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Chlorthalidone: Drug information

Chlorthalidone: Drug information
2024© UpToDate, Inc. and its affiliates and/or licensors. All Rights Reserved.
For additional information see "Chlorthalidone: Patient drug information" and "Chlorthalidone: Pediatric drug information"

For abbreviations, symbols, and age group definitions show table
Brand Names: US
  • Thalitone
Brand Names: Canada
  • APO-Chlorthalidone;
  • JAMP-Chlorthalidone
Pharmacologic Category
  • Antihypertensive;
  • Diuretic, Thiazide-Related
Dosing: Adult
Calcium nephrolithiasis, prevention

Calcium nephrolithiasis, prevention (off-label use): Oral: Initial: 12.5 to 25 mg once daily; after several weeks, may titrate based on urinary calcium response and tolerability up to a maximum of 100 mg once daily; usual effective dose: 25 to 50 mg once daily (Ref).

Edema or general volume overload

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

Note: Optimize loop diuretic therapy before adding chlorthalidone; 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, sodium); prior to and during therapy, electrolytes should be monitored and appropriately managed (Ref).

Oral: Initial: 12.5 to 25 mg once daily; may administer every other day or on specific days of the week; may increase dose as needed based on response and tolerability up to a maximum of 100 mg/day; 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 overdiuresis. Continue until euvolemia is restored, although some patients may require maintenance therapy (Ref).

Hypertension, chronic

Hypertension, chronic:

Note: 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: Usual dosage range: 12.5 to 25 mg once daily evaluate response after ~2 to 4 weeks and titrate dose, as needed; doses higher than 25 mg/day are not recommended due to greater adverse effects with minimal added antihypertensive benefit; if additional blood pressure control is needed, consider combination therapy. Patients with severe asymptomatic hypertension and no signs of acute end organ damage should be evaluated for medication titration within 1 week (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Adult

The renal dosing recommendations are based upon the best available evidence and clinical expertise. Senior Editorial Team: Bruce Mueller, PharmD, FCCP, FASN, FNKF; Jason A. Roberts, PhD, BPharm (Hons), B App Sc, FSHP, FISAC; Michael Heung, MD, MS.

Altered kidney function:

CrCl ≥10 mL/minute: No dosage adjustment necessary. The diuretic effect is diminished with CrCl <30 mL/minute, but small, short-term studies suggest antihypertensive effect may be preserved (Ref). Switching to a loop diuretic may be considered if BP is no longer controlled or if management of fluid overload is required (Ref). Alternatively, thiazides may augment diuresis when combined with a loop diuretic in patients unresponsive to monotherapy; closer monitoring of electrolytes is necessary when utilizing this approach (Ref).

CrCl <10 mL/minute: Use not recommended due to lack of efficacy (Ref).

Hemodialysis, intermittent (thrice weekly): Use not recommended due to lack of efficacy (Ref).

Peritoneal dialysis: Use not recommended due to lack of efficacy (Ref).

CRRT: In general, use not recommended; fluid management can be more effectively managed using CRRT ultrafiltration (Ref).

PIRRT (eg, sustained, low-efficiency diafiltration) : In general, use not recommended; fluid management can be more effectively managed using PIRRT ultrafiltration (Ref).

Dosing: Hepatic Impairment: Adult

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

Dosing: Older Adult

Calcium nephrolithiasis, prevention (off-label use): Refer to adult dosing.

Edema, refractory: Refer to adult dosing.

Hypertension, chronic: Oral: Initial: 6.25 to 12.5 mg once daily or every other day; maximum: 25 mg/day (Ref).

Dosing: Pediatric

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

Hypertension

Hypertension: Children and Adolescents: Oral: Initial: 0.3 mg/kg/dose once daily; may titrate up to a maximum daily dose: 2 mg/kg/day or 50 mg/day (Ref).

Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.

Dosing: Kidney Impairment: Pediatric

Altered kidney function:

There are no dosage adjustments provided in the manufacturer's labeling; based on experience in adult patients, use is contraindicated in anuria and considered ineffective in patients with end-stage renal disease (Ref).

