Atenolol/Chlorthalidone Side Effects

Please note - some side effects for Atenolol/Chlorthalidone may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Atenolol/Chlorthalidone - for the Consumer

Atenolol/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 Atenolol/Chlorthalidone:

Cold fingers or toes; diarrhea; dizziness; drowsiness; headache; lack of energy; lightheadedness; nausea; tiredness.

Severe allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); blue fingernails, toenails, or palms; decreased urination; fainting; fast, slow, or irregular heartbeat; increased thirst; mental or mood changes (eg, depression); muscle pain, cramps, or weakness; restlessness; severe joint pain (especially in the big toe); severe or persistent dizziness, drowsiness, or weakness; severe or persistent nausea, vomiting, or dry mouth; sluggishness; swelling of the hands or feet; trouble breathing; unusual bruising or bleeding; yellowing of the skin and eyes.

Side Effects by Body System

General

Atenolol-chlorthalidone is generally well tolerated. A postmarketing surveillance study of over 28,000 patients revealed that the incidence of any adverse event was less than 1%, except for dizziness (1.5%). Over an eight month study period, 3.1% of patients discontinued therapy due to side effects.

Metabolic

The metabolic side effects of chlorthalidone, as with other thiazide diuretics, may require electrolyte monitoring and/or potassium supplementation. 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.

Metabolic side effects of atenolol have included weight gain.

In a prospective study of 83 patients who were taking daily doses of chlorthalidone 200 mg, 23 (28%) developed a decrease in serum potassium of at least 0.6 mEq/L. Maintenance of normal serum potassium levels during chlorthalidone therapy decreases the risk of arrhythmias, myopathy, hyponatremia and abnormal glucose metabolism.

The mechanism by which atenolol induces weight gain is unknown. Some investigators have reported a 4% to 9% reduction in total energy expenditure and a 25% reduction in thermogenic response to food during beta-blocker treatment.

Cardiovascular

A large, retrospective review of the use of atenolol-chlorthalidone revealed the incidence of bradycardia to be only 0.5%. Other cardiovascular side effects include hypotension, precipitation of heart failure, and cold extremities. Less than 1% of patients report flushing symptoms. These problems may limit the use of the combination product in some patients. Chlorthalidone can cause significant intravascular volume depletion and hypokalemia. Orthostatic hypotension and syncope have been reported rarely. Hypokalemia may induce or provoke arrhythmias in some patients.

Atenolol-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, especially in patients who are predisposed to arrhythmias.

Hypersensitivity

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

Genitourinary

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 levels relative to a control group of 31 unmedicated middle-aged normotensive men. While sexual dysfunction was reported in 42% of treated men on chlorthalidone alone (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.

Genitourinary problems associated with atenolol and chlorthalidone as monotherapy include impotence in up to 14% and 42% of male patients, respectively. However, a large, retrospective study revealed a 0.6% incidence of impotence associated with the combination, atenolol-chlorthalidone. Decreased sexual arousal and orgasm have rarely been reported by female patients.

Nervous system

Rare cases of acute visual loss have been associated with atenolol and atenolol-chlorthalidone. In some cases, there was evidence of retinal arteriolar spasm. At least one affected patient did well on atenolol alone after discontinuation of the combination product.

Nervous system-related complaints of depression, headache, fatigue, and sleep disturbances each occur in approximately 2% to 20% of patients. Fatigue and insomnia, however, have been reported in up to 50% of patients on atenolol monotherapy.

Respiratory

The respiratory system is usually not affected by atenolol because it is relatively specific for beta-1-adrenergic receptors. However, at higher doses, and sometimes even at usual doses, atenolol may block beta-2-adrenergic receptors. Such blockade can result in dyspnea or wheezing, particularly in patients with a history of reactive airways disease.

Endocrine

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.

A 38-year-old woman with hypertension developed oligomenorrhea, then galactorrhea associated with a significantly elevated serum prolactin while taking atenolol. Head CT scan was negative for a pituitary tumor. The serum prolactin level returned to baseline and the patient's symptoms resolved within two months after discontinuation of the drug. Rechallenge was refused.

Endocrinologic abnormalities related to chlorthalidone, and other thiazide diuretics, include decreased glucose tolerance and adverse effects on lipid profiles. Atenolol may increase serum triglycerides. Such increases may be important in some patients with a history of diabetes or coronary artery disease. A rare case of hyperprolactinemia with galactorrhea has been associated with atenolol. Beta-blockers can mask signs and symptoms of hypoglycemia (sweating and tachycardia) and hyperthyroidism.

Among patients with hyperthyroidism, atenolol has been reported to have decreased T3 concentrations slightly (but did not change T4 concentrations).

Renal

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

Gastrointestinal

A 68-year-old woman with hypertension developed vomiting, abdominal pain, and progressive renal failure associated with extensive retroperitoneal fibrosis and urethral obstruction. While the patient was also taking oral iron preparations, metoclopramide, and ibuprofen, the authors of this case report implicated atenolol due to previous associations of retroperitoneal fibrosis to other beta-blockers.

Gastrointestinal problems are generally mild. Approximately 5% to 10% of patients on chlorthalidone monotherapy complain of nausea, vomiting, abdominal cramping, diarrhea, or constipation. A large, retrospective study of over 28,000 patients who received atenolol-chlorthalidone reported none of these complaints in more than 1% of patients. Rare cases of retroperitoneal fibrosis have been associated with some beta-blockers, including atenolol.

Psychiatric

Psychiatric problems associated with beta-blockers include depression. Rare cases of acute psychosis have been associated with atenolol.

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 was substituted for hydrochlorothiazide. Within three weeks of initiation of 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.

Rare hematologic side effects have been associated with chlorthalidone, including neutropenia, agranulocytosis, thrombocytopenia, and aplastic anemia.

Hepatic

Hepatic injury associated with either drug is rare. Cases of acute hepatic cholestasis have been associated with atenolol.

A 73-year-old man with hypertension developed pruritus and right upper quadrant abdominal pain associated with elevated serum liver function tests within nine months after switching from methyldopa to atenolol. Liver biopsy revealed canalicular and centrolobular cholestasis. No other etiology was found. The patient's signs and symptoms of hepatitis resolved within one to four weeks after stopping atenolol. Rechallenge was not done.

Musculoskeletal

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

Musculoskeletal weakness and cramps have each been reported in up to 7% of patients on chlorthalidone monotherapy. Chlorthalidone-induced hypokalemia has resulted in hypokalemic myopathy in rare cases.

Ocular

The mechanism of myopia is unknown. There is evidence of an allergic reaction in which the ciliary body may become edematous, and evidence of a direct disturbance by chlorthalidone of the normal salinity of the lens. Either effect 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.

A rare ocular side effect, transient myopia, has been associated with chlorthalidone.

Immunologic

A 64-year-old woman with hypertension developed fever and chest pain associated with pericardial effusion, progressive renal dysfunction, and elevated serum anti-IgG antibodies while taking atenolol. The signs and symptoms of the syndrome resolved two months after discontinuation of the drug.

Immunologic effects associated with atenolol include a single report of drug-induced systemic lupus erythematosus.

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.