Major interaction on record — check this product against your medications before combining. Based on 13 of 16 ingredients. Check your meds →
Dietary supplement

Arthri-Flex Advantage + Vitamin D3 Ingredients & Drug Interactions

by 21st Century

Arthri-Flex Advantage + Vitamin D3 label
See full label image
Tablet Or Pill Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking Arthri-Flex Advantage + Vitamin D3 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

Arthri-Flex Advantage + Vitamin D3 is a dietary supplement by 21st Century with 16 active ingredients. Its ingredients are commonly taken for antioxidant support, heart and circulation health, vein problems (such as varicose veins).Based on those ingredients, 1,330 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Boswellia serrata extract, Grape seed extract, Vitamin D3. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

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Check Your Meds Against Arthri-Flex Advantage + Vitamin D3 by 21st Century

Ask about any prescription or over-the-counter medication and we check it for interactions with Arthri-Flex Advantage + Vitamin D3 by 21st Century — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Arthri-Flex Advantage + Vitamin D3 by 21st Century

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

Partial disclosure
Ingredient Transparency · database check
Partial

Most active ingredients list an amount, but at least one is hidden in a blend or missing.

Why this rating?
  • The label discloses an exact amount for 11 of its 16 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (1,045 mg) without saying how much of each component you get.

Arthri-Flex Advantage + Vitamin D3 contains 16 active ingredients designed to support joint health and bone strength. The formula includes vitamin D3 for calcium absorption and bone metabolism, vitamin C as an antioxidant, glucosamine sulfate (a building block for cartilage), and boswellia serrata extract (traditionally used for joint flexibility).

Also present are minerals — magnesium, zinc, manganese, molybdenum, copper, potassium, and boron — plus hyaluronic acid for joint lubrication, MSM, white willow bark extract, grape seed extract, type II collagen from chicken sternum, and a proprietary blend. The product is made with cellulose and stearic acid as inactive ingredients.

Does it work?

Strong 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
Strong

Clinical evidence supports at least one of this product's ingredients for its stated purpose.

Why this rating?
  • The label markets this product for: Joint health and flexibility with vitamin D3.
  • We looked for evidence on: Boron deficiency, Osteoarthritis, Joint pain, Cartilage support.
  • The strongest evidence on file: Glucosamine is rated "Likely Effective" for Osteoarthritis (Natural Medicines).
  • Also on file: Boron is rated "Likely Effective" for Boron deficiency.
  • Also on file: Boswellia Serrata is rated "Possibly Effective" for Osteoarthritis.

Vitamin D3 in this product is effective for treating vitamin D deficiency, rickets, osteomalacia, renal bone disease, hypoparathyroidism, and familial hypophosphatemia. Glucosamine sulfate (also in the formula) is likely effective for osteoarthritis.

Vitamin C is effective for vitamin C deficiency and possibly effective for anemia of chronic disease and several other conditions. Boswellia serrata extract is possibly effective for osteoarthritis.

Other ingredients like hyaluronic acid, grape seed extract, and boron have limited or insufficient evidence in our data — hyaluronic acid is possibly effective for dry eye and venous leg ulcers, while the evidence for many other claimed uses is not established. Zinc is effective for zinc deficiency and possibly effective for acne and age-related macular degeneration.

Magnesium is effective for constipation and indigestion.

The evidence, ingredient by ingredient Grape Boron Boswellia Serrata Vitamin D Vitamin C Hyaluronic Acid Potassium Zinc

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 13 of the 13 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 13 of 13.
  • General safety write-ups exist for 13 of 13.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

At recommended doses, most ingredients in this product are generally well tolerated. Vitamin D3 is safe at normal amounts but can cause toxicity with very high long-term doses, leading to symptoms of high blood calcium (hypercalcemia).

Vitamin C is safe at normal doses but high doses can cause kidney stones, diarrhea, and other gastrointestinal upset. Glucosamine is generally well tolerated orally, though rare allergic reactions including anaphylaxis have been reported.

Magnesium commonly causes diarrhea and gastrointestinal irritation. Zinc at high doses may increase the risk of copper deficiency.

Boron should be avoided in pregnancy due to potential harm to the fetus, and boron supplements should not be used while breastfeeding. Boswellia serrata is likely safe in pregnancy but should be avoided while breastfeeding.

