Bendroflumethiazide Side Effects

Not all side effects for bendroflumethiazide may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

Applies to bendroflumethiazide: compounding powder, oral tablet

Cardiovascular

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]

Dermatologic

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]

Endocrine

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]

Endocrinologic changes associated with bendroflumethiazide, 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]

Gastrointestinal

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. Bendroflumethiazide-induced hypercholesterolemia or hypertriglyceridemia may enhance the formation of some types of gallstones.[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]

Hematologic

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

Hypersensitivity

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]

Metabolic

Metabolic changes associated with bendroflumethiazide, 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 bendroflumethiazide diuresis can provoke hepatic encephalopathy in patients with hepatic cirrhosis. This may be pertinent due to this patient's liver disease.[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]

Musculoskeletal

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

Nervous system

Side effects related to the nervous system include mild, transient dizziness, fatigue, or headache.[Ref]

Renal

New or worsened renal insufficiency associated with bendroflumethiazide 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]

References

1. Medical Research Council Working Party on Mild to Moderate Hypertension. "Ventricular extrasystoles during thiazide treatment: substudy of MRC mild hypertension trial." Br Med J (Clin Res Ed) 287 (1983): 1249-53

2. Starr JM, Whalley LJ "Hypertensive Old People in Edinburgh (HOPE) Study: electrocardiographic changes after captopril or bendrofluazide treatment." Age Ageing 22 (1993): 343-8

3. Nielsen EG, Nielsen JL "Biochemical and electrocardiographic changes following the intake of bendroflumethiazide with potassium chloride (Centyl with potassium chloride) in a 16 month old child." Dan Med Bull 15 (1968): 143-6

4. "Product Information. Naturetin (bendroflumethiazide)" Apothecon Inc, Princeton, NJ.

5. O'Keefe JC, Butrous GS, Dymond DS, Littlejohns P, Peters N, Banim SO "Ventricular arrhythmias complicating weight reduction therapy in a patient with a prolonged QT interval." Postgrad Med J 61 (1985): 419-21

6. Ragnarsson J, Hardarson T, Snorrason SP "Ventricular dysrhythmias in middle-aged hypertensive men treated either with a diuretic agent or a beta-blocker." Acta Med Scand 221 (1987): 143-8

7. Diffey BL, Langtry J "Phototoxic potential of thiazide diuretics in normal subjects." Arch Dermatol 125 (1989): 1355-8

8. Klimiuk PS, Davies M, Adams PH "Primary hyperparathyroidism and thiazide diuretics." Postgrad Med J 57 (1981): 80-3

9. Riis B, Christiansen C "Actions of thiazide on vitamin D metabolism: a controlled therapeutic trial in normal women early in the postmenopause." Metabolism 34 (1985): 421-4

10. Berglund G, Andersson O, Larsson O, Wilhelmsen L "Antihypertensive effect and side-effects of bendroflumethiazide and propranolol." Acta Med Scand 199 (1976): 499-506

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

12. Jorgensen FS, Brunner S "The long-term effect of bendroflumethiazide on renal calcium and magnesium excretion and stone formation in patients with recurring renal stones." Scand J Urol Nephrol 8 (1974): 128-31

13. Fichman MP, Vorherr H, Kleeman CR, Telfer N "Diuretic-induced hyponatremia." Ann Intern Med 75 (1971): 853-63

14. Ljunghall S, Backman U, Danielson BG, Fellstrom B, Johansson G, Wikstrom B "Calcium and magnesium metabolism during long-term treatment with thiazides." Scand J Urol Nephrol 15 (1981): 257-62

15. Husby S, Marthedal NJ "Hyponatraemia due to a thiazide diuretic. A case report." Acta Med Scand 210 (1981): 523-4

16. Struthers AD, Whitesmith R, Reid JL "Prior thiazide diuretic treatment increases adrenaline-induced hypokalaemia." Lancet 1 (1983): 1358-61

