Major interaction on record — check this product against your medications before combining. Based on 11 of 12 ingredients. Check your meds →
Dietary supplement

Calm & Clear Ingredients & Drug Interactions

by Pacific BioLogic

Calm & Clear label
See full label image
Capsule Category: Botanical
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 9, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Calm & Clear 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

Calm & Clear is a dietary supplement by Pacific BioLogic with 12 active ingredients. Its ingredients are commonly taken for wound healing, varicose veins and poor circulation, anxiety and stress.Based on those ingredients, 1,566 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Fo-Ti, Grass-Leaf Sweetflag, Chinese Salvia. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Calm & Clear by Pacific BioLogic

Ask about any prescription or over-the-counter medication and we check it for interactions with Calm & Clear by Pacific BioLogic — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of Calm & Clear by Pacific BioLogic

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 12, 2026

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

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

Why this rating?
  • The label discloses an exact amount for 0 of its 12 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (500 mg) without saying how much of each component you get.

Calm & Clear contains 12 active ingredients in a proprietary blend, including well-known traditional herbs: gotu kola, valerian, lemon balm, white peony, Chinese skullcap, passionflower, fo-ti, Chinese salvia (danshen), grass-leaf sweetflag, tangerine, schisandra, and polygala. The product also contains cellulose as an inactive ingredient (a binder in the capsule).

These herbs are traditionally used to support mood and mental clarity. Gotu kola and lemon balm are known for their calming properties, while valerian and passionflower have long histories as sleep and relaxation aids.

The blend also includes Chinese salvia, which is traditionally used for circulation, and schisandra and fo-ti, which are adaptogens in traditional Chinese medicine meant to support overall resilience.

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: Calm and stress relief.
  • We looked for evidence on: Anxiety, Generalized anxiety disorder (GAD), Adjustment disorders, Benzodiazepine withdrawal, Depression, Nervousness — and 3 related terms.
  • The strongest evidence on file: Lemon Balm is rated "Possibly Effective" for Depression (Natural Medicines).
  • Also on file: Passion Flower is rated "Possibly Effective" for Pre-procedural anxiety.
  • Also on file: Lemon Balm is rated "Insufficient Reliable Evidence To Rate" for Anxiety.

Our data show limited evidence for most of these ingredients. Lemon balm is possibly effective for stress and depression, and both valerian and passionflower are possibly effective for insomnia and pre-procedural anxiety.

Gotu kola is possibly effective for venous insufficiency and burns, though research on its use for cognitive function and anxiety is insufficient. For white peony, Chinese skullcap, fo-ti, danshen, grass-leaf sweetflag, schisandra, and polygala, the evidence we hold does not establish effectiveness for any claimed use.

Tangerine's data show insufficient evidence as well. Because this is a blend and the doses of individual ingredients are not disclosed, it's difficult to know whether the amounts present are the same as those studied.

The evidence, ingredient by ingredient Gotu Kola Valerian Lemon Balm Peony Baikal Skullcap Passion Flower Fo-ti Danshen

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 11 of the 11 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 11 of 11.
  • General safety write-ups exist for 11 of 11.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Most ingredients are generally well tolerated for short-term use. Common side effects reported include dizziness, drowsiness, nausea, and gastrointestinal upset.

Gotu kola, valerian, and fo-ti carry cautions regarding liver health; there are case reports of liver damage associated with each, though the evidence remains limited and causation is not always clear. Fo-ti is the most concerning—around 450 cases of hepatitis linked to fo-ti have been documented in medical literature, ranging from full recovery to severe cirrhosis.

Grass-leaf sweetflag contains beta-asarone, a constituent that the FDA has deemed a possible carcinogen and banned from food. Passionflower may cause confusion and serious cases of heart rhythm changes have been reported.

Valerian can cause withdrawal symptoms if stopped abruptly after long-term use, so doses should be tapered slowly.

Side effects, ingredient by ingredient Gotu Kola Valerian Lemon Balm Peony Baikal Skullcap Passion Flower Fo-ti Danshen

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?
  • 11 of the 11 matched ingredients can interact with medications — Peony, Schisandra, Lemon Balm, Gotu Kola, Fo-ti, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; lithium.
  • For scale: 1,567 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking Calm & Clear, double-check these medication types with your pharmacist: blood thinners and antiplatelet drugs (like warfarin, clopidogrel, and aspirin) — Chinese salvia poses a Major risk of increased bleeding; digoxin and other heart medications (Major risk with Chinese salvia); sedative and anti-anxiety drugs, including benzodiazepines, sleep aids, and alcohol (Moderate risk with gotu kola, valerian, lemon balm, passionflower, and grass-leaf sweetflag); medications processed by your liver's CYP enzymes (CYP1A2, CYP2C9, CYP2D6, CYP3A4, CYP2C19, and others), including some antidepressants, statins, and immunosuppressants (Moderate risks from multiple ingredients); thyroid and estrogen medications (Moderate risk with white peony, Chinese skullcap, and lemon balm); blood pressure medications (Moderate risk with Chinese skullcap, danshen, and grass-leaf sweetflag); and lithium, diuretics, and antidiabetes medications. No interactions are documented for Polygala—we hold no data for it.

