Major interaction on record — check this product against your medications before combining. Based on 6 of 7 ingredients. Check your meds →
Dietary supplement

A.C. Formula II Ingredients & Drug Interactions

by Pure Encapsulations

A.C. Formula II label
See full label image
Capsule Category: Other Combinations
Most serious interaction: Major
Clinical methodology reviewed by · Updated Sep 16, 2026 · Label data from the NIH DSLD
What is this page for?

First and foremost: checking A.C. Formula II 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

A.C. Formula II is a dietary supplement by Pure Encapsulations with 7 active ingredients. Its ingredients are commonly taken for candida and yeast overgrowth, gut health support, antimicrobial.Based on those ingredients, 1,445 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Berberine Sulfate, Grapefruit (Citrus x paradisi) extract, Magnesium. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against A.C. Formula II by Pure Encapsulations

Ask about any prescription or over-the-counter medication and we check it for interactions with A.C. Formula II by Pure Encapsulations — and tell you which ingredient is responsible.

Pharmacist-reviewed data Checks every ingredient Answer in seconds
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HelloPharmacist Scorecard of A.C. Formula II by Pure Encapsulations

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 7 of its 7 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

A.C. Formula II contains 7 active ingredients.

Caprylic acid is a medium-chain fatty acid thought to have effects on certain conditions. Bromelain is an enzyme from pineapple.

Undecylenic acid is included for its antimicrobial properties. Grapefruit extract concentrates compounds from the fruit.

Berberine sulfate is an alkaloid compound from plants like goldenseal. Calcium and magnesium are essential minerals.

The capsule also contains inactive ingredients—cellulose, water, and hypoallergenic plant fiber—which are fillers and binders.

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

This product doesn't appear to be marketed for a specific use, so we graded its ingredients' overall clinical evidence instead.

Strong

Strong clinical evidence supports its ingredients for:

Why this rating?
  • We looked at the product name, claims, and label statements and couldn't find a stated purpose to grade.
  • Since the label doesn't commit to one use, we graded the ingredients' overall clinical evidence instead.
  • On file: Constipation — rated "Effective" (Magnesium) (Natural Medicines).
  • On file: Dyspepsia — rated "Effective" (Calcium) (Natural Medicines).
  • On file: Hypocalcemia — rated "Effective" (Calcium) (Natural Medicines).
  • On file: Hypomagnesemia — rated "Effective" (Magnesium) (Natural Medicines).
  • On file: Pre-eclampsia — rated "Effective" (Magnesium) (Natural Medicines).

The evidence supporting most of these ingredients is limited. Caprylic acid, bromelain, grapefruit extract, and undecylenic acid all show insufficient reliable evidence in the data we hold for the conditions they're used for.

Berberine sulfate is rated possibly effective for several uses: high cholesterol (hyperlipidemia), polycystic ovary syndrome (PCOS), Helicobacter pylori infection, high blood pressure (hypertension), and diabetes. Calcium is effective for kidney failure, upset stomach (dyspepsia), low blood calcium (hypocalcemia), and high potassium (hyperkalemia), and likely effective for bone loss (osteoporosis).

Magnesium is effective for upset stomach, constipation, low blood magnesium (hypomagnesemia), and a serious pregnancy complication (pre-eclampsia).

The evidence, ingredient by ingredient Caprylic Acid Bromelain Grapefruit Berberine Calcium Magnesium

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 6 of the 6 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 6 of 6.
  • General safety write-ups exist for 6 of 6.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Caprylic acid is generally recognized as safe in food amounts but lacks robust safety data at supplement doses; most oral side effects are mild—stomach discomfort and changes in taste—though dizziness, headache, and fatigue have been rarely reported. It appears naturally in breast milk, but concentrated supplement safety is unknown.

Bromelain is generally well tolerated short-term, but long-term safety data is limited; most common side effects are diarrhea, gas, stomach upset, and headache, though it can rarely trigger allergic reactions (including asthma if inhaled). It should be avoided in pregnancy and while breastfeeding due to insufficient safety data.

Grapefruit extract is generally well tolerated, but concentrated supplements should be avoided unless your doctor approves; eating the fruit itself is usually fine. Berberine sulfate is generally well tolerated short-term but should be avoided in pregnancy (it may cross the placenta and has been linked to newborn harm) and while breastfeeding (it passes into milk); common side effects are stomach pain, bloating, constipation, diarrhea, gas, nausea, and vomiting.

Calcium is generally safe at recommended doses in pregnancy and breastfeeding, though very high doses raise concerns about prostate cancer risk and possibly cardiovascular risk. Magnesium is generally safe for healthy adults at recommended amounts; pregnancy requires doctor guidance, and breastfeeding amounts should be discussed with your provider; common side effects are diarrhea, stomach irritation, nausea, and vomiting.

Side effects, ingredient by ingredient Caprylic Acid Bromelain Grapefruit Berberine Calcium Magnesium

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?
  • 6 of the 6 matched ingredients can interact with medications — Calcium, Bromelain, Grapefruit, Magnesium, Berberine, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,446 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 whether you use cyclosporine, scopolamine, amiodarone, dolutegravir, elvitegravir, or ceftriaxone (Major severity). Also double-check if you take blood thinners (anticoagulants or antiplatelets), NSAIDs, warfarin, levothyroxine, blood pressure medications, diabetes medications, or liver-metabolized drugs (ask your pharmacist if you're unsure about this last category)—the ingredients here may increase or decrease their levels or effects.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with strong clinical evidence behind its ingredients' uses. Major medication interactions have been identified, and safety information is well characterized.

A.C. Formula II has serious documented interactions with many common medications, especially blood thinners, heart drugs, HIV medications, diabetes drugs, and blood pressure medications.

If you take any prescription or over-the-counter medication, check your exact drugs with the interaction tool on this page before starting. Talk with your pharmacist or doctor—they can help you decide if this product is right for you and how to space doses safely.

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

Assessment coverage: 6 of 7 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jul 18, 2023.

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

At a glance

General information

Key facts about A.C. Formula II, straight from the product label.

Brand Pure Encapsulations
Barcode (UPC) 766298014012
Net contents 120 Capsule(s)
Market status On market
Date entered into DSLD Jul 18, 2023
DSLD ID 293871
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Women (not pregnant or lactating), 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 A.C. Formula II by Pure Encapsulations, 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
60
UPC/BARCODE
766298014012
IngredientAmount% DV
Caprylic Acid400 mg--
Bromelain250 mg--
Undecylenic Acid125 mg--
Grapefruit (Citrus x paradisi) extract100 mg--
Berberine Sulfate50 mg--
Calcium44 mg3%
Magnesium17 mg4%

Other ingredients: Cellulose, Water, hypoallergenic Plant Fiber

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.
Storage

Store in a cool, dry place.

Suggested/Recommended/Usage/Directions

Recommendations: As a dietary supplement, take 2-capsules, 1-3 times daily, just before meals, with 6-8 oz water.

Precautions

Warning: Not to be taken by pregnant or lactating women. If you have any health condition or are taking any medication, consult your health professional before use.

Keep out of the reach of children.

Use only if safety seal is intact.

General Statements

Contents may not fill package in order to accommodate required labeling. Please rely on stated quantity. Scan to learn about our hypoallergenic supplements

Formulation

Certified Gluten-Free by the Gluten-Free Certification Organization, www.gluten.org

Supports intestinal microbial balance Gluten-free, Non-GMO & hypoallergenic

Gluten-free, Non-GMO & hypoallergenic

Seals/Symbols

GFCO.org (Gluten-Free Certification Organization)

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

A.C. Formula II by Pure Encapsulations label

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

A.C. Formula II 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 A.C. Formula II by Pure Encapsulations

These are the 7 active ingredients this product is made of. Select any to open its full monograph.

Serving size2 Capsule(s) Dosage formCapsule Servings per container60 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.

Caprylic Acid

Interacts with
262 drugs
400 mg per serving Form: Calcium Caprylate, Magnesium Caprylate

Caprylic acid is a medium-chain fatty acid found in coconut oil and palm kernel oil that is popularly used for yeast overgrowth and gut health. While...

Caprylic Acid monograph & interactions

Bromelain

Interacts with
141 drugs
250 mg per serving Form: Pineapple

Bromelain is a group of protein-digesting enzymes from pineapple that people take mainly for inflammation, swelling, and sinus problems. Some early st...

Bromelain monograph & interactions

Undecylenic Acid

125 mg per serving

Grapefruit (Citrus x paradisi) extract

Interacts with
990 drugs
100 mg per serving

Grapefruit is a nutritious citrus fruit rich in vitamin C and other nutrients, and it is generally safe to eat. However, grapefruit is famous for seri...

Grapefruit (Citrus x paradisi) extract monograph & interactions

Berberine Sulfate

Interacts with
1,160 drugs
50 mg per serving

Berberine is a yellow plant compound that has shown promise for lowering blood sugar and cholesterol in some studies, but the quality of research vari...

Berberine Sulfate monograph & interactions

Calcium

Interacts with
168 drugs
44 mg per serving Form: Calcium Caprylate, Calcium Undecylenate

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

Calcium monograph & interactions

Magnesium

Interacts with
295 drugs
17 mg per serving Form: Magnesium Caprylate

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

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

Interaction report

A.C. Formula II by Pure Encapsulations Drug Interactions

Want to check YOUR meds against A.C. Formula II?

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
1,445Drugs
785 Major 623 Moderate 37 Minor

Ingredients driving the most interactions

Berberine Sulfate 1,160
Grapefruit (Citrus x paradisi) extract 990
Magnesium 295
Caprylic Acid 262
Calcium 168

Individual Drug Interactions

The ingredients in A.C. Formula II interact with 1,445 drugs. Click any drug to see the details.

6 of the 7 ingredients in A.C. Formula II interact with drugs. Each result below shows which ingredient is responsible. Berberine Sulfate Grapefruit (Citrus x paradisi) extract Magnesium Caprylic Acid Calcium Bromelain

Each ingredient & the kinds of drugs it affects

For each ingredient in A.C. Formula II 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.

Berberine Sulfate15 drug types · 1,160 drugs

Cyclosporine (Neoral, Sandimmune)

Berberine can increase serum levels of cyclosporine.
Berberine can reduce metabolism and increase serum levels of cyclosporine. Berberine might inhibit cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine.