Grape seed extract is likely safe in pregnancy but concentrated supplements should be avoided. Most other ingredients lack sufficient pregnancy and breastfeeding data — talk with your doctor or pharmacist before using this product if you are pregnant or nursing.

Side effects, ingredient by ingredient Grape Boron Boswellia Serrata Vitamin D Vitamin C Hyaluronic Acid Potassium Zinc

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?
  • 10 of the 13 matched ingredients can interact with medications — Boswellia Serrata, Manganese, Grape, Glucosamine, Potassium, 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; Parkinson's medications.
  • For scale: 1,331 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 Arthri-Flex Advantage + Vitamin D3, check with your pharmacist if you take warfarin or other blood thinners (Major interaction with glucosamine), thiazide diuretics or heart rhythm medications like verapamil or digoxin (Moderate with vitamin D3), quinolone or tetracycline antibiotics (Moderate with zinc and magnesium), levodopa for Parkinson's disease (Moderate with magnesium), or calcium channel blockers for high blood pressure (Moderate with magnesium). Also double-check if you take atorvastatin, estrogen-containing contraceptives, levothyroxine, or cyclosporine.

Check your own medication Run your meds through the checker above

The bottom line

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

This product may help support joint health and bone strength through glucosamine, vitamin D, and several minerals, but it carries meaningful medication interactions — particularly with blood thinners, heart medications, antibiotics, and blood pressure drugs. If you take any prescription medications, use the checker on this page to verify safety before starting.

Pregnant or nursing individuals should discuss the formula with their pharmacist first, especially regarding boron and other high-dose minerals.

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

Assessment coverage: 13 of 16 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Sep 24, 2019.

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 Arthri-Flex Advantage + Vitamin D3, straight from the product label.

Brand 21st Century
Barcode (UPC) 740985270660
Net contents 180 Coated Tablet(s)
Market status On market
Date entered into DSLD Sep 24, 2019
DSLD ID 207404
Product type Other Combinations
Supplement form Tablet Or Pill
Dietary claims / uses Nutrient, All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten 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 Arthri-Flex Advantage + Vitamin D3 by 21st Century, 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:
4 Tablet(s)
Maximum serving Sizes:
4 Tablet(s)
Servings per container
45
UPC/BARCODE
740985270660
IngredientAmount% DV
Proprietary Blend1045 mg--
Vitamin D350 mcg250%
Vitamin C100 mg110%
MSM1500 mg--
Hyaluronic Acid80 mg--
Potassium195 mg4%
Zinc15 mg140%
Manganese5 mg220%
White Willow bark extract0 NP--
Grape seed extract0 NP--
Molybdenum220 mcg490%
premium Chicken Sternum Type II Collagen0 NP--
Boron Glycinate0 NP--
Boswellia serrata extract0 NP--
Glucosamine Sulfate1500 mg--
Magnesium200 mg50%
Copper0.5 mg60%

Other ingredients: Cellulose, Stearic Acid, Contains <2% of

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.
Formula

Arthri-Flex Advantage + Vitamin D3 combines Glucosamine Sulfate & MSM (Methylsulfonylmethane) with our Proprietary Blend of premium Chicken Sternum Type II Collagen (naturally containing Chondroitin Sulfate), Hyaluronic Acid, herbal extracts, and mineral nutrients, that may work in synergy to support joints & cartilage. Now with Vitamin D3 for its bone support potential.

Glucosamine, Chondroitin, MSM & Hyaluronic Acid Vitamin D3 for bone health 80 mg Hyaluronic Acid per serving

Contains shellfish (shrimp, crab, lobster, crayfish).

Suggested/Recommended/Usage/Directions

Directions: As a dietary supplement, adults take four (4) tablets daily, two (2) in the morning and two (2) in the afternoon, preferably with meals, or as directed by a healthcare provider. Do not exceed recommended dosage.

General Statements

Individual results may vary.

Joint & cartilage support

Lexibility support

Precautions

Warning: If you are diabetic, consult your physician before using this product.

If you have a Shellfish allergy please consult your physician before using this product.

Warning: Consult a healthcare provider prior to use if pregnant, nursing, on medications, have a medical condition or are planning a medical procedure.

Stop use and contact a physician if adverse reactions occur.

Keep out of reach of children.

Do not use if product appears to be tampered with or seal is broken.

