| Ingredients | Each Film Coated Tablet Contains |
|---|---|
|
(Andrographis paniculata )
|
222.22 mg |
|
(Andrographis paniculata )
(herb top)
(3.33 g (min.))
|
3.33 Gram(s) |
|
(std. to contain andrographolide 66.67 mg)
|
66.67 mg |
|
(Salix alba )
|
160 mg |
|
(Salix alba )
(stem bark)
(4.8 g (min.))
|
4.8 Gram(s) |
|
Salicin
(std. to contain salicin 80 mg)
|
80 mg |
|
(Vitamin C)
|
50 mg |
|
(equiv. quercetin 333.33 mg)
|
373.07 mg |
Below is general information about the effectiveness of the known ingredients contained in the product Nutra + Andro Max. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
INSUFFICIENT RELIABLE EVIDENCE to RATE
Below is general information about the safety of the known ingredients contained in the product Nutra + Andro Max. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
LIKELY SAFE ...when used orally and appropriately, short-term. Andrographis has been used with apparent safety in doses of up to 6 grams daily for up to 7 days. Andrographis extract has been used with apparent safety at doses of up to 340 mg daily for up to 12 months, 600 mg daily for up to 3 months, or 1200 mg daily for up to 8 weeks (2748,31220,31223,31231,91838,91839,101116). Andrographolide, a constituent of andrographis, has been used with apparent safety at a dose of 280 mg daily for 24 months (104821). A specific combination product containing andrographis extract 178-206 mg and eleuthero (Kan Jang, Swedish Herbal Institute) has been taken three times daily with apparent safety for up to 4-7 days (2744,2748,2773,2774,10441,10795,13016).
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Andrographis, in combination with other herbs, has been used with apparent safety in clinical trials at doses up to 48 mg daily in children 3-15 years of age for up to one month (12381,12382).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Andrographis is thought to have abortifacient effects (12); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Quercetin has been used with apparent safety in doses up to 1 gram daily for up to 12 weeks (481,1998,1999,16418,16429,16430,16431,96774,96775,96782)(99237,102539,102540,102541,104229,104679,106498,106499,107450,109620)(109621). ...when used intravenously and appropriately. Quercetin has been used with apparent safety in doses less than 945 mg/m2. Higher doses have been reported to cause nephrotoxicity (9564,16418). There is insufficient reliable information available about the safety of quercetin when used topically.
POSSIBLY UNSAFE ...when used intravenously in large amounts. Doses greater than 945 mg/m2 have been reported to cause nephrotoxicity (9564,16418).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally, topically, intramuscularly, or intravenously and appropriately. Vitamin C is safe when taken orally in doses below the tolerable upper intake level (UL). Tell patients not to exceed the UL of 2000 mg daily (1959,4713,4714,4844). ...when used intravenously or intramuscularly and appropriately. Injectable vitamin C is an FDA-approved prescription product (15).
POSSIBLY UNSAFE ...when used orally in excessive doses. Doses greater than the tolerable upper intake level (UL) of 2000 mg daily can significantly increase the risk of adverse effects such as osmotic diarrhea and gastrointestinal upset (4844).
CHILDREN: LIKELY SAFE
when used orally and appropriately (4844,10352,14443).
CHILDREN: POSSIBLY UNSAFE
when used orally in excessive amounts.
Tell patients not to use doses above the tolerable upper intake level (UL) of 400 mg daily for children ages 1 to 3 years, 650 mg daily for children 4 to 8 years, 1200 mg daily for children 9 to 13 years, and 1800 mg daily for adolescents 14 to 18 years. Higher doses can cause osmotic diarrhea and gastrointestinal upset (4844).
PREGNANCY AND LACTATION: LIKELY SAFE
when used orally and appropriately (4844).
PREGNANCY AND LACTATION: POSSIBLY UNSAFE
when used orally in excessive doses.
Tell patients over age 19 not to use doses exceeding the UL of 2000 mg daily when pregnant or breast-feeding and for those 14-18 years of age not to use doses exceeding 1800 mg daily when pregnant or breast-feeding. Higher doses can cause osmotic diarrhea and gastrointestinal upset. Large doses of vitamin C during pregnancy can also cause newborn scurvy (4844); avoid using.
POSSIBLY SAFE ...when used orally and appropriately, short-term. Willow bark has been used safely for up to 12 weeks (6456,12474,12475,12804,12811,86473,91406).