Likelihood Probable Evidence A
Anticoagulant/Antiplatelet Drugs

Theoretically, berberine might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
In vitro and in vivo research suggest that berberine can inhibit platelet aggregation. Theoretically, berberine might have additive effects when used with anticoagulant and antiplatelet drugs and increase the risk of bleeding.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, berberine may increase the risk of hypoglycemia when taken with antidiabetes drugs.
Clinical research shows that berberine may lower blood glucose levels. Theoretically, berberine might have additive effects with antidiabetes drugs and increase the risk of hypoglycemia.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, berberine might have additive effects with antihypertensive drugs.
Animal research suggests that berberine can have hypotensive effects. Also, a clinical study suggests that taking berberine in combination with amlodipine can lower systolic and diastolic blood pressure when compared with amlodipine alone.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, berberine might increase the sedative effects of CNS depressants.
Animal research suggests that berberine may have sedative effects. Theoretically, use of berberine along with CNS depressants might produce additive therapeutic and adverse effects.

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

Theoretically, berberine might increase serum levels of drugs metabolized by CYP2C9.
Preliminary clinical research shows that berberine can inhibit CYP2C9. Theoretically, taking berberine with drugs metabolized by CYP2C9 might increase drug levels and increase the risk of adverse effects.

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

Theoretically, berberine might increase serum levels of drugs metabolized by CYP2D6.
In vitro research and preliminary clinical evidence show that berberine can inhibit CYP2D6. Theoretically, use of berberine with drugs metabolized by CYP2D6 might increase drug levels and increase the risk of adverse effects.

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

Theoretically, berberine might increase serum levels of drugs metabolized by CYP3A4.
In vitro research and preliminary clinical research show that berberine moderately inhibits CYP3A4. Theoretically, use of berberine with drugs metabolized by CYP3A4 might increase drug levels and increase the risk of adverse effects.

Likelihood Possible Evidence A
Dextromethorphan (Robitussin Dm, Others)

Theoretically, berberine may increase serum levels of dextromethorphan.
Preliminary clinical research shows that berberine can inhibit cytochrome P450 2D6 (CYP2D6) activity and reduce the metabolism of dextromethorphan. This may increase the effects and side effects of dextromethorphan.

Likelihood Possible Evidence B
Losartan (Cozaar)

Berberine might reduce the therapeutic effects of losartan by decreasing its conversion to its active form.
Preliminary clinical research suggests that berberine can inhibit cytochrome P450 2C9 (CYP2C9) activity and reduce metabolism of losartan.

Likelihood Possible Evidence B
Metformin (Glucophage)

Theoretically, berberine might increase the therapeutic and adverse effects of metformin.
In vitro and animal studies show that berberine can increase the systemic exposure and half-life of metformin, potentially increasing metformin's effects and side effects. This interaction seems to be most apparent when berberine is administered 2 hours prior to metformin. Taking berberine and metformin at the same time does not appear to increase systemic exposure to metformin.

Likelihood Possible Evidence D
Midazolam (Versed)

Berberine can reduce metabolism of midazolam, which might increase the risk of severe adverse effects.
Preliminary clinical research shows that berberine can inhibit cytochrome P450 3A4 (CYP3A4) activity and reduce metabolism of midazolam.

Likelihood Possible Evidence B
Pentobarbital (Nembutal)

Berberine might increase the sedative effect of pentobarbital.
Evidence from animal research shows that berberine can prolong pentobarbital-induced sleeping time. Theoretically, combining berberine and pentobarbital might increase the sedative effects of pentobarbital.

Likelihood Possible Evidence D
Tacrolimus (Prograf)

Berberine has been associated with increased blood levels of tacrolimus.
In a 16-year-old patient with idiopathic nephrotic syndrome who was being treated with tacrolimus 6.5 mg twice daily, intake of berberine 200 mg three times daily increased the blood concentration of tacrolimus from 8 to 22 ng/mL. Following a reduction of the tacrolimus dose to 3 mg daily, blood levels of tacrolimus decreased to 12 ng/mL.

Likelihood Possible Evidence D
Acetazolamide

Laboratory studies and initial clinical findings suggest that berberine has the potential to increase acetazolamide concentrations in the body. More research is needed to confirm this interaction.

Likelihood Possible Evidence C
Berberine Sulfate full monograph & interactions

Grapefruit (Citrus x paradisi) extract62 drug types · 990 drugs

Amiodarone (Cordarone)

Grapefruit juice can increase blood levels of amiodarone, potentially increasing the effects and adverse effects of amiodarone.
Clinical research shows that grapefruit juice inhibits metabolism and increases absorption of amiodarone. Grapefruit juice increases amiodarone plasma levels by 50% and peak concentration by 84%.

Likelihood Probable Evidence B
Artemether (Artenam, Paluther)

Grapefruit juice can increase blood levels of oral artemether, potentially increasing the effects and adverse effects of artemether.
Clinical research shows that grapefruit juice increases the levels of oral artemether by 90% to 250% in healthy males.

Likelihood Likely Evidence B
Benzodiazepines

Grapefruit juice might increase blood levels of some oral benzodiazepines, potentially increasing the effects and adverse effects of these drugs.
Clinical research shows that grapefruit juice can increase plasma triazolam concentrations. Repeated consumption of grapefruit juice greatly increases triazolam concentrations and prolongs the half-life, probably due to inhibition of cytochrome P450 3A4 (CYP3A4). Some studies show that grapefruit juice, particularly when taken in large quantities, reduces the clearance and increases the maximum blood levels, area under the plasma concentration curve (AUC), and duration of effect of midazolam. However, there is no effect on intravenous midazolam. Grapefruit juice has also been shown to increase the maximum blood levels and duration of effect of diazepam, but the clinical significance of this is not known. This interaction does not appear to occur with alprazolam.

Likelihood Likely Evidence B
Buspirone (Buspar)

Grapefruit juice can increase blood levels of buspirone, potentially increasing the effects and adverse effects of buspirone.
Clinical research shows that grapefruit juice increases absorption and plasma concentrations of buspirone.

Likelihood Likely Evidence B
Calcium Channel Blockers

Grapefruit juice can increase blood levels of oral calcium channel blockers, potentially increasing the effects and adverse effects of these drugs.
Clinical research shows that grapefruit juice increases absorption and plasma concentrations of amlodipine, nifedipine, nisoldipine, verapamil, felodipine, nimodipine, nicardipine, diltiazem, pranidipine, nitrendipine, and manidipine, This interaction is likely the result of the inhibition of intestinal metabolism of these drugs by CYP3A4, although some research suggests grapefruit may alter plasma drug levels by reducing the rate of gastric emptying. Consuming grapefruit juice 1 liter daily increases steady state concentrations of verapamil by as much as 50%. However, some references dispute the clinical relevance of the interactions with amlodipine, diltiazem, and verapamil. Other research in healthy individuals suggests plasma levels of felodipine and nifedipine are not affected when given intravenously. There is considerable interindividual variability in the effect of grapefruit juice on drug metabolism, which might account for inconsistent study results. In healthy older adults, the hemodynamic response to felodipine plus grapefruit juice might be influenced by altered autonomic regulation. In older healthy adults, a single dose of grapefruit juice and felodipine enhanced the blood pressure-lowering effects of felodipine. However, after a week of grapefruit juice and felodipine (steady state), the hypotensive activity was reduced, possibly due to compensatory tachycardia. Research indicates it is necessary to withhold grapefruit juice for as long as 3 days to avoid interactions with felodipine and nisoldipine.

Likelihood Likely Evidence B
Carbamazepine (Tegretol)

Grapefruit juice can increase blood levels of carbamazepine, potentially increasing the effects and adverse effects of carbamazepine.
Clinical research shows that grapefruit juice increases absorption and plasma concentrations of carbamazepine.

Likelihood Likely Evidence B
Carvedilol (Coreg)

Grapefruit juice can increase blood levels of carvedilol, potentially increasing the effects and adverse effects of carvedilol.
Clinical research shows that grapefruit juice increases the bioavailability of a single dose of carvedilol by 16%.

Likelihood Likely Evidence B
Celiprolol (Celicard)

Grapefruit juice can decrease blood levels of celiprolol, potentially decreasing the clinical effects of celiprolol.
In human research, taking grapefruit juice within two hours of celiprolol appears to decrease absorption and blood levels of celiprolol by approximately 85%. This interaction is due to grapefruit-induced inhibition of organic anion transporting polypeptide (OATP). Grapefruit juice is thought to affect OATP for only a short time. Therefore, separating drug administration and consumption of grapefruit by at least 4 hours is likely to prevent this interaction.

Likelihood Probable Evidence B
Cisapride (Propulsid)

Grapefruit juice can increase blood levels of cisapride, potentially increasing the effects and adverse effects of cisapride.
Clinical research shows that grapefruit juice increases the absorption and plasma concentrations of cisapride. According to the cisapride prescribing information, grapefruit juice is contraindicated in patients taking cisapride.

Likelihood Likely Evidence B
Clomipramine (Anafranil)

Theoretically, grapefruit juice might increase blood levels of clomipramine, potentially increasing the effects and adverse effects of clomipramine.
Case reports have shown that clomipramine trough levels increase significantly after the addition of grapefruit juice to the therapeutic regimen.

Likelihood Probable Evidence D
Clopidogrel (Plavix)

Grapefruit juice can decrease blood levels of the active metabolite of clopidogrel, thereby decreasing the antiplatelet effect of clopidogrel.
Clopidogrel is an antiplatelet prodrug that is metabolized primarily by cytochrome P450 2C19 (CYP2C19) to form the active metabolite. A small clinical study shows that taking grapefruit juice with clopidogrel decreases plasma levels of the active metabolite by more than 80% and impairs the antiplatelet effect of clopidogrel. This effect is possibly due to grapefruit-induced inhibition of CYP2C19.

Likelihood Probable Evidence B
Cyclosporine (Neoral, Sandimmune)

Grapefruit juice can increase blood levels of oral cyclosporine, potentially increasing the effects and adverse effects of cyclosporine.
Clinical research shows that grapefruit juice increases the absorption and plasma concentrations of cyclosporine. The mechanism of action is unclear. However, there is no effect on intravenous cyclosporine.

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

Grapefruit juice can increase levels of drugs metabolized by CYP3A4.
Clinical research shows that grapefruit juice can inhibit CYP3A4 metabolism of drugs, causing increased drug levels and potentially increasing the risk of adverse effects. When taken orally, effects of grapefruit juice on CYP3A4 levels appear to last at least 48 hours. Grapefruit's ability to inhibit CYP3A4 has even been harnessed to intentionally increase levels of venetoclax, which is metabolized by CYP3A4, in an elderly patient with acute myeloid leukemia who could not afford full dose venetoclax. The lower dose of venetoclax in combination with grapefruit juice resulted in serum levels of venetoclax in the therapeutic reference range of full dose venetoclax and positive treatment outcomes for the patient.
Professional consensus recommends the consideration of patient age, existing medical conditions, additional medications, and the potential for additive adverse effects when evaluating the risks of concomitant use of grapefruit juice with any medication metabolized by CYP3A4. While all patients are at risk for interactions with grapefruit juice consumption, patients older than 70 years of age and those taking multiple medications are at the greatest risk for a serious or fatal interaction with grapefruit juice.

