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Dietary supplement

Lysine Extra Ingredients & Drug Interactions

by Vitanica

Lysine Extra label
See full label image
Capsule Category: Botanical With Nutrients
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 Lysine Extra 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

Lysine Extra is a dietary supplement by Vitanica with 9 active ingredients. Its ingredients are commonly taken for cold sores (herpes labialis), genital herpes outbreaks, supporting protein and collagen formation.Based on those ingredients, 1,570 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Oregon Grape, St. John's wort aerial parts extract, Lemon Balm Leaf, Stem 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 Lysine Extra by Vitanica

Ask about any prescription or over-the-counter medication and we check it for interactions with Lysine Extra by Vitanica — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Lysine Extra by Vitanica

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

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 9 of its 9 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

Lysine Extra contains 9 active ingredients. The primary ingredient is L-lysine hydrochloride, an amino acid used for cold sores.

It also includes calcium for bone and metabolic health, vitamin C for immune support, astragalus (an herb traditionally used in Chinese medicine), myrrh (a resinous plant extract), Oregon grape (containing the alkaloid berberine), zinc for immune function and wound healing, St. John's wort (an herbal extract for mood support), and lemon balm leaf and stem extract.

The product also contains inactive ingredients—hydroxypropylmethylcellulose, water, and L-leucine—which serve as binders and capsule material.

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: immune support with lysine benefits.
  • We looked for evidence on: Anxiety, Atopic dermatitis (eczema), Acute bronchitis, Chronic bronchitis, Cold sores, Genital herpes — and 2 related terms.
  • The strongest evidence on file: Lysine is rated "Possibly Effective" for Herpes labialis (cold sores) (Natural Medicines).
  • Also on file: Lemon Balm is rated "Possibly Effective" for Herpes labialis (cold sores).
  • Also on file: Zinc is rated "Possibly Effective" for Herpes labialis (cold sores).

L-lysine is possibly effective for cold sores (herpes labialis) based on clinical evidence. For other uses like child growth, pressure ulcers, and diabetic foot ulcers, evidence is insufficient to rate.

Calcium is effective for kidney failure, dyspepsia, and hypocalcemia, and likely effective for osteoporosis. Vitamin C is effective for vitamin C deficiency and possibly effective for anemia of chronic disease, atrial fibrillation, cataracts, and exercise-induced respiratory infections.

For the other herbs—astragalus, myrrh, Oregon grape, zinc, St. John's wort, and lemon balm—the evidence we hold is insufficient to rate most conditions, though St.

John's wort is likely effective for depression, and Oregon grape is possibly effective for psoriasis. Zinc is effective for zinc deficiency and likely effective for Wilson disease, and possibly effective for acne and age-related macular degeneration.

The evidence, ingredient by ingredient Lysine Calcium Vitamin C Astragalus Myrrh Oregon Grape Zinc St. John's Wort

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 9 of the 9 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 9 of 9.
  • General safety write-ups exist for 9 of 9.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

The product is generally well tolerated at typical doses. L-lysine may cause abdominal pain, diarrhea, or stomach upset at high amounts; supplement safety in pregnancy is not well studied, and there is not enough data on breastfeeding use.

Calcium is generally safe at recommended amounts and is likely safe in pregnancy and during breastfeeding within those amounts, though very high doses can cause problems including rare kidney stones and calciphylaxis. Vitamin C is generally safe at normal dietary doses but can cause abdominal cramps, heartburn, diarrhea, and nausea at very high doses (above 2 grams daily); normal amounts in pregnancy are fine, but high-dose supplements should be avoided unless your doctor advises.

Astragalus is well tolerated short-term but should be avoided in pregnancy and breastfeeding due to insufficient safety data. Myrrh traditionally stimulates the uterus and should not be used in pregnancy; safety data for breastfeeding is lacking.

Oregon grape should be avoided in pregnancy and breastfeeding. Zinc is generally safe in recommended amounts but can cause metallic taste, nausea, and diarrhea; high doses may increase copper deficiency risk.

St. John's wort can cause sun sensitivity (photodermatitis) and has rare reports of mood changes including psychosis; it should be avoided in pregnancy and breastfeeding.

Lemon balm is generally well tolerated short-term and should be avoided in pregnancy unless advised by your doctor; caution is advised while breastfeeding.

Side effects, ingredient by ingredient Lysine Calcium Vitamin C Astragalus Myrrh Oregon Grape Zinc St. John's Wort

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?
  • 9 of the 9 matched ingredients can interact with medications — Lysine, St. John's Wort, Lemon Balm, Oregon Grape, Myrrh, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; cancer treatments; diabetes medications; heart-rhythm medications; lithium.
  • For scale: 1,571 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 this product, check with your pharmacist if you take any of the following: St. John's wort affects digoxin, seizure medications (phenobarbital, phenytoin, mephenytoin), cancer drugs (irinotecan, docetaxel), HIV protease inhibitors, or tacrolimus—all at Major severity.

Calcium reduces HIV integrase inhibitors (dolutegravir, elvitegravir) and cannot be given intravenously with ceftriaxone. Several ingredients have Moderate interactions with blood thinners (warfarin), antidiabetes drugs, antibiotics (quinolones, tetracyclines, cephalexin), levothyroxine, blood pressure drugs, chemotherapy agents, and HIV medications.

Oregon grape and zinc inhibit drug-metabolizing enzymes and may raise levels of many prescription drugs. No interactions are documented for lemon balm with respect to the ingredients we could fully check, but interactions cannot be ruled out.

Search your medications on this page.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with some supporting evidence for its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

Lysine Extra may help with cold sores and provides calcium, vitamin C, and zinc, which have established roles in various health areas. However, this product contains St.

John's wort and multiple other ingredients with serious interactions—particularly with HIV medications, seizure drugs, heart drugs, chemotherapy, and immunosuppressants—and you should not take it without checking your specific medications first. If you're on any prescription drug, especially for seizures, heart rhythm, HIV, cancer, or immune suppression, talk to your pharmacist before starting.

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

Assessment coverage: 9 of 9 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Feb 22, 2024.

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

At a glance

General information

Key facts about Lysine Extra, straight from the product label.

Brand Vitanica
Barcode (UPC) 708118020308
Net contents 60 Vegetarian Capsule(s)
Market status On market
Date entered into DSLD Feb 22, 2024
DSLD ID 302795
Product type Botanical With Nutrients
Supplement form Capsule
Dietary claims / uses Nutrient, All Other, Structure/Function
Intended target group(s) Vegan, Vegetarian, Adult (18 - 50 Years), Women (not pregnant or lactating), Gluten Free, Dairy Free
From the label
Everything in this section is reproduced from the manufacturer’s own product label — it’s the label speaking, not HelloPharmacist. We show it so you can see exactly what the maker states; we don’t verify or endorse those statements.

Supplement Facts

The label details for Lysine Extra by Vitanica, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
2 Capsule(s)
Maximum serving Sizes:
2 Capsule(s)
Servings per container
30
UPC/BARCODE
708118020308
IngredientAmount% DV
L-Lysine Hydrochloride800 mg--
Calcium4 mg--
Vitamin C40 mg67%
Astragalus110 mg--
Myrrh50 mg--
Oregon Grape110 mg--
Zinc30 mg200%
St. John's wort aerial parts extract120 mg--
Lemon Balm Leaf, Stem Extract110 mg--

Other ingredients: Hydroxypropylmethylcellulose, Water, L-Leucine

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

Formulated by Dr. Tori Hudson, a Naturopathic Physician specializing in women's natural health.

Actual Size

Formulated by Dr. Tori Hudson

Formula

Lysine Extra provides botanicals and nutrients for immune support with the benefits of lysine.

Suggested/Recommended/Usage/Directions

Suggested Use: Maintenance support - Two (2) capsules per day. Temporary support - Two (2) capsules, two to three times per day for up to 10 days. Also suitable for men.

Precautions

Avoid use of this product during pregnancy and while nursing. Consult your health care practitioner if taking Coumadin or anti-coagulant/anti-platelet agents.

Tamper resistant: please do not use if safety seal is broken or missing.

Keep in a cool, dry place out of reach of children.

Formulation

This product contains no: preservatives, binders, artificial colorings or flavorings, lactose, salt, wheat, gluten, soybeans, milk derivatives, eggs, peanuts, tree nuts, fish or shellfish.

Membrane Immune Support

Lysine Extra is suitable for vegetarians and vegans.

Storage

Keep in a cool, dry place out of reach of children.

FDA Statement of Identity

Dietary Supplement

FDA Disclaimer Statement

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

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

See for yourself

Lysine Extra by Vitanica label

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

Lysine Extra 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 Lysine Extra by Vitanica

These are the 9 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Capsule(s) Dosage formCapsule Servings per container30 Amounts shown are per serving.

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

L-Lysine Hydrochloride

Interacts with
1 drug
800 mg per serving

Lysine is an essential amino acid your body cannot make on its own, so it must come from food or supplements. People most often take extra lysine to t...

L-Lysine Hydrochloride monograph & interactions

Calcium

Interacts with
168 drugs
4 mg per serving Form: Calcium Ascorbate

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

Calcium monograph & interactions

Vitamin C

Interacts with
207 drugs
40 mg per serving Form: Calcium Ascorbate

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for im...

Vitamin C monograph & interactions

Astragalus

Interacts with
208 drugs
110 mg per serving

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

Astragalus monograph & interactions

Myrrh

Interacts with
88 drugs
50 mg per serving

Myrrh is a fragrant gum resin from Commiphora trees that has long been used in mouthwashes, throat remedies, and skin care. Modern evidence for most o...

Myrrh monograph & interactions

Oregon Grape

Interacts with
1,218 drugs
110 mg per serving

Oregon grape is a shrub whose root contains berberine and related compounds. The strongest (though still modest) evidence is for topical creams that m...

Oregon Grape monograph & interactions

Zinc

Interacts with
67 drugs
30 mg per serving Form: L-Methionine

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

Zinc monograph & interactions

St. John's wort aerial parts extract

Interacts with
1,143 drugs
120 mg per serving

St. John's wort is a well-studied herb most often used for mild to moderate depression, and some research suggests it may help with this. However, it...

St. John's wort aerial parts extract monograph & interactions

Lemon Balm Leaf, Stem Extract

Interacts with
264 drugs
110 mg per serving Form: Melissa officinalis Leaf Extract, Melissa officinalis Stem Extract

Lemon balm is a gentle, lemon-scented mint-family herb traditionally used to ease stress, support sleep, and calm digestion, and topically for cold so...

Lemon Balm Leaf, Stem Extract monograph & interactions

Other (inactive) ingredients: Hydroxypropylmethylcellulose, Water, L-Leucine. These complete the product’s ingredient list but are not active constituents.

Interaction report

Lysine Extra by Vitanica Drug Interactions

Want to check YOUR meds against Lysine Extra?

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
1,570Drugs
756 Major 810 Moderate 4 Minor

Ingredients driving the most interactions

Oregon Grape 1,218
St. John's wort aerial parts extract 1,143
Lemon Balm Leaf, Stem Extract 264
Astragalus 208
Vitamin C 207

Individual Drug Interactions

The ingredients in Lysine Extra interact with 1,570 drugs. Click any drug to see the details.

9 of the 9 ingredients in Lysine Extra interact with drugs. Each result below shows which ingredient is responsible. Oregon Grape St. John's wort aerial parts extract Lemon Balm Leaf, Stem Extract Astragalus Vitamin C Calcium Myrrh Zinc L-Lysine Hydrochloride

Each ingredient & the kinds of drugs it affects

For each ingredient in Lysine Extra 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.

Oregon Grape9 drug types · 1,218 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, Oregon grape might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.
In vitro and in vivo research suggests that berberine, a constituent of Oregon grape, can inhibit platelet aggregation.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, Oregon grape might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Clinical research suggests that berberine, a constituent of Oregon grape, can lower blood glucose levels.

Likelihood Possible Evidence A
Antihypertensive Drugs

Theoretically, Oregon grape might increase the risk of hypotension when taken with antihypertensive drugs.
Animal research suggests that berberine, a constituent of Oregon grape, can have hypotensive effects. Also, an analysis of clinical evidence suggests that taking berberine in combination with amlodipine (Norvasc) can lower systolic and diastolic blood pressure when compared with taking amlodipine alone.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, Oregon grape might increase the sedative effects of CNS depressants.
Animal research suggests that berberine, a constituent of Oregon grape, can have sedative effects.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, Oregon grape might increase the effects and adverse effects of cyclosporine.
Berberine, a constituent of Oregon grape, can reduce metabolism of cyclosporine and increase serum levels. It might inhibit cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine.

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

Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP2C9.
Preliminary clinical evidence suggests that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2C9 (CYP2C9).

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

Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP2D6.
In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, can inhibit cytochrome P450 2D6 (CYP2D6).

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

Theoretically, Oregon grape might increase serum levels of drugs metabolized by CYP3A4.
In vitro research and preliminary clinical evidence suggest that berberine, a constituent of Oregon grape, moderately inhibits cytochrome P450 3A4 (CYP3A4).

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, Oregon grape might increase serum levels of drugs that are P-glycoprotein (P-gp) substrates.
In vitro research suggests that Oregon grape extracts inhibit P-gp efflux.

Likelihood Possible Evidence D
Oregon Grape full monograph & interactions

St. John's wort aerial parts extract47 drug types · 1,143 drugs

Alprazolam (Xanax)

St. John's wort increases the clearance of alprazolam and decreases its effects.
Alprazolam, which is used as a probe for cytochrome P450 3A4 (CYP3A4) activity, has a two-fold increase in clearance when given with St. John's wort. St. John's wort reduces the half-life of alprazolam from 12.4 hours to 6 hours.

Likelihood Likely Evidence B
Contraceptive Drugs

St. John's wort increases the clearance of contraceptive drugs and reduces their clinical effects.
Females taking St. John's wort and oral contraceptives concurrently should use an additional or alternative form of birth control. St. John's wort can decrease norethindrone and ethinyl estradiol levels by 13% to 15%, resulting in breakthrough bleeding, irregular menstrual bleeding, or unplanned pregnancy. Bleeding irregularities usually occur within a week of starting St. John's wort and regular cycles usually return when St. John's wort is discontinued. Unplanned pregnancy has occurred with concurrent use of oral contraceptives and St. John's wort extract. St. John's wort is thought to induce the cytochrome P450 1A2 (CYP1A2), 2C9 (CYP2C9), and 3A4 (CYP3A4) enzymes, which are responsible for metabolism of progestins and estrogens in contraceptives.

Likelihood Probable Evidence B
Cyclosporine (Neoral, Sandimmune)

St. John's wort reduces the levels and clinical effects of cyclosporine.
Concomitant use can decrease plasma cyclosporine levels by 30% to 70%. Using St. John's wort with cyclosporine in patients with heart, kidney, or liver transplants can cause subtherapeutic cyclosporine levels and acute transplant rejection. This interaction has occurred with a St. John's wort extract standardized to 0.3% hypericin and dosed at 300-600 mg per day. Withdrawal of St. John's wort can result in a 64% increase in cyclosporine levels. St. John's wort induces cytochrome P450 3A4 (CYP3A4) and the multi-drug transporter, P-glycoprotein/MDR-1, which increases cyclosporine clearance.

