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Dietary supplement

Internal Harmony For Women Sleep Aid Ingredients & Drug Interactions

by DreamBrands

Internal Harmony For Women Sleep Aid label
See full label image
Capsule Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Internal Harmony For Women Sleep Aid against your medications. The heart of this page is the interaction checker and the full interaction report — how this product’s ingredients may interact with prescription and over-the-counter medicines you may be taking.

Around that, we add a pharmacist’s high-level view of the product as a whole — what’s inside, the evidence for its stated use, how transparent the label is, and what safety data exists — so you can see the full picture in one place. It’s educational information from our licensed clinical databases and the clinical staff at HelloPharmacist — not medical advice — and we don’t sell or endorse products. Our editorial policy

The interaction bottom line Most serious interaction: Major

Internal Harmony For Women Sleep Aid is a dietary supplement by DreamBrands with 12 active ingredients. Its ingredients are commonly taken for morning sickness in pregnancy, premenstrual syndrome (pms), preventing or treating b6 deficiency.Based on those ingredients, 1,713 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Melatonin, Chamomile extract, Valerian extract. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Internal Harmony For Women Sleep Aid by DreamBrands

Ask about any prescription or over-the-counter medication and we check it for interactions with Internal Harmony For Women Sleep Aid by DreamBrands — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Internal Harmony For Women Sleep Aid by DreamBrands

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

From our pharmacy team — supplement deep dive

Generated from HelloPharmacist’s pharmacist-curated databases and editorial rules · Last generated Jul 11, 2026

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

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

Why this rating?
  • The label discloses an exact amount for 5 of its 12 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (330 mg) without saying how much of each component you get.

Internal Harmony For Women Sleep Aid contains 12 ingredients. The active ingredients include vitamins B6 and B12, vitamin D3, L-theanine (an amino acid), 5-HTP (a serotonin precursor), magnesium, melatonin, and herbal extracts of valerian, dong quai, black cohosh, chamomile, and chaste tree.

There's also a proprietary blend listed separately. The inactive ingredients are a vegetable capsule, magnesium stearate, and cellulose.

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: sleep aid for women's needs.
  • We looked for evidence on: Anxiety, Beta blocker-induced insomnia, Insomnia, Sleep quality, Restlessness, Menopause-related sleep disruption.
  • The strongest evidence on file: Valerian is rated "Possibly Effective" for Insomnia (Natural Medicines).
  • Also on file: Melatonin is rated "Possibly Effective" for Pre-procedural anxiety, Beta blocker-induced insomnia.
  • Also on file: 5-htp is rated "Insufficient Reliable Evidence To Rate" for Anxiety, Insomnia.

The evidence for this product's sleep-supporting ingredients is mixed. Valerian and melatonin are rated possibly effective for insomnia based on available research.

Magnesium is effective for constipation and dyspepsia, though that's not the intended use here. Vitamin B6 is effective for certain deficiency states and epilepsy, but the evidence for its role in sleep support specifically isn't established in our data.

L-theanine, 5-HTP, and the herbal extracts (dong quai, black cohosh, chamomile, chaste tree) lack sufficient evidence in our monographs to support or refute their effectiveness for sleep or the conditions marketed on women's formulas. Vitamin B12 doesn't have a sleep-related indication in our data either.

The evidence, ingredient by ingredient Vitamin B6 Vitamin B12 Vitamin D Theanine 5-htp Valerian Dong Quai Black Cohosh

How safe is it?

Well-documented data
Safety Information · database check
Well characterized

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

Why this rating?
  • We hold adverse-effect (side-effect) data for 12 of the 12 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 12 of 12.
  • General safety write-ups exist for 12 of 12.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most of these ingredients are generally well tolerated at recommended doses. Vitamin B12 is very safe with no upper limit documented.

Magnesium and vitamin D are safe at recommended amounts, though very high doses of vitamin D can cause toxicity over time. Vitamin B6, however, can cause nerve damage (sensory neuropathy) at high doses or with long-term use — doses exceeding 1000 mg daily carry the most risk, though neuropathy can occur at lower doses too.

L-theanine, valerian, and melatonin are generally well tolerated short-term, but long-term safety data are limited. Common side effects include headache, drowsiness, dizziness, and gastrointestinal upset.

5-HTP can cause nausea, diarrhea, and headache, especially at higher doses. Dong quai may increase skin sensitivity to sunlight and has constituents that are potentially carcinogenic at high doses.

Side effects, ingredient by ingredient Vitamin B6 Vitamin B12 Vitamin D Theanine 5-htp Valerian Dong Quai Black Cohosh

Meds to double-check

Major interaction found
Known Interaction Concern · database check
Major identified

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

Why this rating?
  • 12 of the 12 matched ingredients can interact with medications — 5-htp, Black Cohosh, Valerian, Vitamin B12, Vitamin D, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; seizure medications; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; Parkinson's medications.
  • For scale: 1,714 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.

The most critical medication types to check: levodopa/carbidopa (Parkinson's), blood thinners (warfarin and other anticoagulants), antiplatelets, antihypertensive drugs, thiazide diuretics, calcium channel blockers (verapamil, diltiazem, nifedipine), digoxin, and anticonvulsants. Also watch for interactions with muscle relaxants, quinolone antibiotics, bisphosphonates, diabetes medications, and estrogen therapy.

These interactions range from moderate to major severity depending on the ingredient and drug combination.

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 sleep formula suited to someone looking for natural support, but it's not one to take without checking your medications first — the ingredient list includes some heavy hitters that interact with common prescriptions, especially blood thinners, heart drugs, and Parkinson's medications. If you take any regular medication, run it through the checker on this page.

Talk with your pharmacist before starting, especially if you're on a blood thinner or any heart or seizure medication.

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

Assessment coverage: 12 of 12 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jul 25, 2018.

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

At a glance

General information

Key facts about Internal Harmony For Women Sleep Aid, straight from the product label.

Brand DreamBrands
Barcode (UPC) 852388001632
Net contents 30 Vegi Capsule(s)
Market status On market
Date entered into DSLD Jul 25, 2018
DSLD ID 179038
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses Nutrient, All Other, Structure/Function
Intended target group(s) Adult Female (18 - 50 Years)
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Internal Harmony For Women Sleep Aid by DreamBrands, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
1 Capsule(s)
Maximum serving Sizes:
1 Capsule(s)
UPC/BARCODE
852388001632
IngredientAmount% DV
Vitamin B61 mg50%
Vitamin B123 mcg50%
Vitamin D3400 IU100%
L-Theanine0 NP--
5-HTP0 NP--
Proprietary Blend330 mg--
Magnesium125 mg30%
Valerian extract0 NP--
Melatonin2 mg--
Dong Quai extract0 NP--
Black Cohosh extract0 NP--
Chamomile extract0 NP--
Chaste Tree extract0 NP--

Other ingredients: Vegi Capsule, Magnesium Stearate, Cellulose

Tap any ingredient to jump to its full detail below.

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

Live life in balance

With 5 other specific ingredient blends, Internal Harmony Sleep fully supports relaxation and what you need to fall asleep, stay asleep and help ensure recovery.

Relax Sleep Replenish You will enjoy the relaxing sensation Internal Harmony creates prior to falling into a deeper sleep. There is satisfaction in knowing you have done something nice for your body. In return, you will appreciate the added vitality your body will have in the morning.

DreamBrands 60 day guarantee 100% satisfaction We recognize there may be a small percentage of consumers that will not be completely satisfied with the results of this formula. To ensure 100% satisfaction, we offer a 60-day money back guarantee from the date of purchase. Please Call 888-300-9181 for details. Hours: 9am-5pm (Arizona time) M-F

For the things you love to do and the people you love doing them with

Relaxation Restful sleep plus replenishing vitamins Complete rest formula For occasional sleeplessness Natural extracts

Formula

Internal Harmony is a sleep aid specifically formulated for a woman’s unique needs.

Formulated with melatonin and natural herbal extracts, Internal Harmony helps ensure a deeper more restful sleep while replenishing the body with magnesium and vitamins B6, B12, and D3.

Why Internal Harmony Sleep? Because Internal Harmony Sleep goes beyond other sleep aids. It contains melatonin but only as a starting point.

Complete rest formula Internal Harmony contains 5 proprietary blends specific to a woman’s needs: 1 Melatonin and Valerian have been shown to decrease the time it takes to fall asleep as well as improve sleep quality. 2 5HTP and Chamomile were added to help the body cope with stress and calm the stomach. 3 L-Theanine provides physical and mental relaxation. 4 Chaste Tree, Dong Quai and Black Cohosh make this formula unique to a woman’s needs. These herbal extracts have been used in traditional medicines to help reduce PMS and menopausal symptoms. 5 Internal Harmony’s vitamin and mineral blend includes Vitamins D3, B6 and B12 supported by the mineral Magnesium.

Precautions

Cautions: Do not use in conjunction with alcoholic beverages, driving or operating heavy machinery

If you have a medical condition or are taking prescription drugs (anti-depressants, sedatives) consult your physician

Keep out of reach of children

Do not use if inner seal is torn or broken

Do not use if pregnant or lactating

11645 N Cave Creek Rd / Phoenix / AZ / 85020 / 888-300-9181 Adverse events may be reported to this address. 888-300-9181 / Hours: 9am - 5pm (AZ time) M-F

Storage

Store at room temperature

Suggested/Recommended/Usage/Directions

Suggested Use: For adults, take 1 capsule one hour before bedtime.

Brand IP Statement(s)

2008-2015 Owned and distributed by DreamBrands, Inc.

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.

General

54433-032015 CC# 022-015

FDA Statement of Identity

Dietary Supplement

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

See for yourself

Internal Harmony For Women Sleep Aid by DreamBrands label

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

Internal Harmony For Women Sleep Aid label

Label images are published by the NIH Dietary Supplement Label Database for the version of this product on file. Always read your actual product label.

View the full label (PDF)
What’s inside

The Ingredients in Internal Harmony For Women Sleep Aid by DreamBrands

These are the 12 active ingredients this product is made of. Select any to open its full monograph.

Serving size1 Capsule(s) Dosage formCapsule Amounts shown are per serving.

Most supplement products combine several ingredients, and a medication can interact with the product through any one of them. Each ingredient below shows whether it has known drug interactions.

Vitamin B6

Interacts with
210 drugs
1 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

Vitamin B12

Interacts with
20 drugs
3 mcg per serving Form: Cyanocobalamin

Vitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very h...

Vitamin B12 monograph & interactions

Vitamin D3

Interacts with
715 drugs
400 IU per serving Form: Cholecalciferol

Vitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people,...

Vitamin D3 monograph & interactions

Proprietary Blend

330 mg per serving

Magnesium

Interacts with
295 drugs
125 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

Melatonin

Interacts with
1,461 drugs
2 mg per serving

Melatonin is a hormone your body makes naturally to help control your sleep-wake cycle, and the supplement form is widely used to help with sleep timi...

Melatonin monograph & interactions

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

Interaction report

Internal Harmony For Women Sleep Aid by DreamBrands Drug Interactions

Want to check YOUR meds against Internal Harmony For Women Sleep Aid?

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
1,713Drugs
8 Major 1,702 Moderate 3 Minor

Ingredients driving the most interactions

Melatonin 1,461
Chamomile extract 960
Valerian extract 902
Vitamin D3 715
Black Cohosh extract 652

Individual Drug Interactions

The ingredients in Internal Harmony For Women Sleep Aid interact with 1,713 drugs. Click any drug to see the details.

12 of the 12 ingredients in Internal Harmony For Women Sleep Aid interact with drugs. Each result below shows which ingredient is responsible. Melatonin Chamomile extract Valerian extract Vitamin D3 Black Cohosh extract L-Theanine 5-HTP Magnesium Vitamin B6 Dong Quai extract Chaste Tree extract Vitamin B12

Each ingredient & the kinds of drugs it affects

For each ingredient in Internal Harmony For Women Sleep Aid 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.

Melatonin18 drug types · 1,461 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, melatonin may have anticoagulant effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
There are isolated case reports of minor bleeding and decreased prothrombin activity in people taking melatonin with warfarin (Coumadin). The mechanism, if any, of this interaction is unknown. Taking melatonin orally seems to decrease coagulation activity within one hour of dosing in healthy men.

Likelihood Possible Evidence B
Anticonvulsants

Theoretically, melatonin may reduce the effects of anticonvulsants. Some clinical research suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological impairment.

Likelihood Possible Evidence B
Antidiabetes Drugs

Theoretically, taking melatonin with antidiabetes drugs might increase the risk of hypoglycemia.
Some clinical research shows that melatonin reduces levels of fasting blood glucose and improves glycemic control. However, other research suggests that melatonin might impair glucose utilization and increase insulin resistance, while other research has found no effect on glucose levels. Until more is known, use melatonin cautiously in combination with antidiabetes drugs.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking melatonin with antihypertensive drugs might increase the risk of hypotension or hypertension.
Some clinical research suggests that taking melatonin decreases blood pressure in healthy adults. Also, melatonin seems to lower systolic and diastolic blood pressure in individuals with high blood pressure at nighttime or untreated essential hypertension. However, melatonin seems to worsen blood pressure in patients who are taking antihypertensive medications. Immediate-release melatonin 5 mg at night in combination with nifedipine GITS (Procardia XL) increases systolic blood pressure an average of 6.5 mmHg, diastolic blood pressure by an average of 4.9 mmHg, and heart rate by 3.9 bpm. Also, results from animal research suggest that melatonin reduces the effectiveness of certain antihypertensive drugs, including methoxamine and clonidine.

Likelihood Possible Evidence A
Caffeine

Theoretically, taking caffeine with melatonin might increase levels of melatonin.
Some evidence suggests that caffeine consumption can decrease endogenous melatonin levels, while other evidence suggests that caffeine increases endogenous melatonin levels. When administered in combination with melatonin supplements, caffeine seems to increase melatonin effects and levels. The reason for this discrepancy is not completely clear. Part of the discrepancy may result from the fact that caffeine can inhibit melatonin synthesis as well as inhibit melatonin metabolism. By functioning as an adenosine receptor antagonist, caffeine may indirectly inhibit the synthesis of melatonin. Conversely, because melatonin and caffeine are both metabolized by cytochrome P450 1A2 (CYP1A2) enzyme, concomitant use of melatonin and caffeine may reduce the metabolism of melatonin, resulting in higher serum levels.

Likelihood Probable Evidence B
Cns Depressants

Theoretically, taking melatonin might increase the sedative effects of CNS depressants.
Melatonin has sedative effects. Theoretically, concomitant use of melatonin with alcohol, benzodiazepines, or other sedative drugs might cause additive sedation.

Likelihood Possible Evidence D
Contraceptive Drugs

Theoretically, taking contraceptive drugs with melatonin might increase the effects and adverse effects of melatonin.
Contraceptive drugs can increase the levels of endogenous melatonin. Theoretically, these drugs may increase the effects and adverse effects of oral melatonin.

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

Theoretically, melatonin might increase levels of drugs metabolized by CYP1A2. Also, other CYP1A2 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with drugs metabolized by the CYP1A2 enzyme might reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP1A2 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

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

Theoretically, melatonin might increase levels of drugs metabolized by CYP2C19. Also, other CYP2C19 substrates might decrease the metabolism of melatonin, increasing melatonin levels.
Melatonin is metabolized in the liver primarily by the CYP2C19 and CYP1A2 enzymes. Theoretically, combined administration of melatonin with certain drugs metabolized by the CYP2C19 enzyme may reduce the metabolism of these drugs, resulting in increased serum levels. Conversely, some drugs metabolized by CYP2C19 may inhibit the metabolism of melatonin, resulting in increased serum levels of melatonin. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Probable Evidence D
Fluvoxamine (Luvox)

Theoretically, taking fluvoxamine with melatonin might increase levels of melatonin.
Fluvoxamine can significantly increase melatonin levels. In some cases, fluvoxamine might increase bioavailability of exogenously administered melatonin by up to 20 times. Some researchers think this might be a beneficial interaction and be potentially useful for cases of refractory insomnia. However, this interaction might also cause unwanted excessive drowsiness and possibly other adverse effects. Fluvoxamine is known to increase endogenous melatonin secretion. It seems to increase serum levels of exogenously administered melatonin possibly by decreasing melatonin metabolism by inhibiting cytochrome P450 (CYP450) 1A2 and 2C19 or by inhibiting melatonin elimination. This effect has been found in healthy people taking fluvoxamine 50-75 mg and melatonin 5 mg.