Likelihood Likely Evidence B
Dextromethorphan (Robitussin Dm, Others)

Grapefruit juice can increase blood levels of dextromethorphan, potentially increasing the effects and adverse effects of dextromethorphan.
Clinical research shows that grapefruit juice can inhibit cytochrome P450 3A4 (CYP3A4) metabolism, causing increased dextromethorphan levels.

Likelihood Probable Evidence B
Estrogens

Grapefruit juice can increase blood levels of estrogens, potentially increasing the effects and adverse effects of estrogens.
Clinical research shows that grapefruit increases the levels of endogenous and exogenous estrogens by inhibiting cytochrome P450 3A4 (CYP3A4) enzymes. Grapefruit juice increases exogenously administered 17-beta-estradiol by about 20% in females without ovaries and ethinyl-estradiol in healthy females.

Likelihood Probable Evidence B
Etoposide (Vepesid)

Grapefruit juice can decrease blood levels of etoposide, potentially decreasing the clinical effects of etoposide.
Clinical research shows that grapefruit juice decreases the absorption and plasma concentrations of etoposide. There is some evidence that grapefruit juice co-administered with oral etoposide can reduce levels of etoposide by about 26%. Grapefruit juice seems to inhibit organic anion transporting polypeptide (OATP), which is a drug transporter in the gut, liver, and kidney. Grapefruit juice is thought to affect OATP for only a short time. Therefore, separating drug administration and consumption of grapefruit by at least 4 hours is likely to prevent this interaction.

Likelihood Probable Evidence B
Halofantrine

Grapefruit juice can increase blood levels of halofantrine, potentially increasing the effects and adverse effects of halofantrine.
Clinical research shows that grapefruit juice inhibits cytochrome P450 3A4 (CYP3A4) metabolism, which increases halofantrine levels and peak concentration, as well as a marker of ventricular tachyarrhythmia potential.

Likelihood Probable Evidence B
Hmg-Coa Reductase Inhibitors ("Statins")

Grapefruit juice can increase blood levels of statins that are metabolized by cytochrome P450 3A4 (CYP3A4), potentially increasing the effects and adverse effects of these statins. Additionally, grapefruit juice might interfere with the bioavailability of statins that are substrates of organic anion transporting polypeptides (OATP).
Clinical research shows that grapefruit juice inhibits metabolism and increases absorption and plasma concentrations of statins that are metabolized by CYP3A4. These include lovastatin, simvastatin, and atorvastatin. Keep in mind that there is considerable variability in the effect of grapefruit juice on drug metabolism, so individual patient response is difficult to predict.
Some statins, including pravastatin, fluvastatin, pitavastatin, and rosuvastatin, are not metabolized by CYP3A4. However, grapefruit juice might still affect the bioavailability of these statins. These statins are substrates of OATP. Grapefruit juice can inhibit OATP. Therefore, grapefruit juice may reduce the bioavailability or increase drug levels of these statins depending on the type of OATP. However, grapefruit juice affects OATP for only a short time. Therefore, separating drug administration by at least 4 hours is likely to avoid this interaction.

Likelihood Likely Evidence B
Methadone (Dolophine)

Grapefruit juice can increase blood levels of methadone, potentially increasing the effects and adverse effects of methadone.
Clinical research shows that grapefruit juice inhibits the metabolism of methadone, increasing methadone levels and peak concentrations. In one case, a 51-year-old male taking methadone 90 mg daily and no other medications was found unresponsive. The patient reported drinking grapefruit juice 500 mL daily for 3 days prior to the event. Methadone is a substrate of cytochrome P450 3A4 (CYP3A4), and grapefruit juice-induced inhibition of CYP3A4 is the likely cause of this interaction.

Likelihood Probable Evidence B
Methylprednisolone

Grapefruit juice can increase blood levels of methylprednisolone, potentially increasing the effects and adverse effects of methylprednisolone.
Clinical research shows that grapefruit juice can increase the plasma concentration of orally administered methylprednisolone. Grapefruit juice 200 mL three times daily given with methylprednisolone 16 mg increased methylprednisolone half-life by 35%, peak plasma concentration by 27%, and total area under the curve by 75%.

Likelihood Likely Evidence B
Organic Anion-Transporting Polypeptide Substrates (Oatp)

Grapefruit juice can decrease levels of drugs that are substrates of OATP.
In vitro and clinical research show that consuming grapefruit juice inhibits OATP, which reduces the bioavailability of oral drugs that are substrates of OATP. Various clinical studies have shown reduced absorption of OATP substrates when taken with grapefruit, including fexofenadine, acebutolol, aliskiren, celiprolol, levothyroxine, nadolol, and pitavastatin. Grapefruit juice is thought to affect OATP for only a short time. Therefore, separating drug administration and consumption of grapefruit by at least 4 hours is likely to prevent this interaction.

Likelihood Likely Evidence B
Praziquantel (Biltricide)

Grapefruit juice can increase blood levels of praziquantel, potentially increasing the effects and adverse effects of praziquantel.
Clinical research shows that grapefruit juice can inhibit cytochrome P450 3A4 (CYP3A4) metabolism of praziquantel. Plasma concentrations of praziquantel can increase by as much as 160% when administered with 250 mL of commercially available grapefruit juice.

Likelihood Probable Evidence B
Qt Interval-Prolonging Drugs

Grapefruit or grapefruit juice, especially if consumed in large amounts, can cause additive QT interval prolongation when taken with QT interval-prolonging drugs, potentially increasing the risk of ventricular arrhythmias.
Clinical research in healthy volunteers shows that drinking 6 liters of grapefruit juice over 6 hours prolonged the QTc by a peak amount of 14 milliseconds (ms). This prolongation was similar to the QT prolongation caused by the drug moxifloxacin. In individuals with long QT syndrome, a smaller dose of grapefruit juice, 1.5 liters, resulted in a greater peak QTc prolongation of about 30 ms. The effect of smaller quantities of grapefruit juice on the QT interval is unclear.

Likelihood Probable Evidence B
Quetiapine (Seroquel)

Grapefruit juice may increase blood levels of quetiapine, increasing the effects and adverse effects of quetiapine.
Quetiapine is metabolized by cytochrome P450 3A4 (CYP3A4). Grapefruit can inhibit CYP3A4. In one case report, a healthy 28-year-old female with bipolar disorder stabilized on quetiapine 800 mg daily presented with quetiapine toxicity considered to be related to consuming a gallon of grapefruit juice over the past 24 hours.

Likelihood Probable Evidence B
Quinidine

Grapefruit juice can alter blood levels of quinidine, potentially increasing or decreasing the clinical effects of quinidine.
Clinical research shows that grapefruit juice decreases quinidine absorption, clearance, and metabolism, and prolongs the half-life by about 20%.

Likelihood Probable Evidence B
Grapefruit (Citrus x paradisi) extract full monograph & all 62 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

Caprylic Acid3 drug types · 262 drugs

Antihypertensive Drugs

Theoretically, caprylic acid might increase the risk of hypotension when used with antihypertensive drugs.
Animal research suggests that caprylic acid might have positive inotropic effects, resulting in reduced arterial pressure and vascular resistance and increased cardiac output.

Likelihood Possible Evidence D
Nonsteroidal Anti-Inflammatory Drugs (Nsaids)

Theoretically, caprylic acid might increase plasma concentrations of NSAIDs.
In vitro research suggests that caprylic acid might displace NSAIDs from binding sites on albumin. This effect has not been reported in humans.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, caprylic acid might increase plasma concentrations of warfarin.
In vitro research suggests that high doses of caprylic acid might displace warfarin from albumin binding sites. This effect has not been reported in humans.

Likelihood Possible Evidence D
Caprylic Acid 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

Bromelain2 drug types · 141 drugs

Anticoagulant/Antiplatelet Drugs

Bromelain may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
There is one case report of a patient experiencing minor bruising while taking bromelain with naproxen. Bromelain is thought to have antiplatelet activity. Whether this interaction is of concern with topical bromelain is unclear. Interference with coagulation of burn wounds has been reported in a patient receiving bromelain-based enzymatic debridement. However, observational research has found that topical bromelain debridement is not associated with increases or decreases in laboratory markers of coagulation when compared with surgical debridement.

Likelihood Possible Evidence D
Tetracycline Antibiotics

Theoretically, bromelain might increase levels of tetracycline antibiotics.
Laboratory research suggests that bromelain might increase the absorption of tetracycline antibiotics. However, a study in healthy adults reported no difference in tetracycline plasma levels when a 500 mg dose was taken with or without bromelain 80 mg.

Likelihood Possible Evidence B
Bromelain full monograph & interactions
The maker

Brand information

Manufacturer and brand details for A.C. Formula II, from the product label.

Pure Encapsulations

See all Pure Encapsulations products
Name
Pure Encapsulations
Street Address
490 Boston Post Road
City
Sudbury
State
MA
Phone Number
1-800-753-2277
Web Address
www.PureEncapsulations.com
Pharmacist Counseling Corner

A.C. Formula II by Pure Encapsulations: Common Questions

Does A.C. Formula II by Pure Encapsulations interact with any medications?
Yes. Based on its ingredients, A.C. Formula II has a known interaction with 1,445 medications, including 785 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
A.C. Formula II contains 7 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 product if I'm pregnant or breastfeeding?
No—bromelain and berberine sulfate should be avoided in pregnancy and while breastfeeding; safety data is insufficient or shows potential harm. Caprylic acid's safety at supplement doses in pregnancy and nursing is unknown. Calcium and magnesium are needed in pregnancy and breastfeeding, but talk with your doctor or pharmacist about the right amount and whether this formula is appropriate for you, especially given the other ingredients.
What's caprylic acid for?
Caprylic acid is a fatty acid included for potential effects on epilepsy and essential tremor, but evidence supporting it is insufficient. It's recognized as safe in food but supplement safety is less studied.
Will this help my stomach or digestive issues?
Bromelain may help with digestion for some people, and both calcium and magnesium are effective for upset stomach. However, the formula also contains ingredients that commonly cause stomach side effects—like diarrhea, gas, and discomfort—so results vary by person.
What's berberine sulfate in here for?
Berberine sulfate is possibly effective for high cholesterol, PCOS, certain infections, high blood pressure, and diabetes. It does interact with many medications, so check with your pharmacist first if you take any prescriptions.
Is this product safe to use long-term?
Bromelain and berberine safety is studied mainly short-term; long-term safety data is limited. Calcium and magnesium can be used long-term at appropriate doses. Given the interaction risk with this multi-ingredient formula, talk with your pharmacist about your specific situation and how long you plan to take it.
What's the grapefruit extract doing in this formula?
Grapefruit extract is included for potential benefits in several conditions—acne, asthma, atherosclerosis, headache, and infection—but evidence is insufficient. More importantly, it has Major interactions with multiple medications, so it's a key reason to check your drug list before taking this 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.