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.

Calm & Clear may appeal to people seeking herbal support for stress and sleep, but it carries meaningful medication interactions—especially if you take blood thinners, heart drugs, sedatives, or medications metabolized by your liver. The presence of fo-ti and grass-leaf sweetflag adds safety concerns that warrant a conversation with your pharmacist.

Talk to your pharmacist or doctor before starting, particularly if you take any prescription medications or have liver concerns.

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

Assessment coverage: 11 of 12 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Dec 14, 2023.

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 Calm & Clear, straight from the product label.

Brand Pacific BioLogic
Barcode (UPC) 065367400702
Net contents 60 Vegetarian Capsule(s)
Market status On market
Date entered into DSLD Dec 14, 2023
DSLD ID 299694
Product type Botanical
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years)
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Calm & Clear by Pacific BioLogic, 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:
3 Capsule(s)
Servings per container
20
UPC/BARCODE
065367400702
IngredientAmount% DV
Proprietary Blend500 mg--
Gotu Kola0 NP--
Valerian0 NP--
Lemon Balm0 NP--
White Peony0 NP--
Chinese Skullcap0 NP--
Polygala0 NP--
Passionflower0 NP--
Fo-Ti0 NP--
Chinese Salvia0 NP--
Grass-Leaf Sweetflag0 NP--
Tangerine0 NP--
Schizandra0 NP--

Other ingredients: 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.
Suggested/Recommended/Usage/Directions

Suggested dosage 1-3 capsules 1-3 times daily. Take as needed according to the severity of symptoms or recommended by your healthcare provider.

Precautions

Caution Do not take with pharmaceutical sedative drugs. If pregnant or nursing, consult your healthcare provider before using this, or any other product.

To report a serious adverse event or obtain product information, contact (800) 869-8783

Storage

Store in a cool, dry place. Do not refrigerate.

Formulation

Calm & Clear is a proprietary formula of Pacific BioLogic Co. manufactured in and FDA compliant facility in the United States of America from imported and domestic ingredients.

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.

Brand IP Statement(s)

Pacific BioLogic Powerful tools for gentle healing

FDA Statement of Identity

Herbal Supplement

Seals/Symbols

Product of USA

Formula

Calm & Clear 500 mg

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

See for yourself

Calm & Clear by Pacific BioLogic label

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

Calm & Clear 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 Calm & Clear by Pacific BioLogic

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

Serving size1 Capsule(s) Dosage formCapsule Servings per container20 Amounts shown are per serving.

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

Proprietary Blend

500 mg per serving

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

Interaction report

Calm & Clear by Pacific BioLogic Drug Interactions

Want to check YOUR meds against Calm & Clear?

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
1,566Drugs
123 Major 1,425 Moderate 18 Minor

Ingredients driving the most interactions

Fo-Ti 1,257
Grass-Leaf Sweetflag 1,117
Chinese Salvia 1,059
Chinese Skullcap 946
Valerian 902

Individual Drug Interactions

The ingredients in Calm & Clear interact with 1,566 drugs. Click any drug to see the details.

11 of the 12 ingredients in Calm & Clear interact with drugs. Each result below shows which ingredient is responsible. Fo-Ti Grass-Leaf Sweetflag Chinese Salvia Chinese Skullcap Valerian Passionflower White Peony Schizandra Tangerine Gotu Kola Lemon Balm

Each ingredient & the kinds of drugs it affects

For each ingredient in Calm & Clear 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.

Fo-Ti17 drug types · 1,257 drugs

Anticoagulant/Antiplatelet Drugs

Fo-ti has been linked to cases of acute liver failure which can decrease clotting factor production and increase the effects of anticoagulants. In one case, a patient who had been stable on warfarin presented with acute hepatitis and an INR elevated to 14.98. The patient had been taking fo-ti for 90 days prior to admission. Discontinuation of warfarin and fo-ti lead to a decrease in the INR and full recovery. Theoretically, concomitant use of fo-ti with anticoagulant or antiplatelet drugs may increase the risk of bleeding in some patients. Until more is known, monitor patients taking fo-ti and drugs that affect bleeding.
Some of these drugs include aspirin, clopidogrel (Plavix), dalteparin (Fragmin), dipyridamole (Persantine), enoxaparin (Lovenox), heparin, ticlopidine (Ticlid), warfarin (Coumadin), and others.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, fo-ti might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Fo-ti reportedly has hypoglycemic effects.

