Hydrochlorothiazide

Tell your doctor if you are breastfeeding or plan to breastfeed. Hydrochlorothiazide is excreted in human breast milk. There is some evidence it may reduce the amount of breast milk produced by women who take it. Because of the possibility for serious adverse effects in nursing infants, you and your doctor will need to decide if you should stop breastfeeding or stop taking hydrochlorothiazide.

Store hydrochlorothiazide tablets and capsules at room temperature away from excess light and moisture. Keep this and all medications out of the reach of children.

Contraindications

• Anuria.b 109

• Known hypersensitivity to hydrochlorothiazide, other thiazides, or any ingredient in the formulation.b

• Although manufacturers state allergy to other sulfonamide derivatives is a contraindication,109 evidence to support cross-sensitivity is limited, and history of sensitivity to sulfonamide anti-infectives (“sulfa sensitivity”) should not be considered an absolute contraindication.

Warnings/Precautions

Warnings

May potentiate effects of other hypotensive agents.109 Although additive or potentiated antihypertensive effects usually are used to therapeutic advantage,500 hypotension could occur.109 b (See Interactions.)

Possible exacerbation or activation of systemic lupus erythematosus.109

Generally, do not use with lithium salts.109 (See Interactions.)

Sensitivity Reactions

May occur with or without history of allergy or bronchial asthma.109

Sulfonamide cross-sensitivity unlikely. (See Contraindications under Cautions.)

General Precautions

Monitor for fluid or electrolyte imbalance (hyponatremia, hypochloremic alkalosis, hypokalemia).b 109

Observe for signs of electrolyte imbalance (e.g., dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, oliguria, muscle pains, cramps, muscular fatigue, hypotension, tachycardia, nausea, vomiting).109

Perform periodic serum electrolyte determinations (particularly of potassium, sodium, chloride, and bicarbonate); institute measures to maintain normal serum concentrations if necessary.b

Serum and urinary electrolyte measurements are especially important with diabetes mellitus, vomiting, diarrhea, parenteral fluid therapy, or expectations of excessive diuresis.b

Weekly (or more frequent) electrolyte measurement recommended early in treatment; possible to extend interval between measurements to ≥3 months when electrolyte response has stabilized.b

May occur after brisk diuresis, when cirrhosis is present, or with prolonged therapy; inadequate oral electrolyte intake may contribute.109

May cause cardiac arrhythmias, exaggerate cardiac response to cardiac glycoside toxicity (increase ventricular irritability).109

Use potassium-sparing diuretics and/or potassium supplementation to avoid or treat hypokalemia.109

Generally mild, usually does not require specific treatment except in renal or hepatic impairment.109

Chloride replacement may be required for metabolic acidosis.109

Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate treatment usually is water restriction rather than salt administration except when hyponatremia is life-threatening.109

In actual salt depletion, appropriate replacement is treatment of choice.109

Hyperuricemia or, rarely, precipitation of gout may occur; generally avoid or use with caution in patients with history of gout or elevated uric acid concentrations.109 500 502

In diabetic patients, dosage adjustment of insulin or oral hypoglycemics may be required; hyperglycemia may occur and latent diabetes mellitus may become evident.109

Antihypertensive effect may be enhanced after sympathectomy.109

May increase magnesium urinary excretion, resulting in hypomagnesemia.109

May decrease calcium urinary excretion, cause slight intermittent serum calcium increase in absence of known calcium metabolism disorder; marked hypercalcemia may indicate hyperparathyroidism.109

Discontinue prior to performing parathyroid tests.109

May increase cholesterol and triglyceride concentrations.109

Clinical importance of these changes is unknown.b Diet low in saturated fat and cholesterol usually compensates.b

Orthostatic hypotension rarely occurs.b

Specific Populations

Category B.109

Diuretics are considered second-line agents for control of chronic hypertension in pregnant women;142 500 if initiation of antihypertensive therapy is necessary during pregnancy, other antihypertensives (i.e., methyldopa, nifedipine, labetalol) are preferred.142 540

Diuretics are not recommended for prevention or management of gestational hypertension or preeclampsia.141 539 540

Edema associated with pregnancy generally responds well to thiazides except when caused by renal disease; however, do not use as routine therapy in pregnant women with mild edema who are otherwise healthy.b

Distributed into milk.h 109 141 Manufacturer states to discontinue nursing or the drug;109 however, considered to be compatible with breast-feeding.141

No controlled studies in children; use is supported by experience and published literature about hypertension treatment in children.109 111

Elderly may be at increased risk of dilutional hyponatremia, especially underweight females with poor oral fluid and electrolyte intake or excessive low-sodium nutritional supplement intake.b (See Hyponatremia under Cautions.)

