Each tablet contains: Proprietary Blend 550 mg: Astragalus root, Eleuthero root, Red Korean Panax Ginseng Red Korean Panax Ginseng (Form: 1% Ginsenosides) PlantPart: root Genus: Panax Species: ginseng Note: A 12:1 extract equivalent to 4,800 mg of Red Korean Ginseng roots root extract, Schizandra fruit, ligustrum fruit, Oryza sprout, Licorice root.
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Below is general information about the effectiveness of the known ingredients contained in the product Astra 8. 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
There is insufficient reliable information available about the effectiveness of glossy privet.
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 Astra 8. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
POSSIBLY SAFE ...when used orally and appropriately. Doses of astragalus up to 60 grams daily for up to 4 months have been used without reported adverse effects (32920,33038,95909,114804). ...when used intravenously. Infusion of doses up to 80 grams daily for up to 4 months under the supervision of a medical professional have been used with apparent safety (32811,32812,32828,95909,114688,114804). There is insufficient reliable information available about the safety of astragalus when used topically.
PREGNANCY AND LACTATION:
There is insufficient reliable information in humans.
However, astragaloside, a constituent of astragalus, has maternal and fetal toxic effects in animals (32881). Avoid using.
LIKELY SAFE ...when used orally and appropriately, short-term. Eleuthero root extract 300-2000 mg has been used safely in clinical trials lasting up to 3 months (730,1427,2574,7522,11099,15586,91509). There is insufficient reliable information available about the safety of eleuthero when used long-term.
CHILDREN: POSSIBLY SAFE
when used orally in adolescents aged 12-17 years, short-term.
Eleuthero 750 mg three times daily was used for 6 weeks with apparent safety in one clinical trial (75028). There is insufficient reliable information available about the safety of eleuthero in children or adolescents when used long-term.
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately (12).
PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally in amounts commonly found in foods. Licorice has Generally Recognized as Safe (GRAS) status in the US (4912).
POSSIBLY SAFE ...when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes. Licorice flavonoid oil 300 mg daily for 16 weeks, and deglycyrrhizinated licorice products in doses of up to 4.5 grams daily for up to 16 weeks, have been used with apparent safety (6196,11312,11313,17727,100984,102960). ...when licorice products containing glycyrrhizin are used orally in low doses, short-term. Licorice extract 272 mg, containing glycyrrhizin 24.3 mg, has been used daily with apparent safety for 6 months (102961). A licorice extract 1000 mg, containing monoammonium glycyrrhizinate 240 mg, has been used daily with apparent safety for 12 weeks (110320). In addition, a syrup providing licorice extract 750 mg has been used twice daily with apparent safety for 5 days (104558). ...when applied topically. A gel containing 2% licorice root extract has been applied to the skin with apparent safety for up to 2 weeks. (59732). A mouth rinse containing 5% licorice extract has been used with apparent safety four times daily for up to one week (104564).
POSSIBLY UNSAFE ...when licorice products containing glycyrrhizin are used orally in large amounts for several weeks, or in smaller amounts for longer periods of time. The European Scientific Committee on Food recommends that a safe average daily intake of glycyrrhizin should not exceed 10 mg (108577). In otherwise healthy people, consuming glycyrrhizin daily for several weeks or longer can cause severe adverse effects including pseudohyperaldosteronism, hypertensive crisis, hypokalemia, cardiac arrhythmias, and cardiac arrest. Doses of 20 grams or more of licorice products, containing at least 400 mg glycyrrhizin, are more likely to cause these effects; however, smaller amounts have also caused hypokalemia and associated symptoms when taken for months to years (781,3252,15590,15592,15594,15596,15597,15599,15600,16058)(59731,59740,59752,59785,59786,59787,59792,59795,59805,59811)(59816,59818,59820,59822,59826,59828,59849,59850,59851,59867)(59882,59885,59888,59889,59895,59900,59906,97213,110305). In patients with hypertension, cardiovascular or kidney conditions, or a high salt intake, as little as 5 grams of licorice product or 100 mg glycyrrhizin daily can cause severe adverse effects (15589,15593,15598,15600,59726).
PREGNANCY: UNSAFE
when used orally.
Licorice has abortifacient, estrogenic, and steroid effects. It can also cause uterine stimulation. Heavy consumption of licorice, equivalent to 500 mg of glycyrrhizin per week (about 250 grams of licorice per week), during pregnancy seems to increase the risk of delivery before gestational age of 38 weeks (7619,10618). Furthermore, high intake of glycyrrhizin, at least 500 mg per week, during pregnancy is associated with increased salivary cortisol levels in the child by the age of 8 years. This suggests that high intake of licorice during pregnancy may increase hypothalamic-pituitary-adrenocortical axis activity in the child (26434); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
LIKELY SAFE ...when used orally and appropriately, short-term. Panax ginseng seems to be safe when used for up to 6 months (8813,8814,17736,89741,89743,89745,89746,89747,89748,103044,103477).
POSSIBLY UNSAFE ...when used orally, long-term. There is some concern about the long-term safety due to potential hormone-like effects, which might cause adverse effects with prolonged use (12537). Tell patients to limit continuous use to less than 6 months. There is insufficient reliable information available about the safety of Panax ginseng when used topically.
CHILDREN: LIKELY UNSAFE
when used orally in infants.
Use of Panax ginseng in newborns is associated with intoxication that can lead to death (12). There is limited reliable information available about use in older children (24109,103049); avoid using.
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Ginsenoside Rb1, an active constituent of Panax ginseng, has teratogenic effects in animal models (10447,24106,24107); avoid using.