A.C. Formula II label
Go deeper

The Full Monographs Behind A.C. Formula II’s Ingredients

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

Herb & supplement monograph

Caprylic Acid

Interacts with 262 drugs

Caprylic acid is a medium-chain fatty acid found in coconut oil and palm kernel oil that is popularly used for yeast overgrowth and gut health. While laboratory studies show it has antimicro...

Read the full Caprylic Acid monograph → Herb & supplement monograph

Bromelain

Interacts with 141 drugs

Bromelain is a group of protein-digesting enzymes from pineapple that people take mainly for inflammation, swelling, and sinus problems. Some early studies are promising, but the overall evi...

Read the full Bromelain monograph → Herb & supplement monograph

Grapefruit

Interacts with 990 drugs

Grapefruit is a nutritious citrus fruit rich in vitamin C and other nutrients, and it is generally safe to eat. However, grapefruit is famous for serious interactions with many prescription...

Read the full Grapefruit monograph → Herb & supplement monograph

Berberine

Interacts with 1,160 drugs

Berberine is a yellow plant compound that has shown promise for lowering blood sugar and cholesterol in some studies, but the quality of research varies and it is not a replacement for presc...

Read the full Berberine monograph → Herb & supplement monograph

Calcium

Interacts with 168 drugs

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

Read the full Calcium monograph → Herb & supplement monograph

Magnesium

Interacts with 295 drugs

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

Read the full Magnesium monograph →
Sources

Sources & How We Checked

A.C. Formula II'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 366 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.

Caprylic Acid 5 references
  1. Massolini G, Aubry AF, McGann A, Wainer IW. Determination of the magnitude and enantioselectivity of ligand binding to rat and rabbit serum albumins using immobilized-protein high performance liquid chromatography stationary phases. Biochem Pharmacol 1993 PubMed
  2. Kristev A, Mitkov D, Lukanov Y, Chapkynov P. The effect of octanoic fatty acid on the cardiovascular system of the guinea pig. Cor Vasa 1989;31(4):321-7.
  3. Hayball PF, Holman JW, Nation RL. Influence of octanoic acid on the reversible protein binding of ketorolac enantiomers to human serum albumin (HSA): comparative liquid chromatographic studies using a HSA chiral stationary phase. J Chromatogr B Biomed App PubMed
  4. Noctor TA, Wainer IW, Hage DS. Allosteric and competitive displacement of drugs from human serum albumin by octanoic acid, as revealed by high-performance liquid affinity chromatography, on a human serum albumin-based stationary phase. J Chromatogr 1992;5 PubMed
  5. Voller B, Lines E, McCrossin G, et al. Dose-escalation study of octanoic acid in patients with essential tremor. J Clin Invest. 2016;126(4):1451-7. PubMed

See these in context on the Caprylic Acid monograph →

Bromelain 19 references
  1. Nettis E, Napoli G, Ferrannini A, Tursi A. IgE-mediated allergy to bromelain. Allergy 2001;56:257-8. PubMed
  2. Taussig SJ, Batkin S. Bromelain, the enzyme complex of pineapple (Ananas comosus) and its clinical application. An update. J Ethnopharmacol 1988;22:191-203.. PubMed
  3. Bradbrook ID, Morrison PJ, Rogers HJ. The effect of bromelain on the absorption of orally administered tetracycline. Br J Clin Pharmacol 1978;6:552-4. PubMed
  4. Bush TM, Rayburn KS, Holloway SW, et al. Adverse interactions between herbal and dietary substances and prescription medications: a clinical survey. Altern Ther Health Med 2007;13:30-5.
  5. Brien S, Lewith G, Walker AF, et al. Bromelain as an adjunctive treatment for moderate-to-severe osteoarthritis of the knee: a randomized placebo-controlled pilot study. QJM 2006;99:841-50. PubMed
  6. Mori S, Ojima Y, Hirose T, et al. The clinical effect of proteolytic enzyme containing bromelain and trypsin on urinary tract infection evaluated by double blind method. Acta Obstet Gynaecol Jpn 1972;19:147-53.
  7. Glaser D, Hilberg T. The influence of bromelain on platelet count and platelet activity in vitro. Platelets 2006;17:37-41. PubMed
  8. Heinicke R M, van der Wal L, Yokoyama M. Effect of bromelain (Ananase) on human platelet aggregation. Experientia 1972;28:844-5. PubMed
  9. Gailhofer, G., Wilders-Truschnig, M., Smolle, J., and Ludvan, M. Asthma caused by bromelain: an occupational allergy. Clin Allergy 1988;18(5):445-450. PubMed
  10. Mattei, O., Fabri, G., and Farina, G. [Occupational health experience regarding four cases of asthma due to bromelain (author's transl)]. Medicina del Lavoro 1979;70(5):404-409.
  11. Galleguillos, F. and Rodriguez, J. C. Asthma caused by bromelin inhalation. Clin Allergy 1978;8(1):21-24. PubMed
  12. Perez-Camo I, Quirce S, Duran MA, and et al. Latex allergy: evidence of cross-reactivity with papain and bromelain [abstract]. Allergy 1996;51(suppl 31):48.
  13. Martin GJ, Ehrenreich J, and Asbell N. Bromelain: pineapple proteases with anti-edema activity. Exp Med Surg 1962;20:227-247.
  14. Kasemsuk T, Saengpetch N, Sibmooh N, Unchern S. Improved WOMAC score following 16-week treatment with bromelain for knee osteoarthritis. Clin Rheumatol. 2016 Oct;35(10):2531-40. PubMed
  15. Kutlu Ö, DemirbaS A, Elmas ÖF, Güvenç U, Metin A. Fixed drug eruption: a new side effect of bromelain. Contact Dermatitis 2020. Online ahead of print. PubMed
  16. Shoham Y, Shapira E, Haik J, et al. Bromelain-based enzymatic debridement of chronic wounds: Results of a multicentre randomized controlled trial. Wound Repair Regen 2021;29(6):899-907. PubMed
  17. Pfister P, Garcia Wendel PD, Kim BS, et al. Coagulation side effects of enzymatic debridement in burned patients. Burns 2022. PubMed
  18. Hasham S, Riyat H, Fletcher A, O'Boyle CP, Alexander S. To bleed or not to bleed? Case series and discussion of haemorrhage risk with enzymatic debridement in burn injuries. Scars Burn Heal 2023;9:20595131231168333. PubMed
  19. Leelakanok N, Petchsomrit A, Janurai T, Saechan C, Sunsandee N. Efficacy and safety of bromelain: A systematic review and meta-analysis. Nutr Health 2023. PubMed