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

St. John's wort increases the metabolism and reduces the levels of CYP3A4 substrates.
St. John's wort induces CYP3A4 enzymes and increases metabolism of CYP3A4 substrates. Clinically significant interactions have been reported with St. John's wort products containing hyperforin 1 mg or more.

Likelihood Probable Evidence B
Digoxin (Lanoxin)

St. John's wort reduces the levels and clinical effects of digoxin.
St. John's wort can reduce the bioavailability, serum levels, and therapeutic effects of digoxin. Taking an extract of St. John's wort 900 mg, containing hyperforin 7.5 mg or more, daily for 10-14 days, can reduce serum digoxin levels by 25% in healthy people. St. John's wort is thought to affect the multidrug transporter, P-glycoprotein, which mediates the absorption and elimination of digoxin and other drugs. St. John's wort products providing less than 7.5 mg of hyperforin daily do not appear to affect digoxin levels.

Likelihood Likely Evidence B
Docetaxel (Taxotere)

St. John's wort reduces the levels and clinical effects of docetaxel.
Clinical research shows that taking a specific St. John's wort product (Hyperiplant, VSM) 300 mg three times daily for 14 days increases docetaxel clearance by about 14%, resulting in decreased plasma concentrations of docetaxel in cancer patients. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort.

Likelihood Probable Evidence B
Imatinib (Gleevec)

St. John's wort reduces the levels and clinical effects of imatinib.
Taking St. John's wort 900 mg daily for 2 weeks reduces the bioavailability and half-life of a single dose of imatinib and decreases its serum levels by 30% in healthy volunteers. This is most likely due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort, which increases clearance of imatinib.

Likelihood Likely Evidence A
Irinotecan (Camptosar)

St. John's wort reduces the levels and clinical effects of irinotecan.
St. John's wort 900 mg daily for 18 days decreases serum levels of irinotecan by at least 50%. Clearance of the active metabolite of irinotecan, SN-38, is also increased, resulting in a 42% decrease in the area under the concentration-time curve. This is thought to be due to induction of cytochrome P450 3A4 (CYP3A4) by St. John's wort.

Likelihood Likely Evidence A
Mephenytoin (Mesantoin)

St. John's wort reduces the levels and clinical effects of mephenytoin.
Preliminary clinical research in healthy males shows that taking St. John's wort for 14 days induces cytochrome P450 2C19 (CYP2C19) and significantly increases metabolism of mephenytoin (Mesantoin). In people with wild-type 2C19, metabolism was almost 4-fold greater in subjects who received St. John's wort compared to placebo. In contrast, patients with 2C19*2/*2 and *2/*3 genotypes did not demonstrate a similar increase in metabolism.

Likelihood Likely Evidence B
Non-Nucleoside Reverse Transcriptase Inhibitors (Nnrtis)

St. John's wort decreases the levels and clinical effects of NNRTIs.
St. John's wort increases the oral clearance of nevirapine (Viramune) by 35%. Subtherapeutic concentrations are associated with therapeutic failure, development of viral resistance, and development of drug class resistance. St. John's wort induces intestinal and hepatic cytochrome P450 3A4 (CYP3A4) and intestinal P-glycoprotein/MDR-1, a drug transporter.

Likelihood Likely Evidence B
Omeprazole (Prilosec)

St. John's wort decreases the levels and clinical effects of omeprazole.
Taking St. John's wort, 300 mg orally three times daily for 14 days, reduces serum concentrations of omeprazole by inducing its metabolism via cytochrome P450 (CYP) 2C19 and 3A4. The reduction of omeprazole serum levels is dependent on CYP2C19 genotype, with reductions up to 50% in extensive metabolizers and 38% in poor metabolizers.

Likelihood Likely Evidence B
Oxycodone (Oxycontin)

St. John's wort decreases the levels and clinical effects of oxycodone.
St. John's wort can increase oxycodone metabolism by inducing cytochrome P450 3A4 (CYP3A4), reducing plasma levels and analgesic activity.

Likelihood Probable Evidence B
P-Glycoprotein Substrates

St. John's wort decreases the levels and clinical effects of P-glycoprotein substrates.
St. John's wort induces P-glycoprotein. P-glycoprotein is a carrier mechanism responsible for transporting drugs and other substances across cell membranes. When P-glycoprotein is induced in the gastrointestinal (GI) tract, it can prevent the absorption of some medications. In addition, induction of p-glycoprotein can decrease entry of drugs into the central nervous system (CNS) and decrease access to other sites of action.

Likelihood Probable Evidence B
Phenobarbital (Luminal)

St. John's wort decreases the levels and clinical effects of phenobarbital.
St. John's wort may increase the metabolism of phenobarbital. Plasma concentrations of phenobarbital should be monitored carefully. The dose of phenobarbital may need to be increased when St. John's wort is started and decreased when it is stopped.

Likelihood Likely Evidence B
Phenprocoumon (Marcoumar, Others)

St. John's wort decreases the levels and clinical effects of phenprocoumon.
St. John's wort appears to increase the metabolism of phenprocoumon (an anticoagulant that is not available in the US) by increasing the activity of the cytochrome P450 2C9 (CYP2C9) enzyme. This may result in decreases in the anticoagulant effect and international normalized ratio (INR).

Likelihood Likely Evidence B
Phenytoin (Dilantin)

St. John's wort decreases the levels and clinical effects of phenytoin.
St. John's wort may increase the metabolism of phenytoin. Plasma concentrations of phenytoin should be monitored closely. The dose of phenytoin may need to be increased when St. John's wort is started and decreased when it is stopped.

Likelihood Likely Evidence B
Protease Inhibitors (Pis)

St. John's wort reduces the levels and clinical effects of PIs.
In healthy volunteers, St. John's wort can reduce the plasma concentrations of indinavir (Crixivan) by inducing cytochrome P450 3A4 (CYP3A4). This might result in treatment failure and viral resistance. St. John's wort also induces P-glycoprotein, which can result in decreased intracellular protease inhibitor concentrations and increased elimination.

Likelihood Likely Evidence B
Rivaroxaban (Xarelto)

St. John's wort decreases the levels and clinical effects of rivaroxaban.
A small pharmacokinetic study in healthy volunteers shows that taking a single dose of rivaroxaban 20 mg after using a specific St. John's wort extract (Jarsin, Vifor SA) 450 mg orally twice daily for 14 days reduces the bioavailability of rivaroxaban by 24% and reduces rivaroxaban's therapeutic inhibition of factor Xa by 20%.

Likelihood Probable Evidence B
Tacrolimus (Prograf)

St. John's wort decreases the levels and clinical effects of tacrolimus.
Taking a St. John's wort extract (Jarsin) 600 mg daily significantly decreases tacrolimus serum levels. Dose increases of 60% may be required to maintain therapeutic tacrolimus levels in patients taking St. John's wort. St. John's wort is thought to lower tacrolimus levels by inducing cytochrome P450 3A4 (CYP3A4) enzymes. A small clinical study in healthy adults also shows that taking St. John's wort 300 mg three times daily for 10 days decreases the total systemic exposure to tacrolimus by 27% and 33% after taking a single 5 mg dose of immediate-release or prolonged-release tacrolimus, respectively.

Likelihood Likely Evidence B
Warfarin (Coumadin)

St. John's wort decreases the levels and clinical effects of warfarin.
Taking St. John's wort significantly increases clearance of warfarin, including both its R- and S-isomers. This is likely due to induction of cytochrome P450 (CYP) 1A2 and CYP3A4. St. John's wort can also significantly decrease International Normalized Ratio (INR) in people taking warfarin. In addition, taking warfarin at the same time as St. John's wort might reduce warfarin bioavailability. When a dried extract is mixed with warfarin in an aqueous medium, up to 30% of warfarin is bound to particles, reducing its absorption.

Likelihood Likely Evidence B
Aminolevulinic Acid

St. John's wort might have additive phototoxic effects with aminolevulinic acid.
Concomitant use with St. John's wort extract may cause synergistic phototoxicity. Delta-aminolevulinic acid can cause a burning erythematous rash and severe swelling of the face, neck, and hands when taken with St. John's wort.

Likelihood Possible Evidence D
Bupropion (Wellbutrin)

St. John's wort might reduce the levels and effects of bupropion.
Clinical research shows that taking St. John's wort 325 mg three times daily for 14 days along with bupropion reduces the area under the concentration-time curve by approximately 14% and increases the clearance of bupropion by approximately 20%. This effect is attributed to the induction of cytochrome P450 2B6 (CYP2B6) by St. John's wort.

Likelihood Probable Evidence B
Clopidogrel (Plavix)

St. John's wort might increase the levels and effects of clopidogrel.
Taking St. John's wort with clopidogrel seems to increase the activity of clopidogrel. In clopidogrel non-responders, taking St. John's wort seems to induce metabolism of clopidogrel to its active metabolite by cytochrome P450 enzymes 3A4 and 2C19. This leads to increased antiplatelet activity. Theoretically, this might lead to an increased risk of bleeding in clopidogrel responders.

Likelihood Possible Evidence B
Clozapine (Clozaril)

St. John's wort might decrease the levels and clinical effects of clozapine.
A case report describes a female with schizophrenia controlled on clozapine who had a return of symptoms when she started taking St. John's wort. The plasma concentration of clozapine was reduced, likely because its clearance was increased due to induction of the cytochrome P450 enzymes 3A4, 1A2, 2C9, and 2C19 by St. John's wort.

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

St. John's wort may increase the metabolism and reduce the levels of CYP1A2 substrates.
Clinical and in vitro research shows that St. John's wort induces CYP1A2, but to a lesser extent than CYP3A4.

Likelihood Possible Evidence B
St. John's wort aerial parts extract full monograph & all 47 interactions

Lemon Balm Leaf, Stem Extract2 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 Leaf, Stem Extract full monograph & interactions

Astragalus4 drug types · 208 drugs

Antidiabetes Drugs

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

Likelihood Probable Evidence A
Cyclophosphamide

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

Likelihood Possible Evidence D
Immunosuppressants

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

Likelihood Possible Evidence D
Lithium

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

Likelihood Probable Evidence D
Astragalus full monograph & interactions

Vitamin C13 drug types · 207 drugs

Alkylating Agents

Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Aluminum

Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.
Research in animals and humans shows that vitamin C increases aluminum absorption, theoretically by chelating aluminum and keeping it in solution where it is available for absorption. In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely. Patients with renal failure who take aluminum-containing compounds such as phosphate binders should avoid vitamin C supplements in doses above the recommended dietary allowances.

Likelihood Probable Evidence B
Antitumor Antibiotics

Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as doxorubicin. In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells. More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.

Likelihood Possible Evidence D
Estrogens

Vitamin C might increase blood levels of estrogens.
Increases in plasma estrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products. It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall. When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. Increases in plasma estrogen levels may occur when patients who are deficient in vitamin C take supplements. Monitor these patients for estrogen-related side effects.

Likelihood Probable Evidence B
Fluphenazine (Prolixin)

Theoretically, vitamin C might decrease levels of fluphenazine.
In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started. The mechanism is not known, and there is no further data to confirm this interaction.

Likelihood Possible Evidence D
Indinavir (Crixivan)

Vitamin C can modestly reduce indinavir levels.
One pharmacokinetic study shows that taking vitamin C 1 gram orally once daily along with indinavir 800 mg orally three times daily reduces the area under the concentration-time curve of indinavir by 14%. The mechanism of this interaction is unknown, but it is unlikely to be clinically significant in most patients. The effect of higher doses of vitamin C on indinavir levels is unknown.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Vitamin C can increase levothyroxine absorption.
Two clinical studies in adults with poorly controlled hypothyroidism show that swallowing levothyroxine with a glass of water containing vitamin C 500-1000 mg in solution reduces thyroid stimulating hormone (TSH) levels and increases thyroxine (T4) levels when compared with taking levothyroxine alone. This suggests that vitamin C increases the oral absorption of levothyroxine, possibly due to a reduction in pH.

Likelihood Probable Evidence B
Warfarin (Coumadin)

High-dose vitamin C might reduce the levels and effectiveness of warfarin.
Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption. There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time. Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant. However, a case of warfarin resistance has been reported for a patient who took vitamin C 500 mg twice daily. Cessation of vitamin C supplementation resulted in a rapid increase in international normalized ratio (INR). Tell patients taking warfarin to avoid taking vitamin C in excessively high doses (greater than 10 grams daily). Lower doses may be safe, but the anticoagulation activity of warfarin should be monitored. Patients who are stabilized on warfarin while taking vitamin C should avoid adjusting vitamin C dosage to prevent the possibility of warfarin resistance.

Likelihood Possible Evidence D
Acetaminophen (Tylenol, Others)

High-dose vitamin C might slightly prolong the clearance of acetaminophen.
A small pharmacokinetic study in healthy volunteers shows that taking high-dose vitamin C (3 grams) 1.5 hours after taking acetaminophen 1 gram slightly increases the apparent half-life of acetaminophen from around 2.3 hours to 3.1 hours. Ascorbic acid competitively inhibits sulfate conjugation of acetaminophen. However, to compensate, elimination of acetaminophen glucuronide and unconjugated acetaminophen increases. This effect is not likely to be clinically significant.

Likelihood Probable Evidence B
Aspirin

Acidification of the urine by vitamin C might increase aspirin levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction is not clinically significant.

Likelihood Possible Evidence B
Choline Magnesium Trisalicylate (Trilisate)

Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B
Niacin

Vitamin C might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease. It is not known whether this adverse effect is due to a single antioxidant such as vitamin C, or to the combination. It also is not known whether it will occur in other patient populations.

Likelihood Possible Evidence A
Salsalate (Disalcid)

Acidification of the urine by vitamin C might increase salsalate levels.
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels. However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion, suggesting this interaction probably is not clinically significant.

Likelihood Possible Evidence B
Vitamin C full monograph & interactions

Calcium18 drug types · 168 drugs

Ceftriaxone (Rocephin)

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

Likelihood Probable Evidence D
Dolutegravir (Tivicay)

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

Likelihood Probable Evidence B
Elvitegravir (Vitekta)

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

Likelihood Probable Evidence B
Aluminum

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

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

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

Likelihood Probable Evidence D
Bisphosphonates

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

Likelihood Probable Evidence C
Calcipotriene (Dovonex)

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

Likelihood Possible Evidence B
Digoxin (Lanoxin)

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

Likelihood Possible Evidence B
Diltiazem (Cardizem, Others)

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

Likelihood Probable Evidence D
Levothyroxine (Synthroid, Others)

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

Likelihood Probable Evidence B
Lithium

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

Likelihood Possible Evidence B
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Raltegravir (Isentress)

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

Likelihood Possible Evidence B
Sotalol (Betapace)

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

Likelihood Possible Evidence B
Tetracycline Antibiotics

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

Likelihood Probable Evidence C
Thiazide Diuretics

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

Likelihood Probable Evidence C
Verapamil (Calan, Others)

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

Likelihood Probable Evidence D
Calcium Channel Blockers

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

Likelihood Unlikely Evidence D
Calcium full monograph & interactions

Myrrh2 drug types · 88 drugs

Antidiabetes Drugs

Theoretically, myrrh might increase the risk of hypoglycemia when taken with antidiabetes drugs.
In vitro and animal research suggests that myrrh has hypoglycemic effects.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, myrrh might decrease the effectiveness of warfarin.
In one case, a patient who was previously stable on warfarin had a significant decline in international normalized ratio (INR) following consumption of an aqueous extract of myrrh.

