Chlorothiazide
Regulatory sources consulted
Approved indications
- Adjunctive treatment of edema associated with congestive heart failure, hepatic cirrhosis, corticosteroid or estrogen therapy, and renal dysfunction including nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.
Contraindications
Absolute
- Anuria.
- Hypersensitivity to chlorothiazide, any component, or other sulfonamide-derived drugs.
Clinical warnings
- Major warning · Severe renal disease may cause azotemia and accumulation; reassess and consider discontinuation if renal impairment progresses. — DailyMed setid 377dc515-e381-4196-8bc7-b738606c57ac
- Major warning · Monitor for fluid and electrolyte imbalance, particularly hyponatremia, hypochloremic alkalosis, and hypokalemia; minor shifts may precipitate hepatic coma in cirrhosis or progressive liver disease. — DailyMed setid 377dc515-e381-4196-8bc7-b738606c57ac
- Thiazides may activate or exacerbate systemic lupus erythematosus. — DailyMed setid 377dc515-e381-4196-8bc7-b738606c57ac
Drug interactions
- HighLithium
Mechanism: Reduced renal lithium clearance increases lithium exposure and toxicity.
Recommendation: Generally avoid the combination; if essential, monitor lithium closely.
DailyMed setid 377dc515-e381-4196-8bc7-b738606c57ac
- ModerateCorticosteroids or ACTH
Mechanism: They increase electrolyte depletion, particularly hypokalemia.
Recommendation: Monitor potassium and fluid-electrolyte status.
DailyMed setid 377dc515-e381-4196-8bc7-b738606c57ac
- ModerateNonsteroidal anti-inflammatory drugs
Mechanism: They may reduce diuretic, natriuretic, and antihypertensive effects.
Recommendation: Monitor clinical response and renal function.
DailyMed setid 377dc515-e381-4196-8bc7-b738606c57ac
- HighDigitalis glycosides
Mechanism: Chlorothiazide-induced hypokalemia may increase myocardial sensitivity to digitalis toxicity and promote arrhythmias.
Recommendation: Monitor potassium, ECG, and signs of digitalis toxicity; correct hypokalemia.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=377dc515-e381-4196-8bc7-b738606c57ac
- ModerateInsulin and oral antidiabetic drugs
Mechanism: Thiazides may alter glucose tolerance and change antidiabetic treatment requirements.
Recommendation: Monitor blood glucose and adjust the antidiabetic drug if needed.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=377dc515-e381-4196-8bc7-b738606c57ac
- ModerateAlcohol, barbiturates, narcotics, and other antihypertensive drugs
Mechanism: They may potentiate orthostatic hypotension or produce an additive antihypertensive effect.
Recommendation: Monitor blood pressure and adjust concomitant treatments according to clinical response.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=377dc515-e381-4196-8bc7-b738606c57ac
- ModerateNondepolarizing neuromuscular blockers such as tubocurarine
Mechanism: Chlorothiazide may increase responsiveness to the neuromuscular blocker.
Recommendation: Anticipate an increased response and monitor neuromuscular blockade.
https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=377dc515-e381-4196-8bc7-b738606c57ac
Adverse events
Common (≥1%)
Weakness · Hypotension · Nausea · Vomiting · Diarrhea · Hyperuricemia · Hyperglycemia · Electrolyte imbalance
Rare but serious
Pancreatitis · Cholestatic jaundice · Stevens-Johnson syndrome or toxic epidermal necrolysis · Renal failure or interstitial nephritis · Severe blood dyscrasias
Pregnancy and lactation
Thiazides cross the placenta; use during pregnancy only if clearly needed. Chlorothiazide may cause fetal or neonatal jaundice and thrombocytopenia. Because of the potential for serious adverse reactions in the nursing infant, decide whether to discontinue nursing or discontinue the drug, taking into account the importance of treatment to the mother.
