Each two gram serving contains: Aconitum Carmichaelii 5.75:1 extract (DHE: 167 mg) 29 mg • Anemarrhena Asphodeloides 5.75:1 extract (DHE: 500 mg) 87 mg • Atractylodes Macrocephala 5.75:1 extract (DHE: 500 mg) 87 mg • Cinnamomum aromaticum 5.75:1 extract (DHE: 500 mg) 87 mg • Ephedra Intermedia 5.75:1 extract (DHE: 334 mg) 58 mg • Glycyrrhiza uralensis 5.75:1 extract (DHE: 167 mg) 29 mg • Paeonia lactiflora 5.75:1 extract (DHE: 500 mg) 87 mg • Saposhnikovia Divaricata 5.75:1 extract (DHE: 500 mg) 87 mg • Zingiber officinale 5.75:1 extract (DHE: 667 mg) 116 mg. Other Ingredients: Corn Starch.
Brand name products often contain multiple ingredients. To read detailed information about each ingredient, click on the link for the individual ingredient shown above.
Below is general information about the effectiveness of the known ingredients contained in the product Gui Zhi Shao Yao Zhi Mu Tang. 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
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 Gui Zhi Shao Yao Zhi Mu Tang. Some ingredients may not be listed. This information does NOT represent a recommendation for or a test of this specific product as a whole.
UNSAFE ...when used orally or topically. Aconite root contains toxic alkaloids that are strong, fast-acting poisons that affect the heart and central nervous system, causing severe arrhythmias, reduced consciousness, and death (15499,19669,30294,30300,30301,30303,30309,30334,30335,30336,92276,104514,106706). All species of this plant are dangerous. Severe poisoning has been reported after ingestion of 0.2-2 mg of aconitine, 1 gram of the raw plant, or 6 grams of processed and cured aconite (3490,104514). Even when a processed product is used, aconite can cause toxicity including nausea, vomiting, dizziness, muscle spasms, hypothermia, paralysis of the respiratory system, and heart rhythm disorders (15499). Aconite can also be absorbed through the skin and cause significant toxicity (12).
PREGNANCY AND LACTATION: UNSAFE
when used orally or topically (15499).
There is insufficient reliable information available about the safety of atractylodes.
PREGNANCY: POSSIBLY UNSAFE
when used orally.
In animals, atractylodes has caused reproductive toxicity, including fetal death, as well as changes in gestation, growth, and skeletal formation (94304).
LACTATION:
There is insufficient reliable information available about the safety of atractylodes when used during breast-feeding.
LIKELY SAFE ...when consumed in amounts commonly found in foods. Cassia cinnamon has Generally Recognized As Safe (GRAS) status in the US for use as a spice or flavoring agent (4912) ...when used orally and appropriately, short-term. Cassia cinnamon 1-2 grams daily has been used safely for up to 3 months (17011,21914). Cassia cinnamon 3-6 grams daily has been used safely for up to 6 weeks (11347,14344). Cassia cinnamon extract corresponding to 3 grams daily of cassia cinnamon powder has also been used safely for up to 4 months (21916).
POSSIBLY SAFE ...when used topically, short-term. Cassia cinnamon oil 5% cream applied topically to the legs has been used safely in one clinical trial (59580).
POSSIBLY UNSAFE ...when used orally in high doses, long-term. Some cassia cinnamon products contain high levels of coumarin. Coumarin can cause hepatotoxicity in animal models (15299,21920). In humans, very high doses of coumarin from 50-7000 mg daily can result in hepatotoxicity that resolves when coumarin use is discontinued (15302). In most cases, ingestion of cassia cinnamon will not provide a high enough amount of coumarin to cause significant toxicity; however, in especially sensitive people, such as those with liver disease, prolonged ingestion of large amounts of cassia cinnamon might exacerbate the condition.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Cassia cinnamon 1 gram daily has been used safely in adolescents 13-18 years of age for up to 3 months (89648).
PREGNANCY AND LACTATION: LIKELY SAFE
when consumed in amounts commonly found in foods (4912).
There is insufficient reliable information available about the safety of cassia cinnamon when used in medicinal amounts during pregnancy and breast-feeding. Stay on the safe side and stick to food amounts.
LIKELY UNSAFE ...when used orally. Ephedra can cause severe life-threatening or disabling adverse effects in some people. Ephedra is banned in the US. Several case reports have linked ephedra to serious side effects including hypertension, myocardial infarction (MI), seizure, stroke, psychosis, and others (1276,2729,6486,6998,9167,10689). Prolonged use or use of high doses might increase the risk of serious adverse effects (2729). Some suggest that ephedra is only harmful when used inappropriately in excessive doses or for prolonged periods. However, there are several cases of significant adverse events in patients who used ephedra short-term in relatively low doses ranging from 20-60 mg of ephedra alkaloids (2729,6486). There is some evidence that people who take doses greater than 32 mg per day might have more than triple the risk of hemorrhagic stroke, including subarachnoid hemorrhage and intracerebral hemorrhage (9167). It is not possible to determine who is at the greatest risk. However, people with pre-existing conditions such as cardiovascular disease or those using ephedra products in combination with other stimulants such as caffeine, might be at increased risk.