LACTATION:
Insufficient reliable information available; avoid using.
POSSIBLY SAFE ...when used orally and appropriately. Schisandra extract up to 1 gram daily has been used for up to 12 weeks with apparent safety (12,96632,105562,105563,112887).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Some evidence suggests schisandra fruit is a uterine stimulant (11).
LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Astra 8. 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, taking astragalus with antidiabetes drugs might increase the risk of hypoglycemia.
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Theoretically, astragalus might interfere with cyclophosphamide therapy.
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Theoretically, astragalus might interfere with immunosuppressive therapy.
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Theoretically, astragalus might increase levels and adverse effects of lithium.
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Animal research suggests that astragalus has diuretic properties (15103). Theoretically, due to this diuretic effect, astragalus might reduce excretion and increase levels of lithium.
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Theoretically, eleuthero may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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Theoretically, eleuthero might have additive effects when used with antidiabetes drugs.
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Animal research suggests that certain constituents of eleuthero have hypoglycemic activity in both healthy and diabetic animals (7591,73535,74932,74956,74988,74990). A small study in adults with type 2 diabetes also shows that taking eleuthero for 3 months can lower blood glucose levels (91509). However, one very small study in healthy individuals shows that taking powdered eleuthero 3 grams, 40 minutes prior to a 75-gram oral glucose tolerance test, significantly increases postprandial blood glucose levels when compared with placebo (12536). These contradictory findings might be due to patient-specific variability and variability in active ingredient ratios.
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Theoretically, eleuthero might increase levels of drugs metabolized by CYP1A2.
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In vitro and animal research suggest that standardized extracts of eleuthero inhibit CYP1A2 (7532). This effect has not been reported in humans.
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Theoretically, eleuthero might increase levels of drugs metabolized by CYP2C9.
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In vitro and animal research suggest that standardized extracts of eleuthero might inhibit CYP2C9 (7532). This effect has not been reported in humans.
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Theoretically, eleuthero might increase levels of drugs metabolized by CYP2D6.
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Theoretically, eleuthero might increase levels of drugs metabolized by CYP3A4.
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Eleuthero might increase serum digoxin levels and increase the risk of side effects.
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In one case report, a 74-year-old male who was stabilized on digoxin presented with an elevated serum digoxin level after starting an eleuthero supplement, without symptoms of toxicity. After stopping the supplement, serum digoxin levels returned to normal (543). It is not clear whether this was due to a pharmacokinetic interaction or to interference with the digoxin assay (15585). Although the product was found to be free of digoxin and digitoxin (543), it was not tested for other contaminants (797).
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Theoretically, eleuthero might interfere with immunosuppressive drugs because of its immunostimulant activity.
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Theoretically, eleuthero might decrease levels of drugs metabolized by OATP.
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In vitro research suggests that eleuthero inhibits OATP2B1, which might reduce the bioavailability of oral drugs that are substrates of OATP2B1 (35450). Due to the weak inhibitory effect identified in this study, this interaction is not likely to be clinically significant.
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Theoretically, eleuthero might increase levels of P-glycoprotein substrates.
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Glossy privet is thought to have diuretic properties. Theoretically, due to these potential diuretic effects, glossy privet might reduce excretion and increase levels of lithium. The dose of lithium might need to be decreased.
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Theoretically, licorice might reduce the effects of antihypertensive drugs.
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Theoretically, licorice might reduce the effects of cisplatin.
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In animal research, licorice diminished the therapeutic efficacy of cisplatin (59763).
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Theoretically, concomitant use of licorice and corticosteroids might increase the side effects of corticosteroids.
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Case reports suggest that concomitant use of licorice and oral corticosteroids, such as hydrocortisone, can potentiate the duration of activity and increase blood levels of corticosteroids (3252,12672,20040,20042,48429,59756). Additionally, in one case report, a patient with neurogenic orthostatic hypertension stabilized on fludrocortisone 0.1 mg twice daily developed pseudohyperaldosteronism after recent consumption of large amounts of black licorice (108568).
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Theoretically, licorice might increase levels of drugs metabolized by CYP2B6.
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In vitro research shows that licorice extract and glabridin, a licorice constituent, inhibit CYP2B6 isoenzymes (10300,94822). Licorice extract from the species G. uralensis seems to inhibit CYP2B6 isoenzymes to a greater degree than G. glabra extract in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2B6; however, these interactions have not yet been reported in humans.
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Theoretically, licorice might increase levels of drugs metabolized by CYP2C19.
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In vitro, licorice extracts from the species G. glabra and G. uralensis inhibit CYP2C19 isoenzymes in vitro (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C19; however, this interaction has not yet been reported in humans.
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Theoretically, licorice might increase levels of drugs metabolized by CYP2C8.
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In vitro, licorice extract from the species G. glabra and G. uralensis inhibits CYP2C8 isoenzymes (94822). Theoretically, these species of licorice might increase levels of drugs metabolized by CYP2C8; however, this interaction has not yet been reported in humans.
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Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP2C9.
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There is conflicting evidence about the effect of licorice on CYP2C9 enzyme activity. In vitro research shows that extracts from the licorice species G. glabra and G. uralensis moderately inhibit CYP2C9 isoenzymes (10300,94822). However, evidence from an animal model shows that licorice extract from the species G. uralensis can induce hepatic CYP2C9 activity (14441). Until more is known, licorice should be used cautiously in people taking CYP2C9 substrates.
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Theoretically, licorice might increase or decrease levels of drugs metabolized by CYP3A4.