Likelihood Possible Evidence D
Contraceptive Drugs

Theoretically, taking large amounts of fo-ti might interfere with contraceptive drugs due to competition for estrogen receptors.
In vitro research suggests that fo-ti extract has estrogenic activity.

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

Theoretically, fo-ti might increase or decrease the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that fo-ti might inhibit CYP1A2. Additionally, in vitro research suggests that the degree of CYP1A2 inhibition depends on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts). However, in an animal study, an aqueous extract of fo-ti inhibited CYP1A2 while an alcoholic extract of fo-ti induced CYP1A2. Induction or inhibition of CYP1A2 by fo-ti has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2B6 (Cyp2B6) Substrates

Theoretically, fo-ti might increase the levels and clinical effects of drugs metabolized by CYP2B6.
Animal research suggests that fo-ti might inhibit CYP2B6. One in vitro study suggests that the degree of CYP2B6 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts). However, this interaction has not been reported in humans.

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

Theoretically, fo-ti may increase the levels and clinical effects of drugs metabolized by CYP2C19.
Animal and in vitro research suggests that fo-ti may inhibit CYP2C19. An in vitro study suggests that the degree of CYP2C19 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts). However, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2C8 (Cyp2C8) Substrates

Theoretically, fo-ti might increase the levels and clinical effects of drugs metabolized by CYP2C8.
In vitro research suggests that fo-ti might inhibit CYP2C8. However, this interaction has not been reported in humans.

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

Theoretically, fo-ti may increase the levels and clinical effects of drugs metabolized by CYP2C9.
Animal and in vitro research suggests that fo-ti may inhibit CYP2C9. However, this interaction has not been reported in humans.

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

Theoretically, fo-ti may increase the levels and clinical effects of drugs metabolized by CYP2D6.
Animal research suggests that fo-ti might inhibit CYP2D6. Additionally, an in vitro study suggests that the degree of CYP2D6 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts). However, this interaction has not been reported in humans.

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

Theoretically, fo-ti might increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro research suggests that fo-ti might inhibit CYP3A4. One in vitro study suggests that the degree of CYP3A4 inhibition may depend on the type of fo-ti extract (i.e., the raw plant leads to greater inhibition than extensively processed extracts). However, this evidence conflicts with animal research suggesting that fo-ti does not inhibit CYP3A4. This interaction has not been reported in humans.

Likelihood Possible Evidence D
Digoxin (Lanoxin)

Theoretically, fo-ti, particularly raw fo-ti root, might increase the risk of hypokalemia and cardiotoxicity when taken with digoxin.
Raw fo-ti root contains anthraquinone derivatives, which might have stimulant laxative effects. In vitro research shows that fermented and processed fo-ti root have reduced laxative effects compared with raw fo-ti root.

Likelihood Possible Evidence D
Diuretic Drugs

Theoretically, fo-ti, particularly raw fo-ti root, might increase the risk of hypokalemia when taken with diuretic drugs.
Raw fo-ti root contains anthraquinone derivatives, which might have stimulant laxative effects and compound diuretic-induced potassium loss. In vitro research shows that fermented and processed fo-ti root have reduced laxative effects compared with raw fo-ti root.

Likelihood Possible Evidence D
Estrogens

Theoretically, taking large amounts of fo-ti might interfere with hormone replacement therapy through competition for estrogen receptors.
In vitro research suggests that fo-ti extract has estrogenic activity.

Likelihood Probable Evidence D
Hepatotoxic Drugs

Theoretically, fo-ti might increase the risk of liver damage when taken with hepatotoxic drugs.
Fo-ti has been linked to liver damage in many reports.

Likelihood Possible Evidence D
Stimulant Laxatives

Theoretically, fo-ti, particularly raw fo-ti root, might increase the risk of fluid and electrolyte depletion when taken with stimulant laxatives.
Raw fo-ti root contains anthraquinone derivatives, which might have stimulant laxative effects. However, in vitro research shows that fermented and processed fo-ti root have reduced laxative effects compared with raw fo-ti root.

