hypercalcemia. Theoretically, combining calcipotriene with vitamin D supplements might increase the risk of hypercalcemia.
Digoxin (Lanoxin)
Theoretically, hypercalcemia induced by high-dose vitamin D can increase the risk of arrhythmia from digoxin.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and digoxin concurrently.
Diltiazem (Cardizem, Others)
Theoretically, hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of diltiazem for arrhythmia.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically this could also occur with diltiazem. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and diltiazem concurrently.
Thiazide Diuretics
Theoretically, taking thiazide diuretics and high-dose vitamin D can increase the risk of hypercalcemia.
Thiazide diuretics decrease urinary calcium excretion, which could lead to hypercalcemia if vitamin D supplements are taken concurrently. This has been reported in people being treated with vitamin D for hypoparathyroidism, and also in elderly people with normal parathyroid function who were taking a thiazide, vitamin D, and calcium-containing antacids daily.
Verapamil (Calan, Others)
Hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of verapamil for arrhythmia.
Hypercalcemia due to high doses of vitamin D can reduce the effectiveness of verapamil in atrial fibrillation. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and verapamil concurrently.
Cytochrome P450 3A4 (Cyp3A4) Substrates
Vitamin D might induce CYP3A4 enzymes and reduce the bioavailability of CYP3A4 substrates.
There is some concern that vitamin D might induce CYP3A4. In vitro research suggests that vitamin D induces CYP3A4 transcription. Additionally, observational research has found that increased UV light exposure and serum vitamin D levels are associated with decreased serum levels of CYP3A4 substrates such as tacrolimus and sirolimus, while no association between UV light exposure or vitamin D levels and levels of mycophenolic acid, a non-CYP3A4 substrate, was found. A small, low-quality clinical study shows that taking vitamin D reduces levels of the CYP3A4 substrate atorvastatin and its active metabolites by up to 55%; however, the clinical effects of atorvastatin were not reduced. While researchers theorized that vitamin D might induce CYP3A4, this proposed mechanism was not specifically studied.
Black Cohosh Root Extract
Atorvastatin (Lipitor)
Taking black cohosh with atorvastatin might increase the risk for elevated liver function tests.
In one case report, a patient taking atorvastatin (Lipitor) developed significantly elevated liver function enzymes after starting black cohosh 100 mg four times daily. Liver enzymes returned to normal when black cohosh was discontinued. It is unclear whether the elevated liver enzymes were due to black cohosh itself or an interaction between atorvastatin and black cohosh.
Cisplatin (Platinol-Aq)
Theoretically, black cohosh may reduce the clinical effects of cisplatin.
Animal research suggests that black cohosh might decrease the cytotoxic effect of cisplatin on breast cancer cells.
Cytochrome P450 2D6 (Cyp2D6) Substrates
Some research suggests that black cohosh might inhibit CYP2D6, but there is conflicting evidence.
Some clinical research suggests that black cohosh might modestly inhibit CYP2D6 and increase levels of drugs metabolized by this enzyme. However, contradictory clinical research shows a specific black cohosh product (Remifemin, Enzymatic Therapy) 40 mg twice daily does not significantly inhibit metabolism of a CYP2D6 substrate in healthy study volunteers. Until more is known, use black cohosh cautiously in patients taking drugs metabolized by CYP2D6.
Estrogens
Theoretically, black cohosh may alter the effects of estrogen therapy.
Some research suggests that black cohosh has estrogenic effects. This may enhance or inhibit the effects of estrogen therapy.
Hepatotoxic Drugs
Theoretically, taking black cohosh with hepatotoxic drugs may increase the risk of liver damage.
There is concern that black cohosh might be linked to cases of liver failure and autoimmune hepatitis.
Serotonergic Drugs
Combining serotonergic drugs with black cohosh might cause additive serotonergic effects.
Black cohosh might increase the risk of serotonin syndrome when combined with other serotonergic drugs. Black cohosh acts as an agonist at several serotonin receptor subtypes and might interact with other serotonergic medications. In one case, a 55-year-old female who had been on stable treatment with sertraline 50 mg and duloxetine 60 mg daily developed serotonin syndrome after taking black cohosh extract 40 mg daily for 3 days.