See these in context on the Bromelain monograph →

Grapefruit 157 references
  1. Penzak SR, Gubbins PO, Gurley BJ, et al. Grapefruit juice decreases the systemic availability of itraconazole capsules in healthy volunteers. Ther Drug Monit 1999;21:304-9. PubMed
  2. Ioannides-Demos LL, Christophidis N, et al. Dosing implications of a clinical interaction between grapefruit juice and cyclosporine and metabolite concentrations in patients with autoimmune diseases. J Rheumatol 1997;24:49-54.
  3. Josefsson M, Zackrisson AL, Ahlner J. Effect of grapefruit juice on the pharmacokinetics of amlodipine in healthy volunteers. Eur J Clin Pharmacol 1996;51:189-93. PubMed
  4. Garg SK, Kumar N, Bhargava VK, Prabhakar SK. Effect of grapefruit juice on carbamazepine bioavailability in patients with epilepsy. Clin Pharmacol Ther 1998;64:286-8. PubMed
  5. Weber A, Jager R, Borner A, et al. Can grapefruit juice influence ethinylestradiol bioavailability? Contraception 1996;53:41-7.
  6. Schubert W, Cullberg G, Edgar B, Hedner T. Inhibition of 17 beta-estradiol metabolism by grapefruit juice in ovariectomized women. Maturitas 1994;20:155-63.
  7. Kantola T, Kivisto KT, Neuvonen PJ, et al. Grapefruit juice greatly increases serum concentrations of lovastatin and lovastatin acid. Clin Pharmacol Ther 1998 63:397-402. PubMed
  8. Bailey DG, Spence JD, Munoz C, Arnold JM. Interaction of citrus juices with felodipine and nifedipine. Lancet 1991;337:268-9. PubMed
  9. Bailey DG, Arnold JM, Strong HA, et al. Effect of grapefruit juice and naringin on nisoldipine pharmacokinetics. Clin Pharmacol Ther 1993;54:589-94. PubMed
  10. Rau SE, Bend JR, Arnold MO, et al. Grapefruit juice-terfenadine single-dose interaction: magnitude, mechanism, and relevance. Clin Pharmacol Ther 1997 61:401-9. PubMed
  11. Offman EM, Freeman DJ, Dresser GK, et al. Cisapride interaction with grapefruit juice and red wine. Clin Pharmacol Ther 2000;67:110 (abstract PI-83).
  12. Bailey DG, Dresser GK, Kreeft JH, et al. Grapefruit juice-felodipine interaction: Effect of segments and an extract from unprocessed fruit. Clin Pharmacol Ther 2000;67:107 (abstract PI-71).
  13. Soldner A, Christians U, Susanto M, et al. Grapefruit juice activates P-glycoprotein-mediated drug transport. Pharm Res 1999;16:478-85. PubMed
  14. Zaidenstein R, Avni B, Dishi V, et al. Effect of grapefruit juice on the pharmacokinetics of losartan in healthy volunteers. Clin Pharmacol Ther 1998;65:(abstract PI-60). DOI
  15. Dresser GK, Bailey DG, Carruthers SG. Grapefruit juice-felodipine interaction in healthy seniors. Clin Pharmacol Ther 1998;65:(abstract PIII-63).
  16. Varis T, Kivisto KT, Neuvonen PJ. Grapefruit juice can increase the plasma concentration of methylprednisolone. Eur J Clin Pharmacol 2000;56:489-93.
  17. Gross AS, Goh YD, Addison RS, et al. Influence of grapefruit juice on cisapride pharmacokinetics. Clin Pharmacol Ther 1999;65:395-401. PubMed
  18. Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice increases serum concentrations of atorvastatin and has no effect on pravastatin. Clin Pharmacol Ther 1999;66:118-27. DOI
  19. Ozdemir M, Aktan Y, Boydag BS. Interaction between grapefruit juice and diazepam in humans. Eur J Drug Metab Pharmacokinet 1998;23:55-9. PubMed
  20. Zaidenstein R, Dishi V, Gips M, et al. The effect of grapefruit juice on the pharmacokinetics of orally administered verapamil. Eur J Clin Pharmacol 1998;54:337-40. PubMed
  21. Lilja JJ, Kivisto KT, Backman JT, et al. Grapefruit juice substantially increases plasma concentrations of buspirone. Clin Pharmacol Ther 1998;64:655-60. PubMed
  22. Kupferschmidt HH, Fattinger KE, Ha HR, et al. Grapefruit juice enhances the bioavailability of the HIV protease inhibitor saquinavir in man. Br J Clin Pharmacol 1998;45:355-9. DOI
  23. Lilja JJ, Kivisto KT, Neuvonen PJ. Grapefruit juice-simvastatin interaction: effect on serum concentrations of simvastatin, simvastatin acid, and HMG-CoA reductase inhibitors. Clin Pharmacol Ther 1998;64:477-83. PubMed
  24. Curhan GC, Willett WC, Speizer FE, Stamfer MJ. Beverage use and risk of kidney stones in women. Ann Intern Med 1998;128:534-40.
  25. Fuhr U. Drug Interactions with Grapefruit Juice. Drug Saf 1998;18:251-72. DOI
  26. Oesterheld J, Kallepalli BR. Grapefruit juice and clomipramine: shifting metabolitic ratios. J Clin Psychopharmacol 1997;17:62-3. PubMed
  27. van Agtmael MA, Gupta V, van der Wosten TH, et al. Grapefruit juice increases the bioavailability of artemether. Eur J Clin Pharmacol 1999;55:405-10. PubMed
  28. van Agtmael MA, Gupta V, van der Graaf CA, van Boxtel CJ. The effect of grapefruit juice on the time-dependent decline of artemether plasma levels in healthy subjects. Clin Pharmacol Ther 1999;66:408-14.
  29. Damkier P, Hansen LL, Brosen K. Effect of diclofenac, disulfiram, itraconazole, grapefruit juice and erythromycin on the pharmacokinetics of quinidine. Br J Clin Pharmacol 1999;48:829-38. PubMed
  30. Takanaga H, Ohnishi A, Murakami H, et al. Relationship between time after intake of grapefruit juice and the effect on pharmacokinetics and pharmacodynamics of nisoldipine in healthy subjects. Clin Pharmacol Ther 2000:67:201-14. PubMed
  31. Takanaga H, Ohnishi A, Matsuo H, et al. Pharmacokinetic analysis of felodipine-grapefruit juice interaction based on an irreversible enzyme inhibition model. Br J Clin Pharmacol 2000;49:49-58. PubMed
  32. Coreg monograph. In: Gillis MC, Ed. Compendium of Pharmaceuticals and Specialities (CPS). 34th ed. Ottawa, Ontario, CAN:Canadian Pharmacists Assn, 1999:395.
  33. Dresser GK, Bailey DG, Carruthers SG. Grapefruit juice-felodipine interaction in the elderly. Clin Pharmacol Ther 2000;68:28-34. PubMed
  34. Bailey DG, Dresser GK, Munoz C, et al. Reduction of fexofenadine bioavailability by fruit juices. Clin Pharmacol Ther 2001;69:P21.
  35. Lilja JJ, Kivisto KT, Backman JT, Neuvonen PJ. Effect of grapefruit juice dose on grapefruit juice-triazolam interaction: repeated consumption prolongs triazolam half-life. Eur J Clin Pharmacol 2000;56:411-5. PubMed
  36. Erlund I, Meririnne E, Alfthan G, Aro A. Plasma kinetics and urinary excretion of the flavanones naringenin and hesperetin in humans after ingestion of orange juice and grapefruit juice. J Nutr 2001;131:235-41. PubMed
  37. Ho PC, Ghose K, Saville D, Wanwimolruk S. Effect of grapefruit juice on pharmacokinetics and pharmacodynamics of verapamil enantiomers in healthy volunteers. Eur J Clin Pharmacol 2000;56:693-8. PubMed
  38. Uno T, Ohkubo T, Sugawara K, et al. Effects of grapefruit juice on the stereoselective disposition of nicardipine in humans: evidence for dominant presystemic elimination at the gut site. Eur J Clin Pharmacol 2000;56:643-9. PubMed
  39. Bailey DG, Dresser GK. Grapefruit juice-lovastatin interaction. Clin Pharmacol Ther 2000;67:690.
  40. Lilja JJ, Kivisto KT, Neuvonen PJ. Duration of effect of grapefruit juice on the pharmacokinetics of the CYP3A4 substrate simvastatin. Clin Pharmacol Ther 2000;68:384-90. PubMed
  41. Castro N, Jung H, Medina R, et al. Interaction between grapefruit juice and praziquantel in humans. Antimicrob Agents Chemother 2002;46:1614-6. PubMed
  42. Jetter A, Kinzig-Schippers M, Walchner-Bonjean M, et al. Effects of grapefruit juice on the pharmacokinetics of sildenafil. Clin Pharmacol Ther 2002;71:21-9. PubMed
  43. Ebert U, Oertel R, Kirch W. Influence of grapefruit juice on scopolamine pharmacokinetics and pharmacodynamics in healthy male and female subjects. Int J Clin Pharmacol Ther 2000;38:523-31. PubMed
  44. Fuhr U, Muller-Peltzer H, Kern R, et al. Effects of grapefruit juice and smoking on verapamil concentrations in steady state. Eur J Clin Pharmacol 2002;58:45-53. PubMed
  45. Kanazawa S, Ohkubo T, Sugawara K. The effects of grapefruit juice on the pharmacokinetics of erythromycin. Eur J Clin Pharmacol 2001;56:799-803. PubMed
  46. Reif S, Nicolson M, Bisset D, et al. Effect of grapefruit juice intake on etoposide bioavailability. Eur J Clin Pharmacol 2002;58:491-4.. PubMed
  47. Greenblatt DJ, von Moltke LL, Harmatz JS. Time course of recovery of cytochrome P450 3A function after single doses of grapefruit juice. Clin Pharmacol Ther 2003;74:121-29 . PubMed
  48. Gupta MC, Garg SK, Badyal D, et al. Effect of grapefruit juice on the pharmacokinetics of theophylline in healthy male volunteers. Methods Find Exp Clin Pharmacol 1999;21:679-82. PubMed
  49. Edwards DJ, Fitzsimmons ME, Schuetz EG, et al. 6',7'-Dihydroxybergamottin in grapefruit juice and Seville orange juice: effects on cyclosporine disposition, enterocyte CYP3A4, and P-glycoprotein. Clin Pharmacol Ther 1999;65:237-44. PubMed
  50. Rogers JD, Zhao J, Liu L, et al. Grapefruit juice has minimal effects on plasma concentrations of lovastatin-derived 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors. Clin Pharmacol Ther 1999;66:358-66. PubMed
  51. Veronese ML, Gillen LP, Burke JP, et al. Exposure-dependent inhibition of intestinal and hepatic CYP3A4 in vivo by grapefruit juice. J Clin Pharmacol 2003;43:831-9. . PubMed
  52. Bailey DG, Dresser GK, Bend JR. Bergamottin, lime juice, and red wine as inhibitors of cytochrome P450 3A4 activity: comparison with grapefruit juice. Clin Pharmacol Ther 2003;73:529-37 . PubMed
  53. Becquemont L, Verstuyft C, Kerb R, et al. Effect of grapefruit juice on digoxin pharmacokinetics in humans. Clin Pharmacol Ther 2001;70:311-6. DOI
  54. Dresser GK, Bailey DG, Leake BF, et al. Fruit juices inhibit organic anion transporting polypeptide-mediated drug uptake to decrease the oral availability of fexofenadine. Clin Pharmacol Ther 2002;71:11-20. PubMed
  55. Parker RB, Yates CR, Soberman JE, Laizure SC. Effects of grapefruit juice on intestinal P-glycoprotein: evaluation using digoxin in humans. Pharmacotherapy 2003;23:979-87. PubMed
  56. Di Marco MP, Edwards DJ, Wainer IW, Ducharme MP. The effect of grapefruit juice and seville orange juice on the pharmacokinetics of dextromethorphan: the role of gut CYP3A and P-glycoprotein. Life Sci 2002;71:1149-60. PubMed
  57. Gaudineau C, Beckerman R, Welbourn S, Auclair K. Inhibition of human P450 enzymes by multiple constituents of the Ginkgo biloba extract. Biochem Biophys Res Comm 2004;318:1072–8. PubMed
  58. Sullivan DM, Ford MA, Boyden TW. Grapefruit juice and the response to warfarin. Am J Health-Syst Pharm 1998;55:1581-3. PubMed
  59. Fukazawa I, Uchida N, Uchida E, Yasuhara H. Effects of grapefruit juice on the pharmacokinetics of atorvastatin and pravastatin in Japanese. Br J Clin Pharmacol 2003;57:448-55.
  60. Unger M, Frank A. Simultaneous determination of the inhibitory potency of herbal extracts on the activity of six major cytochrome P450 enzymes using liquid chromatography/mass spectrometry and automated online extraction. Rapid Commun Mass Spectrom 2004;1 PubMed
