hydrochlorothiazide (HCTZ)
Apo-Hydro ◆, Diuchlor H ◆, Esidrix, Ezide, Hydro-chlor, HydroDIURIL, Hydro-Par, Microzide, Neo-Codema ◆, Novo-Hydrazide ◆, Oretic, Urozide ◆

Available forms
Available by prescription only
Capsules: 12.5 mg
Solution: 50 mg/5 ml, 100 mg/ml
Tablets: 25 mg, 50 mg, 100 mg

Indications and dosages
 Edema. Adults: Initially, 25 to 200 mg P.O. daily for several days or until dry weight is attained. Maintenance dosage is 25 to 100 mg P.O. daily or intermittently. A few refractory cases may require up to 200 mg daily.
 Hypertension. Adults: 12.5 to 50 mg P.O. once daily. Daily dose increased or decreased based on blood pressure. Doses greater than 25 mg usually don’t show added benefit.
Children ages 6 months to 12 years: 2.2 mg/kg or 60 mg/m² P.O. daily in two divided doses.
Children younger than age 6 months: Up to 3.3 mg/kg P.O. daily in two divided doses.

Pharmacodynamics
Diuretic action: HCTZ increases urinary excretion of sodium and water by inhibiting sodium reabsorption in the cortical diluting tubule of the nephron, thus relieving edema.
Antihypertensive action: Exact mechanism of antihypertensive effect of drug is unknown. It may result partially from direct arteriolar vasodilation and a decrease in total peripheral resistance.

Pharmacokinetics
Absorption: 65% to 75% absorbed from the GI tract.
Distribution: Unknown.
Metabolism: None.
Excretion: Excreted unchanged in urine, usually within 24 hours; half-life is 5 1/2 to 14 1/4 hours.

Contraindications and precautions
Contraindicated in patients with anuria, hepatic coma, or hypersensitivity to other thiazides or other sulfonamide derivatives. Use cautiously in patients with severely impaired renal or hepatic function or progressive hepatic disease. Drug isn’t effective if creatinine clearance is less than 50 ml/minute.

Interactions
Drug-drug. Amphetamine, methenamine compounds (such as methenamine mandelate), quinidine: Causes alkaline urine, decreased urinary excretion of some amines, decreased therapeutic efficacy. Monitor patient for drug effect.
Antihypertensives: Increases hypotensive effect; this may be used to therapeutic advantage. Check blood pressure frequently.
Cholestyramine, colesevelam, colestipol: May bind HCTZ, preventing its absorption. Give HCTZ 1 hour before or 6 hours after these drugs.
Diazoxide: Increases hyperglycemic, hypotensive, and hyperuricemic effects. Insulin dosage may need to be adjusted.
Lithium: Reduces renal clearance, elevating serum lithium levels. Reduction in lithium dosage by 50% may be needed.
Drug-herb. Dandelion: May interfere with diuretic activity. Discourage use together.

Adverse reactions
CNS: dizziness, vertigo, headache, paresthesia, weakness, restlessness.
CV: volume depletion and dehydration, orthostatic hypotension, allergic myocarditis, vasculitis.
GI: anorexia, nausea, pancreatitis, epigastric distress, vomiting, abdominal pain, diarrhea, constipation.
GU: polyuria, frequent urination, renal failure, interstitial nephritis.
Hematologic: aplastic anemia, agranulocytosis, leukopenia, thrombocytopenia, hemolytic anemia.
Hepatic: jaundice.
Metabolism: hypokalemia; asymptomatic hyperuricemia; hyperglycemia and impaired glucose tolerance; fluid and electrolyte imbalances, including dilutional hyponatremia, hypochloremia, metabolic alkalosis, hypercalcemia.
Musculoskeletal: muscle cramps.
Respiratory: respiratory distress, pneumonitis.
Skin: dermatitis, photosensitivity, rash, purpura, alopecia.
Other: hypersensitivity reactions, gout, anaphylaxis.

Effects on lab test results
• May increase glucose, cholesterol, triglyceride, calcium, and uric acid levels. May decrease potassium, sodium, and chloride levels.
• May decrease hemoglobin, hematocrit, and granulocyte, WBC, and platelet counts.

Overdose and treatment
Signs and symptoms of overdose include GI irritation and hypermotility, orthostatic hypotension, dizziness, drowsiness, syncope, muscular weakness, diuresis, and lethargy, which may progress to coma.
 Treatment is mainly supportive; monitor and assist respiratory, CV, and renal function as indicated. Monitor fluid and electrolyte balance. Induce vomiting with ipecac in conscious patient; otherwise, use gastric lavage to avoid aspiration. Don’t give cathartics; these promote additional loss of fluids and electrolytes.

Special considerations
• Drug isn’t recommended if creatinine clearance is less than 50 ml/minute.
• To prevent nocturia, give drug in the morning.
• Monitor fluid intake and output, weight, blood pressure, and serum electrolyte levels.
• Watch for signs of hypokalemia, such as muscle weakness and cramps. Drug may be used with potassium-sparing diuretic or with potassium supplements to prevent hypokalemia.
• Discontinue thiazides and thiazide-like diuretics before parathyroid function tests.
• In patients with hypertension, therapeutic response may be delayed several weeks.
• HCTZ may interfere with protein-bound iodine (PBI) test for thyroid function and should be discontinued before such test.
• Drug may cause glucose intolerance. Monitor blood glucose in diabetic patients. May require adjustment of insulin or oral antidiabetic dosage.
• Monitor serum creatinine and BUN levels regularly. Cumulative effects of drug may occur with impaired renal function.
• Monitor blood uric acid levels, especially in patients with history of gout.
Breast-feeding patients
• Drug appears in breast milk. Safety and efficacy in breast-feeding women haven’t been established.
Pediatric patients
• Drug can be given to children.
Geriatric patients
• Elderly and debilitated patients need close observation and may need reduced dosages. They’re more sensitive to excess diuresis because of age-related changes in CV and renal function. Excess diuresis promotes orthostatic hypotension, dehydration, hypovolemia, hyponatremia, hypomagnesemia, and hypokalemia.

Patient education
• Instruct patient to take drug with food to avoid GI upset, to take drug in morning or early afternoon to avoid nocturia, and to avoid sudden postural changes.
• Encourage patient to use sun block to avoid photosensitivity reactions.
• Tell patient to obtain medical approval before taking OTC medications.

Reactions may be common, uncommon, life-threatening, or COMMON AND LIFE THREATENING.
◆ Canada only
◇ Unlabeled clinical use