Contains shellfish (shrimp, crab, lobster, crayfish).

Storage

Store at room temperature.

FDA Disclaimer Statement

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

Formulation

No added Yeast, Soy, Dairy, or Artificial Flavors.

Gluten free Bovine free

Seals/Symbols

Guaranteed quality Laboratory tested

Gluten free Bovine free

FDA Statement of Identity

Dietary Supplement

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

See for yourself

Arthri-Flex Advantage + Vitamin D3 by 21st Century label

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

Arthri-Flex Advantage + Vitamin D3 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 Arthri-Flex Advantage + Vitamin D3 by 21st Century

These are the 16 active ingredients this product is made of. Select any to open its full monograph.

Serving size4 Tablet(s) Dosage formTablet Or Pill Servings per container45 Amounts shown are per serving.

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

Proprietary Blend

1045 mg per serving

Vitamin D3

Interacts with
715 drugs
50 mcg per serving Form: Cholecalciferol

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

Vitamin D3 monograph & interactions

Vitamin C

Interacts with
207 drugs
100 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

MSM

1500 mg per serving

Hyaluronic Acid

No known
interactions
80 mg per serving Form: Sodium Hyaluronate

Hyaluronic acid is a natural substance in the body that helps hold water in the skin, joints, and eyes. Oral and topical products are popular for skin...

Hyaluronic Acid monograph & interactions

Potassium

Interacts with
62 drugs
195 mg per serving Form: Potassium Chloride

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

Potassium monograph & interactions

Zinc

Interacts with
67 drugs
15 mg per serving Form: Zinc Glycinate

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

Manganese

Interacts with
83 drugs
5 mg per serving Form: Manganese Glycinate

Manganese is an essential trace mineral your body needs in small amounts for bone formation, metabolism, and antioxidant defense, and most people get...

Manganese monograph & interactions

Molybdenum

No known
interactions
220 mcg per serving Form: Molybdenum Glycinate

Molybdenum is an essential trace mineral your body needs in tiny amounts to help certain enzymes work. Most people get enough from a normal diet, so s...

Molybdenum monograph & interactions

Glucosamine Sulfate

Interacts with
170 drugs
1500 mg per serving Form: Glucosamine Sulfate 2KCl

Glucosamine is a natural compound found in cartilage and joint fluid, and it is one of the most popular supplements for osteoarthritis, especially of...

Glucosamine Sulfate monograph & interactions

Magnesium

Interacts with
295 drugs
200 mg per serving Form: Magnesium Glycinate

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

Magnesium monograph & interactions

Copper

Interacts with
31 drugs
0.5 mg per serving Form: Copper Glycinate

Copper is an essential trace mineral your body needs in small amounts for making red blood cells, supporting nerves and bones, and helping enzymes wor...

Copper monograph & interactions

Other (inactive) ingredients: Cellulose, Stearic Acid, Contains <2% of. These complete the product’s ingredient list but are not active constituents.

Interaction report

Arthri-Flex Advantage + Vitamin D3 by 21st Century Drug Interactions

Want to check YOUR meds against Arthri-Flex Advantage + Vitamin D3?

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
1,330Drugs
8 Major 1,245 Moderate 77 Minor

Ingredients driving the most interactions

Boswellia serrata extract 952
Grape seed extract 910
Vitamin D3 715
Magnesium 295
Vitamin C 207

Individual Drug Interactions

The ingredients in Arthri-Flex Advantage + Vitamin D3 interact with 1,330 drugs. Click any drug to see the details.

10 of the 16 ingredients in Arthri-Flex Advantage + Vitamin D3 interact with drugs. Each result below shows which ingredient is responsible. Boswellia serrata extract Grape seed extract Vitamin D3 Magnesium Vitamin C Glucosamine Sulfate Manganese Zinc Potassium Copper

Each ingredient & the kinds of drugs it affects

For each ingredient in Arthri-Flex Advantage + Vitamin D3 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.

Boswellia serrata extract6 drug types · 952 drugs

Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, Boswellia serrata might increase the levels of CYP1A2 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP1A2 enzymes.

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

Theoretically, Boswellia serrata might increase the levels of CYP2C19 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP2C19 enzymes.

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

Theoretically, Boswellia serrata might increase the levels of CYP2C9 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP2C9 enzymes.