Dosing: Hepatic Impairment: Pediatric

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

Adverse Reactions (Significant): Considerations
Electrolyte disturbances

Reversible hypokalemia, hypomagnesemia, hypercalcemia, and hyponatremia may occur with chlorthalidone and may increase the risk of arrhythmias. Electrolyte disturbances may be more significant with chlorthalidone compared to hydrochlorothiazide (Ref). Development of electrolyte disturbances may be minimized when used in combination with other electrolyte sparing antihypertensives (eg, angiotensin-converting enzyme, angiotensin receptor blockers, or aldosterone inhibitors) (Ref).

Mechanism: Dose-related; related to the pharmacologic action. Thiazide diuretics block the NaCl cotransporter in the distal convoluted tubule, leading to decreased reabsorption of sodium and chloride and increased delivery of sodium to the collecting duct, which leads to increased potassium wasting. Diluting capacity of the kidney is also impaired, leading to decreased magnesium and increased calcium concentrations (Ref).

Onset: Intermittent to delayed; hypokalemia generally occurs within 2 weeks of initiation (Ref). Hyponatremia onset varies, may range from 2 weeks to 10 years after treatment initiation (Ref).

Risk factors:

• High doses (>25 mg/day) (Ref) or concurrent loop diuretic therapy (Ref)

• Hypokalemia: GI losses (ie vomiting, diarrhea) (Ref)

• Hypomagnesemia: Heart failure, poor magnesium intake, high alcohol intake (Ref)

• Hypercalcemia: Older patients, females (Ref)

• Hyponatremia: Increased water intake (Ref); older patients, females (Ref)

Gout

Chlorthalidone may cause hyperuricemia and precipitate gout or gouty arthritis in susceptible individuals (Ref).

Mechanism: Dose-related; related to the pharmacologic action. Diuretics increase reabsorption of uric acid in the proximal tubule, reducing urinary excretion, increasing the risk of hyperuricemia and gout (Ref). Volume contraction with use of diuretics may also contribute to increased uric acid (Ref).

Onset: Varied; increased uric acid and risk of gout generally occurs within first few days of treatment initiation (Ref) but may occur up to 1 year after treatment initiation (Ref).

Risk factors:

• High doses (Ref)

• Increased duration of therapy (Ref)

• Personal or family history of gout (Ref)

Hypersensitivity reactions (immediate and delayed)

Hypersensitivity reactions, both immediate (urticaria, angioedema) and delayed, have been reported (Ref). Delayed hypersensitivity reactions range from maculopapular skin rash (Ref) and bullous fixed drug eruption (Ref) to rare severe cutaneous adverse reactions, including toxic epidermal necrolysis (Ref).

Mechanism:

Immediate hypersensitivity reactions: Non–dose-related; immunologic (ie, IgE-mediated, with specific antibodies formed against a drug allergen following initial exposure) (Ref).

Delayed hypersensitivity reactions: Non–dose-related; immunologic (ie, involving a T-cell mediated drug-specific immune response) (Ref).

Onset:

Immediate hypersensitivity reactions: Rapid; generally occur within 1 hour of administration but may occur up to 6 hours after exposure (Ref).

Delayed hypersensitivity reactions: Varied; typically occur days to 6 weeks after drug exposure, but may occur more rapidly (usually within 1 to 4 days) upon reexposure (Ref).

Risk factors:

• Cross-reactivity: Although chlorthalidone contains the sulfonamide moiety (Ref), there are no published reports of cross-reactivity with other sulfonamides (Ref). Cross-reactivity due to antibody production (anaphylaxis) is unlikely to occur with nonantibiotic sulfonamides and antibiotic sulfonamides (Ref). Cross-reactivity among chlorthalidone and thiazide diuretics is unknown.

Ocular effects

Sulfa derivatives such as chlorthalidone may cause acute transient myopia and acute angle-closure glaucoma which is generally reversible (Ref).