Likelihood Probable Evidence B
Immunosuppressants

Theoretically, melatonin might interfere with immunosuppressive therapy.
Melatonin can stimulate immune function. Theoretically, melatonin might interfere with immunosuppressive therapy.

Likelihood Possible Evidence B
Methamphetamine (Desoxyn)

Theoretically, taking melatonin with methamphetamine may increase the adverse effects of methamphetamine.
Animal research suggests that melatonin exacerbates the adverse effects of methamphetamine, resulting in greater depression of tryptophan hydroxylase (TPH) and tyrosine hydroxylase (TH) activity, as well as a significant reduction in dopamine levels. This has not been shown in humans.

Likelihood Possible Evidence D
Nifedipine Gits (Procardia Xl)

Theoretically, taking melatonin with extended release nifedipine reduces the effects of nifedipine.
Melatonin can decrease the effectiveness of extended release nifedipine (GITS). Immediate-release melatonin 5 mg at night in combination with nifedipine GITS 30-60 mg daily increases systolic and blood pressure by an average of 6.5 mmHg and 4.9 mmHg, respectively. Concomitant use with melatonin also increases heart rate by 3.9 bpm. The mechanism of this interaction is not known.

Likelihood Probable Evidence B
Seizure Threshold Lowering Drugs

Theoretically, taking melatonin with drugs that lower the seizure threshold might increase the risk of seizure activity.
Some clinical evidence suggests that melatonin may increase the frequency of seizures in certain patients, particularly children with neurological disabilities.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, melatonin may have antiplatelet effects and may increase the risk of bleeding with warfarin.
Three cases of increased prothrombin time have been reported for patients aged 48-72 years who took melatonin orally in combination with warfarin. However, three cases of decreased prothrombin time have also been reported for patients aged 51-84 years who took melatonin orally in combination with warfarin. Until more is known, use melatonin cautiously in patients taking warfarin.

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

Theoretically, melatonin might increase levels of drugs metabolized by CYP2D6.
Laboratory research suggests that certain lots of melatonin inhibit CYP2D6. Theoretically, combined administration of melatonin with certain drugs metabolized by the CYP2D6 enzyme may reduce the metabolism of these drugs, resulting in increased serum levels. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

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

Theoretically, melatonin might increase levels of drugs metabolized by CYP3A4.
Laboratory research shows that certain lots of melatonin inhibit CYP3A4. Theoretically, combined administration of melatonin with certain drugs metabolized by CYP3A4 may reduce the metabolism of these drugs, resulting in increased serum levels. Until more is known, use melatonin cautiously in patients taking drugs metabolized by these enzymes.

Likelihood Possible Evidence D
Flumazenil (Romazicon)

Theoretically, taking flumazenil with melatonin might reduce the effects of melatonin.
Animal research shows that flumazenil may inhibit the effect of melatonin.

Likelihood Possible Evidence D
Melatonin full monograph & interactions

Chamomile extract9 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
Chamomile extract full monograph & interactions

Valerian extract6 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
Valerian extract full monograph & interactions

Vitamin D38 drug types · 715 drugs

Aluminum

Vitamin D might increase aluminum absorption and toxicity, but this has only been reported in people with renal failure.
The protein that transports calcium across the intestinal wall can also bind and transport aluminum. This protein is stimulated by vitamin D, which may therefore increase aluminum absorption. This mechanism may contribute to increased aluminum levels and toxicity in people with renal failure, when they take vitamin D and aluminum-containing phosphate binders chronically.

Likelihood Probable Evidence B
Atorvastatin (Lipitor)

Vitamin D might reduce absorption of atorvastatin.
A small, low-quality clinical study shows that taking vitamin D reduces levels of atorvastatin and its active metabolites by up to 55%. However, while atorvastatin levels decreased, total cholesterol, low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol levels did not substantially change. Atorvastatin is metabolized in the gut by CYP3A4 enzymes, and researchers theorized that vitamin D might induce CYP3A4, causing reduced levels of atorvastatin. However, this proposed mechanism was not specifically studied.

Likelihood Probable Evidence B
Calcipotriene (Dovonex)

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

Likelihood Probable Evidence D
Digoxin (Lanoxin)

Theoretically, hypercalcemia induced by high-dose vitamin D can increase the risk of arrhythmia from digoxin.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia increases the risk of fatal cardiac arrhythmias with digoxin. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and digoxin concurrently.

Likelihood Possible Evidence D
Diltiazem (Cardizem, Others)

Theoretically, hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of diltiazem for arrhythmia.
High doses of vitamin D can cause hypercalcemia. Hypercalcemia can reduce the effectiveness of verapamil in atrial fibrillation. Theoretically this could also occur with diltiazem. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and diltiazem concurrently.

Likelihood Probable Evidence B
Thiazide Diuretics

Theoretically, taking thiazide diuretics and high-dose vitamin D can increase the risk of hypercalcemia.
Thiazide diuretics decrease urinary calcium excretion, which could lead to hypercalcemia if vitamin D supplements are taken concurrently. This has been reported in people being treated with vitamin D for hypoparathyroidism, and also in elderly people with normal parathyroid function who were taking a thiazide, vitamin D, and calcium-containing antacids daily.

Likelihood Probable Evidence D
Verapamil (Calan, Others)

Hypercalcemia induced by high-dose vitamin D can reduce the therapeutic effects of verapamil for arrhythmia.
Hypercalcemia due to high doses of vitamin D can reduce the effectiveness of verapamil in atrial fibrillation. Avoid vitamin D doses above the tolerable upper intake level (4000 IU daily for adults) and monitor serum calcium levels in people taking vitamin D and verapamil concurrently.

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

Vitamin D might induce CYP3A4 enzymes and reduce the bioavailability of CYP3A4 substrates.
There is some concern that vitamin D might induce CYP3A4. In vitro research suggests that vitamin D induces CYP3A4 transcription. Additionally, observational research has found that increased UV light exposure and serum vitamin D levels are associated with decreased serum levels of CYP3A4 substrates such as tacrolimus and sirolimus, while no association between UV light exposure or vitamin D levels and levels of mycophenolic acid, a non-CYP3A4 substrate, was found. A small, low-quality clinical study shows that taking vitamin D reduces levels of the CYP3A4 substrate atorvastatin and its active metabolites by up to 55%; however, the clinical effects of atorvastatin were not reduced. While researchers theorized that vitamin D might induce CYP3A4, this proposed mechanism was not specifically studied.

Likelihood Possible Evidence D
Vitamin D3 full monograph & interactions

Black Cohosh extract7 drug types · 652 drugs

Atorvastatin (Lipitor)

Taking black cohosh with atorvastatin might increase the risk for elevated liver function tests.
In one case report, a patient taking atorvastatin (Lipitor) developed significantly elevated liver function enzymes after starting black cohosh 100 mg four times daily. Liver enzymes returned to normal when black cohosh was discontinued. It is unclear whether the elevated liver enzymes were due to black cohosh itself or an interaction between atorvastatin and black cohosh.

Likelihood Possible Evidence D
Cisplatin (Platinol-Aq)

Theoretically, black cohosh may reduce the clinical effects of cisplatin.
Animal research suggests that black cohosh might decrease the cytotoxic effect of cisplatin on breast cancer cells.

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

Some research suggests that black cohosh might inhibit CYP2D6, but there is conflicting evidence.
Some clinical research suggests that black cohosh might modestly inhibit CYP2D6 and increase levels of drugs metabolized by this enzyme. However, contradictory clinical research shows a specific black cohosh product (Remifemin, Enzymatic Therapy) 40 mg twice daily does not significantly inhibit metabolism of a CYP2D6 substrate in healthy study volunteers. Until more is known, use black cohosh cautiously in patients taking drugs metabolized by CYP2D6.

Likelihood Possible Evidence B
Estrogens

Theoretically, black cohosh may alter the effects of estrogen therapy.
Some research suggests that black cohosh has estrogenic effects. This may enhance or inhibit the effects of estrogen therapy.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, taking black cohosh with hepatotoxic drugs may increase the risk of liver damage.
There is concern that black cohosh might be linked to cases of liver failure and autoimmune hepatitis.

Likelihood Possible Evidence D
Serotonergic Drugs

Combining serotonergic drugs with black cohosh might cause additive serotonergic effects.
Black cohosh might increase the risk of serotonin syndrome when combined with other serotonergic drugs. Black cohosh acts as an agonist at several serotonin receptor subtypes and might interact with other serotonergic medications. In one case, a 55-year-old female who had been on stable treatment with sertraline 50 mg and duloxetine 60 mg daily developed serotonin syndrome after taking black cohosh extract 40 mg daily for 3 days.

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

Black cohosh may inhibit one form of OATP, OATP2B1, which could reduce the bioavailability and clinical effects of OATP2B1 substrates.
In vitro research shows that black cohosh modestly inhibits OATP2B1. OATPs are expressed in the small intestine and liver and are responsible for the uptake of drugs and other compounds into the body. Inhibition of OATP may reduce the bioavailability of oral drugs that are substrates of OATP.

Likelihood Possible Evidence D
Black Cohosh extract full monograph & interactions

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
L-Theanine full monograph & interactions

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
5-HTP full monograph & interactions

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
Magnesium full monograph & interactions

Vitamin B65 drug types · 210 drugs

Amiodarone (Cordarone)

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

Likelihood Possible Evidence B
Antihypertensive Drugs

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

Likelihood Possible Evidence B
Phenobarbital (Luminal)

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

Likelihood Possible Evidence D
Phenytoin (Dilantin)

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

Likelihood Possible Evidence D
Levodopa

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

Likelihood Unlikely Evidence D
Vitamin B6 full monograph & interactions

Dong Quai extract3 drug types · 163 drugs

Warfarin (Coumadin)

Dong quai may increase the risk of bleeding when used with warfarin.
Case reports suggest that concomitant use of dong quai with warfarin can increase the anticoagulant effects of warfarin and increase the risk of bleeding. In one case, after 4 weeks of taking dong quai 565 mg once or twice daily, the international normalized ratio (INR) increased to 4.9. The INR normalized 4 weeks after discontinuation of dong quai.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, dong quai may increase the risk of bleeding when used with anticoagulant or antiplatelet drugs; however, research is conflicting.
Animal studies suggest that dong quai has antithrombin activity and inhibits platelet aggregation due to its coumarin components. Additionally, some case reports in humans suggest that dong quai can increase the anticoagulant effects of warfarin. However, clinical research in healthy adults shows that taking 1 gram of dong quai root daily for 3 weeks does not significantly inhibit platelet aggregation or cause bleeding. Until more is known, use dong quai with caution in patients taking antiplatelet/anticoagulant drugs.

Likelihood Possible Evidence D
Estrogens

Theoretically, dong quai may reduce the effects of estrogens.
Dong quai has estrogenic effects. Theoretically, concomitant use of large amounts of dong quai might interfere with hormone replacement therapy due to competition for estrogen receptors.

Likelihood Possible Evidence D
Dong Quai extract full monograph & interactions

Chaste Tree extract5 drug types · 121 drugs

Antipsychotic Drugs

Theoretically, vitex agnus-castus could interfere with the activity of antipsychotic drugs.
Vitex agnus-castus might interfere with the action of dopamine antagonists such as antipsychotic drugs due to its dopamine agonist effects.

Likelihood Possible Evidence D
Contraceptive Drugs

Theoretically, vitex agnus-castus could interfere with oral contraceptives.
Vitex agnus-castus might interfere with the efficacy of oral contraceptives due to possible hormone modulating activity.

Likelihood Possible Evidence B
Dopamine Agonists

Theoretically, vitex agnus-castus could interfere with dopamine agonists.
Vitex agnus-castus might potentiate the actions of dopaminergic agonists due to possible dopaminergic effects.

Likelihood Possible Evidence D
Estrogens

Theoretically, vitex agnus-castus could interfere with the activity of estrogens.
Vitex agnus-castus has hormone modulating activity that can interfere with the efficacy of hormone replacement therapy.

Likelihood Probable Evidence D
Metoclopramide (Reglan)

Theoretically, dopaminergic effects of vitex agnus-castus could interfere with metoclopramide.
Vitex agnus-castus might interfere with the action of dopamine antagonists such as metoclopramide due to its possible dopaminergic effects.

Likelihood Possible Evidence D
Chaste Tree extract full monograph & interactions

Vitamin B121 drug type · 20 drugs

Metformin (Glucophage)

Metformin, a common medication used to manage type 2 diabetes, has been associated with lower vitamin B12 levels in some individuals. Prolonged use of metformin can interfere with the absorption of B12 in the digestive system, potentially leading to a deficiency in this essential vitamin.

Likelihood Possible Evidence A
Vitamin B12 full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Internal Harmony For Women Sleep Aid, from the product label.

DreamBrands

See all DreamBrands products
Name
DreamBrands, Inc.
Street Address
11645 N Cave Creek Rd
City
Phoenix
State
AZ
ZipCode
85020
Phone Number
888-300-9181
Web Address
HarmonySleep.com
Pharmacist Counseling Corner

Internal Harmony For Women Sleep Aid by DreamBrands: Common Questions

Does Internal Harmony For Women Sleep Aid by DreamBrands interact with any medications?
Yes. Based on its ingredients, Internal Harmony For Women Sleep Aid has a known interaction with 1,713 medications, including 8 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Internal Harmony For Women Sleep Aid contains 12 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.
Can I take this if I'm on a blood thinner like warfarin?
No — not without your doctor's approval. Dong quai in this product can significantly increase warfarin's effects and your bleeding risk. Melatonin and magnesium also have documented concerns with anticoagulants. This is a major interaction, so you must talk with your pharmacist or doctor first.
Does this product have melatonin in it?
Yes. Melatonin is one of the active ingredients. It's commonly used for sleep support and is generally well tolerated short-term, though long-term safety data are limited. It can interact with certain medications, especially blood pressure drugs and anticonvulsants.
Will this help me sleep?
Valerian and melatonin in this formula are rated possibly effective for insomnia based on clinical research. The other ingredients like 5-HTP, magnesium, and the herbal extracts don't have sufficient evidence in our data to confirm they help with sleep specifically, so results may vary from person to person.
Is it safe to take this long-term?
The safety data for long-term use are limited. Vitamin B6 at high doses over time can damage nerves; valerian, L-theanine, and melatonin are all generally well tolerated short-term, but long-term safety hasn't been thoroughly studied. Talk with your pharmacist about duration of use.
What are the most common side effects?
Headache, drowsiness, dizziness, nausea, and gastrointestinal upset are the most frequently reported. Some people may experience vivid dreams or changes in mood. If you have prolonged or bothersome side effects, stop and speak with your pharmacist.
Can I take this during pregnancy?
Safety data are limited or advise against use for most of these ingredients. L-theanine, valerian, melatonin, dong quai, and black cohosh should be avoided in pregnancy — not enough information is on file to know if they're safe. Talk with your doctor before taking any supplement during pregnancy.

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

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Internal Harmony For Women Sleep Aid label
Go deeper

The Full Monographs Behind Internal Harmony For Women Sleep Aid’s Ingredients

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

Herb & supplement monograph

Vitamin B6

Interacts with 210 drugs

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

Read the full Vitamin B6 monograph → Herb & supplement monograph

Vitamin B12

Interacts with 20 drugs

Vitamin B12 (cobalamin) is an essential nutrient your body needs to make red blood cells, keep nerves healthy, and support DNA. Supplements are very helpful for people who are deficient — su...

Read the full Vitamin B12 monograph → Herb & supplement monograph

Vitamin D

Interacts with 715 drugs

Vitamin D is a fat-soluble vitamin that helps your body absorb calcium and is important for healthy bones, muscles, and immune function. Many people, especially those with low sun exposure,...