Likelihood Possible Evidence D
Sulindac (Clinoril)

Theoretically, fo-ti might increase or decrease the levels and clinical effects of sulindac.
Animal research suggests that the type of fo-ti extract might affect the levels of sulindac differently; the raw plant may increase levels, but processed parts may decrease levels. Induction or inhibition of CYP1A2 by fo-ti has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, fo-ti might increase the effects and adverse effects of warfarin.
Fo-ti may have stimulant laxative effects and cause diarrhea, especially when the raw or unprocessed fo-ti root is used. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. Also, fo-ti has been linked to cases of acute liver failure which can decrease clotting factor production and increase the effects of warfarin. In one case, a patient who had been stable on warfarin presented with acute hepatitis and an INR elevated to 14.98. The patient had been taking fo-ti for 90 days prior to admission. Discontinuation of warfarin and fo-ti lead to a decrease in the INR and full recovery.

Likelihood Possible Evidence D
Fo-Ti full monograph & interactions

Grass-Leaf Sweetflag10 drug types · 1,117 drugs

Anticholinergic Drugs

Theoretically, concurrent use of anticholinergic drugs and calamus might decrease the effectiveness of the anticholinergic drug.
In vitro evidence shows that calamus can inhibit acetylcholinesterase (AChE).

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, taking calamus with other antihypertensive medications might increase the risk of hypotension.
Animal research shows that calamus decreases the rate and strength of the heartbeat, which might lower blood pressure. use with caution.

Likelihood Possible Evidence D
Cholinergic Drugs

Theoretically, concurrent use of cholinergic drugs and calamus might have an additive effect and increase the risk of cholinergic effects.
In vitro evidence shows that calamus can inhibit acetylcholinesterase (AChE).

Likelihood Possible Evidence D
Cns Depressants

Theoretically, concurrent use of CNS depressants and calamus might have an additive effect and increase the risk of sedative effects.
Animal research shows that calamus is a CNS depressant and increases gamma-aminobutyric acid levels.

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

Theoretically, taking calamus with drugs metabolized by CYP2D6 might increase drug levels and potentially increase the risk of adverse effects.
In vitro research shows that calamus extract inhibits CYP2D6 enzyme.

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

Theoretically, taking calamus with drugs metabolized by CYP3A4 might increase drug levels and potentially increase the risk of adverse effects.
In vitro research shows that calamus extract inhibits CYP3A4 enzyme.

Likelihood Possible Evidence D
Monoamine Oxidase Inhibitors (Maois)

Theoretically, calamus might potentiate the effects and adverse effects of MAOIs.
Some reports suggest that calamus increases the effects of MAOIs.

Likelihood Possible Evidence D
Antacids

Theoretically, taking calamus might reduce the effectiveness of antacids.
Some research suggests that calamus lowers gastric pH.

Likelihood Possible Evidence D
H2-Blockers

Theoretically, taking calamus might reduce the effectiveness of H2-blockers.
Some research suggests that calamus lowers gastric pH.

Likelihood Possible Evidence D
Proton Pump Inhibitors (Ppis)

Theoretically, taking calamus might reduce the effectiveness of PPIs.
Some research suggests that calamus lowers gastric pH.

Likelihood Possible Evidence D
Grass-Leaf Sweetflag full monograph & interactions

Chinese Salvia16 drug types · 1,059 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, danshen may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Danshen has been reported to have antithrombotic effects. Animal research also suggests that taking a danshen combination formula with clopidogrel exhibits a synergistic increase in antiplatelet aggregation and prolongation of coagulation time when compared with either taken alone.

Likelihood Probable Evidence D
Digoxin (Lanoxin)

Theoretically, using danshen with digoxin might increase the risk of adverse effects.
Danshen has structural and pharmacological similarities to cardiac glycosides.

Likelihood Probable Evidence D
Amlodipine (Norvasc)

Theoretically, taking danshen in combination with amlodipine may decrease the clinical effects of amlodipine.
In animal research, taking danshen orally in combination with amlodipine reduced blood levels of amlodipine by about 52%. This may have been due to induction of cytochrome P450 3A4 (CYP3A4) by danshen, which has been demonstrated in vitro. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, taking danshen with antihypertensive drugs might increase the risk of hypotension.
Animal research suggests that danshen can produce dose-dependent hypotensive effects. Furthermore, concomitant use with captopril appears to potentiate this effect.

Likelihood Possible Evidence D
Aspirin

Theoretically, danshen may increase the levels of aspirin and the risk of bleeding.
Research in healthy adult males shows that taking a combination of danshen and kudzu with aspirin increases plasma aspirin area under the curve by approximately 3.4-fold. Animal research also shows that taking a combination of danshen and kudzu (danshen-gegen formula) with aspirin increases maximal blood levels of aspirin and salicylic acid by approximately 4-fold and 3.7-fold, respectively, without impacting blood loss. Taking danshen increases the antiplatelet activity of aspirin and might increase the side effects of aspirin.