Mechanism: Non–dose-related; idiosyncratic; suggested to involve ciliochoroidal effusion and anterior rotation of the ciliary body, leading to myopic shift and angle closure (Ref).

Onset: Varied; reported to occur between 3 days and 1 week after initiation (Ref).

Adverse Reactions

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

Frequency not defined:

Cardiovascular: Hypersensitivity angiitis, necrotizing angiitis, vasculitis

Dermatologic: Skin photosensitivity, skin rash, toxic epidermal necrolysis, urticaria

Endocrine & metabolic: Glycosuria, hyperuricemia, hypochloremic alkalosis

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

Hematologic & oncologic: Aplastic anemia, leukopenia, nonthrombocytopenic purpura

Hepatic: Intrahepatic cholestatic jaundice

Nervous system: Dizziness, paresthesia, restlessness

Neuromuscular & skeletal: Asthenia, muscle spasm

Ophthalmic: Xanthopsia

Postmarketing:

Cardiovascular: Orthostatic hypotension (Juraschek 2019)

Endocrine & metabolic: Hypercalcemia (Palmer 1978), hyperglycemia (Barzilay 2006), hypokalemia (Hripcsak 2020), hyponatremia (Hripcsak 2020)

Gastrointestinal: Pancreatitis (Mallory 1980)

Genitourinary: Impotence (Hripcsak 2020)

Hematologic & oncologic: Agranulocytosis (Hripcsak 2020), anemia (Hripcsak 2020), neutropenia (Hripcsak 2020), thrombocytopenia (Hripcsak 2020)

Hypersensitivity: Angioedema (Piller 2006), fixed drug eruption (Cuervo-Pardo 2018)

Ophthalmic: Acute angle-closure glaucoma (Durai 2016), myopia (Mahesh 2007)

Nervous system: Headache (Hripcsak 2020), vertigo (Hripcsak 2020)

Neuromuscular & skeletal: Lupus-like syndrome (Vaglio 2018)

Contraindications

Hypersensitivity to chlorthalidone, other sulfonamide-derived drugs, or any component of the formulation; 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:

• 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 not 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/toxic epidermal necrolysis), 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).

• Autosomal-dominant hypoparathyroidism: Use with caution in patients with hypoparathyroidism due to autosomal-dominant hypoparathyroidism (ADH) type 1 and ADH type 2; thiazides may further exacerbate hypokalemia (ES [Brandi 2016]; ESE [Khan 2019]).

• Bariatric surgery: Dehydration: Avoid diuretics in the immediate postoperative period after bariatric surgery; electrolyte disturbances and dehydration may occur. Diuretics may be resumed, if indicated, once oral fluid intake goals are met (Ziegler 2009).

• 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 impairment; in progressive or severe hepatic disease, avoid electrolyte and acid/base imbalances that might lead to hepatic encephalopathy.

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

• 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).

Special populations:

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

Dosage Forms Considerations

Thalitone has been formulated with PVP (povidone polyvinylpyrrolidone), a bioavailability enhancer that provides 104% to 116% bioavailability relative to an oral solution of chlorthalidone. Therefore, Thalitone is not bioequivalent to other formulations of chlorthalidone; do not substitute (manufacturer’s labeling).

Dosage Forms: US

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Thalitone: 15 mg

Generic: 25 mg, 50 mg

Generic Equivalent Available: US

Yes

Pricing: US

Tablets (Chlorthalidone Oral)

25 mg (per each): $1.21 - $2.62

50 mg (per each): $1.48 - $1.49

Tablets (Thalitone Oral)

15 mg (per each): $4.44

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.

Dosage Forms: Canada

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Tablet, Oral:

Generic: 12.5 mg, 25 mg, 50 mg

Administration: Adult

Oral: Administer as a single dose in the morning with food.

Administration: Pediatric

Oral: Administer in the morning with food.