CHILDREN: LIKELY UNSAFE
when used orally.
Ephedra has been linked to several cases of severe side effects (6486).
PREGNANCY AND LACTATION: LIKELY UNSAFE
when used orally.
Ephedra has been linked to several cases of severe side effects (1276,2729,6486,6998,9167,10689).
LIKELY SAFE ...when used orally and appropriately. Ginger has been safely used in multiple clinical trials (721,722,723,5343,7048,7084,7085,7400,7623,11346)(12472,13080,13237,13244,17369,17928,17929,89889,89890,89894)(89895,89898,89899,90102,96252,96253,96259,96260,96669) (101760,101761,101762,103359,107903).
POSSIBLY SAFE ...when used topically and appropriately, short-term (89893,89897).
CHILDREN: LIKELY SAFE
when consumed in the amounts typically found in foods.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Ginger powder has been used with apparent safety at a dose of up to 750 mg daily for 4 days in girls aged 14-18 years (96255).
PREGNANCY: LIKELY SAFE
when consumed in the amounts typically found in foods.
Ginger is considered a first-line nonpharmacological treatment option for nausea in pregnancy by the American College of Obstetrics and Gynecology (ACOG) (111601). However, it should not be used long-term or without medical supervision and close monitoring.
PREGNANCY: POSSIBLY SAFE
when used for medicinal purposes.
Despite some early reports of adverse effects (721,7083) and one observational study suggesting that taking dried ginger and other herbal supplements during the first 20 weeks of pregnancy marginally increased the chance of stillbirth (96254), most research shows that ginger is unlikely to cause harm to the baby. The risk for major malformations in infants of parents who took ginger when pregnant does not appear to be higher than the baseline rate of 1% to 3% (721,1922,5343,11346,13071,13080,96254). Also, other research suggests that ginger intake during various trimesters does not significantly affect the risk of spontaneous abortion, congenital malformations, stillbirth, perinatal death, preterm birth, low birth weight, or low Apgar scores (18211,90103). Ginger use has been associated with an increase in non-severe vaginal bleeding, including spotting, after week 17 of pregnancy (18211).
LACTATION: LIKELY SAFE
when consumed in the amounts typically found in foods.
There is insufficient reliable information available about the safety of ginger when used for medicinal purposes; avoid amounts greater than those found in foods.
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.
POSSIBLY SAFE ...when used orally and appropriately, short term. Total glucosides of peony has been used with apparent safety in doses of up to 1800 mg daily for up to 12 months (92786,97949,97950,98466,100992,110432,112861,112862). Peony root extract has been used with apparent safety at a dose of 2250 mg daily for up to 3 months (97216). There is insufficient reliable information available about the safety of peony when used orally, topically, or rectally, long-term.
CHILDREN: POSSIBLY SAFE
when used orally and appropriately, short-term.
Total glucosides of peony has been used with apparent safety in children 1.5-4 years of age at doses up to 180 mg/kg daily or 1.2 grams daily for up to 12 months (92785). Peony root extract 40 mg/kg daily has also been used with apparent safety in children 1-14 years of age for 4 weeks (106851).
PREGNANCY: POSSIBLY UNSAFE
when used orally.
Preliminary research suggests that peony can cause uterine contractions (13400). However, other preliminary research suggests a combination of peony and angelica with or without motherwort, banksias rose, and ligustica, might be safe (11015,48433). Until more is known, avoid use.
LACTATION:
Insufficient reliable information available; avoid using.
Below is general information about the interactions of the known ingredients contained in the product Gui Zhi Shao Yao Zhi Mu Tang. 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, combining aconite with other antiplatelet or anticoagulant drugs might increase the risk of bruising and bleeding.
 Details
Higenamine, a constituent of aconite, is thought to have antiplatelet and antithrombotic effects. In an animal model of thrombosis, higenamine inhibited platelet aggregation and reduced the size of thrombus formation (92282).
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Theoretically, combining aconite with other stimulant drugs might alter the effects of the stimulant drug or increase the risk of cardiovascular toxicity.
Details
Aconite and its constituents have stimulant effects due to agonist activity at beta-2-adrenoreceptors. In cardiac muscle, aconite appears to have a positive inotropic effect and increases heart rate and blood pressure (2634,15499,30296,92282). However, some constituents of aconite can reduce heart rate and blood pressure (15499,30343).