Likelihood Probable Evidence B
Clopidogrel (Plavix)

Theoretically, danshen may increase the risk of bleeding if taken with clopidogrel.
Clopidogrel is an antiplatelet prodrug that is metabolized by carboxyl esterase 1 (CES1) to an inactive metabolite. Animal research shows that a danshen combination formula decreases the activity of CES1, decreasing levels of the inactive metabolite in the blood and possibly increasing levels of the active metabolite. Animal research also suggests that taking a danshen combination formula with clopidogrel exhibits a synergistic increase in antiplatelet aggregation and prolongation of coagulation time when compared with either taken alone.

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

Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research shows that danshen tincture and various constituents of danshen inhibit the activity of CYP1A2. However, this activity has not been shown in humans when theophylline, a CYP1A2 substrate, was used as a target drug.

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

Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP2C9.
In vitro research shows that various constituents of danshen inhibit the activity of CYP2C9. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Cytochrome P450 2E1 (Cyp2E1) Substrates

Theoretically, danshen may increase the levels and clinical effects of drugs metabolized by CYP2E1.
In vitro research shows that various constituents of danshen inhibit the activity of CYP2E1. So far, this interaction has not been reported in humans.

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

Danshen might alter the levels and clinical effects of drugs metabolized by CYP3A4.
Preliminary clinical research in healthy males shows that the administration of danshen for 10-14 days induces intestinal CYP3A4 and increases the clearance of midazolam, a CYP3A4 substrate. The maximum concentration of midazolam was decreased by 31% to 67%, and drug levels were decreased by 27% to 80%. However, a single dose of danshen has the opposite effect, increasing maximum concentrations of midazolam by 87%.

Likelihood Possible Evidence B
Fexofenadine (Allegra)

Danshen might increase the levels and clinical effects of fexofenadine.
Pharmacokinetic research in healthy volunteers shows that taking danshen extract 1 gram three times daily for 10 days prior to receiving fexofenadine 60 mg increases peak levels of fexofenadine, a p-glycoprotein substrate, by 27.4% and area under the curve (AUC) by 37.2%.

Likelihood Probable Evidence B
Glucuronidated Drugs

Theoretically, danshen might affect the levels and clinical effects of drugs requiring glucuronidation.
In vitro research shows that danshen induces the expression of glucuronosyltransferases. However, it also inhibits the activity of glucuronosyltransferases, including various members of the 1A and 2B families. The extent of inhibition of a specific glucuronosyltransferase seems to be dependent on whether or not the danshen is processed via 'sweating'. This type of processing may affect the levels of constituents in danshen that alter glucuronosyltransferase activity. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Midazolam (Versed)

Danshen might alter the levels and clinical effects of midazolam.
Preliminary clinical research in healthy males shows that the administration of danshen for 10-14 days induces intestinal CYP3A4 and increases midazolam clearance. The maximum concentration was decreased by 31% to 67%, and drug levels were decreased by 27% to 80%. However, a single dose of danshen has the opposite effect, increasing maximum concentrations of midazolam by 87%.

Likelihood Probable Evidence B
P-Glycoprotein Substrates

Danshen might alter the levels of drugs cleared by p-glycoprotein.
Pharmacokinetic research in healthy volunteers suggests that danshen might affect p-glycoprotein activity. Taking danshen extract 1 gram three times daily for 10 days prior to receiving fexofenadine 60 mg increases peak levels of fexofenadine, a p-glycoprotein substrate, by 27.4% and area under the curve (AUC) by 37.2%.

Likelihood Possible Evidence B
Rosuvastatin (Crestor)

Theoretically, danshen might increase the levels and clinical effects of rosuvastatin.
Animal research shows that a single dose of danshen increases levels of rosuvastatin at least 2-fold, possibly by increasing absorption and/or decreasing elimination. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, danshen may increase the risk of bleeding if used with warfarin.
There have been several case reports of increased international normalized ratio (INR) after concomitant use of danshen and warfarin. Elevations in INR have occurred as early as 3-5 days after start of danshen. However, a clinical trial in adults taking warfarin with stable INR found that the addition of compound danshen dripping pills, containing danshen extract, Panax notoginseng, and borneol, 270 mg three times daily for 4 weeks did not alter INR levels or the average required warfarin dose when compared to baseline. These findings are consistent with animal research, which found no change in warfarin pharmacokinetics with the use of danshen. Other research in healthy adult males also shows that taking a combination of danshen and kudzu with warfarin does not increases plasma warfarin area under the curve, but may reduce plasma soluble thrombomodulin levels. However, other research shows that danshen might increase the rate of absorption and decrease the elimination rate of warfarin. Also, research in healthy adult males shows that taking a combination of danshen and kudzu with warfarin increases plasma area under the curve of danshensu, a constituent of danshen, by approximately 29.5-fold. Danshen should be used cautiously in patients taking warfarin.