CHILDREN: POSSIBLY UNSAFE
when used orally for viral infections.
Salicylic acid and aspirin are contraindicated in children with viral infections (12801). Although Reye's syndrome has not been reported, the salicin constituent in willow bark is similar to aspirin and might pose the same risk.
PREGNANCY:
Insufficient reliable information available; avoid using.
LACTATION: POSSIBLY UNSAFE
when used orally.
Willow bark contains salicylates which are excreted in breast milk and have been linked to adverse effects in breast-fed infants (12802,12803).
Below is general information about the interactions of the known ingredients contained in the product Nutra + Andro Max. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
Theoretically, andrographis extract might increase the maximum concentration and decrease the area under the curve of aceclofenac. The clinical significance of these changes is unclear.
 Details
Animal research suggests that andrographis extract taken orally increases the maximum concentration and decreases the area under the curve of aceclofenac (112916).
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Theoretically, andrographis might increase the risk of bleeding when used with anticoagulant or antiplatelet drugs.
Details
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Theoretically, andrographis might increase the risk of hypotension when used with antihypertensive drugs.
Details
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Theoretically, andrographis extract might increase the maximum concentration and time to peak concentration of celecoxib. The clinical significance of these changes is unclear.
Details
Animal research suggests that andrographis extract taken orally increases the maximum concentration and time to peak concentration of celecoxib but does not appear to impact the area under the curve (112916).
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Theoretically, andrographis might decrease the absorption of etoricoxib, although the clinical significance is unclear.
Details
Animal research shows that andrographis extract, or the constituent andrographolide, taken orally with etoricoxib decreases the bioavailability of etoricoxib. However, this reduced bioavailability is not correlated with a reduction in the anti-inflammatory effects of etoricoxib in arthritic mice models (91837). The clinical significance of this interaction is unclear.
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Theoretically, andrographis extract might increase the maximum concentration and area under the curve of glipizide; however, opposite effects are seen with the constituent, andrographolide. The clinical significance of this interaction is unclear.
Details
Animal research suggests that andrographis extract taken orally with glipizide in diabetes-induced rats increases the maximum concentration and area under the curve of glipizide. However, the opposite effect is seen with the constituent, andrographolide, in which the maximum concentration and area under the curve are decreased when taken with glipizide (112917).
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Theoretically, andrographis might interfere with the effects of immunosuppressive drugs.
Details
Laboratory research suggests that andrographolide has immunostimulant activity (2766).
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Theoretically, concomitant use of quercetin and antidiabetes drugs might increase the risk of hypoglycemia.
Details
Clinical research suggests that a combination of quercetin, myricetin, and chlorogenic acid reduce levels of fasting glucose in patients with type 2 diabetes, including those already taking antidiabetes agents (96779). The effect of quercetin alone is unknown. |
Theoretically, taking quercetin with antihypertensive drugs might increase the risk of hypotension.
Details
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Theoretically, concomitant use might increase the levels and adverse effects of cyclosporine.
Details
A small study in healthy volunteers shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of a single dose of cyclosporine, possibly due to inhibition of p-glycoprotein or cytochrome P450 3A4 (CYP3A4), which metabolizes cyclosporin (16434). |
Theoretically, concomitant use might increase the levels and adverse effects of CYP2C8 substrates.
Details
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Theoretically, concomitant use might increase the levels and adverse effects of CYP2C9 substrates.
Details
A small clinical study in healthy volunteers shows that taking quercetin 500 mg twice daily for 10 days prior to taking diclofenac, a CYP2C9 substrate, increases diclofenac plasma levels by 75% and prolongs the half-life by 32.5% (97931). Animal research also shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar), a substrate of CYP2C9 (100968). Furthermore, laboratory research shows that quercetin inhibits CYP2C9 (15549,16433). |
Theoretically, concomitant use might increase the levels and adverse effects of CYP2D6 substrates.
Details
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Theoretically, concomitant use might alter the effects and adverse effects of CYP3A4 substrates.
Details
A small clinical study in healthy volunteers shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of a single dose of cyclosporine (Neoral, Sandimmune), a substrate of CYP3A4 (16434). Animal research also shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar) and quetiapine (Seroquel), substrates of CYP3A4 (100968,104228). Other laboratory research also shows that quercetin inhibits CYP3A4 (15549,16433,16435). However, one clinical study shows that quercetin can increase the metabolism of midazolam, a substrate of CYP3A4, and decrease serum concentrations of midazolam by about 24% in some healthy individuals, suggesting possible induction of CYP3A4 (91573).