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Theoretically, atractylodes might increase the risk of bleeding when used concomitantly with anticoagulant and antiplatelet drugs.
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Laboratory research suggests that atractylenolides II and III, constituents of atractylodes, reduce platelet activation (94299). So far, this has not been shown in humans.
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Theoretically, atractylodes may have an additive effect when used with other aromatase inhibitors.
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Laboratory research suggests that atractylodes and its constituents exhibit aromatase inhibitor effects (94302).
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Theoretically, atractylodes might decrease the levels of CYP1A2 substrates.
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In animals, atractylodes administered at high doses has been shown to induce CYP1A2 activity (112828). This effect has not been shown in humans.
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Theoretically, atractylodes might increase the levels of CYP3A4 substrates.
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In animals, atractylodes administered at high doses has been shown to inhibit CYP3A1 activity, which is a homolog to the human CYP3A4 enzyme (112828). This effect has not been shown in humans.
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Theoretically, taking atractylodes may prolong the therapeutic and adverse effects of hexobarbital.
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In animals, atractylodes has been shown to prolong the effects of hexobarbital (94303). These effects have not been shown in humans.
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Theoretically, cassia cinnamon may have additive effects with antidiabetes drugs.
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Theoretically, large doses of cassia cinnamon might cause additive effects when used with hepatotoxic drugs.
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There is some concern that ingesting large amounts of cassia cinnamon for an extended duration might cause hepatotoxicity in some people. Cassia cinnamon contains coumarin, which can cause hepatotoxicity in animal models (15299,21920). In humans, very high doses of coumarin from 50-7000 mg/day can result in hepatotoxicity that resolves when coumarin use is discontinued (15302,97249). Lower amounts might also cause liver problems in sensitive people, such as those with liver disease or those taking potentially hepatotoxic agents.
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Theoretically, ephedra may reduce the effects of anticonvulsants.
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Ephedra has been associated with reports of seizure (13304).
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Theoretically, taking ephedra with antidiabetes drugs might interfere with blood glucose control.
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One study in animals shows that some components of ephedra may lower blood glucose levels (48835). However, most human research suggests that ephedra and ephedrine, a component of ephedra, can raise blood glucose levels and might decrease the effectiveness of drug therapy (3719,12857,48810). Monitor blood glucose concentrations closely.
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Theoretically, large amounts of ephedra might increase the cardiac inotropic effects of beta-agonists.
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Theoretically, ephedra might decrease levels of drugs metabolized by CYP1A2.
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Some animal research suggests that ephedra induces CYP1A2 and increases the clearance of CYP1A2 substrates such as caffeine (91808).
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Theoretically, concomitant use might reduce the levels and clinical effects of dexamethasone.
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Theoretically, concomitant use might increase the risk of hypertension.
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The ephedrine contained in ephedra might cause excessive vasoconstriction and hypertension when used in combination with ergot derivatives (6009).
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Theoretically, concomitant use might have additive adverse hepatotoxic effects.
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Concomitant use might increase the risk of serious adverse effects.
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Use of ephedra with caffeine or other methylxanthines such as theophylline might increase the risk of stimulatory adverse effects (8641,24180). There is also some evidence that using ephedra with caffeine might increase the risk of serious life-threatening or debilitating adverse effects such as hypertension, myocardial infarction (MI), stroke, seizures, and death (1275,6486,10307,48751,54423,54429).
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Theoretically, concomitant use might increase the risk of serious adverse effects.
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Theoretically, ephedra might have an additive effect with drugs that prolong the QT interval.
Details
Even in healthy volunteers, EKG changes including prolonged QT interval and premature atrial contractions have been reported with ingestion of recommended doses of ephedra (11135,11708). Ephedra may have an additive effect with drugs that prolong the QT interval. This may increase the risk of ventricular arrhythmias (11355,48765).
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Theoretically, concomitant use might increase the risk for serious adverse effects.
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Ginger may have antiplatelet effects and may increase the risk of bleeding if used with anticoagulant or antiplatelet drugs. However, research is conflicting.
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Laboratory research suggests that ginger inhibits thromboxane synthetase and decreases platelet aggregation (7622,12634,20321,20322,20323,96257). However, this has not been demonstrated unequivocally in humans, with mixed results from clinical trials (96257). Theoretically, excessive amounts of ginger might increase the risk of bleeding when used with anticoagulant/antiplatelet drugs.
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Theoretically, taking ginger with antidiabetes drugs might increase the risk of hypoglycemia.
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Theoretically, taking ginger with calcium channel blockers might increase the risk of hypotension.
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Some animal and in vitro research suggests that ginger has hypotensive and calcium channel-blocking effects (12633). Another animal study shows that concomitant administration of ginger and the calcium channel blocker amlodipine leads to greater reductions in blood pressure when compared with amlodipine alone (107901).