Likelihood Possible Evidence D
Myrrh full monograph & interactions

Zinc10 drug types · 67 drugs

Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

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

Likelihood Probable Evidence D
Cephalexin (Keflex)

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

Likelihood Probable Evidence B
Cisplatin (Platinol-Aq)

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

Likelihood Possible Evidence D
Integrase Inhibitors

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

Likelihood Possible Evidence D
Penicillamine (Cuprimine, Depen)

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

Likelihood Probable Evidence B
Quinolone Antibiotics

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

Likelihood Probable Evidence B
Ritonavir (Norvir)

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

Likelihood Probable Evidence B
Tetracycline Antibiotics

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

Likelihood Probable Evidence B
Amiloride (Midamor)

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

Likelihood Probable Evidence B
Atazanavir (Reyataz)

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

Likelihood Probable Evidence B
Zinc full monograph & interactions

L-Lysine Hydrochloride1 drug type · 1 drug

5-Ht4 Agonists

Theoretically, lysine may reduce the effects of 5-HT4 agonists.
Animal research suggests that L-lysine is a partial serotonin receptor 4 (5-HT4) antagonist and inhibits diarrhea induced by the 5-HT4 agonist, 5-hydroxytryptophane.

Likelihood Unlikely Evidence D
L-Lysine Hydrochloride full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Lysine Extra, from the product label.

Vitanica

See all Vitanica products
Name
Vitanica
Street Address
12401 SW Leveton Dr.
City
Tualatin
State
OR
ZipCode
97062
Web Address
www.vitanica.com
Pharmacist Counseling Corner

Lysine Extra by Vitanica: Common Questions

Does Lysine Extra by Vitanica interact with any medications?
Yes. Based on its ingredients, Lysine Extra has a known interaction with 1,570 medications, including 756 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Lysine Extra contains 9 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.
Will this help prevent or treat cold sores?
L-lysine is possibly effective for cold sores based on clinical evidence. It may help if you're prone to them, but it's not a guaranteed cure. Talk to your pharmacist about how much to take and when to start if you feel one coming on.
Can I take this if I'm on birth control or hormone replacement therapy?
Vitamin C in this product might increase blood levels of estrogens in oral contraceptives or hormone replacement therapy. The increase can be up to 55% in some cases. Check with your pharmacist or doctor before adding this product.
What side effects might I notice?
The most common are stomach upset, diarrhea, or abdominal pain from lysine and zinc; metallic taste from zinc; or mild dizziness and sedation from lemon balm. High doses of vitamin C can cause heartburn and osmotic diarrhea. These are usually mild, but stop and contact your pharmacist if they persist.
Is it safe to take while pregnant or breastfeeding?
Safety data is limited. Lysine and vitamin C from food are fine, but supplement safety in pregnancy is not well studied. Myrrh and astragalus should be avoided in pregnancy. Oregon grape should be avoided. Breastfeeding safety is unclear for most ingredients. Talk with your doctor or pharmacist before using any of these while pregnant or breastfeeding.
Does St. John's wort in this product cause sun sensitivity?
Yes, St. John's wort can cause photodermatitis (skin rash from sun exposure). The risk increases at higher doses—generally above 1.8 to 4 grams of extract daily—but lower doses might still cause it in some people. Use sunscreen and limit sun exposure while taking this product.
Can I take this if I'm on antidiabetes medication?
Astragalus, myrrh, and Oregon grape all theoretically increase the risk of low blood sugar when combined with diabetes medications. If you're on any diabetes drug, check with your pharmacist first—you may need blood sugar monitoring or a dose adjustment.

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.

Lysine Extra label
Go deeper

The Full Monographs Behind Lysine Extra’s Ingredients

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

Herb & supplement monograph

Lysine

Interacts with 1 drug

Lysine is an essential amino acid your body cannot make on its own, so it must come from food or supplements. People most often take extra lysine to try to prevent or shorten cold sores, but...

Read the full Lysine monograph → Herb & supplement monograph

Calcium

Interacts with 168 drugs

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

Read the full Calcium monograph → Herb & supplement monograph

Vitamin C

Interacts with 207 drugs

Vitamin C (ascorbic acid) is an essential nutrient your body needs but cannot make, so you must get it from food or supplements. It's important for immune function, collagen, and acts as an...

Read the full Vitamin C monograph → Herb & supplement monograph

Astragalus

Interacts with 208 drugs

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

Read the full Astragalus monograph → Herb & supplement monograph

Myrrh

Interacts with 88 drugs

Myrrh is a fragrant gum resin from Commiphora trees that has long been used in mouthwashes, throat remedies, and skin care. Modern evidence for most of its uses is limited and comes mostly f...

Read the full Myrrh monograph → Herb & supplement monograph

Oregon Grape

Interacts with 1,218 drugs

Oregon grape is a shrub whose root contains berberine and related compounds. The strongest (though still modest) evidence is for topical creams that may slightly ease psoriasis; evidence for...

Read the full Oregon Grape monograph → Herb & supplement monograph

Zinc

Interacts with 67 drugs

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

Read the full Zinc monograph → Herb & supplement monograph

St. John's Wort

Interacts with 1,143 drugs

St. John's wort is a well-studied herb most often used for mild to moderate depression, and some research suggests it may help with this. However, it has many serious interactions with presc...

Read the full St. John's Wort monograph → Herb & supplement monograph

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 →
Sources

Sources & How We Checked

Lysine Extra'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 414 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.

Lysine 7 references
  1. Thein DJ, Hurt WC. Lysine as a prophylactic agent in the treatment of recurrent herpes simplex labialis. Oral Surg Oral Med Oral Pathol 1984;58:659-66. PubMed
  2. McCune MA, Perry HO, Muller SA, O'Fallon WM. Treatment of recurrent herpes simplex infections with L-lysine monohydrochloride. Cutis 1984;34:366-73.
  3. DiGiovanna JJ, Blank H. Failure of lysine in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Arch Dermatol 1984;120:48-51. DOI
  4. Milman N, Scheibel J, Jessen O. Lysine prophylaxis in recurrent herpes simplex labialis: a double-blind, controlled crossover study. Acta Derm Venereol 1980;60:85-7.
  5. Griffith RS, Walsh DE, Myrmel KH, et al. Success of L-lysine therapy in frequently recurrent herpes simplex infection. Treatment and prophylaxis. Dermatologica 1987;175:183-90. DOI
  6. Lo JC, Chertow GM, Rennke H, Seifter JL. Fanconi's syndrome and tubulointerstitial nephritis in association with L-lysine ingestion. Am J Kidney Dis 1996;28:614-7. PubMed
  7. Smriga M, Torii K. L-Lysine acts like a partial serotonin receptor 4 antagonist and inhibits serotonin-mediated intestinal pathologies and anxiety in rats. Proc Natl Acad Sci U S A. 2003 Dec 23;100(26):15370-5.

See these in context on the Lysine monograph →

Calcium 62 references
  1. Shils M, Olson A, Shike M. Modern Nutrition in Health and Disease. 8th ed. Philadelphia, PA: Lea and Febiger, 1994.
  2. Hernandez-Avila M, Gonzalez-Cossio T, Hernandez-Avila JE, et al. Dietary calcium supplements to lower blood lead levels in lactating women: a randomized placebo-controlled trial. Epidemiology 2003;14:206-12.. PubMed
  3. Thys-Jacobs S, Ceccarelli S, Bierman A, et al. Calcium supplementation in premenstrual syndrome: a randomized crossover trial. J Gen Intern Med 1989;4:183-9. PubMed
  4. Maton PN, Burton ME. Antacids revisited: a review of their clinical pharmacology and recommended therapeutic use. Drugs 1999;57:855-70.
  5. Clemens JD, Feinstein AR. Calcium carbonate and constipation: a historical review of medical mythopoeia. Gastroenterology 1977;72:957-61. DOI
  6. Saunders D, Sillery J, Chapman R. Effect of calcium carbonate and aluminum hydroxide on human intestinal function. Dig Dis Sci 1988;33:409-13. PubMed
  7. Friedman PA, Bushinsky DA. Diuretic effects on calcium metabolism. Semin Nephrol 1999;19:551-6.
  8. Koo WK, Walters JC, Esterlitz J, et al. Maternal calcium supplementation and fetal bone mineralization. Obstet Gynecol 1999;94:577-82. DOI
  9. Raman L, Rajalakshmi K, Krishnamachari KAVR, et al. Effect of calcium supplementation to undernourished mothers during pregnancy on the bone density of the neonates. Am J Clin Nutr 1978; 31:466-9. DOI
  10. Murry JJ, Healy MD. Drug-mineral interactions: a new responsibility for the hospital dietician. J Am Diet Assoc 1991;91:66-73.
  11. Chan JM, Giovannucci E, Andersson SO, et al. Dairy products, calcium, phosphorous, vitamin D, and risk of prostate cancer. Cancer Causes Control 1998;9:559-66.
  12. Butner LE, Fulco PP, Feldman G, et al. Calcium carbonate-induced hypothyroidism. Ann Intern Med 2000:132:595. PubMed
  13. Schneyer CR. Calcium carbonate and reduction of levothyroxine efficacy. JAMA 1998;279:750. PubMed
  14. Moser LR, Smythe MA, Tisdale JE. The use of calcium salts in the prevention and management of verapamil-induced hypotension. Ann Pharmacother 2000;34:622-9. PubMed
  15. Singh N, Singh PN, Hershman JM. Effect of calcium carbonate on the absorption of levothyroxine. JAMA 2000;283:2822-5. PubMed
  16. Kahela P, Anttila M, Tikkanen R, Sundquist H. Effect of food, food constituents and fluid volume on the bioavailability of sotalol. Acta Pharmacol Toxicol (Copenh) 1979;44:7-12.. PubMed
  17. Pletz MW, Petzold P, Allen A, et al. Effect of calcium carbonate on bioavailability of orally administered gemifloxacin. Antimicrob Agents Chemother 2003;47:2158-60.. PubMed
  18. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  19. Decktor DL, Robinson M, Maton PN, et al. Effects of aluminum/magnesium hydroxide and calcium carbonate on esophageal and gastric pH in subjects with heartburn. Am J Ther 1995;2:546-52. PubMed
  20. Simoneau G. Absence of rebound effect with calcium carbonate. Eur J Drug Metab Pharmacokinet 1996;21:351-7. PubMed
  21. Peters ML, Leonard M, Licata AA. Role of alendronate and risedronate in preventing and treating osteoporosis. Cleve Clin J Med 2001;68:945-51. PubMed
  22. Bourke JF, Mumford R, Whittaker P, et al. The effects of topical calcipotriol on systemic calcium homeostasis in patients with chronic plaque psoriasis. J Am Acad Dermatol 1997;37:929-34.
  23. Gueguen L, Pointillart A. The bioavailability of dietary calcium. J Am Coll Nutr 2000;19:119s-136s. PubMed
  24. Vella A, Gerber TC, Hayes DL, Reeder GS. Digoxin, hypercalcaemia, and cardiac conduction. Postgrad Med J 1999;75:554-6. PubMed
  25. Bania TC, Blaufeux B, Hughes S, et al. Calcium and digoxin vs. calcium alone for severe verapamil toxicity. Acad Emerg Med 2000;7:1089-96. PubMed
  26. Tseng M, Breslow RA, Graubard BI, Ziegler RG. Dairy, calcium, and vitamin D intakes and prostate cancer risk in the National Health and Nutrition Examination Epidemiologic Follow-up Study cohort. Am J Clin Nutr 2005;81:1147-54. PubMed
  27. Weingarten MA, Zalmanovici A, Yaphe J. Dietary calcium supplementation for preventing colorectal cancer and adenomatous polyps. Cochrane Database Syst Rev 2004;(1):CD003548. PubMed
  28. Tavani A, Bertuccio P, Bosetti C, et al. Dietary intake of calcium, vitamin D, phosphorus and the risk of prostate cancer. Eur Urol 2005;48:27-33. PubMed
  29. Giovannucci E, Liu Y, Stampfer MJ, Willett WC. A prospective study of calcium intake and incident and fatal prostate cancer. Cancer Epidemiol Biomarkers Prev 2006;15:203-10. PubMed
  30. Rocephin (ceftriaxone) and calcium interaction. Pharmacist's Letter / Prescriber's Letter 2007;23(10):231005.
  31. Bolland MJ, Barber PA, Doughty RN, et al. Vascular events in healthy older women receiving calcium supplementation: randomised control trial. BMJ 2008;336:262-6.
  32. Bolland MJ, Avenell A, Baron JA, et al. Effect of calcium supplements on risk of myocardial infarction and cardiovascular events: meta-analysis. BMJ 2010;341:c3691. PubMed
  33. Calcium supplementation and vascular events. Pharmacist's Letter / Prescriber's Letter 2008;24(3):240306.
  34. Dietary reference intakes for calcium and vitamin D. Institute of Medicine, November 30, 2010. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Repo
  35. Coburn JW, Mischel MG, Goodman WG, et al. Calcium citrate markedly enhances aluminum absorption from aluminum hydroxide. Am J Kidney Dis. 1991;17(6):708-11. PubMed
  36. Bradley JS, Wassel RT, Lee L, et al. Intravenous ceftriaxone and calcium in the neonate: assessing the risk for cardiopulmonary adverse events. Pediatrics. 2009;123(4):e609-13. PubMed
  37. Kays MB, Overholser BR, Mueller BA, et al. Effects of sevelamer hydrochloride and calcium acetate on the oral bioavailability of ciprofloxacin. Am J Kidney Dis. 2003;42(6):1253-9. PubMed
  38. Neuhofel, A. L., Wilton, J. H., Victory, J. M., Hejmanowsk, L. G., and Amsden, G. W. Lack of bioequivalence of ciprofloxacin when administered with calcium-fortified orange juice: a new twist on an old interaction. J Clin Pharmacol. 2002;42(4):461-466. DOI
  39. Dickinson, H. O., Nicolson, D. J., Cook, J. V., Campbell, F., Beyer, F. R., Ford, G. A., and Mason, J. Calcium supplementation for the management of primary hypertension in adults. Cochrane.Database.Syst.Rev. 2006;(2):CD004639. PubMed
  40. Jones, B. J. and Twomey, P. J. Requesting patterns for serum calcium concentration in patients on long-term lithium therapy. Int J Clin Pract. 2009;63(1):170-172. PubMed
  41. Levine, M., Nikkanen, H., and Pallin, D. J. The effects of intravenous calcium in patients with digoxin toxicity. J Emerg.Med. 2011;40(1):41-46. PubMed
  42. Castelo-Branco, C., Ciria-Recasens, M., Cancelo-Hidalgo, M. J., Palacios, S., Haya-Palazuelos, J., Carbonell-Abello, J., Blanch-Rubio, J., Martinez-Zapata, M. J., Manasanch, J., and Perez-Edo, L. Efficacy of ossein-hydroxyapatite complex compared with ca
  43. Li K, Kaaks R, Linseisen J, Rohrmann S. Associations of dietary calcium intake and calcium supplementation with myocardial infarction and stroke risk and overall cardiovascular mortality in the Heidelberg cohort of the European Prospective Investigation i
  44. Chung M, Tang AM, Fu Z. Calcium Intake and Cardiovascular Disease Risk: An Updated Systematic Review and Meta-analysis. Ann Intern Med. 2016 Oct 25. PubMed
  45. Nolan CR, Califano JR, Butzin CA. Influence of calcium acetate or calcium citrate on intestinal aluminum absorption. Kidney Int. 1990;38(5):937-41. PubMed
  46. Lewis JR, Radavelli-Bagatini S, Rejnmark L, et al. The effects of calcium supplementation on verified coronary heart disease hospitalization and death in postmenopausal women: a collaborative meta-analysis of randomized controlled trials. J Bone Miner Res PubMed
  47. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  48. Lappe J, Watson P, Travers-Gustafson D, Recker R, Garland C, Gorham E, Baggerly K, McDonnell SL. Effect of Vitamin D and Calcium Supplementation on Cancer Incidence in Older Women: A Randomized Clinical Trial. JAMA. 2017 Mar 28;317(12):1234-1243. PubMed
  49. Grove ML, Cook D. Calcium and heart attacks. Doesn't apply to most calcium prescriptions. BMJ. 2010;341:c5003. PubMed
  50. Insentress [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2014.
  51. Roberts JL, Kiser JJ, Hindman JT, Meditz AL. Virologic failure with a raltegravir-containing antiretroviral regimen and concomitant calcium administration. Pharmacotherapy 2011;31(10):298e-302e. DOI
  52. Vitekta [package insert]. Foster City, CA: Gilead Sciences, Inc.; 2014.
  53. Storan ER, O'Gorman SM, Murphy A, Laing M. Case Report of Calciphylaxis Secondary to Calcium and Vitamin D<sub>3</sub> Supplementation. J Cutan Med Surg. 2017;21(2):162-163. DOI
  54. Jenkins DJA, Spence JD, Giovannucci EL, et al. Supplemental vitamins and minerals for CVD prevention and treatment. J Am Coll Cardiol 2018;71(22):2570-84. PubMed
  55. Borkenhagen JF, Connor EL, Stafstrom CE. Neonatal hypocalcemic seizures due to excessive maternal calcium ingestion. Pediatr Neurol 2013;48(6):469-71. PubMed
  56. WHO recommendations on antenatal care for a positive pregnancy experience. Geneva: World Health Organization; 2016 (http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/ anc-positive-pregnancy-experience/en/).
  57. Aune D, Navarro Rosenblatt DA, Chan DS, et al. Dairy products, calcium, and prostate cancer risk: a systematic review and meta-analysis of cohort studies. Am J Clin Nutr. 2015;101(1):87-117. PubMed
  58. Lan T, Park Y, Colditz GA, et al. Adolescent dairy product and calcium intake in relation to later prostate cancer risk and mortality in the NIH-AARP Diet and Health Study. Cancer Causes Control. 2020;31(10):891-904. PubMed
  59. Zhang Y, Li Y, Liu J, et al. Association of Vitamin D or Calcium Supplementation with Cardiovascular Outcomes and Mortality: A Meta-Analysis with Trial Sequential Analysis. J Nutr Health Aging 2021;25(2):263-270. PubMed
  60. Myung SK, Kim HB, Lee YJ, Choi YJ, Oh SW. Calcium Supplements and Risk of Cardiovascular Disease: A Meta-Analysis of Clinical Trials. Nutrients 2021;13(2):368. PubMed
  61. Hetaimish B. Neonatal Calcinosis Cutis After Treatment of Hypocalcemia with Calcium Gluconate: A Report of 2 Cases. Am J Case Rep 2024;25:e943397. PubMed
  62. US Food and Drug Administration (FDA). Biktarvy Prescribing Information. October 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210251Orig1s020lbl.pdf. Accessed July 16, 2025.

