Major interaction on record — check this product against your medications before combining. Based on 26 of 28 ingredients. Check your meds →
Dietary supplement

Relax Ingredients & Drug Interactions

by Custom Health Centers

Capsule Category: Other Combinations
Most serious interaction: Major
The interaction bottom line Most serious interaction: Major

Relax is a dietary supplement by Custom Health Centers with 28 active ingredients. Its ingredients are commonly taken for anxiety and stress, relaxation and calm, sleep support.Based on those ingredients, 1,788 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Ashwagandha, Rhodiola Root Extract, St. John's Wort. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Relax by Custom Health Centers

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

From our pharmacy team — supplement deep dive

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

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

Why this rating?
  • The label discloses an exact amount for 10 of its 28 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (831 mg) without saying how much of each component you get.

Relax contains 28 active ingredients including the amino acid L-Theanine, the neurotransmitter GABA, lutein (an eye-health compound), valerian root (a traditional sleep aid), and several vitamin B forms—riboflavin (B2), biotin, B6, niacin (B3), and pantothenic acid (B5). It also includes Ashwagandha, hops, rhodiola, several herbal extracts and powders—chamomile, lemon balm, skullcap, hawthorn, bacopa, magnolia, and oat straw—plus mucuna pruriens (which contains the active compound levodopa), and the minerals calcium, magnesium, and zinc.

The product is filled with inactive ingredients including cellulose, rice flour, magnesium stearate, and silicon dioxide. One ingredient, Vitamin B5 (pantothenic acid), could not be checked against our interaction data.

Does it work?

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

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

Why this rating?
  • The label markets this product for: Helps manage daily stress.
  • We looked for evidence on: Anxiety, Adjustment disorders, Nervousness, Restlessness.
  • The strongest evidence on file: Passion Flower is rated "Possibly Effective" for Pre-procedural anxiety (Natural Medicines).
  • Also on file: Ashwagandha is rated "Possibly Effective" for Anxiety, Generalized anxiety disorder (GAD).
  • Also on file: St. John's Wort is rated "Possibly Ineffective" for Social anxiety disorder.

The evidence for most ingredients in this product is limited. L-Theanine is possibly effective for cognitive function but has insufficient evidence for anxiety.

GABA's effectiveness for any condition we have data on is rated insufficient. Valerian is possibly effective for insomnia but has insufficient evidence for anxiety, stress, or other uses.

Lutein is possibly effective for age-related macular degeneration and cataracts. Ashwagandha shows possibly effective evidence for insomnia, anxiety, stress, and generalized anxiety disorder, but insufficient evidence for ADHD.

Lemon balm is possibly effective for cold sores, stress, and depression. Several other ingredients—hops, chamomile, hawthorn, bacopa, magnolia, skullcap, and rhodiola—have insufficient evidence for their commonly promoted uses.

Oat straw is the exception: it has likely effective evidence for dyslipidemia and coronary heart disease. Vitamin B6 is effective for sideroblastic anemia and vitamin B6 deficiency; niacin is likely effective for pellagra.

The rest lack established effectiveness in our data, or the evidence is insufficient to rate.

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

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

Why this rating?
  • We hold adverse-effect (side-effect) data for 26 of the 26 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 26 of 26.
  • General safety write-ups exist for 26 of 26.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients are generally well tolerated for short-term use, but long-term safety data are limited for many of them. L-Theanine may cause headaches, drowsiness, and increased dream activity.

GABA is generally well tolerated but may cause drowsiness, muscle weakness, nausea, and gastric upset. Valerian commonly causes dizziness, drowsiness, and mental slowness; headache and vivid dreams can occur, and abrupt cessation after long use can trigger withdrawal symptoms (anxiety, insomnia, tachycardia).

Ashwagandha is generally well tolerated short-term but has rare case reports of acute hepatitis and liver failure. St.

John's Wort commonly causes diarrhea, dizziness, dry mouth, fatigue, headache, insomnia, and restlessness; it also increases photosensitivity (sun sensitivity) and can trigger mania or psychosis in susceptible people. Hops and chamomile may cause drowsiness and allergic reactions in people sensitive to ragweed.

Several ingredients—L-Theanine, GABA, Valerian, Hops, Ashwagandha, Chamomile, Lemon Balm, Skullcap, Hawthorn, Bacopa, and Magnolia—lack enough safety data for pregnancy and breastfeeding, and the data advises against use in these periods. Lutein, Vitamin B2, Biotin, and Oat Straw are rated likely safe in pregnancy and lactation at recommended amounts.

Calcium and magnesium are likely safe; Vitamin B6 is likely safe in pregnancy but possibly unsafe at high doses, and likely safe in lactation.

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

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

Why this rating?
  • 24 of the 26 matched ingredients can interact with medications — Magnolia, St. John's Wort, Lemon Balm, Gamma-aminobutyric Acid (gaba), Hawthorn, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,789 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking Relax, ask your doctor or pharmacist about interactions if you take any of these: heart medications (particularly digoxin), blood pressure drugs, seizure medications (phenobarbital, phenytoin, mephenytoin), blood thinners (warfarin, antiplatelet drugs), diabetes medications or insulin, thyroid hormone, benzodiazepines, antidepressants or other psychiatric drugs, HIV medications (especially integrase inhibitors, protease inhibitors), chemotherapy drugs, immunosuppressants, antibiotics (quinolones, tetracyclines, cephalexin), or muscle relaxants. Several ingredients—especially St.

John's Wort, Ashwagandha, Valerian, and Calcium—carry documented Major or Moderate risks that require dose adjustment, timing separation, or avoidance.

Check your own medication Run your meds through the checker above

The bottom line

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

This is a multi-ingredient relaxation and wellness blend with limited evidence for most uses and significant drug interaction potential. If you take any prescription medications—especially heart, blood pressure, diabetes, seizure, psychiatric, or HIV medications, or if you take blood thinners—you need to check your specific drugs before starting.

Talk with your doctor or pharmacist first, especially if you're pregnant, breastfeeding, or have liver or heart conditions.

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

Assessment coverage: 26 of 28 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Aug 23, 2022.

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

At a glance

General information

Key facts about Relax, straight from the product label.

Brand Custom Health Centers
Net contents 60 Vegan Capsule(s)
Market status On market
Date entered into DSLD Aug 23, 2022
DSLD ID 272731
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten Free, Dairy Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Relax by Custom Health Centers, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
2 Veggie Capsule(s)
Maximum serving Sizes:
2 Veggie Capsule(s)
Servings per container
30
IngredientAmount% DV
L-Theanine0 NP--
GABA0 NP--
Lutein0 NP--
Proprietary Blend831 mg--
Valerian0 NP--
Vitamin B212 mg923%
Biotin300 mcg1000%
Hops0 NP--
Ashwagandha0 NP--
Vitamin B68 mg471%
St. John's Wort0 NP--
Calcium25 mg2%
Magnesium25 mg6%
Vitamin B328 mg NE175%
Vitamin B516 mg320%
Rhodiola Root Extract0 NP--
Chamomile0 NP--
Lemon Balm0 NP--
Skullcap0 NP--
Hawthorn0 NP--
Bacopa0 NP--
Magnolia0 NP--
Oat Straw0 NP--
Mucuna pruriens0 NP--
Zinc25 mg227%
Vitamin B112 mg1000%
Passion Flower0 NP--
Potassium4 mg--
5-HTP0 NP--

Other ingredients: Cellulose, Rice Flour, Magnesium Stearate, Silicon Dioxide

Tap any ingredient to jump to its full detail below.

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

Directions As a dietary supplement take two (2) veggie capsules once a day. For best results take 20-30 min before a meal with an 8oz. glass of water or as directed by your healthcare professional.

Precautions

Caution: Do not exceed recommended dose.

Pregnant or nursing mothers, children under the age of 18, and individuals with a known medical condition should consult a physician before using this or any dietary supplement.

Pregnant or nursing mothers, children under the age of 18, and individuals with a known medical condition should consult a physician before using this or any dietary supplement.

Keep out of reach of children.

Do not use if safety seal is damaged or missing.