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Pharmacokinetic research shows that the licorice constituent glycyrrhizin, taken in a dosage of 150 mg orally twice daily for 14 days, modestly decreases the area under the concentration-time curve of midazolam by about 20%. Midazolam is a substrate of CYP3A4, suggesting that glycyrrhizin modestly induces CYP3A4 activity (59808). Animal research also shows that licorice extract from the species G. uralensis induces CYP3A4 activity (14441). However, licorice extract from G. glabra species appear to inhibit CYP3A4-induced metabolism of testosterone in vitro. It is thought that the G. glabra inhibits CYP3A4 due to its constituent glabridin, which is a moderate CYP3A4 inhibitor in vitro and not present in other licorice species (10300,94822). Until more is known, licorice should be used cautiously in people taking CYP3A4 substrates.
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Theoretically, concomitant use of licorice with digoxin might increase the risk of cardiac toxicity.
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Overuse or misuse of licorice with cardiac glycoside therapy might increase the risk of cardiac toxicity due to potassium loss (10393).
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Theoretically, concomitant use of licorice with diuretic drugs might increase the risk of hypokalemia.
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Overuse of licorice might compound diuretic-induced potassium loss (10393,20045,20046,59812). In one case report, a 72-year-old male with a past medical history of hypertension, type 2 diabetes, hyperlipidemia, arrhythmia, stroke, and hepatic dysfunction was hospitalized with severe hypokalemia and uncontrolled hypertension due to pseudohyperaldosteronism. This was thought to be provoked by concomitant daily consumption of a product containing 225 mg of glycyrrhizin, a constituent of licorice, and hydrochlorothiazide 12.5 mg for 1 month (108577).
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Theoretically, licorice might increase or decrease the effects of estrogen therapy.
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Theoretically, loop diuretics might increase the mineralocorticoid effects of licorice.
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Theoretically, loop diuretics might enhance the mineralocorticoid effects of licorice by inhibiting the enzyme that converts cortisol to cortisone; however, bumetanide (Bumex) does not appear to have this effect (3255).
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Theoretically, licorice might increase levels of methotrexate.
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Animal research suggests that intravenous administration of glycyrrhizin, a licorice constituent, and high-dose methotrexate may delay methotrexate excretion and increase systemic exposure, leading to transient elevations in liver enzymes and total bilirubin (108570). This interaction has not yet been reported in humans.
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Theoretically, licorice might decrease levels of midazolam.
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In humans, the licorice constituent glycyrrhizin appears to moderately induce the metabolism of midazolam (59808). This is likely due to induction of cytochrome P450 3A4 by licorice. Until more is known, licorice should be used cautiously in people taking midazolam.
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Theoretically, licorice might decrease the absorption of P-glycoprotein substrates.
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In vitro research shows that licorice can increase P-glycoprotein activity (104561).
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Theoretically, licorice might decrease plasma levels and clinical effects of paclitaxel.
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Multiple doses of licorice taken concomitantly with paclitaxel might reduce the effectiveness of paclitaxel. Animal research shows that licorice 3 grams/kg given orally for 14 days before intravenous administration of paclitaxel decreases the exposure to paclitaxel and increases its clearance. Theoretically, this occurs because licorice induces cytochrome P450 3A4 enzymes, which metabolize paclitaxel. Notably, a single dose of licorice did not affect exposure or clearance of paclitaxel (102959).
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Theoretically, licorice might decrease plasma levels and clinical effects of warfarin.
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Licorice seems to increase metabolism and decrease levels of warfarin in animal models. This is likely due to induction of cytochrome P450 2C9 (CYP2C9) metabolism by licorice (14441). Advise patients taking warfarin to avoid taking licorice.
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Although Panax ginseng has shown antiplatelet effects in the laboratory, it is unlikely to increase the risk of bleeding if used with anticoagulant or antiplatelet drugs.
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In vitro evidence suggests that ginsenoside constituents in Panax ginseng might decrease platelet aggregation (1522,11891). However, research in humans suggests that ginseng does not affect platelet aggregation (11890). Animal research indicates low oral bioavailability of Rb1 and rapid elimination of Rg1, which might explain the discrepancy between in vitro and human research (11153). Until more is known, use with caution in patients concurrently taking anticoagulant or antiplatelet drugs.
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Theoretically, taking Panax ginseng with antidiabetes drugs might increase the risk of hypoglycemia.
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Clinical research suggests that Panax ginseng might decrease blood glucose levels (89740). Monitor blood glucose levels closely.
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Theoretically, taking Panax ginseng with caffeine might increase the risk of adverse stimulant effects.
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Theoretically, Panax ginseng might decrease levels of drugs metabolized by CYP1A1.
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In vitro research shows that Panax ginseng can induce the CYP1A1 enzyme (24104).
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Theoretically, Panax ginseng might increase levels of drugs metabolized by CYP2D6. However, research is conflicting.
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There is some evidence that Panax ginseng can inhibit the CYP2D6 enzyme by approximately 6% (1303,51331). In addition, in animal research, Panax ginseng inhibits the metabolism of dextromethorphan, a drug metabolized by CYP2D6, by a small amount (103478). However, contradictory research suggests Panax ginseng might not inhibit CYP2D6 (10847). Until more is known, use Panax ginseng cautiously in patients taking drugs metabolized by these enzymes.
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Theoretically, Panax ginseng might increase or decrease levels of drugs metabolized by CYP3A4.
