Edema (diuresis), heart failure, bronchopulmonary dysplasia, hypertension: Limited data available; Note: Although the manufacturer states that IV and oral dosing are equivalent, some clinicians use lower IV doses due to poor oral absorption.
Oral: 10 to 40 mg/kg/day in 2 divided doses (Eichenwald 2017; Hoffman 2000; Kao 1984; Kao 1994; Stewart 2011; manufacturer's labeling).
IV: Usual: 5 to 10 mg/kg/day in 2 divided doses (Costello 2007; Eichenwald 2017); usual maximum daily dose: 12 mg/kg/day; doses up to 20 mg/kg/day have been described (Carpenter 2020; Moffett 2017). Note: 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 (Carpenter 2020).
Diabetes insipidus (central): Limited data available: 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 (Al Nofal 2015; Rivkees 2007; Sperling 2014).
Hyperinsulinemia hypoglycemia, congenital hyperinsulinism (adjunct therapy): Limited data available: Oral: 7 to 10 mg/kg/day in 2 divided doses in combination with diazoxide (Aynsley-Green 2000; Hussain 2004; Kapoor 2009; Sotiridou 2021).
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 (diuresis), heart failure, hypertension: Limited data available:
Infants, Children, and Adolescents:
Oral: 10 to 40 mg/kg/day in 1 or 2 divided doses (AAP [Flynn 2017]; Ahlfeld 2020; Hobbins 1981; Rossano 2020; manufacturer's labeling).
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 (Costello 2007); doses up to 20 mg/kg/day have been described; maximum dose: 500 mg/dose (Moffett 2017). 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 (Carpenter 2020).
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 (Al Nofal 2015; Rivkees 2007; Sperling 2014).
Infants, Children, and Adolescents: Oral, IV (Aronoff 2007):
Altered kidney function:
GFR <30 mL/minute/1.73 m2: Not recommended.
GFR ≥30 mL/minute/1.73 m2: No adjustment needed.
Hemodialysis, intermittent: Not recommended.
Peritoneal dialysis: Not recommended.
There are no dosage adjustments provided in manufacturer's labeling; use with caution.
(For additional information see "Chlorothiazide: Drug information")
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 (ACC [Hollenberg 2019]; Brater 2011; Brater 2022; Jentzer 2010).
IV: Initial: 500 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 (ACC [Hollenberg 2019]; Brater 2022; Jentzer 2010; manufacturer’s labeling).
CrCl <10 mL/minute: Avoid use. Ineffective with CrCl <30 mL/minute unless in combination with a loop diuretic (Aronoff, 2007).
No dosage adjustments provided in manufacturer’s labeling; use with caution.
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)
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]
Tablet, Oral:
Generic: 250 mg [DSC], 500 mg [DSC]
May be product dependent
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.
IV: Administer slowly by direct IV injection or infusion; do not administer IM or SUBQ. Avoid extravasation.
Powder for injection: Prior to reconstitution, store between 2°C to 25°C (36°F to 77°F). The manufacturer's labeling recommends any unused reconstituted solution be discarded. Precipitation will occur in <24 hours in pH <7.4.
Suspension, tablets: Store at room temperature 15°C to 30°C (59°F to 86°F). Protect from freezing.
Oral: Suspension: Adjunctive treatment of edema due to heart failure, hepatic cirrhosis, and estrogen or corticosteroid therapy (FDA approved in pediatric patients [age not specified] and adults); treatment of edema due to various forms of renal dysfunction, including nephrotic syndrome, acute glomerulonephritis, and chronic renal failure (FDA approved in pediatric patients [age not specified] and adults); management of hypertension either alone or in combination with other antihypertensive agents (FDA approved in pediatric patients [age not specified] and adults); has also been used for bronchopulmonary dysplasia (BPD), hyperinsulinemia hypoglycemia/congenital hyperinsulinism (adjunct therapy), and central diabetes insipidus of infancy.
Parenteral: Adjunctive treatment of edema due to heart failure, hepatic cirrhosis, and estrogen or corticosteroid therapy (FDA approved in adults); treatment of edema due to various forms of renal dysfunction including nephrotic syndrome, acute glomerulonephritis, and chronic renal failure (FDA approved in adults); has also been used for BPD.
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 2019]).
Diuril [US] may be confused with Duorol brand name for acetaminophen [Spain]
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)
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.
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.
None known.
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.
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
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
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 decrease the excretion of Calcium Salts. Continued concomitant use can also result in metabolic alkalosis. 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
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-Containing Products: Blood Pressure Lowering Agents may enhance the hypotensive effect of Levodopa-Containing Products. 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
Porfimer: Photosensitizing Agents may enhance the photosensitizing effect of Porfimer. 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
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
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
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
Chlorothiazide serum levels may be increased if taken with food. Management: Administer without regard to food.
May need to decrease sodium and calcium, may need to increase potassium, zinc, magnesium, and riboflavin in diet. Some products may contain sodium.
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 to treat edema during normal pregnancies is not appropriate; use may be considered when edema is due to pathologic causes (as in the nonpregnant patient); monitor.
Chronic maternal hypertension is associated with adverse events in the fetus/infant. The risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death may be increased with chronic hypertension in pregnancy. Actual risks may be related to duration and severity of maternal hypertension. Diuretics are considered second-line therapy for treating chronic hypertension in pregnancy (ACOG 203 2019).
The treatment of edema associated with chronic heart failure during pregnancy is similar to that of nonpregnant patients. Use of thiazide diuretics may be considered but use with caution due to the potential reduction in placental blood flow. Patients diagnosed after delivery can be treated according to heart failure guidelines (ESC [Bauersachs 2016]; ESC [Regitz-Zagrosek 2018]).
Serum electrolytes, urine output and renal function parameters, blood pressure, fluid balance (body weight).
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.
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
Bioavailability: 9% to 56%; dose-dependent
Half-life elimination: 45 to 120 minutes
Excretion: Urine (10% to 15% [oral], 96% [IV] as unchanged drug)
Note: A chlorothiazide oral suspension (50 mg/mL) is commercially available.
50 mg/mL Oral Suspension
A 50 mg/mL oral suspension may be made with tablets. Crush ten 500 mg chlorothiazide tablets in a mortar and reduce to a fine powder; mix with a small amount of glycerin to form a uniform paste. Add 2 g carboxymethylcellulose gel (mix 2 g carboxymethylcellulose with 5 to 10 mL water to form a paste; add 40 mL water and heat to 60°C with moderate stirring until dissolution occurs; cool and allow to stand for 1 to 2 hours to form a clear gel). Dissolve 500 mg citric acid in 5 mL water and add to chlorothiazide carboxymethylcellulose mixture with 0.1% parabens. Add a quantity of purified water sufficient to make 100 mL (Nahata, 2004). Label "shake well" and "refrigerate". Stable for 30 days.
Solution (reconstituted) (Chlorothiazide Sodium Intravenous)
500 mg (per each): $38.02 - $357.24
Solution (reconstituted) (Sodium Diuril Intravenous)
500 mg (per each): $622.47
Suspension (Diuril Oral)
250 mg/5 mL (per mL): $0.35
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