Seals/Symbols

FDA Registered Facility 3rd party certified GMP Sourced from A GMP Certified Facility Made in the USA

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,

Formulation

Helps manage daily stress

Gluten free. Dairy free.

FDA Statement of Identity

Dietary Supplement

See for yourself

Relax by Custom Health Centers label

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

What’s inside

The Ingredients in Relax by Custom Health Centers

These are the 28 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Veggie 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.

Proprietary Blend

831 mg per serving

Vitamin B2

Interacts with
20 drugs
12 mg per serving Form: Riboflavin

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...

Vitamin B2 monograph & interactions

Biotin

No known
interactions
300 mcg per serving

Biotin (vitamin B7) is a water-soluble vitamin your body needs to turn food into energy and to support healthy hair, skin, and nails. Most people get...

Biotin monograph & interactions

Vitamin B6

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

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

Vitamin B6 monograph & interactions

Calcium

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

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

Calcium monograph & interactions

Magnesium

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

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

Magnesium monograph & interactions

Vitamin B3

Interacts with
727 drugs
28 mg NE per serving Form: Niacin

Niacin (vitamin B3) is an essential nutrient your body needs for energy and metabolism, and deficiency is uncommon in most developed countries. Prescr...

Vitamin B3 monograph & interactions

Vitamin B5

16 mg per serving Form: Calcium D-Pantothenate

Zinc

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

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

Zinc monograph & interactions

Vitamin B1

12 mg per serving Form: Thiamine Mononitrate

Potassium

Interacts with
62 drugs
4 mg per serving Form: Potassium Gluconate

Potassium is an essential mineral your body needs for nerve signals, muscle function, and a steady heartbeat, and most people get enough from a balanc...

Potassium monograph & interactions

Other (inactive) ingredients: Cellulose, Rice Flour, Magnesium Stearate, Silicon Dioxide. These complete the product’s ingredient list but are not active constituents.

Interaction report

Relax by Custom Health Centers Drug Interactions

Want to check YOUR meds against Relax?

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

Go to the checker
1,788Drugs
781 Major 1,004 Moderate 3 Minor

Ingredients driving the most interactions

Ashwagandha 1,372
Chamomile 960
Skullcap 946

Each ingredient & the kinds of drugs it affects

For each ingredient in Relax 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.

Ashwagandha10 drug types · 1,372 drugs

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.

Likelihood Possible Evidence B
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.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence D
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.

Likelihood Probable Evidence B
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.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence D
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/]

Likelihood Possible Evidence C

Rhodiola Root Extract10 drug types · 1,271 drugs

Antidiabetes Drugs

Theoretically, taking rhodiola with antidiabetes drugs might increase the risk of hypoglycemia.
In vitro and animal research shows that rhodiola extract can decrease blood glucose due to alpha-glucosidase activity.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, taking rhodiola with antihypertensive drugs might increase the risk of hypotension.
In vitro and animal research shows that rhodiola extract inhibits angiotensin-converting enzyme (ACE) and might lower blood pressure.

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

Theoretically, rhodiola might increase levels of drugs metabolized by CYP2C9.
In vitro research shows that rhodiola inhibits CYP2C9. This effect is highly variable and appears to be dependent on the rhodiola product studied. Also, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours.

Likelihood Possible Evidence B
Immunosuppressants

Theoretically, rhodiola use might interfere with immunosuppressive therapy.
In vitro and animal research show that rhodiola has immunostimulatory effects.

Likelihood Possible Evidence D
Losartan (Cozaar)

Rhodiola might increase the levels and adverse effects of losartan.
A clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days reduces the metabolism of losartan, a CYP2C9 substrate, by 21% after 4 hours.

Likelihood Probable Evidence B
P-Glycoprotein Substrates

Theoretically, rhodiola might increase levels of P-glycoprotein substrates.
In vitro research shows that rhodiola inhibits P-glycoprotein. Theoretically, using rhodiola with P-glycoprotein substrates might increase drug levels and potentially increase the risk of adverse effects.

Likelihood Possible Evidence D
Antidepressant Drugs

Theoretically, rhodiola might increase the risk of adverse effects when taken with antidepressants.
A review of adverse event reports in Poland identified cases of tachyarrhythmias, myalgia, arthralgia, gum pain, restless leg syndrome, swallowing disorders, and changes in consciousness when rhodiola was taken in combination with paroxetine, escitalopram, fluoxetine, sertraline, trazodone, and/or duloxetine.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, rhodiola might increase the risk of adverse effects when taken with CNS depressants.
A review of adverse event reports in Poland identified cases of excessive sedation, myoclonus, hypotension, and hallucinations when rhodiola was taken with haloperidol, diazepam, or alprazolam.

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

Theoretically, rhodiola might increase levels of drugs metabolized by CYP1A2.
In vitro research shows that rhodiola inhibits CYP1A2. This effect is highly variable and appears to be dependent on the rhodiola product studied. However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of caffeine, a CYP1A2 substrate.

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

Theoretically, rhodiola might increase levels of drugs metabolized by CYP3A4.
In vitro research shows that rhodiola inhibits CYP3A4. This effect is highly variable and appears to be dependent on the rhodiola product studied. However, a clinical study in healthy young males found that taking rhodiola extract 290 mg daily for 14 days does not inhibit the metabolism of midazolam, a CYP3A4 substrate.

Likelihood Possible Evidence B

St. John's Wort47 drug types · 1,143 drugs

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.

Likelihood Likely Evidence B
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.

Likelihood Probable Evidence B
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.

Likelihood Probable Evidence B
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.

Likelihood Probable Evidence B
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.

Likelihood Likely Evidence B
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.

Likelihood Probable Evidence B
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.

Likelihood Likely Evidence A
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.

Likelihood Likely Evidence A
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.

Likelihood Likely Evidence B
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.

Likelihood Likely Evidence B
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.

Likelihood Likely Evidence B
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.

Likelihood Probable Evidence B
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.

Likelihood Probable Evidence B
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.

Likelihood Likely Evidence B
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).

Likelihood Likely Evidence B
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.

Likelihood Likely Evidence B
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.

Likelihood Likely Evidence B
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%.

Likelihood Probable Evidence B
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.

Likelihood Likely Evidence B
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.

Likelihood Likely Evidence B
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.

Likelihood Possible Evidence D
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.

Likelihood Probable Evidence B
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.

Likelihood Possible Evidence B
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.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence B

Chamomile9 drug types · 960 drugs

Cns Depressants

Theoretically, German chamomile might have additive effects when used with CNS depressants.
German chamomile has mild sedative effects. Theoretically, concomitant use with drugs with sedative properties can cause additive effects and side effects.

Likelihood Possible Evidence D
Contraceptive Drugs

Theoretically, large amounts of German chamomile might reduce the effectiveness of oral contraceptives.
In vitro, German chamomile has demonstrated antiestrogenic activity. Theoretically, concomitant use of large amounts of German chamomile might interfere with contraceptive drugs through competition for estrogen receptors.

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

Theoretically, German chamomile might inhibit CYP2C9 and increase levels of drugs metabolized by these enzymes.
In vitro evidence shows that German chamomile might inhibit CYP2C9. So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP2C9 in patients taking German chamomile.

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

Theoretically, German chamomile might inhibit CYP2D6 and increase levels of drugs metabolized by these enzymes.
In vitro evidence shows that German chamomile might inhibit CYP2D6. So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP2D6 in patients taking German chamomile.

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

Theoretically, German chamomile might inhibit CYP3A4 and increase levels of drugs metabolized by these enzymes.
In vitro evidence shows that German chamomile might inhibit CYP3A4. So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP3A4 in patients taking German chamomile.

Likelihood Possible Evidence D
Estrogens

Theoretically, large amounts of German chamomile might reduce the effectiveness of estrogens.
In vitro, German chamomile has demonstrated antiestrogenic activity. Theoretically, large amounts of German chamomile might interfere with hormone replacement therapy through competition for estrogen receptors.

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, large amounts of German chamomile might interfere with the activity of tamoxifen.
In vitro, German chamomile has demonstrated antiestrogenic activity.