Use: Labeled Indications

Edema or general volume overload: Adjunctive treatment (eg, added to loop diuretics) of edema associated with heart failure, renal impairment, hepatic cirrhosis, or corticosteroid and estrogen therapy.

Hypertension, chronic: Management of hypertension.

Use: Off-Label: Adult

Calcium nephrolithiasis, prevention

Medication Safety Issues
Older Adult: High-Risk Medication:

Beers Criteria: Diuretics are identified in the Beers Criteria as potentially inappropriate medications to be used with caution in patients 65 years and older because of 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]).

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 drug interactions program by clicking on the “Launch drug interactions program” link above.

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

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

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

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

Iloperidone: May enhance the hypotensive effect of Blood Pressure Lowering 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

Isocarboxazid: May enhance the hypotensive effect of Diuretics. Risk X: Avoid combination

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]).

Medications considered acceptable for the treatment of chronic hypertension during pregnancy may generally be continued in patients trying to conceive. Diuretics are second-line agents for the treatment of hypertension in pregnant patients (ACC/AHA [Whelton 2018]; ACOG 2019; NICE 2019; SOGC [Magee 2022]).

Pregnancy Considerations

Chlorthalidone crosses the placenta and can be detected in cord blood (Mulley 1978).

Maternal use may cause fetal or neonatal jaundice, thrombocytopenia, hypoglycemia, and electrolyte abnormalities.

Chronic maternal hypertension is associated with adverse events in the fetus/infant. Chronic maternal hypertension may increase the risk of birth defects, low birth weight, premature delivery, stillbirth, and neonatal death. Actual fetal/neonatal risks may be related to the duration and severity of maternal hypertension. Untreated chronic hypertension may also increase the risks of adverse maternal outcomes, including gestational diabetes, preeclampsia, delivery complications, stroke, and myocardial infarction (ACOG 2019). Patients with preexisting hypertension may continue their medication during pregnancy unless contraindications exist (ESC [Regitz-Zagrosek 2018]). Diuretics are second-line agents for the treatment of hypertension in pregnant patients (ACOG 2019; SOGC [Magee 2022]); agents other than chlorthalidone may be preferred (ACOG 2019).

Heart failure in pregnancy is associated with adverse maternal and fetal outcomes, including premature birth, infants born small for gestational age, 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

Chlorthalidone is present in breast milk (Mulley 1978).

Due to the potential for serious adverse reactions in the breastfeeding infant, breastfeeding is not recommended by the manufacturer. In general, thiazide diuretics have the potential to decrease milk volume and suppress lactation; use should be avoided when possible (ACOG 203 2019; WHO 2002).

Monitoring Parameters

BP; fluid intake and output; serum electrolytes, kidney function.

Mechanism of Action

Sulfonamide-derived diuretic that inhibits sodium and chloride reabsorption in the distal convoluted tubule (Gamba 2005; Moes 2014; Rose 1991).

Pharmacokinetics (Adult Data Unless Noted)

Onset of action: ~2.6 hours; Peak effect: 2 to 6 hours (Carter 2004)

Bioavailability: Brand name Thalitone tablet bioavailability is slightly greater (104% to 116%) relative to an oral solution of chlorthalidone.

Duration: Single dose: 24 to 48 hours; Long-term dosing: 48 to 72 hours (Carter 2004)

Protein binding: ~75% (58% to albumin)

Metabolism: Hepatic

Half-life elimination: Single dose: 40 hours; Long-term dosing: 45 to 60 hours (Carter 2004); may be prolonged with renal impairment

Excretion: Urine (primarily as unchanged drug)