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

Theoretically, Boswellia serrata might increase the levels of CYP2D6 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP2D6 enzymes.

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

Theoretically, Boswellia serrata might increase or decrease the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that Boswellia serrata gum resin inhibits CYP3A4 enzymes. Other in vitro research shows that Boswellia serrata extract inhibits CYP3A4 enzymes at most concentrations, although it may modestly induce enzyme activity at low concentrations.

Likelihood Possible Evidence D
Immunosuppressants

Theoretically, Boswellia serrata might alter the effects of immunosuppressive drugs.
Some in vitro research suggests that Boswellia serrata extracts might inhibit mediators of autoimmune disorders such as leukotrienes and reduce production of antibodies and cell-mediated immunity. However, other in vitro research suggests that, when coupled with calcium ions, boswellic acids containing the keto group have immunostimulant properties within specific cell signaling pathways.

Likelihood Possible Evidence D
Boswellia serrata extract full monograph & interactions

Grape seed extract9 drug types · 910 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, grape extracts may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro evidence suggests that grape extracts might decrease platelet aggregation.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Ingesting grape juice with cyclosporine can reduce cyclosporine absorption.
A small pharmacokinetic study in healthy young adults shows that intake of purple grape juice 200 mL along with cyclosporine can decrease the absorption of cyclosporine by up to 30% when compared with water. Separate doses of grape juice and cyclosporine by at least 2 hours to avoid this interaction.

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

Theoretically, grape juice might reduce the levels of CYP1A2 substrates.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of CYP1A2.

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

Theoretically, grape seed extract may increase the levels of CYP2D6 substrates.
In vitro evidence suggests that grape seed extract might inhibit CYP2D6 enzymes. However, this interaction has not been reported in humans.

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

Theoretically, grape seed extract might increase the levels of CYP2E1 substrates.
In vitro and animal research suggests that grape seed proanthocyanidin extract inhibits CYP2E1 enzymes. However, this interaction has not been reported in humans.

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

It is unclear if grape seed extract inhibits or induces CYP3A4; research is conflicting.
In vitro evidence suggests that grape seed extract might inhibit CYP3A4 enzymes. However, evidence from animal research shows that grape seed extract may induce CYP3A4 in the liver. So far, these interactions have not been reported in humans.

Likelihood Possible Evidence D
Midazolam (Versed)

Theoretically, long-term intake of grape seed extract might decrease the effects of midazolam.
Animal research shows that subchronic ingestions of grape seed extract can increase the elimination of intravenous midazolam by increasing hepatic CYP3A4 activity. Single doses of grape seed extract do not appear to affect midazolam elimination.

Likelihood Possible Evidence D
Phenacetin

Grape juice might decrease phenacetin absorption.
A small pharmacokinetic study in healthy adults shows that ingestion of 200 mL of grape juice decreases phenacetin plasma levels. This is thought to be due to induction of cytochrome P450 1A2 (CYP1A2).

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

It is unclear if grape juice or grape seed extract inhibits CYP2C9; research is conflicting.
In vitro evidence shows that grape seed extract or grape juice might inhibit CYP2C9 enzymes. However, a small pharmacokinetic study in healthy adults shows that drinking 8 ounces of grape juice once does not affect the clearance of flurbiprofen, a probe-drug for CYP2C9 metabolism. The effects of continued grape juice consumption are unclear.

Likelihood Unlikely Evidence D
Grape seed extract full monograph & interactions

Vitamin D38 drug types · 715 drugs

Aluminum

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

Likelihood Probable Evidence B
Atorvastatin (Lipitor)

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

Likelihood Probable Evidence B
Calcipotriene (Dovonex)

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

Likelihood Probable Evidence D
Digoxin (Lanoxin)

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

Likelihood Possible Evidence D
Diltiazem (Cardizem, Others)

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

Likelihood Probable Evidence B
Thiazide Diuretics

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

Likelihood Probable Evidence D
Verapamil (Calan, Others)

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

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

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

Likelihood Possible Evidence D
Vitamin D3 full monograph & interactions

Magnesium15 drug types · 295 drugs

Levodopa/Carbidopa (Sinemet)