Likelihood Possible Evidence D
Warfarin (Coumadin)

German chamomile might increase the effects of warfarin and increase the risk of bleeding.
In one case, a 70-year-old female taking warfarin developed retroperitoneal hematoma and bilateral recti muscle bleeding along with an INR of 7.9 following ingestion of German chamomile tea 4-5 cups daily and use of a topical chamomile-based lotion applied 4-5 times daily.

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

Theoretically, German chamomile might inhibit CYP1A2 and increase levels of drugs metabolized by these enzymes.
In vitro and animal research shows that German chamomile might inhibit CYP1A2. So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP1A2 in patients taking German chamomile.

Likelihood Possible Evidence D

Skullcap12 drug types · 946 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, Baikal skullcap might increase the risk of bleeding when used concomitantly with anticoagulant and antiplatelet drugs.
Preliminary clinical research suggests that taking capsules containing a combination of astragalus, goldthread, and Baikal skullcap daily for 4 weeks inhibits platelet aggregation; the effect seems to be similar to that of aspirin 50 mg daily. It is unclear if this effect is due to Baikal skullcap, other ingredients, or the combination.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, concomitant use of Baikal skullcap with antidiabetes drugs might enhance blood glucose lowering effects.
Baicalein, a constituent of Baikal skullcap, has alpha-glucosidase inhibitory activity in vitro. Animal research also suggests that Baikal skullcap enhances the antidiabetic effects of metformin. However, in a small human study, taking Baikal skullcap extract did not enhance the antidiabetic effects of metformin, although it did modestly lower glucose levels during an oral glucose tolerance test (OGTT). Until more is known, use cautiously.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, concomitant use of Baikal skullcap with antihypertensive drugs might have additive effects and increase the risk of hypotension.
Animal research suggests that baicalein, a constituent of Baikal skullcap, might lower blood pressure.

Likelihood Possible Evidence D
Antithyroid Drugs

Theoretically, concomitant use of Baikal skullcap and antithyroid drugs may result in additive activity and increase the risk of hypothyroidism.
In an animal hyperthyroid model, Baikal skullcap improved levels of triiodothyronine (T3), thyroxine (T4), and thyroid stimulating hormone (TSH). The clinical significance of this effect is unclear.

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

Theoretically, Baikal skullcap may increase levels of drugs metabolized by CYP1A2 enzymes.
In vitro evidence suggests that constituents of Baikal skullcap inhibit the activity of CYP1A2. This effect has not been reported in humans.

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

Theoretically, Baikal skullcap might increase levels of drugs metabolized by CYP2C19 enzymes.
In vitro evidence suggest that wogonin, a constituent of Baikal skullcap, modestly inhibits the activity of CYP2C19 enzymes. This effect has not been reported in humans.

Likelihood Possible Evidence D
Estrogens

Theoretically, concomitant use of large amounts of Baikal skullcap might interfere with hormone replacement therapy, due to competition for estrogen receptors.
In vitro evidence suggests that Baikal skullcap has estrogenic activity.

Likelihood Possible Evidence D
Lithium

Theoretically, Baikal skullcap might reduce lithium excretion and increase serum levels of lithium.
Baikal skullcap is thought to have diuretic properties, which may reduce lithium excretion. The dose of lithium might need to be decreased.

Likelihood Possible Evidence D
Alcohol (Ethanol)

Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol.
In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might potentiate the sedative effects of alcohol. Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.

Likelihood Unlikely Evidence D
Cns Depressants

Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties.
In vitro and animal research suggests that Baikal skullcap binds to GABA-A receptors and causes sedation. Theoretically, Baikal skullcap might cause additive therapeutic and adverse effects when used concomitantly with drugs with sedative properties. Preliminary clinical research has not identified clinically relevant sedation after use of Baikal skullcap; however, a thorough evaluation of safety outcomes has not been conducted.

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

Theoretically, Baikal skullcap might alter the levels and clinical effects of OATP substrates.
Some pharmacokinetic research shows that baicalin, a constituent of Baikal skullcap, can decrease plasma levels of rosuvastatin. The mechanism is thought to involve stimulation of the activity of the organic anion-transporting polypeptide 1B1 (OATP1B1), which transports rosuvastatin into the liver. This decreases plasma levels of the drug, but increases levels at the site of action in the liver. The degree to which rosuvastatin levels are affected depends on the OATP1B1 haplotype of the individual. Baikal skullcap might also affect other OATP1B1 substrates.

Likelihood Possible Evidence B
P-Glycoprotein Substrates

Theoretically, Baikal skullcap might increase levels of drugs transported by P-glycoprotein.
In vitro and animal research suggests that baicalein, oroxylin A, and wogonin, constituents of Baikal skullcap, can inhibit P-glycoprotein. This effect has not been reported in humans.

Likelihood Possible Evidence D

Bacopa8 drug types · 930 drugs

Anticholinergic Drugs

Theoretically, concurrent use might decrease the effectiveness of both agents.
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels, which could counteract the effects of anticholinergic drugs. Similarly, anticholinergic drugs might counteract the cholinergic effects of bacopa.

Likelihood Possible Evidence D
Cevimeline (Evoxac)

Theoretically, bacopa might increase the effects and adverse effects of cevimeline.
In one case, a 58-year-old female taking cevimeline long-term for Sjogren syndrome experienced hyperhidrosis, malaise, nausea, and tachycardia shortly after taking a single dose of bacopa. Symptoms resolved after two days. Cevimeline is metabolized by cytochrome P450 (CYP) 2D6 and CYP3A4, and researchers theorize that bacopa may have inhibited these isoenzymes. However, it is unclear if bacopa causes clinically significant inhibition of either CYP2D6 or CYP3A4.

Likelihood Possible Evidence D
Cholinergic Drugs

Theoretically, concurrent use of bacopa with other cholinergic drugs might have additive effects.
Bacopa seems to inhibit acetylcholinesterase and might increase acetylcholine levels. Theoretically, this could result in additive cholinergic effects when used with cholinergic drugs.

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

Theoretically, bacopa might increase the levels and adverse effects of CYP1A2 substrates.
Research on the effects of bacopa extracts on CYP1A2 enzymes is conflicting. Some in vitro evidence shows that bacopa extract can moderately and non-competitively inhibit CYP1A2, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.

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

Theoretically, bacopa might increase the levels and adverse effects of CYP2C19 substrates.
In vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C19 enzymes. It is not known whether this is clinically significant.

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

Theoretically, bacopa might increase the levels and adverse effects of CYP2C9 substrates.
Research on the effect of bacopa extracts on CYP2C9 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and non-competitively inhibit CYP2C9, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.

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

Theoretically, bacopa might increase the levels and adverse effects of CYP3A4 substrates.
Research on the effects of bacopa extracts on CYP3A4 enzymes is conflicting. Some in vitro evidence suggests that bacopa extract can moderately and competitively inhibit CYP3A4, while other in vitro evidence suggests that any effect is unlikely to be clinically significant.

Likelihood Possible Evidence D
Thyroid Hormone

Theoretically, bacopa might have additive effects when used with thyroid hormone.
Animal research suggests that bacopa increases thyroxine (T4) levels in mice by about 40%.

Likelihood Possible Evidence D

Valerian6 drug types · 902 drugs

Alcohol (Ethanol)

Valerian can have additive sedative effects when used concomitantly with alcohol.
Valerian has sedative effects. Theoretically, valerian might have an additive sedative effect when combined with alcohol. Excessive sedation has been reported in an alcohol-abusing individual who took valerian and Gingko biloba. However, the potential interaction between valerian and alcohol has been disputed in other research. Limited evidence suggests that a combination of valerian 160 mg and lemon balm 80 mg (Euvegal) does not cause further deterioration in reaction ability and reaction rate when taken with alcohol as compared to the effects of alcohol alone.

Likelihood Possible Evidence B
Alprazolam (Xanax)

Valerian can have additive sedative effects when used with alprazolam. Also, valerian in high doses might modestly increase alprazolam levels, though this is not likely to be clinically significant.
Valerian has sedative effects. Theoretically, valerian might cause additive sedation when combined with alprazolam. Also, a small pharmacokinetic study shows that taking valerian extract 1000 mg daily (providing 11 mg valerenic acid) might increase alprazolam levels by about 19%. This might be due to valerian's mild inhibition of cytochrome P450 3A4 (CYP3A4). Despite being statistically significant, this increase is not likely to be clinically significant.