Organic Anion-Transporting Polypeptide Substrates (Oatp)
Black cohosh may inhibit one form of OATP, OATP2B1, which could reduce the bioavailability and clinical effects of OATP2B1 substrates.
In vitro research shows that black cohosh modestly inhibits OATP2B1. OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds into the body. Inhibition of OATP may reduce the bioavailability of oral drugs that are substrates of OATP.
Pueraria mirifica root extract
Anticoagulant/Antiplatelet Drugs
Theoretically, kudzu may increase the risk of bleeding if used with antiplatelet or anticoagulant drugs.
Kudzu isoflavones are reported to have antiplatelet activity.
Caffeine
Theoretically, taking kudzu with caffeine might increase levels of caffeine.
In healthy males injected with the kudzu constituent puerarin, caffeine clearance and metabolism is inhibited. This effect has been attributed to inhibition of cytochrome P450 1A2 (CYP1A2) enzyme, which is involved in caffeine metabolism. It is unclear if taking kudzu orally would have this same effect.
Estrogens
Theoretically, kudzu might alter the effects of estrogen therapy.
Some research suggests that kudzu has estrogenic effects. This may enhance or inhibit the effects of estrogen therapy.
Hepatotoxic Drugs
Theoretically, concomitant use might have additive hepatotoxic effects.
There is some concern that kudzu can adversely affect the liver.
Methotrexate (Trexall, Others)
Theoretically, taking kudzu with methotrexate might increase the risk of methotrexate toxicity.
Preclinical research suggests that kudzu extract greatly reduces the elimination and increases the toxicity of methotrexate. Kudzu might inhibit organic anion transporters (OATs) that are responsible for hepatobiliary and renal excretion of anions, similar to the interaction between methotrexate and non-steroidal anti-inflammatory drugs (NSAIDs).
Tamoxifen (Nolvadex)
Theoretically, kudzu might interfere with tamoxifen activity.
Some research suggests that kudzu may have estrogenic effects.
Antidiabetes Drugs
Theoretically, taking kudzu with antidiabetes drugs might increase the risk of hypoglycemia.
Kudzu might lower blood glucose levels and have additive effects in patients treated with antidiabetic agents. The dose of diabetes medications might need to be adjusted.
Magnolia bark extract
Anticoagulant/Antiplatelet Drugs
Theoretically, magnolia might have additive effects and increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
In vitro research shows that the chemicals magnolol and honokiol, isolated from magnolia bark, inhibit platelet aggregation that is experimentally induced by collagen and arachidonic acid. However, they do not inhibit platelet aggregation that is induced by adenosine diphosphate, platelet-activating factor, or thrombin. This interaction has not been reported in humans.
Cns Depressants
Theoretically, concomitant use of large doses of magnolia bark and CNS depressants might have additive effects.
In vitro and animal research shows that constituents extracted from magnolia bark, especially honokiol and magnolol, have sedative effects. These effects may be due to the inhibition of catecholamine release and modulation of gamma-aminobutyric acid-A (GABA-A) receptors.
Selenium
Anticoagulant/Antiplatelet Drugs
Selenium may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Clinical research suggests that taking selenium 10 mcg/kg/day can increase bleeding times by increasing prostacyclin production, which inhibits platelet activity. Other clinical research suggests that taking selenium 75 mcg daily, in combination with ascorbic acid 600 mg, alpha-tocopherol 300 mg, and beta-carotene 27 mg, reduces platelet aggregation.
Barbiturates
Theoretically, selenium might prolong the sedating effects of barbiturates.
Laboratory research suggests that selenium can inhibit the hepatic metabolism of barbiturates. Selenium seems to prolong the sedative effect of pentobarbital in animal models.
Immunosuppressants
Theoretically, selenium supplementation may reduce the effectiveness of immunosuppressant therapy.
In vitro research and preliminary clinical evidence suggests that selenium may stimulate the immune system.
