Major interaction on record — check this product against your medications before combining. Based on 14 of 16 ingredients. Check your meds →
Dietary supplement

Nighttime Formula Ingredients & Drug Interactions

by Health Plus

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

First and foremost: checking Nighttime Formula 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

Nighttime Formula is a dietary supplement by Health Plus with 16 active ingredients. Its ingredients are commonly taken for bone health and osteoporosis prevention, dietary calcium deficiency, heartburn relief (calcium carbonate antacids).Based on those ingredients, 1,695 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Barberry, Garlic, Valerian. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

Jump to a section

Check Your Meds Against Nighttime Formula by Health Plus

Ask about any prescription or over-the-counter medication and we check it for interactions with Nighttime Formula by Health Plus — and tell you which ingredient is responsible.

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HelloPharmacist Scorecard of Nighttime Formula by Health Plus

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 Aug 27, 2026

What’s inside

Low disclosure
Ingredient Transparency · database check
Low

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

Why this rating?
  • The label discloses an exact amount for 6 of its 16 active ingredients.
  • “Proprietary Blend” is a proprietary blend — the label gives one combined amount (345 NP) without saying how much of each component you get.

Health Plus Nighttime Formula contains 16 ingredients in total. The active ingredients are calcium (for bone and mineral support), iron (for oxygen transport and energy), and botanical extracts: psyllium husk powder, garlic, Lactobacillus acidophilus (a beneficial bacteria), sea buckthorn, papaya, echinacea, valerian, peppermint, Indian gooseberry (amla), celery, passion flower, European barberry, and senna powder.

The formula also includes bentonite, which is an inactive ingredient used as a binder or filler. Each ingredient contributes to the overall formulation, though the specific amounts and ratios are proprietary.

Does it work?

Strong evidence
Evidence for Intended Use · database check
By FDA rules, dietary supplements can’t claim to treat, cure, or prevent disease — so labels speak in careful marketing language. We discern each product’s intended use from its name, label claims, and label statements, then grade the clinical evidence for that use. How these ratings are computed
Strong

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

Why this rating?
  • The label markets this product for: Nighttime relaxation and colon cleansing support.
  • We looked for evidence on: Constipation, Bowel preparation, occasional irregularity, digestive wellness.
  • The strongest evidence on file: Senna is rated "Likely Effective" for Constipation (Natural Medicines).
  • Also on file: Senna is rated "Possibly Effective" for Bowel preparation.
  • Also on file: Lactobacillus Acidophilus is rated "Insufficient Reliable Evidence To Rate" for Constipation.

Calcium in this formula is effective for kidney disease support, heartburn relief, low blood calcium (hypocalcemia), high potassium (hyperkalemia), and bone loss (osteoporosis—likely effective). Iron is effective for iron-deficiency anemia and chronic disease anemia, and possibly effective for heart failure support.

Peppermint is likely effective for irritable bowel syndrome and possibly effective for indigestion and nausea. Valerian and passion flower are both possibly effective for sleep.

Garlic, senna, and several other ingredients carry "possibly effective" or "insufficient evidence" ratings for various uses. The evidence supporting this product as a complete nighttime formula is not established in the data we hold.

The evidence, ingredient by ingredient Calcium Iron Garlic Lactobacillus Acidophilus Papaya Echinacea Valerian Peppermint

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 14 of the 14 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 14 of 14.
  • General safety write-ups exist for 14 of 14.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Calcium is generally well tolerated at recommended doses but can cause belching, constipation, diarrhea, and stomach upset. High doses raise concerns about kidney stones and may increase cardiovascular and prostate cancer risk.

Iron is well tolerated but commonly causes constipation, diarrhea, and nausea; high doses carry theoretical concerns about heart disease risk. Garlic may cause breath odor, stomach upset, and increased bleeding risk.

Valerian can cause drowsiness and dizziness; stopping it suddenly after long use may trigger withdrawal symptoms like anxiety and insomnia. Senna is safe short-term but not for daily long-term use—it can cause abdominal cramping and, with overuse, electrolyte loss.

Most other ingredients are generally well tolerated in food or supplement amounts, though allergic reactions are possible with echinacea (especially in people sensitive to ragweed) and celery. Regarding pregnancy and breastfeeding: calcium and iron are likely safe in recommended amounts during both; valerian, passion flower, celery seed, and barberry should be avoided or used only under medical guidance during pregnancy; and barberry should be avoided while breastfeeding.

Side effects, ingredient by ingredient Calcium Iron Garlic Lactobacillus Acidophilus Papaya Echinacea Valerian Peppermint

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?
  • 14 of the 14 matched ingredients can interact with medications — Garlic, European Barberry, Papaya, Senna, Peppermint, 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: 1,696 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.

Check with your doctor or pharmacist before taking this product if you use blood thinners or anticoagulants (warfarin, aspirin, clopidogrel, or other antiplatelet drugs)—calcium, garlic, papaya, buckthorn, celery, and amla all carry Moderate-severity bleeding risk. Also double-check if you take HIV medications (dolutegravir, elvitegravir, protease inhibitors), antibiotics (especially ceftriaxone, quinolones, or tetracyclines), blood pressure drugs, diabetes medications, thyroid hormone, immunosuppressants, or CNS depressants (including sleep aids and anti-anxiety drugs).

No interactions are documented for the ingredients we could not check (psyllium husk powder and bentonite).

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFormula with limited ingredient disclosure with clinical evidence supporting its stated purpose. Major medication interactions have been identified, and safety information is well characterized.

This is a multi-ingredient nighttime blend with some evidence supporting individual components for sleep, digestion, and mineral balance. However, the interactions are extensive—particularly with blood thinners, blood pressure medications, diabetes drugs, antibiotics, thyroid hormones, HIV medications, and CNS depressants.

If you take any prescription or over-the-counter medications, check them against this product with your doctor or pharmacist before starting. It's not appropriate for everyone, especially those on blood thinners, HIV treatments, or sedating medications.

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

Assessment coverage: 14 of 16 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Nov 21, 2012.

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 Nighttime Formula, straight from the product label.

Brand Health Plus
Barcode (UPC) 083502087731
Net contents 90 Capsule(s)
Market status On market
Date entered into DSLD Nov 21, 2012
DSLD ID 15832
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Sugar 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 Nighttime Formula by Health Plus, 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:
3 Capsule(s)
Maximum serving Sizes:
3 Capsule(s)
Servings per container
30
UPC/BARCODE
083502087731
IngredientAmount% DV
Calories5 {Calories}--
Total Carbohydrates1 g1%
Calcium14 mg1%
Iron2 mg9%
Proprietary Blend345 NP--
Psyllium husk powder780 mg--
Garlic0 NP--
Acidophilus0 NP--
Bentonite0 NP--
Buckthorn30 mg--
Papaya0 NP--
Echinacea0 NP--
Valerian0 NP--
Peppermint0 NP--
Amla0 NP--
Celery0 NP--
Passionflower0 NP--
Barberry45 mg--
Senna powder300 mg--

Tap any ingredient to jump to its full detail below.

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

Nighttime Formula 90 capsules for the night 500 mg each

Nighttime Formula Cleansing, Relaxing & Tonifying

RELAXATION AT NIGHT

MADE IN USA

HEALTHY LIVING...NATURALLY Best Value For Your Money Satisfaction Guaranteed

Thank you for making Super Colon Cleanse and Original Colon Cleanse the top selling product for over a decade.

