Hydrochlorothiazide interactions to avoid

In addition to interactions with medications, hydrochlorothiazide can interact with licorice root and alcohol

By Stephanie Melby, Pharm.D. | Mar. 8, 2024

Key takeaways

Hydrochlorothiazide lowers blood pressure, and drug interactions may further increase this effect. Drug interactions may lead to dizziness, lightheadedness, fainting, headache, and severe hypotension (low blood pressure).
Certain drug interactions can lessen the effect of hydrochlorothiazide and negatively impact the treatment of conditions such as hypertension or edema.
Hydrochlorothiazide can cause electrolyte imbalances, including low potassium (hypokalemia), low magnesium (hypomagnesemia), low sodium (hyponatremia), and high calcium (hypercalcemia). Electrolyte imbalances can increase the risk of irregular or abnormal heartbeats.
Diuretics like hydrochlorothiazide can affect blood sugar (blood glucose) levels in the body. Hydrochlorothiazide can lessen the effect of medications used to treat diabetes.
Dose adjustments or dose frequency changes may be needed for hydrochlorothiazide and other medications to avoid serious drug interactions.
To avoid unwanted drug interactions, healthcare providers can review medication lists and make necessary adjustments.
Seek immediate medical help if a dangerous mixture of medications has been consumed.

Drug interactions | Food interactions | Other interactions | Avoiding interactions | When to see a doctor

Hydrochlorothiazide is a generic prescription medication used to treat high blood pressure (hypertension) and edema. Edema is swelling caused by fluid retention in certain body tissues, often due to heart failure, certain kidney conditions, corticosteroid therapy, or estrogen therapy. Hydrochlorothiazide belongs to a group of medications called thiazide diuretics (water pills). Diuretics work to excrete water and electrolytes by increasing the production and volume of urine.

Hydrochlorothiazide interacts with diabetes medications, lithium, certain cholesterol medications, nonsteroidal anti-inflammatory drugs (NSAIDs), and other blood pressure-lowering medications, among other drug classes. Only take hydrochlorothiazide with the anti-arrhythmic medication dofetilide (brand name Tikosyn) with consultation from a healthcare professional. Hydrochlorothiazide also interacts with licorice and alcohol. 

It’s important to be aware of hydrochlorothiazide interactions, as other drugs and foods can affect hydrochlorothiazide’s effectiveness and cause or worsen side effects. Since serious effects may happen with certain hydrochlorothiazide drug interactions, understanding which medications to avoid or use caution with is important.

Hydrochlorothiazide drug interactions

Many prescription and over-the-counter (OTC) medications can interact with hydrochlorothiazide, including diabetes medications, lithium, certain cholesterol medications, nonsteroidal anti-inflammatory drugs (NSAIDs), and other blood pressure-lowering medications.

Diabetes Medications

Diabetes medications control blood sugar levels. Treatment for diabetes includes a healthy lifestyle with both diet modifications and exercise, along with medications to further lower and control blood sugar levels. Thiazide diuretics like hydrochlorothiazide can affect blood sugar levels. When taking an anti-diabetic medication and hydrochlorothiazide, the therapeutic effect of the anti-diabetic medication can be decreased, resulting in higher blood sugar levels.

People with diabetes need to monitor blood sugar levels when using hydrochlorothiazide. This is especially important when starting hydrochlorothiazide or when increasing the hydrochlorothiazide dose. Healthcare providers will monitor therapy and prescribe hydrochlorothiazide at low doses. Tips for monitoring this drug interaction include being aware of the signs of high blood sugar (hyperglycemia), such as frequent urination and increased thirst, and checking blood sugar levels with a glucose monitor.

Examples of common anti-diabetic medications:

Glimepiride
Glipizide
Insulin aspart (Novolog)
Insulin lispro (Humalog)
Invokana (canagliflozin)
Januvia (sitagliptin)
Metformin (Glumetza)
Ozempic (semaglutide)

Lithium

Lithium is a prescription medication that is a mood stabilizer. It is used to treat bipolar disorder and is sometimes prescribed off-label for depression. This medication is available as oral tablets, capsules, oral solutions, and oral extended-release tablets (Lithobid). Lithium has many possible side effects and drug interactions. Certain drug interactions can cause too much lithium in the body and lead to lithium toxicity. Signs of mild lithium toxicity include tremor, nausea, and vomiting. Signs of more severe lithium toxicity include delirium, fast heart rate, confusion, seizures, and even coma.

Taking lithium and diuretics like hydrochlorothiazide can increase the amount of lithium in the body by decreasing the elimination of lithium from the body. Due to the serious risks, providers may decide not to prescribe these medications together. However, if necessary, modifying therapy is recommended when using lithium and hydrochlorothiazide. Healthcare providers will prescribe a low dose of lithium and regularly monitor serum lithium levels in the body. If there are any signs of lithium toxicity, stop the medication and seek immediate medical attention.

Certain Cholesterol Medications

Bile acid sequestrants are a group of medications used to lower cholesterol levels. Along with exercise and diet modifications, bile acid sequestrants can effectively manage hypercholesterolemia (high cholesterol). Bile acid sequestrants can decrease the absorption of many drugs by binding and excretion in the feces.

Taking bile acid sequestrants and hydrochlorothiazide can decrease the amount of hydrochlorothiazide in the body and negatively impact therapy. The diuretic effect of hydrochlorothiazide can be decreased with this drug interaction. Therapy can be modified to try and prevent this drug interaction. Hydrochlorothiazide should be taken at least one hour before or four hours after the bile acid sequestrants. Communicate with the doctor if there are concerns about this interaction, as alternative cholesterol medications may be more suitable.