Warfarin (Coumadin)
Theoretically, selenium might interfere with warfarin activity.
Animal research suggests that selenium can increase warfarin activity. Selenium might interact with warfarin by displacing it from albumin binding sites, reducing its metabolism in the liver, or by decreasing production of vitamin K-dependent clotting factors. Selenium can also prolong bleeding times in humans by increasing prostacyclin production, which inhibits platelet activity.
Contraceptive Drugs
Contraceptive drugs might increase levels of selenium, although the clinical significance of this effect is unclear.
Some research suggests that oral contraceptives increase serum selenium levels in women taking oral contraceptives; however, other research shows no change in selenium levels. It is suggested that an increase could be due to increased carrier proteins, indicating a redistribution of selenium rather than a change in total body selenium.
Niacin
Selenium might reduce the beneficial effects of niacin on high-density lipoprotein (HDL) levels.
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease. It is not known whether this adverse effect is due to a single antioxidant such as selenium, or to the combination. It also is not known whether it will occur in other patient populations.
Vitamin B6
Amiodarone (Cordarone)
Theoretically, vitamin B6 might increase the photosensitivity caused by amiodarone.
Despite initial case reports suggesting that pyridoxine may have a protective effect against amiodarone-induced photosensitivity, preliminary clinical research suggests that pyridoxine may actually exacerbate this adverse effect.
Antihypertensive Drugs
Theoretically, vitamin B6 may have additive effects when used with antihypertensive drugs.
Research in hypertensive rats shows that vitamin B6 can decrease systolic blood pressure. Similarly, clinical research in patients with hypertension shows that taking high doses of vitamin B6 may reduce systolic and diastolic blood pressure, possibly by reducing plasma levels of epinephrine and norepinephrine.
Phenobarbital (Luminal)
High doses of vitamin B6 may reduce the levels and clinical effects of phenobarbital.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenobarbital, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenobarbital to avoid high doses of vitamin B6.
Phenytoin (Dilantin)
High doses of vitamin B6 may reduce the levels and clinical effects of phenytoin.
Preliminary clinical evidence suggests that vitamin B6 200 mg daily can reduce plasma levels of phenytoin, possibly by increasing metabolism. It is not known whether lower doses have any effect. Advise people taking phenytoin to avoid high doses of vitamin B6.
Levodopa
Vitamin B6 may increase the metabolism of levodopa when taken alone, but not when taken in conjunction with carbidopa.
Vitamin B6 (pyridoxine) enhances the metabolism of levodopa, reducing its clinical effects. However, this interaction does not occur when carbidopa is used concurrently with levodopa (Sinemet). Therefore, it is not likely to be a problem in most people.
Chaste Tree extract
Antipsychotic Drugs
Theoretically, vitex agnus-castus could interfere with the activity of antipsychotic drugs.
Vitex agnus-castus might interfere with the action of dopamine antagonists such as antipsychotic drugs due to its dopamine agonist effects.
Contraceptive Drugs
Theoretically, vitex agnus-castus could interfere with oral contraceptives.
Vitex agnus-castus might interfere with the efficacy of oral contraceptives due to possible hormone modulating activity.
Dopamine Agonists
Theoretically, vitex agnus-castus could interfere with dopamine agonists.
Vitex agnus-castus might potentiate the actions of dopaminergic agonists due to possible dopaminergic effects.
Estrogens
Theoretically, vitex agnus-castus could interfere with the activity of estrogens.
Vitex agnus-castus has hormone modulating activity that can interfere with the efficacy of hormone replacement therapy.
Metoclopramide (Reglan)
Theoretically, dopaminergic effects of vitex agnus-castus could interfere with metoclopramide.
Vitex agnus-castus might interfere with the action of dopamine antagonists such as metoclopramide due to its possible dopaminergic effects.
Manganese
Antipsychotic Drugs
Theoretically, the risk for manganese toxicity might increase when taken with antipsychotic drugs.
