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Pronunciation:

(klor THAL i done)

U.S. Brand Names:

Thalitone®

Synonyms:

Hygroton

Generic Available:

Yes

Canadian Brand Names:

Apo-Chlorthalidone®

Use:

Management of mild to moderate hypertension when used alone or in combination with other agents; treatment of edema associated with congestive heart failure or nephrotic syndrome. Recent studies have found chlorthalidone effective in the treatment of isolated systolic hypertension in the elderly.

Pregnancy Risk Factor:

B (manufacturer); D (expert analysis)

Lactation:

Enters breast milk/use caution (AAP rates "compatible")

Contraindications:

Hypersensitivity to chlorthalidone or any component of the formulation; cross-sensitivity with other thiazides or sulfonamides; anuria; renal decompensation; pregnancy

Warnings/Precautions:

Use with caution in patients with hypokalemia, renal disease, hepatic disease, gout, lupus erythematosus, or diabetes mellitus. Use with caution in severe renal diseases. Correct hypokalemia before initiating therapy. Chemical similarities are present among sulfonamides, sulfonylureas, carbonic anhydrase inhibitors, thiazides, and loop diuretics (except ethacrynic acid). Use in patients with thiazide or sulfonamide allergy is specifically contraindicated in product labeling, however, a risk of cross-reaction exists in patients with allergy to any of these compounds; avoid use when previous reaction has been severe.

Adverse Reactions:

1% to 10%:

Dermatologic: Photosensitivity

Endocrine & metabolic: Hypokalemia

Gastrointestinal: Anorexia, epigastric distress

<1% (Limited to important or life-threatening): Agranulocytosis, aplastic anemia, cholecystitis, constipation, cutaneous vasculitis, diarrhea, dizziness, glycosuria, headache, hepatic function impairment, hypercalcemia, hyperglycemia, hyperuricemia or gout, hyponatremia, insomnia, leukopenia, muscle cramps or spasm, nausea, necrotizing angiitis, pancreatitis, paresthesia, polyuria, purpura, rash, restlessness, sexual ability (decreased), thrombocytopenia, urticaria, vomiting, vasculitis, weakness

Overdosage/Toxicology:

Symptoms of overdose include hypermotility, diuresis, lethargy, confusion, muscle weakness, and coma. Treatment is supportive.

Drug Interactions:

ACE inhibitors: Increased hypotension if aggressively diuresed with a thiazide diuretic.

Beta-blockers increase hyperglycemic effects of thiazides in type 2 diabetes mellitus (noninsulin dependent, NIDDM)

Cyclosporine and thiazides can increase the risk of gout or renal toxicity; avoid concurrent use.

Digoxin toxicity can be exacerbated if a thiazide induces hypokalemia or hypomagnesemia.

Lithium toxicity can occur by reducing renal excretion of lithium; monitor lithium concentration and adjust as needed.

Neuromuscular blocking agents can prolong blockade; monitor serum potassium and neuromuscular status.

NSAIDs can decrease the efficacy of thiazides reducing the diuretic and antihypertensive effects.

Ethanol/Nutrition/Herb Interactions:

Herb/Nutraceutical: Avoid dong quai if using for hypertension (has estrogenic activity). Avoid dong quai, St John's Wort (may also cause photosensitization). Avoid ephedra, yohimbe, ginseng (may worsen hypertension).

Mechanism of Action:

Sulfonamide-derived diuretic that inhibits sodium and chloride reabsorption in the cortical-diluting segment of the ascending loop of Henle

Pharmacodynamics/Kinetics:

Onset of action: Peak effect: 2-6 hours

Absorption: 65%

Distribution: Crosses placenta; enters breast milk

Metabolism: Hepatic

Half-life elimination: 35-55 hours; may be prolonged with renal impairment; Anuria: 81 hours

Excretion: Urine (~50% to 65% as unchanged drug)

Dosage:

Oral:

Children (nonapproved): 2 mg/kg/dose 3 times/week or 1-2 mg/kg/day

Adults: 25-100 mg/day or 100 mg 3 times/week; usual dosage range (JNC 7): 12.5-25 mg/day

Elderly: Initial: 12.5-25 mg/day or every other day; there is little advantage to using doses >25 mg/day

Dosage adjustment in renal impairment: Clcr<10 mL/minute: Administer every 48 hours

Monitoring Parameters:

Assess weight, I & O records daily to determine fluid loss; blood pressure, serum electrolytes, renal function

Test Interactions:

Increased creatine phosphokinase [CPK] (S), ammonia (B), amylase (S), calcium (S), chloride (S), cholesterol (S), glucose, increased acid (S), decreased chloride (S), magnesium, potassium (S), sodium (S)

Dietary Considerations:

This product may cause a potassium loss; your healthcare provider may prescribe a potassium supplement, another medication to help prevent the potassium loss, or recommend that you eat foods high in potassium, especially citrus fruits; do not change your diet on your own while taking this medication, especially if you are taking potassium supplements or medications to reduce potassium loss; too much potassium can be as harmful as too little.