  61. Zitron E, Scholz E, Owen RW, et al. QTc prolongation by grapefruit juice and its potential pharmacological basis: HERG channel blockade by flavonoids. Circulation 2005;835:835-8. PubMed
  62. Monroe KR, Murphy SP, Kolonel LN, Pike MC. Prospective study of grapefruit intake and risk of breast cancer in postmenopausal women: the Mutliethnic Cohort Study. Br J Cancer 2007;97:440-5.
  63. Farkas D, Oleson LE, Zhao Y, et al. Pomegranate juice does not impair clearance of oral or intravenous midazolam, a probe for cytochrome P450-3A activity: comparison with grapefruit juice. J Clin Pharmacol 2007;47:286-94. PubMed
  64. Potential drug interactions with grapefruit. Pharmacist's Letter / Prescriber's Letter 2007;23(2):230204.
  65. Dresser GK, Kim RB, Bailey DG. Effect of grapefruit juice volume on the reduction of fexofenadine bioavailability: possible role of organic anion transporting polypeptides. Clin Pharmacol Ther 2005;77:170-7. PubMed
  66. Greenblatt DJ. Analysis of drug interactions involving fruit beverages and organic anion-transporting polypeptides. J Clin Pharmacol 2009;49:1403-7. PubMed
  67. Bailey DG. Fruit juice inhibition of uptake transport: a new type of food-drug interaction. Br J Clin Pharmacol 2010;70:645-55. PubMed
  68. Product information for Cordarone. Wyeth Pharmaceuticals, Inc. Philadelphia, PA 19101. September 2006.
  69. Demarles D, Gillotin C, Bonaventure-Paci S, et al. Single-dose pharmacokinetics of amprenavir coadministered with grapefruit juice. Antimicrob Agents Chemother 2002;46:1589-90. PubMed
  70. Yasui N, Kondo T, Furukori H, et al. Effects of repeated ingestion of grapefruit juice on the single and multiple oral-dose pharmacokinetics and pharmacodynamics of alprazolam. Psychopharmacology (Berl) 2000;150:185-90. PubMed
  71. Hori H, Yoshimura R, Ueda N, et al. Grapefruit juice-fluvoxamine interaction -- is it risky or not? J Clin Psychopharmacol 2003;23:422-4. PubMed
  72. Benmebarek M, Devaud C, Gex-Fabry M, et al. Effects of grapefruit juice on the pharmacokinetics of the enantiomers of methadone. Clin Pharmacol Ther 2004;76:55-63.
  73. Yin OQ, Gallagher N, Li A, et al. Effect of grapefruit juice on the pharmacokinetics of nilotinib in healthy participants. J Clin Pharmacol 2010;50:188-94. PubMed
  74. Lilja JJ, Raaska K, Neuvonen PJ. Effects of grapefruit juice on the pharmacokinetics of acebutolol. Br J Clin Pharmacol 2005;60:659-63. PubMed
  75. Hollander, A. A., van Rooij, J., Lentjes, G. W., Arbouw, F., van Bree, J. B., Schoemaker, R. C., van Es, L. A., van der Woude, F. J., and Cohen, A. F. The effect of grapefruit juice on cyclosporine and prednisone metabolism in transplant patients. Clin Ph PubMed
  76. Sigusch, H., Hippius, M., Henschel, L., Kaufmann, K., and Hoffmann, A. Influence of grapefruit juice on the pharmacokinetics of a slow release nifedipine formulation. Pharmazie 1994;49(7):522-524.
  77. Andersen, V., Pedersen, N., Larsen, N. E., Sonne, J., and Larsen, S. Intestinal first pass metabolism of midazolam in liver cirrhosis --effect of grapefruit juice. Br J Clin Pharmacol 2002;54(2):120-124. PubMed
  78. Hukkinen, S. K., Varhe, A., Olkkola, K. T., and Neuvonen, P. J. Plasma concentrations of triazolam are increased by concomitant ingestion of grapefruit juice. Clin Pharmacol Ther 1995;58(2):127-131. PubMed
  79. Kupferschmidt, H. H., Ha, H. R., Ziegler, W. H., Meier, P. J., and Krahenbuhl, S. Interaction between grapefruit juice and midazolam in humans. Clin Pharmacol Ther 1995;58(1):20-28. PubMed
  80. Libersa, C. C., Brique, S. A., Motte, K. B., Caron, J. F., Guedon-Moreau, L. M., Humbert, L., Vincent, A., Devos, P., and Lhermitte, M. A. Dramatic inhibition of amiodarone metabolism induced by grapefruit juice. Br J Clin Pharmacol 2000;49(4):373-378. PubMed
  81. Min, D. I., Ku, Y. M., Geraets, D. R., and Lee, H. Effect of grapefruit juice on the pharmacokinetics and pharmacodynamics of quinidine in healthy volunteers. J Clin Pharmacol 1996;36(5):469-476. PubMed
  82. Lee, A. J., Chan, W. K., Harralson, A. F., Buffum, J., and Bui, B. C. The effects of grapefruit juice on sertraline metabolism: an in vitro and in vivo study. Clin Ther 1999;21(11):1890-1899. PubMed
  83. Kawakami, M., Suzuki, K., Ishizuka, T., Hidaka, T., Matsuki, Y., and Nakamura, H. Effect of grapefruit juice on pharmacokinetics of itraconazole in healthy subjects. Int J Clin Pharmacol Ther 1998;36(6):306-308.
  84. Benton, R. E., Honig, P. K., Zamani, K., Cantilena, L. R., and Woosley, R. L. Grapefruit juice alters terfenadine pharmacokinetics, resulting in prolongation of repolarization on the electrocardiogram. Clin Pharmacol Ther 1996;59(4):383-388. PubMed
  85. Clifford, C. P., Adams, D. A., Murray, S., Taylor, G. W., Wilkins, M. R., Boobis, A. R., and Davies, D. S. The cardiac effects of terfenadine after inhibition of its metabolism by grapefruit juice. Eur J Clin Pharmacol 1997;52(4):311-315. PubMed
  86. Ando, H., Tsuruoka, S., Yanagihara, H., Sugimoto, K., Miyata, M., Yamazoe, Y., Takamura, T., Kaneko, S., and Fujimura, A. Effects of grapefruit juice on the pharmacokinetics of pitavastatin and atorvastatin. Br J Clin Pharmacol 2005;60(5):494-497. DOI
  87. Lilja, J. J., Neuvonen, M., and Neuvonen, P. J. Effects of regular consumption of grapefruit juice on the pharmacokinetics of simvastatin. Br J Clin Pharmacol 2004;58(1):56-60. PubMed
  88. Charbit, B., Becquemont, L., Lepere, B., Peytavin, G., and Funck-Brentano, C. Pharmacokinetic and pharmacodynamic interaction between grapefruit juice and halofantrine. Clin Pharmacol Ther 2002;72(5):514-523. PubMed
  89. Cuong, B. T., Binh, V. Q., Dai, B., Duy, D. N., Lovell, C. M., Rieckmann, K. H., and Edstein, M. D. Does gender, food or grapefruit juice alter the pharmacokinetics of primaquine in healthy subjects? Br J Clin Pharmacol 2006;61(6):682-689. PubMed
  90. Culm-Merdek, K. E., von Moltke, L. L., Gan, L., Horan, K. A., Reynolds, R., Harmatz, J. S., Court MH, and Greenblatt, D. J. Effect of extended exposure to grapefruit juice on cytochrome P450 3A activity in humans: comparison with ritonavir. Clin Pharmacol
  91. Hugen, P. W., Burger, D. M., Koopmans, P. P., Stuart, J. W., Kroon, F. P., van Leusen, R., and Hekster, Y. A. Saquinavir soft-gel capsules (Fortovase) give lower exposure than expected, even after a high-fat breakfast. Pharm World Sci 2002;24(3):83-86.
  92. Sugimoto, K., Araki, N., Ohmori, M., Harada, K., Cui, Y., Tsuruoka, S., Kawaguchi, A., and Fujimura, A. Interaction between grapefruit juice and hypnotic drugs: comparison of triazolam and quazepam. Eur J Clin Pharmacol 2006;62(3):209-215. PubMed
  93. Lilja, J. J., Backman, J. T., Laitila, J., Luurila, H., and Neuvonen, P. J. Itraconazole increases but grapefruit juice greatly decreases plasma concentrations of celiprolol. Clin Pharmacol Ther 2003;73(3):192-198. PubMed
  94. Schwarz, U. I., Seemann, D., Oertel, R., Miehlke, S., Kuhlisch, E., Fromm, M. F., Kim, R. B., Bailey, D. G., and Kirch, W. Grapefruit juice ingestion significantly reduces talinolol bioavailability. Clin Pharmacol Ther 2005;77(4):291-301. PubMed
  95. Bailey, D. G., Arnold, J. M., Munoz, C., and Spence, J. D. Grapefruit juice--felodipine interaction: mechanism, predictability, and effect of naringin. Clin Pharmacol Ther 1993;53(6):637-642. PubMed
  96. Bailey, D. G., Arnold, J. M., Bend, J. R., Tran, L. T., and Spence, J. D. Grapefruit juice-felodipine interaction: reproducibility and characterization with the extended release drug formulation. Br J Clin Pharmacol 1995;40(2):135-140.
  97. Christensen, H., Asberg, A., Holmboe, A. B., and Berg, K. J. Coadministration of grapefruit juice increases systemic exposure of diltiazem in healthy volunteers. Eur J Clin Pharmacol 2002;58(8):515-520. PubMed
  98. Edgar, B., Bailey, D., Bergstrand, R., Johnsson, G., and Regardh, C. G. Acute effects of drinking grapefruit juice on the pharmacokinetics and dynamics of felodipine--and its potential clinical relevance. Eur J Clin Pharmacol 1992;42(3):313-317.
  99. Goosen, T. C., Cillie, D., Bailey, D. G., Yu, C., He, K., Hollenberg, P. F., Woster, P. M., Cohen, L., Williams, J. A., Rheeders, M., and Dijkstra, H. P. Bergamottin contribution to the grapefruit juice-felodipine interaction and disposition in humans. Cl PubMed
  100. Fuhr, U., Maier-Bruggemann, A., Blume, H., Muck, W., Unger, S., Kuhlmann, J., Huschka, C., Zaigler, M., Rietbrock, S., and Staib, A. H. Grapefruit juice increases oral nimodipine bioavailability. Int J Clin Pharmacol Ther 1998;36(3):126-132.
  101. Hashimoto, K., Shirafuji, T., Sekino, H., Matsuoka, O., Sekino, H., Onnagawa, O., Okamoto, T., Kudo, S., and Azuma, J. Interaction of citrus juices with pranidipine, a new 1,4-dihydropyridine calcium antagonist, in healthy subjects. Eur J Clin Pharmacol 1 PubMed
  102. Lundahl, J., Regardh, C. G., Edgar, B., and Johnsson, G. Effects of grapefruit juice ingestion--pharmacokinetics and haemodynamics of intravenously and orally administered felodipine in healthy men. Eur J Clin Pharmacol 1997;52(2):139-145. PubMed
  103. Lundahl, J., Regardh, C. G., Edgar, B., and Johnsson, G. Relationship between time of intake of grapefruit juice and its effect on pharmacokinetics and pharmacodynamics of felodipine in healthy subjects. Eur J Clin Pharmacol 1995;49(1-2):61-67. PubMed
  104. Rashid, T. J., Martin, U., Clarke, H., Waller, D. G., Renwick, A. G., and George, C. F. Factors affecting the absolute bioavailability of nifedipine. Br J Clin Pharmacol 1995;40(1):51-58. PubMed
  105. Soons, P. A., Vogels, B. A., Roosemalen, M. C., Schoemaker, H. C., Uchida, E., Edgar, B., Lundahl, J., Cohen, A. F., and Breimer, D. D. Grapefruit juice and cimetidine inhibit stereoselective metabolism of nitrendipine in humans. Clin Pharmacol Ther 1991; PubMed
  106. Rashid, J., McKinstry, C., Renwick, A. G., Dirnhuber, M., Waller, D. G., and George, C. F. Quercetin, an in vitro inhibitor of CYP3A, does not contribute to the interaction between nifedipine and grapefruit juice. Br J Clin Pharmacol 1993;36(5):460-463.
  107. Uno, T., Ohkubo, T., Motomura, S., and Sugawara, K. Effect of grapefruit juice on the disposition of manidipine enantiomers in healthy subjects. Br J Clin Pharmacol 2006;61(5):533-537. DOI
  108. Bistrup, C., Nielsen, F. T., Jeppesen, U. E., and Dieperink, H. Effect of grapefruit juice on Sandimmun Neoral absorption among stable renal allograft recipients. Nephrol Dial.Transplant. 2001;16(2):373-377. PubMed
  109. Ducharme, M. P., Warbasse, L. H., and Edwards, D. J. Disposition of intravenous and oral cyclosporine after administration with grapefruit juice. Clin Pharmacol Ther 1995;57(5):485-491. PubMed
