Interactions on record — worth a quick check against your medications. Based on 8 of 12 ingredients. Check your meds →
Dietary supplement

Apex Male Ingredients & Drug Interactions

by Blackstone Labs

Capsule Category: Other Combinations
Most serious interaction: Moderate
The interaction bottom line Most serious interaction: Moderate

Apex Male is a dietary supplement by Blackstone Labs with 12 active ingredients. Its ingredients are commonly taken for mental focus and alertness, coping with stress, fatigue and sleep loss.Based on those ingredients, 1,220 medications have a known interaction with it, the most serious rated moderate. The ingredients most likely to interact are Bioperine Black Pepper fruit extract, Epimedium extract, Bulbine natalensis. Use the checker below to test your specific medication, or read the full HelloPharmacist Interaction Report.

HelloPharmacist Scorecard of Apex Male by Blackstone Labs

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 12 of its 12 active ingredients.
  • No proprietary blends here — you can verify the dose of every single component.

Apex Male contains 12 active ingredients. L-Tyrosine is an amino acid (a building block of protein) that your body uses to make neurotransmitters and thyroid hormone.

Vitamin D3 is a hormone your body produces and uses to support bone health and calcium balance. D-Aspartic Acid, DIM, N-Methyl-D-Aspartate, Bulbine natalensis, fenugreek extract, tribulus terrestris, maca extract, Prunella vulgaris, and epimedium extract are herbal and botanical compounds traditionally used in male-focused supplements.

Bioperine (black pepper fruit extract) is included to help your body absorb other ingredients. The inactive ingredients are gelatin, dicalcium phosphate, magnesium phosphate, silicon dioxide, and titanium dioxide — these are fillers, binders, and capsule materials.

Does it work?

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

Some clinical evidence supports this product's ingredients for its stated purpose, but it isn't conclusive.

Why this rating?
  • The label markets this product for: natural testosterone production and male sexual function.
  • We looked for evidence on: Age-related testosterone deficiency, Erectile dysfunction (ED), Antidepressant-induced sexual dysfunction, Athletic performance, libido, stamina — and 2 related terms.
  • The strongest evidence on file: Tribulus is rated "Possibly Effective" for Sexual dysfunction (Natural Medicines).
  • Also on file: Fenugreek is rated "Possibly Effective" for Sexual dysfunction.
  • Also on file: Tribulus is rated "Possibly Ineffective" for Athletic performance.

The evidence for most of these ingredients is limited. L-Tyrosine is possibly effective for cognitive function and memory, though not for athletic performance.

Vitamin D3 is effective for rickets, osteomalacia, renal bone disease, familial hypophosphatemia, and hypoparathyroidism — but those aren't what this product is marketed for. Tribulus terrestris is possibly effective for sexual dysfunction but possibly ineffective for athletic performance.

Fenugreek is possibly effective for sexual dysfunction and dysmenorrhea, and possibly effective for diabetes. The evidence isn't established in our data for maca extract, Bulbine natalensis, Prunella vulgaris, epimedium, D-Aspartic Acid, DIM, N-Methyl-D-Aspartate, or black pepper for the purposes this product is likely intended for.

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 8 of the 8 matched ingredients.
  • Pregnancy & breastfeeding safety ratings cover 8 of 8.
  • General safety write-ups exist for 8 of 8.
  • Remember: this measures how much safety information exists. Thin data is not the same as being safe.

L-Tyrosine is generally well tolerated but not enough safety data exist for regular supplemental use — talk to your doctor first. Most common side effects are fatigue, headache, heartburn, and nausea.

Vitamin D3 is safe at recommended doses, though very high doses over time can cause toxicity (hypercalcemia). It's often used during pregnancy at recommended amounts, but only under a doctor's guidance.

Fenugreek is generally well tolerated in food amounts, but supplement doses may cause abdominal pain, bloating, diarrhea, flatulence, and nausea — avoid medicinal amounts during pregnancy. Bulbine natalensis has limited human safety data and animal studies suggest possible liver and kidney toxicity at higher doses; avoid it during pregnancy and breastfeeding.

Tribulus is often well tolerated short-term but long-term safety data are limited; avoid during pregnancy and breastfeeding. Maca is generally tolerated as a food but long-term supplement safety hasn't been studied; avoid during pregnancy and breastfeeding.

Black pepper is generally safe in food amounts; safety of supplement-strength doses is less clear. Data on Prunella vulgaris, epimedium, and pregnancy/breastfeeding status for some ingredients aren't on file.

Meds to double-check

Moderate interaction found
Known Interaction Concern · database check
Moderate identified

The most serious documented interaction for these ingredients is Moderate. Check your medications for a personalized result.

Why this rating?
  • 7 of the 8 matched ingredients can interact with medications — Tribulus, Horny Goat Weed, Fenugreek, Black Pepper, Vitamin D, among others.
  • The most serious interaction on file is rated Moderate.
  • Some involve high-stakes drug classes: anticoagulant / antiplatelet drugs; immunosuppressants / transplant drugs; diabetes medications; heart-rhythm medications; lithium; Parkinson's medications.
  • For scale: 1,221 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 pharmacist if you take levodopa (Parkinson's), heart rhythm drugs like verapamil or digoxin, beta-blockers like propranolol, blood thinners like warfarin or clopidogrel, blood-sugar drugs, phenytoin or other seizure medications, theophylline, rifampin, or atorvastatin. If you take lithium, tribulus may raise its levels.

Altogether, these interactions span 1,177 individual medications.

Check your own medication Run your meds through the checker above

The bottom line

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

This product is intended for adult men and contains ingredients with real interactions with heart medications, blood thinners, blood-sugar drugs, and seizure medications. If you take any prescription drugs — especially for your heart, blood pressure, blood sugar, or seizures — talk to your pharmacist or doctor before starting it.

Even if you don't take medications now, several of these ingredients have limited safety data in humans.

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

Assessment coverage: 8 of 12 active ingredients matched to our full ingredient reviews (monographs). Based on the product label dated Jul 24, 2019.

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

At a glance

General information

Key facts about Apex Male, straight from the product label.

Brand Blackstone Labs
Barcode (UPC) 705332717199
Net contents 240 Capsule(s)
Market status On market
Date entered into DSLD Jul 24, 2019
DSLD ID 205025
Product type Other Combinations
Supplement form Capsule
Dietary claims / uses All Other, Structure/Function
Intended target group(s) Adult Male (18-50 Years)
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 Apex Male by Blackstone Labs, sourced from the NIH Dietary Supplement Label Database.