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Theoretically, concomitant use might increase the levels and adverse effects of diclofenac.
Details
A small clinical study in healthy volunteers shows that taking quercetin 500 mg twice daily for 10 days prior to taking diclofenac increases diclofenac plasma levels by 75% and prolongs the half-life by 32.5%. This is thought to be due to inhibition of CYP2C9 by quercetin (97931). |
Theoretically, concomitant use might increase the effects and adverse effects of losartan and decrease the effects of its active metabolite.
Details
Animal research shows that pretreatment with quercetin increases plasma levels and prolongs the half-life of losartan (Cozaar) while decreasing plasma levels of losartan's active metabolite. This metabolite, which is around 10-fold more potent than losartan, is the result of cytochrome P450 (CYP) 2C9- and CYP3A4-mediated transformation of losartan. Additionally, in vitro research shows that quercetin may inhibit P-glycoprotein-mediated efflux of losartan from the intestines, resulting in increased absorption of losartan (100968). These results suggest that concomitant use of quercetin and losartan might increase systemic exposure to losartan while also decreasing plasma concentrations of losartan's active and more potent metabolite. |
Theoretically, concomitant use might decrease the levels and effects of midazolam.
Details
A small clinical study in healthy volunteers shows that quercetin can increase the metabolism of midazolam, with a decrease in AUC of about 24% (91573). |
Theoretically, quercetin might increase the effects and adverse effects of mitoxantrone.
Details
In vitro research shows that quercetin increases the intracellular accumulation and cytotoxicity of mitoxantrone, possibly through inhibition of breast cancer resistance protein (BCRP), of which mitoxantrone is a substrate (107897). So far, this interaction has not been reported in humans.
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Theoretically, concomitant use might increase the effects and adverse effects of OAT1 substrates.
Details
In vitro research shows that quercetin is a strong non-competitive inhibitor of OAT1, with half-maximal inhibitory concentration (IC50) values less than 10 mcM (104454). So far, this interaction has not been reported in humans. |
Theoretically, concomitant use might increase the effects and adverse effects of OAT3 substrates.
Details
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Theoretically, concomitant use might increase the effects and adverse effects of OATP substrates.
Details
In vitro evidence shows that quercetin can inhibit organic anion-transporting peptide (OATP) 1B1-mediated uptake of estrone-3-sulfate and pravastatin (91581). Furthermore, clinical research in healthy males shows that intake of quercetin along with pravastatin increases the AUC of pravastatin by 24%, prolongs its half-life by 14%, and decreases its apparent clearance by 18%, suggesting that quercetin modestly inhibits the uptake of pravastatin in hepatic cells (91581). |
Theoretically, concomitant use might alter the effects and adverse effects of P-glycoprotein substrates.
Details
There is preliminary evidence that quercetin inhibits the gastrointestinal P-glycoprotein efflux pump, which might increase the bioavailability and serum levels of drugs transported by the pump (16433,16434,16435,100968,104228). A small study in healthy volunteers reported that pretreatment with quercetin increased bioavailability and plasma levels after a single dose of cyclosporine (Neoral, Sandimmune) (16434). Also, two small studies have shown that quercetin might decrease the absorption of talinolol, a substrate transported by the gastrointestinal P-glycoprotein efflux pump (91579,91580). However, in another small study, several days of quercetin treatment did not significantly affect the pharmacokinetics of saquinavir (Invirase) (16433). The reason for these discrepancies is not entirely clear (91580). Until more is known, use quercetin cautiously in combination with P-glycoprotein substrates. |
Theoretically, concomitant use might increase the effects and adverse effects of pravastatin.
Details
In vitro evidence shows that quercetin can inhibit OATP 1B1-mediated uptake of pravastatin (91581). Also, preliminary clinical research in healthy males shows that intake of quercetin along with pravastatin increases the maximum concentration of pravastatin by 24%, prolongs its half-life by 14%, and decreases its apparent clearance by 18%, suggesting that quercetin modestly inhibits the uptake of pravastatin in hepatic cells (91581).
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Theoretically, quercetin might increase the effects and adverse effects of prazosin.