Examples of bile acid sequestrants:

Cholestyramine (Questran)
Colesevelam (Welchol)
Colestipol (Colestid)

Nonsteroidal Anti-inflammatory Drugs (NSAIDs)

Nonsteroidal anti-inflammatory drugs, also called NSAIDs, are OTC and prescription medications used to treat fever and a variety of pain-related conditions. NSAIDs are commonly used to help manage muscle pain, dysmenorrhea (pain during the menstrual cycle), arthritic conditions, gout, and migraines. This group of medications has well-known adverse effects affecting the GI tract, kidneys, cardiovascular system, liver, and blood. Certain drug interactions can worsen these adverse effects.

Hydrochlorothiazide may increase the risk of kidney (renal) damage when taken with an NSAID. Additionally, an NSAID can lessen the effect of hydrochlorothiazide because NSAIDs can increase blood pressure. The healthcare team can monitor therapy and the effectiveness of hydrochlorothiazide when starting or increasing the dose of an NSAID. People will also likely be monitored for evidence of acute kidney injury (AKI). Signs of AKI include small amounts of urine leaving the body, shortness of breath, confusion, nausea, chest pain, tiredness, and swelling in the legs, ankles, and around the eyes. Reach out to the provider if there are concerns about this drug interaction.

Examples of common NSAIDs:

Celecoxib (Celebrex)
Diclofenac
Ibuprofen (Advil)
Indomethacin
Meloxicam
Naproxen (Aleve)

Other Blood Pressure Lowering Medications

There are a variety of blood pressure-lowering drugs for treating hypertension (high blood pressure). The most recommended classes used as first-line treatments are thiazide-type diuretics, calcium channel blockers, angiotensin-converting enzyme (ACE) inhibitors, and angiotensin II receptor blockers (ARBs). It’s common for people to use combination therapy when one antihypertensive drug isn’t working well enough. While combining blood pressure-lowering medications can be part of the treatment plan, it is important to understand their risks.

Taking hydrochlorothiazide with another blood pressure-lowering medication can further decrease blood pressure. People with hypertension need to know the signs of low blood pressure (hypotension). Signs include confusion, dizziness, fainting, blurred vision, headache, nausea, and irregular heartbeat or heart palpitations. Healthcare providers can monitor therapy and make dose adjustments as needed.

Examples of common blood pressure-lowering medications:

Amlodipine (Norvasc)
Benazepril (Lotensin)
Irbesartan (Avapro)
Lisinopril (Zestril)
Losartan (Cozaar)
Nifedipine (Procardia)
Valsartan (Diovan)

Hydrochlorothiazide food interactions

In addition to interactions with medications, there are other hydrochlorothiazide interactions. Hydrochlorothiazide has a food interaction with licorice.

Hydrochlorothiazide and licorice

Licorice root is a flavoring in candy, other foods, beverages, and tobacco products. While licorice root is considered safe as a food ingredient, it can cause serious side effects. When consumed in large amounts or for long periods, licorice root can increase blood pressure and decrease potassium levels (hypokalemia). Because of these effects, licorice root can be a concern for people with high blood pressure, heart disease, or kidney disease.

Licorice root can further increase the potassium-lowering effect of hydrochlorothiazide. Communicate with the healthcare team about diet changes and licorice use so they can monitor for the development of hypokalemia.

Other hydrochlorothiazide interactions

Hydrochlorothiazide can interact with other products, such as alcohol. 

Hydrochlorothiazide and alcohol

Alcohol is a depressant that slows down the nervous system. Drinking alcoholic beverages, such as beer or cocktails, can cause unsteady movement and impaired motor control. An additional side effect of alcohol includes low blood pressure. It’s important to use caution when drinking alcohol while taking hydrochlorothiazide and to be aware of the signs of low blood pressure. Alcohol can also further increase dehydration and electrolyte imbalances caused by diuretics. People who drink alcohol should always check with their doctor or pharmacist to see if they can combine alcohol with their medicines.

How to minimize hydrochlorothiazide interactions

Steps can be taken to help minimize hydrochlorothiazide interactions. Regularly update healthcare providers on all health conditions and provide them with current medication lists, including prescription drugs, OTC medications, supplements, and recreational drugs. Serious drug interactions are possible with nonprescription products like OTC medications and supplements. Pharmacists are great resources and can give medical advice and additional drug information.

Certain medical conditions can help determine if a drug will be safe or not for a person. Hydrochlorothiazide should not be used in people with sensitivities or allergic reactions to sulfonamides, also called sulfa drugs. The most common reaction to a sulfa allergy is a skin rash or hives, but more severe reactions, such as trouble breathing, can happen. Caution should be used in people with diabetes, liver disease, or kidney problems. Hydrochlorothiazide can be found in the breast milk of breastfeeding women when taking the drug. The decision to breastfeed while taking hydrochlorothiazide is essential to discuss with the healthcare team, as they will evaluate the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.

When to talk to a healthcare provider about hydrochlorothiazide interactions

While there are several serious drug interactions included above, there are many other hydrochlorothiazide drug interactions that are not included. Communicating openly with healthcare providers about all medications, supplements, dietary habits, and medical conditions is important to ensure safe drug management and monitoring. There are alternative treatment options for hypertension and edema that may be better suited for some people.