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Theoretically, when taken prior to cyclosporine, ginger might decrease cyclosporine levels.
Details
In an animal model, ginger juice taken 2 hours prior to cyclosporine administration reduced the maximum concentration and area under the curve of cyclosporine by 51% and 40%, respectively. This effect was not observed when ginger juice and cyclosporine were administered at the same time (20401).
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Theoretically, ginger might increase the levels of CYP1A2 substrates.
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In vitro research shows that ginger inhibits CYP1A2 activity (111544). However, this interaction has not been reported in humans.
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Theoretically, ginger might increase the levels of CYP2B6 substrates.
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In vitro research shows that ginger inhibits CYP2B6 activity (111544). However, this interaction has not been reported in humans.
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Theoretically, ginger might increase the levels of CYP2C9 substrates.
Details
In vitro research shows that ginger inhibits CYP2C9 activity (111544). However, this interaction has not been reported in humans.
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Ginger might increase or decrease the levels of CYP3A4 substrates.
Details
In vitro research and some case reports suggest that ginger inhibits CYP3A4 activity (111544,111644). Three case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are CYP3A4 substrates (imatinib, dabrafenib, and crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644).
Conversely, other in vitro research suggests that ginger induces CYP3A4 activity, leading to reduced levels of CYP3A4 substrates (111404). However, this interaction has not been reported in humans. |
Theoretically, ginger might increase levels of losartan and the risk of hypotension.
Details
In animal research, ginger increased the levels and hypotensive effects of a single dose of losartan (102459). It is not clear if ginger alters the concentration or effects of losartan when taken continuously. Additionally, this interaction has not been shown in humans.
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Theoretically, ginger might increase levels of metronidazole.
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In an animal model, ginger increased the absorption and plasma half-life of metronidazole. In addition, the elimination rate and clearance of metronidazole was significantly reduced (20350).
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Ginger may have antiplatelet effects and increase the risk of bleeding if used with nifedipine.
Details
Clinical research shows that combined treatment with ginger 1 gram plus nifedipine 10 mg significantly inhibits platelet aggregation when compared to nifedipine or ginger alone (20324).
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Ginger might increase the absorption and blood levels of P-glycoprotein (P-gp) substrates.
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In vitro research and case reports suggest that ginger inhibits drug efflux by P-gp, potentially increasing absorption and serum levels of P-gp substrates (111544,111644). Two case reports from the World Health Organization (WHO) adverse drug reaction database describe increased toxicity in patients taking ginger and cancer medications that are P-gp substrates (trametinib, crizotinib). However, the causality of this interaction is unclear due to the presence of multiple interacting drugs and routes of administration (111644).
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Ginger might increase the risk of bleeding with phenprocoumon.
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Phenprocoumon, a warfarin-related anticoagulant, might increase the international normalized ratio (INR) when taken with ginger. There is one case report of a 76-year-old woman with a stable INR on phenprocoumon that increased to greater than 10 when she began consuming dried ginger and ginger tea (12880).
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Ginger might increase the risk of bleeding with warfarin.
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Laboratory research suggests that ginger might inhibit thromboxane synthetase and decrease platelet aggregation (7622,12634,20321,20322,20323). In one case report, ginger increased the INR when taken with phenprocoumon, which has similar pharmacological effects as warfarin (12880). In another case report, ginger increased the INR when taken with a combination of warfarin, hydrochlorothiazide, and acetaminophen (20349). A longitudinal analysis suggests that taking ginger increases the risk of bleeding in patients taking warfarin for at least 4 months (20348). However, research in healthy people suggests that ginger has no effect on INR, or the pharmacokinetics or pharmacodynamics of warfarin (12881,15176). Until more is known, monitor INRs closely in patients taking large amounts of ginger.
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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.
Details
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.
Details
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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Theoretically, combining peony with anticoagulant or antiplatelet drugs might increase the risk of bleeding.
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In vitro research suggests that peony might have antiplatelet, anticoagulant, and antithrombotic effects (92787).
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Theoretically, peony might increase the levels and clinical effects of clozapine.
Details
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on cytochromes P450 (CYP) 1A2 and CYP3A4 (92790). This effect has not been reported in humans.
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Theoretically, peony might interfere with contraceptive drugs due to competition for estrogen receptors.
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In vitro and animal research shows that peony extract has estrogenic activity (100990). Concomitant use might also increase the risk for estrogen-related adverse effects.
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Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP1A2.
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In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4 (92790). This effect has not been reported in humans.
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Theoretically, use of peony may increase the levels and clinical effects of drugs metabolized by CYP3A4.
Details
In vitro research shows that peony suppresses the metabolism of clozapine via weak-to-moderate inhibitory effects on CYP1A2 and CYP3A4 (92790). This effect has not been reported in humans.
