Major interaction on record — check this product against your medications before combining. Check your meds →
Dietary supplement

Restless Leg Calm Ingredients & Drug Interactions

by Signature Supplements

Capsule Category: Botanical With Nutrients
Most serious interaction: Major
The interaction bottom line Most serious interaction: Major

Restless Leg Calm is a dietary supplement by Signature Supplements with 7 active ingredients. Its ingredients are commonly taken for preventing or treating magnesium deficiency, constipation, muscle cramps.Based on those ingredients, 1,329 medications have a known interaction with it, the most serious rated major. The ingredients most likely to interact are Licorice, Chamomile flower extract, White Peony. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Restless Leg Calm by Signature Supplements

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

What’s inside

Full disclosure
Ingredient Transparency · database check
Full

Every active ingredient lists its own amount on the label.

Why this rating?
  • The label discloses an exact amount for 7 of its 7 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

Restless Leg Calm contains 7 active ingredients. Magnesium citrate is the main one—a mineral that your body uses for muscle and nerve function and is well established for heartburn and constipation.

The product also includes potassium, a mineral critical for heart rhythm and nerve signaling; Angelica sinensis (dong quai), a traditional Chinese herb; chamomile flower extract for its soothing properties; uva ursi, an herbal extract historically used for the urinary tract; licorice, valued in herbal medicine for skin and digestive health; and white peony, another traditional herb. The capsules also contain cellulose and diatomaceous earth as inactive ingredients.

Does it work?

Not established
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
Not established

The graded evidence we hold for these ingredients covers different conditions than the ones this product is marketed for, so there's no established rating for its stated use.

Why this rating?
  • The label markets this product for: calm restless legs and support sleep quality.
  • We looked for evidence on: Restless leg syndrome, Periodic limb movement, Muscle tension.
  • The closest evidence on file: Magnesium is rated "Possibly Ineffective" for Muscle cramps (Natural Medicines).
  • Also on file: Peony is rated "Insufficient Reliable Evidence To Rate" for Muscle cramps, Restless legs syndrome (RLS).
  • Also on file: Licorice is rated "Insufficient Reliable Evidence To Rate" for Muscle cramps.

For magnesium citrate, the data shows it is effective for indigestion and constipation, and also effective for low magnesium levels (hypomagnesemia) and pre-eclampsia in pregnancy. For the other ingredients, the evidence is less established.

Potassium has no effectiveness ratings in our data. Dong quai, uva ursi, licorice, and peony all carry ratings of insufficient reliable evidence for the conditions they are traditionally used for—meaning we don't hold enough solid research to say whether they work.

This product is labeled for restless legs, but none of the ingredients have an established effectiveness rating for that condition in our data.

The evidence, ingredient by ingredient Magnesium Potassium Dong Quai German Chamomile Uva Ursi Licorice Peony

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 7 of the 7 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 7 of 7.
  • General safety write-ups exist for 7 of 7.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

Magnesium citrate is generally well tolerated at normal doses; most common side effects from oral magnesium are diarrhea, nausea, vomiting, and stomach upset. In pregnancy, magnesium is needed and is rated likely safe, but supplements should be used only under your doctor's guidance.

While breastfeeding, dietary magnesium is fine, but check with your doctor before taking supplements. Potassium from food is safe, but supplements can raise blood levels dangerously in people with kidney disease; it's rated likely safe in pregnancy from food, but supplements need medical oversight.

Dong quai may increase bleeding risk and cause skin sensitivity to sunlight; the data advises against it in pregnancy and while breastfeeding. Uva ursi is generally well tolerated short-term at low doses but can be toxic at high doses (20 grams or more); avoid it in pregnancy and while breastfeeding.

Licorice is fine in small food amounts but the active compound glycyrrhizin can cause serious problems with high or prolonged doses; avoid licorice supplements in pregnancy and while breastfeeding. Peony appears well tolerated for short-term use, but safety data are limited; avoid it in pregnancy and breastfeeding.