Details
In vitro research shows that quercetin inhibits the transcellular efflux of prazosin, possibly through inhibition of breast cancer resistance protein (BCRP), of which prazosin is a substrate. BCRP is an ATP-binding cassette efflux transporter in the intestines, kidneys, and liver (107897). So far, this interaction has not been reported in humans.
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Theoretically, concomitant use might increase the effects and adverse effects of quetiapine.
Details
Animal research shows that pretreatment with quercetin can increase plasma levels of quetiapine and prolong its clearance, possibly due to inhibition of cytochrome P450 3A4 (CYP3A4) by quercetin. Additionally, the brain-to-plasma ratio of quetiapine concentrations increased, possibly due to inhibition of P-glycoprotein at the blood-brain barrier (104228). This interaction has not been reported in humans.
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Theoretically, concomitant use might inhibit the effects of quinolone antibiotics.
Details
In vitro, quercetin binds to the DNA gyrase site on bacteria (481), which may interfere with the activity of quinolone antibiotics.
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Theoretically, quercetin might increase the effects and adverse effects of sulfasalazine.
Details
Animal research shows that quercetin increases the maximum serum concentration (Cmax) and area under the curve (AUC) of sulfasalazine, possibly through inhibition of breast cancer resistance protein (BCRP), of which sulfasalazine is a substrate (107897). So far, this interaction has not been reported in humans.
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Theoretically, quercetin may increase the risk of bleeding if used with warfarin.
Details
Animal and in vitro studies show that quercetin might increase serum levels of warfarin (17213,109619). Quercetin and warfarin have the same human serum albumin (HSA) binding site, and in vitro research shows that quercetin has stronger affinity for the HSA binding site and can theoretically displace warfarin, causing higher serum levels of warfarin (17213). Animal research shows that taking quercetin for 2 weeks before initiating warfarin increases the maximum serum level of warfarin by 30%, the half-life by 10%, and the overall exposure by 63% when compared with control. Concomitant administration of quercetin and warfarin, without quercetin pre-treatment, also increased these measures, but to a lesser degree. Researchers theorize that inhibition of CYP3A4 by quercetin may explain these effects (109619). So far, this interaction has not been reported in humans.
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High-dose vitamin C might slightly prolong the clearance of acetaminophen.
Details
A small pharmacokinetic study in healthy volunteers shows that taking high-dose vitamin C (3 grams) 1.5 hours after taking acetaminophen 1 gram slightly increases the apparent half-life of acetaminophen from around 2.3 hours to 3.1 hours. Ascorbic acid competitively inhibits sulfate conjugation of acetaminophen. However, to compensate, elimination of acetaminophen glucuronide and unconjugated acetaminophen increases (6451). This effect is not likely to be clinically significant.
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Theoretically, antioxidant effects of vitamin C might reduce the effectiveness of alkylating agents.
Details
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs that generate free radicals, such as cyclophosphamide, chlorambucil, carmustine, busulfan, and thiotepa (391). In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effect, if any, antioxidants such as vitamin C have on chemotherapy.
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Vitamin C can increase the amount of aluminum absorbed from aluminum compounds.
Details
Research in animals and humans shows that vitamin C increases aluminum absorption, theoretically by chelating aluminum and keeping it in solution where it is available for absorption (10549,10550,10551,21556). In people with normal renal function, urinary excretion of aluminum will likely increase, making aluminum retention and toxicity unlikely (10549). Patients with renal failure who take aluminum-containing compounds such as phosphate binders should avoid vitamin C supplements in doses above the recommended dietary allowances.
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Theoretically, the antioxidant effects of vitamin C might reduce the effectiveness of antitumor antibiotics.
Details
The use of antioxidants like vitamin C during chemotherapy is controversial. There is concern that antioxidants could reduce the activity of chemotherapy drugs which generate free radicals, such as doxorubicin (391). In contrast, some researchers theorize that antioxidants might make chemotherapy more effective by reducing oxidative stress that could interfere with apoptosis (cell death) of cancer cells (14012,14013). More evidence is needed to determine what effects, if any, antioxidants such as vitamin C have on chemotherapy.
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Acidification of the urine by vitamin C might increase aspirin levels.
Details
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels (3046). However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction is not clinically significant.
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Acidification of the urine by vitamin C might increase choline magnesium trisalicylate levels.
Details
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels (3046,4531). However, short-term use of up to 6 grams daily of vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction probably is not clinically significant.