  110. Ku, Y. M., Min, D. I., and Flanigan, M. Effect of grapefruit juice on the pharmacokinetics of microemulsion cyclosporine and its metabolite in healthy volunteers: does the formulation difference matter? J Clin Pharmacol 1998;38(10):959-965. PubMed
  111. Lee, M., Min, D. I., Ku, Y. M., and Flanigan, M. Effect of grapefruit juice on pharmacokinetics of microemulsion cyclosporine in African American subjects compared with Caucasian subjects: does ethnic difference matter? J Clin Pharmacol 2001;41(3):317-323 PubMed
  112. Schwarz, U. I., Johnston, P. E., Bailey, D. G., Kim, R. B., Mayo, G., and Milstone, A. Impact of citrus soft drinks relative to grapefruit juice on ciclosporin disposition. Br J Clin Pharmacol 2006;62(4):485-491. PubMed
  113. Yee, G. C., Stanley, D. L., Pessa, L. J., Dalla, Costa T., Beltz, S. E., Ruiz, J., and Lowenthal, D. T. Effect of grapefruit juice on blood cyclosporin concentration. Lancet 4-15-1995;345(8955):955-956. PubMed
  114. Paine, M. F., Widmer, W. W., Hart, H. L., Pusek, S. N., Beavers, K. L., Criss, A. B., Brown, S. S., Thomas, B. F., and Watkins, P. B. A furanocoumarin-free grapefruit juice establishes furanocoumarins as the mediators of the grapefruit juice-felodipine in
  115. Sigusch, H., Henschel, L., Kraul, H., Merkel, U., and Hoffmann, A. Lack of effect of grapefruit juice on diltiazem bioavailability in normal subjects. Pharmazie 1994;49(9):675-679.
  116. Fingerova, H., Oborna, I., Petrova, P., Budikova, M., and Jezdinsky, J. [Does grapefruit juice increase the bioavailability of orally administered sex steroids?]. Ceska.Gynekol. 2003;68(2):117-121.
  117. Glaeser, H., Bailey, D. G., Dresser, G. K., Gregor, J. C., Schwarz, U. I., McGrath, J. S., Jolicoeur, E., Lee, W., Leake, B. F., Tirona, R. G., and Kim, R. B. Intestinal drug transporter expression and the impact of grapefruit juice in humans. Clin Pharma PubMed
  118. Lilja, J. J., Laitinen, K., and Neuvonen, P. J. Effects of grapefruit juice on the absorption of levothyroxine. Br J Clin Pharmacol 2005;60(3):337-341. PubMed
  119. Kivisto, K. T., Lilja, J. J., Backman, J. T., and Neuvonen, P. J. Repeated consumption of grapefruit juice considerably increases plasma concentrations of cisapride. Clin Pharmacol Ther 1999;66(5):448-453. PubMed
  120. Desta, Z., Kivisto, K. T., Lilja, J. J., Backman, J. T., Soukhova, N., Neuvonen, P. J., and Flockhart, D. A. Stereoselective pharmacokinetics of cisapride in healthy volunteers and the effect of repeated administration of grapefruit juice. Br J Clin Pharm PubMed
  121. Odou, P., Ferrari, N., Barthelemy, C., Brique, S., Lhermitte, M., Vincent, A., Libersa, C., and Robert, H. Grapefruit juice-nifedipine interaction: possible involvement of several mechanisms. J Clin Pharm Ther 2005;30(2):153-158. PubMed
  122. Wason, S., DiGiacinto, J. L., and Davis, M. W. Effects of grapefruit and Seville orange juices on the pharmacokinetic properties of colchicine in healthy subjects. Clin Ther 2012;34(10):2161-2173. PubMed
  123. Bailey, D. G., Dresser, G. K., Kreeft, J. H., Munoz, C., Freeman, D. J., and Bend, J. R. Grapefruit-felodipine interaction: effect of unprocessed fruit and probable active ingredients. Clin Pharmacol Ther 2000;68(5):468-477. PubMed
  124. Kumar, A., Teuber, S. S., Naguwa, S., Prindiville, T., and Gershwin, M. E. Eosinophilic gastroenteritis and citrus-induced urticaria. Clin Rev Allergy Immunol 2006;30(1):61-70. PubMed
  125. Ferdman, R. M., Ong, P. Y., and Church, J. A. Pectin anaphylaxis and possible association with cashew allergy. Ann.Allergy Asthma Immunol. 2006;97(6):759-760. PubMed
  126. Guo, L. Q., Chen, Q. Y., Wang, X., Liu, Y. X., Chu, X. M., Cao, X. M., Li, J. H., and Yamazoe, Y. Different roles of pummelo furanocoumarin and cytochrome P450 3A5*3 polymorphism in the fate and action of felodipine. Curr Drug Metab 2007;8(6):623-630. PubMed
  127. Curhan, G. C., Willett, W. C., Rimm, E. B., Spiegelman, D., and Stampfer, M. J. Prospective study of beverage use and the risk of kidney stones. Am J Epidemiol. 2-1-1996;143(3):240-247. PubMed
  128. Holmberg MT, Tornio A, Joutsi-Korhonen L, Neuvonen M, Neuvonen PJ, Lassila R, Niemi M, Backman JT. Grapefruit juice markedly increases the plasma concentrations and antiplatelet effects of ticagrelor in healthy subjects. Br J Clin Pharmacol. 2013 Jun;75(6 PubMed
  129. Holmberg MT, Tornio A, Neuvonen M, Neuvonen PJ, Backman JT, Niemi M. Grapefruit juice inhibits the metabolic activation of clopidogrel. Clin Pharmacol Ther. 2014 Mar;95(3):307-13. PubMed
  130. Hu M, Mak VW, Yin OQ, Chu TT, Tomlinson B. Effects of grapefruit juice and SLCO1B1 388A>G polymorphism on the pharmacokinetics of pitavastatin. Drug Metab Pharmacokinet. 2013;28(2):104-8.
  131. Ieiri I, Doi Y, Maeda K, Sasaki T, Kimura M, Hirota T, Chiyoda T, Miyagawa M, Irie S, Iwasaki K, Sugiyama Y. Microdosing clinical study: pharmacokinetic, pharmacogenomic (SLCO2B1), and interaction (grapefruit juice) profiles of celiprolol following the or
  132. Misaka S, Miyazaki N, Yatabe MS, Ono T, Shikama Y, Fukushima T, Kimura J. Pharmacokinetic and pharmacodynamic interaction of nadolol with itraconazole, rifampicin and grapefruit juice in healthy volunteers. J Clin Pharmacol. 2013 Jul;53(7):738-45. PubMed
  133. Nieminen TH, Hagelberg NM, Saari TI, Neuvonen M, Neuvonen PJ, Laine K, Olkkola KT. Grapefruit juice enhances the exposure to oral oxycodone. Basic Clin Pharmacol Toxicol. 2010 Oct;107(4):782-8. PubMed
  134. Piccirillo G, Magrì D, Matera S, Magnanti M, Pasquazzi E, Schifano E, Velitti S, Mitra M, Marigliano V, Paroli M, Ghiselli A. Effects of pink grapefruit juice on QT variability in patients with dilated or hypertensive cardiomyopathy and in healthy subject
  135. Seidegård J, Randvall G, Nyberg L, Borgå O. Grapefruit juice interaction with oral budesonide: equal effect on immediate-release and delayed-release formulations. Pharmazie. 2009 Jul;64(7):461-5. DOI
  136. Shoaf SE, Mallikaarjun S, Bricmont P. Effect of grapefruit juice on the pharmacokinetics of tolvaptan, a non-peptide arginine vasopressin antagonist, in healthy subjects. Eur J Clin Pharmacol. 2012 Feb;68(2):207-11. PubMed
  137. Tanaka S, Uchida S, Miyakawa S, Inui N, Takeuchi K, Watanabe H, Namiki N. Comparison of inhibitory duration of grapefruit juice on organic anion-transporting polypeptide and cytochrome P450 3A4. Biol Pharm Bull. 2013;36(12):1936-41. PubMed
  138. Tapaninen T, Neuvonen PJ, Niemi M. Grapefruit juice greatly reduces the plasma concentrations of the OATP2B1 and CYP3A4 substrate aliskiren. Clin Pharmacol Ther. 2010 Sep;88(3):339-42. PubMed
  139. van Erp NP, Baker SD, Zandvliet AS, Ploeger BA, den Hollander M, Chen Z, den Hartigh J, König-Quartel JM, Guchelaar HJ, Gelderblom H. Marginal increase of sunitinib exposure by grapefruit juice. Cancer Chemother Pharmacol. 2011 Mar;67(3):695-703. PubMed
  140. Goldbart A, Press J, Sofer S, Kapelushnik J. Near fatal acute colchicine intoxication in a child. A case report. Eur J Pediatr. 2000;159(12):895-7. PubMed
  141. Dahan A, Amidon GL. Grapefruit juice and its constituents augment colchicine intestinal absorption: potential hazardous interaction and the role of p-glycoprotein. Pharm Res. 2009 Apr;26(4):883-92. PubMed
  142. Bailey DG. Predicting clinical relevance of grapefruit-drug interactions: a complicated process. J Clin Pharm Ther. 2017 Apr;42(2):125-27. PubMed
  143. Mouly S, Lloret-Linares C, Sellire PO, Sene D, Bergmann JF. Is the clinical relevance of drug-food and drug-herb interactions limited to grapefruit juice and Saint-John's Wort? Pharmacol Res. 2017 Apr;118:82-92. PubMed
  144. Tsuji H, Ohmura K, Nakashima R, et al. Efficacy and safety of grapefruit juice intake accompanying tacrolimus treatment in connective tissues disease patients. Intern Med. 2016;55(12):1547-52.
  145. Jia Y, Liu J, Xu J. Influence of grapefruit juice on pharmacokinetics of triptolide in rats grapefruit juice on the effects of triptolide. Xenobiotica. 2017 Apr 16:1-5. PubMed
  146. Kawaguchi-Suzuki M, Nasiri-Kenari N, Shuster J, et al. Effect of low-furanocoumarin hybrid grapefruit juice consumption on midazolam pharmacokinetics. J Clin Pharmacol. 2017 Mar;57(3):305-11. PubMed
  147. Chorin E, Hochstadt A, Granot Y, et al. Grapefruit juice prolongs the QT interval of healthy volunteers and patients with long QT syndrome. Heart Rhythm. 2019. pii: S1547-5271(19)30368-6. PubMed
  148. Ershad M, Cruz MD, Mostafa A, Mckeever R, Vearrier D, Greenberg MI. Opioid toxidrome following grapefruit juice consumption in the setting of methadone maintenance. J Addict Med 2019;[Epub ahead of print]. PubMed
  149. Shen X, Chen F, Wang F, Huang P, Luo W. The effect of grapefruit juice on the pharmacokinetics of tadalafil in rats. Biomed Res Int 2020;2020:1631735. PubMed
  150. Loretz C, Ho MD, Alam N, Mitchell W, Li AP. Application of cryopreserved human intestinal mucosa and cryopreserved human enterocytes in the evaluation of herb-drug interactions: evaluation of CYP3A inhibitory potential of grapefruit juice and commercial f
  151. Holmberg MT, Tornio A, Hyvärinen H, et al. Effect of grapefruit juice on the bioactivation of prasugrel. Br J Clin Pharmacol. 2015;80(1):139-45. PubMed
  152. Guideline on the investigation of drug interactions. CPMP/EWP/560/95/Rev. 1 Corr. 2. European Medicines Agency, 2015. Available at: https://www.ema.europa.eu/en/documents/scientific-guideline/guideline-investigation-drug-interactions-revision-1_en.pdf (As
  153. Cinderella MA, Morell B, Munjal S. Grapefruit Juice Cleanse Mimicking Quetiapine Overdose: Case Report and Review of Literature. J Clin Psychopharmacol 2021;41(6):690-692. PubMed
  154. Long Z, Ruan M, Wu W, Zeng Q, Li Q, Huang Z. The successful combination of grapefruit juice and venetoclax in an unfit acute myeloid leukemia patient with adverse risk: A case report. Front Oncol 2022;12:912696. PubMed
  155. Piscitelli J, Nikanjam M, Capparelli EV, et al. Fexofenadine Plasma Concentrations to Estimate Systemic Exposure in Healthy Adults Using a Limited Sampling Strategy with a Population Pharmacokinetic Approach. Ther Drug Monit 2023;45(4):539-545. PubMed
  156. Abu Dayyih W, Zakaraya Z, Hailat M, et al. The Validation and Determination of Empagliflozin Concentration in the Presence of Grapefruit Juice Using HPLC for Pharmacokinetic Applications. Molecules 2024;29(6):1236. PubMed
  157. Moffid MA, Mostafa EA, Mahmoud ST, Sayed RM. An eco-friendly ultra-performance liquid chromatography-mass spectrometry method for quantification of rivaroxaban and ticagrelor in rat plasma: grapefruit interactions. Bioanalysis 2023;15(22):1327-1341. PubMed