Side effects, ingredient by ingredient Magnesium Potassium Dong Quai German Chamomile Uva Ursi Licorice Peony

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?
  • 7 of the 7 matched ingredients can interact with medications — Peony, Uva Ursi, Potassium, Licorice, Dong Quai, among others.
  • The most serious interaction on file is rated Major.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,330 individual medications appear in the full list. A big number alone doesn't make a product dangerous — what matters is whether YOUR medication is on it, so run yours through the interaction checker on this page.

Before taking Restless Leg Calm, double-check these medication types with your pharmacist: blood thinners like warfarin (Major risk from dong quai); Parkinson's medication levodopa/carbidopa (Major risk from magnesium); blood-pressure and heart drugs, especially calcium channel blockers, ACE inhibitors, and ARBs (Moderate risk); blood-thinning or antiplatelet drugs; diabetes medications; digoxin; muscle relaxants; kidney drugs; and cancer therapies. Also check if you take lithium, any antibiotic (especially quinolones), bone-building drugs (bisphosphonates), or antacids—all carry Moderate interactions.

Check your own medication Run your meds through the checker above

The bottom line

Scorecard at a glanceFully disclosed formula with no established evidence rating for its marketed use. Major medication interactions have been identified, and safety information is well characterized.

This product's main ingredient, magnesium, is useful for constipation and indigestion, but the product as a whole combines multiple ingredients with real interaction risks—especially with blood thinners, Parkinson's medications, diabetes drugs, and heart medications. If you take any prescription medications, check them carefully with the tool below before starting.

Talk to your pharmacist or doctor if you take warfarin, any heart or blood-pressure drug, or any other regular medication.

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

Assessment coverage: 7 of 7 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Sep 25, 2025.

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 Restless Leg Calm, straight from the product label.

Brand Signature Supplements
Net contents 100 Capsule(s)
Market status On market
Date entered into DSLD Sep 25, 2025
DSLD ID 338929
Product type Botanical With Nutrients
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult (18 - 50 Years), Gluten Free, Dairy Free, 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 Restless Leg Calm by Signature Supplements, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
2 Capsule(s)
Maximum serving Sizes:
2 Capsule(s)
Servings per container
50
IngredientAmount% DV
Magnesium Citrate150 mg44%
Potassium99 mg3%
Angelica sinensis150 mg--
Chamomile flower extract70 mg--
Uva-ursi70 mg--
Licorice50 mg--
White Peony150 mg--

Other ingredients: Cellulose, Diatomaceous Earth

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.
Formulation

No: chemical fillers or binders, artificial coloring, artificial flavor, preservatives, yeast, corn, milk or milk derivatives, lactose, salt, sodium, soy, sugar,

From a GMP facility

Restless Leg Calm for the creepy, crawling, tingly feeling. May promote a more peaceful sleep and better blood circulation.

FDA Statement of Identity

Dietary Supplement

Suggested/Recommended/Usage/Directions

Directions: For adults, take two (2) capsules daily, more if needed.

Precautions

As a reminder, discuss the supplements and medications you take with your health care providers.

Keep out of reach of children store in a dry place and avoid excessive heat.

Storage

Keep out of reach of children store in a dry place and avoid excessive heat.

FDA Disclaimer Statement

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

See for yourself

Restless Leg Calm by Signature Supplements label

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

What’s inside

The Ingredients in Restless Leg Calm by Signature Supplements

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

Serving size2 Capsule(s) Dosage formCapsule Servings per container50 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.

Magnesium Citrate

Interacts with
295 drugs
150 mg per serving

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

Magnesium Citrate monograph & interactions

Potassium

Interacts with
62 drugs
99 mg per serving Form: Potassium Gluconate

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

Potassium monograph & interactions

Angelica sinensis

Interacts with
163 drugs
150 mg per serving

Dong Quai is a traditional Chinese herb often called "female ginseng" and is mostly used for menstrual and menopausal complaints. High-quality scienti...

Angelica sinensis monograph & interactions

Chamomile flower extract

Interacts with
960 drugs
70 mg per serving

German chamomile is a widely used herbal remedy taken mainly as a tea for calming, sleep, and digestive complaints. Early research suggests possible b...

