Bendroflumethiazide / nadolol Side Effects

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

For the Consumer

Applies to bendroflumethiazide / nadolol: oral tablet

In addition to its needed effects, some unwanted effects may be caused by bendroflumethiazide / nadolol. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking bendroflumethiazide / nadolol:

Less common
  • Blurred vision
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • chest pain or discomfort
  • confusion
  • cough
  • difficulty breathing
  • dilated neck veins
  • dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
  • extreme fatigue
  • irregular breathing
  • lightheadedness, dizziness, or fainting
  • noisy breathing
  • paleness or cold feeling in fingertips and toes
  • shortness of breath
  • slow or irregular heartbeat
  • slurred speech
  • sweating
  • swelling of face, fingers, feet, or lower legs
  • tightness in chest
  • tingling or pain in fingers or toes when exposed to cold
  • unusual tiredness or weakness
  • weight gain
  • wheezing
Incidence not determined
  • Back or leg pains
  • black, tarry stools
  • bleeding gums
  • bloating
  • blood in urine or stools
  • chills
  • clay-colored stools
  • cloudy urine
  • cold sweats
  • constipation
  • coughing up blood
  • dark urine
  • difficulty swallowing
  • drowsiness
  • dry mouth
  • fast heartbeat
  • fever
  • flushed, dry skin
  • fruit-like breath odor
  • general body swelling
  • general feeling of discomfort or illness
  • general tiredness and weakness
  • headache
  • hives
  • hoarseness
  • increased hunger
  • increased thirst
  • increased urination
  • indigestion
  • joint pain, stiffness, or swelling
  • light-colored stools
  • loss of appetite
  • lower back or side pain
  • muscle tremors
  • nausea and vomiting
  • nosebleeds
  • pain in muscles
  • painful or difficult urination
  • pains in stomach, side, or abdomen, possibly radiating to the back
  • pale skin
  • pinpoint red spots on skin
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • rapid, deep breathing
  • rash
  • redness, soreness, or itching skin
  • restlessness
  • skin rash
  • sore throat
  • sores, ulcers, or white spots on lips or in mouth
  • sores, welting or blisters
  • stomach cramps
  • sugar in the urine
  • swollen or painful glands
  • tenderness of salivary glands
  • thickening of bronchial secretions
  • troubled breathing
  • unpleasant breath odor
  • unusual bleeding or bruising
  • unusual weight loss
  • upper right abdominal pain
  • vomiting of blood
  • yellow eyes or skin

If any of the following symptoms of overdose occur while taking bendroflumethiazide / nadolol, get emergency help immediately:

Symptoms of overdose
  • Change in consciousness
  • decreased urination
  • diarrhea
  • fast, slow, or shallow breathing
  • gas
  • heartburn
  • increase in heart rate
  • increased sweating
  • indigestion
  • loss of consciousness
  • low blood pressure
  • muscle cramps
  • numbness, tingling, pain, or weakness in hands or feet
  • pale or blue lips, fingernails, or skin
  • seizures
  • sunken eyes
  • trembling
  • unusual drowsiness, dullness, or feeling of sluggishness
  • unusual paleness
  • weakness and heaviness of legs
  • wrinkled skin

Some of the side effects that can occur with bendroflumethiazide / nadolol may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

Less common
  • Change in behavior
  • continuing ringing or buzzing or other unexplained noise in ears
  • decreased interest in sexual intercourse
  • dry eyes or skin
  • excess air or gas in stomach or intestines
  • hair loss, thinning of hair
  • hearing loss
  • inability to have or keep an erection
  • loss in sexual ability, desire, drive, or performance
  • relaxed and calm
  • sleepiness
  • stomach soreness or discomfort
  • stuffy nose
  • weight loss
Incidence not determined
  • Cracks in the skin
  • discoloration of skin
  • feeling of constant movement of self or surroundings
  • increased sensitivity of skin to sunlight
  • large, flat, blue or purplish patches in the skin
  • loss of heat from the body
  • muscle spasm, weakness, or restlessness
  • scaly skin
  • sensation of spinning
  • severe sunburn

For Healthcare Professionals

Applies to bendroflumethiazide / nadolol: oral tablet

Cardiovascular

Cardiovascular complications of bendroflumethiazide 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.

Cardiovascular side effects of nadolol are usually mild and transient and rarely require discontinuation of therapy. Bradycardia, hypotension, conduction disturbances, chest pain, and heart failure have each been reported in 1% to 3% of patients. Complaints of cold extremities have been reported in approximately 5% of patients. Edema has rarely been associated with the use of nadolol.[Ref]

Rare cases of A-V heart block during nadolol therapy have been reported.[Ref]

Dermatologic

Dermatologic reactions of bendroflumethiazide 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

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]

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]

Gastrointestinal

Gastrointestinal problems associated with bendroflumethiazide use 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.

