Chlorthalidone, first patented in 1957 and introduced for clinical use in 1960 under the brand name Hygroton, is an oral, long‑acting thiazide‑like diuretic approved by the U.S. Food & Drug Administration (FDA) for hypertension. It is now widely available in generic form and is considered a first‑line treatment for high blood pressure thanks to its extended duration of action and demonstrated cardiovascular benefits (such as reduced risks of stroke and heart failure). Acting at the kidneys, chlorthalidone promotes the removal of excess salt and water by inhibiting the sodium‑chloride cotransporter in the distal convoluted tubule, thereby lowering blood pressure and reducing swelling (edema) associated with heart, kidney, or liver disease; it can be used alone or in combination with other antihypertensive medications.
BRAND NAMES
Chlorthalidone is available under several brand names worldwide. The most common brand names in the United States and internationally include:
Hygroton — This is a trademarked name under which chlorthalidone was sold.
Thalitone — Another brand name for chlorthalidone.
Hemiclor — A more recent brand name for chlorthalidone (12.5 mg tablet) approved by the FDA.
MECHANISM OF ACTION
Chlorthalidone works by inhibiting the sodium‑chloride (Na⁺/Cl⁻) symporter in the distal convoluted tubule of the kidney, which decreases reabsorption of sodium and chloride and thereby increases the elimination of salt and water through urine. In addition, it has some inhibitory effect on carbonic anhydrase in the proximal tubule, which further contributes to its diuretic action. The resulting reduction in fluid volume lowers blood pressure in patients with hypertension and helps reduce swelling (edema) associated with conditions such as heart, kidney, or liver disease.
PHARMACOKINETICS
Absorption
The oral absorption of Chlorthalidone is gradual, with peak plasma concentrations typically occurring between 2 and 6 hours after administration.
Distribution
It shows high plasma protein binding (around 75%, with about 58% bound to albumin), and its affinity for red‑blood‑cell carbonic anhydrase contributes to its extended distribution.
Metabolism
Chlorthalidone undergoes partial hepatic metabolism, though the precise metabolic pathways remain only partially defined.
Excretion
The primary route of elimination is renal—most of the absorbed drug is eliminated unchanged via the kidneys. Its elimination half‑life ranges from about 40 to 60 hours, which supports a sustained duration of action lasting roughly 48 to 72 hours.
PHARMACODYNAMICS
The pharmacodynamics of chlorthalidone involve inhibiting sodium and chloride reabsorption in the kidneys, primarily at the distal convoluted tubule. This action leads to increased urinary excretion of water and electrolytes, resulting in a diuretic and antihypertensive effect.
ADMINISTRATION
Chlorthalidone is available exclusively as an oral tablet and is usually taken once daily, though in some cases a healthcare provider may recommend every other day. The medication should be taken in the morning, ideally with breakfast, to minimize nighttime urination and improve absorption while reducing the risk of stomach upset.
DOSAGE AND STRENGTH
Chlorthalidone is offered in several oral tablet strengths, including 12.5 mg, 15 mg, 25 mg, and 50 mg. The prescribed dose depends on the condition being treated, such as high blood pressure (hypertension) or fluid retention (edema).
Available Strengths:
Generic Chlorthalidone: Commonly available in 25 mg and 50 mg tablets, with a 12.5 mg option sometimes offered under certain brand names.
Brand-name Chlorthalidone (Thalitone): Available in 15 mg and 25 mg tablets.
DRUG INTERACTIONS
Chlorthalidone can interact with several medications, particularly those that affect blood pressure and electrolyte balance. Careful monitoring is important when it is used with certain drugs.
Lithium: Chlorthalidone may reduce the kidneys’ ability to clear lithium, leading to higher lithium levels and an increased risk of toxicity. Regular monitoring or using an alternative combination may be necessary.
Digoxin: By lowering potassium levels, chlorthalidone can make the heart more sensitive to digoxin, increasing the risk of toxicity and abnormal heart rhythms. Electrolytes and digoxin levels should be closely monitored.
Other medications: Chlorthalidone may also interact with corticosteroids, anti-diabetic drugs (including insulin), and NSAIDs, potentially affecting their efficacy or increasing side effects.
FOOD INTERACTIONS
Chlorthalidone should be taken with food to help prevent stomach upset, and alcohol intake should be limited due to possible interactions. Patients are advised to avoid excessive salt, coffee, and grapefruit juice. To support healthy potassium levels, a doctor may suggest consuming potassium-rich foods or taking supplements.
CONTRAINDICATIONS
Chlorthalidone is contraindicated in patients with known hypersensitivity to the drug or other sulfonamide-derived medications. It should not be used in individuals with severe kidney impairment or anuria. Patients with a history of electrolyte imbalances, particularly low potassium or sodium, should avoid it. Chlorthalidone is also not recommended during pregnancy unless clearly necessary. Caution is required in those with severe liver disease, as it may worsen liver function.
SIDE EFFECTS
Chlorthalidone is a diuretic ("water pill") used to treat high blood pressure and fluid retention (edema). Its side effects can range from common and mild to more serious and require medical attention.
Common Side Effects
These usually do not require immediate medical attention, but you should report them to your care team if they are persistent or bothersome:
Increased urination
Dizziness or light-headedness, especially when standing up quickly (orthostatic hypotension)
Headache
Upset stomach, nausea, or vomiting
Loss of appetite, stomach cramps, constipation, or diarrhea
Weakness or unusual tiredness
Increased sensitivity to sunlight (photosensitivity)
Decreased sexual ability or performance (impotence)
OVER DOSE
Symptoms: Overdose may cause severe dehydration, low blood pressure, dizziness, weakness, and electrolyte imbalances such as low potassium or sodium.
Cardiac Effects: Hypokalemia from overdose can lead to abnormal heart rhythms or arrhythmias.
Gastrointestinal Effects: Nausea, vomiting, and abdominal cramps may occur.
Management: Treatment typically includes supportive care, monitoring of vital signs, and correction of fluid and electrolyte imbalances.
Medical Attention: Immediate medical attention is required; activated charcoal may be used if ingestion was recent, and hospitalization may be necessary in severe cases.
TOXICITY
Chlorthalidone toxicity mainly arises from electrolyte disturbances, marked dehydration from excessive fluid loss, and pronounced low blood pressure (hypotension). The risk of these serious complications is higher with overdose or prolonged use of high doses.
