Hydrochlorothiazide with Licorice Interaction Details

Brand Names Associated with Hydrochlorothiazide

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Nov 08, 2023

Interaction Effect

Increased risk of hypokalemia and/or reduced effectiveness of the diuretic

Interaction Summary

Cases have been reported in which patients experienced hypokalemia and hypertension with concomitant use of licorice and diuretics. Symptoms of congestive heart failure and hypokalemia occurred in a patient taking licorice, furosemide, and digoxin . Hypokalemic paralysis has resulted from licorice use; concomitant diuretic use increased the risk . Licorice alone has been reported to be the likely cause of hypokalemia, hypertension, and cardiac arrhythmia . The glycyrrhetinic acid component of licorice is metabolized to 3-monoglucuronyl-glycyrrhetinic acid (3MGA), which inhibits 11-beta-hydroxysteroid dehydrogenase and reduces cortisol breakdown, resulting in a hypermineralocorticoid effect .

Severity

Moderate

Onset

Delayed

Evidence

Probable

How To Manage Interaction

Avoid concurrent use of licorice and diuretics.

Mechanism Of Interaction

Pseudoaldosteronism from licorice ingestion resulting in hypokalemia

Literature Reports

A) An 84-year-old male developed hypokalemia and symptoms of congestive heart failure after 7 days of concurrent use of a licorice-containing Chinese herbal laxative with digoxin and furosemide. The patient complained of fatigue, appetite loss, and lower extremity edema. Pulse rate was 30 beats per minute, potassium was 2.9 milliequivalents/Liter (mEq/L), and digoxin level 2.9 nanograms/milliliter (ng/mL). Chest radiograph revealed an enlarged cardiac silhouette and lung congestion. Partial arterial oxygen pressure and saturation was low, carbon dioxide pressure was high. Plasma renin activity was 0.3 ng/mL/hour (normal 0.3 to 2.9 ng/mL/hour) and aldosterone was 3.8 nanograms/deciliter (ng/dL) (normal 3.6 to 24 ng/dL). Digoxin and the herbal laxative were stopped; after 18 days, the patient's pulse increased to 60 beats per minute and symptoms of congestive heart failure were relieved. Potassium increased to 4.3 mEq/L, renin activity was 1 ng/mL/hour, aldosterone was 12 ng/dL, and digoxin level was 0.6 ng/mL .

B) Fifty-nine cases of glycyrrhizin-induced hypokalemic myopathy (GIHM) were reviewed. The combined use of licorice and hypotensive diuretic agents increased the risk of GIHM in the majority of cases. Of 56 cases which were reported, serum potassium was 1.98 milliequivalents/liter (mEq/L). Average blood aldosterone in 30 patients was normal, though 15 of those patients had below-normal values. Plasma renin activity averaged 0.17 nanograms/milliliter/hour (ng/mL/hour) (normal: 0.8-4.4 ng/mL/hour) in 27 patients. Complete cure was attained in 57 of the 59 cases of GIHM when licorice ingestion was discontinued and potassium supplementation given .

C) A 49-year-old female presented with persistent hypertension and hypokalemia (2.6 mmol/L; normal 3.3 to 4.8 mmol/L) following consumption of licorice. Blood pressure was found to be volume-sensitive and plasma renin activity and plasma aldosterone were low. The patient's hypokalemia was unresponsive to amiloride but normalized with spironolactone. Prior to discontinuing her regular licorice intake, her blood pressure control was unsatisfactory on a combination of furosemide 120 mg daily, felodipine 2.5 mg daily, monoxidine 0.2 mg daily, spironolactone 75 mg daily, and doxazosin 4 mg daily. The patient then admitted to consuming 30 to 40 Pontefract cakes, a licorice-based sweet, per week (approximately 0.25 kilograms). After discontinuing the Pontefract cakes, blood pressure fell steadily allowing progressive withdrawal of antihypertensive treatment .