Read the full Vitamin D monograph → 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

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

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

Dong Quai

Interacts with 163 drugs

Dong Quai is a traditional Chinese herb often called "female ginseng" and is mostly used for menstrual and menopausal complaints. High-quality scientific evidence that it works for these use...

Read the full Dong Quai monograph → Herb & supplement monograph

Black Cohosh

Interacts with 652 drugs

Black cohosh is a North American plant most often used to ease menopause symptoms like hot flashes, but the research is mixed and far from settled. It is generally well tolerated for short-t...

Read the full Black Cohosh monograph → Herb & supplement 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

Vitex Agnus-castus

Interacts with 121 drugs

Vitex (chasteberry) is an herbal remedy most often used for PMS and menstrual cycle problems, and the strongest evidence is for easing some PMS symptoms. It is generally well tolerated by ma...

Read the full Vitex Agnus-castus monograph → Herb & supplement 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

Melatonin

Interacts with 1,461 drugs

Melatonin is a hormone your body makes naturally to help control your sleep-wake cycle, and the supplement form is widely used to help with sleep timing problems and jet lag. The evidence is...

Read the full Melatonin monograph →
Sources

Sources & How We Checked

Internal Harmony For Women Sleep Aid'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 488 references behind this product’s interaction data

Every citation that drives the interaction findings for this product’s ingredients, from the evidence-graded Natural Medicines (TRC Healthcare) database. Open an ingredient to browse its citations — links open the study on PubMed or the publisher’s site.

Vitamin B6 32 references
  1. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  2. Yates AA, Schlicker SA, Suitor CW. Dietary reference intakes: The new basis for recommendations for calcium and related nutrients, B vitamins, and choline. J Am Diet Assoc 1998;98:699-706. PubMed
  3. Geerling BJ, Dagnelie PC, Badart-Smook A, et al. Diet as a risk factor for the development of ulcerative colitis. Am J Gastroenterol 2000;95:1008-13. PubMed
  4. South M. Neonatal seizures after pyridoxine use -- reply. Lancet 1999;354:2083. PubMed
  5. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Thiamin, Riboflavin, Niacin, Vitamin B6, Folate, Vitamin B12, Pantothenic Acid, Biotin, and Choline (2000). Washington, DC: National Academy Press, 2000. Available at: http://b
  6. Baxter P, Aicardi J. Neonatal seizures after pyridoxine use. Lancet 1999;354:2082-3. PubMed
  7. Bendich A, Cohen M. Vitamin B6 safety issues. Ann N Y Acad Sci 1990;585:321-30.
  8. Schaumburg H, Kaplan J, Windebank A. Sensory neuropathy from pyridoxine abuse. A new megavitamin syndrome. N Engl J Med 1983;309:445-8. PubMed
  9. Gordon N. Pyridoxine dependency: an update. Dev Med Child Neurol 1997;39:63-5. PubMed
  10. Lewis PJ. Pain in the hand and wrist. Pyridoxine supplements may help patients with carpal tunnel syndrome. BMJ 1995;310:1534. PubMed
  11. Kaufman G. Pyridoxine against amiodarone-induced photosensitivity (letter). Lancet 1984;1:51-2. PubMed
  12. Mulrow JP, Mulrow CD, McKenna WJ. Pyridoxine and amiodarone-induced photosensitivity. Ann Intern Med 1985;103:68-9. PubMed
  13. Kawada A, Kashima A, Shiraishi H, et al. Pyridoxine-induced photosensitivity and hypophosphatasia. Dermatology 2000;201:356-60.. PubMed
  14. Vasile A, Goldberg R, Kornberg B. Pyridoxine toxicity: report of a case. J Am Osteopath Assoc 1984;83:790-1. DOI
  15. Hansson O, Sillanpaa M. Pyridoxine and serum concentration of phenytoin and phenobarbitone. Lancet 1976;1:256. DOI
  16. Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15:484-5..
  17. Chittumma P, Kaewkiattikun K, Wiriyasiriwach B. Comparison of the effectiveness of ginger and vitamin B6 for treatment of nausea and vomiting in early pregnancy: a randomized double-blind controlled trial. J Med Assoc Thai 2007;90:15-20.
  18. Hatzitolios, A., Iliadis, F., Katsiki, N., and Baltatzi, M. Is the anti-hypertensive effect of dietary supplements via aldehydes reduction evidence based? A systematic review. Clin Exp.Hypertens. 2008;30(7):628-639. PubMed
  19. Vasdev, S., Ford, C. A., Parai, S., Longerich, L., and Gadag, V. Dietary vitamin B6 supplementation attenuates hypertension in spontaneously hypertensive rats. Mol.Cell Biochem. 1999;200(1-2):155-162.
  20. de, Vogel S., Dindore, V., van, Engeland M., Goldbohm, R. A., van den Brandt, P. A., and Weijenberg, M. P. Dietary folate, methionine, riboflavin, and vitamin B-6 and risk of sporadic colorectal cancer. J Nutr 2008;138(12):2372-2378. PubMed
  21. Hagen, I., Nesheim, B. I., and Tuntland, T. No effect of vitamin B-6 against premenstrual tension. A controlled clinical study. Acta Obstet.Gynecol.Scand. 1985;64(8):667-670. PubMed
  22. Aybak, M., Sermet, A., Ayyildiz, M. O., and Karakilcik, A. Z. Effect of oral pyridoxine hydrochloride supplementation on arterial blood pressure in patients with essential hypertension. Arzneimittelforschung. 1995;45(12):1271-1273.
  23. Lal, K. J., Dakshinamurti, K., and Thliveris, J. The effect of vitamin B6 on the systolic blood pressure of rats in various animal models of hypertension. J Hypertens. 1996;14(3):355-363. PubMed
  24. Lauritzen CH, Reuter HD, Repges R, Bohnert K, and Schmidt U. Treatment of premenstrual tension syndrome with Vitex agnus castus. Controlled, double-blind study versus pyridoxine. Phytomed 1997;4(3):183-189. PubMed
  25. Fonseca VA, Lavery LA, Thethi TK, et al. Metanx in type 2 diabetes with peripheral neuropathy: A randomized trial. Am J Med 2013;126(2):141-9. PubMed
  26. Hankey GJ, Eikelboom JW, Yi Q, et al. Treatment with B vitamins and incidence of cancer in patients with previous stroke or transient ischemic attack: Results of a randomized placebo-controlled trial. Stroke 2012;43(6):1572-7. PubMed
  27. Hoyer-Kuhn H, Kohbrok S, Volland R, Franklin J, Hero B, Beck BB, Hoppe B. Vitamin B6 in primary hyperoxaluria I: first prospective trial after 40 years of practice. Clin J Am Soc Nephrol. 2014 Mar;9(3):468-77. PubMed
  28. Mahmoud A, Tabassum S, Al Enazi S, et al. Amelioration of levetiracetam-induced behavioral side effects by pyridoxine. A randomized double blind controlled study. Pediatr Neurol 2021;119:15-21. PubMed
  29. Gupta M, Gallante B, Bamberger JN, et al. Prospective randomized evaluation of idiopathic hyperoxaluria treatments. J Endourol 2021;35(12):1844-1851. PubMed
  30. Li H, Chen M, Liang S, et al. Excessive vitamin B6 during treatment is related to poor prognosis of patients with nasopharyngeal carcinoma: A U-shaped distribution suggests low dose supplement. Clin Nutr 2021;40(4):2293-2300. PubMed
  31. Tanigawa J, Nabatame S, Tominaga K, et al. High-dose pyridoxine treatment for inherited glycosylphosphatidylinositol deficiency. Brain Dev 2021;43(6):680-687. PubMed
  32. Committee on Practice Bulletins-Obstetrics. ACOG Practice Bulletin No. 189: Nausea And Vomiting Of Pregnancy. Obstet Gynecol. 2018;131(1):e15-e30. PubMed

See these in context on the Vitamin B6 monograph →

Vitamin B12 30 references
  1. 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
  2. Hartman TJ, Woodson K, Stolzenberg-Solomon R, et al. Association of the B-vitamins pyridoxal 5'-phosphate (B6), B12, and folate with lung cancer risk in older men. Am J Epidemiol 2001;153:688-94.. DOI
  3. Jansen T, Romiti R, Kreuter A, Altmeyer P. Rosacea fulminans triggered by high-dose vitamins B6 and B12. J Eur Acad Dermatol Venereol 2001;15:484-5..
  4. Lange H, Suryapranata H, De Luca G, et al. Folate therapy and in-stent restenosis after coronary stenting. N Engl J Med 2004;350:2673-81. PubMed
  5. Collin, S. M., Metcalfe, C., Refsum, H., Lewis, S. J., Zuccolo, L., Smith, G. D., Chen, L., Harris, R., Davis, M., Marsden, G., Johnston, C., Lane, J. A., Ebbing, M., Bonaa, K. H., Nygard, O., Ueland, P. M., Grau, M. V., Baron, J. A., Donovan, J. L., Nea
  6. Geissbuhler, P., Mermillod, B., and Rapin, C. H. Elevated serum vitamin B12 levels associated with CRP as a predictive factor of mortality in palliative care cancer patients: a prospective study over five years. J.Pain Symptom.Manage. 2000;20(2):93-103. PubMed
  7. Salles, N., Herrmann, F., Sakbani, K., Rapin, C. H., and Sieber, C. High vitamin B12 level: a strong predictor of mortality in elderly inpatients. J Am Geriatr.Soc 2005;53(5):917-918.
  8. Looker, H. C., Fagot-Campagna, A., Gunter, E. W., Pfeiffer, C. M., Sievers, M. L., Bennett, P. H., Nelson, R. G., Hanson, R. L., and Knowler, W. C. Homocysteine and vitamin B(12) concentrations and mortality rates in type 2 diabetes. Diabetes Metab Res R
  9. Uhl, W., Nolting, A., Golor, G., Rost, K. L., and Kovar, A. Safety of hydroxocobalamin in healthy volunteers in a randomized, placebo-controlled study. Clin Toxicol (Phila) 2006;44 Suppl 1:17-28. PubMed
  10. Borron, S. W., Baud, F. J., Barriot, P., Imbert, M., and Bismuth, C. Prospective study of hydroxocobalamin for acute cyanide poisoning in smoke inhalation. Ann Emerg.Med 2007;49(6):794-801, 801. PubMed
  11. Borron, S. W., Baud, F. J., Megarbane, B., and Bismuth, C. Hydroxocobalamin for severe acute cyanide poisoning by ingestion or inhalation. Am J Emerg.Med 2007;25(5):551-558. PubMed
  12. Lewis, J. G. Gout, Steatorrhoea, and Megaloblastic Anaemia. Ann Rheum.Dis 1962;21(3):284-286. PubMed
  13. Tal, S., Shavit, Y., Stern, F., and Malnick, S. Association between vitamin B12 levels and mortality in hospitalized older adults. J Am Geriatr.Soc 2010;58(3):523-526. PubMed
  14. Baztan, J. J., Gavidia, J. J., Gomez-Pavon, J., Esteve, A., and Ruiperez, I. High vitamin B12 levels and in-hospital mortality. J Am Geriatr.Soc 2010;58(11):2237-2238. PubMed
  15. Omboni, E., Checchini, M., and Longoni, F. [Hypopotassemia and megaloblastic anemia. Presentation of a case]. Minerva Med 8-31-1987;78(16):1255-1257.
  16. Aalfs As, Scholvinck LH, Horvath B. Acneiform eruption in a 5-year old due to vitamin B12 supplementation. Eur J Dermatol 2013;23(5):726-7. PubMed
  17. Balta I, Ozuguz P. Vitamin B12-induced acneiform eruption. Cutan Ocul Toxicol 2014;33(2):94-5. PubMed
  18. Carman KB, Belgemen T, Yis U. Involuntary movements misdiagnosed as seizure during vitamin B12 treatment. Pediatr Emerg Care 2013;29(11):1223-4. PubMed
  19. Djuric V, Bogic M, Popadic AP, et al. Anaphylactic reaction to hydroxycobalamin with tolerance to cyanocobalamin. Ann Allergy Asthma Immunol 2012;108(3):207-8. PubMed
  20. Kartel O, Gulec M, Demirel F, et al. Vitamin B12 allergy and successful desensitization with cyanocobalamin: A case report. Allergol Immunopath (Madr) 2012;40(5):324-5.
  21. Patiroglu T, Unal E, Yildirim S. Infantile tremor syndrome associated with cobalamin therapy: A case report. Clin Neurol Neurosurg 2013;115(9):1903-5. PubMed
  22. Schulte S, Barkema LW, Kardaun SH. Long-lasting atypical acneiform eruption with prominent comedones induced by hydroxocobalamin (vitamin B12). J Dtsch Dermatol Ges 2014;12(6):502-3.
  23. Zanus C, Alberini E, Costa P, et al. Involuntary movements after correction of vitamin B12 deficiency: A video-case report. Epileptic Disord 2012;14(2):174-80. PubMed
  24. Fanidi A, Carreras-Torres R, Larose TL, et al. Is high vitamin B12 status a cause of lung cancer? Int J Cancer. 2019 Sep 15;145(6):1499-1503. PubMed
  25. Fujita Y, Mizukami T, Maya Y, et al. Vitamin B12 allergy manifesting as lymphomatoid contact dermatitis. Eur J Dermatol. 2020;30(3):304-305. PubMed
  26. Dépret F, Hoffmann C, Daoud L, et al. Association between hydroxocobalamin administration and acute kidney injury after smoke inhalation: a multicenter retrospective study. Crit Care. 2019;23(1):421. PubMed
  27. Khairan P, Sobue T, Eshak ES, et al. Association of dietary intakes of vitamin B12, vitamin B6, folate, and methionine with the risk of esophageal cancer: the Japan Public Health Center-based (JPHC) prospective study. BMC Cancer 2021;21(1):982. PubMed
  28. Evans J, Pandya A, Ding Y, Qunibi WY. Hydroxocobalamin-Induced Oxalate Nephropathy in a Patient With Smoke Inhalation. Kidney Int Rep 2021;6(8):2228-2231. PubMed
  29. Lacombe V, Chabrun F, Lacout C, et al. Persistent elevation of plasma vitamin B12 is strongly associated with solid cancer. Sci Rep 2021;11(1):13361. PubMed
  30. Pegalajar-García MD, Cebolla-Verdugo M, Prados-Carmona Á, Llamas-Segura C, Navarro-Triviño FJ. Systemic allergic dermatitis to cobalt present in cyanocobalamin supplementation. Contact Dermatitis 2023;89(3):203-205. PubMed