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

Likelihood Probable Evidence B
Aminoglycoside Antibiotics

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

Likelihood Possible Evidence D
Antacids

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

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

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

Likelihood Probable Evidence D
Bisphosphonates

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

Likelihood Probable Evidence B
Calcium Channel Blockers

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

Likelihood Possible Evidence D
Digoxin

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

Likelihood Possible Evidence B
Potassium-Sparing Diuretics

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

Likelihood Probable Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence D
Skeletal Muscle Relaxants

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

Likelihood Probable Evidence A
Sulfonylureas

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

Likelihood Probable Evidence B
Tetracycline Antibiotics

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

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

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

Likelihood Unlikely Evidence B
Gabapentin (Neurontin)

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

Likelihood Unlikely Evidence B
Sevelamer (Renagel, Renvela)

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

Likelihood Possible Evidence B
Magnesium full monograph & interactions

Vitamin 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

Glucosamine Sulfate4 drug types · 170 drugs

Warfarin (Coumadin)

Glucosamine might increase the anticoagulant effects of warfarin and increase the risk of bruising and bleeding.
In two individual case reports, glucosamine/chondroitin combinations were associated with a significant increase in international normalized ratio (INR) in patients previously stabilized on warfarin. In one case, the increase in INR occurred only after tripling the dose of a glucosamine/chondroitin supplement from 500 mg/400 mg daily to 1500/1200 mg daily. Additionally, 20 voluntary case reports to the U.S. Food & Drug Administration (FDA) have linked glucosamine plus chondroitin with increased INR, bruising, and bleeding in patients who were also taking warfarin. There have also been 20 additional case reports to the World Health Organization (WHO) that link glucosamine alone to increased INR in patients taking warfarin. The mechanism of this interaction is unclear. Glucosamine is a small component of heparin, but is not thought to have anticoagulant activity; however, animal research suggests that it might have antiplatelet activity.

Likelihood Probable Evidence D
Topoisomerase Ii Inhibitors

Theoretically glucosamine may induce resistance to topoisomerase II inhibitors.
In vitro research suggests that glucosamine might induce resistance to etoposide (VP16, VePesid) and doxorubicin (Adriamycin) by reducing inhibition of topoisomerase II, an enzyme required for DNA replication in tumor cells. This effect has not been reported in humans.

Likelihood Possible Evidence D
Acetaminophen (Tylenol, Others)

Acetaminophen might interfere with the activity of glucosamine sulfate by interacting with the sulfate portion.
Anecdotal reports suggest that adding glucosamine to an acetaminophen regimen might decrease pain control in patients with osteoarthritis. Some research suggests that the sulfate portion of glucosamine sulfate might contribute to its effect in osteoarthritis. Since acetaminophen metabolism requires sulfur and reduces serum sulfate concentrations, acetaminophen could theoretically interfere with the action of glucosamine sulfate. Conversely, the administration of sulfate could theoretically decrease the effectiveness of acetaminophen in sulfate-deficient people by increasing its clearance.

Likelihood Possible Evidence B
Antidiabetes Drugs

Despite initial concerns, it is unlikely that glucosamine will interfere with the effects of antidiabetes drugs.
In vitro and animal research has suggested that glucosamine might increase insulin resistance or decrease insulin production. This has raised concerns that taking glucosamine might worsen diabetes and decrease the effectiveness of diabetes drugs. However, clinical research suggests that glucosamine does not have adverse effects on blood glucose or glycated hemoglobin (HbA1C) in healthy, obese, or type 2 diabetes patients.

Likelihood Unlikely Evidence B
Glucosamine Sulfate full monograph & interactions

Manganese3 drug types · 83 drugs

Antipsychotic Drugs

Theoretically, the risk for manganese toxicity might increase when taken with antipsychotic drugs.
Hallucinations and behavioral changes have been reported in a patient with liver disease who was taking haloperidol and manganese. Researchers speculate that taking manganese along with haloperidol, phenothiazine-derivatives, or other antipsychotic medications might increase the risk of manganese toxicity in some patients.

Likelihood Possible Evidence D
Quinolone Antibiotics

Theoretically, manganese might reduce the absorption of quinolone antibiotics.
Manganese is a multivalent cation. Interactions resulting in reduced quinolone absorption have been reported between quinolones and other multivalent cations, such as calcium and iron.