Patient Education:

Inform prescriber of all prescriptions, OTC medications, or herbal products you are taking, and any allergies you have. Do not take any new medication during therapy unless approved by prescriber. Take once-daily dose in morning or last of daily doses early in the day to avoid night-time disturbances. You may need to make dietary changes; follow dietary suggestions of prescriber (see Dietary Considerations). If using oral hypoglycemics, monitor glucose levels closely (this medication may reduce effect of oral hypoglycemics); contact prescriber with any major changes. May cause sensitivity to sunlight (use sunblock, wear protective clothing, and avoid direct sunlight); or anorexia or GI distress (small, frequent meals, frequent mouth care, chewing gum, or sucking lozenges may help). Report muscle twitching or cramps; nausea or vomiting; confusion; numbness of extremities; loss of appetite or GI distress; severe rash, redness, or itching of skin; chest pain or palpitations; or respiratory difficulty. Pregnancy/breast-feeding precautions: Do not get pregnant while taking this medication. Consult prescriber for appropriate contraceptive measures. Consult prescriber if breast-feeding.

Nursing Implications:

Take blood pressure with patient lying down and standing

Cardiovascular Considerations:

Thiazide diuretics are effective first-line therapeutic agents in the management of hypertension and have proven to be of benefit in terms of cardiovascular outcome. They may act synergistically to lower blood pressure when combined with an ACE inhibitor or beta-blocker. The initial concern about thiazide diuretic-induced hypokalemia, glucose intolerance, and lipid profiles does not appear to be of substantial clinical consequence in the treatment of hypertension. The benefits of this class of agents in the treatment of hypertension is established and compares well with other first-line therapeutic agents.

Diuretics are standard therapy for the management of edema in patients with heart failure.

Dental Health: Effects on Dental Treatment:

No significant effects or complications reported

Dental Health: Vasoconstrictor/Local Anesthetic Precautions:

No information available to require special precautions

Mental Health: Effects on Mental Status:

None reported

Mental Health: Effects on Psychiatric Treatment:

Rare reports of blood dyscrasias; use caution with clozapine and carbamazepine; thiazides decrease lithium clearance resulting in elevated serum lithium levels and potential toxicity; monitor serum lithium levels

Dosage Forms:

Tablet: 25 mg, 50 mg, 100 mg

Thalitone®: 15 mg

International Brand Names:

Apo-Chlorthalidone® (CA)

References

"American Academy of Pediatrics Committee on Drugs. The Transfer of Drugs and Other Chemicals Into Human Milk,"Pediatrics, 2001, 108(3):776-89.

Chobanian AV, Bakris GL, Black HR, et al, "The Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure: The JNC 7 Report,"JAMA, 2003, 289(19):2560-71.

Liebson PR, Grandits GA, Dianzumba S, et al, "Comparison of Five Antihypertensive Monotherapies and Placebo for Change in Left Ventricular Mass in Patients Receiving Nutritional-Hygienic Therapy in the Treatment of Mild Hypertension Study (TOMHS),"Circulation, 1995, 91(30):698-706.

"Prevention of Stroke by Antihypertensive Drug Treatment in Older Persons With Isolated Systolic Hypertension. Final Results of the Systolic Hypertension in the Elderly Program (SHEP). SHEP Cooperative Research Group,"JAMA, 1991, 265(24):3255-64.

Savage PJ, Pressel SL, Curb JD, et al, "Influence of Long-Term, Low-Dose, Diuretic-Based, Antihypertensive Therapy on Glucose, Lipid, Uric Acid, and Potassium Levels in Older Men and Women With Isolated Systolic Hypertension: The Systolic Hypertension in the Elderly Program. SHEP Cooperative Research Group,"Arch Intern Med, 1998, 158(7):741-51.

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