Chamomile flower extract monograph & interactions

Uva-ursi

Interacts with
803 drugs
70 mg per serving

Uva ursi is a traditional herb used mainly for urinary tract infections, and its leaves contain a compound called arbutin that may have antimicrobial...

Uva-ursi monograph & interactions

Licorice

Interacts with
1,040 drugs
50 mg per serving

Licorice root is a traditional remedy used for sore throats, coughs, and digestive complaints, but solid human evidence is limited for most uses. Regu...

Licorice monograph & interactions

White Peony

Interacts with
811 drugs
150 mg per serving

Peony root is a traditional Chinese medicine herb often used for menstrual problems, cramps, and inflammation, frequently as part of combination formu...

White Peony monograph & interactions

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

Interaction report

Restless Leg Calm by Signature Supplements Drug Interactions

Want to check YOUR meds against Restless Leg Calm?

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
1,329Drugs
8 Major 1,318 Moderate 3 Minor

Ingredients driving the most interactions

Licorice 1,040
Uva-ursi 803

Each ingredient & the kinds of drugs it affects

For each ingredient in Restless Leg Calm 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.

Licorice18 drug types · 1,040 drugs

Antihypertensive Drugs

Theoretically, licorice might reduce the effects of antihypertensive drugs.
In human research, licorice increases blood pressure in a dose-dependent manner.

Likelihood Possible Evidence B
Cisplatin (Platinol-Aq)

Theoretically, licorice might reduce the effects of cisplatin.
In animal research, licorice diminished the therapeutic efficacy of cisplatin.

Likelihood Possible Evidence D
Corticosteroids

Theoretically, concomitant use of licorice and corticosteroids might increase the side effects of corticosteroids.
Case reports suggest that concomitant use of licorice and oral corticosteroids, such as hydrocortisone, can potentiate the duration of activity and increase blood levels of corticosteroids. Additionally, in one case report, a patient with neurogenic orthostatic hypertension stabilized on fludrocortisone 0.1 mg twice daily developed pseudohyperaldosteronism after recent consumption of large amounts of black licorice.

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

Theoretically, licorice might increase levels of drugs metabolized by CYP2B6.
In vitro research shows that licorice extract and glabridin, a licorice constituent, inhibit CYP2B6 isoenzymes. Licorice extract from the species G. uralensis seems to inhibit CYP2B6 isoenzymes to a greater degree than G. glabra extract in vitro. Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2B6; however, these interactions have not yet been reported in humans.

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

Theoretically, licorice might increase levels of drugs metabolized by CYP2C19.
In vitro, licorice extracts from the species G. glabra and G. uralensis inhibit CYP2C19 isoenzymes in vitro. Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C19; however, this interaction has not yet been reported in humans.

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

Theoretically, licorice might increase levels of drugs metabolized by CYP2C8.
In vitro, licorice extract from the species G. glabra and G. uralensis inhibits CYP2C8 isoenzymes. Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C8; however, this interaction has not yet been reported in humans.

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

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP2C9.
There is conflicting evidence about the effect of licorice on CYP2C9 enzyme activity. In vitro research shows that extracts from the licorice species G. glabra and G. uralensis moderately inhibit CYP2C9 isoenzymes. However, evidence from an animal model shows that licorice extract from the species G. uralensis can induce hepatic CYP2C9 activity. Until more is known, licorice should be used cautiously in people taking CYP2C9 substrates.

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

Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.
Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity. Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity. However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species. Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.

Likelihood Possible Evidence B
Digoxin (Lanoxin)

Theoretically, concomitant use of licorice with digoxin might increase the risk of cardiac toxicity.
Overuse or misuse of licorice with cardiac glycoside therapy might increase the risk of cardiac toxicity due to potassium loss.

Likelihood Possible Evidence D
Diuretic Drugs

Theoretically, concomitant use of licorice with diuretic drugs might increase the risk of hypokalemia.
Overuse of licorice might compound diuretic-induced potassium loss. In one case report, a 72-year-old male with a past medical history of hypertension, type 2 diabetes, hyperlipidemia, arrhythmia, stroke, and hepatic dysfunction was hospitalized with severe hypokalemia and uncontrolled hypertension due to pseudohyperaldosteronism. This was thought to be provoked by concomitant daily consumption of a product containing 225 mg of glycyrrhizin, a constituent of licorice, and hydrochlorothiazide 12.5 mg for 1 month.

