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INSUFFICIENT RELIABLE EVIDENCE to RATE

• Allergic rhinitis (hay fever). Although there has been interest in using oral hu zhang for allergic rhinitis, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Biliary disorders. Although there has been interest in using oral hu zhang for biliary disorders, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Constipation. Although there has been interest in using oral hu zhang for constipation, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Diabetes. Although there has been interest in using oral hu zhang for diabetes, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Gout. Although there has been interest in using oral hu zhang for gout, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Hepatitis. Although there has been interest in using oral hu zhang for hepatitis, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Menopausal symptoms. Although there has been interest in using oral hu zhang for menopausal symptoms, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Osteoarthritis. Although there has been interest in using oral hu zhang for osteoarthritis, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Rheumatoid arthritis (RA). Although there has been interest in using oral hu zhang for RA, there is insufficient reliable information about the clinical effects of hu zhang for this purpose.
• Unstable angina. Oral hu zhang has only been evaluated in combination with other ingredients; its effect when used alone is unclear. Details: One clinical study in patients hospitalized with unstable angina shows that taking hu zhang granules 7.5 grams and hawthorn granules 5 grams twice daily for 4 weeks, along with conventional therapy, improves quality of life and angina symptom scores, but does not reduce the frequency of angina attacks, when compared with conventional therapy alone (109610).
• Wound healing. Although there has been interest in using topical hu zhang for wound healing, there is insufficient reliable information about the clinical effects of hu zhang for this purpose. More evidence is needed to rate hu zhang for these uses.