Recent literature (PubMed)
Diuretics constitute a large family of medications that increase urine flow and induce urinary sodium loss and are widely used for therapy of hypertension, congestive heart failure, and edematous states. Diuretics in current use (and the year of their approval for use in the United States) include chlorothiazide (1958), hydrochlorothiazide (1959), bendroflumethiazide (1959), spironolactone (1960), chlorthalidone (1960), methyclothiazide (1961), polythiazide (1961), triamterene (1964), furosemide (1966), ethacrynic acid (1967), metolazone (1973), bumetanide (1983), indapamide (1983), amiloride (1986), acetazolamide (1986), torsemide (1993), and eplerenone (2002). Diuretics are typically classified as thiazide diuretics (bendroflumethiazide, chlorothiazide, chlorthalidone, hydrochlorothiazide, indapamide, metolazone and polythiazide), loop diuretics (bumetanide, ethacrynic acid, furosemide, and torsemide), and potassium-sparing agents (amiloride, eplerenone, spironolactone, and triamterene). The carbonic anhydrase blockers acetazolamide (1986) and methazolamide (1959) are also diuretics, but are more commonly used for the therapy of glaucoma. Diuretics are some of the most frequently used medications in medicine and are usually well tolerated. Common side effects are those that are caused by the diuresis and mineral loss such as weakness, dizziness, electrolyte imbalance, low sodium and potassium. Diuretics have not been associated with an appreciable increased rate of serum aminotransferase elevations and have rarely been associated with clinically apparent liver injury. Isolated case reports of idiosyncratic hepatotoxicity due to diuretics have been published, but there have been virtually no case series on individual diuretics or even whole class of drugs. The case reports that have been published provide only a very general pattern of injury that has not provided a clear clinical signature or suggestion that hepatotoxicity is a class effect among the thiazides and
Heart failure is a common condition with considerable associated costs, morbidity, and mortality. Patients often present to hospital with dyspnea and edema. Inadequate inpatient decongestion is an important contributor to high readmission rates. There is little evidence concerning diuresis to guide clinicians in caring for patients with acute decompensated heart failure. Contemporary diuretic strategies have been defined by expert opinion and older landmark clinical trials. To present a narrative review of contemporary recommendations, along with their underlying evidence and pharmacologic rationale, for diuretic strategies in inpatients with acute decompensated heart failure. PubMed, OVID, and Embase databases were searched from inception to December 22, 2022, with the following search terms: heart failure, acute heart failure, decompensated heart failure, furosemide, bumetanide, ethacrynic acid, hydrochlorothiazide, indapamide, metolazone, chlorthalidone, spironolactone, eplerenone, and acetazolamide. Randomized controlled trials and systematic reviews involving at least 100 adult patients (> 18 years) were included. Trials involving torsemide, chlorothiazide, and tolvaptan were excluded. Early, aggressive administration of a loop diuretic has been associated with expedited symptom resolution, shorter length of stay, and possibly reduced mortality. Guidelines make recommendations about dose and frequency but do not recommend any particular loop diuretic over another; however, furosemide is most commonly used. Guidelines recommend that the initial furosemide dose (on admission) be 2-2.5 times the patient's home dose. A satisfactory diuretic response can be defined as spot urine sodium content greater than 50-70 mmol/L at 2 hours; urine output greater than 100-150 mL/h in the first 6 hours or 3-5 L in 24 hours; or a change in weight of 0.5-1.5 kg in 24 hours. If congestion persists after the maximization of loop diuretic therapy over the first 24-48 hours, an adjunc
Bronchopulmonary dysplasia (BPD), a respiratory complication associated with neonatal prematurity, presents opportunities for pharmacological intervention due to its contributing risk factors. Despite diuretics' controversial usage in BPD treatment and varying institutional practices, this review aims to consolidate evidence from clinical trials regarding diuretic use in BPD. We conducted a systematic review following PRISMA guidelines, searching EMBASE, Medline, Web of Science and CINAHL databases (PROSPERO 2022: CRD42022328292). Covidence facilitated screening and data extraction, followed by analysis and formatting in Microsoft Excel. Among 430 screened records, 13 were included for analysis. Three studies assessed spironolactone and chlorothiazide combinations, two studied spironolactone and hydrochlorothiazide, while eight examined furosemide. All studies evaluated drug effects on dynamic pulmonary compliance and pulmonary resistance, serving as comparative measures in our review. Diuretics' effectiveness in treating bronchopulmonary dysplasia remains uncertain. The limited number of identified randomised controlled trials (RCTs) hampers high-level evidence-based conclusions when applying the Population, Intervention, Comparison, Outcome (PICO) approach. Conducting large prospective studies of good quality could provide more definitive insights, but the rarity of outcomes and eligible patients poses challenges. Further research, primarily focusing on RCTs assessing diuretics' safety and efficacy in this population, is warranted.