Hallucinations and behavioral changes have been reported in a patient with liver disease who was taking haloperidol and manganese. Researchers speculate that taking manganese along with haloperidol, phenothiazine-derivatives, or other antipsychotic medications might increase the risk of manganese toxicity in some patients.
Quinolone Antibiotics
Theoretically, manganese might reduce the absorption of quinolone antibiotics.
Manganese is a multivalent cation. Interactions resulting in reduced quinolone absorption have been reported between quinolones and other multivalent cations, such as calcium and iron.
Tetracycline Antibiotics
Theoretically, manganese might reduce the absorption of tetracycline antibiotics.
Manganese is a multivalent cation. Interactions resulting in reduced tetracycline absorption have been reported between tetracyclines and other multivalent cations, such as calcium and iron.
Shatavari root extract
Diuretic Drugs
Theoretically, asparagus racemosus root might increase diuresis and electrolyte loss when used with diuretic drugs.
Animal studies show that asparagus racemosus root has diuretic effects when used in high doses. This effect has not been reported in humans.
Lithium
Theoretically, Asparagus racemosus root could reduce excretion and increase levels of lithium.
Animal research suggests that Asparagus racemosus root has diuretic properties when used in high doses. Therefore, it might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.
Zinc
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Riboflavin
Tetracycline Antibiotics
Theoretically, taking riboflavin with tetracycline antibiotics may decrease the potency of these antibiotics.
In vitro research suggests that riboflavin may inhibit the potency of tetracycline antibiotics. It is not clear if this effect is clinically significant, as this interaction has not been reported in humans.
Vitamin B12
Metformin (Glucophage)
Metformin, a common medication used to manage type 2 diabetes, has been associated with lower vitamin B12 levels in some individuals. Prolonged use of metformin can interfere with the absorption of B12 in the digestive system, potentially leading to a deficiency in this essential vitamin.
Thiamine
Trimethoprim (Proloprim)
Trimethoprim might increase blood levels of thiamine.
In vitro, animal, and clinical research suggest that trimethoprim inhibits intestinal thiamine transporter ThTR-2, hepatic transporter OCT1, and renal transporters OCT2, MATE1, and MATE2, resulting in paradoxically increased thiamine plasma concentrations.
Brand information
Manufacturer and brand details for Staying Cool, from the product label.
Eu Natural
See all Eu Natural products- Name
- Eu Natural Inc
- City
- Henderson
- State
- NV
- ZipCode
- 89052
- Phone Number
- 408-256-1387
- Web Address
- EuNatural.com
Staying Cool by Eu Natural: Common Questions
Does Staying Cool by Eu Natural interact with any medications?
How can one product interact with so many drugs?
Where does this information come from?
Can I take this if I'm on a blood thinner like warfarin?
Does this product work for hot flashes and anxiety?
Is this safe during pregnancy?
What are the most common side effects?
Does black pepper (BioPerine) in this product increase how much of the other ingredients I absorb?
I take St. John's Wort for depression separately—is it safe to also take this product?
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.
The Full Monographs Behind Staying Cool’s Ingredients
Every ingredient we hold a full HelloPharmacist monograph for — uses, evidence, safety, and the complete interaction list.
Vitamin B6
Interacts with 210 drugsVitamin B6 (pyridoxine) is an essential water-soluble vitamin that your body needs for metabolism, brain function, and making red blood cells. It is best known for helping with pregnancy-rel...
Read the full Vitamin B6 monograph → Herb & supplement monographPantothenic Acid
Pantothenic acid is vitamin B5, an essential nutrient your body uses to turn food into energy. True deficiency is very rare because it is found in nearly all foods, and most people meet thei...
Read the full Pantothenic Acid monograph → Herb & supplement monographThiamine
Interacts with 3 drugsThiamine (vitamin B1) is an essential nutrient your body needs to turn food into energy and to keep your nerves and heart healthy. Most people get enough from food, but supplements are clear...
Read the full Thiamine monograph → Herb & supplement monographRiboflavin
Interacts with 20 drugsRiboflavin (vitamin B2) is an essential nutrient your body needs to turn food into energy and to keep skin, eyes, and nerves healthy. It is generally very safe at typical doses, and the stro...