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POSSIBLY EFFECTIVE

• Cardiovascular disease (CVD). In otherwise healthy adults, most population research shows that light to moderate consumption of alcoholic beverages, including wine, reduces the risk of developing coronary heart disease, myocardial infarction (MI), and ischemic stroke and reduces the risk of cardiovascular death. However, the definition of "moderate consumption" is unclear. Details: Consumption of alcoholic drinks, including wine, by otherwise healthy adults seems to reduce the risk of developing CVD. Moderate alcohol use (one to two drinks daily) reduces the risk of coronary heart disease, atherosclerosis, and MI by approximately 30% to 50% when compared with nondrinkers (2267,2268,2271,6888,6892,8648,8649,10128,11879,96690). Other observational research has found that drinking one or fewer glasses of wine weekly over 10 years is associated with a 60% lower risk of cardiovascular events. Light to moderate alcohol consumption also seems to reduce the risk of ischemic stroke (2271,2279,6834,6842,6893). But one large analysis has shown that individuals who report light to moderate consumption of alcohol have overall healthier lifestyles than those who abstain from alcohol and that adjusting for these lifestyle factors attenuates any of the cardioprotective epidemiological effects that have been associated with light to moderate alcohol intake (107884). Drinking more than one glass of wine weekly is not associated with lower cardiovascular risk when compared with abstaining from alcohol (102886).There is some evidence that light to moderate consumption of alcoholic drinks (one to two drinks daily), including wine, can also reduce the risk of all-cause mortality in people who are middle-aged or older (2058,6823,6837,6843). Conversely, consuming any amount of alcohol can increase the risk of hemorrhagic stroke (841,2271,6842). Light to moderate consumption of alcohol might also reduce the risk of cardiovascular mortality in otherwise healthy adults (2058,2270,6835,6837). Light to moderate alcohol consumption in the year prior to a first acute MI is associated with reduced cardiovascular and all-cause mortality risk when compared with non-drinkers (8650). Consumption of one alcoholic beverage daily or consuming alcohol on at least 3 to 4 days weekly is a good rule of thumb for people who drink alcohol. Tell patients not to exceed two drinks daily. More than two drinks daily can increase the risk of cardiovascular and overall mortality (841,2060,2261,6173,6890,8648,11879). Alcohol consumption has also been evaluated in patients with existing CVD, with some mixed findings. A meta-analysis of cohort data as well as published observational and randomized controlled studies in patients with existing CVD has found that consumption of 6-8 grams of alcohol daily is associated with a 21%, 27%, and 50% reduction in all-cause mortality, cardiovascular mortality, and cardiovascular events, respectively, when compared with non-drinkers (107817). Conversely, in males with established coronary heart disease (CHD), consumption of 1-14 alcoholic drinks weekly, including wine, does not seem to have any effect on CVD or all-cause mortality when compared with males who drink less than one drink weekly. Further, in males with a history of MI, consuming three or more drinks daily is associated with increased mortality (6173).
• Cognitive function. Consumption of up to one alcoholic drink daily seems to improve general cognitive function in older males. Details: Observational research has found that elderly males who have a history of consuming up to one alcoholic drink daily seem to maintain better general cognitive function during their late 70s and 80s when compared with non-drinkers (6824,6829). However, consumption of more than four drinks daily during middle age seems to be associated with significantly poorer cognitive function in later life (6824).
• Diabetes. Light to moderate consumption of alcohol, including wine, is associated with a reduced risk of developing type 2 diabetes and a reduced risk of coronary heart disease (CHD) in those with existing type 2 diabetes. However, the benefits of wine in the management of type 2 diabetes are unclear. Details: Observational research in healthy males has found that light to moderate alcohol consumption from wine and other sources is associated with a reduced risk of developing type 2 diabetes (6172,6891). A meta-analysis of 13 population studies has found that drinking about 1.5-2 five-oz glasses of wine daily is associated with the greatest reduction in the risk of developing diabetes in both males and females, with a 20% lower risk when compared with never drinking wine (96699). Additionally, in patients with a history of gestational diabetes, consuming approximately 3 servings of wine weekly is associated with a 44% to 54% lower risk of developing type 2 diabetes when compared with no consumption in age-adjusted and multivariate analyses, although this result was no longer significant when adjusted for BMI. Consumption of 1-2 servings of wine weekly was associated with a 42% lower risk of developing type 2 diabetes in age-adjusted analyses only (105948). Light to moderate alcohol consumption, including wine, is also associated with a reduced risk of coronary heart disease (CHD) in males and females with type 2 diabetes when compared with non-drinkers with type 2 diabetes. The risk reduction for CHD associated with light to moderate alcohol consumption in patients with type 2 diabetes is similar to that found in people without diabetes who consume light to moderate amounts of alcohol (8653,8654). Additionally, a cross-sectional study in patients with type 2 diabetes has found an inverse association between moderate alcohol consumption and carotid intima media thickness (107816). However, despite these promising results in observational research, clinical studies specifically addressing wine consumption in patients with type 2 diabetes show mixed results. A meta-analysis of 9 small clinical studies, most of which had a short follow-up period, shows that moderate wine consumption does not improve glycemic control, blood pressure, or lipid levels when compared with control beverages or alcohol abstinence in patients with type 2 diabetes (103187). However, another study not included in the above analysis that evaluated people with diabetes who abstained from alcohol prior to the study shows that drinking 5 oz of white wine, but not red wine, daily for 2 years reduces fasting blood glucose by 17 mg/dL and reduces homeostatic model assessment of insulin resistance (HOMA-IR) score by 1.2 when compared with drinking mineral water. In a subgroup analysis of slow ethanol metabolizers (homozygous carriers of the wild-type C alcohol dehydrogenase alleles, ADH1B*1), drinking red or white wine improves glycemic control when compared with patients that are fast ethanol metabolizers (homozygous for ADH1B*2) (96697). Another clinical study in patients with type 2 diabetes who are consuming a Mediterranean diet shows that drinking 150 mL of red or white wine daily with dinner for 2 years prevents progression of carotid atherosclerosis, though no progression occurred in a control group consuming 150 mL of mineral water daily with dinner (99641).
• Helicobacter pylori. Moderate to high alcohol consumption seems to reduce the risk of Helicobacter pylori infection. Details: Observational research has found that moderate to high consumption of alcohol, more than 75 grams weekly, from beverages such as beer and wine, is associated with a reduced risk of Helicobacter pylori infection (8034).
• Osteopenia. Observational research suggests that moderate alcohol consumption may improve bone mineral density (BMD) in postmenopausal patients. Details: Observational research has found that moderate alcohol consumption in postmenopausal patients is associated with increased BMD in the trochanter, femoral neck, mid-radius, and lumbar spine (6825,6836,8655). Alcohol intake of one-half to one drink daily seems to have the greatest effect on BMD when compared with non-drinkers and heavy drinkers of alcohol (8655).
• Overall mortality. Light to moderate alcohol consumption seems to reduce the risk of all-cause mortality in middle-aged or older adults. Details: Observational research has found that light to moderate consumption of alcohol is associated with a reduced risk of all-cause mortality in people who are middle-aged or older (2058,6823,6837,6843).