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Theoretically, concomitant use of large amounts of peony might interfere with hormone replacement therapy and/or increase the risk for estrogen-related adverse effects.
Details
In vitro and animal research shows that peony extract has estrogenic activity (100990). Theoretically, peony might compete for estrogen receptors and/or cause additive estrogenic effects.
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Theoretically, peony might reduce the levels and clinical effects of phenytoin.
Details
Animal research shows that taking peony root reduces levels of phenytoin (8657). Some researchers suggest that peony root might affect cytochrome P450 (CYP) 2C9, which metabolizes phenytoin. However, preliminary research in humans shows that peony root does not alter levels of losartan (Cozaar), which is also metabolized by CYP2C9 (11480).
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Below is general information about the adverse effects of the known ingredients contained in the product Gui Zhi Shao Yao Zhi Mu Tang. 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 topically, aconite is generally regarded as unsafe for use.
Any benefits of therapy might not outweigh the risk of toxicity.
Most Common Adverse Effects:
All routes of administration: Serious neurologic, cardiovascular, gastrointestinal, and respiratory adverse effects have been reported.
Cardiovascular ...Orally and topically, aconite can cause hypotension, palpitations, chest tightness, pulmonary edema, arrhythmia, bradycardia, tachycardia, sustained or bidirectional ventricular tachycardia, ventricular fibrillation, and Torsade de pointes (558,559,561,562,563,3490,15499,15650,30294,30295)(30300,30305,30323,30336,92276,92277,92278,104514,106706,110473)(112901). Cardioversion has been reported to be ineffective for the reversal of aconite-induced dysrhythmia, but the use of agents such as amiodarone, lidocaine, and magnesium have been successful in some cases (2634,3490,106706,112901).
Gastrointestinal ...Orally, aconite can cause nausea, vomiting, diarrhea, and gastric pain (563,30297,30341,92277,92278). Topically, aconite can cause nausea and vomiting (92276).
Neurologic/CNS ...Orally, aconite can cause weakness, sweating, restlessness, dizziness, numbness, paresthesia, seizures, and reduced consciousness (558,559,561,562,563,3490,15499,15650,30335,30336,30341,92277,92278,104513). Topically, aconite can cause generalized paresthesia, fatigue, sweating, dizziness and tongue numbness (92276).
Ocular/Otic ...Orally, aconite has been reported to cause visual blurring and yellow-green vision with pupil dilation (30319).
Pulmonary/Respiratory ...Orally, aconite overdose can lead to respiratory failure (104513).
Renal ...Orally and topically, aconite can cause hypokalemia and metabolic and/or respiratory acidosis (558,559,561,562,563,3490,15499,15650).
Other
...Orally and topically, aconite has been reported to cause death in both adults and children (559,3490,3491,30301,30334,30341,92276,92278).
In one case report, topical application of aconite to an infant led to cardiogenic shock with multi-organ failure and death (92276). Poisoning has been reported in 15 patients after consuming a homemade liquor containing aconite. Patients presented with tongue or extremity numbness, vomiting, dizziness, or heart palpitations, and 5 died (110471). Death has also been reported in individuals who cooked aconite tubers as vegetables or for health purposes (92278).
The first symptoms of aconite poisoning after oral ingestion of the leaves or root usually occur within 10-90 minutes, although toxicity may be delayed until a second or third dose (559,15499,104513,110471). Recovery time from aconite poisoning ranges from 1.5-2 days for mild intoxication to 7-9 days for patients with cardiovascular complications; fatalities in treated patients are about 5% (15499). Treatment of aconite toxicity is typically supportive, although charcoal hemoperfusion has aided in detoxification (15499,106706).
General
...There is currently a limited amount of information on the adverse effects of atractylodes.
A thorough evaluation of safety outcomes has not been conducted.
Most Common Adverse Effects:
Orally: Allergic reaction, dry mouth, nausea.
Gastrointestinal ...Orally, atractylenolide I, an isolated constituent of atractylodes, can cause bad taste, nausea, and dry mouth (15706).
Immunologic ...Atractylodes can cause an allergic reaction in people sensitive to the Asteraceae/Compositae family (12450). Members of this family include ragweed, chrysanthemums, marigolds, daisies, and many other herbs.
General
...Orally, cassia cinnamon appears to be well-tolerated.
Significant side effects have not been reported in most patients.
Most Common Adverse Effects:
Topically: Burning mouth, stomatitis.
Dermatologic
...In one clinical trial, a rash was reported in one patient taking cassia cinnamon 1 gram daily for 90 days (17011).