Likelihood Possible Evidence B
Cns Depressants

Valerian can have additive sedative effects when used concomitantly with CNS depressant drugs.
Theoretically, concomitant use of valerian and drugs with sedative and anesthetic properties may cause additive therapeutic and adverse effects.

Likelihood Possible Evidence D
Glucuronidated Drugs

Valerian might weakly inhibit glucuronidation and increase concentrations of drugs metabolized by UGT1A1 and UGT2B7.
In vitro research shows that methanolic valerian extract and valerenic acid might competitively inhibit UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1) and UGT2B7.

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

Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP2D6.
Although some in vitro evidence suggests that valerian affects CYP2D6, clinical pharmacokinetic (PK) studies show that valerian is unlikely to affect the CYP2D6 enzyme. In one PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days did not affect the metabolism of dextromethorphan, a CYP2D6 substrate. In another PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of debrisoquine, an accepted CYP2D6 probe-substrate.

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

Valerian does not seem to have a clinically relevant effect on levels of drugs metabolized by CYP3A4.
Although some in vitro evidence suggests that valerian extract might inhibit or induce CYP3A4, clinical pharmacokinetic (PK) studies show that valerian does not have a clinically significant effect on the CYP3A4 enzyme. In one PK study, taking valerian 125 mg three times daily for 28 days did not affect metabolism of midazolam, an accepted CYP3A4 probe-substrate. In another PK study, taking valerian 1000 mg (providing about 11 mg valerenic acid) nightly for 14 days modestly increases levels of alprazolam, a CYP3A4 substrate, suggesting mild inhibition of CYP3A4. However, this mild inhibition is unlikely to be clinically relevant.

Likelihood Possible Evidence B

Hops4 drug types · 863 drugs

Cns Depressants

Theoretically, concomitant use of hops with sedative drugs might cause additive sedation.
Some animal research shows that hops has sedative effects.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence D
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.

Likelihood Unlikely Evidence D
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.

Likelihood Possible Evidence D

Passion Flower3 drug types · 836 drugs

Cns Depressants

Concomitant use of passion flower with sedative drugs might cause additive effects and side effects.
Research in animals and humans shows that passion flower has sedative effects which can be additive when used with sedative medications like lorazepam.

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

Theoretically, passion flower might decrease the effects of CYP3A4 substrates.
In vitro research suggests that passion flower can induce CYP3A4 enzymes, albeit to a much lower degree than rifampin, a known CYP3A4 inducer.

Likelihood Possible Evidence D
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Theoretically, passion flower might reduce the bioavailability of OATP2B1 and OATP1A2 substrates.
In vitro research shows that the passion flower constituents apigenin and vitexin inhibit OATP2B1 and OATP1A2. This inhibition may be dose-dependent. One specific high-flavonoid passion flower extract (Valverde) seems to inhibit OATP2B1 and OATP1A2, while another extract with a lower flavonoid concentration (Arkocaps) shows less potent inhibition. OATPs are responsible for the uptake of drugs and other compounds into the body; however, the specific activities of OATP2B1 and OATP1A2 are not well characterized.

Likelihood Possible Evidence D

Vitamin B315 drug types · 727 drugs

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.

Likelihood Probable Evidence D
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.

Likelihood Probable Evidence C
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.

Likelihood Possible Evidence D
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.

Likelihood Probable Evidence B
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.

Likelihood Possible Evidence B
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%.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence D
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).

Likelihood Possible Evidence D
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.

Likelihood Probable Evidence C
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.

Likelihood Probable Evidence C
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.

Likelihood Probable Evidence D
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.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence D
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.

Likelihood Likely Evidence B

L-Theanine3 drug types · 565 drugs

Antihypertensive Drugs

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

Likelihood Possible Evidence D
Cns Depressants

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

Likelihood Unlikely Evidence D
Serotonergic Drugs

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

Likelihood Unlikely Evidence C

GABA2 drug types · 419 drugs

Antihypertensive Drugs

Theoretically, taking GABA with antihypertensive drugs might increase the risk of hypotension.
Some clinical research shows that GABA can decrease blood pressure in patients with hypertension.

Likelihood Possible Evidence B
Cns Depressants

Theoretically, GABA might have additive sedative effects when used in conjunction with CNS depressants. However, it is unclear if this concern is clinically relevant.
Endogenous GABA has well-established relaxant effects and GABA(A) receptors have an established physiological role in sleep. However, the effects of GABA supplements are unclear, as it is unknown whether exogenous GABA crosses the blood-brain barrier. Although there have been limited reports of drowsiness or tiredness with GABA supplements, these effects have not been widely reported in clinical studies. Additionally, intravenous GABA 0.1-1 mg/kg has been shown to induce anxiety in a dose-dependent manner.

Likelihood Unlikely Evidence D

5-HTP3 drug types · 398 drugs

Carbidopa (Lodosyn)

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

Likelihood Possible Evidence D
Cns Depressants

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

Likelihood Possible Evidence D
Serotonergic Drugs

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

Likelihood Possible Evidence D

Magnolia2 drug types · 351 drugs

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.

Likelihood Possible Evidence D
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.

Likelihood Possible Evidence D

Magnesium15 drug types · 295 drugs

Levodopa/Carbidopa (Sinemet)

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

Likelihood Probable Evidence B
Aminoglycoside Antibiotics

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

Likelihood Possible Evidence D
Antacids

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

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

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

Likelihood Probable Evidence D
Bisphosphonates

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

Likelihood Probable Evidence B
Calcium Channel Blockers

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

Likelihood Possible Evidence D
Digoxin

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

Likelihood Possible Evidence B
Potassium-Sparing Diuretics

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

Likelihood Probable Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence D
Skeletal Muscle Relaxants

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

Likelihood Probable Evidence A
Sulfonylureas

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

Likelihood Probable Evidence B
Tetracycline Antibiotics

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

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

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

Likelihood Unlikely Evidence B
Gabapentin (Neurontin)

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

Likelihood Unlikely Evidence B
Sevelamer (Renagel, Renvela)

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

Likelihood Possible Evidence B

Lemon Balm2 drug types · 264 drugs

Cns Depressants

Theoretically, concomitant use of lemon balm might have additive effects with CNS depressant drugs.
Lemon balm seems to have CNS depressant activity in animals and in humans.

Likelihood Possible Evidence B
Thyroid Hormone

Theoretically, lemon balm might interfere with thyroid hormone replacement therapy.
In vitro, constituents of lemon balm extract bind to thyroid stimulating hormone (TSH), preventing TSH receptor-binding and leading to the inhibition of TSH-stimulated adenylate cyclase activity. In animals, lemon balm extract has been shown to decrease levels of circulating TSH and inhibit thyroid secretion.

Likelihood Possible Evidence D

Vitamin B65 drug types · 210 drugs

Amiodarone (Cordarone)

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

Likelihood Possible Evidence B
Antihypertensive Drugs

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

Likelihood Possible Evidence B
Phenobarbital (Luminal)

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

Likelihood Possible Evidence D
Phenytoin (Dilantin)

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

Likelihood Possible Evidence D
Levodopa

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

Likelihood Unlikely Evidence D

Mucuna pruriens8 drug types · 193 drugs

Levodopa

Concomitant use can increase the risk of levodopa-related adverse effects.
Cowhage contains levodopa. Some cowhage products have been standardized to contain 75-400 mg of levodopa per dose.

Likelihood Likely Evidence D
Methyldopa (Aldomet)

Theoretically, concomitant use of cowhage and methyldopa might increase the risk of hypotension.
Cowhage contains levodopa. Use of levodopa with methyldopa might cause additive hypotension. In addition, methyldopa may inhibit peripheral decarboxylation of levodopa and increase levodopa levels in the central nervous system; avoid using.

Likelihood Probable Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, concomitant use of cowhage and non-selective MAOIs might increase the risk of hypertensive crisis.
Cowhage contains levodopa. Use of levodopa with non-selective MAOIs might cause hypertensive crisis. However, this interaction has not been reported with MAO-B selective inhibitors such as selegiline.