See these in context on the Calcium monograph →

Vitamin C 51 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Back DJ, Breckenridge AM, MacIver M, et al. Interaction of ethinyloestradiol with ascorbic acid in man. Br Med J (Clin Res Ed) 1981;282:1516.
  3. Morris JC, Beeley L, Ballantine N. Interaction of ethinyloestradiol with ascorbic acid in man [letter]. Br Med J (Clin Res Ed) 1981;283:503.
  4. Labriola D, Livingston R. Possible interactions between dietary antioxidants and chemotherapy. Oncology 1999;13:1003-8.
  5. Dwyer JH, Merz NB, Shirocre AM, et al. Progression of early atherosclerosis and intake of vitamin C and vitamin E from supplements and food. The Los Angeles Atherosclerosis Study. 41st Annual Conference on Cardiovascular Disease Epidemiology and Prevent
  6. Levine M, Rumsey SC, Daruwala R, et al. Criteria and recommendations for vitamin C intake. JAMA 1999;281:1415-23. PubMed
  7. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  8. Segal S, Kaminski S. Drug-nutrient interactions. American Druggist 1996 Jul;42-8.
  9. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin C, Vitamin E, Selenium, and Carotenoids. Washington, DC: National Academy Press, 2000. Available at: http://www.nap.edu/books/0309069351/html/.
  10. Houston JB, Levy G. Drug biotransformation interactions in man VI: Acetaminophen and ascorbic acid. J Pharm Sci 1976;65:1218-21. PubMed
  11. Brown BG, Zhao XQ, Chait A, et al. Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease. N Engl J Med 2001;345:1583-93. DOI
  12. Rosenthal G. Interaction of ascorbic acid and warfarin. JAMA 1971;215:1671. DOI
  13. Hume R, Johnstone JM, Weyers E. Interaction of ascorbic acid and warfarin. JAMA 1972;219:1479. DOI
  14. Smith EC, Skalski RJ, Johnson GC, Rossi GV. Interaction of ascorbic acid and warfarin. JAMA 1972;221:1166. DOI
  15. Traxer O, Huet B, Poindexter J, et al. Effect of ascorbic acid consumption on urinary stone risk factors. J Urol 2003;170:397-401.. PubMed
  16. Domingo JL, Gomez M, Llobet JM, Richart C. Effect of ascorbic acid on gastrointestinal aluminum absorption (letter). Lancet 1991;338:1467.
  17. Domingo JL, Gomez M, Llobet JM, Corbella J. Influence of some dietary constituents on aluminum absorption and retention in rats. Kidney Int 1991;39:598-601. PubMed
  18. Partridge NA, Regnier FE, White JL, Hem SL. Influence of dietary constituents on intestinal absorption of aluminum. Kidney Int 1989;35:1413-7. PubMed
  19. Mc Leod DC, Nahata MC. Inefficacy of ascorbic acid as a urinary acidifier (letter). N Engl J Med 1977;296:1413. DOI
  20. Hansten PD, Hayton WL. Effect of antacid and ascorbic acid on serum salicylate concentration. J Clin Pharmacol 1980;20:326-31. PubMed
  21. Dysken MW, Cumming RJ, Channon RA, Davis JM. Drug interaction between ascorbic acid and fluphenazine. JAMA 1979;241:2008. DOI
  22. Vihtamaki T, Parantainen J, Koivisto AM, et al. Oral ascorbic acid increases plasma oestradiol during postmenopausal hormone replacement therapy. Maturitas 2002;42:129-35. PubMed
  23. Slain D, Amsden JR, Khakoo RA, et al. Effect of high-dose vitamin C on the steady-state pharmacokinetics of the protease inhibitor indinavir in healthy volunteers. Pharmacotherapy 2005;25:165-70. PubMed
  24. Cheung MC, Zhao XQ, Chait A, et al. Antioxidant supplements block the response of HDL to simvastatin-niacin therapy in patients with coronary artery disease and low HDL. Arterioscler Thromb Vasc Biol 2001;21:1320-6. PubMed
  25. Feetam CL, Leach RH, Meynell MJ. Lack of a clinically important interaction between warfarin and ascorbic acid. Toxicol Appl Pharmacol 1975;31:544-7. PubMed
  26. Weintraub M, Griner PF. Warfarin and ascorbic acid: lack of evidence for a drug interaction. Toxicol Appl Pharmacol 1974;28:53-6. PubMed
  27. Lee DH, Folsom AR, Harnack L, et al. Does supplemental vitamin C increase cardiovascular disease risk in women with diabetes? Am J Clin Nutr 2004;80:1194-200. PubMed
  28. Taylor EN, Stampfer MJ, Curhan GC. Dietary factors and the risk of incident kidney stones in men: new insights after 14 years of follow-up. J Am Soc Nephrol 2004;15:3225-32. PubMed
  29. Ward NC, Hodgson JM, Croft KD, et al. The combination of vitamin C and grape-seed polyphenols increases blood pressure: a randomized, double-blind, placebo-controlled trial. J Hypertens 2005;23:427-34.. PubMed
  30. Prasad KN. Rationale for using high-dose multiple dietary antioxidants as an adjunct to radiation therapy and chemotherapy. J Nutr 2004;134:3182S-3S. PubMed
  31. Conklin KA. Cancer chemotherapy and antioxidants. J Nutr 2004;134:3201S-3204S. PubMed
  32. Fairweather-Tait S, Hickson K, McGaw B, et al. Orange juice enhances aluminium absorption from antacid preparation. Eur J Clin Nutr. 1994;48(1):71-3.
  33. Gruenwald, J., Graubaum, H. J., Busch, R., and Bentley, C. Safety and tolerance of ester-C compared with regular ascorbic acid. Adv.Ther. 2006;23(1):171-178.
  34. Rahimi, R., Nikfar, S., Rezaie, A., and Abdollahi, M. A meta-analysis on the efficacy and safety of combined vitamin C and E supplementation in preeclamptic women. Hypertens.Pregnancy. 2009;28(4):417-434. PubMed
  35. Einerson, B., Nathorn, C., Kitiyakara, C., Sirada, M., and Thamlikitkul, V. The efficacy of ascorbic acid in suboptimal responsive anemic hemodialysis patients receiving erythropoietin: a meta-analysis. J Med.Assoc.Thai. 2011;94 Suppl 1:S134-S146.
  36. Li, G., Li, L., Yu, C., and Chen, L. Effect of vitamins C and E supplementation on Helicobacter pylori eradication: a meta-analysis. Br.J Nutr 2011;106(11):1632-1637.
  37. Chen X, Shen L, Gu X, et al. High-dose supplementation with vitamin C--induced pediatric urolithiasis: the first case report in a child and literature review. Urology. 2014;84(4):922-4. PubMed
  38. Sattar A, Willman JE, Kolluri R. Possible warfarin resistance due to interaction with ascorbic acid: case report and literature review. Am J Health Syst Pharm. 2013;70(9):782-6. PubMed
  39. Yaich S, Chaabouni Y, Charfeddine K, et al. Secondary oxalosis due to excess vitamin C intake: a cause of graft loss in a renal transplant recipient. Saudi J Kidney Dis Transpl. 2014;25(1):113-6. PubMed
  40. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  41. Rumbold A, Ota E, Nagata C, Shahrook S, Crowther CA. Vitamin C supplementation in pregnancy. Cochrane Database Syst Rev. 2015;(9):CD004072. PubMed
  42. Seo MS, Kim JK, Shim JY. High-dose vitamin C promotes regression of multiple pulmonary metastases originating from hepatocellular carcinoma. Yonsei Med J. 2015;56(5):1449-52. PubMed
  43. Skelin M, Lucijanic T, Amidzic Klaric D, et al. Factors Affecting Gastrointestinal Absorption of Levothyroxine: A Review. Clin Ther. 2017 Feb;39(2):378-403. PubMed
  44. Jiang K, Tang K, Liu H, Xu H, Ye Z, Chen Z. Ascorbic acid supplements and kidney stones incidence among men and women: a systematic review and meta-analysis. Urol J. 2019;16(2):115-120.
  45. Thomas S, Patel D, Bittel B, et al. Effect of High-Dose Zinc and Ascorbic Acid Supplementation vs Usual Care on Symptom Length and Reduction Among Ambulatory Patients With SARS-CoV-2 Infection: The COVID A to Z Randomized Clinical Trial. JAMA Netw Open. 2 PubMed
  46. Giffen MA, McLemore JL. Hyperoxalosis Secondary to Intravenous Vitamin C Administration as a Non-Allopathic Treatment for Cancer. Acad Forensic Pathol 2019;9(1-2):118-126. PubMed
  47. Maike A, Sturgill D, Gallan A. Oxalate Nephropathy in a Renal Transplant Recipient After Receiving High Dose Ascorbic Acid. Am J Med Sci 2021. PubMed
  48. Shen ZY, Chen YR, Wang MC, Chang SS. High-dose vitamin C-induced acute oxalate nephropathy in a renal transplant recipient: a case report and literature review. Asian J Surg 2022. PubMed
  49. Yanase F, Spano S, Maeda A, et al. Mega-dose sodium ascorbate: a pilot, single-dose, physiological effect, double-blind, randomized, controlled trial. Crit Care 2023;27(1):371. PubMed
  50. Sharma Y, Sumanadasa S, Shahi R, et al. Efficacy and safety of vitamin C supplementation in the treatment of community-acquired pneumonia: a systematic review and meta-analysis with trial sequential analysis. Sci Rep 2024;14(1):11846. PubMed
  51. Pejcic AV, Petrovic NZ, Djordjic MD, Milosavljevic MN. Vitamin C Levels in Pregnant Women and the Efficacy of Vitamin C Supplements in Preventing Premature Rupture of Membranes: A Systematic Review and Meta-Analysis. Balkan Med J 2024;41(4):248-260. PubMed