The next step in internal cleansing: While continuing with Colon Cleanse, also use the next 7 products in the Total Body Cleansing System: 2 Liver Cleanse 3 Kidney Cleanse 4 Heart Cleanse 5 Blood Cleanse 6 Adrenal Cleanse 7 Joint Cleanse 8 Prostate Cleanse

2 BOTTLES INSIDE

FOR A THOROUGH CLEANSE

All Natural ~ 100% Pure

ENERGY DURING THE DAY

MADE WITH THE SAME SUPER COLON CLEANSE FORMULA!

ESTABLISHED IN 1981 one #1 IN A SERIES OF 8 BODY CLEANSING PRODUCTS FROM HEALTH PLUS

Safety Seal

Suggested/Recommended/Usage/Directions

SUGGESTED USE: Take 3 capsules every night 30-60 minutes before bedtime with at least 10-20 ounces of water, juice or your favorite beverage.

For best results, use periodically with original COLON CLEANSE(R).

Suggested use for better results: Super Colon Cleanse(R) may be used alternately with our top selling Original Colon Cleanse(R). Use Super Colon Cleanse(R) for a thorough cleansing periodically, followed by Original Colon Cleanse(R) for maintenance in between.

Precautions

Not recommended for children.

Read and follow directions carefully. Do not use if you have or develop diarrhea, loose stools, or abdominal pain because Buckthorn and Senna may worsen these conditions and be harmful to your health.

Consult your physician if you have frequent diarrhea or if you are pregnant, nursing, taking medication, or have a medical condition.

TAMPER EVIDENT: Do not use if the outer neck band or inner seal on bottle is broken

Warning: Accidental overdose of iron containing products is a leading cause of fatal poisoning in children under 6. In case of accidental overdose, call a doctor or poison control center immediately.

Brand IP Statement(s)

The Super Colon Cleanse(R) Day & Night Capsules contain the same herbs that keep your colon healthy in our original Super Colon Cleanse, plus additional herbal support for both day and night. The Day & Night System is designed to keep you energized throughout the day, and relax your body and mind for a good night's sleep.

We use the best quality Psyllium Husk and Herbs in Manufacturing Super Colon Cleanse(R) Day & Night System.

Health Plus(TM) makes many other exciting & wonderful natural products.

Formula

NOTICE: These products contain Buckthorn and Senna.

General

08773/08/3

Formulation

NO Sugar NO Yeast NO Caffeine NO Preservatives NO Artificial Flavors

FDA Disclaimer Statement

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

FDA Statement of Identity

Dietary Supplement

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

See for yourself

Nighttime Formula by Health Plus label

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

Nighttime Formula 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 Nighttime Formula by Health Plus

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

Serving size3 Capsule(s) Dosage formCapsule Servings per container30 Amounts shown are per serving.

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

Calcium

Interacts with
168 drugs
14 mg per serving

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

Iron

Interacts with
80 drugs
2 mg per serving

Iron is an essential mineral your body needs to make hemoglobin and carry oxygen in the blood. Supplements are mainly useful for treating or preventin...

Iron monograph & interactions

Proprietary Blend

345 NP per serving

Psyllium husk powder

780 mg per serving

Buckthorn

Interacts with
289 drugs
30 mg per serving

Sea buckthorn is a berry-bearing shrub rich in vitamins, carotenoids, and fatty acids that people use for skin, eye, digestive, and heart health. Earl...

Buckthorn monograph & interactions

Barberry

Interacts with
1,210 drugs
45 mg per serving

European barberry is a shrub whose root, bark, and berries contain berberine, a bitter plant alkaloid that has been studied mostly in isolated form. S...

Barberry monograph & interactions

Senna powder

Interacts with
140 drugs
300 mg per serving

Senna is a plant-based stimulant laxative that is widely used and generally effective for short-term relief of constipation. It is best used occasiona...

Senna powder monograph & interactions
Interaction report

Nighttime Formula by Health Plus Drug Interactions

Want to check YOUR meds against Nighttime Formula?

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
1,695Drugs
7 Major 1,604 Moderate 84 Minor

Ingredients driving the most interactions

Barberry 1,210
Garlic 989
Valerian 902
Passionflower 836
Echinacea 816

Individual Drug Interactions

The ingredients in Nighttime Formula interact with 1,695 drugs. Click any drug to see the details.

14 of the 16 ingredients in Nighttime Formula interact with drugs. Each result below shows which ingredient is responsible. Barberry Garlic Valerian Passionflower Echinacea Peppermint Celery Buckthorn Amla Acidophilus Calcium Senna powder Papaya Iron

Each ingredient & the kinds of drugs it affects

For each ingredient in Nighttime Formula 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.

Barberry8 drug types · 1,210 drugs

Anticholinergic Drugs

Theoretically, taking European barberry with anticholinergic drugs might cause additive effects.
In vitro evidence suggests that European barberry might have anticholinergic properties.

Likelihood Possible Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, European barberry may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
In vitro and animal evidence suggest that berberine, a constituent of European barberry, might inhibit platelet aggregation. Theoretically, European barberry might have a similar effect.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, taking European barberry with antidiabetes drugs might increase the risk of hypoglycemia.
Preliminary clinical evidence suggests that European barberry juice reduces fasting glucose levels in patients with type 2 diabetes who are also taking antidiabetes drugs. Additionally, some animal studies show that berberine, a constituent of European barberry, has antiglycemic potential. Monitor blood glucose levels closely.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking European barberry with antihypertensive drugs might increase the risk of hypotension.
Animal and human research suggests that European barberry extracts can have hypotensive effects.

Likelihood Possible Evidence D
Cholinergic Drugs

Theoretically, taking European barberry with cholinergic drugs might decrease the effects of cholinergic drugs.
In vitro evidence suggests that European barberry might have anticholinergic properties.

Likelihood Possible Evidence D
Cns Depressants

Theoretically, concomitant use with drugs that have sedative properties may cause additive effects.
Animal research suggests that berberine, a constituent of European barberry, might have sedative effects. Theoretically, European barberry might have a similar effect.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, concomitant use with cyclosporine may cause additive effects.
Berberine, a constituent of European barberry, can reduce the metabolism and increase serum levels of cyclosporine. This effect is attributed to the ability of berberine to inhibit cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporine. Theoretically, European barberry might have a similar effect.

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

Theoretically, European barberry might increase the levels and clinical effects of CYP3A4 substrates.
There is very preliminary evidence suggesting that berberine, a constituent of European barberry, might inhibit the CYP3A4 enzyme. Theoretically, European barberry might have a similar effect.

Likelihood Possible Evidence D
Barberry full monograph & interactions

Garlic12 drug types · 989 drugs

Anticoagulant/Antiplatelet Drugs

Garlic may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Raw garlic and a variety of garlic extracts have antiplatelet activity and can increase prothrombin time.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, taking garlic with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research suggests that garlic and garlic extract lower blood glucose levels in healthy and diabetic individuals.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking garlic with antihypertensive drugs might increase the risk of hypotension.
In human research, both garlic and garlic extracts have blood pressure-lowering effects.