Likelihood Possible Evidence D
Estrogens

Theoretically, licorice might increase or decrease the effects of estrogen therapy.
Theoretically, licorice might interfere with estrogen therapy due to estrogenic and anti-estrogenic effects.

Likelihood Possible Evidence D
Loop Diuretics

Theoretically, loop diuretics might increase the mineralocorticoid effects of licorice.
Theoretically, loop diuretics might enhance the mineralocorticoid effects of licorice by inhibiting the enzyme that converts cortisol to cortisone; however, bumetanide (Bumex) does not appear to have this effect.

Likelihood Possible Evidence D
Midazolam (Versed)

Theoretically, licorice might decrease levels of midazolam.
In humans, the licorice constituent glycyrrhizin appears to moderately induce the metabolism of midazolam. This is likely due to induction of cytochrome P450 3A4 by licorice. Until more is known, licorice should be used cautiously in people taking midazolam.

Likelihood Possible Evidence B
P-Glycoprotein Substrates

Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.
In vitro research shows that licorice can increase P-glycoprotein activity.

Likelihood Possible Evidence D
Paclitaxel (Abraxane, Onxol)

Theoretically, licorice might decrease plasma levels and clinical effects of paclitaxel.
Multiple doses of licorice taken concomitantly with paclitaxel might reduce the effectiveness of paclitaxel. Animal research shows that licorice 3 grams/kg given orally for 14 days before intravenous administration of paclitaxel decreases the exposure to paclitaxel and increases its clearance. Theoretically, this occurs because licorice induces cytochrome P450 3A4 enzymes, which metabolize paclitaxel. Notably, a single dose of licorice did not affect exposure or clearance of paclitaxel.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, licorice might decrease plasma levels and clinical effects of warfarin.
Licorice seems to increase metabolism and decrease levels of warfarin in animal models. This is likely due to induction of cytochrome P450 2C9 (CYP2C9) metabolism by licorice. Advise patients taking warfarin to avoid taking licorice.

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

Theoretically, licorice might decrease the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that licorice induces CYP1A2 enzymes.

Likelihood Possible Evidence D
Methotrexate (Trexall, Others)

Theoretically, licorice might increase levels of methotrexate.
Animal research suggests that intravenous administration of glycyrrhizin, a licorice constituent, and high-dose methotrexate may delay methotrexate excretion and increase systemic exposure, leading to transient elevations in liver enzymes and total bilirubin. This interaction has not yet been reported in humans.

Likelihood Unlikely Evidence D

Chamomile flower extract9 drug types · 960 drugs

Cns Depressants

Theoretically, German chamomile might have additive effects when used with CNS depressants.
German chamomile has mild sedative effects. Theoretically, concomitant use with drugs with sedative properties can cause additive effects and side effects.

Likelihood Possible Evidence D
Contraceptive Drugs

Theoretically, large amounts of German chamomile might reduce the effectiveness of oral contraceptives.
In vitro, German chamomile has demonstrated antiestrogenic activity. Theoretically, concomitant use of large amounts of German chamomile might interfere with contraceptive drugs through competition for estrogen receptors.

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

Theoretically, German chamomile might inhibit CYP2C9 and increase levels of drugs metabolized by these enzymes.
In vitro evidence shows that German chamomile might inhibit CYP2C9. So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP2C9 in patients taking German chamomile.

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

Theoretically, German chamomile might inhibit CYP2D6 and increase levels of drugs metabolized by these enzymes.
In vitro evidence shows that German chamomile might inhibit CYP2D6. So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP2D6 in patients taking German chamomile.

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

Theoretically, German chamomile might inhibit CYP3A4 and increase levels of drugs metabolized by these enzymes.
In vitro evidence shows that German chamomile might inhibit CYP3A4. So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP3A4 in patients taking German chamomile.

