Hydrochlorothiazide – Dose & Effects

Background

Hydrochlorothiazide is the most commonly prescribed thiazide diuretic. It is indicated to treat edema and hypertension. Hydrochlorothiazide use is common but declining in favour of angiotensin converting enzyme inhibitors. Many combination products are available containing hydrochlorothiazide and angiotensin converting enzyme inhibitors or angiotensin II receptor blockers. Hydrochlorothiazide was granted FDA approval on 12 February 1959.

Properties and Characteristics of Hydrochlorothiazide

Drug class	Diuretics
Brand Names	Apo-Hydro, Aquazide, BPZide, Dichlotride, Esidrex, Hydrochlorot, Hydrodiuril, HydroSaluric, Hypothiazid, Microzide, Oretic and many others
Synonyms	HCTZ, Hidroclorotiazida, Hydrochlorothiazide, Hydrochlorothiazidum
Molecular Formula	C₇H₈ClN₃O₄S₂
Molecular Weight	297.7 g/mol
IUPAC Names	6-chloro-1,1-dioxo-3,4-dihydro-2H-1lambda6,2,4-benzothiadiazine-7-sulfonamide
Structural formula of main component
Pure active ingredient	Hydrochlorothiazide
Appearance	White, or practically white crystalline powder
Melting Point	266-268°C
Solubility	In water, 722 mg/L at 25 °C
Excretion	Eliminated in the urine
Available as	Tablet
Storage	Should be stored in tightly closed containers at a controlled room temperature of 15-30 °C and protected from light, moisture, and freezing.
Prescription	Doctor prescription is required

What is Hydrochlorothiazide used for?

High blood pressure
Swelling in the body from fluids (edema), in addition to other medications

Hydrochlorothiazide side effects

Hydrochlorothiazide can cause mild or serious side effects. The following list contains some of the key side effects that may occur while taking hydrochlorothiazide. This list does not include all possible side effects.

For more information on the possible side effects of hydrochlorothiazide, or tips on how to deal with a troubling side effect, talk with your doctor or pharmacist.

More common side effects

The more common side effects that can occur with hydrochlorothiazide include:

Blood pressure that’s lower than usual (especially when standing up after sitting or lying down)
Dizziness
Headache
Weakness
Erectile dysfunction (difficulty getting or keeping an erection)
Tingling in your hands, legs, and feet
Photosensitivity (a condition where your skin is more sensitive to the sun)
Muscle spasms
Diarrhea

These effects may go away within a few days or a couple of weeks. If they’re more severe or don’t go away, talk with your doctor or pharmacist.

Serious side effects

Call your doctor right away if you have serious side effects. Call 911 if your symptoms feel life threatening or if you think you’re having a medical emergency. Serious side effects and their symptoms can include the following:

severe skin reactions such as Stevens-Johnson syndrome and exfoliative dermatitis, with symptoms such as:
- Painful skin rash
- Skin peeling and blisters
- Fever
- mouth sores
kidney failure, with symptoms such as:
- Weakness
- Shortness of breath
- Tiredness
- Confusion
- Abnormal heart rate or chest pain
- Producing less urine than usual
- Increased swelling in your legs, ankles, or feet
blurred vision, with symptoms such as:
- Eye pain
- Trouble seeing
pancreatitis (inflammation in the pancreas), with symptoms such as:
- Upset stomach or vomiting
- Very bad stomach or back pain

Mechanism of action

Hydrochlorothiazide is transported from the circulation into epithelial cells of the distal convoluted tubule by the organic anion transporters OAT1, OAT3, and OAT4. From these cells, hydrochlorothiazide is transported to the lumen of the tubule by multidrug resistance associated protein 4 (MRP4).

Normally, sodium is reabsorbed into epithelial cells of the distal convoluted tubule and pumped into the basolateral interstitium by a sodium-potassium ATPase, creating a concentration gradient between the epithelial cell and the distal convoluted tubule that promotes the reabsorption of water.

Hydrochlorothiazide acts on the proximal region of the distal convoluted tubule, inhibiting reabsorption by the sodium-chloride symporter, also known as Solute Carrier Family 12 Member 3 (SLC12A3). Inhibition of SLC12A3 reduces the magnitude of the concentration gradient between the epithelial cell and distal convoluted tubule, reducing the reabsorption of water.