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Panax ginseng may affect the clearance of drugs metabolized by CYP3A4. One such drug is imatinib. Inhibition of CYP3A4 was believed to be responsible for a case of imatinib-induced hepatotoxicity (89764). In contrast, Panax ginseng has been shown to increase the clearance of midazolam, another drug metabolized by CYP3A4 (89734,103478). Clinical research shows that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29% (89734). Midazolam metabolism was also increased in animals given Panax ginseng (103478). Until more is known, use Panax ginseng cautiously in combination with CYP3A4 substrates.
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Theoretically, concomitant use of large amounts of Panax ginseng might interfere with hormone replacement therapy.
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Theoretically, Panax ginseng might decrease blood levels of oral or intravenous fexofenadine.
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Animal research suggests that taking Panax ginseng in combination with oral or intravenous fexofenadine may reduce the bioavailability of fexofenadine. Some scientists have attributed this effect to the ability of Panax ginseng to increase the expression of P-glycoprotein (24101).
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Theoretically, Panax ginseng might reduce the effects of furosemide.
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There is some concern that Panax ginseng might contribute to furosemide resistance. There is one case of resistance to furosemide diuresis in a patient taking a germanium-containing ginseng product (770).
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Theoretically, Panax ginseng might increase the effects and adverse effects of imatinib.
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A case of imatinib-induced hepatotoxicity has been reported for a 26-year-old male with chronic myelogenous leukemia stabilized on imatinib for 7 years. The patient took imatinib 400 mg along with a Panax ginseng-containing energy drink daily for 3 months. Since imatinib-associated hepatotoxicity typically occurs within 2 years of initiating therapy, it is believed that Panax ginseng affected imatinib toxicity though inhibition of cytochrome P450 3A4. CYP3A4 is the primary enzyme involved in imatinib metabolism (89764).
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Theoretically, Panax ginseng use might interfere with immunosuppressive therapy.
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Panax ginseng might have immune system stimulating properties (3122).
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Theoretically, taking Panax ginseng with insulin might increase the risk of hypoglycemia.
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Clinical research suggests that Panax ginseng might decrease blood glucose levels (89740). Insulin dose adjustments might be necessary in patients taking Panax ginseng; use with caution.
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Although Panax ginseng has demonstrated variable effects on cytochrome P450 3A4 (CYP3A4), which metabolizes lopinavir, Panax ginseng is unlikely to alter levels of lopinavir/ritonavir.
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Lopinavir is metabolized by CYP3A4 and is administered with the CYP3A4 inhibitor ritonavir to increase its plasma concentrations. Panax ginseng has shown variable effects on CYP3A4 activity in humans (89734,89764). However, taking Panax ginseng (Vitamer Laboratories) 500 mg twice daily for 14 days did not alter the pharmacokinetics of lopinavir/ritonavir in 12 healthy volunteers (93578).
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Theoretically, Panax ginseng may increase the clearance of midazolam.
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Midazolam is metabolized by cytochrome P450 3A4 (CYP3A4). Clinical research suggests that Panax ginseng can reduce midazolam area under the curve by 44%, maximum plasma concentration by 26%, and time to reach maximum plasma concentration by 29% (89734). Midazolam metabolism was also increased in animals given Panax ginseng (103478).
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Theoretically, Panax ginseng can interfere with MAOI therapy.
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Theoretically, taking Panax ginseng with nifedipine might increase serum levels of nifedipine and the risk of hypotension.
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Preliminary clinical research shows that concomitant use can increase serum levels of nifedipine in healthy volunteers (22423). This might cause the blood pressure lowering effects of nifedipine to be increased when taken concomitantly with Panax ginseng.
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Theoretically, Panax ginseng has an additive effect with drugs that prolong the QT interval and potentially increase the risk of ventricular arrhythmias. However, research is conflicting.
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Theoretically, taking Panax ginseng with raltegravir might increase the risk of liver toxicity.
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A case report suggests that concomitant use of Panax ginseng with raltegravir can increase serum levels of raltegravir, resulting in elevated liver enzymes levels (23621).
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Theoretically, Panax ginseng might increase or decrease levels of selegiline, possibly altering the effects and side effects of selegiline.
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Animal research shows that taking selegiline with a low dose of Panax ginseng extract (1 gram/kg) reduces selegiline bioavailability, while taking a high dose of Panax ginseng extract (3 grams/kg) increases selegiline bioavailability (103053). More research is needed to confirm these effects.
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Theoretically, taking Panax ginseng with stimulant drugs might increase the risk of adverse stimulant effects.
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Panax ginseng might affect the clearance of warfarin. However, this interaction appears to be unlikely.
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There has been a single case report of decreased effectiveness of warfarin in a patient who also took Panax ginseng (619). However, it is questionable whether Panax ginseng was the cause of this decrease in warfarin effectiveness. Some research in humans and animals suggests that Panax ginseng does not affect the pharmacokinetics of warfarin (2531,11890,17204,24105). However, other research in humans suggests that Panax ginseng might modestly increase the clearance of the S-warfarin isomer (15176). More evidence is needed to determine whether Panax ginseng causes a significant interaction with warfarin.
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Theoretically, schisandra might increase the levels and clinical effects of cyclophosphamide.
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In vitro research shows that schisandra increases the concentration of cyclophosphamide, likely through inhibition of cytochrome P450 3A4. After multiple doses of the schisandra constituents schisandrin A and schisantherin A, the maximum concentration of cyclophosphamide was increased by 7% and 75%, respectively, while the overall exposure to cyclophosphamide was increased by 29% and 301%, respectively (109636).
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Schisandra can increase the levels and clinical effects of cyclosporine.
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A small observational study in children with aplastic anemia found that taking schisandra with cyclosporine increased cyclosporine trough levels by 93% without increasing the risk of adverse events. However, the dose of cyclosporine was reduced in 9% of children to maintain appropriate cyclosporine blood concentrations (109637).