Likelihood Probable Evidence D
Anesthesia

Theoretically, concomitant use of cowhage and anesthesia might increase the risk of arrhythmias.
Cowhage contains levodopa. Use of levodopa with cyclopropane or halogenated hydrocarbon anesthesia has led to arrhythmias. Other anesthetics have not been implicated. Use other anesthetics in patients taking cowhage or tell patients to stop taking cowhage at least 2 weeks before surgery.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, concomitant use of cowhage and antidiabetes drugs might increase the risk of hypoglycemia.
Animal research shows that cowhage might have hypoglycemic effects.

Likelihood Possible Evidence D
Antipsychotic Drugs

Theoretically, use of cowhage might decrease the clinical effects of antipsychotic drugs.
Cowhage contains levodopa. Use of levodopa might counteract the antidopaminergic effects of antipsychotic medications.

Likelihood Possible Evidence D
Guanethidine (Ismelin)

Theoretically, concomitant use of cowhage and guanethidine might increase the risk of hypotension.
Cowhage contains levodopa. Use of levodopa with guanethidine might cause additive hypotension; avoid using.

Likelihood Probable Evidence D
Tricyclic Antidepressants (Tcas)

Theoretically, use of TCAs might reduce the levels and clinical effects of cowhage.
Cowhage contains levodopa. Use of TCAs might reduce the absorption of levodopa. Some case reports describe patients that developed hypertension and dyskinesia when taking both levodopa and TCAs.

Likelihood Possible Evidence D

Hawthorn6 drug types · 191 drugs

Nitrates

Theoretically, concomitant use might cause additive coronary vasodilatory effects.
Some evidence shows that hawthorn might lower blood pressure due to vasodilatory effects.

Likelihood Probable Evidence D
Phosphodiesterase-5 Inhibitors

Theoretically, concomitant use might result in additive vasodilation and hypotension.
Hawthorn might inhibit PDE-5 and cause vasodilation.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, hawthorn may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal research shows that hawthorn can inhibit platelet aggregation. However, its effect in humans is unclear. One observational study shows that patients taking hawthorn shortly before undergoing coronary artery bypass graft (CABG) surgery or valve replacement surgery have a 10% incidence of postoperative bleeding, compared with 1% in those who never consumed hawthorn extract. However, clinical research shows that taking a specific preparation of dried hawthorn leaves and flowers (Crataesor, Soria Natural Lab) 800 mg three times daily for 15 days does not affect platelet aggregation or levels of thromboxane B2, the metabolite of thromboxane A2, in healthy humans.

Likelihood Possible Evidence D
Beta-Blockers

Theoretically, concomitant use might cause additive effects on blood pressure and heart rate.
Some evidence shows that hawthorn might lower blood pressure and heart rate.

Likelihood Possible Evidence D
Calcium Channel Blockers

Theoretically, concomitant use might cause additive coronary vasodilation and hypotensive effects.
Some evidence shows that hawthorn might lower blood pressure due to vasodilatory effects.

Likelihood Possible Evidence D
Digoxin (Lanoxin)

Theoretically, hawthorn might potentiate the effects and adverse effects of digoxin.
Hawthorn appears to improve cardiac output; however, hawthorn does not appear to affect digoxin pharmacokinetics. Case reports suggest that at least one species of hawthorn root extract (Crataegus mexicana) may produce adverse effects similar to digoxin and can cross-react with digoxin assays, leading to falsely elevated plasma digoxin levels.

Likelihood Possible Evidence D

Calcium18 drug types · 168 drugs

Ceftriaxone (Rocephin)

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

Likelihood Probable Evidence D
Dolutegravir (Tivicay)

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

Likelihood Probable Evidence B
Elvitegravir (Vitekta)

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

Likelihood Probable Evidence B
Aluminum

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

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

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

Likelihood Probable Evidence D
Bisphosphonates

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

Likelihood Probable Evidence C
Calcipotriene (Dovonex)

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

Likelihood Possible Evidence B
Digoxin (Lanoxin)

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

Likelihood Possible Evidence B
Diltiazem (Cardizem, Others)

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

Likelihood Probable Evidence D
Levothyroxine (Synthroid, Others)

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

Likelihood Probable Evidence B
Lithium

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

Likelihood Possible Evidence B
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Raltegravir (Isentress)

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

Likelihood Possible Evidence B
Sotalol (Betapace)

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

Likelihood Possible Evidence B
Tetracycline Antibiotics

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

Likelihood Probable Evidence C
Thiazide Diuretics

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

Likelihood Probable Evidence C
Verapamil (Calan, Others)

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

Likelihood Probable Evidence D
Calcium Channel Blockers

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

Likelihood Unlikely Evidence D

Oat Straw2 drug types · 86 drugs

Antidiabetes Drugs

Theoretically, oats may have additive effects with antidiabetic agents and might increase the risk of hypoglycemia.
Consuming oats can decrease blood glucose in patients with diabetes. In those who require insulin, taking oats 100 grams daily for 2 days reduces the insulin dose required to achieve metabolic control.

Likelihood Possible Evidence D
Insulin

Concomitant use of oats and insulin might increase the risk of hypoglycemia.
In patients with insulin-dependent type 2 diabetes, taking oats 100 grams daily for 2 days reduces the insulin dose required to achieve metabolic control.

Likelihood Possible Evidence B

Zinc10 drug types · 67 drugs

Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

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

Likelihood Probable Evidence D
Cephalexin (Keflex)

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

Likelihood Probable Evidence B
Cisplatin (Platinol-Aq)

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

Likelihood Possible Evidence D
Integrase Inhibitors

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

Likelihood Possible Evidence D
Penicillamine (Cuprimine, Depen)

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

Likelihood Probable Evidence B
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Ritonavir (Norvir)

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

Likelihood Probable Evidence B
Tetracycline Antibiotics

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

Likelihood Probable Evidence B
Amiloride (Midamor)

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

Likelihood Probable Evidence B
Atazanavir (Reyataz)

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

Likelihood Probable Evidence B

Potassium3 drug types · 62 drugs

Ace Inhibitors (Aceis)

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

Likelihood Likely Evidence C
Angiotensin Receptor Blockers (Arbs)

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

Likelihood Likely Evidence C
Potassium-Sparing Diuretics

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

Likelihood Likely Evidence C

Vitamin B21 drug type · 20 drugs

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.

Likelihood Possible Evidence D
The maker

Brand information

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

Custom Health Centers

See all Custom Health Centers products
Name
Ketality, LLC
City
Lake Orion
State
MI
ZipCode
48539
Phone Number
(844) 789-8446
Web Address
WWW.CUSTOMHEALTHCENTERS.COM
Pharmacist Counseling Corner

Relax by Custom Health Centers: Common Questions

Does Relax by Custom Health Centers interact with any medications?
Yes. Based on its ingredients, Relax has a known interaction with 1,788 medications, including 781 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Relax contains 28 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Is it safe to take Relax while I'm pregnant?
Most ingredients in Relax lack enough safety data for pregnancy, and the data advises against use. St. John's Wort and Ashwagandha are rated possibly or likely unsafe in pregnancy. Talk with your doctor or pharmacist before using this product if you're pregnant or planning to become pregnant.
Can I take Relax while breastfeeding?
Several key ingredients—L-Theanine, GABA, Valerian, St. John's Wort, Ashwagandha, Hops, Chamomile, Lemon Balm, Skullcap, Hawthorn, Bacopa, Magnolia, and Mucuna pruriens—lack enough safety data for breastfeeding. St. John's Wort may pass into breast milk and cause side effects in infants, and Mucuna pruriens can lower prolactin and reduce milk supply. Talk with your doctor or pharmacist before using this product.
Does this product actually help with relaxation and anxiety?
The evidence is mixed and limited. Ashwagandha is possibly effective for anxiety, and lemon balm is possibly effective for stress. Most other ingredients—including GABA, Valerian, hops, and chamomile—have insufficient evidence to know whether they work for anxiety or relaxation, even though they're traditionally used for these purposes.
What are the most common side effects I might experience?
Drowsiness and dizziness are common with several ingredients. Valerian and St. John's Wort can cause headache and vivid dreams; Vitamin B6 can cause headache and nausea; hops and chamomile may cause allergic reactions; and St. John's Wort increases sun sensitivity. Gastrointestinal upset, nausea, and diarrhea are possible with multiple ingredients.
Can I suddenly stop taking Relax, or do I need to taper it?
If you've used Valerian in this product for an extended period, do not stop abruptly. Withdrawal symptoms—anxiety, insomnia, tachycardia, and irritability—can occur. Taper the dose slowly over time and talk with your doctor or pharmacist about the right schedule.
Will Relax make me drowsy during the day?
Yes, it's possible. L-Theanine, GABA, Valerian, Hops, Ashwagandha, Chamomile, Lemon Balm, and other ingredients can cause drowsiness. The degree depends on your individual response and the amount you take. Start with a lower dose to see how it affects you, and avoid driving or operating machinery until you know.