See these in context on the Vitamin B12 monograph →

Vitamin D 26 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999.
  3. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med 2001;345:66-7. PubMed
  4. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  5. Demontis R, Leflon A, Fournier A, et al. 1 alpha(OH) vitamin D3 increases plasma aluminum in hemodialyzed patients taking AI(OH)3. Clin Nephrol 1986;26:146-9.
  6. Crowe M, Wollner L, Griffiths RA. Hypercalcemia following vitamin D and thiazide therapy in the elderly. Practitioner 1984;228:312-3.
  7. Parfitt AM. Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism. Ann Intern Med 1972;77:557-63. PubMed
  8. Thiazide diuretics and the risk of osteoporosis. Pharmacist's Letter/Prescriber's Letter 2003;19(11):191105.
  9. Moon J. The role of vitamin D in toxic metal absorption. J Am Coll Nutr 1994;13:559-64.
  10. Demontis R, Reissi D, Noel C, et al. Indirect clinical evidence that 1alphaOH vitamin D<SUB>3</SUB> increases the intestinal absorption of aluminum. Clin Nephrol 1989;31:123-7.
  11. Adler AJ, Berlyne GM. Duodenal aluminum absorption in the rat: effect of vitamin D. Am J Physiol 1985;249:G209-13. PubMed
  12. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: A new drug interaction with an unexpected consequence. Clin Pharmacol Ther 2009;85:198-203. PubMed
  13. Dietary reference intakes for calcium and vitamin D. Institute of Medicine, November 30, 2010. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Repo
  14. Cox KA, Dunn MA. Aluminum toxicity alters the regulation of calbindin-D28k protein and mRNA expression in chick intestine. J Nutr 2001;131:2007-13. PubMed
  15. Escribano, J., Balaguer, A., Pagone, F., Feliu, A., and Roque, I. Figuls. Pharmacological interventions for preventing complications in idiopathic hypercalciuria. Cochrane.Database.Syst.Rev. 2009;(1):CD004754. PubMed
  16. Carlton, S., Clopton, D., and Cappuzzo, K. A. Vitamin D deficiency: appropriate replenishment therapies and the effects of vitamin D toxicity. Consult Pharm 2010;25(3):171-177. PubMed
  17. Wang, H., Xia, N., Yang, Y., and Peng, D. Q. Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials. Lipids Health Dis. 2012;11:42. PubMed
  18. Turner AN, Carr Reese P, Fields KS, Anderson J, Ervin M, Davis JA, Fichorova RN, Roberts MW, Klebanoff MA, Jackson RD. A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis. Am J Obstet G PubMed
  19. Weiner M, Epstein FH. Signs and symptoms of electrolyte disorders. Yale J Biol Med. 1970;43(2):76-109.
  20. Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SL. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. JAMA. 2017 Mar 28;317(12):1234-1243. PubMed
  21. Roth DE, Leung M, Mesfin E, Qamar H, Watterworth J, Papp E. Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials. BMJ. 2017;359:j5237. PubMed
  22. Murai IH, Fernandes AL, Sales LP, et al. Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: A randomized clinical trial. JAMA. 2021.
  23. Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol 2013;136:54-8. PubMed
  24. Doyle D, Browne U, Brickley A, Murphy D. Vitamin D-induced hypercalcaemia and acute kidney injury in sarcoidosis. BMJ Case Rep 2023;16(1):e250580. PubMed
  25. Williamson A, Martineau AR, Sheikh A, Jolliffe D, Griffiths CJ. Vitamin D for the management of asthma. Cochrane Database Syst Rev 2023;2(2):CD011511. PubMed
  26. Kinesya E, Santoso D, Gde Arya N, et al. Vitamin D as adjuvant therapy for diabetic foot ulcers: Systematic review and meta-analysis approach. Clin Nutr ESPEN 2023;54:137-143. PubMed

See these in context on the Vitamin D monograph →

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 →

5-htp 32 references
  1. Birdsall TC. 5-Hydroxytryptophan: A Clinically-Effective Serotonin Precursor. Altern Med Rev 1998;3:271-80.
  2. Michelson D, Page SW, Casey R, et al. An eosinophilia-myalgia syndrome related disorder associated with exposure to L-5-hydroxytryptophan. J Rheumatol 1994;21:2261-5.
  3. Cangiano C, Ceci F, Cancino A, et al. Eating behavior and adherence to dietary prescriptions in obese adult subjects treated with 5-hydroxytryptophan. Am J Clin Nutr 1992;56:863-7. PubMed
  4. U.S. Food and Drug Administration. Impurities confirmed in dietary supplement 5-hydroxy-L-tryptophan. FDA Talk Paper, August 31, 1998; T98-48.
  5. Sternberg EM, Van Woert MH, Young SN, et al. Development of a scleroderma-like illness during therapy with L-5-hydroxytryptophan and carbidopa. N Engl J Med 1980;303:782-7. PubMed
  6. Poldinger W, Calanchini B, Schwarz W. A functional-dimensional approach to depression: serotonin deficiency as a target syndrome in a comparison of 5-hydroxytryptophan and fluvoxamine. Psychopathology 1991;24:53-81.
  7. Ribeiro CA. L-5-Hydroxytryptophan in the prophylaxis of chronic tension-type headache: a double-blind, randomized, placebo-controlled study. Headache 2000;40:451-6.
  8. U. S. Food and Drug Administration, Center for Food Safety and Applied Nutrition, Office of Nutritional Products, Labeling, and Dietary Supplements. Information Paper on L-Tryptophan and 5-hydroxy-L-tryptophan, February 2001.
  9. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  10. Johnson KL, Klarskov K, Benson LM, et al. Presence of peak X and related compounds: the reported contaminant in case related 5-hydroxy-L-tryptophan associated with eosinophilia-myalgia syndrome. J Rheumatol 1999;26:2714-7.
  11. Takahashi S, Kondo H, Kato N. Effect of l-5-hydroxytryptophan on brain monoamine metabolism and evaluation of its clinical effect in depressed patients. J Psychiatr Res 1975;12:177-87. PubMed
  12. Iovieno, N., Dalton, E. D., Fava, M., and Mischoulon, D. Second-tier natural antidepressants: review and critique. J Affect.Disord. 2011;130(3):343-357. PubMed
  13. den Boer JA, Westenberg HG. Behavioral, neuroendocrine, and biochemical effects of 5-hydroxytryptophan administration in panic disorder. Psychiatry Res 1990;31:267-78. PubMed
  14. Jangid P, Malik P, Singh P, Sharma M, Gulia AK. Comparative study of efficacy of l-5-hydroxytryptophan and fluoxetine in patients presenting with first depressive episode. Asian J Psychiatr 2013;6:29-34. PubMed
  15. Ceci F, Cangiano C, Cairella M, et al. The effects of oral 5-hydroxytryptophan administration on feeding behavior in obese adult female subjects. J Neural Transm 1989;76:109-17. PubMed
  16. Angst J, Woggon B, Schoepf J. The treatment of depression with L-5-hydroxytryptophan versus imipramine. Results of two open and one double-blind study. Arch Psychiatr Nervenkr 1977;224:175-86. DOI
  17. Titus F, Dávalos A, Alom J, Codina A. 5-Hydroxytryptophan versus methysergide in the prophylaxis of migraine. Randomized clinical trial. Eur Neurol 1986;25:327-9. PubMed
  18. De Benedittis G, Massei R. Serotonin precursors in chronic primary headache. A double-blind cross-over study with L-5-hydroxytryptophan vs. placebo. J Neurosurg Sci 1985;29:239-48.
  19. Van Woert, M. H., Rosenbaum, D., Howieson, J., and Bowers, M. B., Jr. Long-term therapy of myoclonus and other neurologic disorders with L-5- hydroxytryptophan and carbidopa. N Engl J Med 1-13-1977;296(2):70-75. PubMed
  20. Wyatt, R. J., Vaughan, T., Galanter, M., Kaplan, J., and Green, R. Behavioral changes of chronic schizophrenic patients given L-5- hydroxytryptophan. Science 9-22-1972;177(54):1124-1126. PubMed
  21. Chase, T. N., Ng, L. K., and Watanabe, A. M. Parkinson's disease. Modification by 5-hydroxytryptophan. Neurology 1972;22(5):479-484.
  22. van Hiele LJ. l-5-Hydroxytryptophan in depression: the first substitution therapy in psychiatry? The treatment of 99 out-patients with 'therapy-resistant' depressions. Neuropsychobiology 1980;6:230-40. PubMed
  23. Pranzatelli, M. R., Tate, E., Huang, Y., Haas, R. H., Bodensteiner, J., Ashwal, S., and Franz, D. Neuropharmacology of progressive myoclonus epilepsy: response to 5- hydroxy-L-tryptophan. Epilepsia 1995;36(8):783-791. PubMed
  24. Trouillas P, Serratrice G, Laplane D, et al. Levorotatory form of 5-hydroxytryptophan in Friedreich's ataxia. Results of a double-blind drug-placebo cooperative study. Arch Neurol 1995;52:456-60. PubMed
  25. Bastard, J., Truelle, J. L., and Emile, J. [Effectiveness of 5 hydroxy-tryptophan in Parkinson's disease]. Nouv Presse Med 9-11-1976;5(29):1836-1837.
  26. Auffret, M., Comte, H., and Bene, J. Eosinophilia-myalgia syndrome induced by L-5 hydroxytryptophane: about three cases. Fund Clin Pharmacol 2013;Suppl 1(120):poster P2-204.
  27. Wyatt, R. J., Vaughan, T., Kaplan, J., Galanter, M., and Green, R. 5-Hydroxytryptophan and chronic schizophrenia. In: Barchas J and Usdin E. Serotonin and Behavior. New York: Acedemic Press;1973.
  28. Das YT, Bagchi M, Bagchi D, Preuss HG. Safety of 5-hydroxy-L-tryptophan. Toxicol Lett 2004;150:111-22. PubMed
  29. Pardo JV. Mania following addition of hydroxytryptophan to monoamine oxidase inhibitor. Gen Hosp Psychiatry 2012;34(1):102.e13-4. PubMed
  30. Michelson D, Page SW, Casey R, et al. An eosinophilia-myaligia syndrome related disorder associated with exposure to l-5-hydroxytryptophan. J Rheumatol 1994;21(12):2261-5.
  31. Yousefzadeh F, Sahebolzamani E, Sadri A, et al. 5-Hydroxytryptophan as adjuvant therapy in treatment of moderate to severe obsessive-compulsive disorder: a double-blind randomized trial with placebo control. Int Clin Psychopharmacol. 2020;35(5):254-262. PubMed
  32. Maffei ME. 5-Hydroxytryptophan (5-HTP): Natural Occurrence, Analysis, Biosynthesis, Biotechnology, Physiology and Toxicology. Int J Mol Sci. 2020;22(1):181. PubMed