Likelihood Possible Evidence D
Atazanavir (Reyataz)

Theoretically, garlic might decrease levels and effects of atazanavir.
In a case report, a patient consuming six stir-fried garlic cloves three times weekly developed suboptimal atazanavir levels and increases in HIV viral load. While the exact cause of this interaction is unclear, there is speculation that garlic might decrease the intestinal absorption of atazanavir or increase its metabolism by inducing cytochrome P450 3A4 (CYP3A4). Until more is known, advise patients not to consume large amounts of garlic while taking atazanavir.

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

Garlic might increase levels of drugs metabolized by CYP2E1.
Clinical research suggests garlic oil can inhibit the activity of CYP2E1 by 39%. Use garlic oil cautiously in patients taking drugs metabolized by these enzymes.

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

Theoretically, garlic products containing allicin might induce intestinal CYP3A4 and inhibit hepatic CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
Some human research suggests that garlic may induce INTESTINAL CYP3A4, reducing levels of drugs metabolized by this enzyme. This is primarily based on a study showing that taking a specific allicin-containing garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induced CYP3A4 in the gut mucosa. Another study shows that giving docetaxel intravenously, bypassing the CYP3A4 enzymes in the gut mucosa, along with the same specific garlic product for 12 consecutive days, does not affect docetaxel levels. Conversely, there is concern that garlic may inhibit HEPATIC CYP3A4. In a single case report, increased tacrolimus levels and liver injury occurred in a liver transplant patient after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days. Several other studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin.

Likelihood Possible Evidence B
Isoniazid

Theoretically, garlic might decrease levels of isoniazid.
Animal research suggests that an aqueous extract of garlic reduces isoniazid levels by about 65%. Garlic reduced the maximum concentration (Cmax) and area under the curve (AUC), but not the half-life, of isoniazid. This suggests that garlic extract might inhibit isoniazid absorption across the intestinal mucosa; however, the exact mechanism of this potential interaction is not known.

Likelihood Possible Evidence D
Protease Inhibitors (Pis)

Theoretically, garlic products containing allicin might decrease levels of PIs.
Protease inhibitors are metabolized by cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4, reducing plasma levels of protease inhibitors. This is primarily based on a study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces levels of saquinavir, a PI, by approximately 50%. It is speculated that the allicin constituent induce CYP3A4 in the gut mucosa. Several studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin.

Likelihood Possible Evidence B
Saquinavir (Fortovase, Invirase)

Theoretically, garlic containing allicin might decrease levels of saquinavir.
Saquinavir is a substrate of cytochrome P450 3A4 (CYP3A4) isoenzymes. There is concern that garlic products containing allicin might induce intestinal CYP3A4 and cause subtherapeutic levels of saquinavir. This is primarily based on a pharmacokinetic study showing that taking a specific garlic product (GarliPure Maximum Allicin Formula, Natrol Inc.) twice daily for 3 days reduces saquinavir levels by approximately 50%. It is speculated that the allicin constituent induces CYP3A4 in the gut mucosa. Several pharmacokinetic studies have evaluated the impact of other garlic formulations on CYP3A4 substrates and have found no effect. Most of the products in these studies provided little or no allicin. Until more is known about this potential interaction, use garlic containing allicin cautiously in patients taking saquinavir.

Likelihood Possible Evidence B
Sofosbuvir (Sovaldi)

Theoretically, taking garlic with sofosbuvir might decrease its effectiveness.
Animal research in rats shows that giving aged garlic extract 120 mg/kg orally daily for 14 days decreases the area under the concentration time curve (AUC) after a single sofosbuvir dose of 40 mg/kg by 36%, increases the clearance by 63%, and decreases the plasma concentrations at 1 and 8 hours by 35% and 58%, respectively. This interaction is hypothesized to be due to induction of intestinal P-glycoprotein expression by garlic.

Likelihood Possible Evidence D
Tacrolimus (Prograf)

Theoretically, garlic might increase levels of tacrolimus.
In one case report, a liver transplant patient taking tacrolimus experienced increased tacrolimus levels and liver injury after taking a specific garlic supplement (Garlicin Cardio, Nature's Way) at up to three times the manufacturer recommended dose for 7 days. It is speculated that garlic inhibited hepatic cytochrome P450 3A4 (CYP3A4), which increased plasma levels of tacrolimus.

Likelihood Possible Evidence B
Warfarin (Coumadin)

Theoretically, garlic might increase the risk of bleeding with warfarin.
Raw garlic and a variety of garlic extracts have antiplatelet activity and can increase prothrombin time. In addition, there is a report of two patients who experienced an increase in a previously stabilized international normalized ratio (INR) with concomitant garlic and warfarin use. However, this report has been subsequently debated due to limited clinical information. Other clinical studies have not identified an effect of garlic on INR, warfarin pharmacokinetics, or bleeding risk. More evidence is needed to determine the safety of using garlic with warfarin.

Likelihood Possible Evidence D
Garlic full monograph & interactions

Valerian6 drug types · 902 drugs

Alcohol (Ethanol)

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

Likelihood Possible Evidence B
Alprazolam (Xanax)

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

Likelihood Possible Evidence B
Cns Depressants

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

Likelihood Possible Evidence D
Glucuronidated Drugs

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

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

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

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

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

Likelihood Possible Evidence B
Valerian full monograph & interactions

Passionflower3 drug types · 836 drugs

Cns Depressants

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

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

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

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

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

Likelihood Possible Evidence D
Passionflower full monograph & interactions

Echinacea12 drug types · 816 drugs

Caffeine

Echinacea can increase plasma levels of caffeine by inhibiting its metabolism.
Echinacea seems to increase plasma concentrations of caffeine by around 30%. This is likely due to inhibition of cytochrome P450 1A2 (CYP1A2) by echinacea.

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

Echinacea might inhibit the metabolism of CYP1A2 and increase plasma levels of some drugs.
Echinacea appears to inhibit CYP1A2 enzymes in humans. Additionally, echinacea seems to increase plasma concentrations of caffeine, a CYP1A2 substrate, by around 30%. Theoretically, echinacea might increase levels of other drugs metabolized by CYP1A2.

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

Echinacea may induce hepatic CYP3A4 and inhibit intestinal CYP3A4. This may increase or decrease levels of drugs metabolized by CYP3A4.
Several clinical trials have shown that taking echinacea for up to one month does not significantly affect the metabolism of various CYP3A4 substrates, including midazolam, docetaxel, etravirine, lopinavir-ritonavir, and darunavir-ritonavir. However, other clinical research shows that echinacea may increase the clearance of midazolam, suggesting that echinacea might induce CYP3A4. The discrepancy is thought to be due to differing effects of echinacea on intestinal versus hepatic CYP3A4 enzymes. Echinacea appears to induce hepatic CYP3A4 but inhibit intestinal CYP3A4. In some cases, these effects might cancel each other out, but in others, drug levels may be increased or decreased depending on the level of effect at hepatic and intestinal sites. The effect of echinacea on CYP3A4 activity may differ depending on the CYP3A4 substrate.

Likelihood Possible Evidence B
Etoposide (Vepesid)

Echinacea may increase levels of etoposide.
In one report, concomitant use of etoposide and echinacea was associated with more severe thrombocytopenia than the use of etoposide alone, suggesting inhibition of etoposide metabolism. Etoposide is a cytochrome P450 3A4 (CYP3A4) substrate. Echinacea has variable effects on CYP3A4, but some studies have reported inhibition of the enzyme.