Read the full Riboflavin monograph → Herb & supplement monographSelenium
Interacts with 321 drugsSelenium is an essential trace mineral your body needs in small amounts for thyroid function, antioxidant defense, and immune health. Most people who eat a varied diet get enough, and supple...
Read the full Selenium monograph → Herb & supplement monographVitamin D
Interacts with 715 drugsVitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people, especially those with low sun exposure,...
Read the full Vitamin D monograph → Herb & supplement monographNiacin
Interacts with 727 drugsNiacin (vitamin B3) is an essential nutrient your body needs for energy and metabolism, and deficiency is uncommon in most developed countries. Prescription-strength niacin has been used to...
Read the full Niacin monograph → Herb & supplement monographVitamin E
Interacts with 764 drugsVitamin E is an essential fat-soluble vitamin and antioxidant that most people get in adequate amounts from a normal diet. Supplements can help correct a true deficiency, but high-dose vitam...
Read the full Vitamin E monograph → Herb & supplement monographVitamin B12
Interacts with 20 drugsVitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very helpful for people who are deficient — su...
Read the full Vitamin B12 monograph → Herb & supplement monographZinc
Interacts with 67 drugsZinc 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 monographManganese
Interacts with 83 drugsManganese is an essential trace mineral your body needs in small amounts for bone formation, metabolism, and antioxidant defense, and most people get enough from a normal diet. Supplements m...
Read the full Manganese monograph → Herb & supplement monographAshwagandha
Interacts with 1,372 drugsAshwagandha is an Ayurvedic herb most often taken to help with stress, anxiety, and sleep, and some small studies suggest it may help, though the evidence is still limited. It is generally w...
Read the full Ashwagandha monograph → Herb & supplement monographAsparagus Racemosus
Interacts with 76 drugsAsparagus racemosus, often called shatavari, is an Ayurvedic herb traditionally used to support women's health, digestion, and overall vitality. Human evidence for most of these uses is limi...
Read the full Asparagus Racemosus monograph → Herb & supplement monographBoron
Boron is a trace mineral found in many plant foods and sold as a supplement, mainly promoted for bone, joint, and hormone health. The human evidence for most of these uses is limited or prel...
Read the full Boron monograph → Herb & supplement monographBlack Cohosh
Interacts with 652 drugsBlack cohosh is a North American plant most often used to ease menopause symptoms like hot flashes, but the research is mixed and far from settled. It is generally well tolerated for short-t...
Read the full Black Cohosh monograph → Herb & supplement monographVitex Agnus-castus
Interacts with 121 drugsVitex (chasteberry) is an herbal remedy most often used for PMS and menstrual cycle problems, and the strongest evidence is for easing some PMS symptoms. It is generally well tolerated by ma...
Read the full Vitex Agnus-castus monograph → Herb & supplement monographHops
Interacts with 863 drugsHops are most often used for sleep and mild anxiety, frequently combined with valerian, but the human evidence is limited and not very strong. They are generally well tolerated when used sho...
Read the full Hops monograph → Herb & supplement monographMagnolia
Interacts with 351 drugsMagnolia bark and flower buds have a long history in traditional Chinese and Japanese medicine, often for stress, sleep, and digestion. Modern human research is still limited, so we can't be...
Read the full Magnolia monograph → Herb & supplement monographSt. John's Wort
Interacts with 1,143 drugsSt. John's wort is a well-studied herb most often used for mild to moderate depression, and some research suggests it may help with this. However, it has many serious interactions with presc...
Read the full St. John's Wort monograph → Herb & supplement monographKudzu
Interacts with 584 drugsKudzu is a fast-growing vine whose root has long been used in traditional Chinese medicine and is now studied mostly for reducing alcohol intake. Early research is promising for cutting back...
Read the full Kudzu monograph → Herb & supplement monographBlack Pepper
Interacts with 1,019 drugsBlack pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to help the body absorb other ingredients (li...