Likelihood Possible Evidence D
Estrogens

Theoretically, large amounts of German chamomile might reduce the effectiveness of estrogens.
In vitro, German chamomile has demonstrated antiestrogenic activity. Theoretically, large amounts of German chamomile might interfere with hormone replacement therapy through competition for estrogen receptors.

Likelihood Possible Evidence D
Tamoxifen (Nolvadex)

Theoretically, large amounts of German chamomile might interfere with the activity of tamoxifen.
In vitro, German chamomile has demonstrated antiestrogenic activity.

Likelihood Possible Evidence D
Warfarin (Coumadin)

German chamomile might increase the effects of warfarin and increase the risk of bleeding.
In one case, a 70-year-old female taking warfarin developed retroperitoneal hematoma and bilateral recti muscle bleeding along with an INR of 7.9 following ingestion of German chamomile tea 4-5 cups daily and use of a topical chamomile-based lotion applied 4-5 times daily.

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

Theoretically, German chamomile might inhibit CYP1A2 and increase levels of drugs metabolized by these enzymes.
In vitro and animal research shows that German chamomile might inhibit CYP1A2. So far, this interaction has not been reported in humans. However, there might be an increase in the levels of drugs metabolized by CYP1A2 in patients taking German chamomile.

Likelihood Possible Evidence D

White Peony7 drug types · 811 drugs

Anticoagulant/Antiplatelet Drugs

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

Likelihood Possible Evidence D
Clozapine (Clozaril)

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

Likelihood Possible Evidence D
Contraceptive Drugs

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

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

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

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

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

Likelihood Possible Evidence D
Estrogens

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

Likelihood Possible Evidence D
Phenytoin (Dilantin)

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

Likelihood Probable Evidence D

Uva-ursi6 drug types · 803 drugs

Cytochrome P450 2C19 (Cyp2C19) Substrates

Theoretically, uva ursi may decrease the metabolism of CYP2C19 substrates.
In vitro, uva ursi appears to inhibit cytochrome CYP2C19. This effect has not been reported in humans.

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

Theoretically, uva ursi may decrease the metabolism of CYP3A4 substrates.
In vitro, uva ursi appears to inhibit CYP3A4. This effect has not been reported in humans.

Likelihood Possible Evidence D
Glucuronidated Drugs

Theoretically, uva ursi may increase levels of drugs metabolized by glucuronidation.
In vitro, uva ursi extract appears to strongly inhibit UDP-glucuronosyltransferase (UGT) 1A1 (UGT1A1). However, uva ursi extract does not appear to inhibit UGT1A1 in animal models. This effect has not been reported in humans.

Likelihood Possible Evidence D
Lithium

Theoretically, uva ursi may increase lithium levels, necessitating a decrease in dose.
Uva ursi may have diuretic properties. Diuretics may increase lithium reabsorption with sodium in the proximal tubule of the kidney. Theoretically, uva ursi might reduce excretion and increase levels of lithium.

Likelihood Probable Evidence D
Urinary Acidifying Agents

Effects of uva ursi in the urinary tract may be reduced by urinary acidifying agents.
Uva ursi seems to work best in alkaline urine. Theoretically, taking uva ursi with medications known to acidify the urine may decrease any effects of uva ursi on the urinary tract.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, uva ursi may alter the levels of drugs transported by P-glycoprotein.
In vitro, uva ursi appears to inhibit the multi-drug transporter protein, P-glycoprotein. This effect has not been reported in humans.

Likelihood Possible Evidence D

Magnesium Citrate15 drug types · 295 drugs

Levodopa/Carbidopa (Sinemet)

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

Likelihood Probable Evidence B
Aminoglycoside Antibiotics

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

Likelihood Possible Evidence D
Antacids

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

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

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

Likelihood Probable Evidence D
Bisphosphonates

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

Likelihood Probable Evidence B
Calcium Channel Blockers

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

Likelihood Possible Evidence D
Digoxin

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

Likelihood Possible Evidence B
Potassium-Sparing Diuretics

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

Likelihood Probable Evidence D
Quinolone Antibiotics

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

Likelihood Probable Evidence D
Skeletal Muscle Relaxants

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

Likelihood Probable Evidence A
Sulfonylureas

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

Likelihood Probable Evidence B
Tetracycline Antibiotics

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

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

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

Likelihood Unlikely Evidence B
Gabapentin (Neurontin)