Drug Interactions with Hydrochlorothiazide

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is not recommended. Your doctor may decide not to treat you with this medication or change some of the other medicines you take.

Dofetilide

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Acarbose
Benzphetamine
Canagliflozin
Dapagliflozin
Empagliflozin
Felbinac
Glimepiride
Indomethacin and Insulin
Ketanserin
Levomethadyl
Meclofenamate
Nabumetone
Ouabain
Parecoxib
Repaglinide
Salicylic Acid
Tenoxicam
Valdecoxib

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

Aminolevulinic Acid
Bepridil
Carbamazepine
Cholestyramine
Ginkgo
Gossypol
Licorice

Other Interactions

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For fluid retention (edema)

For oral dosage form (tablets):

Adults—The usual dose is 25 to 100 milligrams (mg) daily as a single or divided dose. Your doctor may want you to take this dose every other day or on 3 to 5 days each week.
Children—Dose is based on body weight and must be determined by your doctor.

For high blood pressure

For oral dosage form (capsule):

Adults—At first, 12.5 milligrams (mg) or one capsule once a day. Your doctor may want you to take this alone or together with other blood pressure medicines. Your doctor may increase your dose as needed. However, the dose is usually not more than 50 mg per day.
Children—Use and dose must be determined by your doctor.

For oral dosage form (tablets):

Adults—At first, 25 milligrams (mg) once a day. Your doctor may increase your dose as needed and may be taken as a single dose or divided into two doses.
Children—Dose is based on body weight and must be determined by your doctor.

What should be done in case of overdose?

Do not take more hydrochlorothiazide oral tablets than your doctor prescribes. Using more than this can lead to serious side effects.

Symptoms of overdose

Symptoms caused by an overdose can include:

Dehydration (low fluid level in your body)
Low potassium level
Low chloride level
Low sodium level
Low blood pressure
In rare cases, hepatic encephalopathy (a brain problem that happens due to liver disease)

Call your doctor if you think you’ve taken too much hydrochlorothiazide.

Warnings of Hydrochlorothiazide

Hydrochlorothiazide oral tablets may not be right for you if you have certain medical conditions or other factors that affect your health. Talk with your doctor about your health history before you take hydrochlorothiazide oral tablets. Factors to consider include those in the list below.

Anuria. With anuria, your kidneys stop making urine. This condition is usually caused by kidney disease, such as chronic kidney disease. Having anuria is a contraindication for hydrochlorothiazide, which means people with this condition should not use the drug. If you have anuria, talk with your doctor about safer options to treat your condition.
Kidney disease. When used in people with kidney disease, hydrochlorothiazide may cause azotemia (kidney injury or damage). Hydrochlorothiazide should be used cautiously in people with kidney disease, especially if their kidney condition is severe. Your doctor can help determine whether hydrochlorothiazide is safe for you if you have a kidney condition.
Liver problems. When used in people with liver problems, hydrochlorothiazide may increase their risk for electrolyte problems. If you have a liver problem, your doctor can help determine if hydrochlorothiazide is safe for you to take.
Allergic reaction. If you’ve had an allergic reaction to hydrochlorothiazide oral tablets or any of their ingredients, you should not take the tablets. Ask your doctor what other medications are better options for you.
Sulfa allergy. Hydrochlorothiazide is a sulfonamide, which is also sometimes called a “sulfa” drug. Sulfa drugs can cause a sulfa allergic reaction in some people. You should not take hydrochlorothiazide if you have a sulfa allergy. In fact, this is a contraindication for hydrochlorothiazide, which means the drug should not be used in people with this condition.

Use with alcohol

In general, it’s best to avoid or minimize alcohol consumption while you’re taking hydrochlorothiazide.

This is because alcohol can interact with hydrochlorothiazide and cause your blood pressure to go too low. This can increase your risk for side effects, such as low blood pressure, dizziness, and orthostatic hypotension.

Your doctor can help determine how much alcohol, if any, is safe for you to drink while you’re taking hydrochlorothiazide.

Pregnancy and breastfeeding

This drug may not be safe to take while pregnant. If you’re pregnant or planning to become pregnant, talk with your doctor before you use hydrochlorothiazide.

You should not breastfeed while you’re using hydrochlorothiazide. This is because the drug passes into breast milk. And it could cause serious side effects in a child who’s breastfed. Talk with your doctor about safe ways to feed your child if you’re taking hydrochlorothiazide.

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