Increased incidence of adverse effects and excessive reduction in BP in those >65 years of age.112 (See Geriatric Patients under Dosage and Administration.)

Use with caution in hepatic impairment or progressive liver disease (particularly with associated potassium deficiency); electrolyte imbalance may precipitate hepatic coma.b 109

Discontinue immediately if signs of impending hepatic coma appear.b

Use with caution in severe renal impairment; thiazides decrease GFR and may precipitate azotemia.b 109 Effects may be cumulative in impaired renal function.b 109

Consider interruption or discontinuance if progressive renal impairment (rising nonprotein nitrogen, BUN, or Scr) occurs.109

Common Adverse Effects

Potassium depletion, hyperuricemia (usually asymptomatic rarely leading to gout).b Hypochloremic alkalosis in patients at risk (e.g., hypokalemic patients).b Hyperglycemia and glycosuria in diabetics.b

• Tell all of your health care providers that you take this medicine. This includes your doctors, nurses, pharmacists, and dentists.
• Avoid driving and doing other tasks or actions that call for you to be alert until you see how hydrochlorothiazide affects you.
• To lower the chance of feeling dizzy or passing out, rise slowly if you have been sitting or lying down. Be careful going up and down stairs.
• If you have high blood sugar (diabetes), you will need to watch your blood sugar closely.
• Have your blood pressure checked often. Talk with your doctor.
• Have blood work checked as you have been told by the doctor. Talk with the doctor.
• This medicine may affect certain lab tests. Tell all of your health care providers and lab workers that you take this medicine.
• If you are taking hydrochlorothiazide and have high blood pressure, talk with your doctor before using OTC products that may raise blood pressure. These include cough or cold drugs, diet pills, stimulants, ibuprofen or like products, and some natural products or aids.
• This medicine is a strong fluid-lowering drug (diuretic). Sometimes too much water and major elements (potassium) in the blood may be lost. This can lead to serious health problems. Your doctor will follow you closely to change the dose to match your body's needs.
• You may need extra potassium. Talk with your doctor.
• If you are on a low-salt or salt-free diet, talk with your doctor.
• Talk with your doctor before you drink alcohol or use other drugs and natural products that slow your actions.
• Tell your doctor if you have too much sweat, fluid loss, throwing up, or loose stools. This may lead to low blood pressure.
• If you take cholestyramine or colestipol, talk with your pharmacist about how to take them with this medicine.
• Watch for gout attacks.
• If you have lupus, hydrochlorothiazide can make your lupus active or get worse. Tell your doctor right away if you get any new or worse signs.
• If you are 65 or older, use this medicine with care. You could have more side effects.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using hydrochlorothiazide while you are pregnant.

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

Use with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.

Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.

Thiazides may add to or potentiate the action of other antihypertensive drugs.

Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma.

The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.

Lithium generally should not be given with diuretics (see PRECAUTIONS, Drug Interactions).

Acute Myopia and Secondary Angle-Closure Glaucoma

Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue Hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.

Hydrochlorothiazide Tablets USP, 25 mg are light pink colored, round shaped, flat faced beveled edge uncoated tablets, debossed with ‘D’ and ‘27’ on one side separated by scoring and plain on the other side.

            Bottles of 100                  NDC 65862-133-01
            Bottles of 1,000                NDC 65862-133-99

Hydrochlorothiazide Tablets USP, 50 mg are light pink colored, round shaped, flat faced beveled edge uncoated tablets, debossed with ‘D’ and ‘28’ on one side separated by scoring and plain on the other side.

