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chlorthalidone (Hygroton)

Tradename: Hygroton. Indications: 1) hypertension a) 12.5-50 mg QD b) doses > 50 mg/day do not increase anti-hypertensive effects c) not effective in patients with creatinine clearance < 30 mL/min - useful in patients with stage 4 chronic renal failure eGFR 15-20 mL/min [8] d) not associated with cardiovascular benefits when compared with HCTZ [7,9] - use of chlorthalidone vs HCTZ associated with lower cardiovascular morbidity & mortality after myocardial infarction or ischemic stroke [10] e) may lower risk of hip fracture in elderly (RR=0.79) [6] 2) edema a) 50-100 mg PO QD b) max dose 200 mg/day 3) prevention of calcium stones [5] 4) nephrogenic diabetes insipidus Dosage: - 25 mg PO QD Tabs: 25 mg. Pharmacokinetics: 1) bioavailability varies with different dosage forms 2) 90% bound mostly to erythrocytes 3) onset of action 2 hours 4) 1/2life 54 hours 5) duration of action: 24-72 hours 6) 30-60% of drug is excreted unchanged in the urine Dosage adjustment in renal failure: - QOD dosing if creatinine clearance < 10 mL/min Adverse effects: 1) hyperuricemia 2) rash 3) increased low-density lipoprotein (LDL) 4) hypokalemia (1-10%) 5) hypochloremic alkalosis 6) dilutional hyponatremia 7) electrolyte abnormalities (hypokalemia, hyponatremia) are more common with chlorthalidone than hydrochlorothiazide [4,7] 8) hyperglycemia 9) glucosuria 10) orthostatic hypotension 11) GI complaints 12) photosensitivity 13) pancreatitis 14) vasculitis 15) hypercalcemia (rare) 16) blood dyscrasia (rare) 17) prerenal azotemia Drug interactions: 1) may enhance hypokalemic effects of agents that lower serum K+ levels: i.e. beta-2 adrenergic agonists 2) may decrease lithium clearance 3) may increase requirements for oral hypoglycemic agents &/or insulin 4) probenecid a) blocks thiazide-induced uric acid retention b) enhances excretion of Ca+2, Mg+2, citrate 5) may increase the risk of NSAID-induced renal failure Mechanism of action: 1) enhances secretion of Na+, Cl- & H2O by interfering with Na+ & Cl- transport across the renal tubular epithelium mediated by SLC12A3 2) site of action: distal tubule 3) thiazides also effect the excretion of other electrolytes including K+ & HCO3- 4) thiazides inhibit tubular excretion of Ca+2

Interactions

drug interactions drug adverse effects (more general classes) monitor with thiazide diuretics

General

sulfonamide thiazide diuretic

Properties

MISC-INFO: elimination route KIDNEY 1/2life 56 HOURS protein-binding 90% pregnancy-category B safety in lactation ?

Database Correlations

PUBCHEM cid=2732

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 123
  2. Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998
  3. Kaiser Permanente Northern California Regional Drug Formulary, 1998
  4. Dhalla IA et al Chlorthalidone Versus Hydrochlorothiazide for the Treatment of Hypertension in Older Adults: A Population-Based Cohort Study. Ann Intern Med. 19 March 2013;158(6):447-455 PMID: 23552325 http://annals.org/article.aspx?articleid=1667266
  5. Deprecated Reference
  6. Puttnam R, Davis BR, Pressel SL Association of 3 Different Antihypertensive Medications With Hip and Pelvic Fracture Risk in Older Adults. Secondary Analysis of a Randomized Clinical Trial. JAMA Intern Med. Published online November 21, 2016 PMID: 27893045 http://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2587085 - Colon-Emeric CS, Lee R Cardiovascular Medications and Fractures. Dodging Complexity. JAMA Intern Med. Published online November 21, 2016. PMID: 27893011 http://annals.org/aim/article/2588175/targeting-functional-decline-alzheimer-disease-randomized-trial
  7. Hripcsak G, Suchard MA, Shea S et al Comparison of Cardiovascular and Safety Outcomes of Chlorthalidone vs Hydrochlorothiazide to Treat Hypertension. JAMA Intern Med. Published online February 17, 2020. PMID: 32065600 https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2760777
  8. Agarwal R, Sinha AD, Cramer AE et al. Chlorthalidone for hypertension in advanced chronic kidney disease. N Engl J Med 2021 Nov 5; [e-pub]. PMID: 34739197 https://www.nejm.org/doi/10.1056/NEJMoa2110730
  9. Ishani A, Cushman WC, Leatherman SM et al Chlorthalidone vs. Hydrochlorothiazide for Hypertension - Cardiovascular Events. N Engl J Med 2022. Dec 14 PMID: 26760416 https://www.nejm.org/doi/10.1056/NEJMoa2212270
  10. Ishani A, Hau C, Cushman WC, Leatherman SM et al Chlorthalidone vs Hydrochlorothiazide for Hypertension Treatment After Myocardial Infarction or Stroke: A Secondary Analysis of a Randomized Clinical Trial. JAMA Netw Open. 2024 May 1;7(5):e2411081. PMID: 38743423 PMCID: PMC11094558 Free PMC article. Clinical Trial.

Component-of

atenolol/chlorthalidone (Tenoretic) azilsartan/chlorthalidone (Edarbyclor, Takeda) chlorthalidone/clonidine (Combipres) chlorthalidone/reserpine