Likelihood Possible Evidence B
Chinese Salvia full monograph & interactions

Chinese Skullcap12 drug types · 946 drugs

Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Antidiabetes Drugs

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

Likelihood Possible Evidence B
Antihypertensive Drugs

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

Likelihood Possible Evidence D
Antithyroid Drugs

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

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

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

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

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Possible Evidence D
Lithium

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

Likelihood Possible Evidence D
Alcohol (Ethanol)

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

Likelihood Unlikely Evidence D
Cns Depressants

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

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

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

Likelihood Possible Evidence B
P-Glycoprotein Substrates

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

Likelihood Possible Evidence D
Chinese Skullcap full monograph & interactions

Valerian6 drug types · 902 drugs

Alcohol (Ethanol)

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

Likelihood Possible Evidence B
Alprazolam (Xanax)

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

Likelihood Possible Evidence B
Cns Depressants

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

Likelihood Possible Evidence D
Glucuronidated Drugs

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

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

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

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

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

Likelihood Possible Evidence B
Valerian full monograph & interactions

Passionflower3 drug types · 836 drugs

Cns Depressants

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

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

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

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

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

Likelihood Possible Evidence D
Passionflower full monograph & interactions

White Peony7 drug types · 811 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, combining peony with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
In vitro research suggests that peony might have antiplatelet, anticoagulant, and antithrombotic effects.

Likelihood Possible Evidence D
Clozapine (Clozaril)

Theoretically, peony might increase the levels and clinical effects of clozapine.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on cytochromes P450 (CYP) 1A2 and CYP3A4. This effect has not been reported in humans.

Likelihood Possible Evidence D
Contraceptive Drugs

Theoretically, peony might interfere with contraceptive drugs due to competition for estrogen receptors.
In vitro and animal research shows that peony extract has estrogenic activity. Concomitant use might also increase the risk for estrogen-related adverse effects.

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

Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4. This effect has not been reported in humans.

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

Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4. This effect has not been reported in humans.

Likelihood Possible Evidence D
Estrogens

Theoretically, concomitant use of large amounts of peony might interfere with hormone replacement therapy and/or increase the risk for estrogen-related adverse effects.
In vitro and animal research shows that peony extract has estrogenic activity. Theoretically, peony might compete for estrogen receptors and/or cause additive estrogenic effects.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

Theoretically, peony might reduce the levels and clinical effects of phenytoin.
Animal research shows that taking peony root reduces levels of phenytoin. Some researchers suggest that peony root might affect cytochrome P450 (CYP) 2C9, which metabolizes phenytoin. However, preliminary research in humans shows that peony root does not alter levels of losartan (Cozaar), which is also metabolized by CYP2C9.

Likelihood Probable Evidence D
White Peony full monograph & interactions

Schizandra12 drug types · 803 drugs

Cyclophosphamide

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

Likelihood Probable Evidence D
Cyclosporine (Neoral, Sandimmune)

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

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

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

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

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

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

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

Likelihood Probable Evidence D
Midazolam (Versed)

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

Likelihood Probable Evidence B
P-Glycoprotein Substrates

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

Likelihood Possible Evidence D
Sirolimus (Rapamune)

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

Likelihood Probable Evidence B
Tacrolimus (Prograf)

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

Likelihood Probable Evidence B
Talinolol

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

Likelihood Probable Evidence B
Voriconazole (Vfend)

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

Likelihood Possible Evidence D
Warfarin (Coumadin)

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

Likelihood Possible Evidence D
Schizandra full monograph & interactions

Tangerine2 drug types · 643 drugs

Cytochrome P450 3A4 (Cyp3A4) Substrates

In vitro, tangeretin, a constituent of tangerine, induces a 52% increase in the metabolism of midazolam by cytochrome P450 3A4 (CYP3A4). This suggests that tangeretin may stimulate CYP3A4 activity. However, in humans, drinking tangerine juice 200 mL slightly delayed the absorption, but did not affect the metabolism, of midazolam, a CYP3A4 substrate. Theoretically, tangerine juice might increase CYP3A4 activity and decrease levels of drugs metabolized by this enzyme. However, this effect is unlikely.
Some drugs metabolized by CYP3A4 include amitriptyline (Elavil), amiodarone (Cordarone), citalopram (Celexa), felodipine (Plendil), lansoprazole (Prevacid), ondansetron (Zofran), prednisone (Deltasone, Orasone), sertraline (Zoloft), sibutramine (Meridia), and many others.