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Theoretically, schisandra might increase the levels and clinical effects of CYP2C19 substrates.
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In vitro research shows that schisandra inhibits CYP2C19, and animal research shows that schisandra increases the concentration of voriconazole, a CYP2C19 substrate (105566). Theoretically, schisandra may also inhibit the metabolism of other CYP2C19 substrates. This effect has not been reported in humans.
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Theoretically, schisandra might decrease the levels and clinical effects of CYP2C9 substrates.
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In vitro and animal research suggests that schisandra induces CYP2C9 enzymes (14441). This effect has not been reported in humans.
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Schisandra can increase the levels and clinical effects of drugs metabolized by CYP3A4.
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Most clinical and laboratory research shows that schisandra, administered either as a single dose or up to twice daily for 14 days, inhibits CYP3A4 and increases the concentration of CYP3A4 substrates such as cyclophosphamide, midazolam, tacrolimus, and talinolol (13220,17414,23717,91386,91388,91387,96631,105564,109636,109638,109639,109640,109641). Although one in vitro and animal study shows that schisandra may induce CYP3A4 metabolism (14441), this effect appears to be overpowered by schisandra's CYP3A4 inhibitory activity and has not been reported in humans.
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Schisandra can increase the levels and clinical effects of midazolam.
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A small pharmacokinetic study in healthy adults shows that taking schisandra extract (Hezheng Pharmaceutical Co.) containing deoxyschizandrin 33.75 mg twice daily for 8 days and a single dose of midazolam 15 mg on day 8 increases the overall exposure to midazolam by about 119%, increases the peak plasma level of midazolam by 86%, and decreases midazolam clearance by about 52%. This effect has been attributed to inhibition of CYP3A4 by schisandra (91388).
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Schisandra might increase the levels and clinical effects of P-glycoprotein substrates.
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In vitro research shows that schisandra extracts and constituents such as schisandrin B inhibit P-glycoprotein mediated efflux in intestinal cells and in P-glycoprotein over-expressing cell lines (17414,105643,105644). Additionally, a small clinical study shows that schisandra increases the peak concentration and overall exposure to talinolol, a P-glycoprotein probe substrate (91386). Theoretically, schisandra might inhibit the efflux of other P-glycoprotein substrates.
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Schisandra can increase the levels and clinical effects of sirolimus.
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A small pharmacokinetic study in healthy volunteers shows that taking 3 capsules of schisandra (Hezheng Pharmaceutical Company) containing a total of 33.75 mg deoxyschizandrin twice daily for 13 days and then taking a single dose of sirolimus 2 mg increases the overall exposure and peak level of sirolimus by two-fold. This effect is thought to be due to inhibition of cytochrome P450 3A4 by schisandra, as well as possible inhibition of the P-glycoprotein drug transporter (105643).
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Schisandra can increase the levels and clinical effects of tacrolimus.
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Clinical research in healthy children and adults, transplant patients, and patients with nephrotic syndrome and various rheumatic immunologic disorders shows that taking schisandra with tacrolimus increases tacrolimus peak levels by 183% to 268%, prolongs or delays time to peak tacrolimus concentrations, increases overall exposure to tacrolimus by 126% to 343%, and decreases tacrolimus clearance by 19% to 73% (17414,91387,15570,96631,105623,109638,109639,109640,109641,112889)(112890,112972,112973,112974). This effect is thought to be due to inhibition of P-glycoprotein drug transporter and CYP3A4 and CYP3A5 by schisandra (17414,96631,105623,105643,105644,112974). Some clinical and observational studies suggest that schisandra increases tacrolimus levels similarly in both expressors and non-expressors of CYP3A5, while other studies suggest it does so to a greater degree in CYP3A5 expressors than non-expressors (105623,109638,109639,109640,112889,112890,112973,112974). Animal research suggests that the greatest increase in tacrolimus levels occurs when schisandra is taken either concomitantly or up to 2 hours before tacrolimus (105564), and clinical and observational research in humans suggests that schisandra may increase whole blood levels of tacrolimus and decrease clearance of tacrolimus in a dose-dependent manner (109639,109640,112972).
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Schisandra can increase the levels and clinical effects of talinolol.
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A small pharmacokinetic study in healthy volunteers shows that taking schisandra extract 300 mg twice daily for 14 days with a single dose of talinolol 100 mg on day 14 increases the peak talinolol level by 51% and the overall exposure to talinolol by 47%. This effect is thought to be due to the possible inhibition of cytochrome P450 3A4 and P-glycoprotein by schisandra (91386).
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Theoretically, schisandra might increase the levels and clinical effects of voriconazole.
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Animal research shows that oral schisandra given daily for 1 or 14 days increases levels of intravenously administered voriconazole, a cytochrome P450 (CYP) 2C19 substrate. This effect is thought to be due to inhibition of CYP2C19 by schisandra (105566). However, this interaction has not been reported in humans.
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Theoretically, schisandra might decrease the levels and clinical effects of warfarin.
Details
Animal research suggests that oral schisandra extract, given daily for 6 days, reduces levels of intravenously administered warfarin. This effect might be due to the induction of cytochrome P450 (CYP) 2C9 metabolism by schisandra (14441). However, this interaction has not been reported in humans.
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Below is general information about the adverse effects of the known ingredients contained in the product Astra 8. 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 and intravenously, astragalus root seems to be well tolerated.
Topically, no adverse effects have been reported. However, a thorough evaluation of safety outcomes has not been conducted.