INSUFFICIENT RELIABLE EVIDENCE to RATE

• Alzheimer disease. It is unclear if wine consumption is beneficial for preventing Alzheimer disease. Details: A meta-analysis of observational research has found that light to moderate consumption of alcohol (less than 7.5 drinks weekly or 12.5 grams daily), preferably wine, is associated with a reduced risk of developing dementia, including Alzheimer disease, when compared with non-drinkers. The lowest risk of dementia was observed with consumption of 4 drinks weekly or 6 grams daily (97063).
• Anxiety. It is unclear if alcohol consumption is beneficial for anxiety. Details: The effect of alcohol on anxiety is complex and may be affected by the psychological state of the user. It sometimes reduces anxiety, sometimes increases it, and sometimes has no effect (2266).
• Atherosclerosis. It is unclear if moderate alcohol consumption is beneficial for atherosclerosis. Details: A cross-sectional study in patients with type 2 diabetes has found an inverse association between moderate alcohol consumption and carotid intima media thickness (107816).
• Cancer. It is unclear if wine consumption is beneficial for preventing cancer or cancer-related mortality. The available evidence suggests variable effects depending on cancer type. Details: Observational research has found that intake of up to 21 alcoholic drinks weekly, including wine, might slightly reduce the risk of cancer-related mortality (6823). Moderate consumption of wine has also been associated with a DECREASED risk of developing bladder cancer (97989), brain cancer (96695), renal cell cancer (97060,97064), and multiple myeloma (97990). However, wine intake is not associated with changes in the risk of colorectal cancer (103189), endometrial cancer (97065) or gastric cancer (96694). Furthermore, wine consumption has been associated with an INCREASED risk of breast cancer (96686) and skin cancer (97991). Results of a meta-analysis suggest that moderate to heavy consumption of alcohol, including wine, in males is associated with an 11% reduction in the risk of developing non-Hodgkin lymphoma (99638).
• Congestive heart failure (CHF). While light to moderate consumption of alcohol is associated with a reduced risk of developing CHF in older adults and a reduction in all-cause mortality in those with ischemic left ventricular (LV) dysfunction, it is unclear if moderate wine consumption is associated with these benefits. Details: Observational research in adults 65 years or older has found that consuming 1-4 alcoholic drinks daily is associated with a reduced risk of CHF (8104). There is conflicting evidence about whether moderate alcohol consumption improves outcomes in patients that already have CHF, although no exacerbation of CHF was found. Consumption of 1-14 alcoholic drinks per week is associated with reduced all-cause mortality in people with ischemic LV dysfunction when compared with non-drinkers with ischemic LV dysfunction. This benefit does not seem to occur for those patients with non-ischemic LV dysfunction (6827). However, other observational research has not found an inverse association between moderate wine consumption and rates of all-cause mortality, sudden death, or hospitalization in chronic heart failure patients (96689).
• Dementia. It is unclear if wine consumption is beneficial for dementia. Details: A meta-analysis of observational research has found that light to moderate consumption of alcohol (less than 7.5 drinks weekly or 12.5 grams daily), preferably wine, is associated with a reduced risk of all-cause dementia when compared with non-drinkers. The lowest risk of dementia was observed with consumption of 4 drinks weekly or 6 grams daily. However, consumption of 23 or more alcoholic drinks weekly is associated with an increased risk of all-cause dementia (97063).
• Depression. It is not clear if wine consumption is beneficial for depression. Details: Observational research has found that low to moderate consumption of wine (2-7 drinks weekly) is associated with a 32% lower rate of depression when compared with not consuming wine (96696).
• Metabolic syndrome. There is limited evidence on the consumption of red wine for metabolic syndrome. Details: Observational research has found that moderate red wine consumption (at least one 5-ounce glass daily) is associated with a 44% lower odds of developing metabolic syndrome when compared with not drinking any red wine. The association appears to be strongest for females less than 70 years-old and for people who currently smoke or have a history of smoking. Drinking white wine does not seem to affect the risk of metabolic syndrome (97062).
• Obesity. It is unclear if wine consumption is beneficial in patients with obesity. Details: Some observational research in non-smokers has found that higher wine consumption in adolescence is linked to lower mid-life body mass index (BMI) when compared with lower wine consumption. No association between wine consumption and mid-life BMI was reported in adolescent smokers over a 20-year follow-up (103188). It is unknown if wine consumption reduces the risk of developing obesity or improves weight loss in obese patients.
• Systemic lupus erythematosus (SLE). It is unclear if wine consumption is beneficial in preventing SLE in females. Details: Observational research has found that modest daily alcohol consumption is associated with a reduced risk of developing SLE in females. When the data were stratified by alcohol type, 2 or more servings of wine weekly was associated with a 35% reduced risk of developing SLE when compared with not drinking alcohol (96684).
• Wound healing. Although there has been interest in topical wine for wound healing, there is insufficient reliable information about the clinical effects of alcohol for this purpose. More evidence is needed to rate wine for these uses.