See these in context on the 5-htp monograph →

Magnesium 82 references
  1. Rodin SM, Johnson BF. Pharmacokinetic interactions with digoxin. Clin Pharmacokinet 1988;15:227-44.
  2. Covington TR, et al. Handbook of Nonprescription Drugs. 11th ed. Washington, DC: American Pharmaceutical Association, 1996.
  3. Dahle LO, Berg G, Hammar M, et al. The effect of oral magnesium substitution on pregnancy-induced leg cramps. Am J Obstet Gynecol 1995;173:175-80. PubMed
  4. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  5. Peikert A, Wilimzig C, Kohne-Volland R. Prophylaxis of migraine with oral magnesium: results from a prospective, multi-center, placebo-controlled and double-blind randomized study. Cephalalgia 1996;16:257-63. PubMed
  6. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Calcium, Phosphorus, Magnesium, Vitamin D, and Fluoride. Washington, DC: National Academy Press, 1999. Available at: http://books.nap.edu/books/0309063507/html/index.html.
  7. Birrer RB, Shallash AJ, Totten V. Hypermagnesemia-induced fatality following epsom salt gargles. J Emerg Med 2002;22:185-8. PubMed
  8. Ryan MP. Diuretics and potassium/magnesium depletion. Directions for treatment. Am J Med 1987;82:38-47.. PubMed
  9. Hollifield JW. Magnesium depletion, diuretics, and arrhythmias. Am J Med 1987;82:30-7.. PubMed
  10. Heidenreich O. Mode of action of conventional and potassium-sparing diuretics--aspects with relevance to Mg-sparing effects. Magnesium 1984;3:248-56..
  11. Pfaffenrath V, Wessely P, Meyer C, et al. Magnesium in the prophylaxis of migraine--a double-blind placebo-controlled study. Cephalalgia 1996;16:436-40.. PubMed
  12. Wang F, Van Den Eeden SK, Ackerson LM, et al. Oral magnesium oxide prophylaxis of frequent migrainous headache in children: a randomized, double-blind, placebo-controlled trial. Headache 2003;43:601-10.. PubMed
  13. Sompolinsky D, Samra Z. Influence of magnesium and manganese on some biological and physical properties of tetracycline. J Bacteriol 1972;110:468-76.. PubMed
  14. Jeyabalan A, Caritis SN. Pharmacologic inhibition of preterm labor. Clin Obstet Gynecol 2002;45:99-113. PubMed
  15. Mittendorf R, Dambrosia J, Pryde PG, et al. Association between the use of antenatal magnesium sulfate in preterm labor and adverse health outcomes in infants. Am J Obstet Gynecol 2002;186:1111-8.. PubMed
  16. Witlin AG, Sibai BM. Magnesium sulfate therapy in preeclampsia and eclampsia. Obstet Gynecol 1998;92:883-9.. DOI
  17. Crowther CA, Hiller JE, Doyle LW. Magnesium sulphate for preventing preterm birth in threatened preterm labour. Cochrane Database Syst Rev 2002;4:CD001060. . PubMed
  18. Davey MJ, Teubner D. A randomized controlled trial of magnesium sulfate, in addition to usual care, for rate control in atrial fibrillation. Ann Emerg Med 2005;45:347-53.. PubMed
  19. L'Hommedieu CS, Nicholas D, Armes DA, et al. Potentiation of magnesium sulfate--induced neuromuscular weakness by gentamicin, tobramycin, and amikacin. J Pediatr 1983;102:629-31..
  20. Dunn CJ, Goa KL. Risedronate: a review of its pharmacological properties and clinical use in resorptive bone disease. Drugs 2001;61:685-712..
  21. Kass L, Weekes J, Carpenter L. Effect of magnesium supplementation on blood pressure: a meta-analysis. Eur J Clin Nutr 2012;66:411-8. PubMed
  22. Koontz SL, Friedman SA, Schwartz ML. Symptomatic hypocalcemia after tocolytic therapy with magnesium sulfate and nifedipine. Am J Obstet Gynecol. 2004;190(6):1773-6. PubMed
  23. Snyder SW, Cardwell MS. Neuromuscular blockade with magnesium sulfate and nifedipine. Am J Obstet Gynecol. 1989;161(1):35-6. PubMed
  24. Waisman GD, Mayorga LM, Cámera MI, et al. Magnesium plus nifedipine: potentiation of hypotensive effect in preeclampsia? Am J Obstet Gynecol. 1988;159(2):308-9. PubMed
  25. Brown DD, Juhl RP. Decreased bioavailability of digoxin due to antacids and kaolin-pectin. N Engl J Med. 1976;295(19):1034-7. PubMed
  26. Allen MD, Greenblatt DJ, Harmatz JS, et al. Effect of magnesium--aluminum hydroxide and kaolin--pectin on absorption of digoxin from tablets and capsules. J Clin Pharmacol. 1981;21(1):26-30. PubMed
  27. Ravn HB, Vissinger H, Kristensen SD, et al. Magnesium inhibits platelet activity--an in vitro study. Thromb Haemost. 1996;76(1):88-93. DOI
  28. Ravn HB, Kristensen SD, Vissinger H, et al. Magnesium inhibits human platelets. Blood Coagul Fibrinolysis. 1996;7(2):241-4. PubMed
  29. Ravn HB, Vissinger H, Kristensen SD, et al. Magnesium inhibits platelet activity--an infusion study in healthy volunteers. Thromb Haemost. 1996;75(6):939-44. DOI
  30. Neuvonen PJ, Kivistö KT. The effects of magnesium hydroxide on the absorption and efficacy of two glibenclamide preparations. Br J Clin Pharmacol. 1991;32(2):215-20. PubMed
  31. Kivistö KT, Neuvonen PJ. Enhancement of absorption and effect of glipizide by magnesium hydroxide. Clin Pharmacol Ther. 1991;49(1):39-43. PubMed
  32. Neuvonen PJ, Kivistö KT. Enhancement of drug absorption by antacids. An unrecognised drug interaction. Clin Pharmacokinet. 1994;27(2):120-8. PubMed
  33. Shechter, M., Merz, C. N., Paul-Labrador, M., Meisel, S. R., Rude, R. K., Molloy, M. D., Dwyer, J. H., Shah, P. K., and Kaul, S. Beneficial antithrombotic effects of the association of pharmacological oral magnesium therapy with aspirin in coronary heart
  34. Ganzevoort, J. W., Hoogerwaard, E. M., and van der Post, J. A. [Hypocalcemic delirium due to magnesium sulphate therapy in a pregnant woman with pre-eclampsia]. Ned.Tijdschr.Geneeskd. 8-3-2002;146(31):1453-1456.
  35. Horner, S. M. Efficacy of intravenous magnesium in acute myocardial infarction in reducing arrhythmias and mortality. Meta-analysis of magnesium in acute myocardial infarction. Circulation 1992;86(3):774-779. PubMed
  36. Azria, E., Tsatsaris, V., Goffinet, F., Kayem, G., Mignon, A., and Cabrol, D. [Magnesium sulfate in obstetrics: current data]. J Gynecol.Obstet.Biol.Reprod.(Paris) 2004;33(6 Pt 1):510-517.
  37. Magee, L. A., Miremadi, S., Li, J., Cheng, C., Ensom, M. H., Carleton, B., Cote, A. M., and von Dadelszen, P. Therapy with both magnesium sulfate and nifedipine does not increase the risk of serious magnesium-related maternal side effects in women with p
  38. Henyan, N. N., Gillespie, E. L., White, C. M., Kluger, J., and Coleman, C. I. Impact of intravenous magnesium on post-cardiothoracic surgery atrial fibrillation and length of hospital stay: a meta-analysis. Ann.Thorac.Surg. 2005;80(6):2402-2406. PubMed
  39. Li, J., Zhang, Q., Zhang, M., and Egger, M. Intravenous magnesium for acute myocardial infarction. Cochrane.Database.Syst.Rev. 2007;(2):CD002755. PubMed
  40. Doyle, L. W., Crowther, C. A., Middleton, P., Marret, S., and Rouse, D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane.Database.Syst.Rev. 2009;(1):CD004661. PubMed
  41. Han, S., Crowther, C. A., and Moore, V. Magnesium maintenance therapy for preventing preterm birth after threatened preterm labour. Cochrane.Database.Syst.Rev. 2010;(7):CD000940. PubMed
  42. Duley, L., Gulmezoglu, A. M., Henderson-Smart, D. J., and Chou, D. Magnesium sulphate and other anticonvulsants for women with pre-eclampsia. Cochrane.Database.Syst.Rev. 2010;(11):CD000025. PubMed
  43. Conde-Agudelo, A., Romero, R., and Kusanovic, J. P. Nifedipine in the management of preterm labor: a systematic review and metaanalysis. Am J Obstet.Gynecol. 2011;204(2):134-20. PubMed
  44. Wong, G. K., Boet, R., Poon, W. S., Chan, M. T., Gin, T., Ng, S. C., and Zee, B. C. Intravenous magnesium sulphate for aneurysmal subarachnoid hemorrhage: an updated systemic review and meta-analysis. Crit Care 2011;15(1):R52. PubMed
  45. Magee, L., Sawchuck, D., Synnes, A., and von, Dadelszen P. SOGC Clinical Practice Guideline. Magnesium sulphate for fetal neuroprotection. J Obstet.Gynaecol.Can. 2011;33(5):516-529.
  46. Doyle, L. W. Antenatal magnesium sulfate and neuroprotection. Curr Opin Pediatr 2012;24(2):154-159. PubMed
  47. McDonald, S. D., Lutsiv, O., Dzaja, N., and Duley, L. A systematic review of maternal and infant outcomes following magnesium sulfate for pre-eclampsia/eclampsia in real-world use. Int J Gynaecol.Obstet. 2012;118(2):90-96. PubMed
  48. Gordon, M., Naidoo, K., Akobeng, A. K., and Thomas, A. G. Osmotic and stimulant laxatives for the management of childhood constipation. Cochrane.Database.Syst.Rev. 2012;7:CD009118. PubMed
  49. Dodd, J. M., Crowther, C. A., and Middleton, P. Oral betamimetics for maintenance therapy after threatened preterm labour. Cochrane.Database.Syst.Rev. 2012;12:CD003927. PubMed
  50. Wu, X., Wang, C., Zhu, J., Zhang, C., Zhang, Y., and Gao, Y. Meta-analysis of randomized controlled trials on magnesium in addition to beta-blocker for prevention of postoperative atrial arrhythmias after coronary artery bypass grafting. BMC.Cardiovasc.D PubMed
  51. Thorp, J. M., Jr., Katz, V. L., Campbell, D., and Cefalo, R. C. Hypersensitivity to magnesium sulfate. Am.J.Obstet.Gynecol. 1989;161(4):889-890. PubMed
  52. Duley L and Gulmezoglu AM. Magnesium sulphate versus lytic cocktail for eclampsia. Cochrane Database of Systematic Reviews 2000;(3) PubMed
  53. Gibbins KJ, Browning KR, Lopes VV, Anderson BL, Rouse DJ. Evaluation of the clinical use of magnesium sulfate for cerebral palsy prevention. Obstet Gynecol 2013;121(2 Pt 1):235-40. PubMed
  54. Ji D. Oral magnesium sulfate causes perforation during bowel preparation for fiberoptic colonoscopy in patients with colorectal cancer. J Emerg Med 2012;43(4):716-7. PubMed
  55. Yagi T, Naito T, Mino Y, Umemura K, Kawakami J. Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects. Drug Metab Pharmacokinet 2012;27(2):248-54. PubMed
  56. Yamasaki M, Funakoshi S, Matsuda S, Imazu T, Takeda Y, Murakami T, Maeda Y. Interaction of magnesium oxide with gastric acid secretion inhibitors in clinical pharmacotherapy. Eur J Clin Pharmacol 2014;70(8):921-4. PubMed
  57. Choi ES, Jeong WJ, Ahn SH, Oh AY, Jeon YT, Do SH. Magnesium sulfate accelerates the onset of low-dose rocuronium in patients undergoing laryngeal microsurgery. J Clin Anesth. 2017 Feb;36:102-106. PubMed
  58. Ikee R, Toyoyama T, Endo T, Tsunoda M, Hashimoto N. Impact of sevelamer hydrochloride on serum magnesium concentrations in hemodialysis patients. Magnes Res. 2016 Apr 1;29(4):184-90. PubMed
  59. Miller ES, Sakowicz A, Leger E. Lange E, Yee LM. The association between receipt of intrapartum magnesium and postpartum hemorrhage. Am J Obstet Gynecol 2018;218(1 Suppl):S165.
  60. Rodríguez-Rubio L, Solis Garcia Del Pozo J, Nava E, Jordán J. Interaction between magnesium sulfate and neuromuscular blockers during the perioperative period. A systematic review and meta-analysis. J Clin Anesth. 2016;34:524-34. PubMed
  61. Brown RS. Magnesium Sulfate: Another Cause of a Solute Diuresis. Am J Kidney Dis. 2017;69(4):550-551. PubMed
  62. Park H, Qin R, Smith TJ, et al. North Central Cancer Treatment Group N10C2 (Alliance): a double-blind placebo-controlled study of magnesium supplements to reduce menopausal hot flashes. Menopause. 2015;22(6):627-32. PubMed
  63. Sakanoue M, Sanada J, Kanekura T. Skin eruption elicited by magnesium oxide (Maglax). J Dermatol. 2016;43(2):221-2.
  64. Iwamuro M, Saito S, Yoshioka M, et al. A Magnesium Oxide Bezoar. Intern Med. 2018;57(21):3087-3091. PubMed
  65. Vilchez G, Dai J, Kumar K, Mundy D, Kontopoulos E, Sokol RJ. Racial/ethnic disparities in magnesium sulfate neuroprotection: a subgroup analysis of a multicenter randomized controlled trial. J Matern Fetal Neonatal Med. 2018;31(17):2304-2311. PubMed
  66. Drug Safety Communication: FDA Recommends Against Prolonged Use of Magnesium Sulfate to Stop Pre-term Labor Due to Bone Changes in Exposed Babies. U.S. Food and Drug Administration (FDA), May 30, 2013. https://www.fda.gov/downloads/Drugs/DrugSafety/UCM353
  67. Committee Opinion: Magnesium Sulfate Use in Obstetrics. The American College of Obstetricians and Gynecologists Committee on Obstetric Practice Society for Maternal-Fetal Medicine, Number 652, January 2016. https://www.acog.org/Clinical-Guidance-and-Publi
  68. Kashihara Y, Terao Y, Yoda K, et al. Effects of magnesium oxide on pharmacokinetics of L-dopa/carbidopa and assessment of pharmacodynamic changes by a model-based simulation. Eur J Clin Pharmacol. 2019;75(3):351-361. PubMed
  69. Shepherd E, Salam RA, Manhas D, et al. Antenatal magnesium sulphate and adverse neonatal outcomes: A systematic review and meta-analysis. PLoS Med. 2019;16(12):e1002988. PubMed
  70. Hong JY, Hong JY, Choi YS, et al. Antenatal magnesium sulfate treatment and risk of necrotizing enterocolitis in preterm infants born at less than 32 weeks of gestation. Sci Rep. 2020;10(1):12826. PubMed
  71. Schuh S, Sweeney J, Rumantir M, et al. Effect of nebulized magnesium vs placebo added to albuterol on hospitalization among children with refractory acute asthma treated in the emergency department: a randomized clinical trial. JAMA. 2020;324(20):2038-20 PubMed
  72. Almeida CED, Carvalho LR, Andrade CVC, Nascimento PD Jr, Barros GAM, Modolo NSP. Effects of magnesium sulphate on the onset time of rocuronium at different doses: a randomized clinical trial. Braz J Anesthesiol. 2021;71(5):482-8. PubMed
  73. Gochi Valdovinos A, Arriaga-Redondo M, Dejuan Bitriá E, Pérez Rodríguez I, Márquez Isidro E, Blanco Bravo D. Prenatal therapy with magnesium sulphate and intestinal obstruction due to meconium in preterm newborns. An Pediatr (Engl Ed). 2022 Feb;96(2):138- PubMed
  74. Iio K, Kondo E, Shibata E, et al. Long-term tocolysis with magnesium sulfate as a risk factor for low bone mass: a case series. J Med Cases. 2022 Feb;13(2):47-50. PubMed
  75. Eiraku K, Uozumi Y, Hieda M, Maruyama T, Nomura H. A senile case of heart failure associated with hypermagnesemia induced by magnesium-containing laxative agent. Geriatr Gerontol Int. 2022;22(10):897-899.
  76. Enayati A, Gin JH, Sajeev JK, et al. Efficacy of intravenous magnesium for the management of non-post operative atrial fibrillation with rapid ventricular response: A systematic review and meta-analysis. J Cardiovasc Electrophysiol 2023;34(5):1286-1295. PubMed
  77. Su YH, Luo DC, Pang Y. Effects of intraoperative Magnesium sulfate infusion on emergency agitation during general anesthesia in patients undergoing radical mastectomy: a randomized controlled study. BMC Anesthesiol 2023;23(1):326. PubMed
  78. Han J, Park HY, Shin HJ, Chung SH, Do SH. Effects of magnesium sulphate on neostigmine-induced recovery from moderate neuromuscular blockade with rocuronium: a randomized controlled trial. Magnes Res 2023;36(2):31-39. PubMed
  79. Lee AT, Cordova JC, Jamplis RP, Pomicter GR. Posterior Reversible Encephalopathy Syndrome and Eclampsia in the Setting of Magnesium Toxicity: A Case Report. A A Pract 2023;17(11):e01726. PubMed
  80. Darmawan D, Rengganis I, Rumende CM, et al. Effectiveness and Safety of Nebulized Magnesium as Last Line Treatment in Adults with Acute Asthma Attack: A Systematic Review and Meta-Analysis. Acta Med Indones 2024;56(1):3-12.
  81. Shepherd ES, Goldsmith S, Doyle LW, et al. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2024;5(5):CD004661. PubMed
  82. US Food and Drug Administration (FDA). Biktarvy Prescribing Information. October 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210251Orig1s020lbl.pdf. Accessed July 16, 2025.

See these in context on the Magnesium 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&reg; - 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 →

