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Hydroflumethiazide Side Effects

Applies to hydroflumethiazide: oral tablet.


Metabolic changes associated with hydroflumethiazide, as with other thiazide diuretics, are relatively common, especially when daily doses greater than 100 mg are used. Mild hypokalemia (decrease of 0.5 mEq/L) occurs in up to 50%, and may predispose patients to cardiac arrhythmias. Metabolic alkalosis, hyponatremia, hypomagnesemia, hypophosphatemia, hypercalcemia, hyperglycemia, hypercholesterolemia, and hyperuricemia are also relatively common. The electrolyte and intravascular fluid shifts that may occur during hydroflumethiazide diuresis can provoke hepatic encephalopathy in patients with hepatic cirrhosis.[Ref]

Hyperuricemia may be an important consideration in patients with a history of gout. Hypophosphatemia and low serum magnesium concentrations may occur, but are usually clinically insignificant except in malnourished patients.

Rare cases of hypercalcemia and milk-alkali syndrome (hypercalcemia, metabolic alkalosis, and renal insufficiency) have been associated with thiazide diuretics.[Ref]


Cardiovascular complications of diuretic therapy include orthostatic hypotension secondary to intravascular volume depletion. This has resulted in syncope and, in some patients with glaucoma, temporary loss of vision. Rare cases of cerebrovascular accident associated with thiazide-induced diuresis have been reported.[Ref]


Hypersensitivity reactions usually involve the skin (cutaneous vasculitis, urticaria, rash, purpura), but may involve the gastrointestinal system (nausea, vomiting, or diarrhea), the genitourinary system (interstitial nephritis), and the respiratory system (acute noncardiogenic pulmonary edema, pneumonitis). Thiazide diuretics may induce phototoxic dermatitis.[Ref]

Thiazides may induce allergic reactions in patients who are allergic to sulfonamides.[Ref]


Dermatologic reactions may indicate hypersensitivity to the drug. Erythema multiforme, Stevens-Johnson syndrome, exfoliative dermatitis (including toxic epidermal necrolysis), and alopecia have been reported in rare cases.[Ref]


Gastrointestinal problems include anorexia, gastric irritation, nausea, vomiting, diarrhea, constipation, or abdominal pain in approximately 5% of patients. Thiazide diuretics have been associated with acute cholecystitis, intrahepatic cholestatic jaundice and rare cases of pancreatitis.[Ref]

A retrospective case-controlled drug surveillance study has revealed the relative risk of acute cholecystitis associated with the use of a thiazide diuretic is 2.0. The suspected explanation for this association is the potentially deleterious effect thiazides have on the serum lipid profile. Hydroflumethiazide-induced hypercholesterolemia or hypertriglyceridemia may enhance the formation of some types of gallstones.[Ref]


Renal side effects including new or worsened renal insufficiency associated with hydroflumethiazide therapy is a probable sign of intravascular volume depletion, and serves as a signal to reduce or withhold therapy. Rare cases of allergic interstitial nephritis have been associated with some thiazide diuretics.[Ref]


Endocrinologic changes associated with hydroflumethiazide, as with other thiazide diuretic agents, include decreased glucose tolerance and a potentially deleterious effect on the lipid profile. This may be important in some patients with or who are at risk for diabetes or coronary artery disease.[Ref]

A prospective study of 34 patients who received oral thiazide diuretics for 14 years without interruption revealed an increased mean fasting blood glucose level after treatment. Withdrawal of thiazide therapy for 7 months in 10 of the patients resulted in mean reductions of 10% in fasting blood glucose and 25% in the 2-hour glucose tolerance test values. A control group was not reported.[Ref]

Nervous system

Nervous system side effects have included mild, transient dizziness, fatigue, or headache.[Ref]


Hematologic side effects are rare. Rare cases of immune-complex hemolytic anemia, aplastic anemia, and thrombocytopenia have been associated with thiazide diuretics.[Ref]

A 40-year-old woman with valvular heart disease developed listlessness, fatigue, easy bruising, increased pallor and exercise intolerance over four years after starting hydroflumethiazide 100 mg twice a week. She was taking no other medications. Physical and laboratory examination revealed petechiae, ecchymoses, optic hemorrhages, fever, signs of congestive heart failure, and gross pancytopenia. Sternal marrow aspiration revealed hypoplasia, except for a slight increase in lymphocytes and plasma cells. Iron stores were abundant. The patient fully recovered over a 10-week period after steroids, transfusions, phytohemagglutinin, fluoxymesterone (to suppress menstruation and to induce erythropoiesis), and discontinuation of hydroflumethiazide.[Ref]


Musculoskeletal cramping or spasm are occasionally reported during hydroflumethiazide diuresis.[Ref]


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2. Bell DS. Insulin resistance. An often unrecognized problem accompanying chronic medical disorders. Postgrad Med. 1993;93:99-103,.

3. Raskind M. Psychosis, polydipsia, and water intoxication. Report of a fatal case. Arch Gen Psychiatry. 1974;30:112-4.

4. Jamil MA. A comparative study of spironolactone and hydroflumethiazide alone and together in the treatment of hypertension. Guys Hosp Rep. 1971;120:207-19.

5. Brors O, Enger E, Jacobsen S, Aakvaag A, Foss OP. Effects of hydroflumethiazide in congestive heart failure: renal electrolyte excretion related to urinary thiazide excretion and aldosterone. Acta Pharmacol Toxicol (Copenh). 1981;49:399-406.

6. Brors O, Jacobsen S, Foss OP, Aakvaag A. Effect of repeated doses of hydroflumethiazide on renal excretion of electrolytes and uric acid in healthy subjects. Acta Pharmacol Toxicol (Copenh). 1981;48:145-50.

7. Gifford RW Jr, Williams GW, Vidt DG, Bolen K, Acker C. Duration of effect of single daily doses of reserpine and hydroflumethiazide evaluated by noninvasive technology in hypertensive patients. Cleve Clin Q. 1982;49:209-18.

8. Product Information. Diucardin (hydroflumethiazide). Wyeth-Ayerst Laboratories. 2001;PROD.

9. Akbar FA, Boston PF, Chapman J, Pearce MY. Spironolactone and hydroflumethiazide in the treatment of hypertension. Br J Clin Pract. 1981;35:317-21.

10. Bech K, Skovsted L, Siersbaek-Nielsen K, Hansen JM. Influence of thiazides on thyroid parameters in man. Acta Endocrinol (Copenh). 1978;89:673-8.

11. Schmitz O, Hermansen K, Nielsen OH, Christensen CK, Arnfred J, Hansen HE, Mogensen CE, Orskov H, Beck-Nielsen H. Insulin action in insulin-dependent diabetics after short-term thiazide therapy. Diabetes Care. 1986;9:631-6.

12. Blayac JP, Ribes G, Buys D, Puech R, Loubatieres-Mariani MM. Effects of a new benzothiadiazine derivative, LN 5330, on insulin secretion. Arch Int Pharmacodyn Ther. 1981;253:154-63.

13. Elkowitz EB. Hypertension in the elderly: review of therapy with a hydroflumethiazide-reserpine combination. J Am Geriatr Soc. 1979;27:507-10.

14. Williamson JM, Neilson FJ, Gibbs WN. Hypoplastic anaemia and hydroflumethiazide. Scott Med J. 1966;11:19-20.

Further information

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Some side effects may not be reported. You may report them to the FDA.