Supplement Facts

Daily Value (DV) Target Group(s):
Adults and children 4 or more years of age
Minimum serving Sizes:
4 Capsule(s)
Maximum serving Sizes:
4 Capsule(s)
Servings per container
60
UPC/BARCODE
705332717199
IngredientAmount% DV
L-Tyrosine125 mg--
Vitamin D31250 IU313%
D-Aspartic Acid1500 mg--
DIM100 mg--
N-Methyl-D-Aspartate15 mg--
Bulbine natalensis500 mg--
Fenugreek extract125 mg--
Tribulus terrestris125 mg--
Maca extract125 mg--
Prunella vulgaris75 mg--
Epimedium extract75 mg--
Bioperine Black Pepper fruit extract5 mg--

Other ingredients: Gelatin, Dicalcium Phosphate, Magnesium Phosphate, Silicon Dioxide, Titanium Dioxide

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

Promotes natural testosterone production Great bridge between cycles Supports increased aggression & energy in the gym Promotes a healthy libido and increases stamina

Suggested/Recommended/Usage/Directions

Directions As a dietary supplement, take four (4) capsules (2) times per day with food.

Formula

Apex male is a complete and natural test booster, and requires no cycling or PCT.

Promotes natural testosterone production

Storage

Store in a cool, dry place.

Precautions

Warning Keep out of reach of children.

You must be 18 years of age or older to take this product. Do not use this product if you are at risk for or are being treated for high blood pressure, heart, kidney, thyroid or psychiatric disease, anxiety, depression, seizure disorders, strokes, or any other medical conditions.

Do not take this product if you are using anti-depressant, MAO/MAOI inhibitors or any other prescription drugs.

This product may elevate serum hormone levels which could produce positive results if you are subject to NCAA testing. Consult your medical professional before taking this product. For use by healthy individuals only.

Allergen warning: Manufactured on shared equipment that also processes eggs, wheat, & Soy (Lecithin).

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

See for yourself

Apex Male by Blackstone Labs label

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

What’s inside

The Ingredients in Apex Male by Blackstone Labs

These are the 12 active ingredients this product is made of. Select any to open its full monograph.

Serving size4 Capsule(s) Dosage formCapsule Servings per container60 Amounts shown are per serving.

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

L-Tyrosine

Interacts with
21 drugs
125 mg per serving

L-tyrosine is an amino acid your body uses to make brain chemicals like dopamine and norepinephrine. Some studies suggest it may help mental performan...

L-Tyrosine monograph & interactions

Vitamin D3

Interacts with
715 drugs
1250 IU per serving Form: Cholecalciferol

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

Vitamin D3 monograph & interactions

D-Aspartic Acid

1500 mg per serving

DIM

100 mg per serving

N-Methyl-D-Aspartate

15 mg per serving

Bulbine natalensis

Interacts with
919 drugs
500 mg per serving

Bulbine natalensis is a South African plant marketed mainly as a testosterone-boosting and libido supplement, but the human evidence is essentially ab...

Bulbine natalensis monograph & interactions

Fenugreek extract

Interacts with
389 drugs
125 mg per serving Form: Saponins

Fenugreek is a common kitchen spice that is also taken as a supplement, mainly for blood sugar, cholesterol, and to support breast milk production. So...

Fenugreek extract monograph & interactions

Tribulus terrestris

Interacts with
259 drugs
125 mg per serving Form: Saponins

Tribulus is a plant supplement most often marketed to boost libido, testosterone, and athletic performance, but the human evidence behind these claims...

Tribulus terrestris monograph & interactions

Maca extract

No known
interactions
125 mg per serving Form: Macamides and Macaenes

Maca is a nutrient-rich Andean root often used for energy, libido, and menopause symptoms. Early studies suggest it may modestly help sexual desire an...

Maca extract monograph & interactions

Prunella vulgaris

75 mg per serving

Epimedium extract

Interacts with
963 drugs
75 mg per serving

Horny goat weed (Epimedium) is a traditional Chinese herb most often marketed for low libido and erectile problems, but solid human evidence for these...

Epimedium extract monograph & interactions

Bioperine Black Pepper fruit extract

Interacts with
1,019 drugs
5 mg per serving

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to he...

Bioperine Black Pepper fruit extract monograph & interactions

Other (inactive) ingredients: Gelatin, Dicalcium Phosphate, Magnesium Phosphate, Silicon Dioxide, Titanium Dioxide. These complete the product’s ingredient list but are not active constituents.

Interaction report

Apex Male by Blackstone Labs Drug Interactions

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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
1,220Drugs
1,218 Moderate 2 Minor

Ingredients driving the most interactions

Each ingredient & the kinds of drugs it affects

For each ingredient in Apex Male 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.

Bioperine Black Pepper fruit extract17 drug types · 1,019 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, black pepper might increase the risk of bleeding when taken with antiplatelet or anticoagulant drugs.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit platelet aggregation. This has not been reported in humans.

Likelihood Possible Evidence D
Antidiabetes Drugs

Theoretically, black pepper might increase the risk of hypoglycemia when taken with antidiabetes drugs.
Animal research shows that piperine, a constituent of black pepper, can reduce blood glucose levels. Monitor blood glucose levels closely. Dose adjustments might be necessary.

Likelihood Possible Evidence D
Atorvastatin (Lipitor)

Theoretically, black pepper might increase blood levels of atorvastatin.
Animal research shows that taking piperine, a constituent of black pepper, 35 mg/kg can increase the maximum serum concentration of atorvastatin three-fold. This has not been reported in humans.

Likelihood Possible Evidence D
Cyclosporine (Neoral, Sandimmune)

Theoretically, black pepper might increase the effects and side effects of cyclosporine.
In vitro research shows that piperine, a constituent of black pepper, increases the bioavailability of cyclosporine. This has not been reported in humans.

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

Theoretically, black pepper might increase levels of drugs metabolized by CYP2D6.
In vitro research suggests that some constituents of black pepper inhibit CYP2D6. This has not been reported in humans.

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

Theoretically, black pepper might increase levels of drugs metabolized by CYP3A4.
In vitro research and pharmacokinetic simulation data suggest that piperine, a constituent of black pepper, as well as the pepper fruit seem to inhibit CYP3A4. This has not been reported in humans.

Likelihood Possible Evidence D
Lithium

Theoretically, black pepper might increase blood levels of lithium due to its diuretic effects. The dose of lithium might need to be reduced.
Black pepper is thought to have diuretic properties.

Likelihood Probable Evidence D
Nevirapine (Viramune)

Black pepper might increase blood levels of nevirapine.
Clinical research shows that piperine, a constituent of black pepper, increases the plasma concentration of nevirapine. However, no adverse effects were observed in this study.

Likelihood Probable Evidence D
P-Glycoprotein Substrates

Theoretically, black pepper might increase levels of P-glycoprotein substrates.
In vitro research shows that piperine, a constituent of black pepper, seems to inhibit P-glycoprotein.

Likelihood Possible Evidence D
Pentobarbital (Nembutal)

Theoretically, black pepper might increase the sedative effects of pentobarbital.
Animal research shows that piperine, a constituent of black pepper, increases pentobarbital-induced sleeping time.

Likelihood Possible Evidence D
Phenytoin (Dilantin)

Black pepper might increase blood levels of phenytoin.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption, slow elimination, and increase levels of phenytoin. Taking a single dose of black pepper 1 gram along with phenytoin seems to double the serum concentration of phenytoin. Consuming a soup with black pepper providing piperine 44 mg/200 mL of soup along with phenytoin also seems to increase phenytoin levels when compared with consuming the same soup without black pepper.