Melatonin 118 references
  1. Voordouw BC, Euser R, Verdonk RE, et al. Melatonin and melatonin-progestin combinations alter pituitary-ovarian function in women and can inhibit ovulation. J Clin Endocrinol Metab 1992;74:108-17. DOI
  2. Ellis CM, Lemmens G, Parkes JD. Melatonin and insomnia. J Sleep Res 1996;5:61-5. PubMed
  3. Petrie K, Dawson AG, Thompson L, Brook R. A double-blind trial of melatonin as a treatment for jet lag in international cabin crew. Biol Psychiatr 1993;33:526-30. PubMed
  4. Claustrat B, Brun J, David M, et al. Melatonin and jet lag: confirmatory result using a simplified protocol. Biol Psychiatr 1992;32:705-11.
  5. Fauteck J, Schmidt H, Lerchl A, et al. Melatonin in epilepsy: first results of replacement therapy and first clinical results. Biol Signals Recept 1999;8:105-10. PubMed
  6. Arangino S, Cagnacci A, Angiolucci M, et al. Effects of melatonin on vascular reactivity, catecholamine levels, and blood pressure in healthy men. Am J Cardiol 1999;83:1417-9. PubMed
  7. Pierce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York: The Stonesong Press, 1999:19.
  8. Lancioni GE, O'Reilly MF, Basili G. Review of strategies for treating sleep problems in persons with severe or profound mental retardation or multiple handicaps. Am J Ment Retard 1999;104:170-86. PubMed
  9. Carman JS, Post RM, Buswell R, et al. Negative effects of melatonin on depression. Am J Psychiatry 1976;133:1181-1186. PubMed
  10. Hartter S, Grozinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.
  11. Fetrow CW, Avila JR. Professional's Handbook of Complementary & Alternative Medicines. 1st ed. Springhouse, PA: Springhouse Corp., 1999.
  12. Lusardi P, et al. Cardiovascular effects of melatonin in hypertensive patients well controlled by nifedipine: a 24-hour study. Br J Clin Pharmacol 2000;49:423-7. PubMed
  13. von Bahr C, Ursing C, Yasui N, et al. Fluvoxamine but not citalopram increases serum melatonin in healthy subjects – an indication that cytochrome P450 CYP1A2 and CYP2C19 hydroxylate melatonin. Eur J Clin Pharmacol 2000;56:123-7.
  14. Grozinger M, Hartter S, Wang X, et al. Fluvoxamine strongly inhibits melatonin metabolism in a patient with low-amplitude melatonin profile. Arch Gen Psychiatry 2000 Aug;57:812-3. PubMed
  15. Lissoni P, Barni S, Mandala M, et al. Decreased toxicity and increased efficacy of cancer chemotherapy using the pineal hormone melatonin in metastatic solic tumor patients with poor clinical status. Eur J Cancer 1999;35:1688-92.
  16. Sheldon SH. Pro-convulsant effects of oral melatonin in neurologically disabled children. Lancet 1998;351:1254. PubMed
  17. Hartter S, Grozinger M, Weigmann H, et al. Increased bioavailability of oral melatonin after fluvoxamine coadministration. Clin Pharmacol Ther 2000;67:1-6.
  18. Wright KP Jr, Myers BL, Plenzler SC, et al. Acute effects of bright light and caffeine on nighttime melatonin and temperature levels in women taking and not taking oral contraceptives. Brain Res 2000;873:310-7.
  19. Herxheimer A, Petrie KJ. Melatonin for preventing and treating jet lag. Cochrane Database Syst Rev 2001;(1):CD001520.
  20. Briggs, Freeman, Yafee. Update Drugs in Pregnancy and Lactation. Lippincott Williams & Wilkins, 2001.
  21. Suhner A, Schlagenhauf P, Johnson R, et al. Comparative study to determine the optimal melatonin dosage form for the alleviation of jet lag. Chronobiol Int 1998;15:655-66. PubMed
  22. Herxheimer A, Petrie KJ. Melatonin for the prevention and treatment of jet lag. Cochrane Database Syst Rev 2002;2:CD001520. PubMed
  23. Munoz-Hoyos A, Sanchez-Forte M, Molina-Carballo A, et al. Melatonin's role as an anticonvulsant and neuronal protector: experimental and clinical evidence. J Child Neurol 1998;13:501-9.. PubMed
  24. Sandyk R, Tsagas N, Anninos PA. Melatonin as a proconvulsive hormone in humans. Int J Neurosci 1992;63:125-35.. PubMed
  25. Golombek DA, Escolar E, Burin LJ, et al. Chronopharmacology of melatonin: inhibition by benzodiazepine antagonism. Chronobiol Int 1992;9:124-31.. PubMed
  26. Smits MG, Nagtegaal EE, van der Heijden J, et al. Melatonin for chronic sleep onset insomnia in children: a randomized placebo-controlled trial. J Child Neurol 2001;16:86-92.. PubMed
  27. Cagnacci A, Arangino S, Renzi A, et al. Influence of melatonin administration on glucose tolerance and insulin sensitivity of postmenopausal women. Clin Endocrinol (Oxf) 2001;54:339-46.. PubMed
  28. Williamson BL, Tomlinson AJ, Naylor S, Gleich GJ. Contaminants in commercial preparations of melatonin. Mayo Clin Proc 1997;72:1094-5. PubMed
  29. Williamson BL, Tomlinson AJ, Mishra PK, et al. Structural characterization of contaminants found in commercial preparations of melatonin: similarities to case-related compounds from L-tryptophan associated with eosinophilia-myalgia syndrome. Chem Res To
  30. Stewart LS. Endogenous melatonin and epileptogenesis: facts and hypothesis. Int J Neurosci 2001;107:77-85.. PubMed
  31. Molina-Carballo A, Munoz-Hoyos A, Reiter RJ, et al. Utility of high doses of melatonin as adjunctive anticonvulsant therapy in a child with severe myoclonic epilepsy: two years' experience. J Pineal Res 1997;23:97-105.. PubMed
  32. Tjon Pian Gi CV, Broeren JP, Starreveld JS, A Versteegh FG. Melatonin for treatment of sleeping disorders in children with attention deficit/hyperactivity disorder: a preliminary open label study. Eur J Pediatr 2003;162:554-5. PubMed
  33. Secreto G, Chiechi LM, Amadori A, et al. Soy isoflavones and melatonin for the relief of climacteric symptoms: a multicenter, double-blind, randomized study. Maturitas 2004;47:11-20. PubMed
  34. Weiss MD, Wasdell MB, Bomben MM, et al. Sleep hygiene and melatonin treatment for children and adolescents with ADHD and initial insomnia. J Am Acad Child Adolesc Psychiatry 2006;45:512-9. DOI
  35. Saha L, Malhotra S, Rana S, et al. A preliminary study of melatonin in irritable bowel syndrome. J Clin Gastroenterol 2007;41:29-32. PubMed
  36. Hussain, SA, Khadim, HM, Khalaf, BH, et al. Effects of melatonin and zinc on glycemic control in type 2 diabetic patients poorly controlled with metformin. Saudi Med J 2006;27:1483-8. DOI
  37. Kadhim, HM, Ismail, SH, Hussein, KI, et al. Effects of melatonin and zinc on lipid profile and renal function in type 2 diabetic patients poorly controlled with metformin. J Pineal Res 2006;41:189-93. PubMed
  38. Mutluay R. Elbeg S. Karakus R. et al. The Impact of Melatonin on Glucose Homeostasis. Turkish Journal of Endocrinology and Metabolism 2009;13:52-55.
  39. Wright KP Jr, Badia P, Myers BL, et al. Caffeine and light effects on nighttime melatonin and temperature levels in sleep-deprived humans. Brain Res. 1997;747(1):78-84. PubMed
  40. Peuhkuri K, Sihvola N, Korpela R. Dietary factors and fluctuating levels of melatonin. Food Nutr Res. 2012;56. doi: 10.3402/fnr.v56i0.17252. Epub 2012 Jul 20. PubMed
  41. Gibb JW, Bush L, Hanson GR. Exacerbation of methamphetamine-induced neurochemical deficits by melatonin. J Pharmacol Exp Ther. 1997;283(2):630-5. DOI
  42. Sunami E, Usuda K, Nishiyama Y, et al. A preliminary study of fluvoxamine maleate on depressive state and serum melatonin levels in patients after cerebral infarction. Intern Med. 2012;51(10):1187-93. PubMed
  43. Babkoff, H., French, J., Whitmore, J., and Sutherlin, R. Single-dose bright light and/or caffeine effect on nocturnal performance. Aviat.Space Environ.Med. 2002;73(4):341-350.
  44. Rossignol, D. A. Novel and emerging treatments for autism spectrum disorders: a systematic review. Ann.Clin Psychiatry 2009;21(4):213-236. DOI
  45. Yeleswaram, K., Vachharajani, N., and Santone, K. Involvement of cytochrome P-450 isozymes in melatonin metabolism and clinical implications. J Pineal Res 1999;26(3):190-191. PubMed
  46. Jan, J. E., Connolly, M. B., Hamilton, D., Freeman, R. D., and Laudon, M. Melatonin treatment of non-epileptic myoclonus in children. Dev.Med Child Neurol. 1999;41(4):255-259. PubMed
  47. Edwards, B. J., Atkinson, G., Waterhouse, J., Reilly, T., Godfrey, R., and Budgett, R. Use of melatonin in recovery from jet-lag following an eastward flight across 10 time-zones. Ergonomics 2000;43(10):1501-1513. PubMed
  48. Cagnacci, A., Arangino, S., Angiolucci, M., Melis, G. B., Facchinetti, F., Malmusi, S., and Volpe, A. Effect of exogenous melatonin on vascular reactivity and nitric oxide in postmenopausal women: role of hormone replacement therapy. Clin Endocrinol (Oxf PubMed
  49. Wakatsuki, A., Okatani, Y., Ikenoue, N., Kaneda, C., and Fukaya, T. Effects of short-term melatonin administration on lipoprotein metabolism in normolipidemic postmenopausal women. Maturitas 4-20-2001;38(2):171-177. PubMed
  50. Kitajima, T., Kanbayashi, T., Saitoh, Y., Ogawa, Y., Sugiyama, T., Kaneko, Y., Sasaki, Y., Aizawa, R., and Shimisu, T. The effects of oral melatonin on the autonomic function in healthy subjects. Psychiatry Clin Neurosci. 2001;55(3):299-300. PubMed
  51. Calvo, J. R., Guerrero, J. M., Osuna, C., Molinero, P., and Carrillo-Vico, A. Melatonin triggers Crohn's disease symptoms. J Pineal Res 2002;32(4):277-278. PubMed
  52. Luboshitzky, R., Shen-Orr, Z., Nave, R., Lavi, S., and Lavie, P. Melatonin administration alters semen quality in healthy men. J Androl 2002;23(4):572-578. DOI
  53. Rufo-Campos, M. [Melatonin and epilepsy]. Rev Neurol. 2002;35 Suppl 1:S51-S58.
  54. Ursing, C., Wikner, J., Brismar, K., and Rojdmark, S. Caffeine raises the serum melatonin level in healthy subjects: an indication of melatonin metabolism by cytochrome P450(CYP)1A2. J.Endocrinol.Invest 2003;26(5):403-406. PubMed
  55. Smits, M. G., van Stel, H. F., van der, Heijden K., Meijer, A. M., Coenen, A. M., and Kerkhof, G. A. Melatonin improves health status and sleep in children with idiopathic chronic sleep-onset insomnia: a randomized placebo-controlled trial. J Am Acad.Chi PubMed
  56. Boeve, B. F., Silber, M. H., and Ferman, T. J. Melatonin for treatment of REM sleep behavior disorder in neurologic disorders: results in 14 patients. Sleep Med. 2003;4(4):281-284. PubMed
  57. Hartter, S., Nordmark, A., Rose, D. M., Bertilsson, L., Tybring, G., and Laine, K. Effects of caffeine intake on the pharmacokinetics of melatonin, a probe drug for CYP1A2 activity. Br.J.Clin.Pharmacol. 2003;56(6):679-682. PubMed
  58. Scheer, F. A., Van Montfrans, G. A., van Someren, E. J., Mairuhu, G., and Buijs, R. M. Daily nighttime melatonin reduces blood pressure in male patients with essential hypertension. Hypertension 2004;43(2):192-197. PubMed
  59. Buscemi, N., Vandermeer, B., Pandya, R., Hooton, N., Tjosvold, L., Hartling, L., Baker, G., Vohra, S., and Klassen, T. Melatonin for treatment of sleep disorders. Evid.Rep.Technol.Assess.(Summ.) 2004;(108):1-7.
  60. Cavallo, A., Ris, M. D., Succop, P., and Jaskiewicz, J. Melatonin treatment of pediatric residents for adaptation to night shift work. Ambul.Pediatr. 2005;5(3):172-177. PubMed
  61. Faber, M. S., Jetter, A., and Fuhr, U. Assessment of CYP1A2 activity in clinical practice: why, how, and when? Basic Clin Pharmacol Toxicol. 2005;97(3):125-134. PubMed
  62. Cagnacci, A., Cannoletta, M., Renzi, A., Baldassari, F., Arangino, S., and Volpe, A. Prolonged melatonin administration decreases nocturnal blood pressure in women. Am J Hypertens. 2005;18(12 Pt 1):1614-1618. PubMed
  63. Weekley, L. B. Melatonin-induced relaxation of rat aorta: interaction with adrenergic agonists. J Pineal Res 1991;11(1):28-34. PubMed
  64. Grossman, E., Laudon, M., Yalcin, R., Zengil, H., Peleg, E., Sharabi, Y., Kamari, Y., Shen-Orr, Z., and Zisapel, N. Melatonin reduces night blood pressure in patients with nocturnal hypertension. Am J Med 2006;119(10):898-902. PubMed
  65. van der Heijden, K. B., Smits, M. G., van Someren, E. J., Ridderinkhof, K. R., and Gunning, W. B. Effect of melatonin on sleep, behavior, and cognition in ADHD and chronic sleep-onset insomnia. J Am Acad.Child Adolesc.Psychiatry 2007;46(2):233-241. PubMed
  66. Klupinska, G., Poplawski, T., Drzewoski, J., Harasiuk, A., Reiter, R. J., Blasiak, J., and Chojnacki, J. Therapeutic effect of melatonin in patients with functional dyspepsia. J.Clin.Gastroenterol. 2007;41(3):270-274. PubMed
  67. Bjorvatn, B., Stangenes, K., Oyane, N., Forberg, K., Lowden, A., Holsten, F., and Akerstedt, T. Randomized placebo-controlled field study of the effects of bright light and melatonin in adaptation to night work. Scand.J Work Environ.Health 2007;33(3):204 PubMed
  68. Wirtz, P. H., Spillmann, M., Bartschi, C., Ehlert, U., and von Kanel, R. Oral melatonin reduces blood coagulation activity: a placebo-controlled study in healthy young men. J Pineal Res 2008;44(2):127-133. PubMed
  69. Bendz, L. M. and Scates, A. C. Melatonin treatment for insomnia in pediatric patients with attention-deficit/hyperactivity disorder. Ann.Pharmacother. 2010;44(1):185-191. PubMed
  70. Elkhayat, H. A., Hassanein, S. M., Tomoum, H. Y., Abd-Elhamid, I. A., Asaad, T., and Elwakkad, A. S. Melatonin and sleep-related problems in children with intractable epilepsy. Pediatr.Neurol. 2010;42(4):249-254. PubMed
  71. van Geijlswijk, I. M., van der Heijden, K. B., Egberts, A. C., Korzilius, H. P., and Smits, M. G. Dose finding of melatonin for chronic idiopathic childhood sleep onset insomnia: an RCT. Psychopharmacology (Berl) 2010;212(3):379-391. PubMed
  72. Wade AG, Ford I, Crawford G, et al. Nightly treatment of primary insomnia with prolonged release melatonin for 6 months: a randomized placebo controlled trial on age and endogenous melatonin as predictors of efficacy and safety. BMC Med 2010;8:51. PubMed
  73. Al-Aama, T., Brymer, C., Gutmanis, I., Woolmore-Goodwin, S. M., Esbaugh, J., and Dasgupta, M. Melatonin decreases delirium in elderly patients: a randomized, placebo-controlled trial. Int.J.Geriatr.Psychiatry 2011;26(7):687-694. PubMed
  74. Alstadhaug, K. B., Odeh, F., Salvesen, R., and Bekkelund, S. I. Prophylaxis of migraine with melatonin: a randomized controlled trial. Neurology 10-26-2010;75(17):1527-1532. PubMed
  75. Wade, A. G., Crawford, G., Ford, I., McConnachie, A., Nir, T., Laudon, M., and Zisapel, N. Prolonged release melatonin in the treatment of primary insomnia: evaluation of the age cut-off for short- and long-term response. Curr.Med.Res.Opin. 2011;27(1):87 PubMed
  76. van Geijlswijk, I. M., Korzilius, H. P., and Smits, M. G. The use of exogenous melatonin in delayed sleep phase disorder: a meta-analysis. Sleep 2010;33(12):1605-1614. PubMed
  77. Guenole, F., Godbout, R., Nicolas, A., Franco, P., Claustrat, B., and Baleyte, J. M. Melatonin for disordered sleep in individuals with autism spectrum disorders: systematic review and discussion. Sleep Med.Rev. 2011;15(6):379-387. PubMed
  78. Rossignol, D. A. and Frye, R. E. Melatonin in autism spectrum disorders: a systematic review and meta-analysis. Dev.Med.Child Neurol. 2011;53(9):783-792. PubMed
  79. Eryilmaz, O. G., Devran, A., Sarikaya, E., Aksakal, F. N., Mollamahmutoglu, L., and Cicek, N. Melatonin improves the oocyte and the embryo in IVF patients with sleep disturbances, but does not improve the sleeping problems. J.Assist.Reprod.Genet. 2011;28 PubMed
  80. Batioglu, A. S., Sahin, U., Gurlek, B., Ozturk, N., and Unsal, E. The efficacy of melatonin administration on oocyte quality. Gynecol.Endocrinol. 2012;28(2):91-93.
  81. Grossman, E., Laudon, M., and Zisapel, N. Effect of melatonin on nocturnal blood pressure: meta-analysis of randomized controlled trials. Vasc.Health Risk Manag. 2011;7:577-584. PubMed
  82. Nickelsen, T., Demisch, L., Demisch, K., Radermacher, B., and Schoffling, K. Influence of subchronic intake of melatonin at various times of the day on fatigue and hormonal levels: a placebo-controlled, double-blind trial. J Pineal Res 1989;6(4):325-334. PubMed
  83. Wright, J., Aldhous, M., Franey, C., English, J., and Arendt, J. The effects of exogenous melatonin on endocrine function in man. Clin Endocrinol (Oxf) 1986;24(4):375-382. PubMed
  84. Papavasiliou, P. S., Cotzias, G. C., Duby, S. E., Steck, A. J., Bell, M., and Lawrence, W. H. Melatonin and parkinsonism. JAMA 7-3-1972;221(1):88-89. DOI
  85. Middleton, B. A., Stone, B. M., and Arendt, J. Melatonin and fragmented sleep patterns. Lancet 8-24-1996;348(9026):551-552. PubMed
  86. Holliman, B. J. and Chyka, P. A. Problems in assessment of acute melatonin overdose. South.Med J 1997;90(4):451-453. PubMed
  87. Hong, Y. G. and Riegler, J. L. Is melatonin associated with the development of autoimmune hepatitis? J Clin Gastroenterol 1997;25(1):376-378. PubMed
  88. Cagnacci, A., Arangino, S., Angiolucci, M., Maschio, E., and Melis, G. B. Influences of melatonin administration on the circulation of women. Am J Physiol 1998;274(2 Pt 2):R335-R338. PubMed
  89. U.S.Food and Drug Administration. Special Nutritionals Adverse Events Monitoring System: registered case reports.
  90. Brueske V, Allen J, Kepic T, and et al. Melatonin inhibition of seizure activity in man [abstract]. Electroencephalog Clin Neurophysiol 1981;51:20P.
  91. Siddiqui MA, Nazmi AS, Karim S, and et al. Effect of melatonin and valproate in epilepsy and depression. Indian J Pharmacol 2001;33:378-381.
  92. Appleton RE, Jones AP, Gamble C, et al. The use of MElatonin in children with neurodevelopmental disorders and impaired sleep: a randomised, double-blind, placebo-controlled, parallel study (MENDS). Health Technol Assess. 2012;16(40):i-239. PubMed
  93. Bardazzi F, Placucci F, Neri I, D&apos;Antuono A, Patrizi A. Fixed drug eruption due to melatonin. Acta Derm Venereol. 1998 Jan;78(1):69-70. PubMed
  94. Eckerberg B, Lowden A, Nagai R, Akerstedt T. Melatonin treatment effects on adolescent students&apos; sleep timing and sleepiness in a placebo-controlled crossover study. Chronobiol Int. 2012;29(9):1239-48.
  95. Khezri MB, Merate H. The effects of melatonin on anxiety and pain scores of patients, intraocular pressure, and operating conditions during cataract surgery under topical anesthesia. Indian J Ophthalmol. 2013;61(7):319-24. PubMed
  96. Khezri MB, Oladi MR, Atlasbaf A. Effect of melatonin and gabapentin on anxiety and pain associated with retrobulbar eye block for cataract surgery: a randomized double-blind study. Indian J Pharmacol. 2013;45(6):581-6. PubMed
  97. Nishihara T, Hashimoto S, Ito K, et al. Oral melatonin supplementation improves oocyte and embryo quality in women undergoing in vitro fertilization-embryo transfer. Gynecol Endocrinol. 2014;30(5):359-62.
  98. De Bleecker JL, Lamont BH, Verstraete AG, Schelfhout VJ. Melatonin and painful gynecomastia. Neurology. 1999 Jul 22;53(2):435-6. PubMed
  99. Waldron DL, Bramble D, Gringras P. Melatonin: prescribing practices and adverse events. Arch Dis Child. 2005 Nov;90(11):1206-7. PubMed
  100. Chojnacki C, Walecka-Kapica E, Lokiec K, et al. Influence of melatonin on symptoms of irritable bowel syndrome in postmenopausal women. Endokrynol Pol. 2013;64(2):114-20.
  101. Kim MK, Park EA, Kim HJ, et al. Does supplementation of in-vitro culture medium with melatonin improve IVF outcome in PCOS? Reprod Biomed Online. 2013;26(1):22-9. PubMed
  102. Silman RE. Melatonin: a contraceptive for the nineties. Eur J Obstet Gynecol Reprod Biol. 1993;49(1-2):3-9. PubMed
  103. Briggs GG, Freeman RK, Forinash AB, Towers CV. Drugs in Pregnancy and Lactation. 11th ed. Philadelphia, PA: Wolters Kluwer, 2017.
  104. Onseng K, Johns NP, Khuayjarernpanishk T, et al. Beneficial Effects of Adjuvant Melatonin in Minimizing Oral Mucositis Complications in Head and Neck Cancer Patients Receiving Concurrent Chemoradiation. J Altern Complement Med 2017;23(12):957-63. PubMed
  105. Foster BC, Cvijovic K, Boon HS, et al. Melatonin Interaction Resulting in Severe Sedation. J Pharm Pharm Sci 2015;18(2):124-31. PubMed
  106. Gonçalves AL, Martini Ferreira A, Ribeiro RT, Zukerman E, Cipolla-Neto J, Peres MF. Randomised clinical trial comparing melatonin 3 mg, amitriptyline 25 mg and placebo for migraine prevention. J Neurol Neurosurg Psychiatry 2016;87(10):1127-32. PubMed
  107. Gringras P, Nir T, Breddy J, Frydman-Marom A, Findling RL. Efficacy and Safety of Pediatric Prolonged-Release Melatonin for Insomnia in Children With Autism Spectrum Disorder. J Am Acad Child Adolesc Psychiatry 2017;56(11):948-57.e4. PubMed
  108. Baandrup L, Lindschou J, Winkel P, Gluud C, Glenthoj BY. Prolonged-release melatonin versus placebo for benzodiazepine discontinuation in patients with schizophrenia or bipolar disorder: A randomised, placebo-controlled, blinded trial. World J Biol Psychi PubMed
  109. Lui MFG, Chow HKD, Wong WMK, Tsang WNW. Melatonin affects postural control in community-dwelling older adults while dual-tasking: a randomized observation study. J Aging Phys Act. 2018 May 29:1-24. PubMed
  110. Fallah R, Shoroki FF, Ferdosian F. Safety and efficacy of melatonin in pediatric migraine prophylaxis. Curr Drug Saf. 2015;10(2):132-5. PubMed
  111. Scheuer C, Pommergaard HC, Rosenberg J, Gogenur I. Effect of topical application of melatonin cream 12.5% on cognitive parameters: a randomized, placebo-controlled, double-blind crossover study in healthy volunteers. J Dermatolog Treat. 2016 Nov;27(6):488 PubMed
  112. Doosti-Irani A, Ostadmohammadi V, Mirhosseini N et al. The effects of melatonin supplementation on glycemic control: A systematic review and meta-analysis of randomized controlled trials. Horm Metab Res. 2018;50(11):783-790. PubMed
  113. Farrokhian A, Tohidi M, Ahanchi NS, et al. Effect of bedtime melatonin administration in patients with type 2 diabetes: A triple-blind, placebo-controlled, randomized trial. Iran J Pharm Res. 2019;18(Suppl1):258-268.
  114. Hayashi M, Mishima K, Fukumizu M, et al. Melatonin treatment and adequate sleep hygiene interventions in children with autism spectrum disorder: A randomized controlled trial. J Autism Dev Disord 2021. PubMed
  115. Esmaeili A, Nassiri Toosi M, Taher M, et al. A pilot randomized, clinical trial of the anti-pruritus effect of melatonin in patients with chronic liver disease. Iran J Pharm Res 2021;20(2):462-472.
  116. Yan W, Li C, Song X, Zhou W, Chen Z. Prophylactic melatonin for delirium in critically ill patients: A systematic review and meta-analysis with trial sequential analysis. Medicine (Baltimore) 2022;101(43):e31411. PubMed
  117. Ameri A, Frouz Asadi M, Ziaei A, et al. Efficacy and safety of oral melatonin in patients with severe COVID-19: a randomized controlled trial. Inflammopharmacology 2023;31(1):265-274. PubMed
  118. Ha M, Yoon D, Lee CY, et al. Investigating the safety profiles of exogenous melatonin and associated adverse events: A pharmacovigilance study using WHO-VigiBase. J Pineal Res 2024;76(2):e12949. PubMed

