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Hydrochlorothiazide

Pronunciation

Pronunciation: HYE-droe-KLOR-oh-THYE-a-zide
Class: Thiazide diuretic

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Trade Names

Hydrochlorothiazide
- Tablets 12.5 mg
- Tablets 25 mg
- Tablets 50 mg

Microzide
- Capsules 12.5 mg

Apo-Hydro (Canada)
PMS-Hydrochlorothiazide (Canada)

Pharmacology

Enhances excretion of sodium, chloride, and water by interfering with transport of sodium ions across renal tubular epithelium.

Pharmacokinetics

Absorption

Bioavailability is 65% to 75%, C _max is 70 to 490 ng/mL (dose dependent), and T _max is 1 to 5 h. Food reduces the bioavailability 10% and the C _max 20% and increases the T _max from 1.6 to 2.9 h. Plasma concentrations are linearly related to administered dose.

Distribution

Protein binding is 40% to 68% and crosses the placenta but not the blood brain barrier. It is also excreted in breast milk.

Metabolism

Hydrochlorothiazide is not metabolized.

Elimination

Hydrochlorothiazide is eliminated primarily by renal pathways (as unchanged by the kidneys; 55% to 77% of the administered dose appears in urine with more than 95% of the absorbed dose excreted in urine unchanged). Plasma half-life is 5.6 to 14.8 h.

Peak

The time to peak effect is approximately 4 h.

Duration

Hydrochlorothiazide activity may persist for up to 24 h.

Special Populations

Renal Function Impairment

Hydrochlorothiazide plasma concentration is increased and the half-life is prolonged.

Indications and Usage

Adjunctive therapy for edema associated with CHF, hepatic cirrhosis, renal function impairment, and corticosteroid and estrogen therapy; treatment of hypertension.

Unlabeled Uses

Therapy for nephrogenic diabetes insipidus.

Contraindications

Hypersensitivity to thiazides, related diuretics, or sulfonamide-derived drugs; anuria; renal decompensation.

Dosage and Administration

Diuresis (tablets only)
Children (6 mo to 12 y of age)

PO 1 to 2 mg/kg/day in single or 2 divided doses. Max dose for children 2 to 12 y of age is 100 mg/day; for 6 mo to 2 y of age is 37.5 mg/day.

Edema (tablets only)
Adults

PO 25 to 100 mg/day as a single or divided dose.

Hypertension
Tablets Adults

PO 25 to 50 mg/day as a single dose or 2 divided doses.

Children (6 mo to 12 y of age)

PO 1 to 2 mg/kg/day in a single dose or 2 divided doses. Max dose for children 2 to 12 y of age is 100 mg/day; for 6 mo to 2 y of age is 37.5 mg/day.

Infants (younger than 6 mo)

PO Doses up to 3 mg/kg/day in 2 divided doses may be required.

Capsules Adults

PO 12.5 mg daily (max, 50 mg/day) given alone or in combination with other antihypertensives.

Storage/Stability

Store tablets in tightly closed container at 15° to 30°C (59° to 86°F).

Drug Interactions

Bile acid sequestrants

May reduce thiazide absorption; give thiazide at least 2 h before resin.

Diazoxide

May cause hyperglycemia.

Digitalis glycosides

Diuretic-induced hypokalemia and hypomagnesemia may precipitate digitalis-induced arrhythmias.

Insulin sulfonylureas

May decrease hypoglycemic effect of sulfonylureas. May need to increase dosage of sulfonylureas or insulin.

Lithium

May decrease renal excretion of lithium.

Loop diuretics

Synergistic effects may result in profound diuresis and serious electrolyte abnormalities.

Laboratory Test Interactions

May decrease serum protein-bound iodine levels without signs of thyroid disturbance. May cause diagnostic interference of serum electrolyte levels, blood and urine glucose levels, serum bilirubin levels, and serum uric acid levels. May increase serum magnesium levels in uremic patients. May cause increased concentrations of total serum cholesterol, total triglycerides, and LDL.

Adverse Reactions

Cardiovascular

Orthostatic hypotension.

CNS

Dizziness, headache, insomnia, light-headedness, paresthesias, restlessness, vertigo, weakness.

Dermatologic

Alopecia, erythema multiforme, exfoliative dermatitis, necrotizing angiitis (vasculitis and cutaneous vasculitis), photosensitivity, purpura, rash, Stevens-Johnson syndrome, TEN, urticaria.

EENT

Blurred vision, xanthopsia (yellow vision).

GI

Abdominal pain or cramping, anorexia, bloating, constipation, diarrhea, gastric irritation, nausea, pancreatitis, sialadenitis, vomiting.

Genitourinary

Impotence, interstitial nephritis, reduced libido.

Hematologic

Agranulocytosis, aplastic or hypoplastic anemia, hemolytic anemia, leukopenia, thrombocytopenia.

Hepatic

Jaundice.

Metabolic

Electrolyte imbalance, glycosuria, hyperglycemia, hyperuricemia.

Respiratory

Pneumonitis, pulmonary edema, respiratory distress.

Miscellaneous

Anaphylactic reactions, fever, muscle cramp or spasm.

Precautions

Pregnancy

Category B .

Lactation

Excreted in breast milk.

Children

Safety and efficacy have not been established in controlled clinical studies.

Hypersensitivity

May occur in patients with or without history of allergy or bronchial asthma; cross-sensitivity with sulfonamides may also occur.

Renal Function

May precipitate azotemia; use with caution.

Hepatic Function

Minor alterations of fluid and electrolyte balance may precipitate hepatic coma; use with caution.

Lupus erythematosus

Exacerbation or activation may occur.

Postsympathectomy patients

May enhance antihypertensive effects.

Overdosage

Symptoms

Anuria, confusion, cramps of calf muscles, dizziness, electrolyte abnormalities, lethargy, nausea, potassium deficiency, orthostatic or general hypotension, polyuria, shock, syncope, tachycardia, thirst, vomiting, weakness.

Patient Information

Instruct patient to take medication early in day with food or milk.
Instruct patient to monitor weight daily.
Advise patient to avoid exposure to sunlight and to use sunblock or wear protective clothing to avoid photosensitivity reaction.
Instruct diabetic patients to report increased levels of blood glucose to health care provider.
Caution patient to avoid intake of alcoholic beverages.
Caution patient to rise slowly from lying or sitting position and to lie down if blurred vision or dizziness occurs.
Tell patient to report these symptoms to health care provider: blurred vision, decrease in urinary output, dizziness, GI disturbances, jaundice, muscle cramps, nausea, weakness.
Instruct patient to drink 2 to 3 L of fluids daily unless advised otherwise by health care provider.
Advise patient that drug may cause dizziness and blurred vision and to use caution while driving or performing other tasks requiring mental alertness.
Tell patient that therapeutic effect may require 2 to 3 wk.