Likelihood Unlikely Evidence B
Midazolam (Versed)

In vitro, tangeretin, a constituent of tangerine, appears to increase the metabolism of midazolam in human liver microsomes by up to 52%. However, in humans, drinking tangerine juice 200 mL slightly delayed the absorption, but did not affect the metabolism, of midazolam. Theoretically, tangerine juice might increase the metabolism and reduce the effects of midazolam. However, this effect is unlikely.

Likelihood Unlikely Evidence B
Tangerine full monograph & interactions

Gotu Kola2 drug types · 579 drugs

Cns Depressants

Theoretically, taking gotu kola might increase the sedative effects of CNS depressants.
In vitro research suggests that gotu kola may have sedative effects via binding of GABA receptors.

Likelihood Possible Evidence D
Hepatotoxic Drugs

Theoretically, taking gotu kola with hepatotoxic drugs might have additive adverse effects.
There are at least four case reports of hepatotoxicity associated with the use of gotu kola. However, more information is needed to determine if gotu kola was the causative factor in these cases.

Likelihood Possible Evidence D
Gotu Kola full monograph & interactions

Lemon Balm2 drug types · 264 drugs

Cns Depressants

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

Likelihood Possible Evidence B
Thyroid Hormone

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

Likelihood Possible Evidence D
Lemon Balm full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Calm & Clear, from the product label.

Pacific BioLogic

See all Pacific BioLogic products
Name
Pacific BioLogic Co.
City
Concord
State
CA
ZipCode
94521
Phone Number
800 869-8783
Web Address
www.pacificbiologic.com
Pharmacist Counseling Corner

Calm & Clear by Pacific BioLogic: Common Questions

Does Calm & Clear by Pacific BioLogic interact with any medications?
Yes. Based on its ingredients, Calm & Clear has a known interaction with 1,566 medications, including 123 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Calm & Clear 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.
Is Calm & Clear safe to take during pregnancy or while breastfeeding?
The data advise against most of these ingredients during pregnancy and breastfeeding. Gotu kola is rated possibly safe in pregnancy but should be avoided while nursing. Valerian, white peony, passionflower, fo-ti, Chinese skullcap, and grass-leaf sweetflag are rated unsafe or likely unsafe in pregnancy; none have reliable breastfeeding data. Lemon balm is rated possibly unsafe in pregnancy and caution is advised while breastfeeding. Talk with your doctor or pharmacist for personalized advice if you're pregnant or nursing—this product is not recommended without professional guidance.
What are the most common side effects?
Most commonly, you might experience dizziness, drowsiness, nausea, or mild stomach upset. Valerian can cause headache and vivid dreams. Gotu kola may cause gastric irritation, and grass-leaf sweetflag can cause nausea and vomiting. These tend to be mild and occur in a small number of users, but drowsiness is the most likely with this blend given the sedative ingredients.
Can I take this product long-term?
Long-term safety is not well studied for most of these ingredients. Valerian should be tapered slowly rather than stopped suddenly after extended use to avoid withdrawal symptoms like anxiety and insomnia. Gotu kola and grass-leaf sweetflag are associated with rare cases of liver damage, which is a concern with prolonged use. Talk with your pharmacist about how long you plan to use this product.
Does Calm & Clear actually work for anxiety, stress, or sleep?
Some ingredients have research support: lemon balm is possibly effective for stress and depression, and valerian and passionflower are possibly effective for insomnia and anxiety before procedures. For the other herbs in this blend—gotu kola for anxiety, white peony, Chinese skullcap, fo-ti, danshen, and schisandra—we do not hold evidence establishing effectiveness for mood or sleep. Because the ingredients are in a proprietary blend, you don't know the actual dose of each, so effectiveness is harder to predict.
Why does this product have so many interactions with medications?
Many of these herbs affect how your liver breaks down drugs (through enzymes called cytochromes) or interfere with how your body absorbs them. Additionally, several ingredients are sedative, so they add to the drowsiness of sleep aids and anxiety medications. Chinese salvia and fo-ti also affect blood clotting. The more ingredients a product has, the more drug interactions are possible overall.
Is the Cellulose in this product a 'filler' I should worry about?
No. Cellulose is a standard binder used in capsules to hold the ingredients together—it's inert and plays no active role. It's a common, well-tolerated ingredient in supplements and medications.