Serious Adverse Effects (Rare):
Orally: A case report raises concerns about liver and kidney cysts with astragalus use.
Cardiovascular ...Orally, astragalus has reportedly been associated with lacunar angina in one clinical trial. However, this may not have been caused by astragalus (17355). In addition, rapid intravenous administration of astragalus has resulted in temporary palpitations (32812).
Dermatologic ...Intravenously, astragalus may cause rash, eczema, and pruritus (33034).
Gastrointestinal ...Orally, astragalus has reportedly been associated with enterocolitis and nausea in one clinical trial. However, these effects may not have been caused by astragalus (17355).
Genitourinary ...Orally, astragalus has reportedly been associated with vulvitis in one clinical trial. However, this effect may not have been caused by astragalus (17355).
Hepatic ...A case of high serum CA19-9 levels and small liver and kidney cysts has been reported for a 38-year-old woman who drank astragalus tea daily for one month. Levels returned to normal after one month, and cysts disappeared after ten months. Both symptoms returned following a resumption of astragalus use. The authors state that astragalus was the likely cause given the temporal relationship (90658).
Musculoskeletal ...Orally, astragalus has been associated with reports of musculoskeletal pain in one clinical trial. However, these effects may not have been caused by astragalus (114803).
Neurologic/CNS ...Intravenously, administration of astragalus has been associated with temporary dizziness in patients with heart failure in clinical research (32812,114804). Orally, astragalus has also been associated with dizziness in one clinical study. However, these effects may not have been caused by astragalus (114803).
Pulmonary/Respiratory ...Orally, astragalus has reportedly been associated with rhinosinusitis and pharyngitis in one clinical trial. However, these effects may not have been caused by astragalus (17355).
Renal ...A case of high serum CA19-9 levels and small liver and kidney cysts has been reported for a 38-year-old woman who drank astragalus tea daily for one month. Levels returned to normal after one month, and cysts disappeared after ten months. Both symptoms returned following a resumption of astragalus use. The authors state that astragalus was the likely cause given the temporal relationship (90658).
General
...Orally, eleuthero root is generally well tolerated when used short-term.
Most Common Adverse Effects:
Orally: Diarrhea, dyspepsia, gastrointestinal upset, headache, nausea, and urticaria.
Cardiovascular ...Orally, increased blood pressure has been reported in children with hypotension taking eleuthero in one clinical study (74980). Eleuthero has been reported to cause tachycardia, hypertension, and pericardial pain in patients with rheumatic heart disease or atherosclerosis. It is unclear if these effects were caused by eleuthero, or by the cardioglycoside-containing herb, silk vine (Periploca sepium), which is a common adulterant found in eleuthero products (12,797,6500).
Dermatologic ...Orally, eleuthero has been reported to cause rash in some clinical studies (75013,75028).
Gastrointestinal ...Orally, eleuthero has been reported to cause dyspepsia, nausea, diarrhea, and gastrointestinal upset in some patients (74938,75028,91510).
Genitourinary ...Orally, mastalgia and uterine bleeding were reported in 7. 3% of females taking eleuthero 2 grams daily in one clinical study (6500,11099). These adverse effects seem to be more likely with higher doses.
Neurologic/CNS
...Orally, headaches have been reported in 9.
8% of people taking eleuthero in one clinical study (11099).
In one case report, a 53-year-old female developed spontaneous subarachnoid hemorrhage associated with the use of an herbal supplement containing red clover, dong quai, and eleuthero (70419). It is unclear if this event was related to the use of eleuthero, the other ingredients, the combination, or another cause entirely.
Psychiatric ...Orally, nervousness has been reported in 7. 3% of people taking eleuthero in one clinical study (11099). Eleuthero has also been reported to cause slight anxiety, irritability, and melancholy in some patients (6500,11099). These adverse effects seem to be more likely to occur with higher doses.
General
...Orally, licorice is generally well tolerated when used in amounts commonly found in foods.
It seems to be well tolerated when licorice products that do not contain glycyrrhizin (deglycyrrhizinated licorice) are used orally and appropriately for medicinal purposes or when used topically, short-term.
Most Common Adverse Effects:
Orally: Headache, nausea, and vomiting.
Topically: Contact dermatitis.
Intravenously: Diarrhea, itching, nausea, and rash.
Serious Adverse Effects (Rare):
Orally: Case reports have raised concerns about acute renal failure, cardiac arrest, cardiac arrhythmias, hypertension, hypokalemia, muscle weakness, paralysis, pseudohyperaldosteronism, and seizure associated with long-term use or large amounts of licorice containing glycyrrhizin.
Cardiovascular
...Orally, excessive licorice ingestion can lead to pseudohyperaldosteronism, which can precipitate cardiovascular complications such as hypertension and hypertensive crisis, ventricular fibrillation or tachycardia, sinus pause, and cardiac arrest.
These effects are due to the licorice constituent glycyrrhizin and usually occur when 20-30 grams or more of licorice product is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,97213) (104563,108574,108576,110305,112234). In one case report, an 89-year-old female taking an herbal medicine containing licorice experienced a fatal arrhythmia secondary to licorice-induced hypokalemia. The patient presented to the hospital with recurrent syncope, weakness, and fatigue for 5 days after taking an herbal medicine containing licorice for 2 months. Upon admission to the hospital, the patient developed seizures, QT prolongation, and ventricular arrhythmia requiring multiple defibrillations. Laboratory tests confirmed hypokalemia and pseudohyperaldosteronism (112234).