Likelihood Possible Evidence B
Propranolol (Inderal)

Black pepper might increase blood levels of propranolol.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of propranolol.

Likelihood Possible Evidence B
Rifampin (Rifadin)

Black pepper might increase blood levels of rifampin.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and serum levels of rifampin.

Likelihood Possible Evidence B
Theophylline

Black pepper might increase blood levels of theophylline.
Clinical research shows that piperine, a constituent of black pepper, seems to increase absorption and slow elimination of theophylline.

Likelihood Possible Evidence D
Amoxicillin (Amoxil, Trimox)

Theoretically, black pepper might increase the effects and side effects of amoxicillin.
Animal research shows that taking piperine, a constituent of black pepper, with amoxicillin increases plasma levels of amoxicillin. This has not been reported in humans.

Likelihood Possible Evidence D
Carbamazepine (Tegretol)

Theoretically, black pepper might increase blood levels of carbamazepine, potentially increasing the effects and side effects of carbamazepine.
One clinical study in patients taking carbamazepine 300 mg or 500 mg twice daily shows that taking a single 20 mg dose of purified piperine, a constituent of black pepper, increases carbamazepine levels. Piperine may increase carbamazepine absorption by increasing blood flow to the GI tract, increasing the surface area of the small intestine, or inhibiting cytochrome P450 3A4 (CYP3A4) in the gut wall. Absorption was significantly increased by 7-10 mcg/mL/hour. The time to eliminate carbamazepine was also increased by 4-8 hours. Although carbamazepine levels were increased, this did not appear to increase side effects. In vitro research also shows that piperine can increase carbamazepine levels by 11% in a time-dependent manner.

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

Theoretically, black pepper might decrease levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that black pepper induces CYP1A2. This has not been reported in humans.

Likelihood Possible Evidence D

Epimedium extract6 drug types · 963 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, horny goat weed might increase the risk of bleeding.
In vitro research and animal research shows that horny goat weed can inhibit platelet aggregation and thrombus formation. This effect has not been reported in humans.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, horny goat weed might increase the risk of hypotension.
Laboratory research suggests that horny goat weed might have hypotensive effects. This effect has not been reported in humans.

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

Theoretically, horny goat weed might increase the effects and side effects of CYP1A2 substrates.
In vitro, horny goat weed leaf extract inhibits CYP1A2. This effect has not been reported in humans.

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

Theoretically, horny goat weed might increase the effects and side effects of CYP2B6 substrates.
In vitro, horny goat weed leaf extract inhibits CYP2B6. This effect has not been reported in humans.

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

Theoretically, horny goat weed might increase the effects and side effects of CYP3A4 substrates.
In vitro, horny goat weed extract inhibits CYP3A4 and suppresses CYP3A4 mRNA expression. This effect has not been reported in humans.

Likelihood Possible Evidence D
Estrogens

Theoretically, concomitant use of horny goat weed with estrogens might increase their therapeutic and adverse effects.
In vitro evidence suggests that horny goat weed has estrogenic activity. In clinical research, horny goat weed has been shown to increase blood levels of estrogen in some females.

Likelihood Possible Evidence D

Bulbine natalensis7 drug types · 919 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, combining Bulbine natalensis leaf with drugs that have anticoagulant or antiplatelet activity might increase the risk of bruising and bleeding.
In vitro research shows that Bulbine natalensis ground leaf extract inhibits platelet aggregation.

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

Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP1A2 substrates.
In vitro research shows that Bulbine natalensis stem extract slightly induces CYP1A2 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP1A2 substrates; however, this has not been studied in humans.

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

Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP2C9 substrates.
In vitro research shows that Bulbine natalensis stem extract induces CYP2C9 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP2C9 substrates; however, this has not been studied in humans.

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

Theoretically, Bulbine natalensis stem might reduce the levels and clinical effects of CYP3A4 substrates.
In vitro research shows that Bulbine natalensis stem extract induces CYP3A4 mRNA expression and enzyme activity. Theoretically, this may increase the metabolism of CYP3A4 substrates, but this has not been studied in humans.

Likelihood Possible Evidence D
Digoxin (Lanoxin)

Theoretically, Bulbine natalensis stem might increase the risk of adverse effects and toxicity when taken with digoxin.
Bulbine natalensis stem may contain cardiac glycosides, although it is unclear if these chemicals are present in clinically relevant concentrations.

Likelihood Possible Evidence D
P-Glycoprotein Substrates

Theoretically, Bulbine natalensis stem might increase the levels and clinical effects of p-glycoprotein substrates.
In vitro research shows that Bulbine natalensis stem extract induces p-glycoprotein mRNA expression; however, effects on transporter expression were not evaluated.

Likelihood Possible Evidence D
Testosterone

Theoretically, using Bulbine natalensis stem with testosterone replacement therapy might increase the risk of adverse effects.
Animal research shows that Bulbine natalensis stem can increase testosterone levels.

Likelihood Possible Evidence D

Vitamin D38 drug types · 715 drugs

Aluminum

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

Likelihood Probable Evidence B
Atorvastatin (Lipitor)

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

Likelihood Probable Evidence B
Calcipotriene (Dovonex)

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

Likelihood Probable Evidence D
Digoxin (Lanoxin)

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

Likelihood Possible Evidence D
Diltiazem (Cardizem, Others)

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

Likelihood Probable Evidence B
Thiazide Diuretics

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

Likelihood Probable Evidence D
Verapamil (Calan, Others)

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

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

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

Likelihood Possible Evidence D

Fenugreek extract9 drug types · 389 drugs

Anticoagulant/Antiplatelet Drugs

Theoretically, fenugreek might have additive effects when used with anticoagulant or antiplatelet drugs.
Some of the constituents in fenugreek have antiplatelet effects in animal and in vitro research. However, common fenugreek products might not contain sufficient concentrations of these constituents for clinical effects. A clinical study in patients with coronary artery disease or diabetes shows that taking fenugreek seed powder 2.5 grams twice daily for 3 months does not affect platelet aggregation, fibrinolytic activity, or fibrinogen levels .

Likelihood Unlikely Evidence B
Antidiabetes Drugs

Theoretically, fenugreek seed might have additive hypoglycemic effects when used with antidiabetes drugs.
Clinical research shows that fenugreek seed can reduce fasting blood glucose and 2-hour postprandial glucose levels in adults with type 2 diabetes.

Likelihood Probable Evidence B
Clopidogrel (Plavix)

Theoretically, fenugreek seed might alter the clinical effects of clopidogrel by inhibiting its conversion to the active form.
Animal research shows that fenugreek seed 200 mg/kg daily for 14 days increases the maximum serum concentration of clopidogrel by 21%. It is unclear how this affects the pharmacokinetics of the active metabolite of clopidogrel; however, this study found that concomitant use of fenugreek seed and clopidogrel prolonged bleeding time by an additional 11%.