See these in context on the Vitamin C monograph →

Astragalus 13 references
  1. Upton R, ed. Astragalus Root: Analytical, quality control, and therapeutic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia. 1999:1-25.
  2. Khoo KS, Ang PT. Extract of astragalus membranaceus and ligustrum lucidum does not prevent cyclophosphamide-induced myelosuppression. Singapore Med J 1995;36:387-90.
  3. Chu DT, Wong WL, Mavligit GM. Immunotherapy with Chinese medicinal herbs. II. Reversal of cyclophosphamide-induced immune suppression by administration of fractionated Astragalus membranaceus in vivo. J Clin Lab Immunol 1988;25:125-9.
  4. Sun Y, Hersh EM, Lee SL, et al. Preliminary observations on the effects of the Chinese medicinal herbs Astragalus membranaceus and Ligustrum lucidum on lymphocyte blastogenic responses. J Biol Response Mod 1983;2:227-37..
  5. Ma J, Peng A, Lin S. Mechanisms of the therapeutic effect of astragalus membranaceus on sodium and water retention in experimental heart failure. Chin Med J (Engl) 1998;111:17-23.
  6. Matkovic Z, Zivkovic V, Korica M, et al. Efficacy and safety of Astragalus membranaceus in the treatment of patients with seasonal allergic rhinitis. Phytother Res 2010;24:175-81.
  7. Zhang, J. G., Yang, N., He, H., Wei, G. H., Gao, D. S., Wang, X. L., Wang, X. Z., and Song, G. Y. [Effect of Astragalus injection on plasma levels of apoptosis-related factors in aged patients with chronic heart failure.]. Chin J Integr.Med 2005;11(3):18 PubMed
  8. Chen, H. W., Lin, I. H., Chen, Y. J., Chang, K. H., Wu, M. H., Su, W. H., Huang, G. C., and Lai, Y. L. A novel infusible botanically-derived drug, PG2, for cancer-related fatigue: a phase II double-blind, randomized placebo-controlled study. Clin Invest PubMed
  9. Tian H, Lu J, He H, et al.The effect of Astragalus as an adjuvant treatment in type 2 diabetes mellitus: A (preliminary) meta-analysis. J Ethnopharmacol. 2016;191:206-215. doi: 10.1016/j.jep.2016.05.062. PubMed
  10. Hong KF, Liu PY, Zhang W, Gui DK, Xu YH. The Efficacy and Safety of Astragalus as an Adjuvant Treatment for Type 2 Diabetes Mellitus: A Systematic Review and Meta-Analysis. J Integr Complement Med 2023. PubMed
  11. Chan KW, Kwong ASK, Tsui PN, et al. Add-on astragalus in type 2 diabetes and chronic kidney disease: A multi-center, assessor-blind, randomized controlled trial. Phytomedicine 2024;130:155457. PubMed
  12. Han X, Yu T, Chen X, Du Z, Yu M, Xiong J. Effect of Astragalus membranaceus on left ventricular remodeling in HFrEF: a systematic review and meta-analysis. Front Pharmacol 2024;15:1345797. PubMed
  13. Jing P, Hongzheng H, Zhenqi WU, Meijuan Z, Zuojing LI, Gang C. Long-term efficacy and safety of Huangqi ()-based Traditional Chinese Medicine in diabetic peripheral neuropathy: a Meta-analysis of randomized controlled trials. J Tradit Chin Med 2024;44(2):

See these in context on the Astragalus monograph →

Myrrh 8 references
  1. Newall CA, Anderson LA, Philpson JD. Herbal Medicine: A Guide for Healthcare Professionals. London, UK: The Pharmaceutical Press, 1996.
  2. The Review of Natural Products by Facts and Comparisons. St. Louis, MO: Wolters Kluwer Co., 1999.
  3. McGuffin M, Hobbs C, Upton R, Goldberg A, eds. American Herbal Products Association's Botanical Safety Handbook. Boca Raton, FL: CRC Press, LLC 1997.
  4. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  5. Al Faraj S. Antagonism of the anticoagulant effect of warfarin caused by the use of Commiphora molmol as a herbal medication: a case report. Ann Trop Med Parasitol 2005;99:219-20.
  6. Al-Jaroudi D, Kaddour O, Al-Amin N. Risks of myrrh use in pregnancy. JBRA Assist Reprod 2016;20(4):257-8.
  7. Xu YY, Li L, Xuan L, Guan K. Patch test diagnosis of non-immediate cutaneous reaction to myrrh following oral intake of a traditional Chinese medicine decoction. Contact Dermatitis. 2019;80(2):135-136. PubMed
  8. Al-Romaiyan A, Huang GC, Jones P, Persaud S. Commiphora myrrha stimulates insulin secretion from mouse and human islets of Langerhans. J Ethnopharmacol. 2021 Jan 10;264:113075. PubMed

See these in context on the Myrrh monograph →

Oregon Grape 21 references
  1. Wiesenauer M, Lydtke R. Mahonia aquifolium in patients with Psoriasis vulgaris; an intraindividual study. Phytomedicine 1996;3:231-5.
  2. Chan E. Displacement of bilirubin from albumin by berberine. Biol Neonate 1993;63:201-8. PubMed
  3. Janbaz KH, Gilani AH. Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia 2000;71:25-33.. PubMed
  4. Wu X, Li Q, Xin H, Yu A, Zhong M. Effects of berberine on the blood concentration of cyclosporin A in renal transplanted recipients: clinical and pharmacokinetic study. Eur J Clin Pharmacol 2005;61:567-72. PubMed
  5. Gulliver WP, Donsky HJ. A report on three recent clinical trials using Mahonia aquifolium 10% topical cream and a review of the worldwide clinical experience with Mahonia aquifolium for the treatment of plaque psoriasis. Am J Ther 2005;12:398-406. PubMed
  6. Zhang Y, Li X, Zou D, et al. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol Metab 2008;93:2559-65. PubMed
  7. 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
  8. Chatterjee P, Franklin MR. Human cytochrome p450 inhibition and metabolic-intermediate complex formation by goldenseal extract and its methylenedioxyphenyl components. Drug Metab Dispos 2003;31:1391-7. PubMed
  9. Shanbhag, S. M., Kulkarni, H. J., and Gaitonde, B. B. Pharmacological actions of berberine on the central nervous system. Jpn.J Pharmacol 1970;20(4):482-487. PubMed
  10. Wu, J. F. and Liu, T. P. [Effects of berberine on platelet aggregation and plasma levels of TXB2 and 6-keto-PGF1 alpha in rats with reversible middle cerebral artery occlusion]. Yao Xue.Xue.Bao. 1995;30(2):98-102.
  11. Peng, W. H., Hsieh, M. T., and Wu, C. R. Effect of long-term administration of berberine on scopolamine-induced amnesia in rats. Jpn J Pharmacol 1997;74(3):261-266. DOI
  12. Sabir M and Bhide NK. Study of some pharmacological actions of berberine. Ind J Physiol & Pharmac 1971;15(3):111-132.
  13. Tripathi YB and Shukla SD. Berberis artistata inhibits PAF induced aggregation of rabbit platelets. Phytotherapy Research 1996;10:628-630.
  14. Yin, J., Xing, H., and Ye, J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 2008;57(5):712-717. PubMed
  15. Zhang, H., Wei, J., Xue, R., Wu, J. D., Zhao, W., Wang, Z. Z., Wang, S. K., Zhou, Z. X., Song, D. Q., Wang, Y. M., Pan, H. N., Kong, W. J., and Jiang, J. D. Berberine lowers blood glucose in type 2 diabetes mellitus patients through increasing insulin re
  16. Guo, Y., Chen, Y., Tan, Z. R., Klaassen, C. D., and Zhou, H. H. Repeated administration of berberine inhibits cytochromes P450 in humans. Eur J Clin Pharmacol 2012;68(2):213-217. PubMed
  17. Wei, W., Zhao, H., Wang, A., Sui, M., Liang, K., Deng, H., Ma, Y., Zhang, Y., Zhang, H., and Guan, Y. A clinical study on the short-term effect of berberine in comparison to metformin on the metabolic characteristics of women with polycystic ovary syndro
  18. Hermann, R. and von, Richter O. Clinical evidence of herbal drugs as perpetrators of pharmacokinetic drug interactions. Planta Med 2012;78(13):1458-1477. PubMed
  19. Chun YT, Yip TT, Lau KL, and et al. A biochemical study on the hypotensive effect of berberine in rats. Gen Pharmac 1979;10:177-182. PubMed
  20. Lan J, Zhao Y, Dong F, et al. Meta-analysis of the effect and safety of berberine in the treatment of type 2 diabetes mellitus, hyperlipemia and hypertension. J Ethnopharmacol. 2015;161:69-81. PubMed
  21. Fan Y, Zhou Z, Zhang L. Effect of Oregon grape root extracts on P-glycoprotein mediated transport in in vitro cell lines. J Pharm Pharm Sci 2024;26:11927. PubMed