However, people with cardiovascular or kidney conditions may be more sensitive, so these adverse events may occur with doses as low as 5 grams of licorice product or glycyrrhizin 100 mg daily (15589,15593,15598,15600,59726). A case report in a 54-year-old male suggests that malnutrition might increase the risk of severe adverse effects with excessive licorice consumption. This patient presented to the emergency room with cardiac arrest and ventricular fibrillation after excessive daily consumption of licorice for about 3 weeks. This caused pseudohyperaldosteronism and then hypokalemia, leading to cardiovascular manifestations. In spite of resuscitative treatment, the patient progressed to kidney failure, refused dialysis, and died shortly thereafter (103791).
Dermatologic
...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912).
There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578). Burning sensation, itching, redness, and scaling were reported rarely in patients applying a combination of licorice, calendula, and snail secretion filtrate to the face. The specific role of licorice is unclear (110322).
In rare cases, the glycyrrhizin constituent of licorice has caused rash and itching when administered intravenously (59712).
Endocrine
...Orally, excessive licorice ingestion can cause a syndrome of apparent mineralocorticoid excess, or pseudohyperaldosteronism, with sodium and water retention, increased urinary potassium loss, hypokalemia, and metabolic alkalosis due to its glycyrrhizin content (781,10619,15591,15592,15593,15594,15595,15596,15597,15598)(15600,16057,16835,25659,25660,25673,25719,26439,59818,59822)(59832,59864,91722,104563,108568,108574,110305,112234).
These metabolic abnormalities can lead to hypertension, edema, EKG changes, fatigue, syncope, arrhythmias, cardiac arrest, headache, lethargy, muscle weakness, dropped head syndrome (DHS), rhabdomyolysis, myoglobinuria, paralysis, encephalopathy, respiratory impairment, hyperparathyroidism, and acute kidney failure (10393,10619,15589,15590,15593,15594,15596,15597,15599)(15600,16057,16835,25660,25673,25719,26439,31562,59709,59716)(59720,59740,59787,59820,59826,59882,59889,59900,91722,97214,100522) (104563,108576,108577). These effects are most likely to occur when 20-30 grams of licorice products containing glycyrrhizin 400 mg or more is consumed daily for several weeks (781,15590,15592,15594,15596,15597,15599,15600,16835,108574). However, some people may be more sensitive, especially those with hypertension, diabetes, heart problems, or kidney problems (15589,15593,15598,15600,59726,108576,108577) and even low or moderate consumption of licorice may cause hypertensive crisis or hypertension in normotensive individuals (1372,97213). The use of certain medications with licorice may also increase the risk of these adverse effects (108568,108577). One case report determined that the use of large doses of licorice in an elderly female stabilized on fludrocortisone precipitated hypokalemia and hypertension, requiring inpatient treatment (108568). Another case report describes severe hypokalemia necessitating intensive care treatment due to co-ingestion of an oral glycyrrhizin-specific product and hydrochlorothiazide for 1 month (108577). Glycyrrhetinic acid has a long half-life, a large volume of distribution, and extensive enterohepatic recirculation. Therefore, it may take 1-2 weeks before hypokalemia resolves (781,15595,15596,15597,15600). Normalization of the renin-aldosterone axis and blood pressure can take up to several months (781,15595,108568). Treatment typically includes the discontinuation of licorice, oral and intravenous potassium supplementation, and short-term use of aldosterone antagonists, such as spironolactone (108574,108577).
Chewing tobacco flavored with licorice has also been associated with toxicity. Chewing licorice-flavored tobacco, drinking licorice tea, or ingesting large amounts of black licorice flavored jelly beans or lozenges has been associated with hypertension and suppressed renin and aldosterone levels (12671,12837,97214,97215,97217,108574). One case report suggests that taking a combination product containing about 100 mg of licorice and other ingredients (Jintan, Morishita Jintan Co.) for many decades may be associated with hypoaldosteronism, even up to 5 months after discontinuation of the product (100522). In another case report, licorice ingestion led to hyperprolactinemia in a female (59901). Licorice-associated hypercalcemia has also been noted in a case report (59766).
Gastrointestinal ...Nausea and vomiting have been reported rarely following oral use of deglycyrrhizinated licorice (25694,59871). Intravenously, the glycyrrhizin constituent of licorice has rarely caused gastric discomfort, diarrhea, or nausea (59712,59915).
Immunologic ...There have been reports of contact allergy, resulting in an itchy reddish eruption, occurring in patients that applied cosmetic products containing oil-soluble licorice extracts (59912). There have also been at least 3 cases of allergic contact dermatitis reported with the topical application of glycyrrhizin-containing products to damaged skin. In one case report, a 31-year-old female with acne presented with a 2-year history of pruritic erythematous-scaly plaques located predominantly on the face and neck after the use of a cosmetic product containing licorice root extract 1%. The patient had a positive skin patch test to licorice root extract, leading the clinicians to hypothesize that the use of benzoyl peroxide, a strong irritant, might have sensitized the patient to licorice (108578).
Musculoskeletal ...In a case report, excessive glycyrrhizin-containing licorice consumption led to water retention and was thought to trigger neuropathy and carpal tunnel syndrome (59791).
Neurologic/CNS ...Orally, licorice containing larger amounts of glycyrrhizin may cause headaches. A healthy woman taking glycyrrhizin 380 mg daily for 2 weeks experienced a headache (59892). Intravenously, the glycyrrhizin constituent of licorice has rarely caused headaches or fatigue (59721). In a case report, licorice candy ingestion was associated with posterior reversible encephalopathy syndrome accompanied by a tonic-clonic seizure (97218).