Likelihood Possible Evidence D
Metoprolol (Toprol)

Theoretically, fenugreek seed might have additive hypotensive effects when used with metoprolol.
Animal research shows that fenugreek seed 300 mg/kg daily for 2 weeks decreases systolic and diastolic blood pressure by 9% and 11%, respectively, when administered alone, and by 15% and 22%, respectively, when given with metoprolol 10 mg/kg.

Likelihood Probable Evidence B
Phenytoin (Dilantin)

Theoretically, fenugreek might decrease plasma levels of phenytoin.
Animal research shows that taking fenugreek seeds for 1 week decreases maximum concentrations and the area under the curve of a single dose of phenytoin by 44% and 72%, respectively. This seems to be related to increased clearance. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Sildenafil (Viagra)

Theoretically, concurrent use of sildenafil and fenugreek might reduce levels and therapeutic effects of sildenafil.
Animal research shows that taking fenugreek seeds for 1 week reduces maximum concentrations and the area under the curve of a single dose of sildenafil by 27% and 48%, respectively. So far, this interaction has not been reported in humans.

Likelihood Possible Evidence D
Theophylline

Theoretically, fenugreek may reduce the levels and clinical effects of theophylline.
Animal research shows that fenugreek 50 grams daily for 7 days reduces the maximum serum concentration (Cmax) of theophylline by 28% and the area under the plasma drug concentration-time curve (AUC) by 22%.

Likelihood Possible Evidence D
Warfarin (Coumadin)

Theoretically, fenugreek might have additive effects with warfarin and increase the international normalized ratio (INR).
Some fenugreek constituents have antiplatelet effects, although these might not be present in concentrations that are clinically significant. In one case report, a patient taking warfarin experienced an increased INR when starting to take fenugreek in combination with boldo.

Likelihood Possible Evidence D
Antihypertensive Drugs

Fenugreek may also have an additive effect on blood pressure-lowering medications. Studies on animals have shown that fenugreek seed can decrease both systolic and diastolic blood pressure by up to 22% when combined with metoprolol. Therefore, it is essential to monitor your blood pressure regularly if you are taking fenugreek and metoprolol together or any other antihypertensive drugs.

Likelihood Possible Evidence C

Tribulus terrestris3 drug types · 259 drugs

Antidiabetes Drugs

Taking tribulus with antidiabetes drugs might increase the risk of hypoglycemia.
Clinical research shows that Tribulus can lower blood glucose levels in adults with type 2 diabetes who are taking antidiabetes medications.

Likelihood Possible Evidence D
Antihypertensive Drugs

Theoretically, taking tribulus with antihypertensive drugs might increase the risk of hypotension.
Animal research shows that tribulus can lower blood pressure by inhibiting angiotensin-converting enzyme (ACE). Tribulus has also demonstrated hypotensive effects in pre-hypertensive adults.

Likelihood Possible Evidence D
Lithium

Theoretically, tribulus might increase the levels and clinical effects of lithium.
Tribulus is thought to have diuretic properties. Due to these potential diuretic effects, tribulus might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.

Likelihood Probable Evidence D

L-Tyrosine2 drug types · 21 drugs

Levodopa

Theoretically, tyrosine might decrease the effectiveness of levodopa.
Tyrosine and levodopa compete for absorption in the proximal duodenum by the large neutral amino acid (LNAA) transport system. Advise patients to separate doses of tyrosine and levodopa by at least 2 hours.

Likelihood Probable Evidence D
Thyroid Hormone

Theoretically, tyrosine might have additive effects with thyroid hormone medications.
Tyrosine is a precursor to thyroxine and might increase levels of thyroid hormones.

Likelihood Probable Evidence D
The maker

Brand information

Manufacturer and brand details for Apex Male, from the product label.

Blackstone Labs

See all Blackstone Labs products
Name
Blackstone Labs
City
Boca Raton
State
FL
ZipCode
33487
Phone Number
1-877-454-6861
Web Address
www.BlackStoneLabs.com
Pharmacist Counseling Corner

Apex Male by Blackstone Labs: Common Questions

Does Apex Male by Blackstone Labs interact with any medications?
Yes. Based on its ingredients, Apex Male has a known interaction with 1,220 medications. Use the checker to see how it interacts with a specific drug.
How can one product interact with so many drugs?
Apex Male contains 12 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 a blood thinner like warfarin?
Not without talking to your doctor or pharmacist first. Fenugreek in this product can have blood-thinning effects and may increase warfarin's strength or clopidogrel's activity, raising your risk of bleeding. Your provider needs to know.
Is there enough evidence this actually works for what it claims?
Evidence for most ingredients is limited or not established in our data. Tribulus and fenugreek are possibly effective for sexual function, but the product contains many other ingredients with insufficient evidence to rate their effectiveness.
Can I take this if I'm pregnant or breastfeeding?
No. Bulbine natalensis and fenugreek are unsafe or possibly unsafe during pregnancy, and most of the herbal ingredients lack reliable safety data for breastfeeding. Talk to your doctor before considering it.
What are the most common side effects?
L-Tyrosine can cause fatigue, headache, heartburn, and nausea. Fenugreek may cause bloating, gas, diarrhea, and abdominal pain. Black pepper in the blend is generally well tolerated but might cause a burning aftertaste or indigestion.
Why is black pepper in this formula?
Black pepper (Bioperine) is included to help your body absorb the other ingredients better. However, it can also increase how much of certain medications your body absorbs — which is why you need to check with your pharmacist if you take any prescriptions.
Can I take this with my heart or blood pressure medication?
Not safely without checking first. Vitamin D3 at high doses, L-Tyrosine, and black pepper can all interact with heart and blood-pressure drugs. Your pharmacist needs to review your specific medications.

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.

Apex Male label
Go deeper

The Full Monographs Behind Apex Male’s Ingredients

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

Herb & supplement monograph

Tyrosine

Interacts with 21 drugs

L-tyrosine is an amino acid your body uses to make brain chemicals like dopamine and norepinephrine. Some studies suggest it may help mental performance during short-term stress, sleep loss,...

Read the full Tyrosine monograph →
Herb & supplement monograph

Vitamin D

Interacts with 715 drugs

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

Read the full Vitamin D monograph →
Herb & supplement monograph

Bulbine Natalensis

Interacts with 919 drugs

Bulbine natalensis is a South African plant marketed mainly as a testosterone-boosting and libido supplement, but the human evidence is essentially absent and most claims come from animal st...

Read the full Bulbine Natalensis monograph →
Herb & supplement monograph

Fenugreek

Interacts with 389 drugs

Fenugreek is a common kitchen spice that is also taken as a supplement, mainly for blood sugar, cholesterol, and to support breast milk production. Some early research is encouraging for blo...

Read the full Fenugreek monograph →
Herb & supplement monograph

Tribulus

Interacts with 259 drugs

Tribulus is a plant supplement most often marketed to boost libido, testosterone, and athletic performance, but the human evidence behind these claims is weak and inconsistent. It is general...