In one case, a 58-year-old female with a documented allergy to topically applied cinnamic alcohol presented with eyelid dermatitis, which was found to be a manifestation of systemic contact dermatitis to cinnamon in the diet. Symptoms improved in two days and completely cleared five days after discontinuing the addition of cinnamon to food products (95599). In other case reports, two adults presented with allergic contact cheilitis following the ingestion of chai tea with cinnamon and yogurt with cinnamon. Cinnamon components were confirmed as the causative allergic agents with patch tests, and both cases of allergic contact cheilitis completely resolved upon cessation of the cinnamon-containing products (113516,113515).
Topically, allergic skin reactions and stomatitis from toothpaste flavored with cassia cinnamon have been reported (11915,11920). Intraoral allergic reactions with symptoms of tenderness and burning sensations of the oral mucosa have also been reported in patients using breath fresheners, toothpaste, mouthwash, candy, or chewing gum containing cinnamon, cinnamic aldehyde or cinnamic alcohol as flavoring agents. Glossodynia, or burning mouth syndrome, has also been reported in a 62-year-old female who ate apples dipped in cinnamon nightly (95598), and allergic contact dermatitis has been reported in a teenage female using a homemade cinnamon sugar face scrub (95596).
Endocrine ...In one clinical trial, a hypoglycemic seizure was reported in one patient taking cassia cinnamon 1 gram daily for 3 months. The event occurred one day after enrolling in the study (89648). It is unclear if cassia cinnamon caused this event.
Hepatic ...There is some concern about the safety of ingesting large amounts of cassia cinnamon for extended durations due to its coumarin content. Coumarin can cause hepatotoxicity in animal models (15299). In humans, very high doses of coumarin from 50-7000 mg/day can result in hepatotoxicity that resolves when coumarin is discontinued (15302). In clinical trials, taking cassia cinnamon 360 mg to 12 grams daily for 3 months did not significantly increase levels of aspartate transaminase (AST) or alanine transaminase (ALT) (21918,96280,108259). However, in one case report, acute hepatitis with elevated AST and ALT occurred in a 73-year-old female who started taking a cinnamon supplement (dose unknown) one week prior to admission. The cinnamon supplement was added on to high-dose rosuvastatin, which may have led to additive adverse hepatic effects. After discontinuing both products, liver function returned to normal, and the patient was able to restart rosuvastati without further complications (97249). In most cases, ingestion of cassia cinnamon won't provide a high enough amount of coumarin to cause significant toxicity; however, in especially sensitive people, such as those with liver disease or taking potentially hepatotoxic agents, prolonged ingestion of large amounts of cassia cinnamon might exacerbate the condition.
Immunologic ...An unspecified allergic reaction was reported in one patient taking cassia cinnamon 1 gram daily for 3 months (89648).
General
...Orally, ephedra is frequently associated with adverse reactions and is banned in the US.
In some cases, adverse effects can be severe or life-threatening. Large studies looking at the safety of ephedra have not been performed. Since most of the adverse effect data are from case reports, it is impossible to determine the overall incidence of these adverse effects. It is also difficult to determine which patient groups might be most likely to experience an adverse event.
Most Common Adverse Effects:
Orally: Anorexia, anxiety, difficulty concentrating, difficulty urinating, dizziness, dry mouth, flushing, headache, heartburn, hyperthermia, hypertension, insomnia, irritability, nausea, personality changes, polydipsia, restlessness, tachycardia, tingling, and vomiting.
Serious Adverse Effects (Rare):
Orally: Cardiac arrest, cardiac arrhythmia, cardiomyopathy, heart failure, hepatotoxicity, myocardial infarction, myopathies, psychosis, seizure, stroke, and sudden death.
Cardiovascular
...The use of ephedra causes a 2.
2- to 3.6-fold increase in the risk of developing psychiatric, autonomic, or gastrointestinal (GI) symptoms and cardiac palpitations (9740,48878). Orally, ephedra use has been associated with cardiomyopathy (1270,48801), hypersensitivity myocarditis (1271,6487,48738,48739), chest tightness, myocardial infarction (6486), cardiac arrest and sudden death (1274,6486), hypertension, tachycardia, and cardiac arrhythmias (6009,8643,35749,35750,37689,48736,48737,48805,48847,48870,48872). Ephedrine abuse has led to heart failure (48813). Even in healthy volunteers, EKG changes including prolonged QT interval and premature atrial contractions can occur with ingestion of recommended doses of ephedra containing products (11135,11708). In a review of 926 cases reported to the FDA of possible adverse effects of ephedra, 37 patients had serious or fatal adverse reactions. Ephedra use was temporally related to 16 strokes, 10 myocardial infarctions, and 11 sudden deaths. These effects occurred in people aged 30-56 years. There is some evidence that people who take doses greater than 32 mg daily might have more than triple the risk of hemorrhagic stroke, including subarachnoid hemorrhage and intracerebral hemorrhage, when compared with those taking doses of less than 32 mg daily (9167,48771).