            Bottles of 100                 NDC 65862-134-01
            Bottles of 1,000               NDC 65862-134-99

PHARMACIST: Dispense in a well-closed container as defined in the USP. Use child-resistant closure (as required).

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [ see USP Controlled Room Temperature] .

Distributed by:
Aurobindo Pharma USA, Inc.
2400 Route 130 North
Dayton, NJ 08810 

Manufactured by:
Aurobindo Pharma Limited
Hyderabad - 500 038, India

Revised: 07/2017

NDC 65862-134-01
Rx only 
Hydrochlorothiazide Tablets, USP
50 mg
AUROBINDO                        100 Tablets

Edema: Treatment of edema due to heart failure, hepatic cirrhosis (see "Note"), various forms of renal dysfunction (eg, nephrotic syndrome, acute glomerulosclerosis, chronic renal failure) (see "Note"), corticosteroid and estrogen therapy

Note: The use of hydrochlorothiazide in the treatment of edema for hepatic cirrhosis has largely been replaced by spironolactone. The use of hydrochlorothiazide in the management of edema in patients with renal dysfunction has largely been replaced by the use of loop diuretics (eg, furosemide).

Hypertension: Management of mild-to-moderate hypertension

Guideline recommendations:

Hypertension: The 2014 guideline for the management of high blood pressure in adults (Eighth Joint National Committee [JNC 8]) recommends initiation of pharmacologic treatment to lower blood pressure for the following patients:

• Patients ≥60 years of age with systolic blood pressure (SBP) ≥150 mm Hg or diastolic blood pressure (DBP) ≥90 mm Hg. Goal of therapy is SBP <150 mm Hg and DBP <90 mm Hg.

• Patients <60 years of age with SBP ≥140 mm Hg or DBP is ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

• Patients ≥18 years of age with diabetes and SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

• Patients ≥18 years of age with chronic kidney disease (CKD) and SBP ≥140 mm Hg or DBP ≥90 mm Hg. Goal of therapy is SBP <140 mm Hg and DBP <90 mm Hg.

Chronic kidney disease (CKD) and hypertension: Regardless of race or diabetes status, the use of an ACE inhibitor (ACEI) or angiotensin receptor blocker (ARB) as initial therapy is recommended to improve kidney outcomes. In the general nonblack population (without CKD) including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic, calcium channel blocker, ACEI, or ARB. In the general black population (without CKD), including those with diabetes, initial antihypertensive treatment should consist of a thiazide-type diuretic or a calcium channel blocker instead of an ACEI or ARB.

Coronary artery disease (CAD) and hypertension: The American Heart Association, American College of Cardiology and American Society of Hypertension (AHA/ACC/ASH) 2015 scientific statement for the treatment of hypertension in patients with coronary artery disease (CAD) recommends the use of a thiazide (or thiazide-like diuretic) as part of a regimen in patients with hypertension and chronic stable angina. A BP target of <140/90 mm Hg is reasonable for the secondary prevention of cardiovascular events. A lower target BP (<130/80 mm Hg) may be appropriate in some individuals with CAD, previous MI, stroke or transient ischemic attack, or CAD risk equivalents (AHA/ACC/ASH [Rosendorff 2015]).

Canadian labeling: Additional uses (not in US labeling):

Premenstrual tension with edema: Management of premenstrual tension with edema

Toxemia of pregnancy: Management of toxemia of pregnancy (including eclampsia). Note: Guidelines recommend alternative agents (Magee 2008)

Calcium nephrolithiasis

Data from a randomized, double-blind, placebo-controlled study supports the use of hydrochlorothiazide for the prevention of recurrent calcium nephrolithiasis [Laerum 1984]. Additional trials may be necessary to further define the role of hydrochlorothiazide in the treatment of this condition.

Based on the American Urologic Association (AUA) guidelines for the medical management of kidney stones, hydrochlorothiazide is effective and recommended for the prevention of recurrent calcium stones in patients with high or relatively high urine calcium concentrations.

Lithium-induced diabetes insipidus

Data from a limited number of patients studied (case reports) suggest that hydrochlorothiazide may be beneficial for the treatment of lithium-induced diabetes insipidus [Constandis 1981], [Meinardi 1997]. Additional data may be necessary to further define the role of hydrochlorothiazide in this condition.

