Hygroton Side Effects

Generic Name: chlorthalidone

Note: This page contains information about the side effects of chlorthalidone. Some of the dosage forms included on this document may not apply to the brand name Hygroton.

Not all side effects for Hygroton 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 chlorthalidone: oral tablet

In addition to its needed effects, some unwanted effects may be caused by chlorthalidone (the active ingredient contained in Hygroton). 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 chlorthalidone:

Incidence not known
  • Abdominal or stomach pain
  • black, tarry stools
  • bleeding gums
  • blistering, peeling, or loosening of skin
  • bloating
  • blood in urine or stools
  • blurred vision
  • burning, crawling, itching, numbness, prickling, "pins and needles", or tingling feelings
  • chest pain
  • chills
  • clay-colored stools
  • cold sweats
  • confusion
  • constipation
  • cough or hoarseness
  • coughing up blood
  • darkened urine
  • diarrhea
  • dizziness, faintness, or lightheadedness when getting up from a lying or sitting position suddenly
  • dry mouth
  • fast heartbeat
  • fatigue
  • fever
  • flushed, dry skin
  • fruit-like breath odor
  • general feeling of tiredness or weakness
  • headache
  • increased hunger
  • increased thirst
  • increased urination
  • indigestion
  • itching
  • joint pain, stiffness, or swelling
  • loss of appetite
  • lower back or side pain
  • nausea
  • pain in joints or muscles
  • painful or difficult urination
  • pains in stomach, side, or abdomen, possibly radiating to the back
  • pinpoint red spots on skin
  • red irritated eyes
  • red skin lesions, often with a purple center
  • redness, soreness or itching skin
  • shortness of breath
  • skin rash
  • sore throat
  • sores, ulcers, or white spots on lips or in mouth
  • sores, welting, or blisters
  • sugar in the urine
  • sweating
  • swelling of feet or lower legs
  • swollen glands
  • tightness in chest
  • troubled breathing
  • unpleasant breath odor
  • unusual bleeding or bruising
  • unusual tiredness or weakness
  • unusual weight loss
  • vomiting
  • vomiting of blood
  • weight loss
  • wheezing
  • yellow eyes or skin

Some of the side effects that can occur with chlorthalidone 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:

Incidence not known
  • Cramping
  • decreased interest in sexual intercourse
  • difficulty having a bowel movement (stool)
  • feeling of constant movement of self or surroundings
  • hives
  • inability to have or keep an erection
  • increased sensitivity of skin to sunlight
  • loss in sexual ability, desire, drive, or performance
  • muscle spasm
  • redness or other discoloration of skin
  • restlessness
  • sensation of spinning
  • severe sunburn
  • weakness

For Healthcare Professionals

Applies to chlorthalidone: oral tablet

Metabolic

In a prospective study of 83 patients who were taking daily doses of chlorthalidone (the active ingredient contained in Hygroton) 200 mg, 23 (28%) developed a decrease in their serum potassium (K+) concentration by at least 0.6 mEq/L. Keeping the serum K+ replenished during therapy decreases the risk of arrhythmias, myopathy, hyponatremia and abnormal glucose metabolism. Concomitant administration of an angiotensin converting enzyme (ACE) inhibitor can decrease the risk of hypokalemia. (ACE inhibitors decrease serum aldosterone.)[Ref]

There may be significant metabolic side effects of chlorthalidone, as with other thiazide diuretics. Approximately 14% of patients develop hypokalemia during therapy. The risk of hypokalemia, hypomagnesemia, hyponatremia, and hypochloremia appears to be dose-related. Hypercalcemia and an increased serum bicarbonate may result from chlorthalidone diuresis.[Ref]

Cardiovascular

The initial report from the Multiple Risk Factor Intervention Trial (MRFIT) raised the possibility that the increased coronary heart disease (CHD) mortality observed in a subset of men with hypertension who were taking diuretics may be misleading. Subsequent analysis of the data reveals no consistent relationship between CHD mortality and the dose of chlorthalidone (the active ingredient contained in Hygroton) the most recent serum potassium concentration, or the presence of premature ventricular depolarizations (PVDs). It is probable that these men had left ventricular hypertrophy, which is associated with a greater incidence of PVDs, even in the absence of diuretic therapy.