Read the full Tribulus monograph →
Herb & supplement monograph

Maca

Maca is a nutrient-rich Andean root often used for energy, libido, and menopause symptoms. Early studies suggest it may modestly help sexual desire and some menopause symptoms, but the evide...

Read the full Maca monograph →
Herb & supplement monograph

Horny Goat Weed

Interacts with 963 drugs

Horny goat weed (Epimedium) is a traditional Chinese herb most often marketed for low libido and erectile problems, but solid human evidence for these uses is lacking. While short-term use s...

Read the full Horny Goat Weed monograph →
Herb & supplement monograph

Black Pepper

Interacts with 1,019 drugs

Black pepper is a common kitchen spice that is generally safe in the amounts used in food. Its extract, piperine, is mostly added to supplements to help the body absorb other ingredients (li...

Read the full Black Pepper monograph →
Sources

Sources & How We Checked

Apex Male'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 119 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.

Tyrosine 4 references
  1. Meyer JS, Welch KM, Deshmukh VD, et al. Neurotransmitter precursor amino acids in the treatment of multi-infarct dementia and Alzheimer's disease. J Amer Geriat Soc 1977;25:289-98.
  2. DiPiro JT, Talbert RL, Yee GC, et al; eds. Pharmacotherapy: A pathophysiologic approach. 4th ed. Stamford, CT: Appleton & Lange, 1999.
  3. Wood DR, Reimherr FW, Wender PH. Amino acid precursors for the treatment of attention deficit disorder, residual type. Psychopharmacol Bull 1985;21:146-9.
  4. van Spronsen FJ, van Rijn M, Bekhof J. Phenylketonuria: tyrosine supplementation in phenylalanine-restricted diets. Am J Clin Nutr 2001;73:153-7. PubMed

See these in context on the Tyrosine monograph →

Vitamin D 26 references
  1. McEvoy GK, ed. AHFS Drug Information. Bethesda, MD: American Society of Health-System Pharmacists, 1998.
  2. Tatro DS, ed. Drug Interactions Facts. Facts and Comparisons Inc., St. Louis, MO. 1999.
  3. Koutkia P, Chen TC, Holick MF. Vitamin D intoxication associated with an over-the-counter supplement. N Engl J Med 2001;345:66-7. PubMed
  4. Bar-Or D, Yoel G. Calcium and calciferol antagonize effect of verapamil in atrial fibrillation. Br Med J 1981;282:1585-6.
  5. Demontis R, Leflon A, Fournier A, et al. 1 alpha(OH) vitamin D3 increases plasma aluminum in hemodialyzed patients taking AI(OH)3. Clin Nephrol 1986;26:146-9.
  6. Crowe M, Wollner L, Griffiths RA. Hypercalcemia following vitamin D and thiazide therapy in the elderly. Practitioner 1984;228:312-3.
  7. Parfitt AM. Thiazide-induced hypercalcemia in vitamin D-treated hypoparathyroidism. Ann Intern Med 1972;77:557-63. PubMed
  8. Thiazide diuretics and the risk of osteoporosis. Pharmacist's Letter/Prescriber's Letter 2003;19(11):191105.
  9. Moon J. The role of vitamin D in toxic metal absorption. J Am Coll Nutr 1994;13:559-64.
  10. Demontis R, Reissi D, Noel C, et al. Indirect clinical evidence that 1alphaOH vitamin D<SUB>3</SUB> increases the intestinal absorption of aluminum. Clin Nephrol 1989;31:123-7.
  11. Adler AJ, Berlyne GM. Duodenal aluminum absorption in the rat: effect of vitamin D. Am J Physiol 1985;249:G209-13. PubMed
  12. Schwartz JB. Effects of vitamin D supplementation in atorvastatin-treated patients: A new drug interaction with an unexpected consequence. Clin Pharmacol Ther 2009;85:198-203. PubMed
  13. Dietary reference intakes for calcium and vitamin D. Institute of Medicine, November 30, 2010. Available at: http://www.iom.edu/~/media/Files/Report%20Files/2010/Dietary-Reference-Intakes-for-Calcium-and-Vitamin-D/Vitamin%20D%20and%20Calcium%202010%20Repo
  14. Cox KA, Dunn MA. Aluminum toxicity alters the regulation of calbindin-D28k protein and mRNA expression in chick intestine. J Nutr 2001;131:2007-13. PubMed
  15. Escribano, J., Balaguer, A., Pagone, F., Feliu, A., and Roque, I. Figuls. Pharmacological interventions for preventing complications in idiopathic hypercalciuria. Cochrane.Database.Syst.Rev. 2009;(1):CD004754. PubMed
  16. Carlton, S., Clopton, D., and Cappuzzo, K. A. Vitamin D deficiency: appropriate replenishment therapies and the effects of vitamin D toxicity. Consult Pharm 2010;25(3):171-177. PubMed
  17. Wang, H., Xia, N., Yang, Y., and Peng, D. Q. Influence of vitamin D supplementation on plasma lipid profiles: a meta-analysis of randomized controlled trials. Lipids Health Dis. 2012;11:42. PubMed
  18. Turner AN, Carr Reese P, Fields KS, Anderson J, Ervin M, Davis JA, Fichorova RN, Roberts MW, Klebanoff MA, Jackson RD. A blinded, randomized controlled trial of high-dose vitamin D supplementation to reduce recurrence of bacterial vaginosis. Am J Obstet G PubMed
  19. Weiner M, Epstein FH. Signs and symptoms of electrolyte disorders. Yale J Biol Med. 1970;43(2):76-109.
  20. 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
  21. Roth DE, Leung M, Mesfin E, Qamar H, Watterworth J, Papp E. Vitamin D supplementation during pregnancy: state of the evidence from a systematic review of randomised trials. BMJ. 2017;359:j5237. PubMed
  22. Murai IH, Fernandes AL, Sales LP, et al. Effect of a single high dose of vitamin D3 on hospital length of stay in patients with moderate to severe COVID-19: A randomized clinical trial. JAMA. 2021.
  23. Wang Z, Schuetz EG, Xu Y, Thummel KE. Interplay between vitamin D and the drug metabolizing enzyme CYP3A4. J Steroid Biochem Mol Biol 2013;136:54-8. PubMed
  24. Doyle D, Browne U, Brickley A, Murphy D. Vitamin D-induced hypercalcaemia and acute kidney injury in sarcoidosis. BMJ Case Rep 2023;16(1):e250580. PubMed
  25. Williamson A, Martineau AR, Sheikh A, Jolliffe D, Griffiths CJ. Vitamin D for the management of asthma. Cochrane Database Syst Rev 2023;2(2):CD011511. PubMed
  26. Kinesya E, Santoso D, Gde Arya N, et al. Vitamin D as adjuvant therapy for diabetic foot ulcers: Systematic review and meta-analysis approach. Clin Nutr ESPEN 2023;54:137-143. PubMed