Likelihood Possible Evidence D
Immunosuppressants

Echinacea has immunostimulant activity which may interfere with immunosuppressant therapy.
Theoretically, echinacea may interfere with immunosuppressant therapy because of its immunostimulant activity.

Likelihood Possible Evidence B
Darunavir (Prezista)

Theoretically, echinacea may interfere with the metabolism of darunavir; however, a small clinical study found no effect.
Darunavir is metabolized by cytochrome P450 3A4 (CYP3A4) and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Echinacea has variable effects on CYP3A4, but administration of an E. purpurea root extract (Arkocapsulas Echinacea, Arkopharma) 500 mg four times daily for 14 days did not affect darunavir/ritonavir pharmacokinetics in 15 HIV-infected patients.

Likelihood Unlikely Evidence B
Dayquil Severe

Echinacea is reported to have varying effects on a number of Cytochrome P450 metabolizing enzymes in the liver, including CYP1A2 and CYP3A4, which play a role in acetaminophen and dextromethorphan metabolism (both contained in DayQuil Severe), respectively. Studies have reported both enzyme inhibition and induction, making it difficult to predict clinically significant drug interactions with reliability. Specific drug interaction studies reporting definitive results are rare, and potential drug interactions involving echinacea should likely be taken on a case-by-case basis. Based on what we know about how acetaminophen and dextromethorphan are metabolized, the risk of a clinically significant interaction between echinacea and DayQuil Severe is low.

Likelihood Unlikely Evidence A
Docetaxel (Taxotere)

Theoretically, echinacea may interfere with the metabolism of docetaxel; however, a small clinical study found no effect.
Docetaxel is metabolized by cytochrome P450 3A4 (CYP3A4). Echinacea has variable effects on CYP3A4, but taking E. purpurea whole plant extract (Echinaforce, A. Vogel Biopharma AG) 20 drops three times daily for 2 weeks did not alter the pharmacokinetics of docetaxel in one clinical study.

Likelihood Unlikely Evidence B
Etravirine (Intelence)

Theoretically, echinacea may interfere with the metabolism of etravirine; however, a small clinical study found no effect.
Etravirine is metabolized by cytochrome P450 3A4 (CYP3A4). Echinacea has variable effects on CYP3A4, but taking E. purpurea root extract (Arkocapsulas Echinacea, Arkopharma) 500 mg three times daily for 14 days did not alter the pharmacokinetics of etravirine in HIV-infected patients.

Likelihood Unlikely Evidence B
Lopinavir/Ritonavir (Kaletra)

Theoretically, echinacea may interfere with the metabolism of lopinavir; however, a small clinical study found no effect.
Lopinavir is metabolized by cytochrome P450 3A4 (CYP3A4) and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Echinacea has variable effects on CYP3A4, but taking E. purpurea (Echinamide, Natural Factors Nutritional Products, Inc.) 500 mg three times daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in healthy volunteers.

Likelihood Unlikely Evidence B
Midazolam (Versed)

Theoretically, echinacea may increase the metabolism of intravenous midazolam.
Echinacea induces hepatic CYP3A4 and might decrease plasma levels of midazolam by about 20%, reducing the effectiveness of intravenous midazolam. Echinacea also appears to inhibit intestinal CYP3A4, which could theoretically increase the bioavailability of oral midazolam. This may cancel out the decrease in availability caused by induction of hepatic CYP3A4, such that overall plasma levels after oral administration of midazolam are not affected by echinacea.

Likelihood Possible Evidence B
Warfarin (Coumadin)

Echinacea seems to increase the clearance of warfarin, although the effect may not be clinically significant.
Preliminary clinical research in healthy male volunteers suggests that taking echinacea increases the clearance of the active S-isomer of warfarin after a single dose of warfarin, but there was not a clinically significant effect on the INR.

Likelihood Possible Evidence B
Echinacea full monograph & interactions

Peppermint5 drug types · 796 drugs

Cyclosporine (Neoral, Sandimmune)

Theoretically, peppermint oil might increase the levels and adverse effects of cyclosporine.
In animal research, peppermint oil inhibits cyclosporine metabolism and increases cyclosporine levels. Inhibition of cytochrome P450 3A4 (CYP3A4) may be partially responsible for this interaction. An interaction between peppermint oil and cyclosporine has not been reported in humans.

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

Theoretically, peppermint might increase the levels of CYP2C19 substrates.
In vitro research shows that peppermint oil inhibits CYP2C19. So far, this interaction has not been reported in humans.

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

Theoretically, peppermint might increase the levels of CYP2C9 substrates.
In vitro research shows that peppermint oil inhibits CYP2C9. So far, this interaction has not been reported in humans.

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

Theoretically, peppermint might increase the levels of CYP3A4 substrates.
Clinical research in healthy volunteers shows that a single dose of peppermint oil 600 mg inhibits CYP3A4 enzymes and increases the AUC of felodipine, a CYP3A4 substrate. However, in vitro research suggests that peppermint oil only inhibits CYP3A4 at very high concentrations.

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

Theoretically, peppermint might increase the levels of CYP1A2 substrates.
In vitro and animal research shows that peppermint oil and peppermint leaf inhibit CYP1A2. However, in clinical research, peppermint tea did not significantly affect the metabolism of caffeine, a CYP1A2 substrate. It is possible that the 6-day duration of treatment may have been too short to identify a difference.

Likelihood Possible Evidence B
Peppermint full monograph & interactions

Celery8 drug types · 651 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, celery root might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.
Celery root contains the constituents falcarinol and falcarindiol. Laboratory research suggests that these constituents can inhibit platelet aggregation. This effect has not been reported in humans.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, celery seed extract might have additive effects with antihypertensive drugs.
Clinical research suggests that taking celery seed extract may reduce daytime systolic blood pressure by about 12 mmHg compared to less than 1 mmHg with placebo.

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

Theoretically, celery might increase levels of drugs metabolized by CYP1A2.
In vitro and animal research suggests that constituents of celery can inhibit CYP1A2. This effect has not been reported in humans.

Likelihood Possible Evidence D
Levothyroxine (Synthroid, Others)

Theoretically, celery seed might decrease the effects of levothyroxine.
Several cases of hypothyroidism with low T4 levels have been reported in people who were previously stabilized on levothyroxine and then started taking celery seed tablets. They presented with symptoms such as lethargy, bloating, and dry skin, and recovered when celery seed was stopped. However, celery stem and leaf has been associated with case reports of hyperthyroidism in patients with no pre-existing thyroid disorders.

Likelihood Possible Evidence D
Lithium

Theoretically, celery might reduce excretion and increase levels of lithium due to potential diuretic effects.
Celery is thought to have diuretic properties. However, this effect has not been confirmed in humans.

Likelihood Probable Evidence D
Venlafaxine (Effexor)

Theoretically, celery root extract might increase blood levels of venlafaxine.
There is one case report of a patient who experienced medication-induced bipolar disorder after beginning to take celery root extract 1000 mg daily along with venlafaxine 75 mg and St. John's wort 600 mg daily. Symptoms included confusion, speech abnormalities, manic affect, and visual hallucinations. The plasma level of venlafaxine was 476.8 ng/mL (normal range 195-400 ng/mL). It is theorized that celery root increased venlafaxine levels by inhibiting cytochrome P450 2D6.