Chlorthalidone-induced hypokalemia can rarely cause serious arrhythmias in otherwise healthy patients. It is recommended that the serum potassium concentration be kept within normal limits during chlorthalidone therapy, especially in patients who are predisposed to arrhythmias.[Ref]

Cardiovascular side effects are related to decreased intravascular volume and hypokalemia. Hypokalemia may induce or provoke arrhythmias in some patients. Orthostatic hypotension and syncope have been reported in rare cases.[Ref]

Hypersensitivity

Hypersensitivity reactions to thiazide diuretics usually involve the skin. Thiazides and chlorthalidone (the active ingredient contained in Hygroton) have been implicated as the cause of necrotizing vasculitis, psoriasiform eruptions, and pseudoporphyria (bullous photosensitive lesions) in rare cases.[Ref]

Renal

New or worsened renal insufficiency may develop if patients become too dehydrated. The use of chlorthalidone (the active ingredient contained in Hygroton) has been associated with mild decreases in urine concentrating ability and renal plasma flow, suggestive of interference with renal tubular function.[Ref]

Nervous system

Nervous system side effects include sleep disturbances in 18% of patients, which may be made worse with a sodium-restricted diet. Headache or fatigue have been reported in approximately 7% of patients.[Ref]

Endocrine

Endocrinologic abnormalities related to chlorthalidone (the active ingredient contained in Hygroton) as with other thiazide diuretics, include decreased glucose tolerance and an adverse effect on the lipid profile. This may be important in some patients with a history of diabetes or coronary artery disease.[Ref]

Use of chlorthalidone has been associated with increases in total serum cholesterol, triglycerides, and LDL cholesterol.

At least one case of severe glucose intolerance, resulting in hyperosmolar hyperglycemic nonketotic coma, has been associated with chlorthalidone. The patient did not have diabetes, had a normal fasting blood glucose prior to chlorthalidone therapy, and did well on no antidiabetic medications after resolution of the acute episode of hyperglycemia. Infection and myocardial infarction were ruled out.[Ref]

Genitourinary

The etiology of sexual dysfunction associated with chlorthalidone (the active ingredient contained in Hygroton) is not known. One study of 19 middle-aged hypertensive men showed no significant decrease in serum zinc or testosterone relative to a control group of 31 unmedicated middle-aged normotensive men. While sexual dysfunction was reported in 42% of treated men (compared to 16% in the control group), serum testosterone and zinc levels were actually higher in the treated group, and were highest in the men on the highest dose of chlorthalidone.

One study revealed that sexual dysfunction associated with chlorthalidone may be worsened by a low sodium diet and ameliorated by a diet designed to help lose weight. The influence of diet alone or the associated nutritional counseling and sense of well-being on sexual function was not measured.

The Treatment of Mild Hypertension Study (TOMHS), a randomized, placebo-controlled, double-blind study has shown that there is a significantly higher incidence of sexual dysfunction (obtaining and maintaining erections) among male patients who were taking chlorthalidone at 24 and 48 months compared with placebo.[Ref]

Genitourinary complaints of decreased sexual libido and erections have been reported in up to 42% of male patients. Decreased sexual arousal and orgasm have rarely been reported among female patients.[Ref]

Musculoskeletal

Musculoskeletal weakness or cramps have been reported in approximately 7% of patients. Chlorthalidone-induced hypokalemia has resulted in hypokalemic myopathy in rare cases.[Ref]

Cases of progressive generalized paralysis associated with chlorthalidone-induced hypokalemia have been reported. In some of these cases, muscle histology is remarkable for vacuolar degeneration.[Ref]

Gastrointestinal

Gastrointestinal complaints are unusual. Approximately 5% to 10% of patients complain of nausea, vomiting, abdominal cramping, diarrhea, or constipation. A case of acute bacterial pancreatitis and rare cases of intrahepatic cholestasis have been associated with chlorthalidone (the active ingredient contained in Hygroton) [Ref]