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

Likelihood Unlikely Evidence B
Sevelamer (Renagel, Renvela)

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

Likelihood Possible Evidence B

Angelica sinensis3 drug types · 163 drugs

Warfarin (Coumadin)

Dong quai may increase the risk of bleeding when used with warfarin.
Case reports suggest that concomitant use of dong quai with warfarin can increase the anticoagulant effects of warfarin and increase the risk of bleeding. In one case, after 4 weeks of taking dong quai 565 mg once or twice daily, the international normalized ratio (INR) increased to 4.9. The INR normalized 4 weeks after discontinuation of dong quai.

Likelihood Probable Evidence D
Anticoagulant/Antiplatelet Drugs

Theoretically, dong quai may increase the risk of bleeding when used with anticoagulant or antiplatelet drugs; however, research is conflicting.
Animal studies suggest that dong quai has antithrombin activity and inhibits platelet aggregation due to its coumarin components. Additionally, some case reports in humans suggest that dong quai can increase the anticoagulant effects of warfarin. However, clinical research in healthy adults shows that taking 1 gram of dong quai root daily for 3 weeks does not significantly inhibit platelet aggregation or cause bleeding. Until more is known, use dong quai with caution in patients taking antiplatelet/anticoagulant drugs.

Likelihood Possible Evidence D
Estrogens

Theoretically, dong quai may reduce the effects of estrogens.
Dong quai has estrogenic effects. Theoretically, concomitant use of large amounts of dong quai might interfere with hormone replacement therapy due to competition for estrogen receptors.

Likelihood Possible Evidence D

Potassium3 drug types · 62 drugs

Ace Inhibitors (Aceis)

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

Likelihood Likely Evidence C
Angiotensin Receptor Blockers (Arbs)

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

Likelihood Likely Evidence C
Potassium-Sparing Diuretics

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

Likelihood Likely Evidence C
The maker

Brand information

Manufacturer and brand details for Restless Leg Calm, from the product label.

Signature Supplements

See all Signature Supplements products
Name
Signature Supplements
Street Address
P.O. Box 1112
City
San Clemente
State
CA
Web Address
yoursignaturesupplements.com
Pharmacist Counseling Corner

Restless Leg Calm by Signature Supplements: Common Questions

Does Restless Leg Calm by Signature Supplements interact with any medications?
Yes. Based on its ingredients, Restless Leg Calm has a known interaction with 1,329 medications, including 8 rated major. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Restless Leg Calm contains 7 active ingredients, and an interaction can come from any of them. We check every ingredient, combine the results into one list per medication, and show which ingredient and mechanism is responsible.
Where does this information come from?
The product label data comes from the NIH Dietary Supplement Label Database (DSLD); the interaction data is built on the Natural Medicines database and reviewed by HelloPharmacist pharmacists.
Can I take this with my blood thinner (warfarin)?
No—not without talking to your doctor first. Dong quai in this product can increase how much warfarin works, raising your bleeding risk. Your doctor may need to check your INR (blood clotting test). Talk to your pharmacist before you start.
Will this help restless legs?
The product is labeled for restless legs, but we don't have established effectiveness data for that use in our facts. Magnesium citrate is proven for constipation and heartburn. If restless legs are a concern, talk to your doctor about what evidence supports treatment.
What side effects should I expect?
Magnesium commonly causes loose stools, nausea, and stomach upset—especially at higher doses. Dong quai, uva ursi, and licorice may cause nausea, upset stomach, or diarrhea. Dong quai can also make your skin more sensitive to sunlight.
Is this safe to take in pregnancy?
Magnesium and potassium from food are needed in pregnancy, but supplements require your doctor's okay. Dong quai, uva ursi, and licorice are advised against in pregnancy—the safety data aren't there or raise concerns. Talk with your doctor or midwife before starting this product.
Can I take this if I'm breastfeeding?
Dietary amounts of magnesium and potassium are fine, but supplements need your doctor's approval. Dong quai, uva ursi, licorice, and peony don't have enough safety data for breastfeeding—the data suggests it's best to avoid them. Check with your doctor first.
Does magnesium in this product interact with my diabetes medication?
Yes—magnesium can increase how much of certain diabetes drugs (sulfonylureas like glyburide) your body absorbs, raising the risk of low blood sugar. If you take a sulfonylurea, tell your pharmacist before starting this product and watch for low-blood-sugar symptoms.

