Chlorthalidone Side Effects

Brand Names: Thalitone

Please note - some side effects for Chlorthalidone may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA.

Side Effects of Chlorthalidone - for the Consumer

Chlorthalidone

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Chlorthalidone:

Constipation; dizziness; headache; lightheadedness, especially when sitting up or standing.

Seek medical attention right away if any of these SEVERE side effects occur when using Chlorthalidone:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); drowsiness; dry mouth; impotence; inflammation of the pancreas; muscle pain or cramps; nausea; rapid or irregular heartbeat; rash or itching; restlessness; unusual thirst; unusual tiredness or weakness; vomiting; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

Chlorthalidone/Clonidine

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Chlorthalidone/Clonidine:

Constipation; dizziness; drowsiness; dry mouth; tiredness.

Seek medical attention right away if any of these SEVERE side effects occur when using Chlorthalidone/Clonidine:

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); agitation; confusion; dark urine; decreased urination; depression; fast, slow, or irregular heartbeat; fever, chills, or sore throat; hallucinations; inability to have sex; increased thirst; joint pain (gout); muscle pain or cramps; nausea; numbness or tingling of the skin; pounding in the chest; rapid breathing; red, swollen, blistered, or peeling skin; restlessness; severe or persistent drowsiness or dry mouth; sluggishness; unusual bruising or bleeding; unusual tiredness or weakness; vision changes; vomiting; weakness; yellowing of the skin or eyes.

This is not a complete list of all side effects that may occur. If you have questions about side effects, contact your health care provider. Call your doctor for medical advice about side effects. To report side effects to the appropriate agency, please read the Guide to Reporting Problems to FDA.

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Chlorthalidone Side Effects - for the Professional

Chlorthalidone

The following adverse reactions have been observed, but there is not enough systematic collection of data to support an estimate of their frequency.

Gastrointestinal System Reactions: anorexia, gastric irritation, nausea, vomiting, cramping, diarrhea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis.

Central Nervous System Reactions: dizziness, vertigo, paresthesias, headache, xanthopsia.

Hematologic Reactions: leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia.

Dermatologic-Hypersensitivity Reactions: purpura, photosensitivity, rash, urticaria, necrotizing angiitis (vasculitis, cutaneous vasculitis), Lyell's syndrome (toxic epidermal necrolysis).

Cardiovascular Reactions: orthostatic hypotension may occur and may be aggravated by alcohol, barbiturates, or narcotics.

Other Adverse Reactions: hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness, impotence.

Whenever adverse reactions are moderate or severe, Chlorthalidone dosage should be reduced or therapy withdrawn.

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Side Effects by Body System - for Healthcare Professionals

Metabolic

In a prospective study of 83 patients who were taking daily doses of chlorthalidone 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.)

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.

Cardiovascular

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.

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 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.

Hypersensitivity

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

Renal

New or worsened renal insufficiency may develop if patients become too dehydrated. The use of chlorthalidone has been associated with mild decreases in urine concentrating ability and renal plasma flow, suggestive of interference with renal tubular function.

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.

Endocrine

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.

Endocrinologic abnormalities related to chlorthalidone, 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.

Genitourinary

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.

The etiology of sexual dysfunction associated with chlorthalidone 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.

Musculoskeletal

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.

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

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.

Hematologic

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

A 63-year-old man with hypertension, ischemic heart disease, chronic bronchitis, and type II diabetes mellitus was stable on multiple medications until chlorthalidone 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.

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 therapy.

Transient myopia is a rarely reported ocular side effect.

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