See these in context on the Melatonin monograph →

Dong Quai 19 references
  1. Hirata JD, Swiersz LM, Zell B, et al. Does dong quai have estrogenic effects in postmenopausal women? A double-blind, placebo-controlled trial. Fertil Steril 1997;68:981-6. PubMed
  2. Page RL II, Lawrence JD. Potentiation of warfarin by dong quai. Pharmacotherapy 1999;19:870-6. PubMed
  3. Heck AM, DeWitt BA, Lukes AL. Potential interactions between alternative therapies and warfarin. Am J Health Syst Pharm 2000;57:1221-7. DOI
  4. Eagon PK, Elm MS, Hunter DS, et al. Medicinal herbs: modulation of estrogen action. Era of Hope Mtg, Dept Defense; Breast Cancer Res Prog, Atlanta, GA 2000;Jun 8-11.
  5. Dr. Duke's Phytochemical and Ethnobotanical Databases. Available at: http://www.ars-grin.gov/duke/.
  6. Amato P, Christophe S, Mellon PL. Estrogenic activity of herbs commonly used as remedies for menopausal symptoms. Menopause 2002;9:145-50. PubMed
  7. Shi M, Chang L, He G. [Stimulating action of Carthamus tinctorius L., Angelica sinensis (Oliv.) Diels and Leonurus sibiricus L. on the uterus]. Zhongguo Zhong Yao Za Zhi 1995;20:173-5, 192.
  8. Hoult JR, Paya M. Pharmacological and biochemical actions of simple coumarins: natural products with therapeutic potential. Gen Pharmacol 1996;27:713-22.. PubMed
  9. Cheong JL, Bucknall R. Retinal vein thrombosis associated with a herbal phytoestrogen preparation in a susceptible patient. Postgrad Med J 2005;81:266-7.. PubMed
  10. Chang CJ, Chiu JH, Tseng LM, et al. Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells. Eur J Clin Invest 2006;36:588-96. PubMed
  11. Chuang CH, Doyle P, Wang JD, et al. Herbal medicines used during the first trimester and major congenital malformations: an analysis of data from a pregnancy cohort study. Drug Saf 2006;29:537-48. PubMed
  12. Lau CBS, Ho TCY, Chan TWL, Kim SCF. Use of dong quai (Angelica sinensis) to treat peri- and postmenopausal symptoms in women with breast cancer: is it appropriate? Menopause 2005;12:734-40.
  13. Ellis GR, Stephens MR. Untitled (photograph and a brief case report). BMJ 1999;319:650.
  14. Nambiar, S., Schwartz, R. H., and Constantino, A. Hypertension in mother and baby linked to ingestion of Chinese herbal medicine. West J Med 1999;171(3):152.
  15. Lee, S. K., Cho, H. K., Cho, S. H., Kim, S. S., Nahm, D. H., and Park, H. S. Occupational asthma and rhinitis caused by multiple herbal agents in a pharmacist. Ann.Allergy Asthma Immunol. 2001;86(4):469-474. PubMed
  16. Xu, J. and Li, G. [Observation on short-term effects of Angelica injection on chronic obstructive pulmonary disease patients with pulmonary hypertension]. Zhongguo Zhong Xi Yi Jie He Za Zhi 2000;20(3):187-189.
  17. Scott, G. N. and Elmer, G. W. Update on natural product--drug interactions. Am J Health Syst.Pharm 2-15-2002;59(4):339-347. PubMed
  18. Circosta, C., Pasquale, R. D., Palumbo, D. R., Samperi, S., and Occhiuto, F. Estrogenic activity of standardized extract of Angelica sinensis. Phytother.Res. 2006;20(8):665-669.
  19. Fung FY, Wong WH, Ang SK, et al. A randomized, double-blind, placebo- controlled study on the anti-haemostatic effects of Curcuma longa, Angelica sinensis and Panax ginseng. Phytomedicine. 2017;32:88-96. PubMed