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Zinc 88 references
  1. Barceloux DG. Zinc. J Toxicol Clin Toxicol 1999;37:279-92.
  2. Eby GA, Davis DR, Halcomb WW. Reduction in duration of common colds by zinc gluconate lozenges in a double-blind study. Antimicrob Agents Chemother 1984;25:20-4. DOI
  3. Smith DS, Helzner EC, Nuttall CE Jr, et al. Failure of zinc gluconate in treatment of acute upper respiratory tract infections. Antimicrob Agents Chemother 1989;33:646-8. PubMed
  4. Blondeau JM. Expanded activity and utility of the new fluoroquinolones: a review. Clin Ther 1999;21:3-40. PubMed
  5. Reyes AJ, Olhaberry JV, Leary WP, et al. Urinary zinc excretion, diuretics, zinc deficiency and some side-effects of diuretics. S Afr Med J 1983;64:936-41.
  6. Kugelmas M. Preliminary observation: oral zinc sulfate replacement is effective in treating muscle cramps in cirrhotic patients. J Am Coll Nutr 2000;19:13-5. PubMed
  7. Hebel SK, ed. Drug Facts and Comparisons. 52nd ed. St. Louis: Facts and Comparisons, 1998.
  8. Chan S, Gerson B, Subramaniam S. The role of copper, molybdenum, selenium, and zinc in nutrition and health. Clin Lab Med 1998;18:673-85. DOI
  9. Brewer GJ, Yuzbasiyan-Gurkan V, Johnson V, et al. Treatment of Wilson's disease with zinc: XI. Interaction with other anticopper agents. J Am Coll Nutr 1993;12:26-30. PubMed
  10. Fosmire GJ. Zinc toxicity. Am J Clin Nutr 1990;51:225-7.
  11. Lomaestro BM, Bailie GR. Absorption interactions with fluoroquinolones. 1995 update. Drug Saf 1995;12:314-33. PubMed
  12. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  13. Seelig MS. Auto-immune complications of D-penicillamine - A possible result of zinc and magnesium depletion and of pyridoxine inactivation. J Am Coll Nutr 1982;1:207-14. PubMed
  14. Neuvonen PJ. Interactions with the absorption of tetracyclines. Drugs 1976;11:45-54.. PubMed
  15. Hirt M, Nobel S, Barron E. Zinc nasal gel for the treatment of common cold symptoms: A double-blind, placebo-controlled trial. Ear Nose Throat J 2000;79:778-82.. DOI
  16. Simkin PA. Oral zinc sulphate in rheumatoid arthritis. Lancet 1976;2:539-42. PubMed
  17. Wray D. A double-blind trial of systemic zinc sulfate in recurrent aphthous stomatitis. Oral Surg Oral Med Oral Pathol 1982;53:469-72. PubMed
  18. Douglas RM, Miles HB, Moore BW, et al. Failure of effervescent zinc acetate lozenges to alter the course of upper respiratory tract infections in Australian adults. Antimicrob Agents Chemother 1987;31:1263-5. PubMed
  19. Lagiou P, Wuu J, Trichopoulou A, et al. Diet and benign prostatic hyperplasia: a study in Greece. Urology 1999;54:284-90. PubMed
  20. Ewing CI, Gibbs AC, Ashcroft C, David TJ. Failure of oral zinc supplementation in atopic eczema. Eur J Clin Nutr 1991;45:507-10.
  21. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  22. Age-Related Eye Disease Study Research Group. A randomized, placebo-controlled, clinical trial of high-dose supplementation with vitamins C and E, beta carotene, and zinc for age-related macular degeneration and vision loss. AREDS report no. 8. Arch Oph
  23. Greenberg JE, Lynn M, Kirsner RS, et al. Mucocutaneous pigmented macule as a result of zinc deposition. J Cutan Pathol 2002;29:613-5. PubMed
  24. Godfrey HR, Godfrey NJ, Godfrey JC, Riley D. A randomized clinical trial on the treatment of oral herpes with topical zinc oxide/glycine. Altern Ther Health Med 2001;7:49-56.
  25. Turner RB. Ineffectiveness of intranasal zinc gluconate for prevention of experimental rhinovirus colds. Clin Infect Dis 2001;33:1865-70. PubMed
  26. Belongia EA, Berg R, Liu K. A randomized trial of zinc nasal spray for the treatment of upper respiratory illness in adults. Am J Med 2001;111:103-8. PubMed
  27. Mossad SB. Effect of zincum gluconicum nasal gel on the duration and symptom severity of the common cold in otherwise healthy adults. QJM 2003;96:35-43. DOI
  28. Leitzmann MF, Stampfer MJ, Wu K, et al. Zinc supplement use and risk of prostate cancer. J Natl Cancer Inst 2003;95:1004-7.. PubMed
  29. Jafek BW, Linschoten M, Murrow BW. Zicam Induced Anosmia. American Rhinologic Society 49th Annual Fall Scientific Meeting abstract. Orlando, Florida. September 20, 2003. http://app.american-rhinologic.org/programs/2003ARSFallProgram071503.pdf (Accessed 24
  30. Uebayashi H, Hatanaka T, Kanemura F, Tonosaki K. Acute anosmia in the mouse: behavioral discrimination among the four basic taste substances. Physiol Behav 2001;72:291-6.. PubMed
  31. Barrett S. Zicam Marketers Sued. United States District Court Western District of Michigan Southern Division, Filed October 14, 2003, Case No. 4:03CV0146.
  32. Bilici M, Yildirim F, Kandil S, et al. Double-blind, placebo-controlled study of zinc sulfate in the treatment of attention deficit hyperactivity disorder. Prog Neuropsychopharmacol Biol Psychiatry 2004;28:181-90.. PubMed
  33. Polk RE, Healy DP, Sahai J, et al. Effect of ferrous sulfate and multivitamins with zinc on absorption of ciprofloxacin in normal volunteers. Antimicrob Agents Chemother 1989;33:1841-4. PubMed
  34. Mery C, Delrieu F, Ghozlan R, et al. Controlled trial of D-penicillamine in rheumatoid arthritis. Dose effect and the role of zinc. Scand J Rheumatol 1976;5:241-7. PubMed
  35. Penttila O, Hurme H, Neuvonen PJ. Effect of zinc sulfate on the absorption of tetracycline and doxycycline in man. Eur J Clin Pharmacol 1975;9:131-4.
  36. Kondo Y, Yamagata K, Satoh M, et al. Optimal administration schedule of cisplatin for bladder tumor with minimal induction of metallothionein. J Urol 2003;170:2467-70. PubMed
  37. Doz F, Berens ME, Deschepper CF, et al. Experimental basis for increasing the therapeutic index of cis-diamminedicarboxylatocyclobutaneplatinum(II) in brain tumor therapy by a high-zinc diet. Cancer Chemother Pharmacol 1992;29:219-26.
  38. Wester PO. Urinary zinc excretion during treatment with different diuretics. Acta Med Scand 1980;208:209-12. PubMed
  39. Golik A, Modai D, Weissgarten J, et al. Hydrochlorothiazide-amiloride causes excessive urinary zinc excretion. Clin Pharmacol Ther 1987;42:42-4. PubMed
  40. Leary WP, Reyes AJ, Van der Byl K. Urinary magnesium and zinc excretion after two different single doses of amiloride in healthy adults. Curr Ther Res 1983;34:205-16.
  41. McBride K, Slotnick B, Margolis FL. Does intranasal application of zinc sulfate produce anosmia in the mouse? An olfactometric and anatomical study. Chem Senses 2003;28:659-70. PubMed
  42. Burd GD. Morphological study of the effects of intranasal zinc sulfate irrigation on the mouse olfactory epithelium and olfactory bulb. Microsc Res Tech 1993;24:195-213. PubMed
  43. Ducray A, Bondier JR, Michel G, et al. Recovery following peripheral destruction of olfactory neurons in young and adult mice. Eur J Neurosci 2002;15:1907-17. PubMed
  44. Mayer AD, Rosenblatt JS. Peripheral olfactory deafferentation of the primary olfactory system in rats using ZnSO4 nasal spray with special reference to maternal behavior. Physiol Behav 1993;53:587-92. PubMed
  45. DeCook CA, Hirsch AR. Anosmia due to inhalational zinc: a case report (abstract). Chem Senses 2000;25:659.
  46. Tisdall FF, Brown A, Defries RD. Persistent anosmia following zinc sulfate nasal spraying. JPed 1938;18:60-2. DOI
  47. Lawson KA, Wright ME, Subar A, et al. Multivitamin use and risk of prostate cancer in the National Institutes of Health-AARP Diet and Health Study. J Natl Cancer Inst 2007;99:754-64. PubMed
  48. Public Health Advisory. Loss of sense of smell with intranasal cold remedies containing zinc. U.S. Food and Drug Administration, June 16, 2009. Available at: http://www.fda.gov/Drugs/DrugSafety/PublicHealthAdvisories/ucm166059.htm (Accessed 16 June 2009)
  49. Dooren JC. FDA warns against use of Zicam. The Wall Street Journal, June 16, 2009. Available at: http://online.wsj.com/article/SB124516778692319231.html#mod=djemHL?mg=com-wsj (Accessed 16 June 2009).
  50. Alexander TH, Davidson TM. Intranasal zinc and anosmia: the zinc-induced anosmia syndrome. Laryngoscope 2006;116:217-20.
  51. Health Canada / GlaxoSmithKline Consumer Healthcare. Association of long-term, excessive use of zinc-containing Poli-Grip products with myeloneuropathy and blood dyscrasias. February 18, 2010. Available at: http://hc-sc.gc.ca/dhp-mps/alt_formats/pdf/medef
  52. GlaxoSmithKline Consumer Advisory. GlaxoSmithKline (GSK) warns about a potential health risk associated with long-term, excessive use of GSK's zinc-containing denture adhesives Super Polygrip Original, Ultra Fresh and Extra Care. February 18, 2010. Availa
  53. Science M, Johnstone J, Roth DE, et al. Zinc for the treatment of the common cold: a systematic review and meta-analysis of randomized controlled trials. CMAJ 2012;184:E551-61. PubMed
  54. Castilla-Higuero, L., Romero-Gomez, M., Suarez, E., and Castro, M. Acute hepatitis after starting zinc therapy in a patient with presymptomatic Wilson's disease. Hepatology 2000;32(4 Pt 1):877. PubMed
  55. Sharquie, K. E., Najim, R. A., Farjou, I. B., and Al Timimi, D. J. Oral zinc sulphate in the treatment of acute cutaneous leishmaniasis. Clin.Exp.Dermatol. 2001;26(1):21-26. PubMed
  56. Dreno, B., Moyse, D., Alirezai, M., Amblard, P., Auffret, N., Beylot, C., Bodokh, I., Chivot, M., Daniel, F., Humbert, P., Meynadier, J., and Poli, F. Multicenter randomized comparative double-blind controlled clinical trial of the safety and efficacy of
  57. Moore, R. Bleeding gastric erosion after oral zinc sulphate. Br.Med J 3-25-1978;1(6115):754. PubMed
  58. Jafek, B. W., Linschoten, M. R., and Murrow, B. W. Anosmia after intranasal zinc gluconate use. Am J Rhinol. 2004;18(3):137-141. DOI
  59. Simonart, T. and de, Maertelaer, V. Systemic treatments for cutaneous warts: a systematic review. J Dermatolog.Treat. 2012;23(1):72-77. PubMed
  60. Cochran, R. J., Tucker, S. B., and Flannigan, S. A. Topical zinc therapy for acne vulgaris. Int.J Dermatol. 1985;24(3):188-190. DOI
  61. Morgan, A. A. Bleeding gastric erosion after oral zinc sulphate. Br.Med.J. 5-13-1978;1(6122):1283-1284. PubMed
  62. Murphy, J. V. Intoxication following ingestion of elemental zinc. JAMA 6-22-1970;212(12):2119-2120.
  63. Lang, C. J., Rabas-Kolominsky, P., Engelhardt, A., Kobras, G., and Konig, H. J. Fatal deterioration of Wilson's disease after institution of oral zinc therapy. Arch Neurol. 1993;50(10):1007-1008. PubMed
  64. Fjellner, B. Drug-induced lupus erythematosus aggravated by oral zinc therapy. Acta Derm.Venereol. 1979;59(4):368-370. DOI
  65. Varas Lorenzo, M. J. Zinc acexamate and ranitidine in the short- and mid-term management of gastroduodenal ulcers. Curr Ther Res 21986;39:19-29.
  66. Bosch, F. and Jimenez, E. Post-marketing surveillance of zinc acexamate in peptic ulcer treatment. Clin Trials J 1990;27:301-312.
  67. DeCook, C. A. and Hirsch, A. R. Anosmia due to inhalational zinc: a case report (abstract). Chem Senses 2000;25:659.
  68. Crown LA, May JA. Zinc toxicity: denture adhesives, bone marrow failure and polyneuropathy. Tenn Med. 2012 Feb;105(2):39-40, 42.
  69. Dadamio J, Van Tournout M, Teughels W, Dekeyser C, Coucke W, Quirynen M. Efficacy of different mouthrinse formulations in reducing oral malodour: a randomized clinical trial. J Clin Periodontol. 2013 May;40(5):505-13. PubMed
  70. Moyle G, Else L, Jackson A, Back D, Yapa MH, Seymour N, Ringner-Nackter L, Karolia Z, Gazzard B, Boffito M. Coadministration of atazanavir-ritonavir and zinc sulfate: impact on hyperbilirubinemia and pharmacokinetics. Antimicrob Agents Chemother. 2013 Aug PubMed
  71. Zittel S, Ufer F, Gerloff C, Münchau A, Rosenkranz M. Severe myelopathy after denture cream use--is copper deficiency or excess zinc the cause? Clin Neurol Neurosurg. 2014 Jun;121:17-8. PubMed
  72. Jalloh MA, Gregory PJ, Hein D, et al. Dietary supplement interactions with antiretrovirals: a systematic review. Int J STD AIDS. 2017 Jan;28(1):4-15. PubMed
  73. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents: Drug Interactions between Integrase Inhibitors and Other Drugs. AIDSinfo. July 14, 2016. Available at: https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescen
  74. Ding Y, Jia YY, Li F, et al. The effect of staggered administration of zinc sulfate on the pharmacokinetics of oral cephalexin. Br J Clin Pharmacol. 2012 Mar;73(3):422-7. PubMed
  75. Fallah R, Sabbaghzadegan S, Karbasi SA, Binesh F. Efficacy of zinc sulfate supplement on febrile seizure recurrence prevention in children with normal serum zinc level: A randomised clinical trial. Nutrition. 2015;31(11-12):1358-61. PubMed
  76. Lazzerini M, Wanzira H. Oral zinc for treating diarrhoea in children. Cochrane Database Syst Rev. 2016;12:CD005436. PubMed
  77. Mahmoud AM, Al-Alem U, Dabbous F, et al. Zinc intake and risk of prostate cancer: Case-control study and meta-analysis. PLoS One. 2016;11(11):e0165956. PubMed
  78. Nagraj SK, George RP, Shetty N, Levenson D, Ferraiolo DM, Shrestha A. Interventions for managing taste disturbances. Cochrane Database Syst Rev. 2017 Dec 20;12(12):CD010470. PubMed
  79. Yee BE, Richards P, Sui JY, Marsch AF. Serum zinc levels and efficacy of zinc treatment in acne vulgaris: A systematic review and meta-analysis. Dermatol Ther. 2020:e14252. PubMed
  80. Janyajirawong R, Vilaichone RK, Sethasine S. Efficacy of zinc supplement in minimal hepatic encephalopathy: A prospective, randomized controlled study (Zinc-MHE Trial). Asian Pac J Cancer Prev 2021;22(9):2879-2887. PubMed
  81. Nakano M, Nakamura Y, Miyazaki A, Takahashi J. Zinc pharmacotherapy for elderly osteoporotic patients with zinc deficiency in a clinical setting. Nutrients 2021;13(6):1814. PubMed
  82. Tolino E, Skroza N, Mambrin A, et al. An open-label study comparing oral zinc to lymecycline in the treatment of acne vulgaris. J Clin Aesthet Dermatol 2021;14(5):56-58.
  83. Hunter J, Arentz S, Goldenberg J, et al. Zinc for the prevention or treatment of acute viral respiratory tract infections in adults: a rapid systematic review and meta-analysis of randomised controlled trials. BMJ Open. 2021;11(11):e047474. PubMed
  84. Yamazaki K, Kageyama H, Fujiyama T, Ito T, Urano S, Honda T. A case of systemic contact dermatitis due to zinc supplements. Int J Dermatol 2022. PubMed
  85. Magham K, Han J, Eilbert W, Bunney EB. Severe copper deficiency anemia caused by zinc supplement use. Am J Emerg Med 2023;72:222. PubMed
  86. Sivakumar RR, Chinnaiah Govindareddy D, Sahoo J, Bobby Z, Chinnakali P. Effect of daily zinc supplementation for 12 weeks on serum thyroid auto-antibody levels in children and adolescents with autoimmune thyroiditis - a randomized controlled trial. J Pedi PubMed
  87. AlDhasee O, AlMalki H, AlKharashi N, AlJeraisy N, Al Deeb M. Acute zinc sulfate overdose: clinical presentation and management. BMJ Case Rep 2025;18(1):e263899. PubMed
  88. 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 Zinc monograph →