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

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

Calm & Clear label
Go deeper

The Full Monographs Behind Calm & Clear’s Ingredients

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

Herb & supplement monograph

Gotu Kola

Interacts with 579 drugs

Gotu kola is a traditional Ayurvedic and Asian herb that people use for wound healing, circulation, skin problems, and as a calming or memory-supporting herb. Some early studies suggest poss...

Read the full Gotu Kola 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

Lemon Balm

Interacts with 264 drugs

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

Read the full Lemon Balm monograph → Herb & supplement monograph

Peony

Interacts with 811 drugs

Peony root is a traditional Chinese medicine herb often used for menstrual problems, cramps, and inflammation, frequently as part of combination formulas. Human evidence for most uses is lim...

Read the full Peony monograph → Herb & supplement monograph

Baikal Skullcap

Interacts with 946 drugs

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

Read the full Baikal Skullcap monograph → Herb & supplement monograph

Passion Flower

Interacts with 836 drugs

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

Read the full Passion Flower monograph → Herb & supplement monograph

Fo-ti

Interacts with 1,257 drugs

Fo-ti (He Shou Wu) is a root used in traditional Chinese medicine, often promoted for healthy aging and hair. High-quality human evidence for these benefits is limited, and processed Fo-ti h...

Read the full Fo-ti monograph → Herb & supplement monograph

Danshen

Interacts with 1,059 drugs

Danshen is a root used in traditional Chinese medicine, mainly for heart and circulation problems. Some early research is promising, but the evidence is not strong enough to confirm it works...

Read the full Danshen monograph → Herb & supplement monograph

Calamus

Interacts with 1,117 drugs

Calamus is a swamp plant with a long history in Ayurvedic and traditional Chinese medicine, mostly for digestive and nervous-system complaints. However, it contains beta-asarone, a compound...

Read the full Calamus monograph → Herb & supplement monograph

Tangerine

Interacts with 643 drugs

Tangerine is a sweet citrus fruit that is a good source of vitamin C and other nutrients, and is widely enjoyed as food. While the peel and essential oil are used in traditional medicine and...

Read the full Tangerine monograph → Herb & supplement monograph

Schisandra

Interacts with 803 drugs

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

Read the full Schisandra monograph →
Sources

Sources & How We Checked

Calm & Clear'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 233 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.

Gotu Kola 18 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. Pointel JP, Boccalon H, Cloarec M, et al. Titrated extract of Centella asiatica (TECA) in the treatment of venous insufficiency of the lower limbs. Angiol 1987;38:46-50. PubMed
  3. Brinkhaus B, Lindner M, Schuppan D, Hahn EG. Chemical, pharmacological and clinical profile of the east Asian medical plant Centella asiatica. Phytomedicine 2000;7:427-48.
  4. Eun HC, Lee AY. Contact dermatitis due to madecassol. Contact Dermatitis 1985;13:310-3.. PubMed
  5. Hausen BM. Centella asiatica (Indian pennywort), an effective therapeutic but a weak sensitizer. Contact Dermatitis 1993;29:175-9..
  6. Bilbao I, Aguirre A, Zabala R, et al. Allergic contact dermatitis from butoxyethyl nicotinic acid and Centella asiatica extract. Contact Dermatitis 1995;33:435-6.
  7. Cesarone MR, Incandela L, De Sanctis MT, et al. Evaluation of treatment of diabetic microangiopathy with total triterpenic fraction of Centella asiatica: a clinical prospective randomized trial with a microcirculatory model. Angiology 2001;52 Suppl 2 DOI
  8. Bradwejn J, Zhou Y, Koszycki D, Shlik J. A double-blind, placebo-controlled study on the effects of Gotu Kola (Centella asiatica) on acoustic startle response in healthy subjects. J Clin Psychopharmacol 2000;20:680-4. PubMed
  9. Young GL, Jewell D. Creams for preventing stretch marks in pregnancy. Cochrane Database Syst Rev 2000;(2):CD000066. PubMed
  10. Jorge OA, Jorge AD. Hepatotoxicity associated with the ingestion of Centella asiatica. Rev Esp Enferm Dig 2005;97:115-24. PubMed
  11. Mallol J, Belda MA, Costa D, et al. Prophylaxis of striae gravidarum with a topical formulation. A double blind trial. Int J Cosmet Sci 1991;3:51-7.
  12. Izu, R., Aguirre, A., Gil, N., and Diaz-Perez, J. L. Allergic contact dermatitis from a cream containing Centella asiatica extract. Contact Dermatitis 1992;26(3):192-193.
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Lemon Balm 12 references
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Schisandra 26 references
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DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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