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There is insufficient reliable information available about the safety of hu zhang.

PREGNANCY AND LACTATION:
Insufficient reliable information available; avoid using.

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LIKELY SAFE ...when used orally, responsibly, and in moderation (11880,97061).

POSSIBLY UNSAFE ...when used orally in excess of 1 to 2 five-oz glasses of wine daily. Larger amounts can cause significant adverse effects (11880). There is insufficient reliable information available about the safety of wine when used topically.

PREGNANCY: LIKELY UNSAFE
when used orally; alcohol is a teratogen. Use during pregnancy is associated with significant risk of spontaneous abortion, fetal alcohol syndrome, and developmental and behavioral dysfunction in infants and children exposed to alcohol in utero (8100); avoid using.

LACTATION: LIKELY UNSAFE
when used orally. Alcohol is secreted in breast milk. Chronic use can cause abnormal psychomotor development and disrupt the infant's sleep-wake pattern. Alcohol also seems to reduce milk production (11878); avoid using.

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ANTICOAGULANT/ANTIPLATELET DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase the risk of bleeding when taken with anticoagulant or antiplatelet drugs.  Details Hu zhang contains the constituent resveratrol. Resveratrol seems to have antiplatelet effects (2949,2950,2951,2952,2961,70813,70828,70831,70892,70968,71106).

CARBAMAZEPINE (Tegretol) Interaction Rating = Minor Be watchful with this combination. Severity = Mild •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase the effects and adverse effects of carbamazepine.  Details In animals, blood and tissue levels of carbamazepine were increased when given in combination with hu zhang. It is thought that increased levels of carbamazepine are due to cytochrome P450 3A4 (CYP3A4) inhibition (101418). This interaction has not been reported in humans.

CYTOCHROME P450 1A1 (CYP1A1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP1A1.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP1A1 enzyme (70862,70811). This interaction has not been reported in humans.

CYTOCHROME P450 1A2 (CYP1A2) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP1A2.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP1A2 enzyme (21733). This interaction has not been reported in humans.

CYTOCHROME P450 1B1 (CYP1B1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP1B1.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP1B1 enzyme (70834). This interaction has not been reported in humans.

CYTOCHROME P450 2C19 (CYP2C19) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP2C19.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP2C19 enzyme (70896). This interaction has not been reported in humans.

CYTOCHROME P450 2E1 (CYP2E1) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP2E1.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP2E1 enzyme (7864,70896). Also, a pharmacokinetic study shows that taking resveratrol 500 mg daily for 10 days prior to taking a single dose of chlorzoxazone 250 mg increases the maximum concentration of chlorzoxazone by about 54%, the area under the curve of chlorzoxazone by about 72%, and the half-life of chlorzoxazone by about 35% (95824). Chlorzoxazone is used as a probe drug for CYP2E1.

CYTOCHROME P450 3A4 (CYP3A4) SUBSTRATES Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might increase levels of drugs metabolized by CYP3A4.  Details Hu zhang contains the constituent resveratrol. In vitro research shows that resveratrol might inhibit the CYP3A4 enzyme (7864,70896). However, a clinical study in adults with NAFLD found that adding resveratrol 3000 mg daily for 8 weeks did not necessitate dose adjustments to any established medications metabolized by CYP3A4 (91327).

ESTROGENS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, hu zhang might competitively inhibit the effects of estrogen replacement therapy.  Details In vitro research shows that hu zhang might have estrogenic activity (13124,16061).

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ACITRETIN (Soriatane) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Concomitant use increases the risk of long-term teratogenic effects.  Details Alcohol increases the transesterification of acitretin to etretinate, which is a teratogen that can remain in the body for years after discontinuation of acitretin. Patients of reproductive potential should avoid alcohol completely while taking acitretin and at least 2 months after discontinuation (108003).