Hematologic

A 63-year-old man with hypertension, ischemic heart disease, chronic bronchitis, and type II diabetes mellitus was stable on multiple medications until chlorthalidone (the active ingredient contained in Hygroton) was substituted for hydrochlorothiazide. Within three weeks after beginning chlorthalidone, the patient developed a diffuse, upper extremity pruritic rash, fever, dyspnea, malaise, and fatigue associated with a peripheral leukocyte count of 2,000/mm3. Bone marrow aspiration revealed hypocellularity of the myeloid line only. Within nine days after stopping chlorthalidone, the patient's leukocyte count returned to normal. No other cause of neutropenia was discovered; the presence of an antineutrophil antibody was not proven.[Ref]

Hematologic side effects that have been rarely associated with chlorthalidone include neutropenia, agranulocytosis, thrombocytopenia, and aplastic anemia.[Ref]

Ocular

The mechanism of myopia is unknown. There is evidence of an allergic reaction, where the ciliary body may become edematous, and of a direct disturbance of the normal salinity of the lens. Either may alter the refractive index. In some cases, ultrasonography of affected eyes has shown a difference both in the anterior chamber depth and in the lens thickness during chlorthalidone (the active ingredient contained in Hygroton) therapy.[Ref]

Transient myopia is a rarely reported ocular side effect.[Ref]

References

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2. Falch DK, Schreiner AM "Changes in urinary electrolytes versus serum electrolytes during treatment of primary hypertension with chlorthalidone alone and in combination with spironolactone." Acta Med Scand 209 (1981): 111-4

3. Remenchik AP, Johnston LC "Potassium depletion produced by administration of chlorthalidone to nonedematous patients with arterial hypertensin." Am J Med Sci 252 (1966): 171-6

4. Perry HM, Jr "Some wrong-way chemical changes during antihypertensive treatment: comparison of indapamide and related agents." Am Heart J 106 (1983): 251-7

5. Katz FH, Eckert RC, Gebott MD "Hypokalemia caused by surreptitious self-administration of diuretics." Ann Intern Med 76 (1972): 85-90

6. Cembrowski GS, Huntington RW, 3d "Probable fatal cardiac dysrhythmia secondary to diuretic-induced hypokalemia." Am J Forensic Med Pathol 2 (1981): 243-8

7. Landmann-Suter R, Struyvenberg A "Initial potassium loss and hypokalaemia during chlorthalidone administration in patients with essential hypertension: the influence of dietary sodium restriction." Eur J Clin Invest 8 (1978): 155-64

8. Berg KJ, Gisholt K, Wideroe TE "Potassium deficiency in hypertensives treated with diuretics. Analysis of three alternative treatments by an oral test for potassium deficiency." Eur J Clin Pharmacol 7 (1974): 401-5

9. Navarro RP, O'Brien DK, Nuffort P, Spencer DL "Diuretic induced hypokalemia in the elderly." J Fam Pract 14 (1982): 685-9

10. Kuller L, Farrier N, Caggiula A, Borhani N, Dunkle S "Relationship of diuretic therapy and serum magnesium levels among participants in the Multiple Risk Factor Intervention Trial." Am J Epidemiol 122 (1985): 1045-59

11. Sumiye L, Vivian AS, Frisof KB, Podany EC "Potassium loss associated with hydrochlorothiazide versus chlorthalidone." Clin Ther 4 (1981): 308-20

12. Chowdhury FR, Bleicher SJ "Chlorthalidone--induced hypokalemia and abnormal carbohydrate metabolism." Horm Metab Res 2 (1970): 13-6

13. Palmer FJ "Letter: Chlorthalidone-induced hypercalcemia." JAMA 229 (1974): 267

14. Curtis J, Horrigan F, Ahearn D, Varney R, Sandler SG "Chlorthalidone-induced hyperosmolar hyperglycemic nonketotic coma." JAMA 220 (1972): 1592-3

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

16. Jensen OB, Mosdal C, Reske-Nielsen E "Hypokalemic myopathy during treatment with diuretics." Acta Neurol Scand 55 (1977): 465-82

17. Carney SL, Morgan TO "Diuretic-induced hypokalemia and altered renal function." Int J Clin Pharmacol Ther Toxicol 24 (1986): 665-7