Read the full Black Pepper monograph →Sources & How We Checked
Staying Cool'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.
- NIH Dietary Supplement Label Database (DSLD) — The official product label on file for this supplement.
- Natural Medicines (Therapeutic Research Center) — Evidence-graded clinical reference behind the ingredient interaction data.
Content is written and reviewed by licensed HelloPharmacist pharmacists. See our data sources and editorial standards for how this information is built and checked.
The 742 references behind this product’s interaction data
Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.
Vitamin B6 32 references
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- Geerling BJ, Dagnelie PC, Badart-Smook A, et al. Diet as a risk factor for the development of ulcerative colitis. Am J Gastroenterol 2000;95:1008-13. PubMed
- South M. Neonatal seizures after pyridoxine use -- reply. Lancet 1999;354:2083. PubMed
- Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
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- Bendich A, Cohen M. Vitamin B6 safety issues. Ann N Y Acad Sci 1990;585:321-30.
- Schaumburg H, Kaplan J, Windebank A. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983;309:445-8. PubMed
- Gordon N. Pyridoxine dependency: an update. Dev Med Child Neurol 1997;39:63-5. PubMed
- Lewis PJ. Pain in the hand and wrist. Pyridoxine supplements may help patients with carpal tunnel syndrome. BMJ 1995;310:1534. PubMed
- Kaufman G. Pyridoxine against amiodarone-induced photosensitivity (letter). Lancet 1984;1:51-2. PubMed
- Mulrow JP, Mulrow CD, McKenna WJ. Pyridoxine and amiodarone-induced photosensitivity. Ann Intern Med 1985;103:68-9. PubMed
- Kawada A, Kashima A, Shiraishi H, et al. Pyridoxine-induced photosensitivity and hypophosphatasia. Dermatology 2000;201:356-60.. PubMed
- Vasile A, Goldberg R, Kornberg B. Pyridoxine toxicity: report of a case. J Am Osteopath Assoc 1984;83:790-1. DOI
- Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256. DOI
- Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15:484-5..
- Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 2007;90:15-20.
- Hatzitolios, A., Iliadis, F., Katsiki, N., and Baltatzi, M. Is the anti-hypertensive effect of dietary supplements via aldehydes reduction evidence based? A systematic review. Clin Exp.Hypertens. 2008;30(7):628-639. PubMed
- Vasdev, S., Ford, C. A., Parai, S., Longerich, L., and Gadag, V. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Mol.Cell Biochem. 1999;200(1-2):155-162.
- de, Vogel S., Dindore, V., van, Engeland M., Goldbohm, R. A., van den Brandt, P. A., and Weijenberg, M. P. Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 2008;138(12):2372-2378. PubMed
- Hagen, I., Nesheim, B. I., and Tuntland, T. No effect of vitamin B-6 against premenstrual tension. A controlled clinical study. Acta Obstet.Gynecol.Scand. 1985;64(8):667-670. PubMed
- Aybak, M., Sermet, A., Ayyildiz, M. O., and Karakilcik, A. Z. Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension. Arzneimittelforschung. 1995;45(12):1271-1273.