St. John's Wort 152 references
  1. Miller LG. Herbal Medicinals: Selected clinical considerations focusing on known or potential drug-herb interactions. Arch Intern Med 1998;158:2200-11.
  2. Gulick RM, McAuliffe V, Holden-Wiltse J, et al. Phase I studies of hypericin, the active compound in St. John's Wort, as an antiretroviral agent in HIV-infected adults. AIDS Clinical Trials Group Protocols 150 and 258. Ann Intern Med 1999;130:510-4. PubMed
  3. O'Breasail AM, Argouarch S. Hypomania and St John's wort. Can J Psychiatry 1998;43:746-7.
  4. Johne A, Brockmoller J, Bauer S, et al. Pharmacokinetic interaction of digoxin with an herbal extract from St John's wort (Hypericum perforatum). Clin Pharmacol Ther 1999;66:338-45.
  5. Gordon JB. SSRIs and St. John's Wort: possible toxicity? Am Fam Physician 1998;57:950, 953.
  6. Golsch S, Vocks E, Rakoski J, et al. [Reversible increase in photosensitivity to UV-B caused by St. John's wort extract]. Hautarzt 1997;48:249-52.
  7. Bove GM. Acute neuropathy after exposure to sun in a patient treated with St. John's Wort. Lancet 1998;352:1121-2. PubMed
  8. Brockmoller J, Reum T, Bauer S, et al. Hypericin and pseudohypericin: pharmacokinetics and effects on photosensitivity in humans. Pharmacopsychiatry 1997;30:94-101. PubMed
  9. Upton R, ed. St. John's wort, Hypericum perforatum: Quality control, analytical and therapeutic monograph. Santa Cruz, CA: American Herbal Pharmacopoeia 1997;1-32.
  10. Muller WE, Singer A, Wonnemann M, et al. Hyperforin represents the neurotransmitter reuptake inhibiting constituent of hypericum extract. Pharmacopsychiatry 1998;31:16-21.
  11. Abul-Ezz SR, Barone GW, Gurley BJ, et al. Effect of herbal supplements on cyclosporine blood levels and associated acute rejection. Am Soc of Nephrol Ann Mtg, Toronto, CAN 2000;Oct. 11-16:abstract A3754.
  12. Piscitelli SC, Burstein AH, Chaitt D, et al. Indinavir concentrations and St John's wort. Lancet 2000;355:547-8. PubMed
  13. Yue QY, Bergquist C, Gerden B. Safety of St. John's wort (Hypericum perforatum). Lancet 2000;355:576-7. PubMed
  14. Ruschitzka F, Meier PJ, Turina M, et al. Acute heart transplant rejection due to Saint John's wort. Lancet 2000;355:548-9. PubMed
  15. Roberts JE, Wang RH, Tan IP, et al. Hypericin (active ingredient in St. John's wort) photo-oxidation of lens proteins. Photochem Photobiol 1999;69:42S.
  16. Gurley BJ, Barone GW. Herb-drug interaction involving St. John's wort and cyclosporine. AAPS Ann Mtg & Expo Indianapolis, IN:2000;Oct 29- Nov 2: presentation #3443.
  17. Durr D, Stieger B, Kullak-Ublick GA, et al. St. John's Wort induces intestinal P-glycoprotein/MDR1 and intestinal and hepatic CYP3A4. Clin Pharmacol Ther 2000;68:598-604. PubMed
  18. Lee A, Minhas R, Ito S, et al. Safety of St. John's wort during breastfeeding. Clin Pharmacol Ther 2000;67:130, abstract PII-64.
  19. Schneck C. St. John's wort and hypomania. J Clin Psychiatry 1998;59:689. PubMed
  20. Nierenberg AA, Burt T, Matthews J, et al. Mania associated with St. John's wort. Biol Psychiatry 1999;46:1707-8. PubMed
  21. Nebel A, Schneider BJ, Baker RA, et al. Potential metabolic interaction between St. John's wort and theophylline. Ann Pharmacother 1999;33:502. PubMed
  22. Moses EL, Mallinger AG. St. John's wort: Three cases of possible mania induction. J Clin Psychopharmacol 2000;20:115-7. PubMed
  23. Beckman SE, Sommi RW, Switzer J. Consumer use of St. John's wort: A survey of effectiveness, safety, and tolerability. Pharmacotherapy 2000;20:568-74.
  24. Peirce A. The American Pharmaceutical Association Practical Guide to Natural Medicines. New York, NY: William Morrow and Co., 1999.
  25. Mai I, Kruger H, Budde K, et al. Hazardous pharmacokinetic interaction of Saint John's wort (Hypericum perforatum) with the immunosuppressant cyclosporin. Int J Clin Pharmacol Ther 2000;38:500-2. PubMed
  26. Schempp CM, Muller K, Winghofer B, et al. Single-dose and steady-state administration of Hypericum perfotatum extract (St. John's wort) does not influence skin sensitivity to UV radiation, visible light, and solar-stimulated radiation. Arch Dermatol 2001;
  27. Schempp CM, Ludtke R, Winghofer B, Simon JC. Effect of topical application of hypericum perforatum extract on skin sensitivity to solar simulated radiation. Photodermatol Photoimmunol Photomed 2000;16:125-8.
  28. Jacobson JM, Feinman L, Liebes L, et al. Pharmacokinetics, safety, and antiviral effects of hypericin, a derivative of St. John's Wort plant, in patients with chronic hepatitis C virus infection. Antimicrob Agents Chemother 2001;45:517-24. PubMed
  29. Moschella C, Jaber BL. Interaction between cyclosporine and Hypericum perforatum (St. John's wort) after organ transplantation. Amer J Kidney Dis 2001;38:1105-7. PubMed
  30. Karliova M, Treichel U, Malago M, et al. Interaction of Hypericum perforatum (SJW) with cyclosporin A metabolism in a patient after liver transplantation. J Hepatol 2000;33:853-5.
  31. Mandelbaum A, Pertzborn F, Martin-Facklam M, Wiesel M. Unexplained decrease of cyclosporin trough levels in a compliant renal transplant patient. Nephrol Dial Transplant 2000;15:1473-4. PubMed
  32. Assalian P. Sildenafil for SJW-induced sexual dysfunction. J Sex Marital Ther 2000;26:357-8.
  33. de Maat M, Hoetelmans R, Mathot R, et al. Drug interaction between St. John's wort and nevirapine. AIDS 2001;15:420-1. PubMed
  34. Schrader E. Equivalence of St. John's wort extract (Ze 117) and fluoxetine: a randomized, controlled study in mild-moderate depression. Int Clin Psychopharmacol 2000;15:61-8.
  35. Ernst E, Rand JI, Barnes J, Stevinson C. Adverse effects profile of the herbal antidepressant St. John's wort (Hypericum perforatum L.). Eur J Clin Pharmacol 1998;54:589-94. PubMed
  36. Shelton RC, Keller MB, Gelenberg A, et al. Effectiveness of St. John's wort in major depression: A randomized, placebo-controlled trial. JAMA 2001;285:1978-86. DOI
  37. Breidenbach T, Hoffmann MW, Becker T, et al. Drug interaction of St. John's wort with cyclosporin. Lancet 2000;355:1912.
  38. Brown TM. Acute St. John's wort toxicity. Am J Emerg Med 2000;18:231-2. PubMed
  39. Kleber E, Obry T, Hippeli S, et al. Biochemical activities of extracts from Hypericum perforatum L. 1st Communication: inhibition of dopamine-beta-hydroxylase. Arzneimittelforschung 1999;49:106-9.
  40. Barone GW, Gurley BJ, Ketel BL, et al. Drug interaction between St. John's wort and cyclosporin. Ann Pharmacother 2000;34:1013-6.
  41. Cheng TO. St. John's wort interaction with digoxin [letter]. Arch Intern Med 2000;160:2548. PubMed
  42. Lane-Brown MM. Photosensitivity associated with herbal preparations of St. John's wort (Hypericum perforatum). Med J Aust 2000;172:302.
  43. Mathijssen RHJ, Verweij J, De Bruijn P, et al. Modulation of irinotecan (CPT-11) metabolism by St. John's wort in cancer patients. American Association for Cancer Research Annual Meeting, San Francisco, April 2002. Abstract 2443.
  44. Mai I, Bauer S, Krueger H, et al. Wechselwirkungen von Johaniskraut mit tacrolismus bei nierentransplantierten patienten. Symposium Phytopharmaka VII. Forschung und Klinische Anwendung, Berlin, October, 2001.
  45. Bhopal JS. St John's wort-induced sexual dysfunction. Can J Psychiatry 2001;46:456-457. PubMed
  46. Schulz V. Incidence and clinical relevance of the interactions and side effects of Hypericum preparations. Phytomedicine 2001;8:152-60.
  47. Gorski JC, Hamman MA, Wang Z, et al. The effect of St. John's wort on the efficacy of oral contraceptives (abstract MPI-80). Clin Pharmacol Ther 2001;71:P25.
  48. Hennessy M, Kelleher D, Spiers JP, et al. St Johns wort increases expression of P-glycoprotein: implications for drug interactions. Br J Clin Pharmacol 2002;53:75-82.
  49. Parker V, Wong AH, Boon HS, Seeman MV. Adverse reactions to St John's Wort. Can J Psychiatry 2001;46:77-9. PubMed
  50. Patel S, Robinson R, Burk M. Hypertensive crisis associated with St. John's Wort. Am J Med 2002;112:507-8. PubMed
  51. Singhal AB, Caviness VS, Begleiter AF, et al. Cerebral vasoconstriction and stroke after use of serotonergic drugs. Neurology 2002;58:130-3. PubMed
  52. Holme SA, Roberts DL. Erythroderma associated with St John's wort. Br J Dermatol 2000;143:1127-8. PubMed
  53. Irefin S, Sprung J. A possible cause of cardiovascular collapse during anesthesia: long-term use of St. John's Wort. J Clin Anesth 2000;12:498-9. PubMed
  54. Calapai G, Crupi A, Firenzuoli F, et al. Serotonin, norepinephrine and dopamine involvement in the antidepressant action of hypericum perforatum. Pharmacopsychiatry 2001;34:45-9. PubMed
  55. Henderson L, Yue QY, Bergquist C, et al. St John's wort (Hypericum perforatum): drug interactions and clinical outcomes. Br J Clin Pharmacol 2002;54:349-56..
  56. Mathijssen RH, Verweij J, de Bruijn P, et al. Effects of St. John's wort on irinotecan metabolism. J Natl Cancer Inst 2002;94:1247-9.. PubMed
  57. Ladner DP, Klein SD, Steiner RA, Walt H. Synergistic toxicity of delta-aminolaevulinic acid-induced protoporphyrin IX used for photodiagnosis and hypericum extract, a herbal antidepressant. Br J Dermatol 2001;144:916-8. PubMed
  58. Ernst E. St. John's Wort supplements endanger the success of organ transplantation. Arch Surg 2002;137:316-9. PubMed
  59. Wang Z, Hamman MA, Huang SM, et al. Effect of St. John's wort on the pharmacokinetics of fexofenadine. Clin Pharmacol Ther 2002;71:414-20.. PubMed
  60. Chan LY, Chiu PY, Lau TK. A study of hypericin-induced teratogenicity during organogenesis using a whole rat embryo culture model. Fertil Steril 2001;76:1073-4. PubMed
  61. Schwarz UI, Buschel B, Kirch W. Unwanted pregnancy on self-medication with St John's wort despite hormonal contraception. Br J Clin Pharmacol 2003;55:112-3. PubMed
  62. Logan JL, Ahmed J. Critical hypokalemic renal tubular acidosis due to Sjogren's syndrome: association with the purported immune stimulant echinacea. Clin Rheumatol 2003;22:158-9.
  63. Mai I, Stormer E, Bauer S, et al. Impact of St John's wort treatment on the pharmacokinetics of tacrolimus and mycophenolic acid in renal transplant patients. Nephrol Dial Transplant 2003;18:819-22.. PubMed
  64. Groning R, Breitkreutz J, Muller RS. Physico-chemical interactions between extracts of Hypericum perforatum L. and drugs. Eur J Pharm Biopharm 2003;56:231-6.. PubMed
  65. Sugimoto K, Ohmori M, Tsuruoka S, et al. Different effects of St John's wort on the pharmacokinetics of simvastatin and pravastatin. Clin Pharmacol Ther 2001;70:518-24.. DOI
  66. Bauer S, Stormer E, Johne A, et al. Alterations in cyclosporin A pharmacokinetics and metabolism during treatment with St John's wort in renal transplant patients. Br J Clin Pharmacol 2003;55:203-11.. PubMed
  67. Markowitz JS, Donovan JL, DeVane CL, et al. Effect of St. John's wort on drug metabolism by induction of cytochrome P450 3A4 enzyme. JAMA 2003;290:1500-4.. PubMed
  68. Hypericum Depression Trial Study Group. Effect of Hypericum perforatum (St. John's wort) in major depressive disorder: a randomized controlled trial. JAMA 2002;287:1807-14. PubMed
  69. Hammerness P, Basch E, Ulbricht C, et al. St. John's wort: a systematic review of adverse effects and drug interactions for the consultation psychiatrist. Psychosomatics 2003;44:271-82. PubMed
  70. Gurley BJ, Gardner SF, Hubbard MA, et al. Cytochrome P450 phenotypic ratios for predicting herb-drug interactions in humans. Clin Pharmacol Ther 2002;72:276-87.. PubMed
  71. Foster BC, Vandenhoek S, Hana J, et al. In vitro inhibition of human cytochrome P450-mediated metabolism of marker substrates by natural products. Phytomedicine 2003;10:334-42.. PubMed
  72. Kim RB. Drugs as P-glycoprotein substrates, inhibitors, and inducers. Drug Metab Rev 2002;34:47-54. PubMed
  73. Dean AJ, Moses GM, Vernon JM. Suspected withdrawal syndrome after cessation of St. John's wort. Ann Pharmacother 2003;37:150. PubMed
  74. Morimoto T, Kotegawa T, Tsutsumi K, et al. Effect of St. John's wort on the pharmacokinetics of theophylline in healthy volunteers. J Clin Pharmacol 2004;44:95-101. PubMed
  75. Pfrunder A, Schiesser M, Gerber S, et al. Interaction of St John's wort with low-dose oral contraceptive therapy: a randomized controlled trial. Br J Clin Pharmacol 2003;56:683-90. PubMed
  76. Hall SD, Wang Z, Huang SM, et al. The interaction between St John's wort and an oral contraceptive. Clin Pharmacol Ther 2003;74:525-35. PubMed
  77. Frye RF, Fitzgerald SM, Lagattuta TT, et al. Effect of St. John's wort on imatinib mesylate pharmacokinetics. Clin Pharmacol Ther 2004;76:323-9. PubMed
  78. Komoroski BJ, Zhang S, Cai H, et al. Induction and inhibition of cytochromes P450 by the St. John's wort constituent hyperforin in human hepatocyte cultures. Drug Metab Dispos 2004;32:512-8. PubMed
  79. Jiang X, Williams KM, Liauw WS, et al. Effect of St John's wort and ginseng on the pharmacokinetics and pharmacodynamics of warfarin in healthy subjects. Br J Clin Pharmacol 2004;57:592-9. PubMed
  80. Shimizu K, Nakamura M, Isse K, Nathan PJ. First-episode psychosis after taking an extract of Hypericum perforatum (St John's Wort). Hum Psychopharmacol 2004;19:275-6.
  81. Szegedi A, Kohnen R, Dienel A, Kieser M. Acute treatment of moderate to severe depression with hypericum extract WS 5570 (St John's wort): randomised controlled double blind non-inferiority trial versus paroxetine. BMJ 2005;330:503. PubMed
  82. Lau WC, Carville DGM, Guyer KE, et al. St. John's Wort Enhances the Platelet Inhibitory Effect of Clopidogrel in Clopidogrel "Resistant" Healthy Volunteers. American College of Cardiology Annual Meeting, Orlando, FL 2005: Presentation 1043-129.
  83. Murphy PA, Kern SE, Stanczyk FZ, Westhoff CL. Interaction of St. John's Wort with oral contraceptives: effects on the pharmacokinetics of norethindrone and ethinyl estradiol, ovarian activity and breakthrough bleeding. Contraception 2005;71:402-8. PubMed
  84. Linde K, Knuppel L. Large-scale observational studies of hypericum extracts in patients with depressive disorders - a systematic review. Phytomedicine 2005;12:148-57. PubMed
  85. Dasgupta A, Hovanetz M, Olsen M, et al. Drug-herb interaction: effect of St John's wort on bioavailability and metabolism of procainamide in mice. Arch Pathol Lab Med 2007;131:1094-8. PubMed
  86. Dugoua JJ, Mills E, Perri D, Koren G. Safety and efficacy of St. John's wort (hypericum) during pregnancy and lactation. Can J Clin Pharmacol 2006;13:e268-76.
  87. Jiang X, Blair EY, McLachlan AJ. Investigation of the effects of herbal medicines on warfarin response in healthy subjects: a population pharmacokinetic-pharmacodynamic modeling approach. J Clin Pharmacol 2006;46:1370-8. PubMed
  88. Niederhofer H. St. John's wort may diminish methylphenidate's efficacy in treating patients suffering from attention deficit hyperactivity disorder. Med Hypotheses 2007;68:1189. PubMed
  89. Bell EC, Ravis WR, Lloyd KB, Stokes TJ. Effects of St. John's wort supplementation on ibuprofen pharmacokinetics. Ann Pharmacother 2007;41:229-34. PubMed
  90. Booth JN, McGwin G. The association between self-reported cataracts and St. John's Wort. Curr Eye Res 2009;34:863-6. PubMed
  91. Samadi S, Khadivzadeh T, Emami A, et al. The effect of Hypericum perforatum on the wound healing and scar of cesarean. J Altern Complement Med 2010;16:113-7.
  92. Wang LS, Zhu B, Abd El-Aty A, et al. The influence of St. John's wort on CYP2C19 activity with respect to genotype. J Clin Pharmacol 2004;44:577-81. PubMed
  93. Weber W, Vander Stoep A, McCarty RL, et al. Hypericum perforatum (St John's wort) for attention-deficit/hyperactivity disorder in children and adolescents: a randomized controlled trial. JAMA 2008;299:2633-41. PubMed
  94. Lee, A., Minhas, R., Matsuda, N., Lam, M., and Ito, S. The safety of St. John's wort (Hypericum perforatum) during breastfeeding. J Clin Psychiatry 2003;64(8):966-968.
  95. Eich-Hochli, D., Oppliger, R., Golay, K. P., Baumann, P., and Eap, C. B. Methadone maintenance treatment and St. John's Wort - a case report. Pharmacopsychiatry 2003;36(1):35-37. PubMed
  96. Smith M, Lin KM, and Zheng YP. PIII-89 an open trial of nifedipine-herb interactions: Nifedipine with St. John's wort, ginseng or ginkgo biloba. Clin Pharm Ther 2001;69:P86.
  97. Kawaguchi, A., Ohmori, M., Tsuruoka, S., Nishiki, K., Harada, K., Miyamori, I., Yano, R., Nakamura, T., Masada, M., and Fujimura, A. Drug interaction between St John's Wort and quazepam. Br.J.Clin Pharmacol. 2004;58(4):403-410. PubMed
  98. Dresser, G. K., Schwarz, U. I., Wilkinson, G. R., and Kim, R. B. Coordinate induction of both cytochrome P4503A and MDR1 by St John's wort in healthy subjects. Clin Pharmacol Ther 2003;73(1):41-50. PubMed
  99. Patel, J., Buddha, B., Dey, S., Pal, D., and Mitra, A. K. In vitro interaction of the HIV protease inhibitor ritonavir with herbal constituents: changes in P-gp and CYP3A4 activity. Am.J.Ther. 2004;11(4):262-277. PubMed
  100. Xu, H., Williams, K. M., Liauw, W. S., Murray, M., Day, R. O., and McLachlan, A. J. Effects of St John's wort and CYP2C9 genotype on the pharmacokinetics and pharmacodynamics of gliclazide. Br.J.Pharmacol. 2008;153(7):1579-1586.
  101. Wang, L. S., Zhou, G., Zhu, B., Wu, J., Wang, J. G., Abd El-Aty, A. M., Li, T., Liu, J., Yang, T. L., Wang, D., Zhong, X. Y., and Zhou, H. H. St John's wort induces both cytochrome P450 3A4-catalyzed sulfoxidation and 2C19-dependent hydroxylation of omepr
  102. Hojo, Y., Echizenya, M., Ohkubo, T., and Shimizu, T. Drug interaction between St John's wort and zolpidem in healthy subjects. J.Clin.Pharm.Ther. 2011;36(6):711-715. PubMed
  103. Izzo, A. A. and Ernst, E. Interactions between herbal medicines and prescribed drugs: an updated systematic review. Drugs 2009;69(13):1777-1798. PubMed
  104. Barbenel, D. M., Yusufi, B., O'Shea, D., and Bench, C. J. Mania in a patient receiving testosterone replacement postorchidectomy taking St John's wort and sertraline. J Psychopharmacol 2000;14(1):84-86.
  105. Ratz, A. E., von Moos, M., and Drewe, J. [St. John's wort: a pharmaceutical with potentially dangerous interactions]. Schweiz Rundsch.Med Prax. 5-10-2001;90(19):843-849.
  106. Guzelcan, Y., Scholte, W. F., Assies, J., and Becker, H. E. [Mania during the use of a combination preparation with St. John's wort (Hypericum perforatum)]. Ned.Tijdschr.Geneeskd. 10-6-2001;145(40):1943-1945.
  107. van Gurp, G., Meterissian, G. B., Haiek, L. N., McCusker, J., and Bellavance, F. St John's wort or sertraline? Randomized controlled trial in primary care. Can Fam Physician 2002;48:905-912.
  108. Lecrubier, Y., Clerc, G., Didi, R., and Kieser, M. Efficacy of St. John's wort extract WS 5570 in major depression: a double-blind, placebo-controlled trial. Am J Psychiatry 2002;159(8):1361-1366. PubMed
  109. Schempp, C. M., Winghofer, B., Muller, K., Schulte-Monting, J., Mannel, M., Schopf, E., and Simon, J. C. Effect of oral administration of Hypericum perforatum extract (St. John's Wort) on skin erythema and pigmentation induced by UVB, UVA, visible light
  110. Zullino, D. and Borgeat, F. Hypertension induced by St. John's Wort - a case report. Pharmacopsychiatry 2003;36(1):32. PubMed
  111. Nanayakkara, P. W., Meijboom, M., and Schouten, J. A. [Suicidal and aggressive thoughts as a result of taking a Hypericum preparation (St. John's wort)]. Ned.Tijdschr.Geneeskd. 6-11-2005;149(24):1347-1349.
  112. Fava, M., Alpert, J., Nierenberg, A. A., Mischoulon, D., Otto, M. W., Zajecka, J., Murck, H., and Rosenbaum, J. F. A Double-blind, randomized trial of St John's wort, fluoxetine, and placebo in major depressive disorder. J.Clin.Psychopharmacol. 2005;25(5 PubMed
  113. Gastpar, M., Singer, A., and Zeller, K. Comparative efficacy and safety of a once-daily dosage of hypericum extract STW3-VI and citalopram in patients with moderate depression: a double-blind, randomised, multicentre, placebo-controlled study. Pharmacops PubMed
  114. Cappuzzo, K. A. Herbal product use in a patient with polypharmacy. Consult Pharm. 2006;21(11):911-915. PubMed
  115. Papakostas, G. I., Crawford, C. M., Scalia, M. J., and Fava, M. Timing of clinical improvement and symptom resolution in the treatment of major depressive disorder. A replication of findings with the use of a double-blind, placebo-controlled trial of Hyp DOI
  116. Sardella, A., Lodi, G., Demarosi, F., Tarozzi, M., Canegallo, L., and Carrassi, A. Hypericum perforatum extract in burning mouth syndrome: a randomized placebo-controlled study. J.Oral Pathol.Med. 2008;37(7):395-401.
  117. Etogo-Asse, F., Boemer, F., Sempoux, C., and Geubel, A. Acute hepatitis with prolonged cholestasis and disappearance of interlobular bile ducts following tibolone and Hypericum perforatum (St. John's wort). Case of drug interaction? Acta Gastroenterol.Be
  118. Andreescu, C., Mulsant, B. H., and Emanuel, J. E. Complementary and alternative medicine in the treatment of bipolar disorder--a review of the evidence. J.Affect.Disord. 2008;110(1-2):16-26. PubMed
  119. Kasper, S., Volz, H. P., Moller, H. J., Dienel, A., and Kieser, M. Continuation and long-term maintenance treatment with Hypericum extract WS 5570 after recovery from an acute episode of moderate depression--a double-blind, randomized, placebo controlled
  120. Al-Akoum, M., Maunsell, E., Verreault, R., Provencher, L., Otis, H., and Dodin, S. Effects of Hypericum perforatum (St. John's wort) on hot flashes and quality of life in perimenopausal women: a randomized pilot trial. Menopause. 2009;16(2):307-314. PubMed
  121. Brattstrom, A. Long-term effects of St. John's wort (Hypericum perforatum) treatment: a 1-year safety study in mild to moderate depression. Phytomedicine. 2009;16(4):277-283. PubMed
  122. Canning, S., Waterman, M., Orsi, N., Ayres, J., Simpson, N., and Dye, L. The efficacy of Hypericum perforatum (St John's wort) for the treatment of premenstrual syndrome: a randomized, double-blind, placebo-controlled trial. CNS.Drugs 2010;24(3):207-225. PubMed
  123. Van Strater, A. C. and Bogers, J. P. Interaction of St John's wort (Hypericum perforatum) with clozapine. Int.Clin.Psychopharmacol. 2012;27(2):121-124. PubMed
  124. Sultana D, Peindl KS Wisner KL. Rash associated with St. John's wort treatment in premenstrual dysphoric disorder. Arch Women Ment Health 2000;3:99-101. DOI
  125. Bernd A, Ramirez-Bosca A, Kippenberger S, and et al. Phototoxic effects of Hypericum extract in cultures of human keratinocytes compared with those of psoralen. Photochem Photobiol 1999;2(69):218-221.
  126. Woelk H, Burkard G, and Grunwald J. Nutzen und Risikobewertung des Hypericum-extraktes LI 160 auf der Basis einer Drug-Monitoring-Studie mit 3250 patienten. Nervenheilkunde 1993;12:308-313.
  127. Schakau D, Hiller K, Schultz-Zehden W, and et al. Risk/benefit profile of St.John's wort extract: STEI 300 in 2404 patients with various degrees of psychiatric disturbance. Psychopharmakotherapie 1996;3:116-122.
  128. Laird RD and Webb M. Psychotic episode during use of St John's wort. J Herbal Pharmacother 2001;1(2):81-87. DOI
  129. Schrader E, Meier B, and Brattstrom A. Hypericum treatment of mild-moderate depression in a placebo-controlled study. A prospective, double-blind, randomized, placebo-controlled, multicentre study. Human Psychopharm 1998;13:163-169. DOI
  130. Dolton MJ, Mikus G, Weiss J, et al. Understanding variability with voriconazole using a population pharmacokinetic approach: implications for optimal dosing. J Antimicrob Chemother 2014;69(6):1633-41. PubMed
  131. Goey AK, Meijerman I, Rosing H, et al. The effect of St John's wort on the pharmacokinetics of docetaxel. Clin Pharmacokinet 2014;53(1):103-10. PubMed
  132. Lei HP, Yu XY, Xie HT, et al. Effect of St. John's wort supplementation on the pharmacokinetics of bupropion in healthy male Chinese volunteers. Xenobiotica 2010;40(4):275-81. PubMed
  133. Gurok MG, Mermi O, Kilic F, et al. Psychotic episode induced by St. John's wort (Hypericum perforatum): a case report. J Mood Dis 2014;4(1):38-40. DOI
  134. Yildirim O, Canan F. A case of panic attack induced by St John's wort. Prim Care Companion CNS Disord 2013;15(1). pii: PCC.12l01453. PubMed
  135. Abdali K, Khajehei M, Tabatabaee HR. Effect of St John's wort on severity, frequency, and duration of hot flashes in premenopausal, perimenopausal and postmenopausal women: a randomized, double-blind, placebo-controlled study. Menopause 2010;17(2):326-31. PubMed
  136. Trana C, Toth G, Wijns W, Barbato E. St. John's Wort in patients non-responders to clopidogrel undergoing percutaneous coronary intervention: a single-center randomized open-label trial (St. John's Trial). J Cardiovasc Transl Res 2013;6(3):411-4. PubMed
  137. Agollo MC, Miszputen SJ, Diament J. Hypericum perforatum-induced hepatotoxicity with possible association with copaiba (copaifera langsdorffii desf): a case report. Einstein (Sao Paulo) 2014;12(3):355-7.
  138. Hohmann N, Maus A, CarlsA, Haefeli WE, Mikus G. St. John's wort treatment in women bears risks beyond pharmacokinetic drug interactions. Arch Toxico. 2016;90(4):1013-15. doi:10.1007/s00204-015-1532-7. PubMed
  139. Jackson A, D'Avolio A, Moyle G, et al. Pharmacokinetics of the co-administration of boceprevir and St. John's wort to male and female healthy volunteers. J Antimicrob Chemother 2014;69:1911-1915. PubMed
  140. Jones D. Tourian LT, Margolese H. Possible association of syndrome of Inappropriate secretion of antidiuretic hormone with St. John's wort use. J of Clin Psychopharmacol 2014:34(6):759-60. PubMed
  141. Soleymani S, Bahramsoltani R, Rahimi R, Abdollahi M. Clinical risks of St John's Wort (Hypericum perforatum) co-administration. Expert Opin Drug Metab Toxicol. 2017;13(10):1047-62.
  142. Chrubasik-Hausmann S, Vlachojannis J, McLachlan AJ. Understanding drug interactions with St John's wort (Hypericum perforatum L.): impact of hyperforin content. J Pharm Pharmacol. 2018.
  143. Market C, Kastner IM, Hellwig, et al. The effect of induction of CYP3A4 by St. John's wort on ambrisentan plasma kinetics in volunteers of known CY2C19 genotype. Basic & Clinical Pharmacology & Toxicology 2015;116:423-428.
  144. Loughren MJ, Kharasch ED, Kelton-Rehkopf MC, Syrjala KL, Shen DD. Influence of St. John's wort on intravenous fentanyl pharmacokinetics, pharmacodynamics, and clinical effects: a randomized clinical trial. Anesthesiology 2020;132(3):491-503. PubMed
  145. Scholz I, Liakoni E, Hammann F, et al. Effects of Hypericum perforatum (St. John's wort) on the pharmacokinetics and pharmacodynamics of rivaroxaban in humans. Br J Clin Pharmacol. 2020. doi: 10.1111/bcp.14553.
  146. Fisher KA, Patel P, Abualula S, Concepion L. St. John's Wort-Induced Supraventricular Tachycardia. Cureus. 2021 Apr 7;13(4):e14356. PubMed
  147. Schäfer W, Wentzell N, Schink T, Haug U. Characterization of pregnancies exposed to St. John's wort and their outcomes: A claims data analysis. Reprod Toxicol. 2021 Jun;102:90-97. PubMed
  148. Adibelli Z, Karacay I, Demir M, Duran C. St. John's Wort (Hypericum perforatum)-related acute kidney injury. Blood Purif. 2021 Aug 24:1-3. doi: 10.1159/000518349.
  149. 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
  150. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
  151. Pochet S, Lechon AS, Lescrainier C, et al. Herb-anticancer drug interactions in real life based on VigiBase, the WHO global database. Sci Rep 2022;12(1):14178. PubMed
  152. Gümüs KS, Teegelbekkers A, Sauter M, et al. Effect of Tacrolimus Formulation (Prolonged-Release vs Immediate-Release) on Its Susceptibility to Drug-Drug Interactions with St. John's Wort. Clin Pharmacol Drug Dev 2024. PubMed