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

  • (AE) United Arab Emirates: Ctd | Hygroton;
  • (AR) Argentina: Clortalidona | Euretico | Hygroton;
  • (AT) Austria: Hydrosan | Hygroton;
  • (AU) Australia: Hygroton;
  • (BD) Bangladesh: Clortha | Dydroton | Thalin | Thiocard;
  • (BE) Belgium: Chlortalidone eurogenerics | Hygroton;
  • (BG) Bulgaria: Zornichka;
  • (BR) Brazil: Clorat | Clordilon | Clortalidona | Clortalil | Clortil | Clorton | Clotadona | Diureflux | Drenidra | Higromil | Higroton | Neolidona | Taluron;
  • (CH) Switzerland: Hygroton;
  • (CL) Chile: Clotakem | Diuprol | Hiprex | Metorene;
  • (CO) Colombia: Cardiol | Clortax | Dichlor | Hidroten;
  • (CZ) Czech Republic: Urandil;
  • (DE) Germany: Chlortalidon hexal | Hydro-long | Hygroton;
  • (DO) Dominican Republic: Clortal | Diuclort | Nonydra;
  • (EC) Ecuador: Clortalidona | Hidroten | Higroton;
  • (EE) Estonia: Hygroton;
  • (ES) Spain: Higrotona;
  • (FI) Finland: Hydopan | Hygroton | Hypertol;
  • (FR) France: Hygroton;
  • (GB) United Kingdom: Chlortalidone Ivax | Hygroton | Hylaton;
  • (GR) Greece: Higrotona | Hygroton | Unidone;
  • (HK) Hong Kong: Hygroton;
  • (HR) Croatia: Hygroton;
  • (HU) Hungary: Huma-thalidone | Hygroton;
  • (ID) Indonesia: Hygroton | Thalidone-50;
  • (IE) Ireland: Hygroton;
  • (IL) Israel: Aquadon | Hygroton;
  • (IN) India: Chlohat | Chlornol | Ctd | Klorzid | New CH | Nexclor | Thalizide | Thaloric | Thiaklor | Thiovas;
  • (IT) Italy: Igroton | Zambesil;
  • (JP) Japan: Hygroton;
  • (KE) Kenya: Dichlor;
  • (KR) Korea, Republic of: Chlorthalidone | Hygroton;
  • (KW) Kuwait: Hygroton;
  • (LB) Lebanon: Hygroton;
  • (LT) Lithuania: Hygroton | Oxodolin | Urandil;
  • (LU) Luxembourg: Hygroton;
  • (LV) Latvia: Hygroton | Oxodolin | Urandil;
  • (MX) Mexico: Bioralin | Clortalidon | Clortalidona | Diuprol | Donaclor | Hidrona | Hidropharm | Higroton | Lortal | Salimbest | Tensoral;
  • (MY) Malaysia: Apo-chlorthalidone;
  • (NG) Nigeria: Side press;
  • (NL) Netherlands: Chloortalidon | Chloortalidon Accord | Chloortalidon flx | Chloortalidon focus care | Chloortalidon ratiopharm | Chloortalidon sandoz | Hygroton;
  • (NZ) New Zealand: Hygroton | Igroton;
  • (PE) Peru: Ipiclor;
  • (PL) Poland: Hygroton | Urandil;
  • (PR) Puerto Rico: Chlorthalidone | Hygroton;
  • (PT) Portugal: Clorotalidona | Hygroton;
  • (PY) Paraguay: Clortaland | Drenur | Hecoton | Hygroton | Nefrofil;
  • (RO) Romania: Clortalidon | Hygroton;
  • (RU) Russian Federation: Oxodolin;
  • (SA) Saudi Arabia: Apo-chlorthalidone | Hygroton;
  • (SE) Sweden: Hygropax | Hygroton;
  • (SI) Slovenia: Hydrosan | Hygroton;
  • (SK) Slovakia: Urandil;
  • (TH) Thailand: Chotalin | Hygroton;
  • (TN) Tunisia: Hygroton;
  • (TR) Turkey: Hygroton;
  • (TW) Taiwan: Hygroton;
  • (UA) Ukraine: Dichlor | Hygroton | Taklor;
  • (UG) Uganda: Dichlor;
  • (VE) Venezuela, Bolivarian Republic of: Hidroten;
  • (ZA) South Africa: Hygroton;
  • (ZW) Zimbabwe: Dichlor
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