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Vitamin C might increase blood levels of estrogens.
Details
Increases in plasma estrogen levels of up to 55% occur under some circumstances when vitamin C is taken concurrently with oral contraceptives or hormone replacement therapy, including topical products (129,130,11161). It is suggested that vitamin C prevents oxidation of estrogen in the tissues, regenerates oxidized estrogen, and reduces sulfate conjugation of estrogen in the gut wall (129,11161). When tissue levels of vitamin C are high, these processes are already maximized and supplemental vitamin C does not have any effect on estrogen levels. Increases in plasma estrogen levels may occur when patients who are deficient in vitamin C take supplements (11161). Monitor these patients for estrogen-related side effects.
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Theoretically, vitamin C might decrease levels of fluphenazine.
Details
In one patient there was a clinically significant decrease in fluphenazine levels when vitamin C (500 mg twice daily) was started (11017). The mechanism is not known, and there is no further data to confirm this interaction.
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Vitamin C can modestly reduce indinavir levels.
Details
One pharmacokinetic study shows that taking vitamin C 1 gram orally once daily along with indinavir 800 mg orally three times daily reduces the area under the concentration-time curve of indinavir by 14%. The mechanism of this interaction is unknown, but it is unlikely to be clinically significant in most patients. The effect of higher doses of vitamin C on indinavir levels is unknown (11300,93578).
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Vitamin C can increase levothyroxine absorption.
Details
Two clinical studies in adults with poorly controlled hypothyroidism show that swallowing levothyroxine with a glass of water containing vitamin C 500-1000 mg in solution reduces thyroid stimulating hormone (TSH) levels and increases thyroxine (T4) levels when compared with taking levothyroxine alone. This suggests that vitamin C increases the oral absorption of levothyroxine, possibly due to a reduction in pH (102978).
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Vitamin C might decrease the beneficial effects of niacin on high-density lipoprotein (HDL) cholesterol levels.
Details
A combination of niacin and simvastatin (Zocor) effectively raises HDL cholesterol levels in patients with coronary disease and low HDL levels. Clinical research shows that taking a combination of antioxidants (vitamin C, vitamin E, beta-carotene, and selenium) along with niacin and simvastatin (Zocor) attenuates this rise in HDL, specifically the HDL-2 and apolipoprotein A1 fractions, by more than 50% in patients with coronary disease (7388,11537). It is not known whether this adverse effect is due to a single antioxidant such as vitamin C, or to the combination. It also is not known whether it will occur in other patient populations.
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Acidification of the urine by vitamin C might increase salsalate levels.
Details
It has been suggested that acidification of the urine by vitamin C could increase reabsorption of salicylates by the renal tubules, and increase plasma salicylate levels (3046). However, short-term use of up to 6 grams/day vitamin C does not seem to affect urinary pH or salicylate excretion (10588,10589), suggesting this interaction probably is not clinically significant.
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High-dose vitamin C might reduce the levels and effectiveness of warfarin.
Details
Vitamin C in high doses may cause diarrhea and possibly reduce warfarin absorption (11566). There are reports of two people who took up to 16 grams daily of vitamin C and had a reduction in prothrombin time (9804,9806). Lower doses of 5-10 grams daily can also reduce warfarin absorption. In many cases, this does not seem to be clinically significant (9805,9806,11566,11567). However, a case of warfarin resistance has been reported for a patient who took vitamin C 500 mg twice daily. Cessation of vitamin C supplementation resulted in a rapid increase in international normalized ratio (INR) (90942). Tell patients taking warfarin to avoid taking vitamin C in excessively high doses (greater than 10 grams daily). Lower doses may be safe, but the anticoagulation activity of warfarin should be monitored. Patients who are stabilized on warfarin while taking vitamin C should avoid adjusting vitamin C dosage to prevent the possibility of warfarin resistance.
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Theoretically, willow bark might result in additive adverse effects associated with acetazolamide.
Details
Willow bark contains salicin, a plant salicylate. Human case reports suggests that a combination of acetazolamide and salicylate increases unbound plasma levels of acetazolamide, as well as adverse effects related to acetazolamide (86481).
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Theoretically, willow bark might increase the risk of bleeding when taken with anticoagulant/antiplatelet drugs.
Details
Willow bark has antiplatelet effects, but less so than aspirin (12810).
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Theoretically, willow bark might increase the effects and adverse effects of aspirin.