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Lemon Balm 12 references
  1. Wolbling RH, Leonhardt K. Local therapy of herpes simplex with dried extract from Melissa officinalis. Phytomedicine 1994;1:25-31.
  2. Akhondzadeh S, Noroozian M, Mohammadi M, et al. Melissa officinalis extract in the treatment of patients with mild to moderate Alzheimer's disease: a double blind, randomised, placebo controlled trial. J Neurol Neurosurg Psychiatry 2003;74:863-6. PubMed
  3. Kennedy DO, Scholey AB, Tildesley NT, et al. Modulation of mood and cognitive performance following acute administration of Melissa officinalis (lemon balm). Pharmacol Biochem Behav 2002;72:953-64. PubMed
  4. 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.
  5. Herberg, KW. Nebenwirkungen pflanzlicher Beruhigungsmittel/ Leistung und Befinden nach Einnahme einer Baldrian-Hopfen-Kombination. Z.Allg Med 1996;72:234-240.
  6. Soulimani R, Fleurentin J, Mortier F, et al. Neurotropic action of the hydroalcoholic extract of Melissa officinalis in the mouse. Planta Med. 1991 Apr;57:105-9.
  7. Sourgens H, Winterhoff H, Gumbinger HG, et al. Antihormonal effects of plant extracts. TSH- and prolactin-suppressing properties of Lithospermum officinale and other plants. Planta Med. 1982 Jun;45:78-86. DOI
  8. Auf'mkolk M, Ingbar JC, Amir SM, et al. Inhibition by certain plant extracts of the binding and adenylate cyclase stimulatory effect of bovine thyrotropin in human thyroid membranes. Endocrinology. 1984 Aug;115:527-34. PubMed
  9. Santini F, Vitti P, Ceccarini G, et al. In vitro assay of thyroid disruptors affecting TSH-stimulated adenylate cyclase activity. J Endocrinol Invest. 2003 Oct;26:950-5. PubMed
  10. Alijaniha F, et al. Heart palpitation relief with Melissa officinalis leaf extract: double blind, randomized, placebo controlled trial of efficacy and safety. J Ethnopharmacol. 2015;164:378-384. doi: 10.1016/j.jep.2015.02.007. Epub 2015 Feb 11. PubMed
  11. Araj-Khodaei M, Noorbala AA, Yarani R, et al. A double-blind, randomized pilot study for comparison of Melissa officinalis L. and Lavandula angustifolia Mill. with Fluoxetine for the treatment of depression. BMC Complement Med Ther. 2020;20(1):207. PubMed
  12. Kucuk U, Pham M, Raza Raja MH, Saad Shaukat MH, Clark R. Transient complete atrioventricular block associated with herbal supplement use. S D Med 2023;76(7):311-313.

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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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