Likelihood Possible Evidence D
Acetaminophen (Tylenol, Others)

Theoretically, celery juice might increase the effects and side effects of acetaminophen.
Animal research suggests that concomitant use of celery juice plus acetaminophen prolongs the effects of acetaminophen. This effect has been attributed to a decrease in hepatic cytochrome P450 activity. However, other animal research shows that pretreatment with celery root extract protects against acetaminophen-induced acute liver failure. These effects have not been reported in humans.

Likelihood Possible Evidence D
Photosensitizing Drugs

Theoretically, celery might increase the risk of photosensitivity reactions when taken with photosensitizing drugs.
Laboratory research shows that celery contains photosensitizing agents such as phenols and psoralens.

Likelihood Possible Evidence D
Celery full monograph & interactions

Buckthorn2 drug types · 289 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, sea buckthorn may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
Clinical research suggests that sea buckthorn fruit extracts can inhibit platelet aggregation and adhesion to collagen and fibrinogen.

Likelihood Possible Evidence B
Antihypertensive Drugs

Theoretically, taking sea buckthorn with antihypertensive drugs might increase the risk of hypotension.
Taking sea buckthorn appears to reduce blood pressure in some patients.

Likelihood Possible Evidence D
Buckthorn full monograph & interactions

Amla4 drug types · 208 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, Indian gooseberry may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs; however, research is conflicting.
Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking Indian gooseberry 500 mg along with clopidogrel 75 mg or ecosprin 75 mg, as a single dose or for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with clopidogrel 75 mg or ecosprin 75 mg alone. Until more is known, use caution when taking Indian gooseberry in combination with anticoagulant/antiplatelet drugs.

Likelihood Possible Evidence B
Antidiabetes Drugs

Taking Indian gooseberry with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research shows that taking Indian gooseberry fruit or fruit extract alone or in conjunction with antidiabetes medications can lower blood glucose levels. Dose adjustments to diabetes medications might be necessary.

Likelihood Possible Evidence B
Aspirin

Theoretically, Indian gooseberry may increase the risk of bleeding if used with aspirin; however, research is conflicting.
Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking a single dose of Indian gooseberry 500 mg along with ecosprin 75 mg, or taking a combination of Indian gooseberry 500 mg twice daily plus ecosprin 75 mg once daily for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with ecosprin 75 mg alone.

Likelihood Possible Evidence B
Clopidogrel (Plavix)

Theoretically, Indian gooseberry may increase the risk of bleeding if used with clopidogrel; however, research is conflicting.
Clinical research shows that taking Indian gooseberry 500 mg as a single dose or twice daily for 10 days reduces platelet aggregation by about 24% to 36%, increases bleeding time by about 3.8-5.9 seconds, and increases clotting time by about 9.8-12.7 seconds when compared to baseline. However, taking a single dose of Indian gooseberry 500 mg along with clopidogrel 75 mg, or taking a combination of Indian gooseberry 500 mg twice daily plus clopidogrel 75 mg once daily for 10 days, does not significantly reduce platelet aggregation or increase bleeding time or clotting time when compared with clopidogrel 75 mg alone.

Likelihood Possible Evidence B
Amla full monograph & interactions

Acidophilus1 drug type · 182 drugs

Antibiotic Drugs

Theoretically, taking Lactobacillus acidophilus with antibiotic drugs might decrease the effectiveness of L. acidophilus.
L. acidophilus preparations usually contain live and active organisms. Therefore, simultaneously taking antibiotics might kill a significant number of the organisms. Tell patients to separate administration of antibiotics and L. acidophilus preparations by at least two hours.

Likelihood Probable Evidence D
Acidophilus 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

Senna powder5 drug types · 140 drugs

Digoxin (Lanoxin)

Theoretically, senna might increase the risk of adverse effects when taken with digoxin.
Overuse/abuse of senna increases the risk of adverse effects from cardiac glycosides, such as digoxin, due to potassium depletion.

Likelihood Possible Evidence D
Diuretic Drugs

Theoretically, senna might increase the risk of hypokalemia when taken with diuretic drugs.
Overuse of senna might compound diuretic-induced potassium loss and increase the risk for hypokalemia.

Likelihood Possible Evidence D
Estrogens

Theoretically, taking senna may interfere with the absorption of exogenous estrogens.
Some preliminary clinical evidence suggests that senna reduces the absorption of estradiol and decreases serum concentrations of estrone and estrone sulfate by decreasing intestinal transit time.

Likelihood Possible Evidence B
Stimulant Laxatives

Theoretically, senna might increase the risk for fluid and electrolyte loss when taken with other stimulant laxatives.
Senna is a stimulant laxative; concomitant use with other stimulant laxatives might compound fluid and electrolyte loss.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, excessive use of senna might increase the effects of warfarin.
Senna has stimulant laxative effects and can cause diarrhea. Diarrhea can increase the effects of warfarin, increase international normalized ratio (INR), and increase the risk of bleeding. In one case report, excessive use of senna for 3 weeks resulted in diarrhea, bloody stools, and an elevated INR of 11.9.

Likelihood Possible Evidence D
Senna powder full monograph & interactions

Papaya4 drug types · 92 drugs

Amiodarone (Cordarone)

Theoretically, papaya extract may increase the levels and clinical effects of amiodarone.
Animal research in rats shows that a single oral dose of papaya extract, as well as multiple doses of papaya extract daily over 14 days, prior to a single dose of amiodarone delays the time to maximum amiodarone concentration. However, only the 14-day papaya extract regimen increases systemic amiodarone exposure by 60% to 70%. This interaction has not been reported in humans.

Likelihood Probable Evidence D
Antidiabetes Drugs

Concomitant use of antidiabetic drugs with fermented papaya can produce additive effects. It is unclear if other forms of papaya have the same effect.
A small low-quality clinical study in patients with type 2 diabetes who are taking glibenclamide shows that taking a fermented papaya preparation 3 grams daily for 2 months decreases fasting and postprandial blood glucose levels when compared to baseline. Additionally, of the 25 patients in the study, 9 required a reduction in glibenclamide dose.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Theoretically, consuming large quantities of papaya fruit can reduce the clinical effects of levothyroxine.
In one case-report, a 37-year-old male with a history of thyroidectomy who was stabilized on levothyroxine for 5 years presented with hypothyroidism after consuming 5-6 papaya fruits daily for 14 days during vacation. In a controlled re-challenge test involving 5-6 papayas daily, the patient remained euthyroid for 7 days, but developed mild hypothyroidism after 14 days. Both times, thyroid levels normalized 40-45 days after discontinuing papaya.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, concomitant use of warfarin with papain-containing papaya extract might increase the effects and side effects of warfarin.
In one case report, a patient previously stable on warfarin was found to have an international normalization ratio (INR) of 7.4, which was attributed to ingestion of a supplement containing papain from papaya extract.

Likelihood Possible Evidence D
Papaya full monograph & interactions

Iron13 drug types · 80 drugs

Bictegravir/Emtricitabine/Tenofovir Alafenamide (Biktarvy)

Iron 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 iron 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, iron containing products.