See these in context on the Vitamin D monograph →

Bulbine Natalensis 8 references
  1. Afolayan AJ, Yakubu MT. Effect of Bulbine natalensis Baker Stem Extract on the Functional Indices and Histology of the Liver and Kidney of Male Wistar Rats. J Med Food. 2009;12(4):814-820.
  2. Mosa RA, Lazarus GG, Gwala PE, Oyedeji AO, Opoku AR. In Vitro Anti-platelet Aggregation, Antioxidant and Cytotoxic Activity of Extracts of Some Zulu Medicinal Plants. J Nat Prod. 2011;4(2011):136-146.
  3. Okem A, Southway C, Stirk WA, et al. Heavy metal contamination in South African medicinal plants: A cause for concern. South African J Bot. 2014;93(2014):125-130. DOI
  4. Yakubu MT, Afolayan AJ. Reproductive toxicologic evaluations of Bulbine natalensis Baker stem extract in albino rats. Theriogenology. 2009;72(3):322-32. PubMed
  5. Yakubu MT, Afolayan AJ. Effect of aqueous extract of Bulbine natalensis (Baker) stem on the sexual behaviour of male rats. Int J Androl. 2009;32(6):629-36.
  6. Yakubu MT, Afolayan AJ. Anabolic and androgenic activities of Bulbine natalensis stem in male Wistar rats. Pharm Biol. 2010;48(5):568-76.
  7. Husain I, Manda V, Alhusban M, et al. Modulation of CYP3A4 and CYP2C9 activity by Bulbine natalensis and its constituents: An assessment of HDI risk of B. natalensis containing supplements. Phytomedicine 2021;81:153416. PubMed
  8. Husain I, Dale OR, Manda V, et al. Bulbine natalensis (currently Bulbine latifolia) and select bulbine knipholones modulate the activity of AhR, CYP1A2, CYP2B6, and P-gp. Planta Med 2022;88(12):975-984. PubMed

See these in context on the Bulbine Natalensis monograph →

Fenugreek 30 references
  1. Madar Z, Thorne R. Dietary fiber. Prog Food Nutr Sci 1987;11:153-74.
  2. Sharma RD, Raghuram TC, Rao NS. Effect of fenugreek seeds on blood glucose and serum lipids in type I diabetes. Eur J Clin Nutr 1990;44:301-6.
  3. Patil SP, Niphadkar PV, Bapat MM. Allergy to fenugreek (Trigonella foenum graecum). Ann Allergy Asthma Immunol 1997;78:297-300. PubMed
  4. Lambert J, Cormier J. Potential interaction between warfarin and boldo-fenugreek. Pharmacotherapy 2001;21:509-12. PubMed
  5. Bordia A, Verma SK, Srivastava KC. Effect of ginger (Zingiber officinale Rosc.) and fenugreek (Trigonella foenumgraecum L.) on blood lipids, blood sugar and platelet aggregation in patients with coronary artery disease. Prostaglandins Leukot Essent Fatty PubMed
  6. Yalcin SS, Tekinalp G, Ozalp I. Peculiar odor of traditional food and maple syrup urine disease. Pediatr Int 1999;41:108-9. PubMed
  7. Sewell AC, Mosandl A, Bohles H. False diagnosis of maple syrup urine disease owing to ingestion of herbal tea. N Engl J Med 1999;341:769.. PubMed
  8. Abdo MS, al-Kafawi AA. Experimental studies on the effect of Trigonella foenum-graecum (abstract). Planta Med 1969;17:14-8.
  9. Gupta A, Gupta R, Lal B. Effect of Trigonella foenum-graecum (fenugreek) seeds on glycaemic control and insulin resistance in type 2 diabetes mellitus: a double blind placebo controlled study. J Assoc Physicians India 2001;49:1057-61.
  10. Gabay MP. Galactogogues: medications that induce lactation. J Hum Lact 2002;18:274-9. PubMed
  11. Chevassus H, Gaillard JB, Farret A, et al. A fenugreek seed extract selectively reduces spontaneous fat intake in overweight subjects. Eur J Clin Pharmacol 2010;66(5):449-55. PubMed
  12. Turkyilmaz C, Onal E, Hirfanoglu IM, et al. The effect of galactagogue herbal tea on breast milk production and short-term catch-up of birth weight in the first week of life. J Altern Complement Med 2011;17(2):139-42. PubMed
  13. Swafford S, Berens P. Effect of fenugreek on breast milk volume. Abstract presented at: 5th International Meeting of the Academy of Breastfeeding Medicine; September 11-13,2000, Tucson, Arizona.
  14. Abdel-Barry, J. A., Abdel-Hassan, I. A., Jawad, A. M., and al Hakiem, M. H. Hypoglycaemic effect of aqueous extract of the leaves of Trigonella foenum-graecum in healthy volunteers. East Mediterr.Health J 2000;6(1):83-88. DOI
  15. Parvizpur, A., Ahmadiani, A., and Kamalinejad, M. Probable role of spinal purinoceptors in the analgesic effect of Trigonella foenum (TFG) leaves extract. J Ethnopharmacol 3-8-2006;104(1-2):108-112. PubMed
  16. Mora, A., Herrrera, A., Lopez, C., Dahbi, G., Mamani, R., Pita, J. M., Alonso, M. P., Llovo, J., Bernardez, M. I., Blanco, J. E., Blanco, M., and Blanco, J. Characteristics of the Shiga-toxin-producing enteroaggregative Escherichia coli O104:H4 German ou
  17. Blanco, J. [Stx2a-producing enteroaggregative Escherichia coli O104:H4-ST678. Microbiological diagnostic already, for this and other STEC/VTEC serotypes!]. Enferm.Infecc.Microbiol.Clin. 2012;30(2):84-89.
  18. Beutin, L. and Martin, A. Outbreak of Shiga toxin-producing Escherichia coli (STEC) O104:H4 infection in Germany causes a paradigm shift with regard to human pathogenicity of STEC strains. J Food Prot. 2012;75(2):408-418. PubMed
  19. King LA, Nogareda F, Weill FX, Mariani-Kurkdjian P, Loukiadis E, Gault G, Jourdan-DaSilva N, Bingen E, Macé M, Thevenot D, Ong N, Castor C, Noël H, Van Cauteren D, Charron M, Vaillant V, Aldabe B, Goulet V, Delmas G, Couturier E, Le Strat Y, Combe C, Delm
  20. Reeder C, Legrand A, O'Connor-Von SK. The Effect of Fenugreek on Milk Production and Prolactin Levels in Mothers of Preterm Infants. Clinical Lactation 2013;4(4):159-165. DOI
  21. Al-Jenoobi FI, Ahad A, Mahrous GM, Al-Mohizea AM, AlKharfy KM, Al-Suwayeh SA. Effects of fenugreek, garden cress, and black seed on theophylline pharmacokinetics in beagle dogs. Pharm Biol 2015;53(2):296-300. PubMed
  22. Rao A, Steels E, Inder WJ, Abraham S, Vitetta L. Testofen, a specialised Trigonella foenum-graecum seed extract reduces age-related symptoms of androgen decrease, increases testosterone levels and improves sexual function in healthy aging males in a doubl
  23. Steels E, Rao A, Vitetta L. Physiological aspects of male libido enhanced by standardized Trigonella foenum-graecum extract and mineral formulation. Phytother Res. 2011 Sep;25(9):1294-300.
  24. Gong J, Fang K, Dong H, Wang D, Hu M, Lu F. Effect of fenugreek on hyperglycaemia and hyperlipidemia in diabetes and prediabetes: A meta-analysis. J Ethnopharmacol. 2016 Dec 24;194:260-268. PubMed
  25. Ouzir M, El Bairi K, Amzazi S. Toxicological properties of fenugreek (Trigonella foenum graecum). Food Chem Toxicol. 2016 Oct;96:145-54. PubMed
  26. Khodamoradi K, Khosropanah MH, Ayati Z, et al. The Effects of Fenugreek on Cardiometabolic Risk Factors in Adults: A Systematic Review and Meta-analysis. Complement Ther Med. 2020;52:102416. PubMed
  27. Alkharfy K, Jan B, Alotaibi K, et al. Clopidogrel-herb Interactions: A Pharmacokinetic and Pharmacodynamic Assessment in a Rat Model. Curr Drug Metab 2021;22(12):969-977. PubMed
  28. Bin Jardan YA, Ahad A, Raish M, Alam MA, Al-Mohizea AM, Al-Jenoobi FI. Effects of garden cress, fenugreek and black seed on the pharmacodynamics of metoprolol: an herb-drug interaction study in rats with hypertension. Pharm Biol 2021;59(1):1088-1097. PubMed
  29. Al-Mohizea AM, Ahad A, El-Maghraby GM, et al. Effects of Nigella sativa, Lepidium sativum and Trigonella foenum-graecum on sildenafil disposition in beagle dogs. Eur J Drug Metab Pharmacokinet. 2015;40(2):219-24. PubMed
  30. Alkharfy KM, Al-Jenoobi FI, Al-Mohizea AM, et al. Effects of Lepidium sativum, Nigella sativa and Trigonella foenum-graceum on phenytoin pharmacokinetics in beagle dogs. Phytother Res. 2013;27(12):1800-4.

