Atenolol / chlorthalidone Side Effects

Not all side effects for atenolol / chlorthalidone 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 atenolol / chlorthalidone: oral tablet

In addition to its needed effects, some unwanted effects may be caused by atenolol / chlorthalidone. 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 atenolol / chlorthalidone:

More common
  • Cold arms or legs
  • difficult or labored breathing
  • shortness of breath
  • tightness in chest
  • wheezing
Less common
  • Chest pain or discomfort
  • chills
  • cold sweats
  • confusion
  • dizziness, faintness, or lightheadedness when getting up from lying or sitting position
  • leg pain
  • lightheadedness, dizziness, or fainting
  • slow or irregular heartbeat
  • unusual tiredness or weakness
Incidence not determined
  • Black, tarry stools
  • bleeding gums
  • blood in urine or stools
  • feeling that others are watching you or controlling your behavior
  • feeling that others can hear your thoughts
  • fever
  • general feeling of discomfort, illness, or weakness
  • paleness or cold feeling in fingertips and toes
  • pinpoint red spots on skin
  • seeing, hearing, or feeling things that are not there
  • severe mood or mental changes
  • skin irritation or rash, including rash that looks like psoriasis
  • tingling or pain in fingers or toes when exposed to cold
  • unusual behavior
  • unusual bleeding or bruising

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

Symptoms of overdose
  • Blurred vision
  • decreased urination
  • dry mouth
  • increase in heart rate
  • muscle cramps or pain
  • numbness, tingling, pain, or weakness in hands or feet
  • rapid breathing
  • seizures
  • sunken eyes
  • sweating
  • thirst
  • trembling
  • weakness and heaviness of legs
  • wrinkled skin

Some of the side effects that can occur with atenolol / 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:

More common
  • Discouragement
  • feeling sad or empty
  • irritability
  • lack of appetite
  • loss of interest or pleasure
  • tiredness
  • trouble concentrating
  • trouble sleeping
Less common
  • Diarrhea
  • feeling of constant movement of self or surroundings
  • nausea
  • sensation of spinning
  • unusual drowsiness, dullness, or feeling of sluggishness
Incidence not determined
  • Decreased interest in sexual intercourse
  • disturbed color perception
  • double vision
  • hair loss, thinning of hair
  • halos around lights
  • headache
  • inability to have or keep an erection
  • loss in sexual ability, desire, drive, or performance
  • loss of vision
  • night blindness
  • overbright appearance of lights
  • pain of penis on erection
  • tunnel vision

For Healthcare Professionals

Applies to atenolol / chlorthalidone: oral tablet

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.[Ref]

Metabolic

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

Genitourinary

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

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).[Ref]

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.[Ref]

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.[Ref]

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.[Ref]

Psychiatric

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

Hematologic

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

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.[Ref]

Hepatic

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

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.[Ref]

Musculoskeletal

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.[Ref]

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.[Ref]

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.[Ref]

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

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.[Ref]

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

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