Details
Willow bark contains salicin, a plant salicylate. It might have an additive effect when taken with other salicylate-containing drugs such as aspirin (12808).
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Theoretically, willow bark might increase the effects and adverse effects of choline magnesium trisalicylate.
Details
Willow bark contains salicin, a plant salicylate. It might have an additive effect when taken with other salicylate-containing drugs such as choline magnesium trisalicylate (12808).
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Theoretically, willow bark might increase the effects and adverse effects of salsalate.
Details
Willow bark contains salicin, a plant salicylate. It might have an additive effect when taken with other salicylate-containing drugs such as salsalate (12808).
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Below is general information about the adverse effects of the known ingredients contained in the product Nutra + Andro Max. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
General
...Orally, andrographis is generally well tolerated.
Adverse effects are more likely when doses reach or exceed 5-10 mg/kg of andrographolide content and when treatment duration exceeds 14 days.
Most Common Adverse Effects:
Orally: Abdominal discomfort, altered taste, diarrhea, dizziness, fatigue, headache, nausea and vomiting, pruritus, rash, and urticaria.
Serious Adverse Effects (Rare):
Orally: Severe allergic reactions, including anaphylaxis.
Cardiovascular ...Orally, andrographis has been reported to cause vasculitis, edema, and increased sweating (12380,13016,91841).
Dermatologic
...Orally, andrographis has been frequently reported to cause maculopapular, erythematous rash, pruritus, and urticaria (31223,31222,31233,12380,31231,31220,13016,91838,91841,104821)(107783,112921).
Andrographis consumption has also been reported to cause angioedema, exfoliative dermatitis, skin exfoliation, Stevens-Johnson syndrome, acute generalized exanthematous pustulosis, bullous eruption, fixed eruption, stomatitis, allergic purpura, flushing, and swelling (91841).
Parenterally, there have been reports of maculopapular rash, urticaria, pruritus, and flushing with the use of andrographolide derivative injections; about one-third of patients experienced skin or subcutaneous reactions (112921).
Gastrointestinal
...Orally, andrographis has been reported to cause nausea, vomiting, diarrhea, dyspepsia, flatulence, altered or metallic taste, and abdominal discomfort (6767,31213,2748,13016,31220,31222,91841,104821,107783,112921).
Andrographis intake has also been reported to cause epigastric pain, ulcerative stomatitis, melena, dry mouth, and dry lips (31213,10795,13016,91841).
Parenterally, there have been reports of diarrhea, nausea, vomiting, and abdominal discomfort with the use of andrographolide derivative injections; over 40% of patients experienced gastrointestinal events (112921).
Genitourinary ...Orally, there is one case report of increased urinary frequency associated with andrographis use (91841)
Hematologic ...Orally, there is one case report of epistaxis (nosebleed) associated with andrographis use (31222).
Hepatic ...Orally, there is one case report of hepatitis associated with andrographis use (91841).
Immunologic
...Orally, andrographis has been reported to cause anaphylactic shock in 2 cases with determined causality, and 7 cases with probable causality.
Anaphylactic shock developed in 5 minutes to one day after oral intake, and included symptoms such as hypotension, chest pain, urticaria, angioedema, wheezing, and tachycardia (91841). Additionally, andrographis intake has been associated with cases of eosinophilia and fever (91841,107783). High doses of the andrographolide constituent (5-10 mg/kg daily) have been associated with two cases of lymphadenopathy and three cases of lymph node pain (6767).
Parenterally, there have been 97 cases reporting severe or life-threatening anaphylaxis after andrographolide derivative injections, 3 of which resulted in death (112921).
Musculoskeletal ...Orally, andrographis has been associated with case reports of pain, muscle weakness, cramps, and paralysis (31220,91841,107783).
Neurologic/CNS ...Orally, andrographis has been reported to cause headache, fatigue, anorexia, somnolence, insomnia, lethargy, malaise, and drowsiness (2748,5784,6767,10795,12380,13016,31220,31213,31222,91841,107783). Headache and fatigue occurred more often with high doses of the andrographolide constituent (5-10 mg/kg daily) in one clinical trial (6767).
Pulmonary/Respiratory ...Orally, andrographis has been reported to cause dyspnea, coughing, bronchospasm, increased sputum, and nasal congestion (10795,13016,31213,91841,107783).
