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Chlorothiazide: Drug information

Chlorothiazide: Drug information
(For additional information see "Chlorothiazide: Patient drug information" and see "Chlorothiazide: Pediatric drug information")

For abbreviations, symbols, and age group definitions used in Lexicomp (show table)
Brand Names: US
  • Diuril;
  • Sodium Diuril [DSC]
Pharmacologic Category
  • Antihypertensive;
  • Diuretic, Thiazide
Dosing: Adult
Edema or general volume overload

Edema or general volume overload (adjunct to loop diuretic):

Note: Optimize loop diuretic therapy before adding chlorothiazide; combination diuretic therapy is typically for short-term use to restore euvolemia in patients already taking high-dose loop diuretic therapy who are resistant (eg, furosemide total daily dose of 160 to 320 mg/day IV or the oral equivalent). Combination diuretic therapy can cause severe electrolyte depletion (eg, potassium, magnesium, and sodium); prior to and during therapy, electrolytes should be monitored and appropriately repleted or managed (Ref).

IV/Oral: Usual dosage range: 250 mg to 1 g once or twice daily; maximum daily dose: 2 g/day; may administer every other day or on specific days of the week; may be administered in combination with or shortly before the scheduled loop diuretic. Assess volume status frequently (eg, daily or at least every 2 to 3 days) to determine effectiveness and to avoid over-diuresis (Ref).

Hypertension, chronic

Hypertension, chronic:

Note : When a thiazide diuretic is chosen, chlorthalidone or indapamide is preferred (Ref). For patients who warrant combination therapy (blood pressure ≥20/10 mm Hg above goal or suboptimal response to initial monotherapy), may use in combination with another appropriate agent (eg, angiotensin-converting enzyme inhibitor, angiotensin II receptor blocker, dihydropyridine calcium channel blocker) (Ref). However, some experts prefer regimens that do not include thiazide diuretics for combination therapy (Ref).

Oral: 500 mg to 1 g daily in 1 or 2 divided doses; may increase up to 2 g daily in 1 or 2 divided doses based on response and tolerability (Ref).

Dosing: Kidney Impairment: Adult

CrCl <10 mL/minute: Avoid use. Ineffective with CrCl <30 mL/minute unless in combination with a loop diuretic (Ref).

Dosing: Hepatic Impairment: Adult

No dosage adjustments provided in manufacturer’s labeling; use with caution.

Dosing: Older Adult

Refer to adult dosing.

Dosing: Pediatric

(For additional information see "Chlorothiazide: Pediatric drug information")

Note: Although the manufacturer states that IV and oral dosing are equivalent; some clinicians use lower IV doses due to the poor oral absorption.

Edema, heart failure, hypertension

Edema (diuresis), heart failure, hypertension: Limited data available:

Infants, Children, and Adolescents:

Oral: 10 to 40 mg/kg/day in 1 or 2 divided doses (Ref).

Maximum daily doses:

Infants and Children <2 years: Oral: 375 mg/day.

Children ≥2 years: Oral: 1,000 mg/day.

Adolescents: Oral: 2,000 mg/day.

IV: 5 to 10 mg/kg/day in divided doses once or twice daily (Ref); doses up to 20 mg/kg/day have been described; maximum dose: 500 mg/dose (Ref). Note: In infants <6 months of age, lower doses of 1 to 2 mg/kg/dose every 6 to 12 hours have effectively been used as adjunctive treatment with high-dose furosemide in postoperative management following cardiothoracic surgery (Ref).

Diabetes insipidus

Diabetes insipidus (central): Limited data available: Infants: Oral: Initial: 10 mg/kg/day in 2 divided doses; may need to titrate dose to target urine osmolality: 100 to 150 mOsm/L; an effective dosing range of 5 to 10 mg/kg/dose twice or three times daily has been suggested (Ref).

Dosing: Kidney Impairment: Pediatric

Infants, Children, and Adolescents: Oral, IV (Ref):

Altered kidney function:

GFR ≥30 mL/minute/1.73 m2: No adjustment needed.

GFR <30 mL/minute/1.73 m2: Not recommended.

Hemodialysis, intermittent: Not recommended.

Peritoneal dialysis: Not recommended.

Dosing: Hepatic Impairment: Pediatric

There are no dosage adjustments provided in manufacturer's labeling; use with caution.

Adverse Reactions

The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified.