ANTIDIABETES DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Concomitant use may interfere with blood glucose control.  Details Alcohol can impair gluconeogenesis and may increase the risk of acute hypoglycemia when used concomitantly with antidiabetes drugs (2262). However, the carbohydrates in wine may also worsen glycemic control in patients with diabetes.

ANTIHYPERTENSIVE DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = B Theoretically, concomitant use may interfere with blood pressure control.  Details Clinical research suggests that consumption of alcohol can increase both systolic and diastolic blood pressure (34015,34050,34052,34053). However, acute alcohol intoxication can also increase the risk of hypotension and additive effects with antihypertensive drugs (2262).

ASPIRIN Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = C Concomitant use may increase the risk of gastrointestinal (GI) bleeding.  Details Concomitant use of aspirin with alcohol may increase the risk of GI bleeding (2262).

BUPROPION (Wellbutrin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use may increase the risk of adverse effects from alcohol.  Details In patients taking bupropion, there have been rare reports of adverse psychiatric events or reduced alcohol tolerance. Additionally, in chronic alcohol users, abrupt discontinuation of alcohol while taking bupropion may increase the risk of seizure (108023).

CEFAMANDOLE (Mandol) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = C Concomitant use may cause a disulfiram-like reaction.  Details Cefamandole can cause a disulfiram-like reaction when taken with alcohol (2262).

CEFOPERAZONE (Cefobid) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = C Concomitant use may cause a disulfiram-like reaction.  Details Cefoperazone can cause a disulfiram-like reaction when taken with alcohol (2262).

CETIRIZINE (Zyrtec) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk of CNS impairment.  Details Cetirizine may cause somnolence in some patients. There is some concern that taking cetirizine in conjunction with alcohol might reduce alertness and impair CNS performance (108022).

CHLORPROPAMIDE (Diabinese) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Concomitant use may cause a disulfiram-like reaction.  Details Chlorpropamide can cause a disulfiram-like reaction when taken with alcohol (506).

CISAPRIDE (Propulsid) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B Concomitant use may increase blood alcohol levels and adverse effects.  Details Concomitant use of alcohol can increase blood alcohol levels and adverse effects (2262). Also, red wine increases plasma cisapride concentrations, possibly by reducing metabolism (1383).

CITALOPRAM (Celexa) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk of adverse effects from alcohol.  Details Some case reports suggest that citalopram may reduce alcohol tolerance and increase the risk of adverse effects from alcohol (108024).

CNS DEPRESSANTS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Likely •  Level of Evidence = C Concomitant use may increase sedative and other adverse effects.  Details Concomitant use of alcohol with CNS depressants can increase sedative and other adverse effects, potentially through inhibition of the metabolism of certain CNS depressants (2262).

CYCLOSPORINE (Neoral, Sandimmune) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B Red wine can reduce the levels and clinical effects of cyclosporine.  Details Red wine reduces plasma cyclosporine concentrations, possibly by reducing cyclosporine absorption. There is evidence the reduction in cyclosporine AUC by red wine is less in Asians (8% to 14%) than Caucasians (35% to 36%) (1384,1387,8977).

DISULFIRAM (Antabuse) Interaction Rating = Major Do not take this combination. Severity = Moderate •  Occurrence = Likely •  Level of Evidence = C Concomitant use may cause a disulfiram reaction.  Details Disulfiram can cause a disulfiram reaction when taken with alcohol (2262). Patients taking disulfiram should not consume any alcohol.

DOXYCYCLINE (Vibramycin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = B Chronic alcohol use might reduce the levels and clinical effects of doxycycline.  Details Although acute alcohol ingestion does not seem to significantly impact the pharmacokinetics of doxycycline, chronic alcohol ingestion has been shown to significantly reduce the half-life and serum concentration of doxycycline (107998).

ELUXADOLINE (Viberzi) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = A Chronic or excessive alcohol use might increase the risk of pancreatitis from eluxadoline.  Details In clinical studies, the risk of pancreatitis with eluxadoline was increased in chronic alcohol users and in those with acute intake of 3 or more alcoholic beverages daily (108004).

ERYTHROMYCIN Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = C Concomitant use may increase blood alcohol levels and adverse effects.  Details Concomitant use of erythromycin with alcohol can increase blood alcohol levels and adverse effects (2262).