Likelihood Probable Evidence D
Bisphosphonates

Iron reduces the absorption of bisphosphonates.
Advise patients that doses of bisphosphonates should be separated by at least two hours from doses of all other medications, including supplements such as iron. Divalent cations, including iron, can decrease absorption of bisphosphonates by forming insoluble complexes in the gastrointestinal tract.

Likelihood Probable Evidence D
Denosumab (Prolia, Others)

Administration of intravenous iron within one month of denosumab administration might increase the risk of severe hypophosphatemia and hypocalcemia.
A case of severe hypocalcemia (albumin corrected calcium 6.88 mg/dL, ionized calcium 3.68 mg/dL) and hypophosphatemia (<0.5 mg/dL) with respiratory acidosis, QT interval prolongation, and nonsustained ventricular tachycardia was reported in a 76-year-old male who had received an iron polymaltose infusion within 2 weeks of a subcutaneous injection of denosumab. Serum parathyroid hormone was also elevated (348 pg/mL). Subsequent iron infusions with iron polymaltose and ferric carboxymaltose were followed by transient hypophosphatemia, but without hypocalcemia. Additionally, a literature review describes 6 additional cases of hypophosphatemia and hypocalcemia in patients 52-92 years of age who had been administered intravenous iron as either ferric carboxymaltose or iron polymaltose and subcutaneous denosumab within 1-4 weeks of each other.

Likelihood Possible Evidence D
Dolutegravir (Tivicay)

Iron might decrease dolutegravir levels by reducing its absorption.
Advise patients to take dolutegravir at least 2 hours before or 6 hours after taking iron. Pharmacokinetic research shows that iron can decrease the absorption of dolutegravir from the gastrointestinal tract through chelation. When taken under fasting conditions, a single dose of ferrous fumarate 324 mg orally along with dolutegravir 50 mg reduces overall exposure to dolutegravir by 54%.

Likelihood Probable Evidence B
Integrase Inhibitors

Theoretically, taking iron along with integrase inhibitors might decrease the levels and clinical effects of these drugs.
Iron is a divalent cation. There is concern that iron may decrease the absorption of integrase inhibitors from the gastrointestinal tract through chelation. One pharmacokinetic study shows that iron can decrease blood levels of the specific integrase inhibitor dolutegravir through chelation. Also, other pharmacokinetic research shows that other divalent cations such as calcium can decrease the absorption and levels of some integrase inhibitors through chelation.

Likelihood Possible Evidence D
Levodopa

Iron might decrease levodopa levels by reducing its absorption.
Advise patients to separate doses of levodopa and iron as much as possible. There is some evidence in healthy people that iron forms chelates with levodopa, reducing the amount of levodopa absorbed by around 50%. The clinical significance of this hasn't been determined.

Likelihood Probable Evidence B
Levothyroxine (Synthroid, Others)

Iron might decrease levothyroxine levels by reducing its absorption.
Advise patients to separate levothyroxine and iron doses by at least 2 hours. Iron can decrease the absorption and efficacy of levothyroxine by forming insoluble complexes in the gastrointestinal tract.

Likelihood Probable Evidence B
Methyldopa (Aldomet)

Iron might decrease methyldopa levels by reducing its absorption.
Advise patients to separate methyldopa and iron doses by at least 2 hours. Iron can decrease the absorption of methyldopa from the gastrointestinal tract through chelation, resulting in increases in blood pressure.

Likelihood Probable Evidence B
Mycophenolate Mofetil (Cellcept)

Theoretically, iron might decrease mycophenolate mofetil levels by reducing its absorption.
Advise patients to take iron 4-6 hours before, or 2 hours after, mycophenolate mofetil. It has been suggested that a decrease of absorption is possible, probably by forming nonabsorbable chelates. However, mycophenolate pharmacokinetics are not affected by iron supplementation in available clinical research.

Likelihood Unlikely Evidence D
Penicillamine (Cuprimine, Depen)

Iron might decrease penicillamine levels by reducing its absorption.
Advise patients to separate penicillamine and iron doses by at least 2 hours. Oral iron supplements can reduce absorption of penicillamine by 30% to 70%, probably due to chelate formation. In people with Wilson's disease, this interaction has led to reduced efficacy of penicillamine.

Likelihood Probable Evidence D
Quinolone Antibiotics

Iron might decrease levels of quinolone antibiotics by reducing their absorption.
Advise patients to separate quinolone antibiotics and iron doses by at least 2 hours. Iron decreases the absorption of quinolones due to formation of insoluble complexes in the gastrointestinal tract.

Likelihood Probable Evidence D
Tetracycline Antibiotics

Iron might decrease levels of tetracycline antibiotics by reducing their absorption.
Advise patients to take iron at least 2 hours before or 4 hours after tetracycline antibiotics. Concomitant use can decrease absorption of tetracycline antibiotics from the gastrointestinal tract by 50% to 90%.

Likelihood Probable Evidence D
Chloramphenicol

Theoretically, taking chloramphenicol with iron might reduce the response to iron therapy in iron deficiency anemia.
Chloramphenicol interferes with erythrocyte maturation. However, since chloramphenicol isn't usually taken for prolonged periods, this isn't likely to be clinically significant.

Likelihood Unlikely Evidence D
Iron full monograph & interactions
The maker

Brand information

Manufacturer and brand details for Nighttime Formula, from the product label.

Health Plus

See all Health Plus products
Name
health Plus Inc
City
CHINO
State
CA
ZipCode
91710
Phone Number
(800) 822-6225
Web Address
www.healthplusinc.com
Pharmacist Counseling Corner

Nighttime Formula by Health Plus: Common Questions

Does Nighttime Formula by Health Plus interact with any medications?
Yes. Based on its ingredients, Nighttime Formula has a known interaction with 1,695 medications, including 7 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Nighttime Formula contains 16 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take this if I'm on blood thinners like warfarin?
No—not without checking with your doctor or pharmacist first. Several ingredients in this formula, including garlic, papaya, buckthorn, celery, and amla, may increase bleeding risk when combined with warfarin or other blood thinners. The interaction is Moderate severity, so it needs a professional review of your specific situation.
Is this formula safe to take during pregnancy?
Some ingredients are likely safe in food or recommended amounts—calcium and iron, for example—but several others should be avoided or used only under medical guidance, including valerian, passion flower, celery seed, and barberry. Talk with your doctor or prenatal care provider before starting this product.
Will this help me sleep?
The formula contains valerian and passion flower, both rated possibly effective for insomnia in our data. However, evidence is limited, and the product is a multi-ingredient blend, so the sleep benefit isn't guaranteed. Your results may vary.
Does this interact with antibiotics?
Yes—iron can significantly reduce absorption of quinolone and tetracycline antibiotics if taken at the same time. Calcium can also interact with the antibiotic ceftriaxone intravenously. Separate doses by at least 2 hours or as directed by your pharmacist.
Can I take this with my diabetes medication?
Check with your doctor first. Garlic, papaya, amla, barberry, and celery all carry Moderate-severity interactions with diabetes drugs and may lower blood sugar further, risking low blood sugar (hypoglycemia). Your doses may need adjustment.
What are the most common side effects?
Calcium commonly causes constipation, diarrhea, and stomach upset. Iron often causes constipation, nausea, and abdominal pain. Valerian and garlic can cause drowsiness and digestive upset. Senna may cause cramping and diarrhea, especially with regular use. Most other ingredients are generally well tolerated.