Ephedrine, the primary active ingredient in ephedra, has been associated with coronary artery spasm, myocardial injury with pulmonary edema, and cardiovascular collapse (48867,48872,48783). However, several clinical trials evaluating ephedrine-caffeine combinations for weight loss reported no differences in mean heart rate or blood pressure when compared to placebo (37617,48792,48865,48882). Other preliminary clinical research showed that ephedrine and caffeine use by prescription did not result in increased risk of adverse cardiovascular outcomes (48806).
Endocrine ...One study in animals shows that some components of ephedra may lower blood glucose levels (48835). However, most human research suggests that ephedra and ephedrine, a component of ephedra, can raise blood glucose and insulin levels (3719,12857,48810).
Gastrointestinal ...The use of ephedra causes a 2. 2- to 3.6-fold increase in the risk of developing psychiatric, autonomic, or gastrointestinal (GI) symptoms and cardiac palpitations (9740,48878). Orally and intravenously, ephedra and ephedrine most commonly cause dry mouth, anorexia, nausea, vomiting, heartburn, abdominal discomfort, and changes in stool consistency (1276,3719,6008,6486,8647,10004,10382,37831,48817,48837). One case of ischemic colitis and symptoms of abdominal pain and bloody diarrhea associated with the use of a weight loss supplement containing ephedra has been reported (48803).
Hepatic ...Cases of hepatotoxicity such as acute hepatitis and liver failure from ephedra-containing supplements have been reported. Some cases of hepatotoxicity resolved after discontinuation of ephedra, while others required liver transplantation. In obese patients using ephedra for weight loss, it is possible that ephedra exacerbated pre-existing liver disease. Onset of liver injury seems to occur an average of 3 months after ephedra ingestion, suggesting an idiosyncratic mechanism of liver injury (1273,48747,48800,94875,94876,94877,81600,98441). Previously, it was thought that the cause of ephedra hepatotoxicity was an immune reaction or a contamination. However, since the majority of evidence suggests that hepatotoxicity is idiosyncratic, these prior postulations have since been dismissed (1273,48747,81600,98441).
Musculoskeletal ...Orally, ephedra has been reported to cause myopathies, including myalgia, rhabdomyolysis, and eosinophilia-myalgia syndrome (1270,16054,48791).
Neurologic/CNS
...The use of ephedra causes a 2.
2- to 3.6-fold increase in the risk of developing psychiatric, autonomic, or gastrointestinal (GI) symptoms and cardiac palpitations (9740,48878). Ephedra most commonly causes dizziness, restlessness, anxiety, irritability, personality changes, difficulty concentrating, insomnia, and headache (1276,3719,6008,6486,8647,10004,10382).
Ephedra can cause seizures in otherwise healthy people, as well as in people with underlying seizure disorders (10307,48870). Of 33 seizures linked to dietary supplement use that were reported to the FDA over 7 years, 27 involved ephedra (13304). Other adverse events reported with ephedra use include sudden hearing loss, stroke, transient ischemic attack, cerebral hemorrhage, and loss of consciousness (1275,1381,2729,6486,8643,9167,10005,48746,48862). In one case-control study, doses of ephedra above 32 mg daily have been associated with an increased risk for hemorrhagic stroke (9167). A case of encephalopathy syndrome with multi-organ failure and transient cortical blindness after ingestion of a performance-enhancing ephedra supplement has been reported. Symptoms were resolved after blood pressure was corrected (48788).
Ocular/Otic ...A case of encephalopathy syndrome with transient cortical blindness after ingestion of an ephedra supplement has been reported. Symptoms were resolved after blood pressure was corrected (48788). A case of sudden hearing loss following the use of ephedra has also been reported (48761).
Psychiatric
...The use of ephedra causes a 2.
2- to 3.6-fold increase in the risk of developing psychiatric, autonomic, or gastrointestinal (GI) symptoms and cardiac palpitations (9740,48878). Ephedra most commonly causes anxiety, irritability, personality changes, difficulty concentrating, and insomnia (1276,3719,6008,6486,8647,10004,10382).
Cases of ephedrine-induced psychiatric complications (6998) include mania (48855), psychosis (1276,6998,10689,48751,48841,48843), and hallucinations (48857). In some cases psychosis can be prolonged for several months after discontinuation (1276,6998,10689). A case of a suicide attempt and mood disorder associated with the use of a diet pill containing ephedra has also been reported (48752).
Long-term use of ephedra or use in high doses has been associated with dependence and tolerance (1381).
Renal ...Orally, ephedra has been reported to cause nephrolithiasis (1272,48877), diuresis, urinary retention, and dysuria (16054,48791).
General
...Orally, ginger is generally well tolerated.
However, higher doses of 5 grams per day increase the risk of side effects and reduce tolerability. Topically, ginger seems to be well tolerated.