FELODIPINE (Plendil) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = B Consumption of red wine can rapidly increase felodipine levels and adverse effects.  Details Red wine taken on an empty stomach can cause "dose dumping" of extended-release felodipine, possibly by changing absorption or metabolism. Red wine can delay the appearance of felodipine in plasma until 4 hours after dosing and can rapidly increase its plasma concentration, producing peak serum levels 3 to 4 times higher than when felodipine is given with water. This can cause an increase in adverse effects 5 hours after dosing (11976).

FLIBANSERIN (Addyi) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = A Concomitant use increases the risk of severe hypotension and syncope.  Details Alcohol use is contraindicated in patients taking flibanserin due to the risk of severe hypotension and syncope (108002).

GRISEOFULVIN (Fulvicin) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = C Concomitant use may cause a disulfiram-like reaction.  Details Griseofulvin can cause a disulfiram-like reaction, including tachycardia and facial flushing, when taken with alcohol (2262).

H2-BLOCKERS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = C Concomitant use might increase blood alcohol levels and adverse effects.  Details Concomitant use of the H2-blockers cimetidine and ranitidine with low doses of alcohol (0.15 grams/kg) might increase blood alcohol levels and adverse effects. Effects with higher doses of alcohol (0.3-1.5 grams/kg) are variable (2262).

HEPATOTOXIC DRUGS Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = C Concomitant use of alcohol with hepatotoxic drugs may increase the risk of hepatotoxicity.  Details Concomitant use of excessive amounts of alcohol with potentially hepatotoxic drugs can increase the risk of liver damage (2262).

LEVOCETIRIZINE (Xyzal) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use might increase the risk of CNS impairment.  Details Levocetirizine may cause somnolence in some patients. There is some concern that taking levocetirizine in conjunction with alcohol might reduce alertness and impair CNS performance (108026).

LEVOMILNACIPRAN (Fetzima) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use may increase the absorption and elimination of levomilnacipran.  Details In vitro research shows that alcohol increases the release of levomilnacipran from extended-release capsules, resulting in complete drug release in 4 hours (108024). This effect has not been evaluated in humans.

METFORMIN (Glucophage) Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = C Concomitant use may increase the risk of lactic acidosis.  Details Concomitant consumption of large amounts of alcohol can increase the risk of lactic acidosis with metformin (107995).

METRONIDAZOLE (Flagyl) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = C Concomitant use may cause a disulfiram-like reaction.  Details Although there is some disagreement over the likelihood of a disulfiram-like reaction with concomitant use of alcohol and metronidazole (108000), prescribing materials recommend discontinuing alcohol intake during the use of metronidazole. In the US, it is recommended to discontinue alcohol during and for at least three days after therapy with metronidazole (107999); in Canada, it is recommended to discontinue alcohol during and for at least 1 day after therapy with metronidazole (108001).

MONOAMINE OXIDASE INHIBITORS (MAOIs) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = D Concomitant use may cause hypertensive crisis.  Details Wine contains tyramine (105702), which is metabolized by monoamine oxidase. Concurrent use of MAOIs with tyramine-containing beverages can lead to elevated levels of tyramine in the body. This can increase the effects of tyramine, which has been reported to cause hypertension, headache, and hypertensive crisis in numerous cases (100189,100192,101010). Sensitivity to tyramine can increase up to 10-fold to 100-fold in people using an MAOI (100189,101010).

NARCOTIC DRUGS Interaction Rating = Moderate Be cautious with this combination. Severity = High •  Occurrence = Possible •  Level of Evidence = C Concomitant use of large amounts of alcohol may decrease the metabolism of narcotic drugs.  Details Concomitant consumption of large amounts of alcohol can decrease the metabolism of narcotic drugs (2262).

NONSTEROIDAL ANTI-INFLAMMATORY DRUGS (NSAIDs) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = C Concomitant use may increase the risk of gastrointestinal (GI) bleeding.  Details Concomitant use of NSAIDs with alcohol may increase the risk of GI bleeding (2262).

PHENYTOIN (Dilantin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = C Concomitant use may decrease the effectiveness of phenytoin.  Details Chronic, heavy alcohol use can induce the metabolism, reducing therapeutic effectiveness of phenytoin (2262).