See these in context on the Grapefruit monograph →

Berberine 41 references
  1. Chan E. Displacement of bilirubin from albumin by berberine. Biol Neonate 1993;63:201-8. PubMed
  2. Janbaz KH, Gilani AH. Studies on preventive and curative effects of berberine on chemical-induced hepatotoxicity in rodents. Fitoterapia 2000;71:25-33.. PubMed
  3. 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
  4. 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
  5. Huang XS, Yang GF, Pan YC. Effect of berberin hydrochloride on blood concentration of cyclosporine A in cardiac transplanted patients. Zhongguo Zhong Xi Yi Jie He Za Zhi 2008;28:702-4.
  6. Budzinski JW, Foster BC, Vandenhoek S, Arnason JT. An in vitro evaluation of human cytochrome P450 3A4 inhibition by selected commercial herbal extracts and tinctures. Phytomedicine 2000;7:273-82. PubMed
  7. 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
  8. Marin-Neto, J. A., Maciel, B. C., Secches, A. L., and Gallo, Junior L. Cardiovascular effects of berberine in patients with severe congestive heart failure. Clin.Cardiol. 1988;11(4):253-260. PubMed
  9. Choudhry, V. P., Sabir, M., and Bhide, V. N. Berberine in giardiasis. Indian Pediatr. 1972;9(3):143-146.
  10. 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
  11. 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.
  12. 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
  13. Sharda DC. Berberine in the treatment of diarrhoea of infancy and childhood. J Indian M A 1970;54(1):22-24.
  14. Sabir M and Bhide NK. Study of some pharmacological actions of berberine. Ind J Physiol & Pharmac 1971;15(3):111-132.
  15. Tripathi YB and Shukla SD. Berberis artistata inhibits PAF induced aggregation of rabbit platelets. Phytotherapy Research 1996;10:628-630.
  16. Seery TM and Bieter RN. A contribution to the pharmacology of berberine. J Pharmacol Exp Ther 1940;69:64-67. DOI
  17. Xin, H. W., Wu, X. C., Li, Q., Yu, A. R., Zhong, M. Y., and Liu, Y. Y. The effects of berberine on the pharmacokinetics of cyclosporin A in healthy volunteers. Methods Find.Exp.Clin Pharmacol 2006;28(1):25-29.
  18. Zhang, Y., Li, X., Zou, D., Liu, W., Yang, J., Zhu, N., Huo, L., Wang, M., Hong, J., Wu, P., Ren, G., and Ning, G. Treatment of type 2 diabetes and dyslipidemia with the natural plant alkaloid berberine. J Clin Endocrinol.Metab 2008;93(7):2559-2565. PubMed
  19. Yin, J., Xing, H., and Ye, J. Efficacy of berberine in patients with type 2 diabetes mellitus. Metabolism 2008;57(5):712-717. PubMed
  20. 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
  21. 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
  22. 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
  23. Marazzi, G., Cacciotti, L., Pelliccia, F., Iaia, L., Volterrani, M., Caminiti, G., Sposato, B., Massaro, R., Grieco, F., and Rosano, G. Long-term effects of nutraceuticals (berberine, red yeast rice, policosanol) in elderly hypercholesterolemic patients. PubMed
  24. Meng, S., Wang, L. S., Huang, Z. Q., Zhou, Q., Sun, Y. G., Cao, J. T., Li, Y. G., and Wang, C. Q. Berberine ameliorates inflammation in patients with acute coronary syndrome following percutaneous coronary intervention. Clin Exp.Pharmacol Physiol 2012;39 PubMed
  25. 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
  26. 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
  27. Saksena HC, Tomar VN, and Soangra MR. Efficacy of a new salt of Berberine Uni-Berberine in oriental sore. Current Medical Practice 1970;14:247-252.
  28. Abascal K, Yarnell E. Recent clinical advances with berberine. Altern Complement Ther 2010;16(5):281-7. DOI
  29. Dong H, Zhao Y, Zhao L, Lu F. The effects of berberine on blood lipids: a systemic review and meta-analysis of randomized controlled trials. Planta Med 2013;79(6):437-46. PubMed
  30. Hou Q, Han W, Fu X. Pharmacokinetic interaction between tacrolimus and berberine in a child with idiopathic nephrotic syndrome. Eur J Clin Pharmacol 2013;69(10):1861-2. PubMed
  31. 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
  32. Li G, Zhao M, Qiu F, Sun Y, Zhao L. Pharmacokinetic interactions and tolerability of berberine chloride with simvastatin and fenofibrate: an open-label, randomized, parallel study in healthy Chinese subjects. Drug Des Devel Ther. 2018;13:129-139. PubMed
  33. Ju J, Li J, Lin Q, Xu H. Efficacy and safety of berberine for dyslipidaemias: A systematic review and meta-analysis of randomized clinical trials. Phytomedicine. 2018;50:25-34. PubMed
  34. Xu L, Zhang Y, Xue X, et al. A phase I trial of berberine in Chinese with ulcerative colitis. Cancer Prev Res (Phila). 2020;13(1):117-26. PubMed
  35. Lyu Y, Zhang Y, Yang M, et al. Pharmacokinetic interactions between metformin and berberine in rats: Role of oral administration sequences and microbiota. Life Sci. 2019;235:116818. PubMed
  36. Chen YX, Gao QY, Zou TH, et al. Berberine versus placebo for the prevention of recurrence of colorectal adenoma: a multicentre, double-blinded, randomised controlled study. Lancet Gastroenterol Hepatol. 2020;5(3):267-75. PubMed
  37. Zhang J, Wang Y, Jiang H, et al. Preventive effect of berberine on postoperative atrial fibrillation. Circ Arrhythm Electrophysiol 2022;15(10):e011160. PubMed
  38. Blais JE, Huang X, Zhao JV. Overall and Sex-Specific Effect of Berberine for the Treatment of Dyslipidemia in Adults: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials. Drugs 2023;83(5):403-427. PubMed
  39. Panigrahi A, Mohanty S. Efficacy and safety of HIMABERB® Berberine on glycemic control in patients with prediabetes: double-blind, placebo-controlled, and randomized pilot trial. BMC Endocr Disord 2023;23(1):190. PubMed
  40. Nie Q, Li M, Huang C, et al. The clinical efficacy and safety of berberine in the treatment of non-alcoholic fatty liver disease: a meta-analysis and systematic review. J Transl Med 2024;22(1):225. PubMed
  41. Koperska A, Moszak M, Seraszek-Jaros A, Bogdanski P, Szulinska M. Does berberine impact anthropometric, hepatic, and metabolic parameters in patients with metabolic dysfunction-associated fatty liver disease? Randomized, double-blind placebo-controlled tr

See these in context on the Berberine 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 →

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

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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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