17. Lee MR, Morgan DB "Familial hyperkalaemia responsive to benzothiadiazine diuretic." Lancet 1 (1980): 879

18. Gudbrandsson T, Hansson L "Combination therapy with saluretics and atenolol in essential hypertension. Effects on blood pressure, electrolytes and uric acid." Acta Med Scand Suppl 625 (1979): 86-91

19. Elmfeldt D, Berglund G, Wedel H, Wilhelmsen L "Incidence and importance of metabolic side-effects during antihypertensive therapy." Acta Med Scand Suppl 672 (1983): 79-83

20. Winchester JF, Kellett RJ, Boddy K, Boyle P, Dargie HJ, Mahaffey ME, Ward DM, Kennedy AC "Metolazone and bendroflumethiazide in hypertension: physiologic and metabolic observations." Clin Pharmacol Ther 28 (1980): 611-8

21. Hilker RR "Reversible hypercalcemia associated with prolonged thiazide administration to control hypertension." J Occup Med 12 (1970): 444-5

22. Condon JR, Nassim R "Hypophosphataemia and hypokalaemia." Br Med J 1 (1970): 110

23. Spitzer TQ, Harris BA "Controlled evaluation of bendroflumethiazide in the treatment of essential hypertension." Curr Ther Res Clin Exp 17 (1975): 75-9

24. Ljunghall S, Backman U, Danielson BG, Fellstrom B, Johansson G, Odlind B, Wikstrom B "Effects of bendroflumethiazide on urate metabolism during treatment of patients with renal stones." J Urol 127 (1982): 1207-10

25. Nielsen S, Schmitz A, Knudsen RE, Dollerup J, Mogensen CE "Enalapril versus bendroflumethiazide in type 2 diabetes complicated by hypertension." Q J Med 87 (1994): 747-54

26. Pickkers P, Schachter M, Hughes AD, Feher MD, Sever PS "Thiazide-induced hyperglycaemia: a role for calcium-activated potassium channels?" Diabetologia 39 (1996): 861-4

27. Petri M, Cumber P, Grimes L, Treby D, Bryant R, Rawlins D, Ising H "The metabolic effects of thiazide therapy in the elderly: a population study." Age Ageing 15 (1986): 151-5

28. Berglund G, Andersson O, Widgren B "Low-dose antihypertensive treatment with a thiazide diuretic is not diabetogenic. A 10-year controlled trial with bendroflumethiazide." Acta Med Scand 220 (1986): 419-24

29. Toner JM, Ramsay LE "Thiazide-induced hypokalaemia; prevalence higher in women." Br J Clin Pharmacol 18 (1984): 449-52

30. Hesp R, Wilkinson PR "Potassium supplementation of thiazide therapy." Lancet 2 (1976): 1144

31. Gerrard L, Wheeldon NM, McDevitt DG "Central effects of combined bendrofluazide and atenolol administration. A single dose study in normal subjects." Eur J Clin Pharmacol 45 (1993): 539-43

32. Hine KR, Simmons JP, Baker SE, Man AM "Bendrofluazide convulsions." Lancet 1 (1982): 564

33. Mcdevitt DG, Currie D, Nicholson AN, Wright NA, Zetlein MB "Central effects of the diuretic, bendrofluazide." Br J Clin Pharmacol 38 (1994): 249-56

34. Petersen V, Hvidt S, Thomsen K, Schou M "Effect of prolonged thiazide treatment on renal lithium clearance." Br Med J 3 (1974): 143-5

35. Larsson GB, Langer L, Nassberger L "Thiazide-induced kidney damage with circulating antibodies against myeloperoxidase and cardiolipin." J Intern Med 233 (1993): 493-4

36. Pusey CD, Saltissi D, Bloodworth L, Rainford DJ, Christie JL "Drug associated acute interstitial nephritis: clinical and pathological features and the response to high dose steroid therapy." Q J Med 52 (1983): 194-211

37. Boer WH, Koomans HA, Dorhout Mees EJ "Acute effects of thiazides, with and without carbonic anhydrase inhibiting activity, on lithium and free water clearance in man." Clin Sci 76 (1989): 539-45

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