Most Common Adverse Effects:
Orally: Abdominal discomfort, burping, diarrhea, heartburn, and a pepper-like irritant effect in the mouth and throat. However, some of these mild symptoms may be reduced by ingesting encapsulated ginger in place of powdered ginger.
Topically: Dermatitis in sensitive individuals.
Cardiovascular ...Orally, use of ginger resulted in mild arrhythmia in one patient in a clinical trial (16306).
Dermatologic
...Orally, ginger can cause hives (17933), as well as bruising and flushing (20316) or rash (20316).
Topically, ginger can cause dermatitis in sensitive individuals (12635,46902).
Gastrointestinal
...Orally, common side effects of ginger include nausea (17933,22602,89898,101761), belching (10380,103359), dry mouth (103359), dry retching (10380), vomiting (10380), burning sensation (10380), oral numbness (22602), abdominal discomfort (5343,89898,96253), heartburn (5343,7624,12472,16306,20316,51845,89894,89895,89898,89899)(101760,101761,101762,111543), diarrhea (5343,101760), constipation (89898,101760,101761), or a transient burning or "chilly hot" sensation of the tongue and throat (52076).
Orally, Number Ten, a specific product composed of rhubarb, ginger, astragalus, red sage, and turmeric, can increase the incidence of loose stools (20346).
Four cases of small bowel obstruction due to ginger bolus have been reported following the ingestion of raw ginger without sufficient mastication (chewing). In each case, the bolus was removed by enterotomy. Ginger is composed of cellulose and therefore is resistant to digestion. It can absorb water, which may cause it to swell and become lodged in narrow areas of the digestive tract (52115).
Genitourinary ...In one clinical trial, some patients reported increased menstrual bleeding while taking a specific ginger extract (Zintoma, Goldaru) 250 mg four times daily orally for 3 days (17931). An "intense" urge to urinate after 30 minutes was reported in two of eight patients given 0.5-1 gram of ginger (7624). However, this effect has not been corroborated elsewhere. Dysuria, flank pain, perineal pain, and urinary stream interruption have been reported in a 43-year-old male who drank ginger tea, containing 2-3 teaspoons of dry ginger, daily over 15 years. The adverse effects persisted for 4 years and were not associated with increases in urinary frequency or urgency. Upon discontinuing ginger, the patient's symptoms began to improve within one week and completely resolved after eight weeks, with no relapses six months later (107902).
Immunologic ...In one case report, a 59-year-old Japanese female with multiple allergic sensitivities developed pruritus and then anaphylactic shock after taking an oral ginger-containing herbal supplement for motion sickness (Keimei Gashinsan, Keimeido). The patient had used this supplement previously for over 20 years with no allergic reaction. The authors theorized the development of a cross-reactivity to ginger after the use of an oral supplement containing zedoary and turmeric, which are also in the Zingiberaceae family (102463).
Neurologic/CNS ...Orally, ginger may cause sedation, drowsiness, or dizziness (16306,17933,51845).
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, peony seems to be well tolerated when used alone and as part of Chinese herbal formulas.
Most Common Adverse Effects:
Orally: Abdominal distension, anorexia, diarrhea, gastrointestinal discomfort, nausea.
Topically: Dermatitis.
Dermatologic ...Topically, peony has been reported to cause contact dermatitis (13555).
Endocrine ...Orally, a specific traditional Chinese medicine preparation called DDT has been reported to lower follicle-stimulating hormone (FSH) levels and increase estradiol levels. It is not known if this effect is due to peony or the other ingredients (48404). Another specific traditional Chinese medicine preparation, Toki-shakuyaku-san, has been reported to increase plasma progesterone levels in some patients. It is not known if this effect is due to peony or the other ingredients (15294).
Gastrointestinal ...Orally, peony and total glucosides of peony (TGP) have been reported to cause gastrointestinal discomfort, including abdominal distension, anorexia, diarrhea, and nausea, in some patients (13538,92785,97949,98466,100992). In one clinical study, diarrhea was reported in 5% of patients taking TGP 600 mg three times daily for 24 weeks versus 1% of patients taking placebo (100992).
Hematologic ...Orally, there is one case report of easy gum bleeding, epistaxis, and skin bruising with an international normalized ratio (INR) above 6 in a 61-year-old male who was previously stable on warfarin therapy. This patient had switched from one brand of quilinggao, a popular Chinese herbal product, to another brand 5 days prior. This product contained Fritillaria spp. (beimu), Paeonia rubra, Chinese peony (chishao), Lonicera japonica (jinyinhua), and Poncirus trifoliata (jishi). The patient's INR decreased to 1.9 after temporary withdrawal of warfarin therapy. Upon re-initiation of quilinggao, his INR increased to 5.2. It is not known if the increased INR is due to peony or the other ingredients (68343).