Likelihood Probable Evidence D
Tetracycline Antibiotics

Theoretically, manganese might reduce the absorption of tetracycline antibiotics.
Manganese is a multivalent cation. Interactions resulting in reduced tetracycline absorption have been reported between tetracyclines and other multivalent cations, such as calcium and iron.

Likelihood Probable Evidence D
Manganese 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

Potassium3 drug types · 62 drugs

Ace Inhibitors (Aceis)

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

Likelihood Likely Evidence C
Angiotensin Receptor Blockers (Arbs)

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

Likelihood Likely Evidence C
Potassium-Sparing Diuretics

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

Likelihood Likely Evidence C
Potassium full monograph & interactions

Copper2 drug types · 31 drugs

Penicillamine (Cuprimine, Depen)

Theoretically, taking copper with penicillamine might decrease the absorption of penicillamine; separate dosing by at least 2 hours.
Copper chelates penicillamine, which decreases its absorption and may reduce its clinical effects.

Likelihood Probable Evidence D
Contraceptive Drugs

Theoretically, taking copper with contraceptive drugs might increase the levels and toxic effects of copper.
A meta-analysis of clinical studies suggests that chronic use of oral contraceptives increases serum copper levels by a mean of 57 mcg/dL. In most people, this resulted in levels above the normal reference range for copper.

Likelihood Possible Evidence D
Copper full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Arthri-Flex Advantage + Vitamin D3, from the product label.

21st Century

See all 21st Century products
Name
21st Century HealthCare, Inc.
Street Address
2119 S. Wilson St.
City
Tempe
State
AZ
ZipCode
85282
Web Address
www.21stcenturyvitamins.com
Pharmacist Counseling Corner

Arthri-Flex Advantage + Vitamin D3 by 21st Century: Common Questions

Does Arthri-Flex Advantage + Vitamin D3 by 21st Century interact with any medications?
Yes. Based on its ingredients, Arthri-Flex Advantage + Vitamin D3 has a known interaction with 1,330 medications, including 8 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Arthri-Flex Advantage + Vitamin D3 contains 16 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take this if I'm on warfarin or other blood thinners?
No — glucosamine sulfate in this product may increase warfarin's blood-thinning effects and raise your bleeding risk. Talk to your doctor or pharmacist before adding this supplement; you may need monitoring or a different product.
What is glucosamine sulfate, and does it really work for arthritis?
Glucosamine sulfate is a compound derived from shellfish shells; it's a building block your body uses to make and repair cartilage. The data shows it's likely effective for osteoarthritis, though individual results vary.
Is it safe to take this while pregnant?
There isn't enough safety data for several ingredients in this formula during pregnancy — boron supplements should be avoided, and others lack clear guidance. Talk with your doctor or pharmacist before using it while pregnant or nursing.
Why is there vitamin D3 in an arthritis supplement?
Vitamin D3 helps your body absorb calcium and maintain bone strength, which supports overall bone and joint health. It's also effective for vitamin D deficiency and certain bone diseases.
Can I take this with antibiotics?
The zinc and magnesium in this product can reduce absorption of quinolone and tetracycline antibiotics. If you're on one of these, take it at least 2–6 hours apart from this supplement and ask your pharmacist which antibiotic you're using.
What are the most common side effects?
Mild gastrointestinal effects like diarrhea, nausea, heartburn, or bloating are most common. These tend to be dose-related and often settle with time, but if they persist, talk to your pharmacist about whether to adjust or stop the product.

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

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

Arthri-Flex Advantage + Vitamin D3 label
Go deeper

The Full Monographs Behind Arthri-Flex Advantage + Vitamin D3’s Ingredients

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

Herb & supplement monograph

Grape

Interacts with 910 drugs

Grapes and grape products like grape seed extract contain antioxidant compounds such as resveratrol and proanthocyanidins that may support heart and blood vessel health. While the food is he...

Read the full Grape monograph → Herb & supplement monograph

Boron

Boron is a trace mineral found in many plant foods and sold as a supplement, mainly promoted for bone, joint, and hormone health. The human evidence for most of these uses is limited or prel...

Read the full Boron monograph → Herb & supplement monograph

Boswellia Serrata

Interacts with 952 drugs

Boswellia serrata is a tree resin used in traditional medicine, mainly for joint pain and inflammation. Some studies suggest it may help with osteoarthritis symptoms, but the overall evidenc...