See these in context on the Fenugreek monograph →

Tribulus 10 references
  1. Sharifi AM, Darabi R, Akbarloo N. Study of antihypertensive mechanism of Tribulus terrestris in 2K1C hypertensive rats: role of tissue ACE activity. Life Sci 2003;73:2963-71. PubMed
  2. Walker D, Bird A, Flora T, O'Sullivan B. Some effects of feeding Tribulus terrestris, Ipomoea lonchophylla and the seed of Abelmoschus ficulneus on fetal development and the outcome of pregnancy in sheep. Reprod Fertil Dev 1992;4:135-44. PubMed
  3. Al-Ali M, Wahbi S, Twaij H, Al-Badr A. Tribulus terrestris: preliminary study of its diuretic and contractile effects and comparison with Zea mays. J Ethnopharmacol 2003;85:257-60. PubMed
  4. Tabakova, P., Dimitrov, M., Ognyanov, K., and et al. Clinical study of Tribestan in females with endocrine sterility. Documentation for Registration (unpublished) 1999.
  5. Akhtari E, Raisi F, Keshavarz M, et al. Tribulus terrestris for treatment of sexual dysfunction in women: randomized double-blind placebo-controlled study. Daru 2014;22:40. PubMed
  6. Ryan M, Lazar I, Nadasdy GM, et al. Acute kidney injury and hyperbilirubinemia in a young male after ingestion of Tribulus terrestris. Clin Nephrol 2015;83(3):177-83. PubMed
  7. Postigo S, Lima SM, Yamada SS, et al. Assessment of the effects of Tribulus terrestris on sexual function of menopausal women. Rev Bras Ginecol Obstet 2016;38(3):140-6. PubMed
  8. Talasaz AH, Abbasi MR, Abkhiz S, Dashti-Khavidaki S. Tribulus terrestris-induced severe nephrotoxicity in a young healthy male. Nephrol Dial Tranplant 2010;25(11):3792-3. PubMed
  9. Samani NB, Jokar A, Soveid M, Heydari M, Mosavat SH. Efficacy of the hydroalcoholic extract of Tribulus terrestris on the serum glucose and lipid profile of women with diabetes mellitus: a double-blind randomized placebo-controlled clinical trial. J Evid
  10. Siddiqui MA, Itrat M, Mobeen A, Khan MI. Efficacy of khar-i-khasak (Tribulus terrestris Linn.) in prehypertension: a randomized, double-blind, placebo-controlled trial. J Complement Integr Med. 2021.

See these in context on the Tribulus monograph →

Maca 1 reference
  1. Valerio, L. G., Jr. and Gonzales, G. F. Toxicological aspects of the South American herbs cat's claw (Uncaria tomentosa) and Maca (Lepidium meyenii) : a critical synopsis. Toxicol.Rev 2005;24(1):11-35. PubMed

See these in context on the Maca monograph →

Horny Goat Weed 11 references
  1. Cirigliano MD, Szapary PO. Horny goat weed for erectile dysfunction. Alt Med Alert 2001;4:19-22.
  2. Partin JF, Pushkin YR. Tachyarrhythmia and hypomania with horny goat weed. Psychosomatics 2004;45:536-7. PubMed
  3. De Naeyer A, Pocock V, Milligan S, De Keukeleire D. Estrogenic activity of a polyphenolic extract of the leaves of Epimedium brevicornum. Fitoterapia 2005;76:35-40. PubMed
  4. Zhang CZ, Wang SX, Zhang Y, et al. In vitro estrogenic activities of Chinese medicinal plants traditionally used for the management of menopausal symptoms. J Ethnopharmacol 2005;98:295-300. PubMed
  5. Yap SP, Shen P, Li J, et al. Molecular and pharmacodynamic properties of estrogenic extracts from the traditional Chinese medicinal herb, Epimedium. J Ethnopharmacol 2007;113:218-24. PubMed
  6. Yan, F. F., Liu, Y., Liu, Y. F., and Zhao, Y. X. Herba Epimedii water extract elevates estrogen level and improves lipid metabolism in postmenopausal women. Phytother.Res. 2008;22(9):1224-1228. PubMed
  7. Ramanathan VS, Mitropoulos E, Shlopov B, et al. An Enzyte'ing' case of acute hepatitis. J Clin Gastroenterol 2011;45(9):834-5. PubMed
  8. Zhong Q, Shi Z, Zhang L, et al. The potential of Epimedium koreanum Nakai for herb-drug interaction. J Pharm Pharmacol 2017;69(10):1398-408. doi: 10.1111/jphp.12773.
  9. Irfan M, Kwon TH, Lee DH, et al. Antiplatelet and Antithrombotic Effects of Epimedium koreanum Nakai. Evid Based Complement Alternat Med. Apr 2021;2021:7071987. PubMed
  10. Tan K, Yang W, Pang L, Hou F. Differences in clinical characteristics among 726 patients with Chinese herbal medicine- or Western medicine-induced liver injury. Medicine (Baltimore) 2022;101(32):e29909. PubMed
  11. Li K, Yu XH, Maskey AR, et al. Cytochrome P450 3A4 suppression by epimedium and active compound kaempferol leads to synergistic anti-inflammatory effect with corticosteroid. Front Pharmacol 2023;13:1042756. PubMed