General ...Orally and intravenously, quercetin seems to be well tolerated in appropriate doses. Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Gastrointestinal ...Intravenous administration of quercetin is associated with nausea and vomiting (9564).
Neurologic/CNS ...Orally, quercetin may cause headache and tingling of the extremities (481,111500). Intravenously, quercetin may cause pain at the injection site. Injection pain can be minimized by premedicating patients with 10 mg of morphine and administering amounts greater than 945 mg/m2 over 5 minutes (9564). In addition, intravenous administration of quercetin is associated with flushing and sweating (9564).
Pulmonary/Respiratory ...Intravenous administration of quercetin at doses as high as 2000 mg/m2 is associated with dyspnea that may persist for up to 5 minutes (9564).
Renal ...Intravenously, nephrotoxicity has been reported with quercetin in amounts greater than 945 mg/m2 (9563,9564,70304).
General
...Orally, intravenously, and topically, vitamin C is well-tolerated.
Most Common Adverse Effects:
Orally: Abdominal cramps, esophagitis, heartburn, headache, osmotic diarrhea, nausea, vomiting. Kidney stones have been reported in those prone to kidney stones. Adverse effects are more likely to occur at doses above the tolerable upper intake level of 2 grams daily.
Topically: Irritation and tingling.
Serious Adverse Effects (Rare):
Orally: There have been rare case reports of carotid inner wall thickening after large doses of vitamin C.
Intravenously: There have been case reports of hyperoxalosis and oxalate nephropathy following high-dose infusions of vitamin C.
Cardiovascular
...Evidence from population research has found that high doses of supplemental vitamin C might not be safe for some people.
In postmenopausal adults with diabetes, supplemental vitamin C intake in doses greater than 300 mg per day is associated with increased risk of cardiovascular mortality. However, dietary intake of vitamin C is not associated with this risk. Also, vitamin C intake is not associated with an increased risk of cardiovascular mortality in patients without diabetes (12498).
Oral supplementation with vitamin C has also been associated with an increased rate of carotid inner wall thickening in men. There is preliminary evidence that supplemental intake of vitamin C 500 mg daily for 18 months can cause a 2.5-fold increased rate of carotid inner wall thickening in non-smoking men and a 5-fold increased rate in men who smoked. The men in this study were 40-60 years old (1355). This effect was not associated with vitamin C from dietary sources (1355).
There is also some concern that vitamin C may increase the risk of hypertension in some patients. A meta-analysis of clinical research suggests that, in pregnant patients at risk of pre-eclampsia, oral intake of vitamin C along with vitamin E increases the risk of gestational hypertension (83450). Other clinical research shows that oral intake of vitamin C along with grape seed polyphenols can increase both systolic and diastolic blood pressure in hypertensive patients (13162).
Dental ...Orally, vitamin C, particularly chewable tablets, has been associated with dental erosion (83484).
Dermatologic ...Topically, vitamin C might cause tingling or irritation at the site of application (6166). A liquid containing vitamin C 20%, red raspberry leaf cell culture extract 0.0005%, and vitamin E 1% (Antioxidant and Collagen Booster Serum, Max Biocare Pty Ltd.) has been reported to cause mild tingling and skin tightness (102355). It is unclear if these effects are due to vitamin C, the other ingredients, or the combination.
Gastrointestinal ...Orally, the adverse effects of vitamin C are dose-related and include nausea, vomiting, esophagitis, heartburn, abdominal cramps, gastrointestinal obstruction, and diarrhea. Doses greater than the tolerable upper intake level (UL) of 2000 mg per day can increase the risk of adverse effects such as osmotic diarrhea and severe gastrointestinal upset (3042,4844,96707,104450). Mineral forms of vitamin C, such as calcium ascorbate (Ester-C), seem to cause fewer gastrointestinal adverse effects than regular vitamin C (83358). In a case report, high dose intravenous vitamin C was associated with increased thirst (96709).
Genitourinary ...Orally, vitamin C may cause precipitation of urate, oxalate, or cysteine stones or drugs in the urinary tract (10356). Hyperoxaluria, hyperuricosuria, hematuria, and crystalluria have occurred in people taking 1 gram or more per day (3042,90943). Supplemental vitamin C over 250 mg daily has been associated with higher risk for kidney stones in males. There was no clear association found in females, but the analysis might not have been adequately powered to evaluate this outcome (104029). In people with a history of oxalate kidney stones, supplemental vitamin C 1 gram per day appears to increase kidney stone risk by 40% (12653). A case of hematuria, high urine oxalate excretion, and the presence of a ureteral stone has been reported for a 9-year-old male who had taken about 3 grams of vitamin C daily since 3 years of age. The condition resolved with cessation of vitamin C intake (90936).