Read the full Boswellia Serrata monograph → Herb & supplement monograph

Vitamin D

Interacts with 715 drugs

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

Read the full Vitamin D monograph → Herb & supplement monograph

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

Hyaluronic Acid

Hyaluronic acid is a natural substance in the body that helps hold water in the skin, joints, and eyes. Oral and topical products are popular for skin moisture and joint comfort, and the evi...

Read the full Hyaluronic Acid monograph → Herb & supplement monograph

Potassium

Interacts with 62 drugs

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

Read the full Potassium monograph → 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

Manganese

Interacts with 83 drugs

Manganese is an essential trace mineral your body needs in small amounts for bone formation, metabolism, and antioxidant defense, and most people get enough from a normal diet. Supplements m...

Read the full Manganese monograph → Herb & supplement monograph

Molybdenum

Molybdenum is an essential trace mineral your body needs in tiny amounts to help certain enzymes work. Most people get enough from a normal diet, so supplements are rarely needed unless a do...

Read the full Molybdenum monograph → Herb & supplement monograph

Glucosamine

Interacts with 170 drugs

Glucosamine is a natural compound found in cartilage and joint fluid, and it is one of the most popular supplements for osteoarthritis, especially of the knee. The evidence is mixed, with so...

Read the full Glucosamine monograph → Herb & supplement monograph

Magnesium

Interacts with 295 drugs

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

Read the full Magnesium monograph → Herb & supplement monograph

Copper

Interacts with 31 drugs

Copper is an essential trace mineral your body needs in small amounts for making red blood cells, supporting nerves and bones, and helping enzymes work. Most people get enough copper from fo...

Read the full Copper monograph →
Sources

Sources & How We Checked

Arthri-Flex Advantage + Vitamin D3'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 417 references behind this product’s interaction data

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

Vitamin D 26 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999.
  3. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med 2001;345:66-7. PubMed
  4. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  5. Demontis R, Leflon A, Fournier A, et al. 1 alpha(OH) vitamin D3 increases plasma aluminum in hemodialyzed patients taking AI(OH)3. Clin Nephrol 1986;26:146-9.
  6. Crowe M, Wollner L, Griffiths RA. Hypercalcemia following vitamin D and thiazide therapy in the elderly. Practitioner 1984;228:312-3.
  7. Parfitt AM. Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism. Ann Intern Med 1972;77:557-63. PubMed
  8. Thiazide diuretics and the risk of osteoporosis. Pharmacist's Letter/Prescriber's Letter 2003;19(11):191105.
  9. Moon J. The role of vitamin D in toxic metal absorption. J Am Coll Nutr 1994;13:559-64.
  10. Demontis R, Reissi D, Noel C, et al. Indirect clinical evidence that 1alphaOH vitamin D<SUB>3</SUB> increases the intestinal absorption of aluminum. Clin Nephrol 1989;31:123-7.
  11. Adler AJ, Berlyne GM. Duodenal aluminum absorption in the rat: effect of vitamin D. Am J Physiol 1985;249:G209-13. PubMed
  12. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: A new drug interaction with an unexpected consequence. Clin Pharmacol Ther 2009;85:198-203. PubMed
  13. Dietary reference intakes for calcium and vitamin D. Institute of Medicine, November 30, 2010. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Repo
  14. Cox KA, Dunn MA. Aluminum toxicity alters the regulation of calbindin-D28k protein and mRNA expression in chick intestine. J Nutr 2001;131:2007-13. PubMed
  15. Escribano, J., Balaguer, A., Pagone, F., Feliu, A., and Roque, I. Figuls. Pharmacological interventions for preventing complications in idiopathic hypercalciuria. Cochrane.Database.Syst.Rev. 2009;(1):CD004754. PubMed
  16. Carlton, S., Clopton, D., and Cappuzzo, K. A. Vitamin D deficiency: appropriate replenishment therapies and the effects of vitamin D toxicity. Consult Pharm 2010;25(3):171-177. PubMed
  17. Wang, H., Xia, N., Yang, Y., and Peng, D. Q. Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials. Lipids Health Dis. 2012;11:42. PubMed
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Manganese 21 references
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Grape 34 references
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Molybdenum 8 references
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Boron 6 references
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Boswellia Serrata 16 references
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Glucosamine 58 references
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Copper 11 references
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DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

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