See these in context on the Dong Quai monograph →

Black Cohosh 68 references
  1. McFarlin BL, Gibson MH, O'Rear J, Harman P. A national survey of herbal preparation use by nurse-midwives for labor stimulation. Review of the literature and recommendations for practice. J Nurse Midwifery 1999;44:205-16. PubMed
  2. Whiting PW, Clouston A, Kerlin P. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2002;177:440-3. PubMed
  3. Pepping J. Black cohosh: Cimicifuga racemosa. Am J Health Syst Pharm 1999;56:1400-2. PubMed
  4. Liske E. Therapeutic efficacy and safety of Cimicifuga racemosa for gynecologic disorders. Adv Ther 1998;15:45-53.
  5. Kruse SO, Lohning A, Pauli GF, et al. Fukiic and piscidic acid esters from the rhizome of Cimicifuga racemosa and the in vitro estrogenic activity of fukinolic acid. Planta Med 1999;65:763-4.
  6. Jacobson JS, Troxel AB, Evans J, et al. Randomized trial of black cohosh for the treatment of hot flashes among women with a history of breast cancer. J Clin Oncol 2001;19:2739-45. PubMed
  7. Gunn TR, Wright IM. The use of black and blue cohosh in labour. N Z Med J 1996;109:410-1.
  8. Baillie N, Rasmussen P. Black and blue cohosh in labour. N Z Med J 1997;110:20-1.
  9. Lontos S, Jones RM, Angus PW, Gow PJ. Acute liver failure associated with the use of herbal preparations containing black cohosh. Med J Aust 2003;179:390-1.. DOI
  10. Wuttke W, Seidlova-Wuttke D, Gorkow C. The Cimicifuga preparation BNO 1055 vs. conjugated estrogens in a double-blind placebo-controlled study: effects on menopause symptoms and bone markers. Maturitas 2003;44:S67-77. PubMed
  11. Huntley A, Ernst E. A systematic review of the safety of black cohosh. Menopause 2003;10:58-64.. DOI
  12. Cohen SM, O'Connor AM, Hart J, et al. Autoimmune hepatitis associated with the use of black cohosh: a case study. Menopause 2004;11:575-7. PubMed
  13. Vitetta L, Thomsen M, Sali A. Black cohosh and other herbal remedies associated with acute hepatitis. Med J Aust 2003;178:411-2.. PubMed
  14. Thomsen M, Vitetta L, Schmidt M, Sali A. Acute liver failure associated with the use of herbal preparations containing black cohosh. Med J Aust 2004;180:598-600.. DOI
  15. Cohen B, Schardt D. Center for Science in the Public Interest. Letter to Food and Drug Administration. Commissioner Mark McClellan, MD, PhD. March 4, 2004.
  16. Seidlova-Wuttke D, Hesse O, Jarry H, et al. Evidence for selective estrogen receptor modulator activity in a black cohosh (Cimicifuga racemosa) extract: comparison with estradiol-17beta. Eur J Endocrinol 2003;149:351-62. PubMed
  17. Rockwell S, Liu Y, Higgins SA. Alteration of the effects of cancer therapy agents on breast cancer cells by the herbal medicine black cohosh. Breast Cancer Res Treat 2005;90:233-9. PubMed
  18. Levitsky J, Alli TA, Wisecarver J, Sorrell MF. Fulminant liver failure associated with the use of black cohosh. Dig Dis Sci 2005;50:538-9. PubMed
  19. Cheong JL, Bucknall R. Retinal vein thrombosis associated with a herbal phytoestrogen preparation in a susceptible patient. Postgrad Med J 2005;81:266-7.. PubMed
  20. Nappi RE, Malavasi B, Brundu B, Facchinetti F. Efficacy of Cimicifuga racemosa on climacteric complaints: a randomized study versus low-dose transdermal estradiol. Gynecol Endocrinol 2005;20:30-5.
  21. 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
  22. Minciullo PL, Saija A, Patafi M, et al. Muscle damage induced by black cohosh (Cimicifuga racemosa). Phytomedicine 2006;13:115-8. PubMed
  23. Wuttke W, Gorkow C, Seidlova-Wuttke D. Effects of black cohosh (Cimicifuga racemosa) on bone turnover, vaginal mucosa, and various blood parameters in postmenopausal women: a double-blind, placebo-controlled, and conjugated estrogens-controlled study. Men PubMed
  24. MHRA. Black cohosh (Cimicifuga racemosa) - risk of liver problems. Herbal Safety News July 2006. Available at: http://www.mhra.gov.uk/home/idcplg?IdcService=SS_GET_PAGE&useSecondary= true&ssDocName=CON2024131&ssTargetNodeId=663.
  25. Dugoua JJ, Seely D, Perri D, et al. Safety and efficacy of black cohosh (cimicifuga racemosa) during pregnancy and lactation. Can J Clin Pharmacol 2006;13:e257-61.
  26. Raus K, Brucker C, Gorkow C, Wuttke W. First-time proof of endometrial safety of the special black cohosh extract (Actaea or Cimicifuga racemosa extract) CR BNO 1055. Menopause 2006;13:678-91. PubMed
  27. Lynch CR, Folkers ME, Hutson WR. Fulminant hepatic failure associated with the use of black cohosh: a case report. Liver Transpl 2006;12:989-92. PubMed
  28. Bai W, Henneicke-von Zepelin HH, Wang S, et al. Efficacy and tolerability of a medicinal product containing an isopropanolic black cohosh extract in Chinese women with menopausal symptoms: A randomized, double blind, parallel-controlled study versus tibol
  29. Meyer S, Vogt T, Obermann EC, et al. Cutaneous pseudolymphoma induced by Cimicifuga racemosa. Dermatology 2007;214:94-6.
  30. Gori L, Firenzuoli F. Is black cohosh a hepatotoxic medicinal herb? Forsch Komplementarmed 2007;14:109-10. PubMed
  31. Assessment of case reports connected to herbal medicinal products containing cimicifugae racemosa rhizoma (black cohosh, root). Doc. Ref. EMEA/269259/2006. Available at: www.emea.eu.int/pdfs/human/hmpc/26925806en.pdf (Accessed 30 November 2007).
  32. Chung DJ, Kim HY, Park KH, et al. Black cohosh and St. John's wort (GYNO-Plus) for climacteric symptoms. Yonsei Med J 2007;48:289-94. PubMed
  33. Chow ECY, Teo M, Ring JA, Chen JW. Liver failure associated with the use of black cohosh for menopausal symptoms. Med J Aust 2008;188:420-2. PubMed
  34. Mahady GB, Low Dog T, Barrett ML, et al. United States Pharmacopeia review of the black cohosh case reports of hepatotoxicity. Menopause 2008;15:628-38. PubMed
  35. Hepatotoxicity with black cohosh. Australian Adv Drug Reactions Bull 2006;25:6. Available at: www.tga.gov.au/adr/aadrb/aadr0604.htm#a1.
  36. Dunbar K, Solga SF. Black cohosh, safety, and public awareness. Liver Int 2007;27:1017. PubMed
  37. Patel NM, Derkits RM. Possible increase in liver enzymes secondary to atorvastatin and black cohosh administration. J Pharm Pract 2007;20:341-6. DOI
  38. Joy D, Joy J, Duane P. Black cohosh: a cause of abnormal postmenopausal liver function tests. Climacteric 2008;11:84-8. PubMed
  39. Australian Adverse Drug Reactions Advisory Committee. Black cohosh and liver toxicity - an update. Aust Adv Drug Reactions Bull 2007;26:11.
  40. Gurley BJ, Swain A, Hubbard MA, et al. Clinical assessement of CYP2D6-mediated herb-drug interactions in humans: Effects of milk-thistle, black cohosh, goldenseal, kava kava, St. John's wort, and Echinacea. Mol Nutr Food Res 2008;52:755-63.
  41. Spangler L, Newton KM, Grothaus LC, et al. The effects of black cohosh therapies on lipids, fibrinogen, glucose and insulin. Maturitas 2007;57:195-204. PubMed
  42. Teschke R, Bahre R, Genthner A, et al. Suspected black cohosh hepatotoxicity - challenges and pitfalls of causality assessment. Maturitas 2009;63:302-14. PubMed
  43. Brasky TM, Lampe JW, Potter JD, et al. Specialty supplements and breast cancer risk in the VITamins And Lifestyle (VITAL) cohort. Cancer Epidemiol Biomarkers Prev 2010;19:1696-708. PubMed
  44. Fuchikami H, Satoh H, Tsujimoto M, Ohdo S, Ohtani H, Sawada Y. Effects of herbal extracts on the function of human organic anion-transporting polypeptide OATP-B. Drug Metab Dispos 2006;34:577-82. PubMed
  45. Vermes G, Bánhidy F, Acs N. The effects of remifemin on subjective symptoms of menopause. Adv Ther 2005;22:148-54. PubMed
  46. Nuntanakorn, P., Jiang, B., Einbond, L. S., Yang, H., Kronenberg, F., Weinstein, I. B., and Kennelly, E. J. Polyphenolic constituents of Actaea racemosa. J Nat Prod 2006;69(3):314-318.
  47. Oktem M, Eroglu D, Karahan HB, Taskintuna N, Kuscu E, Zeyneloglu HB. Black cohosh and fluoxetine in the treatment of postmenopausal symptoms: a prospective, randomized trial. Adv Ther 2007;24:448-61. PubMed
  48. Briese V, Stammwitz U, Friede M, Henneicke-von Zepelin HH. Black cohosh with or without St. John's wort for symptom-specific climacteric treatment--results of a large-scale, controlled, observational study. Maturitas 2007;57:405-14. PubMed
  49. Naser, B. and Liske, E. Liver failure associated with the use of black cohosh for menopausal symptoms. Med J Aust. 1-19-2009;190(2):99. PubMed
  50. van de Meerendonk, H. W., van Hunsel, F. P., and van der Wiel, H. E. [Autoimmune hepatitis induced by Actaea racemosa. Side affects of an herb extract]. Ned.Tijdschr.Geneeskd. 2-7-2009;153(6):246-249.
  51. Wong, V. C., Lim, C. E., Luo, X., and Wong, W. S. Current alternative and complementary therapies used in menopause. Gynecol.Endocrinol. 2009;25(3):166-174. PubMed
  52. Pierard, S., Coche, J. C., Lanthier, P., Dekoninck, X., Lanthier, N., Rahier, J., and Geubel, A. P. Severe hepatitis associated with the use of black cohosh: a report of two cases and an advice for caution. Eur J Gastroenterol Hepatol. 2009;21(8):941-945 PubMed
  53. Vannacci, A., Lapi, F., Gallo, E., Vietri, M., Toti, M., Menniti-Ippolito, F., Raschetti, R., Firenzuoli, F., and Mugelli, A. A case of hepatitis associated with long-term use of Cimicifuga racemosa. Altern.Ther Health Med 2009;15(3):62-63.
  54. Zimmermann, R., Witte, A., Voll, R. E., Strobel, J., and Frieser, M. Coagulation activation and fluid retention associated with the use of black cohosh: a case study. Climacteric. 2010;13(2):187-191. PubMed
  55. Amsterdam JD, Yao Y, Mao JJ, Soeller I, Rockwell K, Shults J. Randomized, double-blind, placebo-controlled trial of Cimicifuga racemosa (black cohosh) in women with anxiety disorder due to menopause. J Clin Psychopharmacol 2009;29:478-83. PubMed
  56. Bai WP, Wang SY, Liu JL, Geng L, Hu LN, Zhang ZL, Chen SL, Zheng SR. [Efficacy and safety of remifemin compared to tibolone for controlling of perimenopausal symptoms]. Zhonghua Fu Chan Ke Za Zhi 2009;44:597-600.
  57. McKenzie, S. C. and Rahman, A. Bradycardia in a patient taking black cohosh. Med J Aust. 10-18-2010;193(8):479-481. PubMed
  58. Stolze H. [An alternative to treat menopausal complaints]. Gynecologie 1982;1:14-16.
  59. Guzman G, Kallwitz ER, Wojewoda C, et al. Liver Injury with Features Mimicking Autoimmune Hepatitis following the Use of Black Cohosh. Case Rep Med. 2009;2009:918156. PubMed
  60. Enbom ET, Le MD, Oesterich L, Rutgers J, French SW. Mechanism of hepatotoxicity due to black cohosh (Cimicifuga racemosa): histological, immunohistochemical and electron microscopy analysis of two liver biopsies with clinical correlation. Exp Mol Pathol. PubMed
  61. Sen A. Orobuccolingual dyskinesia after long-term use of black cohosh and ginseng. J Neuropsychiatry Clin Neurosci 2013 Fall;25(4):E50. PubMed
  62. Hoban CL, Byard RW, Musgrave IF. Analysis of spontaneous adverse drug reactions to echinacea, valerian, black cohosh and ginkgo in Australia from 2000 to 2015. J Integr Med. 2019;17(5):338-343. PubMed
  63. Pkhaladze L, Davidova N, Khomasuridze A, Shengelia R, Panossian AG. Actaea racemosa L. is more effective in combination with Rhodiola rosea L. for relief of menopausal symptoms: a randomized, double-blind, placebo-controlled study. Pharmaceuticals (Basel) PubMed
  64. Yalçin M, Oguz A, Bestepe EE, Saglam NGU, Ergelen M. Black cohosh associated mania in a patient with unipolar depression. Int J Psychiatry Med 2020 Sep 21:91217420961185. doi: 10.1177/0091217420961185. PubMed
  65. Brar HS, Marathi R. Case of cholestatic drug-induced liver injury (DILI) associated with black cohosh. BMJ Case Rep 2021;14(5):e240408. PubMed
  66. Castelo-Branco C, Navarro C, Beltrán E, Losa F, Camacho M; on the behalf of the Natural Products Study Group of the Spanish Menopause Society. Black cohosh efficacy and safety for menopausal symptoms. The Spanish Menopause Society statement. Gynecol Endoc PubMed
  67. Trant AA, Chagpar A, Wei W, et al. The Effect of Black Cohosh on Ki67 expression and Tumor Volume: A Pilot Study of Ductal Carcinoma in Situ Patients. Integr Cancer Ther 2022;21:15347354221137290. PubMed
  68. Dernbach MR, Carpenter JE, Shah N, Carter GB. Black Cohosh Interactions with Prescription Medications Associated with Serotonin Toxicity and Rhabdomyolysis: A Case Report. J Emerg Med 2024;66(5):e592-e596. PubMed

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German Chamomile 15 references
  1. Subiza J, Subiza JL, Hinojosa M, et al. Anaphylactic reaction after the ingestion of chamomile tea; a study of cross-reactivity with other composite pollens. J Allergy Clin Immunol 1989;84:353-8. PubMed
  2. 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
  3. Viola H, Wasowski C, Levi de Stein M, et al. Apigenin, a component of Matricaria recutita flowers, is a central benzodiazepine receptors-ligand with anxiolytic effects. Planta Med 1995;61:213-6.
  4. van Ketel WG. Allergy to Matricaria chamomilla. Contact Dermatitis 1982;8:143. PubMed
  5. van Ketel WG. Allergy to Matricaria chamomilla. Contact Dermatitis 1987;16:50-1. PubMed
  6. Hormann HP, Korting HC. Evidence for the efficacy and safety of topical herbal drugs in dermatology: part I: anti-inflammatory agents. Phytomedicine 1994;1:161-71. PubMed
  7. Avallone R, Zanoli P, Puia G, et al. Pharmacological profile of apigenin, a flavonoid isolated from Matricaria chamomilla. Biochem Pharmacol 2000;59:1387-94. PubMed
  8. Kassi E, Papoutsi Z, Fokialakis N, et al. Greek plant extracts exhibit selective estrogen receptor modulator (SERM)-like properties. J Agric Food Chem 2004;52:6956-61. PubMed
  9. Maliakal PP, Wanwimolruk S. Effect of herbal teas on hepatic drug metabolizing enzymes in rats. J Pharm Pharmacol 2001;53:1323-9. PubMed
  10. Segal R, Pilote L. Warfarin interaction with Matricaria chamomilla. CMAJ 2006;174:1281-2. PubMed
  11. Loggia RD, Traversa U, Scarcia V, et al. Depressive effects of Chamomilla recutita (L.) Rausch, tubular flowers, on central nervous system in mice. Pharmacol Res Commun 1982;14(2):153-162. PubMed
  12. Ganzera M, Schneider P, Stuppner H. Inhibitory effects of the essential oil of chamomile (Matricaria recutita L.) and its major constituents on human cytochrome P450 enzymes. Life Sci 2006;78(8):856-861. PubMed
  13. Benito P, Rodríguez-Perez R, García F, Juste S, Moneo I, Caballero ML. Occupational allergic rhinoconjunctivitis induced by Matricaria chamomilla with tolerance of chamomile tea. J Investig Allergol Clin Immunol. 2014;24(5):369-70. No abstract available.
  14. Braga FT, Santos AC, Bueno PC, et al. Use of Chamomilla recutita in the prevention and treatment of oral mucositis in patients undergoing hematopoietic stem cell transplantation: a randomized, controlled, phase II clinical trial. Cancer Nurs 2015;38(4):32 PubMed
  15. Sarris J, Ravindran A, Yatham LN, et al. Clinician guidelines for the treatment of psychiatric disorders with nutraceuticals and phytoceuticals: The World Federation of Societies of Biological Psychiatry (WFSBP) and Canadian Network for Mood and Anxiety T

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Vitex Agnus-castus 23 references
  1. Wuttke W. Dopaminergic action of extracts of Agnus Castus. Forschende Komplementarmedizen 1996;3:329-30.
  2. Jarry H, Leonhardt S., Gorkow C, Wuttke W. In vitro prolactin but not LH and FSH release is inhibited by compounds in extracts of Agnus Castus: direct evidence for a dopaminergic principle by the dopamine receptor assay. Exp Clin Endocrinol 1994;102:448- PubMed
  3. Schellenberg R. Treatment for the premenstrual syndrome with agnus castus fruit extract: prospective, randomised, placebo-controlled study. BMJ 2001;322:134-7. PubMed
  4. Lauritzen CH, Reuter HD, Repges R, et al. Treatment of premenstrual tension syndrome with Vitex agnus castus: Controlled-double blind versus pyridoxine. Phytomedicine 1997;4:183-9.
  5. Berger D, Schaffner W, Schrader E, et al. Efficacy of Vitex agnus castus L. extract Ze 440 in patients with premenstrual syndrome (PMS). Arch Gynecol Obstet 2000;264:150-3.
  6. Loch EG, Selle H, Boblitz N. Treatment of premenstrual syndrome with a phytopharmaceutical formulation containing Vitex agnus castus. J Womens Health Gend Based Med 2000;9:315-20. PubMed
  7. Meier B, Berger D, Hoberg E, et al. Pharmacological activities of Vitex agnus-castus extracts in vitro. Phytomedicine 2000;7:373-81. PubMed
  8. Liu J, Burdette JE, Xu H, et al. Evaluation of estrogenic activity of plant extracts for the potential treatment of menopausal symptoms. J Agric Food Chem 2001;49:2472-9.. PubMed
  9. Wuttke W, Jarry H, Christoffel V, et al. Chaste tree (Vitex agnus-castus)--pharmacology and clinical indications. Phytomedicine 2003;10:348-57. PubMed
  10. Atmaca M, Kumru S, Tezcan E. Fluoxetine versus Vitex agnus castus extract in the treatment of premenstrual dysphoric disorder. Hum Psychopharmacol 2003;18:191-5..
  11. Daniele C, Thompson Coon J, Pittler MH, Ernst E. Vitex agnus castus: a systematic review of adverse events. Drug Saf 2005;28:319-32..
  12. Halaska M, Beles P, Gorkow C, Sieder C. Treatment of cyclical mastalgia with a solution containing a Vitex agnus castus extract: results of a placebo-controlled double-blind study. Breast 1999;8:175-81. PubMed
  13. Prilepskaya VN, Ledina AV, Tagiyeva AV, Revazova FS. Vitex agnus castus: Successful treatment of moderate to severe premenstrual syndrome. Maturitas 2006;55 Suppl 1:S55-63. DOI
  14. Ma, L., Lin, S., Chen, R., and Wang, X. Treatment of moderate to severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women. Gynecol.Endocrinol. 2010;26(8):612-616. PubMed
  15. Ma, L., Lin, S., Chen, R., Zhang, Y., Chen, F., and Wang, X. Evaluating therapeutic effect in symptoms of moderate-to-severe premenstrual syndrome with Vitex agnus castus (BNO 1095) in Chinese women. Aust.N.Z.J Obstet.Gynaecol. 2010;50(2):189-193. PubMed
  16. Dinç T, Coskun F. Comparison of fructus agni casti and flurbiprofen in the treatment of cyclic mastalgia in premenopausal women. Ulus Cerrahi Derg. 2014 Mar 1;30(1):34-8 PubMed
  17. Momoeda M, Sasaki H, Tagashira E, Ogishima M, Takano Y, Ochiai K. Efficacy and safety of Vitex agnus-castus extract for treatment of premenstrual syndrome in Japanese patients: a prospective, open-label study. Adv Ther. 2014 Mar;31(3):362-73. PubMed
  18. Yavarikia P, Shahnazi M, Hadavand Mirzaie S, Javadzadeh Y, Lutfi R. Comparing the effect of mefenamic Acid and vitex agnus on intrauterine device induced bleeding. J Caring Sci. 2013 Aug 31;2(3):245-54.
  19. Van Die MD, Burger HC, Teede HG, Bone KM. Vitex agnus castus extracts for female reproductive disorders: a systematic review of clinical trials. Planta Med 2013:79:562-575. PubMed
  20. Ooi SL, Watts S, McClean R, Pak SC. Vitex agnus-castus for the treatment of cyclic mastalgia: A systematic review and meta-analysis. J Womens Health (Larchmt). 2020;29(2):262-278. PubMed
  21. Mollazadeh S, Mirghafourvand M, Abdollahi NG. The effects of Vitex agnus-castus on menstrual bleeding: A systematic review and meta-analysis. J Complement Integr Med. 2019;17(1). pii: /j/jcim.2019.17.issue-1/jcim-2018-0053/jcim-2018-0053.xml.
  22. Najib FS, Poordast T, Mahmudi MS, Shiravani Z, Namazi N, Omrani GR. Does Vitex Agnus-Castus L. Have Deleterious Effect on Fertility and Pregnancy Outcome? An Experimental Study on Rats for Prediction of Its Safety. J Pharmacopuncture 2022;25(2):106-113. PubMed
  23. Somuncu E, Solak IHA. Colonic Obstruction Secondary to Phytobezoar Caused by Vitex Agnus-Castus Seeds: A Case Report. J Coll Physicians Surg Pak 2022;32(8):S115-S117. PubMed

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DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

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