- Lal, K. J., Dakshinamurti, K., and Thliveris, J. The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension. J Hypertens. 1996;14(3):355-363. PubMed
- Lauritzen CH, Reuter HD, Repges R, Bohnert K, and Schmidt U. Treatment of premenstrual tension syndrome with Vitex agnus castus. Controlled, double-blind study versus pyridoxine. Phytomed 1997;4(3):183-189. PubMed
- Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: A randomized trial. Am J Med 2013;126(2):141-9. PubMed
- Hankey GJ, Eikelboom JW, Yi Q, et al. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: Results of a randomized placebo-controlled trial. Stroke 2012;43(6):1572-7. PubMed
- Hoyer-Kuhn H, Kohbrok S, Volland R, Franklin J, Hero B, Beck BB, Hoppe B. Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice. Clin J Am Soc Nephrol. 2014 Mar;9(3):468-77. PubMed
- Mahmoud A, Tabassum S, Al Enazi S, et al. Amelioration of levetiracetam-induced behavioral side effects by pyridoxine. A randomized double blind controlled study. Pediatr Neurol 2021;119:15-21. PubMed
- Gupta M, Gallante B, Bamberger JN, et al. Prospective randomized evaluation of idiopathic hyperoxaluria treatments. J Endourol 2021;35(12):1844-1851. PubMed
- Li H, Chen M, Liang S, et al. Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement. Clin Nutr 2021;40(4):2293-2300. PubMed
- Tanigawa J, Nabatame S, Tominaga K, et al. High-dose pyridoxine treatment for inherited glycosylphosphatidylinositol deficiency. Brain Dev 2021;43(6):680-687. PubMed
- Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed
Pantothenic Acid 11 references
- McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
- Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
- Debourdeau PM, Djezzar S, Estival JL, et al. Life-threatening eosinophilic pleuropericardial effusion related to vitamins B5 and H. Ann Pharmacother 2001;35:424-6. DOI
- Schmuth, M., Wimmer, M. A., Hofer, S., Sztankay, A., Weinlich, G., Linder, D. M., Elias, P. M., Fritsch, P. O., and Fritsch, E. Topical corticosteroid therapy for acute radiation dermatitis: a prospective, randomized, double-blind study. Br.J.Dermatol. 2 PubMed
- Schreck, U., Paulsen, F., Bamberg, M., and Budach, W. Intraindividual comparison of two different skin care conceptions in patients undergoing radiotherapy of the head-and-neck region. Creme or powder? Strahlenther.Onkol. 2002;178(6):321-329. PubMed
- Herbst, R. A., Uter, W., Pirker, C., Geier, J., and Frosch, P. J. Allergic and non-allergic periorbital dermatitis: patch test results of the Information Network of the Departments of Dermatology during a 5-year period. Contact Dermatitis 2004;51(1):13-1 PubMed
- Champault, G. and Patel, J. C. [Treatment of constipation with Bepanthene]. Med.Chir Dig. 1977;6(1):57-59.
- Scott LN, Fiume M, Bergfeld WF, et al. Safety Assessment of Panthenol, Pantothenic Acid, and Derivatives as Used in Cosmetics. Int J Toxicol 2022;41(3_suppl):77-128. PubMed
- Han J, Warshaw EM. Allergic Contact Dermatitis to Panthenol in "Hypoallergenic" Products. Dermatitis 2023;34(1):62-63. PubMed
- Blanchard G, Kerre S, Walker A, et al. Allergic contact dermatitis from pantolactone and dexpanthenol in wound healing creams. Contact Dermatitis 2022;87(5):468-471. PubMed
- Peltier E, Trapp S, de Salvo R, et al. A new dexpanthenol-containing liquid cleanser for atopic-prone skin: Results from two prospective clinical studies evaluating cutaneous tolerability, moisturization potential, and effects on barrier function. J Cosme PubMed
Thiamine 7 references
- McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
- Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
- Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
- Rogovik, A. L., Vohra, S., and Goldman, R. D. Safety considerations and potential interactions of vitamins: should vitamins be considered drugs? Ann.Pharmacother. 2010;44(2):311-324. PubMed
- Arruti N, Bernedo N, Audicana MT, Villarreal O, Uriel O, Muñoz D. Systemic allergic dermatitis caused by thiamine after iontophoresis. Contact Dermatitis. 2013 Dec;69(6):375-6. PubMed
- Thiamine hydrochloride injection package insert. Lake Zurich, IL: Fresenius Kabi, LLC; September 2019.
- Vora B, Wen A, Yee SW, et al. The Effect of Trimethoprim on Thiamine Absorption: A Transporter-Mediated Drug-Nutrient Interaction. Clin Pharmacol Ther 2023;114(2):381-392.