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.

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Go deeper

The Full Monographs Behind Relax’s Ingredients

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

Herb & supplement monograph

Theanine

Interacts with 565 drugs

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

Read the full Theanine monograph →
Herb & supplement monograph

Gamma-aminobutyric Acid (gaba)

Interacts with 419 drugs

GABA is a calming chemical messenger (neurotransmitter) that your body makes on its own, and it is sold as a supplement for stress, anxiety, and sleep. The science behind oral GABA supplemen...

Read the full Gamma-aminobutyric Acid (gaba) monograph →
Herb & supplement monograph

Lutein

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

Read the full Lutein monograph →
Herb & supplement monograph

Valerian

Interacts with 902 drugs

Valerian is an herb whose root is widely used as a natural sleep aid and for calming nerves. The evidence is mixed and often weak, so it may help some people sleep but does not work reliably...

Read the full Valerian monograph →
Herb & supplement monograph

Hops

Interacts with 863 drugs

Hops 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 monograph

Ashwagandha

Interacts with 1,372 drugs

Ashwagandha 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 monograph

St. John's Wort

Interacts with 1,143 drugs

St. 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 monograph

Rhodiola

Interacts with 1,271 drugs

Rhodiola is an herb traditionally used to fight fatigue and help the body cope with stress. Some small studies suggest it may modestly reduce fatigue and improve mood, but the evidence is li...

Read the full Rhodiola monograph →
Herb & supplement monograph

German Chamomile

Interacts with 960 drugs

German chamomile is a widely used herbal remedy taken mainly as a tea for calming, sleep, and digestive complaints. Early research suggests possible benefits for mild anxiety and some skin o...

Read the full German Chamomile monograph →
Herb & supplement monograph

Lemon Balm

Interacts with 264 drugs

Lemon balm is a gentle, lemon-scented mint-family herb traditionally used to ease stress, support sleep, and calm digestion, and topically for cold sores. Early studies are promising but gen...

Read the full Lemon Balm monograph →
Herb & supplement monograph

Baikal Skullcap

Interacts with 946 drugs

Baikal skullcap is a traditional Chinese herb (Huang Qin) used for inflammation, allergies, and infections, with active compounds like baicalin and baicalein studied mostly in the lab. Human...

Read the full Baikal Skullcap monograph →
Herb & supplement monograph

Hawthorn

Interacts with 191 drugs

Hawthorn is a plant traditionally used for heart-related complaints, and some studies suggest it may modestly help symptoms of mild heart failure when added to standard care. However, the ev...

Read the full Hawthorn monograph →
Herb & supplement monograph

Bacopa

Interacts with 930 drugs

Bacopa is an Ayurvedic herb most often used for memory and thinking. Some small studies suggest it may modestly help memory when taken regularly for several weeks, but the evidence is limite...

Read the full Bacopa monograph →
Herb & supplement monograph

Magnolia

Interacts with 351 drugs

Magnolia 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 monograph

Oats

Interacts with 86 drugs

Oats are a well-studied whole grain whose soluble fiber (beta-glucan) can help lower cholesterol and support heart health when eaten regularly. As a food, oats are safe for most people, and...

Read the full Oats monograph →
Herb & supplement monograph

Cowhage

Interacts with 193 drugs

Cowhage (Mucuna pruriens) is a tropical legume best known as a natural source of L-dopa, the compound the body turns into dopamine. It is most studied for Parkinson's disease symptoms and ma...

Read the full Cowhage monograph →
Herb & supplement monograph

Passion Flower

Interacts with 836 drugs

Passion flower is a traditional calming herb that many people use for anxiety and sleep. Early studies hint it may help with mild anxiety and restlessness, but the evidence is limited and mo...

Read the full Passion Flower monograph →
Herb & supplement monograph

5-htp

Interacts with 398 drugs

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

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

Riboflavin

Interacts with 20 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 very safe at typical doses, and the stro...

Read the full Riboflavin monograph →
Herb & supplement monograph

Biotin

Biotin (vitamin B7) is a water-soluble vitamin your body needs to turn food into energy and to support healthy hair, skin, and nails. Most people get plenty from a normal diet, and true defi...

Read the full Biotin monograph →
Herb & supplement monograph

Vitamin B6

Interacts with 210 drugs

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

Read the full Vitamin B6 monograph →
Herb & supplement monograph

Calcium

Interacts with 168 drugs

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

Read the full Calcium monograph →
Herb & supplement monograph

Magnesium

Interacts with 295 drugs

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

Read the full Magnesium monograph →
Herb & supplement monograph

Niacin

Interacts with 727 drugs

Niacin (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 monograph

Zinc

Interacts with 67 drugs

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

Read the full Zinc monograph →
Herb & supplement monograph

Potassium

Interacts with 62 drugs

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

Read the full Potassium monograph →
Sources

Sources & How We Checked

Relax's label data comes from the NIH Dietary Supplement Label Database; the ingredient interaction data is from the Natural Medicines database, reviewed by our pharmacists.

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

The 803 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.

Theanine 6 references
  1. Yokogoshi H, Kobayashi M. Hypotensive effect of gamma-glutamylethylamide in spontaneously hypertensive rats. Life Sci 1998;62:1065-8.
  2. Haskell, C. F., Kennedy, D. O., Milne, A. L., Wesnes, K. A., and Scholey, A. B. The effects of L-theanine, caffeine and their combination on cognition and mood. Biol.Psychol. 2008;77(2):113-122. PubMed
  3. Yokogoshi, H., Kato, Y., Sagesaka, Y. M., Takihara-Matsuura, T., Kakuda, T., and Takeuchi, N. Reduction effect of theanine on blood pressure and brain 5-hydroxyindoles in spontaneously hypertensive rats. Biosci.Biotechnol.Biochem. 1995;59(4):615-618. PubMed
  4. Lyon MR, Kapoor MP, Juneja LR. The effects of L-theanine (Suntheanine®) on objective sleep quality in boys with attention deficit hyperactivity disorder (ADHD): a randomized, double-blind, placebo-controlled clinical trial. Altern Med Rev. 2011;16(4):348-
  5. Hidese S, Ota M, Wakabayashi C, et al. Effects of chronic l-theanine administration in patients with major depressive disorder: an open-label study. Acta Neuropsychiatr 2017;29(2):72-9.
  6. Tsuchiya T, Honda H, Oikawa M, et al. Oral administration of the amino acids cystine and theanine attenuates the adverse events of S-1 adjuvant chemotherapy in gastrointestinal cancer patients. Int J Clin Oncol 2016;21(6):1085-90. PubMed