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.

Nighttime Formula label
Go deeper

The Full Monographs Behind Nighttime Formula’s Ingredients

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

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

Iron

Interacts with 80 drugs

Iron is an essential mineral your body needs to make hemoglobin and carry oxygen in the blood. Supplements are mainly useful for treating or preventing iron deficiency and iron-deficiency an...

Read the full Iron monograph → Herb & supplement monograph

Garlic

Interacts with 989 drugs

Garlic is a common food and supplement that may modestly help with blood pressure and cholesterol, though the evidence is mixed and effects are usually small. It is generally safe in food am...

Read the full Garlic monograph → Herb & supplement monograph

Lactobacillus Acidophilus

Interacts with 182 drugs

Lactobacillus acidophilus is a 'friendly' bacterium used as a probiotic to support gut and vaginal health. It is generally well tolerated in healthy people, and there is reasonable evidence...

Read the full Lactobacillus Acidophilus monograph → Herb & supplement monograph

Papaya

Interacts with 92 drugs

Papaya is a tropical fruit that is nutritious and generally safe to eat as food, and it contains an enzyme called papain used as a digestive aid and meat tenderizer. Papaya leaf extract is b...

Read the full Papaya monograph → Herb & supplement monograph

Echinacea

Interacts with 816 drugs

Echinacea is a popular herb taken to help prevent or shorten the common cold, but study results are mixed and the overall benefit appears small at best. It is generally well tolerated for sh...

Read the full Echinacea monograph → Herb & supplement monograph

Valerian

Interacts with 902 drugs

Valerian is an herb whose root is widely used as a natural sleep aid and for calming nerves. The evidence is mixed and often weak, so it may help some people sleep but does not work reliably...

Read the full Valerian monograph → Herb & supplement monograph

Peppermint

Interacts with 796 drugs

Peppermint is a popular herb with the best evidence supporting enteric-coated peppermint oil for easing IBS symptoms. It is generally well tolerated for most adults, but it can cause heartbu...

Read the full Peppermint monograph → Herb & supplement monograph

Indian Gooseberry

Interacts with 208 drugs

Indian gooseberry (amla) is a vitamin C-rich fruit used in Ayurvedic medicine for many purposes, from antioxidant support to cholesterol and digestion. Early research is promising for some u...

Read the full Indian Gooseberry monograph → Herb & supplement monograph

Celery

Interacts with 651 drugs

Celery is a common vegetable that is also taken as a seed extract or oil supplement, mainly for blood pressure, fluid retention, and joint discomfort. Human evidence for these supplement use...

Read the full Celery monograph → Herb & supplement monograph

Passion Flower

Interacts with 836 drugs

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

Read the full Passion Flower monograph → Herb & supplement monograph

Sea Buckthorn

Interacts with 289 drugs

Sea buckthorn is a berry-bearing shrub rich in vitamins, carotenoids, and fatty acids that people use for skin, eye, digestive, and heart health. Early research is promising for a few uses l...

Read the full Sea Buckthorn monograph → Herb & supplement monograph

European Barberry

Interacts with 1,210 drugs

European barberry is a shrub whose root, bark, and berries contain berberine, a bitter plant alkaloid that has been studied mostly in isolated form. Some early research on berberine is promi...

Read the full European Barberry monograph → Herb & supplement monograph

Senna

Interacts with 140 drugs

Senna is a plant-based stimulant laxative that is widely used and generally effective for short-term relief of constipation. It is best used occasionally and for only a few days at a time, s...

Read the full Senna monograph →
Sources

Sources & How We Checked

Nighttime Formula'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 583 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.

Calcium 62 references
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  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 →