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.

Restless Leg Calm label
Go deeper

The Full Monographs Behind Restless Leg Calm’s Ingredients

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

Herb & supplement monograph

Magnesium

Interacts with 295 drugs

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

Read the full Magnesium monograph →
Herb & supplement monograph

Potassium

Interacts with 62 drugs

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

Read the full Potassium monograph →
Herb & supplement monograph

Dong Quai

Interacts with 163 drugs

Dong Quai is a traditional Chinese herb often called "female ginseng" and is mostly used for menstrual and menopausal complaints. High-quality scientific evidence that it works for these use...

Read the full Dong Quai monograph →
Herb & supplement monograph

German Chamomile

Interacts with 960 drugs

German chamomile is a widely used herbal remedy taken mainly as a tea for calming, sleep, and digestive complaints. Early research suggests possible benefits for mild anxiety and some skin o...

Read the full German Chamomile monograph →
Herb & supplement monograph

Uva Ursi

Interacts with 803 drugs

Uva ursi is a traditional herb used mainly for urinary tract infections, and its leaves contain a compound called arbutin that may have antimicrobial effects in the urine. Evidence in people...

Read the full Uva Ursi monograph →
Herb & supplement monograph

Licorice

Interacts with 1,040 drugs

Licorice root is a traditional remedy used for sore throats, coughs, and digestive complaints, but solid human evidence is limited for most uses. Regular licorice contains glycyrrhizin, whic...

Read the full Licorice monograph →
Herb & supplement monograph

Peony

Interacts with 811 drugs

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

Read the full Peony monograph →
Sources

Sources & How We Checked

Restless Leg Calm'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 243 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.