Ocular/Otic ...Orally, consuming glycyrrhizin-containing licorice 114-909 grams has been associated with transient visual loss (59714).
Pulmonary/Respiratory ...Orally, large amounts of licorice might lead to pulmonary edema. In one case report, a 64-year old male consumed 1020 grams of black licorice (Hershey Twizzlers) containing glycyrrhizin 3.6 grams over 3 days, which resulted in pulmonary edema secondary to pseudohyperaldosteronism (31561). Intravenously, the glycyrrhizin constituent of licorice has caused cold or flu-like symptoms, although these events are not common (59712,59721).
General
...Orally, Panax ginseng is generally well tolerated when used for up to 6 months.
There is some concern about the long-term safety due to potential hormone-like effects.
Topically, no adverse effects have been reported when ginseng is used as a single ingredient. However, a thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Insomnia.
Serious Adverse Effects (Rare):
Orally: Anaphylaxis, arrhythmia, ischemia, Stevens-Johnson syndrome.
Cardiovascular ...Panax ginseng may cause hypertension, hypotension, and edema when used orally in high doses, long-term (3353). However, single doses of Panax ginseng up to 800 mg are not associated with changes in electrocardiogram (ECG) parameters or increases in heart rate or blood pressure (96218). There is a case report of menometrorrhagia and tachyarrhythmia in a 39-year-old female who took Panax ginseng 1000-1500 mg/day orally and also applied a facial cream topically that contained Panax ginseng. Upon evaluation for menometrorrhagia, the patient also reported a history of palpitations. It was discovered that she had sinus tachycardia on ECG. However, the patient was a habitual consumer of coffee 4-6 cups/day and at the time of evaluation was also mildly anemic. The patient was advised to discontinue taking Panax ginseng. During the 6 month period following discontinuation the patient did not have any more episodes of menometrorrhagia or tachyarrhythmia (13030). Also, a case of transient ischemic attack secondary to a hypertensive crisis has been reportedly related to oral use of Panax ginseng (89402).
Dermatologic
...Orally, Panax ginseng may cause itching or an allergic response consisting of systemic rash and pruritus (89743,89760,104953).
Skin eruptions have also been reported with use of Panax ginseng at high dosage, long-term (3353). Uncommon side effects with oral Panax ginseng include Stevens-Johnson syndrome (596).
In one case report, a 6-year-old male with a previous diagnosis of generalized pustular psoriasis, which had been in remission for 18 months, presented with recurrent pustular lesions after consuming an unspecified dose of Panax ginseng. The patient was diagnosed with pityriasis amiantacea caused by subcorneal pustular dermatosis. Treatment with oral dapsone 25 mg daily was initiated, and symptoms resolved after 4 weeks (107748).
Topically, when a specific multi-ingredient cream preparation (SS Cream) has been applied to the glans penis, mild pain, local irritation, and burning have occurred (2537).
Endocrine
...The estrogenic effects of ginseng are controversial.
Some clinical evidence suggests it doesn't have estrogen-mediated effects (10981). However, case reports of ginseng side effects such as postmenopausal vaginal bleeding suggest estrogenic activity (590,591,592,10982,10983).
In a 12-year-old Korean-Japanese male, enlargement of both breasts with tenderness in the right breast (gynecomastia) occurred after taking red ginseng extract 500 mg daily orally for one month. Following cessation of the product, there was no further growth or pain (89733). Swollen and tender breasts also occurred in a 70-year-old female using Panax ginseng orally (590).
Gastrointestinal ...Orally, Panax ginseng can cause decreased appetite (3353), diarrhea (3353,89734,103477,112841), abdominal pain (89734,87984,112841), and nausea (589,87984). However, these effects are typically associated with long-term, high-dose usage (3353). Some evidence suggests that fermented Panax ginseng is more likely to cause abdominal pain and diarrhea when compared with unfermented Panax ginseng (112841).
Genitourinary
...Amenorrhea has been reported with oral use of Panax ginseng (3353).
Topically, when a specific multi-ingredient cream preparation (SS Cream) has been applied to the glans penis, sporadic erectile dysfunction and excessively delayed ejaculation have occurred (2537). Less commonly, patients can experience vaginal bleeding (591,592,3354,23630).
Hepatic ...It is unclear if Panax ginseng is associated with adverse hepatic effects. Cholestatic hepatitis has been reported in a 65-year old male following oral use of a combination product containing Panax ginseng and other ingredients (Prostata). However, it is unclear if this adverse effect was due to Panax ginseng, other ingredients, or the combination (598).
Immunologic ...A case of anaphylaxis, with symptoms of hypotension and rash, has been reported following ingestion of a small amount of Panax ginseng syrup (11971).
Neurologic/CNS ...Orally, one of the most common side effects to Panax ginseng is insomnia (589,89734,111336). Headache (594,23638,112840), vertigo, euphoria, and mania (594) have also been reported. Migraine and somnolence occurred in single subjects in a clinical trial (87984). In a case report of a 46-year-old female, orobuccolingual dyskinesia occurred following oral use of a preparation containing black cohosh 20 mg and Panax ginseng 50 mg twice daily for menopausal symptoms. The patient's condition improved once the product was stopped and treatment with baclofen 40 mg and clonazepam 20 mg daily was started (89735).
General
...Orally, schisandra seems to be generally well tolerated.
Most Common Adverse Effects:
Orally: Decreased appetite, heartburn, stomach upset, and urticaria.
Dermatologic ...Orally, schisandra can cause urticaria in some patients (11).
Gastrointestinal ...Orally, schisandra can cause heartburn, decreased appetite, and stomach upset (11).