18. Papademetriou V, Fletcher R, Khatri IM, Freis ED "Diuretic-induced hypokalemia in uncomplicated systemic hypertension: effect of plasma potassium correction on cardiac arrhythmias." Am J Cardiol 52 (1983): 1017-22

19. Simunic M, Rumboldt Z, Ljutic D, Sardelic S "Ramipril decreases chlorthalidone-induced loss of magnesium and potassium in hypertensive patients." J Clin Pharmacol 35 (1995): 1150-5

20. Stewart DE, Ikram H, Espiner EA, Nicholls MG "Arrhythmogenic potential of diuretic induced hypokalaemia in patients with mild hypertension and ischaemic heart disease." Br Heart J 54 (1985): 290-7

21. 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

22. "Product Information. Thalitone (chlorthalidone)." Monarch Pharmaceuticals Inc, Bristol, TN.

23. MacGregor GA, Tasker PR, de Wardener HE "Diuretic-induced oedema." Lancet 1 (1975): 489-92

24. Obel AO "Efficacy and tolerability of long term oxprenolol and chlorthalidone singly and in combination in hypertensive blacks." Jpn Heart J 31 (1990): 183-92

25. Burris JF, Davidov ME, Jenkins P, Rofman B, Ginsberg D, Rosenbaum R, Ryan JR, Jain AK, Mroczek WJ "Comparison of the antihypertensive effects of betaxolol and chlorthalidone as monotherapy and in combination." Arch Intern Med 149 (1989): 2437-41

26. Kuller LH, Hulley SB, Cohen JD, Neaton J "Unexpected effects of treating hypertension in men with electrocardiographic abnormalities: a critical analysis." Circulation 73 (1986): 114-23

27. Baker EJ, Reed KD, Dixon SL "Chlorthalidone-induced pseudoporphyria: clinical and microscopic findings of a case." J Am Acad Dermatol 21 (1989): 1026-9

28. Smith N "Acute stomatitis medicamentosa. Two case reports." Aust Dent J 23 (1978): 305-7

29. Pallin O, Ericsson R "Ultrasound studies in a case of hygroton-induced myopia." Acta Ophthalmol (Copenh) 43 (1965): 692-6

30. Bjornberg A, Gisslen H "Thiazides: A cause of necrotising vasculitis?" Lancet 2 (1965): 982-3

31. Snaith RP, McCoubrie M "Antihypertensive drugs and depression." Psychol Med 4 (1974): 393-8

32. Wassertheil-Smoller S, Oberman A, Blaufox MD, Davis B, Langford H "The Trial of Antihypertensive Interventions and Management (TAIM) Study. Final results with regard to blood pressure, cardiovascular risk, and quality of life." Am J Hypertens 5 (1992): 37-44

33. Andersen OO, Persson I "Carbohydrate metabolism during treatment with chlorthalidone and ethacrynic acid." Br Med J 2 (1968): 798-801

34. Ames RP, Hill P "Increase in serum-lipids during treatment of hypertension with chlorthalidone." Lancet 1 (1976): 721-3

35. Stessman J, Ben-Ishay D "Chlorthalidone-induced impotence." Br Med J 281 (1980): 714

36. Geissler AH, Turnlund JR, Cohen RD "Effect of chlorthalidone on zinc levels, testosterone, and sexual function in man." Drug Nutr Interact 4 (1986): 275-83

37. Grimm RH, Granditis GA, Prineas RJ, et al. "Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women: treatment of mild hypertension study (TOMHS)." Hypertension 29 (1997): 8-14

38. Oh SJ, Douglas JE, Brown RA "Hypokalemic vacuolar myopathy associated with chlorthalidone treatment." JAMA 216 (1971): 1858-9

39. Eckhauser ML, Dokler M, Imbembo AL "Diuretic-associated pancreatitis: a collective review and illustrative cases." Am J Gastroenterol 82 (1987): 865-70

40. Writer ST, Stevens DL, Starkebaum G "Chlorthalidone-associated neutropenia." West J Med 136 (1982): 59-61

41. Stennis SD "Drug-induced myopia: a case report." Am J Optom Physiol Opt 53 (1976): 422-3

42. D'Alena P, Robinson M "Hygroton-induced myopia." Calif Med 110 (1969): 134-5

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