SECNIDAZOLE (Solosec) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use may cause a disulfiram-like reaction.  Details Although high quality evidence is lacking, there is concern that secnidazole can cause a disulfiram-like reaction when taken with alcohol. Prescribing materials in the US recommend discontinuation of alcohol during and for at least two days after therapy with secnidazole (107996).

SULFONAMIDE ANTIBIOTICS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = C Concomitant use may cause a disulfiram-like reaction.  Details Sulfonamide antibiotics can cause a disulfiram-like reaction when taken with alcohol (2262).

TINIDAZOLE (Tindamax) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Concomitant use may cause a disulfiram-like reaction.  Details Although high quality evidence is lacking, there is concern that tinidazole can cause a disulfiram-like reaction when taken with alcohol. Prescribing materials in the US recommend discontinuation of alcohol during and for at least three days after therapy with tinidazole (107997).

TOLBUTAMIDE (Orinase) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = C Theoretically, concomitant use may cause a disulfiram-like reaction.  Details Tolbutamide can cause a disulfiram-like reaction when taken with alcohol (2262).

VARENICLINE (Chantix) Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Possible •  Level of Evidence = D Theoretically, concomitant use may increase the risk of adverse effects from alcohol.  Details There have been reports of patients experiencing increased effects from alcohol while taking varenicline. Some cases involved unusual and sometimes aggressive behavior and were accompanied by amnesia (108021). Caution patients to use alcohol with caution when taking varenicline, as it may alter alcohol tolerance.

VASODILATORS Interaction Rating = Moderate Be cautious with this combination. Severity = Moderate •  Occurrence = Probable •  Level of Evidence = C Concomitant use may increase the risk of acute hypotension.  Details Acute alcohol intoxication can increase the risk of hypotension and additive effects with vasodilators (2262).

WARFARIN (Coumadin) Interaction Rating = Major Do not take this combination. Severity = High •  Occurrence = Probable •  Level of Evidence = C Alcohol can alter the effects of warfarin, although the exact effect depends on the nature of alcohol consumption.  Details Acute alcohol intoxication can decrease metabolism and increase the effects of warfarin. In contrast, chronic, heavy alcohol use can induce metabolism of warfarin, reducing therapeutic effectiveness (2262).

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General ...There is currently a limited amount of information on the adverse effects of hu zhang.

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General ...Orally, the side effects of wine depend on the amount of alcohol ingested and can vary among individuals.
Most Common Adverse Effects:
Orally: Most adverse effects are associated with alcohol content and include abdominal pain, aggression, blackouts, central nervous system (CNS) depression, confusion, diarrhea, drowsiness, emotional lability, flushing, hypoglycemia, hypothermia, indigestion, lack of coordination and trouble walking, migraines, nausea, neuropathies, perceptual and sensational disturbances, and vomiting.
Serious Adverse Effects (Rare):
Orally: Chronic heavy alcohol ingestion (three or more drinks daily) can lead to amnesia, cardiac myopathy, cirrhosis, dementia, hepatotoxicity, malnutrition, myocardial infarction (MI), physical dependence, and somnolence. Other effects of chronic use are chronic cerebellar syndrome, hypomagnesemia, Korsakoff's psychosis, pancreatitis, skeletal myopathies, various types of cancer, and Wernicke's encephalopathy.
Chronic ingestion of three or more alcoholic beverages daily is associated with an increased risk of all-cause mortality, ischemic stroke, and hypertension. Consumption of any amount of alcohol can increase the risk of hemorrhagic stroke.

Cardiovascular ...Orally, chronic heavy alcohol ingestion of three or more drinks daily is associated with an increased risk of all-cause mortality, atrial fibrillation, cardiac myopathy, hypertension, ischemic stroke, and myocardial infarction (MI) (2261,6843,6892,8102,9004,33984,34028,34054,34058,34059). Consumption of any amount of alcohol can increase the risk of hemorrhagic stroke (841,2271).

Gastrointestinal ...Orally, wine can cause a variety of side effects which depend on the amount of alcohol ingested and can vary among individuals. Some common side effects include abdominal pain, diarrhea, indigestion, nausea, and vomiting. (6843,8972,9004,34013,34031). Chronic alcohol use is also associated with pancreatitis (6843,9004).

Hepatic ...Orally, chronic heavy alcohol ingestion (three or more drinks daily) can lead to cirrhosis and hepatotoxicity (6843,9004).