Frequency not defined:

Cardiovascular: Hypotension, necrotizing angiitis, orthostatic hypotension

Central nervous system: Dizziness, headache, paresthesia, restlessness, vertigo

Dermatologic: Alopecia, erythema multiforme, exfoliative dermatitis, skin photosensitivity, skin rash, Stevens-Johnson syndrome, toxic epidermal necrolysis, urticaria

Endocrine & metabolic: Glycosuria, hypercalcemia, hyperglycemia, hyperuricemia, hypochloremic alkalosis, hypokalemia, hypomagnesemia, hyponatremia, increased serum cholesterol, increased serum triglycerides

Gastrointestinal: Abdominal cramps, anorexia, constipation, diarrhea, gastric irritation, nausea, pancreatitis, sialadenitis, vomiting

Genitourinary: Hematuria (IV), impotence

Hematologic & oncologic: Agranulocytosis, aplastic anemia, hemolytic anemia, leukopenia, purpura, thrombocytopenia

Hepatic: Jaundice

Hypersensitivity: Anaphylaxis

Neuromuscular & skeletal: Muscle spasm, systemic lupus erythematosus, weakness

Ophthalmic: Blurred vision, xanthopsia

Renal: Interstitial nephritis, renal failure, renal insufficiency

Respiratory: Pneumonitis, pulmonary edema, respiratory distress

Miscellaneous: Fever

Postmarketing: Dermatologic: Psoriasis (Song 2021)

Contraindications

Hypersensitivity to chlorothiazide, any component of the formulation or sulfonamide-derived drugs; anuria

Note: Although the FDA-approved product labeling states this medication is contraindicated in patients with hypersensitivity to sulfonamide-containing drugs, the scientific basis of this cross-sensitivity has been challenged. See “Warnings/Precautions” for more detail.

Warnings/Precautions

Concerns related to adverse effects:

• Electrolyte disturbances: Hypercalcemia, hypokalemia, hypochloremic alkalosis, hyponatremia, and hypomagnesemia can occur.

• Hypersensitivity reactions: Hypersensitivity reactions may occur.

• Orthostatic hypotension: Concomitant ethanol use may increase the risk of orthostatic hypotension.

• 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).

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

• Gout: In certain patients with a history of gout, a familial predisposition to gout, or chronic kidney failure, gout can be precipitated.

• Hepatic impairment: Use with caution in patients with hepatic impairment; avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.

• 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 with thiazides.

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

• Kidney impairment: Avoid in severe kidney disease (ineffective). May precipitate azotemia; discontinue or consider withholding if kidney impairment occurs.

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

Special populations:

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

Dosage form specific issues:

• Benzyl alcohol and derivatives: Some dosage forms may contain sodium benzoate/benzoic acid; benzoic acid (benzoate) is a metabolite of benzyl alcohol; large amounts of benzyl alcohol (≥99 mg/kg/day) have been associated with a potentially fatal toxicity (“gasping syndrome”) in neonates; the “gasping syndrome” consists of metabolic acidosis, respiratory distress, gasping respirations, CNS dysfunction (including convulsions, intracranial hemorrhage), hypotension, and cardiovascular collapse (AAP ["Inactive" 1997]; CDC, 1982); some data suggests that benzoate displaces bilirubin from protein binding sites (Ahlfors 2001); avoid or use dosage forms containing benzyl alcohol derivative with caution in neonates. See manufacturer’s labeling.

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product

Solution Reconstituted, Intravenous, as sodium [strength expressed as base]:

Sodium Diuril: 500 mg (1 ea [DSC])

Generic: 500 mg (1 ea)

Solution Reconstituted, Intravenous, as sodium [strength expressed as base, preservative free]:

Generic: 500 mg (1 ea)

Suspension, Oral:

Diuril: 250 mg/5 mL (237 mL) [contains alcohol, usp, benzoic acid, methylparaben, propylparaben, quinoline yellow (d&c yellow #10), saccharin sodium]

Generic Equivalent Available: US

May be product dependent

Pricing: US

Solution (reconstituted) (Chlorothiazide Sodium Intravenous)

500 mg (per each): $38.02 - $357.24

Suspension (Diuril Oral)

250 mg/5 mL (per mL): $0.35

Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.

Administration: Adult

IV: Administer slowly by direct IV injection or infusion; do not administer IM or SUBQ. Avoid extravasation.

Oral: Shake suspension well before use.

Administration: Pediatric

Oral: Shake suspension well before use.

Parenteral: Administer by direct IV infusion over 3 to 5 minutes or further dilute and infuse over 30 minutes. Avoid extravasation. Do not administer via IM or SUBQ route.

Use: Labeled Indications

Edema or general volume overload: Adjunctive treatment of edema.

Hypertension, chronic: Management of hypertension.