Oral: Administer with or without food. Take early in day to avoid nocturia. Take the last dose of multiple doses no later than 6 PM unless instructed otherwise.

Store at 20°C to 25°C (68°F to 77°F). Protect from light and moisture.

Concerns related to adverse effects:

• Electrolyte disturbances: Hypokalemia, hypochloremic alkalosis, hypomagnesemia, and hyponatremia may occur. Development of electrolyte disturbances can be minimized when used in combination with other electrolyte sparing antihypertensives (eg, ACE inhibitors or angiotensin receptor blockers) (Sica 2011).

• Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic renal failure, gout can be precipitated by hydrochlorothiazide. This risk may be increased with doses ≥25 mg (Gurwitz 1997).

• Hypersensitivity reactions: Hypersensitivity reactions may occur with hydrochlorothiazide. Risk is increased in patients with a history of allergy or bronchial asthma.

• Ocular effects: May cause acute transient myopia and acute angle-closure glaucoma, typically occurring within hours to weeks following initiation. Discontinue therapy immediately in patients with acute decreases in visual acuity or ocular pain; additional treatments may be needed if uncontrolled intraocular pressure persists. Risk factors may include a history of sulfonamide or penicillin allergy.

• Photosensitivity: Photosensitization may occur.

• Sulfonamide (“sulfa”) allergy: The FDA-approved product labeling for many medications containing a sulfonamide chemical group includes a broad contraindication in patients with a prior allergic reaction to sulfonamides. There is a potential for cross-reactivity between members of a specific class (eg, two antibiotic sulfonamides). However, concerns for cross-reactivity have previously extended to all compounds containing the sulfonamide structure (SO2NH2). An expanded understanding of allergic mechanisms indicates cross-reactivity between antibiotic sulfonamides and nonantibiotic sulfonamides may not occur or at the very least this potential is extremely low (Brackett 2004; Johnson 2005; Slatore 2004; Tornero 2004). In particular, mechanisms of cross-reaction due to antibody production (anaphylaxis) are unlikely to occur with nonantibiotic sulfonamides. T-cell-mediated (type IV) reactions (eg, maculopapular rash) are less well understood and it is not possible to completely exclude this potential based on current insights. In cases where prior reactions were severe (Stevens-Johnson syndrome/TEN), some clinicians choose to avoid exposure to these classes.

Disease-related concerns:

• Adrenal insufficiency: Avoid use of diuretics for treatment of elevated blood pressure in patients with primary adrenal insufficiency (Addison disease). Adjustment of glucocorticoid/mineralocorticoid therapy and/or use of other antihypertensive agents is preferred to treat hypertension (Bornstein 2016; Inder 2015).

• Ascites due to cirrhosis: Use with extreme caution or avoid hydrochlorothiazide in the management of ascites due to cirrhosis; may lead to rapid development of hyponatremia when used in combination with spironolactone and furosemide (AASLD [Runyon 2012]).

• Diabetes: Use with caution in patients with prediabetes or diabetes mellitus; may see a change in glucose control.

• Hepatic impairment: Use with caution in patients with severe hepatic dysfunction; in progressive or severe liver disease, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy/coma.

• Hypercalcemia: Thiazide diuretics may decrease renal calcium excretion; consider avoiding use in patients with hypercalcemia.

• Hypercholesterolemia: Use with caution in patients with moderate or high cholesterol concentrations; increased cholesterol and triglyceride levels have been reported.

• Hypokalemia: Use with caution in patients with hypokalemia; correct before initiating therapy.

• Parathyroid disease: Thiazide diuretics reduce calcium excretion; pathologic changes in the parathyroid glands with hypercalcemia and hypophosphatemia have been observed with prolonged use; should be discontinued prior to testing for parathyroid function.

• Renal impairment: Cumulative effects may develop, including azotemia, in patients with impaired renal function. Avoid in severe renal disease (ineffective).

• Systemic lupus erythematosus (SLE): May cause SLE exacerbation or activation.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information.

Special populations:

• Surgical patients: If given the morning of surgery, hydrochlorothiazide may render the patient volume depleted and blood pressure may be labile during general anesthesia.