Riboflavin 5 references
- Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998;50:466-70. PubMed
- Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
- Leeson LJ, Weidenheimer JF. Stability of tetracycline and riboflavin. J Pharm Sci. 1969;58(3):355-7. PubMed
- MacLennan, S. C., Wade, F. M., Forrest, K. M., Ratanayake, P. D., Fagan, E., and Antony, J. High-dose riboflavin for migraine prophylaxis in children: a double-blind, randomized, placebo-controlled trial. J Child Neurol. 2008;23(11):1300-1304.
- Dietary reference intakes (DRIs): estimated average requirements. Food and Nutrition Board, Institute of Medicine, National Academics. https://www.nal.usda.gov/sites/default/files/fnic_uploads//recommended_intakes_individuals.pdf Accessed July 24, 2017.
Selenium 36 references
- Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
- Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
- Trafikowska U, Zachara BA, Wiacek M, et al. Selenium supply and glutathione peroxidase activity in breastfed Polish infants. Acta Paediatr 1996;85:1143-5. PubMed
- Duffield-Lillico AJ, Slate EH, Reid ME, et al. Selenium supplementation and secondary prevention of nonmelanoma skin cancer in a randomized trial. J Natl Cancer Inst 2003;95:1477-81.. PubMed
- Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
- Schiavon R, Freeman GE, Guidi GC, et al. Selenium enhances prostacyclin production by cultured endothelial cells: possible explanation for increased bleeding times in volunteers taking selenium as a dietary supplement. Thromb Res 1984;34:389-96. PubMed
- Davila JC, Edds GT, Osuna O, Simpson CF. Modification of the effects of aflatoxin B1 and warfarin in young pigs given selenium. Am J Vet Res 1983;44:1877-83. DOI
- Heese HD, Lawrence MA, Dempster WS, Pocock F. Reference concentrations of serum selenium and manganese in healthy nulliparas. S Afr Med J 1988;73:163-5.
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- Capel ID, Jenner M, Williams DC, et al. The effect of prolonged oral contraceptive steroid use on erythrocyte glutathione peroxidase activity. J Steroid Biochem 1981;14:729-32. PubMed
- Contempre B, Dumont JE, Ngo B, et al. Effect of selenium supplementation in hypothyroid subjects of an iodine and selenium deficient area: the possible danger of indiscriminate supplementation of iodine-deficient subjects with selenium. J Clin Endocrinol PubMed
- Hofbauer LC, Spitzweg C, Magerstadt RA, Heufelder AE. Selenium-induced thyroid dysfunction. Postgrad Med J 1997;73:103-4. PubMed
- Debski B, Milner JA. Dietary selenium supplementation prolongs pentobarbital induced hypnosis. J Nutr Biochem 2004;15:548-53. PubMed
- Ishikawa M, Sasaki M, Koiwai K, et al. Inhibition of hepatic mixed-function oxidase enzymes in mice by acute and chronic treatment with selenium. J Pharmacobiodyn 1992;15:377-85. PubMed
- Lippmann SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the selenium and vitamin E cancer prevention trial (SELECT). JAMA 2009;301:39-51. DOI
- Reid SM, Middleton P, Cossich MC, Crowther CA. Interventions for clinical and subclinical hypothyroidism in pregnancy. Cochrane Database Syst Rev 2010;(7):CD007752. PubMed
- Vinceti, M., Wei, E. T., Malagoli, C., Bergomi, M., and Vivoli, G. Adverse health effects of selenium in humans. Rev.Environ.Health 2001;16(4):233-251. PubMed
- Abrams, C. K., Siram, S. M., Galsim, C., Johnson-Hamilton, H., Munford, F. L., and Mezghebe, H. Selenium deficiency in long-term total parenteral nutrition. Nutr Clin Pract 1992;7(4):175-178. PubMed
- Spiller, H. A. and Pfiefer, E. Two fatal cases of selenium toxicity. Forensic Sci Int 8-24-2007;171(1):67-72. PubMed
- Negro, R., Greco, G., Mangieri, T., Pezzarossa, A., Dazzi, D., and Hassan, H. The influence of selenium supplementation on postpartum thyroid status in pregnant women with thyroid peroxidase autoantibodies. J Clin Endocrinol.Metab 2007;92(4):1263-1268. PubMed
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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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