See these in context on the Theanine monograph →

Gamma-aminobutyric Acid (gaba) 12 references
  1. Cavagnini F, Invitti C, Pinto M, et al. Effect of acute and repeated administration of gamma aminobutyric acid (GABA) on growth hormone and prolactin secretion in man. Acta Endocrinol (Copenh) 1980;93:149-54.
  2. Nurnberger JI Jr, Berrettini WH, Simmons-Alling S, et al. Intravenous GABA administration is anxiogenic in man. Psychiatry Res 1986;19:113-7. PubMed
  3. Gershman RN, Vasilenko MA, Iliushina GG, et al. [Gammalon in the rehabilitation in infantile cerebral palsy]. Pediatr.Akus.Ginekol. 1977;(6):26-7.
  4. Loeb C, Benassi E, Bo, GP, et al. Preliminary evaluation of the effect of GABA and phosphatidylserine in epileptic patients. Epilepsy Res. 1987;1:209-12 . PubMed
  5. Inoue K, Shirai T, Ochiai H, et al. Blood-pressure-lowering effect of a novel fermented milk containing gamma-aminobutyric acid (GABA) in mild hypertensives. Eur J Clin Nutr 2003;57:490-95.
  6. ELLIOTT, K. A. and JASPER, H. H. Gammaaminobutyric acid. Physiol Rev. 1959;39(2):383-406.
  7. Winsky-Sommerer, R. Role of GABAA receptors in the physiology and pharmacology of sleep. Eur.J.Neurosci. 2009;29(9):1779-1794.
  8. Meldrum, B. S. GABAergic mechanisms in the pathogenesis and treatment of epilepsy. Br.J.Clin.Pharmacol. 1989;27 Suppl 1:3S-11S. PubMed
  9. Loeb, C., Marinari, U. M., Benassi, E., Besio, G., Cottalasso, D., Cupello, A., Maffini, M., Mainardi, P., Pronzato, M. A., and Scotto, P. A. Phosphatidylserine increases in vivo the synaptosomal uptake of exogenous GABA in rats. Exp.Neurol. 1988;99(2):4 PubMed
  10. Melis, G. B., Paoletti, A. M., Mais, V., and Fioretti, P. Interference of dopamine infusion on gamma-amino butyric acid (GABA)-stimulated prolactin increase. J.Endocrinol.Invest 1980;3(4):445-448.
  11. Boonstra E, de Kleijn R, Colzato LS, Alkemade A, Forstmann BU, Nieuwenhuis S. Neurotransmitters as food supplements: the effects of GABA on brain and behavior. Front Psychol. 2015 Oct 6;6:1520. doi: 10.3389/fpsyg.2015.01520. eCollection 2015. PubMed
  12. de Bie TH, Witkamp RF, Balvers MG, Jongsma MA. Effects of ?-aminobutyric acid supplementation on glucose control in adults with prediabetes: A double-blind, randomized, placebo-controlled trial. Am J Clin Nutr 2023;118(3):708-719. PubMed

See these in context on the Gamma-aminobutyric Acid (gaba) monograph →

Lutein 2 references
  1. Brown L, Rimm EB, Seddon JM, et al. A prospective study of carotenoid intake and risk of cataract extraction in US men. Am J Clin Nutr 1999;70:517-24. PubMed
  2. Chasan-Taber L, Willett WC, Seddon JM, et al. A prospective study of carotenoid and vitamin A intakes and risk of cataract extraction in US women. Am J Clin Nutr 1999;70:509-16. PubMed

See these in context on the Lutein monograph →

Valerian 37 references
  1. Willey LB, Mady SP, Cobaugh DJ, Wax PM. Valerian overdose: a case report. Vet Hum Toxicol 1995;37:364-5.
  2. Kuhlmann J, Berger W, Podzuweit H, Schmidt U. The influence of valerian treatment on "reaction time, alertness and concentration" in volunteers. Pharmacopsychiatry 1999;32:235-41. PubMed
  3. Klepser TB, Klepser ME. Unsafe and potentially safe herbal therapies. Am J Health Syst Pharm 1999;56:125-38. PubMed
  4. Houghton PJ. The scientific basis for the reputed activity of Valerian. J Pharm Pharmacol 1999;51:505-12. PubMed
  5. Garges HP, Varia I, Doraiswamy PM. Cardiac complications and delirium associated with Valerian root withdrawal. [Letter to the Editor]. JAMA 1998;280:1566-7. PubMed
  6. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  7. MacGregor FB, Abernethy VE, Dahabra S, et al. Hepatotoxicity of herbal remedies. BMJ 1989;299:1156-7. PubMed
  8. Leathwood PD, Chauffard F. Aqueous extract of valerian reduces latency to fall asleep in man. Planta Med 1985;2:144-8. PubMed
  9. Hadley S, Petry JJ. Valerian. Am Fam Physician 2003;67:1755-8..
  10. Glass JR, Sproule BA, Herrmann N, et al. Acute pharmacological effects of temazepam, diphenhydramine, and valerian in healthy elderly subjects. J Clin Psychopharmacol 2003;23:260-8. PubMed
  11. Lefebvre T, Foster BC, Drouin CE, et al. In vitro activity of commercial valerian root extracts against human cytochrome P450 3A4. J Pharm Pharmaceut Sci 2004;7:265-73.
  12. Yuan CS, Mehendale S, Xiao Y, et al. The gamma-aminobutyric acidergic effects of valerian and valerenic acid on rat brainstem neuronal activity. Anesth Analg 2004;98:353-8. PubMed
  13. Donovan JL, DeVane CL, Chavin KD, et al. Multiple night-time doses of valerian (Valeriana officinalis) had minimal effects on CYP3A4 activity and no effect on CYP2D6 activity in healthy volunteers. Drug Metab Dispos 2004;32:1333-6. PubMed
  14. Gurley BJ, Gardner SF, Hubbard MA, et al. In vivo effects of goldenseal, kava kava, black cohosh, and valerian on human cytochrome P450 1A2, 2D6, 2E1, and 3A4/5 phenotypes. Clin Pharmacol Ther 2005;77:415-26. PubMed
  15. Gutierrez S, Ang-Lee MK, Walker DJ, Zacny JP. Assessing subjective and psychomotor effects of the herbal medication valerian in healthy volunteers. Pharmacol Biochem Behav 2004;78:57-64. PubMed
  16. Jacobs BP, Bent S, Tice JA, et al. An internet-based randomized, placebo-controlled trial of kava and valerian for anxiety and insomnia. Medicine (Baltimore) 2005;84:197-207. PubMed
  17. National Toxicology Program, US Department of Health and Human Services. Chemical Information Review Document for Valerian (Valeriana officinalis L.) [CAS No. 8057-49-6] and Oils [CAS No. 8008-88-6]. Supporting Nomination for Toxicological Evaluation by t
  18. Fernández-San-Martín MI, Masa-Font R, Palacios-Soler L, et al. Effectiveness of Valerian on insomnia: a meta-analysis of randomized placebo-controlled trials. Sleep Med. 2010 Jun;11:505-11. PubMed
  19. Coxeter PD, Schluter PJ, Eastwood HL, et al. Valerian does not appear to reduce symptoms for patients with chronic insomnia in general practice using a series of randomised n-of-1 trials. Complement Ther Med. 2003 Dec;11:215-22. PubMed
  20. Diaper A, Hindmarch I. A double-blind, placebo-controlled investigation of the effects of two doses of a valerian preparation on the sleep, cognitive and psychomotor function of sleep-disturbed older adults. Phytother Res. 2004 Oct;18:831-6. PubMed
  21. Cuellar NG, Ratcliffe SJ. Does valerian improve sleepiness and symptom severity in people with restless legs syndrome? Altern Ther Health Med 2009;15:22-8.
  22. Chen D, Klesmer J, Giovanniello A, et al. Mental status changes in an alcohol abuser taking valerian and gingko biloba. Am J Addict. 2002 Winter;11:75-7. PubMed
  23. Albrecht M, Berger W, Laux P, Schmidt U, et al. Psychopharmaka und Verkehrssicherheit. Der Einfluß von Euvegal® - Dragees forte auf die Fahrtüchtigkeit und Kombinationswirkungen mit Alkohol Z Allg Med 1995;71:1215-25.
  24. Carrasco MC, Vallejo JR, Pardo-de-Santayana M, et al. Interactions of Valeriana officinalis L. and Passiflora incarnata L. in a patient treated with lorazepam. Phytother Res. 2009 Dec;23:1795-6.
  25. Hellum BH, Nilsen OG. The in vitro inhibitory potential of trade herbal products on human CYP2D6-mediated metabolism and the influence of ethanol. Basic Clin Pharmacol Toxicol. 2007 Nov;101:350-8.
  26. Hellum BH, Hu Z, Nilsen OG. The induction of CYP1A2, CYP2D6 and CYP3A4 by six trade herbal products in cultured primary human hepatocytes. Basic Clin Pharmacol Toxicol. 2007 Jan;100:23-30. PubMed
  27. Alkharfy, K. M. and Frye, R. F. Effect of valerian, valerian/hops extracts, and valerenic acid on glucuronidation in vitro. Xenobiotica 2007;37(2):113-123.
  28. Vassiliadis, T., Anagnostis, P., Patsiaoura, K., Giouleme, O., Katsinelos, P., Mpoumponaris, A., and Eugenidis, N. Valeriana hepatotoxicity. Sleep Med 2009;10(8):935. PubMed
  29. Muller, Z., Sarkany, A., Altorjay, A., Szilagyi, A., Tura, T., and Ozsvar, Z. [Liver failure a la Eastern Europe]. Orv.Hetil. 3-22-2009;150(12):555-557. PubMed
  30. National Toxicology Program, US Department of Health and Human Services. Chemical Information Review Document for Valerian (Valeriana officinalis L.) [CAS No. 8057-49-6] and Oils [CAS No. 8008-88-6]. 2009;
  31. Wells SR. International intravenous administration of a crude valerian root extract. NACCT 1995;33:542.
  32. Aydinoglu U, Özcan H, Yücel A, Yücel N, Mutlu M. Valerian induced hypomania: a case report. Bull Clin Psychopharma 2012;22(Suppl. 1):S63.
  33. Mirabi P, Mojab F. The effects of valerian root on hot flashes in menopausal women. Iran J Pharm Res 2013;12(1):217-22.
  34. Thomas K, Canedo J, Perry PJ, et al. Effects of valerian on subjective sedation, field sobriety testing and driving simulator performance. Accid Anal Prev. 2016 Jul;92:240-4. PubMed
  35. Kia YH, Alexander S, Dowling D, Standish R. A case of steroid-responsive valerian-associated hepatitis. Intern Med J. 2016 Jan;46(1):118-9. PubMed
  36. Burke H, Jiang S, Chatham P, Stern TA. Delirium After Withdrawal From Valerian Root: A Case Report. Psychosomatics. 2020;61(6):787-790. PubMed
  37. Hajizadeh I, Jamshidi M, Kazemi M, Kargar H, Sadeghi T. Comparison the effect of valerian and gabapentin on RLS and sleep quality in hemodialysis patients: A randomized clinical trial. Ther Apher Dial 2023.