Medication Safety Issues
Older Adult: High-Risk Medication:

Beers Criteria: Diuretics (chlorothiazide) are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older due to the potential to cause or exacerbate syndrome of inappropriate antidiuretic hormone secretion (SIADH) or hyponatremia; monitor sodium concentration closely when initiating or adjusting the dose in older adults (Beers Criteria [AGS 2023]).

International issues:

Diuril [US] may be confused with Duorol brand name for acetaminophen [Spain]

Metabolism/Transport Effects

None known.

Drug Interactions

Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.

Ajmaline: Sulfonamides may enhance the adverse/toxic effect of Ajmaline. Specifically, the risk for cholestasis may be increased. Risk C: Monitor therapy

Alcohol (Ethyl): May enhance the orthostatic hypotensive effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Alfuzosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Allopurinol: Thiazide and Thiazide-Like Diuretics may enhance the potential for allergic or hypersensitivity reactions to Allopurinol. Risk C: Monitor therapy

Amifostine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Amifostine. Management: When used at chemotherapy doses, hold blood pressure lowering medications for 24 hours before amifostine administration. If blood pressure lowering therapy cannot be held, do not administer amifostine. Use caution with radiotherapy doses of amifostine. Risk D: Consider therapy modification

Aminolevulinic Acid (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Systemic). Risk X: Avoid combination

Aminolevulinic Acid (Topical): Photosensitizing Agents may enhance the photosensitizing effect of Aminolevulinic Acid (Topical). Risk C: Monitor therapy

Amphetamines: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Angiotensin-Converting Enzyme Inhibitors: Thiazide and Thiazide-Like Diuretics may enhance the hypotensive effect of Angiotensin-Converting Enzyme Inhibitors. Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Angiotensin-Converting Enzyme Inhibitors. Risk C: Monitor therapy

Anticholinergic Agents: May increase the serum concentration of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Antidiabetic Agents: Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antidiabetic Agents: Hyperglycemia-Associated Agents may diminish the therapeutic effect of Antidiabetic Agents. Risk C: Monitor therapy

Antipsychotic Agents (Second Generation [Atypical]): Blood Pressure Lowering Agents may enhance the hypotensive effect of Antipsychotic Agents (Second Generation [Atypical]). Risk C: Monitor therapy

Arginine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Arsenic Trioxide: Thiazide and Thiazide-Like Diuretics may enhance the hypotensive effect of Arsenic Trioxide. Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Arsenic Trioxide. Management: When possible, avoid concurrent use of arsenic trioxide with drugs that can cause electrolyte abnormalities, such as the thiazide and thiazide-like diuretics. Risk D: Consider therapy modification

Barbiturates: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Benperidol: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Beta2-Agonists: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Bile Acid Sequestrants: May decrease the absorption of Thiazide and Thiazide-Like Diuretics. The diuretic response is likewise decreased. Management: Consider separating administraton of bile acid sequestrants and thiazide diuretics by at least 4 hours. Monitor for decreased therapeutic effects of thiazide diuretics if coadministered with a bile acid sequestrant. Risk D: Consider therapy modification

Brigatinib: May diminish the antihypertensive effect of Antihypertensive Agents. Brigatinib may enhance the bradycardic effect of Antihypertensive Agents. Risk C: Monitor therapy

Brimonidine (Topical): May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Bromperidol: May diminish the hypotensive effect of Blood Pressure Lowering Agents. Blood Pressure Lowering Agents may enhance the hypotensive effect of Bromperidol. Risk X: Avoid combination

Calcium Salts: Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Calcium Salts. Risk C: Monitor therapy

Cardiac Glycosides: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Cardiac Glycosides. Specifically, cardiac glycoside toxicity may be enhanced by the hypokalemic and hypomagnesemic effect of thiazide diuretics. Risk C: Monitor therapy

Corticosteroids (Systemic): May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

CycloPHOSphamide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of CycloPHOSphamide. Specifically, granulocytopenia may be enhanced. Risk C: Monitor therapy

Desmopressin: Hyponatremia-Associated Agents may enhance the hyponatremic effect of Desmopressin. Risk C: Monitor therapy

Dexketoprofen: May enhance the adverse/toxic effect of Sulfonamides. Risk C: Monitor therapy

Dexmethylphenidate: May diminish the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Diacerein: May enhance the therapeutic effect of Diuretics. Specifically, the risk for dehydration or hypokalemia may be increased. Risk C: Monitor therapy

Diazoxide: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Diazoxide. Risk C: Monitor therapy

Diazoxide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Dichlorphenamide: Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Dichlorphenamide. Risk C: Monitor therapy