D) A 21-year-old female developed headache and hypertension (190/120 mmHg), associated with licorice consumption (100 grams daily) along with an oral contraceptive. She was advised to discontinue eating licorice. Blood pressure remained elevated with treatment combining atenolol, lisinopril, hydrochlorothiazide, and amlodipine. Drug treatment was discontinued, and 2 weeks later blood pressure was 180/110 mmHg, potassium 2.6 mmol/L (normal 3.8 to 5.0 mmol/L), bicarbonate 35.9 mmol/L (normal 23 to 29 mmol/L). Plasma aldosterone was 160 picomoles/liter (pmol/L) (normal 320 to 2000 pmol/L). The patient then admitted to replacing her licorice intake with two packets of Stimerolol Sugar Free(R) chewing gum per day. This chewing gum contains 585 mg licorice in each 15 gram packet, which equals 8% to 12% glycyrrhizinic acid. Her glycyrrhizinic acid intake was calculated to be 120 mg daily. Within 3 weeks of discontinuing the gum, her blood pressure and potassium level normalized .

E) A 35-year-old woman taking an oral contraceptive and chlorothiazide experienced hypokalemia (2.2 mmol/L). Her blood pressure was 140/80 mmHg. Chlorothiazide was stopped and potassium chloride 600 mg three times daily was started. After one week, potassium remained abnormal at 2.0 mmol/L, after 2 weeks it decreased further to 1.5 mmol/L. Intravenous potassium supplementation was started. Although she denied licorice use, it was discovered that she used BenBits Cool Mint(R) chewing gum (Leaf, United Kingdom), 3 packets daily. This product contained 160 mg licorice in each 16 gram packet, of which 10% was glycyrrhizinic acid. After 2 days of intravenous potassium and 15 days of oral potassium, and within 3 weeks of discontinuing the chewing gum, edema disappeared, blood pressure decreased to 110/80 mmHg and potassium increased to 4.2 mmol/L. The authors attributed the hypokalemia to the licorice intake .

F) A 38-year-old male was hospitalized with respiratory and kidney failure due to complications of somnolence, flaccid paralysis of the extremities, arterial hypertension, edema and severe hypokalemia. He had been ingesting 200 grams of licorice daily for 10 weeks together with a thiazide diuretic for 2 weeks .

G) A 70-year-old male developed hypokalemia (1.9 millimoles/Liter (mmol/L)) and rhabdomyolysis while treated with a thiazide diuretic. Blood pressure and potassium were normalized following treatment with spironolactone, potassium chloride, and verapamil. It was discovered that he had been eating 60 to 100 grams of licorice candies daily for 4 to 5 years, containing 0.3% glycyrrhizic acid. Licorice ingestion was discontinued, then spironolactone and potassium were discontinued. Rechallenge with licorice (300 mg glycyrrhetinic acid) per day resulted in subnormal potassium (3.4 mmol/L), blood pressure 154/72 mmHg, and increased body weight by 4.9 kg. Licorice caused plasma renin activity to fall from 2.4 nanograms/Liter/second (ng/L/second) (normal 0.14 to 1.8 mg/L/second) to 0.2 mg/L/second after the week of licorice. Following the study, verapamil was continued while the patient abstained from licorice. Blood pressure and potassium remained normal .

Hydrochlorothiazide Overview

• Hydrochlorothiazide is used alone or in combination with other medications to treat high blood pressure. Hydrochlorothiazide is used to treat edema (fluid retention; excess fluid held in body tissues) caused by various medical problems, including heart, kidney, and liver disease and to treat edema caused by using certain medications including estrogen and corticosteroids. Hydrochlorothiazide is in a class of medications called diuretics ('water pills'). It works by causing the kidneys to get rid of unneeded water and salt from the body into the urine.

• High blood pressure is a common condition and when not treated, can cause damage to the brain, heart, blood vessels, kidneys and other parts of the body. Damage to these organs may cause heart disease, a heart attack, heart failure, stroke, kidney failure, loss of vision, and other problems. In addition to taking medication, making lifestyle changes will also help to control your blood pressure. These changes include eating a diet that is low in fat and salt, maintaining a healthy weight, exercising at least 30 minutes most days, not smoking, and using alcohol in moderation.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.