See these in context on the Horny Goat Weed monograph →

Black Pepper 29 references
  1. Leung AY, Foster S. Encyclopedia of Common Natural Ingredients Used in Food, Drugs and Cosmetics. 2nd ed. New York, NY: John Wiley & Sons, 1996.
  2. Brinker F. Herb Contraindications and Drug Interactions. 2nd ed. Sandy, OR: Eclectic Medical Publications, 1998.
  3. Bano G, Amla V, Raina RK, et al. The effect of piperine on pharmacokinetics of phenytoin in healthy volunteers. Planta Med 1987;53:568-9. PubMed
  4. Bano G, et al. Effect of piperine on bioavailability and pharmacokinetics of propranolol and theophylline in healthy volunteers. Eur J Clin Pharmacol 1991;41;615-7. PubMed
  5. Cohle SD, Trestrail JD III, Graham MA, et al. Fatal pepper aspiration. Am J Dis Child 1988;142:633-6. PubMed
  6. Bhardwaj RK, Glaeser H, Becquemont L, et al. Piperine, a major constituent of black pepper, inhibits human P-glycoprotein and CYP3A4. J Pharmacol Exp Ther 2002;302:645-50. PubMed
  7. Velpandian T, Jasuja R, Bhardwaj RK, et al. Piperine in food: interference in the pharmacokinetics of phenytoin. Eur J Drug Metab Pharmacokinet 2001;26:241-7. PubMed
  8. Pattanaik S, Hota D, Prabhakar S, et al. Pharmacokinetic interaction of a single dose of piperine with steady-state carbamazepine in epilepsy patients. Phytother Res 2009;23:1281-6.
  9. Munakata, M., Kobayashi, K., Niisato-Nezu, J., Tanaka, S., Kakisaka, Y., Ebihara, T., Ebihara, S., Haginoya, K., Tsuchiya, S., and Onuma, A. Olfactory stimulation using black pepper oil facilitates oral feeding in pediatric patients receiving long-term en
  10. Myers, B. M., Smith, J. L., and Graham, D. Y. Effect of red pepper and black pepper on the stomach. Am J Gastroenterol 1987;82(3):211-214.
  11. Raghavendra, R. H. and Naidu, K. A. Spice active principles as the inhibitors of human platelet aggregation and thromboxane biosynthesis. Prostaglandins Leukot.Essent.Fatty Acids 2009;81(1):73-78. PubMed
  12. Subehan, Usia, T., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of human liver microsomal cytochrome P450 2D6 (CYP2D6) by alkamides of Piper nigrum. Planta Med 2006;72(6):527-532.
  13. Kasibhatta, R. and Naidu, M. U. Influence of piperine on the pharmacokinetics of nevirapine under fasting conditions: a randomised, crossover, placebo-controlled study. Drugs R.D. 2007;8(6):383-391. PubMed
  14. Usia, T., Iwata, H., Hiratsuka, A., Watabe, T., Kadota, S., and Tezuka, Y. CYP3A4 and CYP2D6 inhibitory activities of Indonesian medicinal plants. Phytomedicine. 2006;13(1-2):67-73. PubMed
  15. Mujumdar, A. M., Dhuley, J. N., Deshmukh, V. K., Raman, P. H., Thorat, S. L., and Naik, S. R. Effect of piperine on pentobarbitone induced hypnosis in rats. Indian J Exp.Biol. 1990;28(5):486-487.
  16. Panda, S. and Kar, A. Piperine lowers the serum concentrations of thyroid hormones, glucose and hepatic 5'D activity in adult male mice. Horm.Metab Res. 2003;35(9):523-526. PubMed
  17. Lawless, H. and Stevens, D. A. Effects of oral chemical irritation on taste. Physiol Behav. 1984;32(6):995-998. PubMed
  18. Hiwale, A. R., Dhuley, J. N., and Naik, S. R. Effect of co-administration of piperine on pharmacokinetics of beta-lactam antibiotics in rats. Indian J Exp.Biol. 2002;40(3):277-281.
  19. Han, Y., Chin Tan, T. M., and Lim, L. Y. In vitro and in vivo evaluation of the effects of piperine on P-gp function and expression. Toxicol.Appl.Pharmacol. 8-1-2008;230(3):283-289. PubMed
  20. Sharma, P., Varma, M. V., Chawla, H. P., and Panchagnula, R. In situ and in vivo efficacy of peroral absorption enhancers in rats and correlation to in vitro mechanistic studies. Farmaco 2005;60(11-12):874-883. PubMed
  21. Aher, S., Biradar, S., Gopu, C. L., and Paradkar, A. Novel pepper extract for enhanced P-glycoprotein inhibition. J Pharm.Pharmacol. 2009;61(9):1179-1186. PubMed
  22. Zutshi, R. K., Singh, R., Zutshi, U., Johri, R. K., and Atal, C. K. Influence of piperine on rifampicin blood levels in patients of pulmonary tuberculosis. J Assoc.Physicians India 1985;33(3):223-224.
  23. Marotta, R. B. and Floch, M. H. Diet and nutrition in ulcer disease. Med Clin North Am 1991;75(4):967-979. PubMed
  24. Subehan, Usia, T., Iwata, H., Kadota, S., and Tezuka, Y. Mechanism-based inhibition of CYP3A4 and CYP2D6 by Indonesian medicinal plants. J Ethnopharmacol. 5-24-2006;105(3):449-455. PubMed
  25. Gimenez L, Zacharisen M. Severe pepper allergy in a young child. WMJ. 2011 Jun;110(3):138-9.
  26. Ren T, Yang M, Xiao M, Zhu J, Xie W, Zuo Z. Time-dependent inhibition of carbamazepine metabolism by piperine in anti-epileptic treatment. Life Sci. 2019;218:314-323. PubMed
  27. Thomas AB, Choudhary DC, Raje A, Nagrik SS. Pharmacokinetics and pharmacodynamic herb-drug interaction of piperine with atorvastatin in rats. J Chromatogr Sci 2021;59(4):371-80. PubMed
  28. Haron MH, Dale O, Martin K, et al. Evaluation of the Herb-Drug Interaction Potential of Commonly Used Botanicals on the US Market with Regard to PXR- and AhR-Mediated Influences on CYP3A4 and CYP1A2. J Diet Suppl 2022. PubMed
  29. Lin F, Hu Y, Zhang Y, Zhao L, Zhong D, Liu J. Predicting Food-Drug Interactions between Piperine and CYP3A4 Substrate Drugs Using PBPK Modeling. Int J Mol Sci 2024;25(20):10955. 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.

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