Dofetilide: Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Dofetilide. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Dofetilide. Management: Although hydrochlorothiazide is specifically cited as a contraindication, the risk likely extends to all thiazide and thiazide-like diuretics and may be even greater with chlorthalidone or bendroflumethiazide. Consider alternatives when possible. Risk D: Consider therapy modification

DULoxetine: Blood Pressure Lowering Agents may enhance the hypotensive effect of DULoxetine. Risk C: Monitor therapy

Flunarizine: May enhance the therapeutic effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbal Products with Blood Pressure Increasing Effects: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Herbal Products with Blood Pressure Lowering Effects: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Hypotension-Associated Agents: Blood Pressure Lowering Agents may enhance the hypotensive effect of Hypotension-Associated Agents. Risk C: Monitor therapy

Indoramin: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Ipragliflozin: May enhance the adverse/toxic effect of Thiazide and Thiazide-Like Diuretics. Specifically, the risk for intravascular volume depletion may be increased. Risk C: Monitor therapy

Ivabradine: Thiazide and Thiazide-Like Diuretics may enhance the arrhythmogenic effect of Ivabradine. Risk C: Monitor therapy

Levodopa-Foslevodopa: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Foslevodopa. Risk C: Monitor therapy

Levosulpiride: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Levosulpiride. Risk X: Avoid combination

Licorice: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Lithium: Thiazide and Thiazide-Like Diuretics may decrease the excretion of Lithium. Management: Reduce the lithium dose if coadministered with thiazide or thiazide-like diuretics. Monitor serum lithium levels during coadministration with thiazide and thiazide-like diuretics. Risk D: Consider therapy modification

Loop Diuretics: May enhance the hypotensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Lormetazepam: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Mecamylamine: Thiazide and Thiazide-Like Diuretics may enhance the adverse/toxic effect of Mecamylamine. Management: Consider avoiding the use of mecamylamine and thiazide diuretics. If combined, mecamylamine prescribing information suggests reducing the mecamylamine dose by 50% in order to avoid excessive hypotension. Risk D: Consider therapy modification

Methenamine: Thiazide and Thiazide-Like Diuretics may diminish the therapeutic effect of Methenamine. Risk C: Monitor therapy

Methoxsalen (Systemic): Photosensitizing Agents may enhance the photosensitizing effect of Methoxsalen (Systemic). Risk C: Monitor therapy

Methylphenidate: May diminish the antihypertensive effect of Antihypertensive Agents. Risk C: Monitor therapy

Molsidomine: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Multivitamins/Fluoride (with ADE): May enhance the hypercalcemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Multivitamins/Minerals (with ADEK, Folate, Iron): Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Multivitamins/Minerals (with ADEK, Folate, Iron). Risk C: Monitor therapy

Multivitamins/Minerals (with AE, No Iron): Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Multivitamins/Minerals (with AE, No Iron). Specifically, thiazide diuretics may decrease the excretion of calcium, and continued concomitant use can also result in metabolic alkalosis. Risk C: Monitor therapy

Naftopidil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Neuromuscular-Blocking Agents (Nondepolarizing): Thiazide and Thiazide-Like Diuretics may enhance the neuromuscular-blocking effect of Neuromuscular-Blocking Agents (Nondepolarizing). Risk C: Monitor therapy

Nicergoline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nicorandil: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Nitroprusside: Blood Pressure Lowering Agents may enhance the hypotensive effect of Nitroprusside. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents: Thiazide and Thiazide-Like Diuretics may enhance the nephrotoxic effect of Nonsteroidal Anti-Inflammatory Agents. Nonsteroidal Anti-Inflammatory Agents may diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Nonsteroidal Anti-Inflammatory Agents (Topical): May diminish the therapeutic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Obinutuzumab: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Management: Consider temporarily withholding blood pressure lowering medications beginning 12 hours prior to obinutuzumab infusion and continuing until 1 hour after the end of the infusion. Risk D: Consider therapy modification

Opioid Agonists: May enhance the adverse/toxic effect of Diuretics. Opioid Agonists may diminish the therapeutic effect of Diuretics. Risk C: Monitor therapy

Pentoxifylline: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Pholcodine: Blood Pressure Lowering Agents may enhance the hypotensive effect of Pholcodine. Risk C: Monitor therapy

Phosphodiesterase 5 Inhibitors: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Polyethylene Glycol-Electrolyte Solution: Diuretics may enhance the nephrotoxic effect of Polyethylene Glycol-Electrolyte Solution. Risk C: Monitor therapy

Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. Risk C: Monitor therapy

Prazosin: Antihypertensive Agents may enhance the hypotensive effect of Prazosin. Risk C: Monitor therapy

Promazine: Thiazide and Thiazide-Like Diuretics may enhance the QTc-prolonging effect of Promazine. Risk X: Avoid combination