Hematologic ...Prolonged use of large amounts of vitamin C can result in increased metabolism of vitamin C; subsequent reduction in vitamin C intake may precipitate the development of scurvy (15). In one case, a patient with septic shock and a large intraperitoneal hematoma developed moderate hemolysis and increased methemoglobin 12 hours after a high-dose vitamin C infusion. The patient received a blood transfusion and the hemolysis resolved spontaneously over 48 hours (112479).
Neurologic/CNS ...Orally, the adverse effects of vitamin C are dose-related and include fatigue, headache, insomnia, and sleepiness (3042,4844,83475,83476).
Renal ...Hyperoxalosis and oxalate nephropathy have been reported following high-dose infusions of vitamin C. Hyperoxalosis and acute kidney failure contributed to the death of a 76-year-old patient with metastatic adenocarcinoma of the lung who received 10 courses of intravenous infusions containing vitamins, including vitamin C and other supplements over a period of 1 month. Dosages of vitamin C were not specified but were presumed to be high-dose (106618). In another case, a 34-year-old patient with a history of kidney transplant and cerebral palsy was found unresponsive during outpatient treatment for a respiratory tract infection. The patient was intubated for acute hypoxemic respiratory failure, initiated on vasopressors, hydrocortisone, and antibacterial therapy, and received 16 doses of vitamin C 1.5 grams. Serum creatinine level peaked at greater than 3 times baseline and the patient required hemodialysis for oliguria and uncontrolled acidosis. Kidney biopsy revealed oxalate nephropathy with concomitant drug-induced interstitial nephritis (106625). In another case, a 41-year-old patient with a history of kidney transplant presented with fever, nausea, and decreased urine output 4 days after receiving intravenous vitamin C 7 grams for urothelial carcinoma. Serum creatinine levels increased from 1.7 mg/dL to 7.3 mg/dL over those 4 days, and hemodialysis was initiated 3 days after admission due to anuria. Renal biopsy confirmed the diagnosis of acute oxalate nephropathy (109962).
Other ...Intravenously, hypernatremia and falsely elevated ketone levels is reported in a patient with septic shock and chronic kidney disease after a high-dose vitamin C infusion. The hypernatremia resolved over 24 hours after cessation of the infusion (112479).
General
...Orally, willow bark seems to be well tolerated.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, heartburn, and vomiting. May cause itching and rash in sensitive individuals.
Serious Adverse Effects (Rare):
Orally: Gastrointestinal bleeding and renal impairment. May cause serious allergic reactions, including anaphylaxis, in people who are allergic to aspirin.
Cardiovascular ...In one clinical trial, a single patient withdrew from the study investigating oral willow bark due to blood pressure instability that the authors determined was 'possibly' related to treatment (12804).
Dermatologic ...Orally, willow bark may cause itching and rash in some people due to allergy (6456,12474,12475,12804,86459).
Gastrointestinal ...Orally, willow bark extract can cause gastrointestinal adverse effects, but these appear to be less frequent than those caused by NSAIDs. Examples include diarrhea, heartburn, vomiting, and dyspepsia (12474,12475,12804,86459). In a case report of a child, severe gastrointestinal bleeding occurred following use of a specific syrup (FreddoBaby), which contained ribwort plantain, licorice, willow bark, black elder, meadowsweet, and propolis. The adverse effect was attributed to salicylate content of the syrup. This product has since been withdrawn from the market (86477).
Immunologic ...Orally, willow bark may cause serious allergic reactions, including anaphylaxis, in people who are allergic to aspirin (10392)
Neurologic/CNS ...Orally, willow bark may cause headache and dizziness (12804). In a clinical trial evaluating a combination product containing willow bark, black cohosh, sarsaparilla, poplar bark, and guaiac wood (Reumalex), severe headaches occurred (35946).
Ocular/Otic ...Orally, symptoms of allergy to willow bark have included swollen eyes (6456).
Renal ...Salicylates can inhibit prostaglandins, which can reduce renal blood flow (12805). Salicin can cause renal papillary necrosis (12806). The risk for toxicity is greater with high acute doses or chronic use (12805).