Magnesium 82 references
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  10. Heidenreich O. Mode of action of conventional and potassium-sparing diuretics--aspects with relevance to Mg-sparing effects. Magnesium 1984;3:248-56..
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  18. Davey MJ, Teubner D. A randomized controlled trial of magnesium sulfate, in addition to usual care, for rate control in atrial fibrillation. Ann Emerg Med 2005;45:347-53.. PubMed
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  39. Li, J., Zhang, Q., Zhang, M., and Egger, M. Intravenous magnesium for acute myocardial infarction. Cochrane.Database.Syst.Rev. 2007;(2):CD002755. PubMed
  40. Doyle, L. W., Crowther, C. A., Middleton, P., Marret, S., and Rouse, D. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane.Database.Syst.Rev. 2009;(1):CD004661. PubMed
  41. Han, S., Crowther, C. A., and Moore, V. Magnesium maintenance therapy for preventing preterm birth after threatened preterm labour. Cochrane.Database.Syst.Rev. 2010;(7):CD000940. PubMed
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  54. Ji D. Oral magnesium sulfate causes perforation during bowel preparation for fiberoptic colonoscopy in patients with colorectal cancer. J Emerg Med 2012;43(4):716-7. PubMed
  55. Yagi T, Naito T, Mino Y, Umemura K, Kawakami J. Impact of concomitant antacid administration on gabapentin plasma exposure and oral bioavailability in healthy adult subjects. Drug Metab Pharmacokinet 2012;27(2):248-54. PubMed
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  57. Choi ES, Jeong WJ, Ahn SH, Oh AY, Jeon YT, Do SH. Magnesium sulfate accelerates the onset of low-dose rocuronium in patients undergoing laryngeal microsurgery. J Clin Anesth. 2017 Feb;36:102-106. PubMed
  58. Ikee R, Toyoyama T, Endo T, Tsunoda M, Hashimoto N. Impact of sevelamer hydrochloride on serum magnesium concentrations in hemodialysis patients. Magnes Res. 2016 Apr 1;29(4):184-90. PubMed
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  72. Almeida CED, Carvalho LR, Andrade CVC, Nascimento PD Jr, Barros GAM, Modolo NSP. Effects of magnesium sulphate on the onset time of rocuronium at different doses: a randomized clinical trial. Braz J Anesthesiol. 2021;71(5):482-8. PubMed
  73. Gochi Valdovinos A, Arriaga-Redondo M, Dejuan Bitriá E, Pérez Rodríguez I, Márquez Isidro E, Blanco Bravo D. Prenatal therapy with magnesium sulphate and intestinal obstruction due to meconium in preterm newborns. An Pediatr (Engl Ed). 2022 Feb;96(2):138- PubMed
  74. Iio K, Kondo E, Shibata E, et al. Long-term tocolysis with magnesium sulfate as a risk factor for low bone mass: a case series. J Med Cases. 2022 Feb;13(2):47-50. PubMed
  75. Eiraku K, Uozumi Y, Hieda M, Maruyama T, Nomura H. A senile case of heart failure associated with hypermagnesemia induced by magnesium-containing laxative agent. Geriatr Gerontol Int. 2022;22(10):897-899.
  76. Enayati A, Gin JH, Sajeev JK, et al. Efficacy of intravenous magnesium for the management of non-post operative atrial fibrillation with rapid ventricular response: A systematic review and meta-analysis. J Cardiovasc Electrophysiol 2023;34(5):1286-1295. PubMed
  77. Su YH, Luo DC, Pang Y. Effects of intraoperative Magnesium sulfate infusion on emergency agitation during general anesthesia in patients undergoing radical mastectomy: a randomized controlled study. BMC Anesthesiol 2023;23(1):326. PubMed
  78. Han J, Park HY, Shin HJ, Chung SH, Do SH. Effects of magnesium sulphate on neostigmine-induced recovery from moderate neuromuscular blockade with rocuronium: a randomized controlled trial. Magnes Res 2023;36(2):31-39. PubMed
  79. Lee AT, Cordova JC, Jamplis RP, Pomicter GR. Posterior Reversible Encephalopathy Syndrome and Eclampsia in the Setting of Magnesium Toxicity: A Case Report. A A Pract 2023;17(11):e01726. PubMed
  80. Darmawan D, Rengganis I, Rumende CM, et al. Effectiveness and Safety of Nebulized Magnesium as Last Line Treatment in Adults with Acute Asthma Attack: A Systematic Review and Meta-Analysis. Acta Med Indones 2024;56(1):3-12.
  81. Shepherd ES, Goldsmith S, Doyle LW, et al. Magnesium sulphate for women at risk of preterm birth for neuroprotection of the fetus. Cochrane Database Syst Rev 2024;5(5):CD004661. PubMed
  82. US Food and Drug Administration (FDA). Biktarvy Prescribing Information. October 2024. Available at: https://www.accessdata.fda.gov/drugsatfda_docs/label/2024/210251Orig1s020lbl.pdf. Accessed July 16, 2025.

See these in context on the Magnesium monograph →

Potassium 12 references
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  2. Gennaro A. Remington: The Science and Practice of Pharmacy. 19th ed. Lippincott: Williams & Wilkins, 1996.
  3. Whelton PK, He J, Cutler JA, et al. Effects of oral potassium on blood pressure. Meta-analysis of randomized controlled clinical trials. JAMA 1997;277:1624-32. PubMed
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Parts of this content are provided by the Therapeutic Research Center, LLC.

DISCLAIMER: Currently this does not check for drug-drug interactions. This is not an all-inclusive comprehensive list of potential interactions and is for informational purposes only. Not all interactions are known or well-reported in the scientific literature, and new interactions are continually being reported. Input is needed from a qualified healthcare provider including a pharmacist before starting any therapy. Application of clinical judgment is necessary.

© 2021 Therapeutic Research Center, LLC

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