Prostacyclin Analogues: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Quinagolide: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Reboxetine: May enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Selective Serotonin Reuptake Inhibitors: May enhance the hyponatremic effect of Thiazide and Thiazide-Like Diuretics. Risk C: Monitor therapy

Silodosin: May enhance the hypotensive effect of Blood Pressure Lowering Agents. Risk C: Monitor therapy

Sodium Phosphates: Diuretics may enhance the nephrotoxic effect of Sodium Phosphates. Specifically, the risk of acute phosphate nephropathy may be enhanced. Risk C: Monitor therapy

Terazosin: Antihypertensive Agents may enhance the hypotensive effect of Terazosin. Risk C: Monitor therapy

Topiramate: Thiazide and Thiazide-Like Diuretics may enhance the hypokalemic effect of Topiramate. Thiazide and Thiazide-Like Diuretics may increase the serum concentration of Topiramate. Risk C: Monitor therapy

Toremifene: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Toremifene. Risk C: Monitor therapy

Urapidil: Antihypertensive Agents may enhance the hypotensive effect of Urapidil. Risk C: Monitor therapy

Verteporfin: Photosensitizing Agents may enhance the photosensitizing effect of Verteporfin. Risk C: Monitor therapy

Vitamin D Analogs: Thiazide and Thiazide-Like Diuretics may enhance the hypercalcemic effect of Vitamin D Analogs. Risk C: Monitor therapy

Reproductive Considerations

When diuretics are used for the treatment of heart failure in patients planning to become pregnant, adjust dose prior to conception to minimize risk of placental hypoperfusion (AHA/ACC/HFSA [Heidenreich 2022]).

Pregnancy Considerations

Chlorothiazide crosses the placenta and is found in cord blood. Maternal use may cause fetal or neonatal jaundice, thrombocytopenia, or other adverse events observed in adults.

Use of thiazide diuretics during pregnancy may be considered to treat edema due to pathologic causes (as in the nonpregnant patient); monitor.

Heart failure in pregnancy is associated with adverse maternal and fetal outcomes, including premature birth, infants born small for gestational age, and increased risk of maternal and fetal death (Bright 2021). Thiazide diuretics may be used for symptom management in pregnant patients with heart failure complicated by pulmonary congestion; closely monitor volume status and adjust dose to minimize risk of placental hypoperfusion (AHA/ACC/HFSA [Heidenreich 2022]; ESC [Regitz-Zagrosek 2018]).

Breastfeeding Considerations

Chlorothiazide is present in breast milk (Werthmann 1972).

Due to the potential for serious adverse reactions in the breastfeeding infant, the manufacturer recommends a decision be made whether to discontinue breastfeeding or to discontinue the drug, considering the importance of treatment to the mother. In general, thiazide diuretics have the potential to decrease milk volume and suppress lactation; use should be avoided when possible (WHO 2002).

Dietary Considerations

May need to decrease sodium and calcium, may need to increase potassium, zinc, magnesium, and riboflavin in diet. Some products may contain sodium.

Monitoring Parameters

Serum electrolytes, kidney function, blood pressure; fluid intake and output.

Mechanism of Action

Inhibits sodium and chloride reabsorption in the distal tubules causing increased excretion of sodium, chloride, and water resulting in diuresis. Loss of potassium, hydrogen ions, magnesium, phosphate, and bicarbonate also occurs.

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: Diuresis: Oral: Within 2 hours; IV: 15 minutes

Peak effect: Oral: ~4 hours; IV: 30 minutes

Duration of diuretic action: Oral: ~6 to 12 hours; IV: 2 hours

Absorption: Oral: Poor

Metabolism: Not metabolized

Half-life elimination: 45 to 120 minutes

Excretion: Urine (10% to 15% [oral], 96% [IV] as unchanged drug)

Brand Names: International
International Brand Names by Country
For country code abbreviations (show table)

  • (AE) United Arab Emirates: Saluric;
  • (AU) Australia: Chlotride;
  • (FI) Finland: Salutrid;
  • (FR) France: Diurilix;
  • (GB) United Kingdom: Saluric;
  • (JP) Japan: Chlotride;
  • (MY) Malaysia: Chlorzide | Chlotride | CTZ | Diurazide;
  • (NL) Netherlands: Chloorthiazide gf | Chloorthiazide MAE | Chloorthiazide ratiopharm;
  • (NZ) New Zealand: Chlotride;
  • (PR) Puerto Rico: Diuril;
  • (SE) Sweden: Chlotride;
  • (TN) Tunisia: Diurilix;
  • (TW) Taiwan: Chlotride
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