Iron 72 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Bruner AB, Joffe A, Duggan AK, et al. Randomized study of cognitive effects of iron supplementation in non- anaemic iron-deficient adolescent girls. Lancet 1996;348:992-6.
  3. Ullen H, Augustsson K, Gustavsson C, Steineck G. Supplementary iron intake and risk of cancer: reversed causality? Cancer Lett 1997;114:215-6.
  4. Reunanen A, Takkunen H, Knekt P, et al. Body iron stores, dietary iron intake and coronary heart disease mortality. J Intern Med 1995;238:223-30. PubMed
  5. Lund EK, Wharf SG, Fairweather-Tait SJ, Johnson IT. Oral ferrous sulfate supplements increase the free radical-generating capacity of feces from healthy volunteers. Am J Clin Nutr 1999;69:250-5.
  6. Rehman A, Collis CS, Yang M, et al. The effects of iron and vitamin C co-supplementation on oxidative damage to DNA in healthy volunteers. Biochem Biophys Res Comm 1998;246:293-8. PubMed
  7. Klipstein-Grobusch K, Grobbee DE, den Breeijen JH, et al. Dietary iron and risk of myocardial infarction in the Rotterdam Study. Am J Epidemiol 1999;149:421-8. PubMed
  8. Hansten PD, Horn JR. Drug Interactions Analysis and Management. Vancouver, WA: Applied Therapeutics Inc., 1997 and updates.
  9. Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999.
  10. Food and Nutrition Board, Institute of Medicine. Dietary Reference Intakes for Vitamin A, Vitamin K, Arsenic, Boron, Chromium, Copper, Iodine, Iron, Manganese, Molybdenum, Nickel, Silicon, Vanadium, and Zinc. Washington, DC: National Academy Press, 2002.
  11. Campbell N, Paddock V, Sundaram R. Alteration of methyldopa absorption, metabolism, and blood pressure control by ferrous sulfate and ferrous gluconate. Clin Pharmacol Ther 1988;43:381-6..
  12. Schumann K, Borch-Iohnsen B, Hentze MW, Marx JJ. Tolerable upper intakes for dietary iron set by the US Food and Nutrition Board (commentary). Am J Clin Nutr 2002;76:499-500. PubMed
  13. Tuomainen TP, Punnonen K, Nyyssonen K, Salonen JT. Association between body iron stores and the risk of acute myocardial infarction in men. Circulation 1998;97:1461-6.. PubMed
  14. Salonen JT, Nyyssonen K, Korpela H, et al. High stored iron levels are associated with excess risk of myocardial infarction in Eastern Finnish men. Circulation 1992;86:803-11.. PubMed
  15. Campbell NRC, Hasinoff B. Ferrous sulfate reduces levodopa bioavailability: Chelation as a possible mechanism. Clin Pharmacol Ther 1989;45:220-5.. PubMed
  16. Campbell NRC, Hasinoff BB, Stalts H, et al. Ferrous sulfate reduces thyroxine efficacy in patients with hypothyroidism. Ann Int Med 1992;117:1010-3.. PubMed
  17. Kiechl S, Willeit J, Egger G, et al. Body iron stores and the risk of carotid atherosclerosis: prospective results from the Bruneck study. Circulation 1997;96:3300-07. PubMed
  18. Comparison of oral iron supplements. Pharmacist's Letter / Prescriber's Letter 2008;24(8):240811.
  19. Tran T., Wax J. R., Philput C., Steinfeld J. D., Ingardia C. J. Intentional iron overdose in pregnancy--management and outcome. J Emerg Med 2000;18(2):225-228. PubMed
  20. Toblli J. E., Brignoli, R. Iron(III)-hydroxide polymaltose complex in iron deficiency anemia / review and meta-analysis. Arzneimittelforschung 2007;57(6A):431-438. PubMed
  21. Köpcke W., Sauerland M. C. Meta-analysis of efficacy and tolerability data on iron proteinsuccinylate in patients with iron deficiency anemia of different severity. Arzneimittelforschung 1995;45(11):1211-1216.
  22. Campbell N. R., Campbell R. R., Hasinoff B. B. Ferrous sulfate reduces methyldopa absorption: methyldopa: iron complex formation as a likely mechanism. Clin Invest Med 1990;13(6):329-332.
  23. Morii M., Ueno K., Ogawa A., Kato R., Yoshimura H., Wada K., Hashimoto H., Takada M., Tanaka K., Nakatani T., Shibakawa M. Impairment of mycophenolate mofetil absorption by iron ion. Clin Pharmacol Ther 2000;68(6):613-616. PubMed
  24. Gelone D. K., Park J. M., Lake K. D. Lack of an effect of oral iron administration on mycophenolic acid pharmacokinetics in stable renal transplant recipients. Pharmacotherapy 2007;27(9):1272-1278. PubMed
  25. Ducray P. S., Banken L., Gerber M., Boutouyrie B., Zandt H. Absence of an interaction between iron and mycophenolate mofetil absorption. Br J Clin Pharmacol 2006;62(4):492-495. PubMed
  26. Lorenz M., Wolzt M., Weigel G., Puttinger H., Hörl W. H., Födinger M., Speiser W., Sunder-Plassmann G. Ferrous sulfate does not affect mycophenolic acid pharmacokinetics in kidney transplant patients. Am J Kidney Dis 2004;43(6):1098-1103. PubMed
  27. Osman M. A., Patel R. B., Schuna A., Sundstrom W. R., Welling P. G. Reduction in oral penicillamine absorption by food, antacid, and ferrous sulfate. Clin Pharmacol Ther 1983;33(4):465-470. PubMed
  28. Michael, B., Coyne, D. W., Fishbane, S., Folkert, V., Lynn, R., Nissenson, A. R., Agarwal, R., Eschbach, J. W., Fadem, S. Z., Trout, J. R., Strobos, J., and Warnock, D. G. Sodium ferric gluconate complex in hemodialysis patients: adverse reactions compar
  29. Zhang, X., Ouyang, J., Wieczorek, R., and DeSoto, F. Iron medication-induced gastric mucosal injury. Pathol.Res Pract 2009;205(8):579-581. PubMed
  30. Barbieri, P. G. [To-day exposure to occupational carcinogens and their effects. The experience of the rubber industry, iron metallurgy, asphalt work and aviculture]. Epidemiol.Prev 2009;33(4-5 Suppl 2):94-105.
  31. Macedo, A. and Cardoso, S. [Routine iron supplementation in pregnancy]. Acta Med Port. 2010;23(5):785-792.
  32. Bastide, N. M., Pierre, F. H., and Corpet, D. E. Heme iron from meat and risk of colorectal cancer: a meta-analysis and a review of the mechanisms involved. Cancer Prev Res (Phila) 2011;4(2):177-184. PubMed
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  34. van den, Hombergh J., Dalderop, E., and Smit, Y. Does iron therapy benefit children with severe malaria-associated anaemia? A clinical trial with 12 weeks supplementation of oral iron in young children from the Turiani Division, Tanzania. J.Trop.Pediatr. PubMed
  35. Liabeuf S, Gras V, Moragny J, et al. Ulceration of the oral mucosa following direct contact with ferrous sulfate in elderly patients: a case report and a review of the French National Pharmacovigilance Database. Clin Interv Aging. 2014 Apr 25;9:737-40. PubMed
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  37. 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
  38. Guidelines for the Use of Antiretroviral Agents in HIV-1-Infected Adults and Adolescents: Drug Interactions between Integrase Inhibitors and Other Drugs. AIDSinfo. July 14, 2016. Available at: https://aidsinfo.nih.gov/guidelines/html/1/adult-and-adolescen
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  43. Kinnunen TI, Luoto R, Helin A, Hemminki E. Supplemental iron intake and the risk of glucose intolerance in pregnancy: re-analysis of a randomised controlled trial in Finland. Matern Child Nutr. 2016;12(1):74-84.
  44. Low MS, Speedy J, Styles CE, De-Regil LM, Pasricha SR. Daily iron supplementation for improving anaemia, iron status and health in menstruating women. Cochrane Database Syst Rev. 2016;4:CD009747. PubMed
  45. Melit LE, Marginean CO, Mocanu S, Marginean MO. A rare case of iron-pill induced gastritis in a female teenager: A case report and a review of the literature. Medicine (Baltimore). 2017;96(30):e7550. PubMed
  46. Neuberger A, Okebe J, Yahav D, Paul M. Oral iron supplements for children in malaria-endemic areas. Cochrane Database Syst Rev. 2016;2:CD006589. PubMed
  47. Peña-Rosas JP, De-Regil LM, Gomez Malave H, Flores-Urrutia MC, Dowswell T. Intermittent oral iron supplementation during pregnancy. Cochrane Database Syst Rev. 2015;(10):CD009997. PubMed
  48. Brabin B, Gies S, Roberts SA, et al. Excess risk of preterm birth with periconceptional iron supplementation in a malaria endemic area: analysis of secondary data on birth outcomes in a double blind randomized controlled safety trial in Burkina Faso. Mala PubMed
  49. Kaundal R, Bhatia P, Jain A, et al. Randomized controlled trial of twice-daily versus alternate-day oral iron therapy in the treatment of iron-deficiency anemia. Ann Hematol 2020;99(1):57-63. PubMed
  50. Li N, Zhao G, Wu W, et al. The efficacy and safety of vitamin C for iron supplementation in adult patients with iron deficiency anemia: A randomized clinical trial. JAMA Netw Open. 2020;3(11):e2023644.<br> PubMed
  51. Houston BL, Hurrie D, Graham J, et al. Efficacy of iron supplementation on fatigue and physical capacity in non-anaemic iron-deficient adults: a systematic review of randomised controlled trials. BMJ Open. 2018;8(4):e019240. PubMed
  52. Koch RM, Tchernodrinski S, Principe DR. Case report: Rapid onset, ischemic-type gastritis after initiating oral iron supplementation. Front Med (Lausanne) 2022;9:1010897. PubMed
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Peppermint 41 references
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Indian Gooseberry 6 references
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Celery 48 references
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Passion Flower 19 references
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European Barberry 15 references
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  13. Tripathi YB and Shukla SD. Berberis artistata inhibits PAF induced aggregation of rabbit platelets. Phytotherapy Research 1996;10:628-630.
  14. Lazavi F, Mirmiran P, Sohrab G, Nikpayam O, Angoorani P, Hedayati M. The barberry juice effects on metabolic factors and oxidative stress in patients with type 2 diabetes: A randomized clinical trial. Complement Ther Clin Pract. 2018;31:170-174. PubMed
  15. Philips CA, Theruvath AH, Ravindran R. Toxic hepatitis-associated aplastic anaemia after dual homeopathic remedies and Gymnema sylvestre use. BMJ Case Rep 2022;15(3):e247867. PubMed

See these in context on the European Barberry monograph →

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See these in context on the Senna monograph →

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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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