See these in context on the Valerian monograph →

Riboflavin 5 references
  1. Schoenen J, Jacquy J, Lenaerts M. Effectiveness of high-dose riboflavin in migraine prophylaxis. A randomized controlled trial. Neurology 1998;50:466-70. PubMed
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Leeson LJ, Weidenheimer JF. Stability of tetracycline and riboflavin. J Pharm Sci. 1969;58(3):355-7. PubMed
  4. 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.
  5. 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.

See these in context on the Riboflavin monograph →

Biotin 4 references
  1. 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
  2. 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
  3. Mock DM, Quirk JG, Mock NI. Marginal biotin deficiency during normal pregnancy. Am J Clin Nutr 2002;75:295-9. PubMed
  4. Sedel F, Papeix C, Bellanger A, Touitou V, Lebrun-Frenay C, Galanaud D, et al. High doses of biotin in chronic progressive multiple sclerosis: a pilot study.Mult Scler Relat Disord. 2015;4(2):159-69. doi: 10.1016/j.msard.2015.01.005. PubMed

See these in context on the Biotin monograph →

Hops 15 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  3. Zava DT, Dollbaum CM, Blen M. Estrogen and progestin bioactivity of foods, herbs, and spices. Proc Soc Exp Biol Med 1998;217:369-78. PubMed
  4. Milligan SR, Kalita JC, Heyerick A, et al. Identification of a potent phytoestrogen in hops (Humulus lupulus L.) and beer. J Clin Endocrinol Metab 1999;84:2249-52.. PubMed
  5. Milligan SR, Kalita JC, Pocock V, et al. The endocrine activities of 8-prenylnaringenin and related hop (Humulus lupulus L.) flavonoids. J Clin Endocrinol Metab 2000;85:4912-5.. DOI
  6. Henderson MC, Miranda CL, Stevens JF, et al. In vitro inhibition of human P450 enzymes by prenylated flavonoids from hops, Humulus lupulus. Xenobiotica 2000;30:235-51.. PubMed
  7. Mannering, G. J., Shoeman, J. A., and Deloria, L. B. Identification of the antibiotic hops component, colupulone, as an inducer of hepatic cytochrome P-4503A in the mouse. Drug Metab Dispos 1992;20(2):142-147. DOI
  8. Skorska, C., Mackiewicz, B., Gora, A., Golec, M., and Dutkiewicz, J. Health effects of inhalation exposure to organic dust in hops farmers. Ann.Univ Mariae.Curie Sklodowska [Med] 2003;58(1):459-465.
  9. Schiller, H., Forster, A., Vonhoff, C., Hegger, M., Biller, A., and Winterhoff, H. Sedating effects of Humulus lupulus L. extracts. Phytomedicine. 2006;13(8):535-541. PubMed
  10. van Hunsel, F. P. and Kampschoer, P. [Postmenopausal bleeding and dietary supplements: a possible causal relationship with hop- and soy-containing preparations]. Ned.Tijdschr.Geneeskd. 2012;156(41):A5095.
  11. Fenselau, C. and Talalay, P. Is oestrogenic activity present in hops? Food Cosmet.Toxicol. 1973;11(4):597-602. PubMed
  12. Godnic-Cvar, J., Zuskin, E., Mustajbegovic, J., Schachter, E. N., Kanceljak, B., Macan, J., Ilic, Z., and Ebling, Z. Respiratory and immunological findings in brewery workers. Am J Ind Med 1999;35(1):68-75. DOI
  13. Lee KM, Jung JS, Song DK, and et al. Effects of Humulus lupulus extract on the central nervous system in mice. Planta Med 1993;59(Suppl):A691.
  14. Assessment report on Humulus lupulus L., flos. European Medicines Agency, 2014. Available at: https://www.ema.europa.eu/en/documents/herbal-report/final-assessment-report-humulus-lupulus-l-flos_en.pdf. Accessed September 29, 2021.
  15. van Breemen RB, Chen L, Tonsing-Carter A, et al. Pharmacokinetic Interactions of a Hop Dietary Supplement with Drug Metabolism in Perimenopausal and Postmenopausal Women. J Agric Food Chem. 2020;68(18):5212-5220. PubMed

See these in context on the Hops monograph →

Ashwagandha 32 references
  1. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  2. Upton R, ed. Ashwagandha Root (Withania somnifera): Analytical, quality control, and therapuetic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 2000:1-25.
  3. Davis L, Kuttan G. Effect of Withania somnifera on cyclophosphamide-induced urotoxicity. Cancer Lett 2000;148:9-17. PubMed
  4. Davis L, Kuttan G. Suppressive effect of cyclophosphamide-induced toxicity by Withania somnifera extract in mice. J Ethnopharmacol 1998;62:209-14. PubMed
  5. Mishra LC, Singh BB, Dagenais S. Scientific basis for the therapeutic use of Withania somnifera (ashwagandha): a review. Altern Med Rev 2000;5:334-46. DOI
  6. Andallu B, Radhika B. Hypoglycemic, diuretic and hypocholesterolemic effect of winter cherry (Withania somnifera, Dunal) root. Indian J Exp Biol 2000;38:607-9.
  7. Kulkarni RR, Patki PS, Jog VP, et al. Treatment of osteoarthritis with a herbomineral formulation: a double-blind, placebo-controlled, cross-over study. J Ethnopharmacol 1991;33:91-5. PubMed
  8. Ahumada F, Aspee F, Wikman G, Hancke J. Withania somnifera exract. Its effects on arterial blood pressure in anaesthetized dogs. Phytother Res 1991;5:111-14.
  9. Panda S, Kar A. Withania somnifera and Bauhinia purpurea in the regulation of circulating thyroid hormone concentrations in female mice. J Ethnopharmacol 1999;67:233-39. PubMed
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