Dosage form specific issues:

• Propylene glycol: Some dosage forms may contain propylene glycol; large amounts are potentially toxic and have been associated with hyperosmolality, lactic acidosis, seizures and respiratory depression; use caution (AAP 1997; Zar 2007). See manufacturer’s labeling.

• Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

• Patient may experience constipation, diarrhea, dizziness, lack of appetite, nausea, vomiting, or headache. Have patient report immediately to prescriber signs of high blood sugar (confusion, fatigue, more thirst, hunger, polyuria, flushing, fast breathing, or breath that smells like fruit), signs of fluid and electrolyte problems (mood changes, confusion, muscle pain or weakness, abnormal heartbeat, severe dizziness or passing out, tachycardia, more thirst, seizures, loss of strength and energy, lack of appetite, urinary retention or change in the amount of urine produced, dry mouth, dry eyes, or nausea or vomiting), signs of kidney problems (urinary retention, hematuria, change in amount of urine passed, or weight gain), signs of pancreatitis (severe abdominal pain, severe back pain, severe nausea, or vomiting), shortness of breath, dark urine, jaundice, chills, pharyngitis, burning or numbness feeling, bruising, bleeding, severe loss of strength and energy, vision changes, or eye pain (HCAHPS).

• Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for health care professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience, and judgment in diagnosing, treating, and advising patients.

If you are between the ages of 18 and 60, take no other medication or have no other medical conditions, side effects you are more likely to experience include:

• A headache, dizziness on standing, dehydration, skin reactions and depletion of electrolytes. Effects may be aggravated by alcohol, illness, or in hot weather.
• Rarely, may cause an acute angle glaucoma. Symptoms include eye pain and reduced vision and may come on within hours or weeks of drug initiation.
• May cause allergic reactions in people allergic to sulfonamide drugs.
• Dosages greater than 50mg/day are not usually needed when hydrochlorothiazide is given in conjunction with other drugs used for hypertension. Higher dosages are also associated with greater potassium loss.
• May precipitate gout in some people or increase cholesterol or triglyceride levels.
• May interact with some other medications, including other medications used to lower blood pressure, lithium, oral antidiabetics, corticosteroids, and NSAIDs.
• May not be suitable for some people including those gout, diabetes, kidney or liver disease, glaucoma, or asthma.

Notes: In general, seniors or children, people with certain medical conditions (such as liver or kidney problems, heart disease, diabetes, seizures) or people who take other medications are more at risk of developing a wider range of side effects. For a complete list of all side effects, click here.

• Dosages may need to be adjusted depending on the individual; higher dosages need extra monitoring by a doctor.
• Report any symptoms such as confusion, dizziness, muscular weakness, and GI disturbances to a doctor.
• Seek urgent medical advice if you are unable to urinate.
• Report any eye pain or visual disturbances immediately to your doctor.
• Avoid drinking alcohol while you are taking hydrochlorothiazide because this may aggravate some of the side effects such as dizziness and dehydration.
• Be careful not to become overheated or dehydrated in hot weather while taking hydrochlorothiazide. Talk to your doctor about how much fluid you should be drinking; in some cases drinking too much fluid is just as harmful as not drinking enough fluids.
• Talk to your doctor or pharmacist before taking any other medications with hydrochlorothiazide as some may not be suitable (including those bought over the counter).

Taking this medicine with other drugs that make you light-headed can worsen this effect. Ask your doctor before taking a sleeping pill, narcotic pain medicine, muscle relaxer, or medicine for anxiety, depression, or seizures.

Tell your doctor about all your current medicines and any you start or stop using, especially:

• cholestyramine, colestipol;

• insulin or oral diabetes medicine;

• lithium;

• other blood pressure medications;

• steroid medicine; or

• NSAIDs (nonsteroidal anti-inflammatory drugs)--aspirin, ibuprofen (Advil, Motrin), naproxen (Aleve), celecoxib, diclofenac, indomethacin, meloxicam, and others.

This list is not complete. Other drugs may interact with hydrochlorothiazide, including prescription and over-the-counter medicines, vitamins, and herbal products. Not all possible interactions are listed in this medication guide.