Immunologic ...People who are allergic to sulfites and/or yeast might react to wine. Wine is associated with triggering asthmatic reactions in people with a history of asthma, possibly due to salicylates and/or added sulfites contained in wines (6174). A case report describes a 33-year-old female who developed allergic reactions ranging from mild symptoms to anaphylaxis after consumption of beer or wine. The allergy was attributed to the yeast Saccharomyces cerevisiae, which is used in the fermentation of both beverages (107819).

Musculoskeletal ...Orally, wine can cause a variety of side effects which depend on the amount of alcohol ingested and can vary among individuals. Some common side effects include lack of coordination and trouble walking. Other effects of chronic use include skeletal myopathies (6843,8972,9004).

Neurologic/CNS ...Orally, wine can cause a variety of side effects which depend on the amount of alcohol ingested and can vary among individuals. Some common side effects include blackouts, central nervous system (CNS) depression, drowsiness, lack of coordination and trouble walking, migraines, neuropathies, and perceptual and sensational disturbances. Chronic heavy alcohol ingestion (three or more drinks daily) can lead to amnesia, dementia, physical dependence, and somnolence. Other effects of chronic use are chronic cerebellar syndrome, Korsakoff's psychosis, and Wernicke's encephalopathy (6843,8972,9004,34055,34068).
Heavy alcohol consumption (fifteen or more drinks weekly) is also associated with a higher percentage of white matter changes and larger ventricular and sulcal size on magnetic resonance imaging (MRI) of the brain. This suggests that heavy alcohol consumption decreases cerebral blood flow and may contribute to brain atrophy (8651). Consumption of any amount of alcohol can increase the risk of hemorrhagic stroke (841,2271).

Oncologic ...There is evidence that heavy alcohol consumption is associated with the mutation of the p53 gene in individuals with esophageal carcinoma (9005). There is also some evidence that heavy consumption of wine is associated with the highest risk of esophageal cancer when compared with heavy consumption of beer and spirits (8972,9004). Chronic heavy alcohol ingestion (three or more drinks daily) can lead to mouth cancer, esophageal cancer, pharyngeal cancer, laryngeal cancer, and liver cancer (6843,8972,9004,31557,33977,34010,34037,34045,34061,34065,34069,34085). Some research suggests an association between alcohol consumption and an increased risk of pancreatic cancer, but other studies do not support this association (8038). Daily consumption of one or more alcoholic drinks in females might increase the risk of breast cancer by 2% to 15% and increase mortality from breast cancer by as much as 30% (6843,8100,8974,9006,96686). There is also evidence suggesting that females who consume alcohol daily have an increased risk of developing breast cancer when the daily intake of folate is 300 mcg or less (8974,9006). However, the association of wine intake and breast cancer risk in females may vary depending on the type of wine. Red wine results in higher levels of free testosterone and luteinizing hormone (LH) and lower hormone binding globulin (SHBG) levels when compared with white wine. This suggests that red wine has similar activity to aromatase inhibitors and may not increase the risk of breast cancer unlike white wine (97992).
Observational research has found that wine consumption is associated with a higher risk of developing skin cancer in females and a higher risk of invasive melanoma in both males and females (97055,97991).

Psychiatric ...Orally, wine can cause a variety of side effects which depend on the amount of alcohol ingested and can vary among individuals. Some common side effects include aggression, confusion, and emotional lability (6843,9004,34040). Chronic heavy alcohol ingestion (three or more drinks daily) can lead to dementia, physical amnesia, and somnolence (6843,8972,9004).

Pulmonary/Respiratory ...Orally, wine can cause a variety of side effects due to the alcohol content. The side effects depend on the amount ingested and can vary among individuals. A common side effect includes respiratory depression (6843,8972,9004). Wine is also associated with triggering asthmatic reactions in people with a history of asthma, possibly due to salicylates and/or added sulfites contained in wines (6174).

Other ...Orally, chronic heavy alcohol ingestion (three or more drinks daily) can lead to malnutrition and poor glycemic control (6843,8972,9004).
There is some evidence consumption of more than six beers per week is associated with a larger waist-to-hip ratio than those consuming an equivalent amount of hard liquor or wine. However, an association between moderate alcohol intake equivalent to approximately three beers per week or less and waist-to-hip ratio does not seem to exist (10164,10165). It is also unclear whether waist-to-hip ratios associated with the intake of wine, beer, or other alcoholic beverages have any clinical significance (9007).

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