Gastrointestinal problems, such as nausea, diarrhea, constipation, anorexia, bloating, flatulence and general abdominal upset have each been reported in less than 1% of patients receiving nadolol.[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. Bendroflumethiazide-induced hypercholesterolemia or hypertriglyceridemia may enhance the formation of some types of gallstones.[Ref]

Hematologic

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

Nervous system

Side effects related to the nervous system during bendroflumethiazide administration include mild, transient dizziness, vertigo, xanthopsia, paresthesia, fatigue, or headache.

The most common nervous system side effect of nadolol appears to be fatigue (up to 10% of patients). Headache or dizziness have been reported in 5% and 8% of patients, respectively.[Ref]

Nadolol is hydrophilic and is less likely to penetrate into the central nervous system compared to other beta-blockers. Depression and anxiety are reported in one patient while receiving nadolol. The symptoms started two days after an increase in his dosage and resolved within three days of discontinuing nadolol. Organic brain syndrome was diagnosed in two patients receiving nadolol should be considered as a possible cause of acute deterioration in mental or emotional status.[Ref]

Hypersensitivity

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

Hypersensitivity reactions with thiazide diuretics 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]

Metabolic

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]

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.[Ref]

Musculoskeletal

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

Psychiatric

Psychiatric side effects of nadolol have been limited to anxiety-depression in approximately 4% of patients.[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.

Renal insufficiency has not associated with nadolol, but one study of 10 elderly hypertensive patients has shown that the antihypertensive effect of nadolol was associated with a decrease in effective renal blood flow. The glomerular filtration rate in affected patients remained stable, however.[Ref]

Respiratory

At least one case of severe bronchospasm associated with nadolol therapy is reported. This patient had a history of childhood asthma and exercise-induced bronchospasm requiring albuterol inhalations. After one dosage of nadolol the patient had a respiratory arrest and required mechanical ventilation for several days. If nadolol is necessary in a patient with a history of bronchospasm, it is recommended that therapy be initiated in a controlled environment with bronchodilators available.[Ref]

Respiratory system side effects associated with nadolol therapy have been rare (1 in 1,000), but may be important in patients with reactive airways disease. The use of nadolol has been associated with precipitation of bronchospasm in patients with a history of asthma.[Ref]

References

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2. 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

3. Jackson DA "Nadolol, a once daily treatment for hypertension multi-centre clinical evaluation." Br J Clin Pract 34 (1980): 211-21

4. 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

5. 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

6. Frishman WH "Nadolol: a new beta-adrenoceptor antagonist." N Engl J Med 305 (1981): 678-82

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

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9. Herrera J, Vukovich RA, Griffith DL "Elimination of nadolol by patients with renal impairment." Br J Clin Pharmacol 7 (1979): s227-31

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

12. Sung RJ, Olukotun AY, Baird CL, et al "Efficacy and safety of oral nadolol for exercise-induced ventricular arrhythmias." Am J Cardiol 60 (1987): d15-20

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

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

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

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

17. 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

18. Merkel C, Gatta A, Sacerdoti D, et al "Long-term effect of nadolol on quantitative liver function tests in patients with cirrhosis." Eur J Clin Pharmacol 34 (1988): 501-4

19. Kanefsky, TM "Organic brain syndrome with nadolol." Arch Intern Med 141 (1981): 1846-7

20. Russell JW, Schuckit MA "Anxiety and depression in patient on nadolol." Lancet 12/04/82 (1982): 1286-7

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

22. 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

23. Wilbur R, Kulik FA "Acute organic brain syndrome fron nadolol therapy." Arch Intern Med 141 (1981): 1723-4

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

25. Levy MB, Fink JN, Guzzetta PA "Nadolol and hypersensitivity pneumonitis." Ann Intern Med 105 (1986): 806-7

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

27. 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

28. 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

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

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

31. 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

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

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

34. 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

35. 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

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

37. 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

38. 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

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

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

41. 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

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

43. 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

44. 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

45. 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

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

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

48. "Renal blood flow during nadolol administration." N Engl J Med 308 (1983): 49-50

49. Raine JM, Palazzo MG, Kerr JH, Sleight P "Near-fatal bronchospasm after oral nadolol in a young asthmatic and response to ventilation with halothane." Br Med J 282 (1981): 548-9

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