Hydrochlorothiazide Information
Hydrochlorothiazide ()
Hydrochlorothiazide () Description
Hydrochlorothiazide () is a diuretic and antihypertensive. It is the 3,4-dihydro derivative of chlorothiazide. Its chemical name is 6-chloro-3,4-dihydro--1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is CHCINOS and its structural formula is:
It is a white, or practically white, crystalline powder with a molecular weight of 297.74, which is slightly soluble in water, but freely soluble in sodium hydroxide solution.
Hydrochlorothiazide () is supplied as 25 mg and 50 mg tablets for oral use. Each tablet contains the following inactive ingredients: FD&C Yellow #6 Lake, lactose monohydrate, magnesium stearate, microcrystalline cellulose, pregelatinized starch.
Hydrochlorothiazide () Clinical Pharmacology
The mechanism of the antihypertensive effect of thiazides is unknown. Hydrochlorothiazide () does not usually affect normal blood pressure.
Hydrochlorothiazide () affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal therapeutic dosage all thiazides are approximately equal in their diuretic efficacy.
Hydrochlorothiazide () increases excretion of sodium and chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate.
After oral use diuresis begins within 2 hours, peaks in about 4 hours and lasts about 6 to 12 hours.
Hydrochlorothiazide () Indications And Usage
Hydrochlorothiazide () is indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.
Hydrochlorothiazide () has also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.
Hydrochlorothiazide () is indicated in the management of hypertension either as the sole therapeutic agent or to enhance the effectiveness of other antihypertensive drugs in the more severe forms of hypertension.
Hydrochlorothiazide () Contraindications
Anuria.
Hypersensitivity to this product or to other sulfonamide-derived drugs.
Hydrochlorothiazide () Warnings
Use with caution in severe renal disease. In patients with renal disease, thiazides may precipitate azotemia. Cumulative effects of the drug may develop in patients with impaired renal function.
Thiazides should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance may precipitate hepatic coma.
Thiazides may add to or potentiate the action of other antihypertensive drugs.
Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma.
The possibility of exacerbation or activation of systemic lupus erythematosus has been reported.
Lithium generally should not be given with diuretics (see , ).
Hydrochlorothiazide () Precautions
All patients receiving diuretic therapy should be observed for evidence of fluid or electrolyte imbalance: namely, hyponatremia, hypochloremic alkalosis, and hypokalemia. Serum and urine electrolyte determinations are particularly important when the patient is vomiting excessively or receiving parenteral fluids. Warning signs or symptoms of fluid and electrolyte imbalance, irrespective of cause, include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, confusion, seizures, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, and gastrointestinal disturbances such as nausea and vomiting.
Hypokalemia may develop, especially with brisk diuresis, when severe cirrhosis is present or after prolonged therapy.
Interference with adequate oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may cause cardiac arrhythmia and may also sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g., increased ventricular irritability). Hypokalemia may be avoided or treated by use of potassium sparing diuretics or potassium supplements such as foods with a high potassium content.
Although any chloride deficit is generally mild and usually does not require specific treatment except under extraordinary circumstances (as in liver disease or renal disease), chloride replacement may be required in the treatment of metabolic alkalosis.
Dilutional hyponatremia may occur in edematous patients in hot weather; appropriate therapy is water restriction, rather than administration of salt, except in rare instances when the hyponatremia is life threatening. In actual salt depletion, appropriate replacement is the therapy of choice.
Hyperuricemia may occur or acute gout may be precipitated in certain patients receiving thiazides.
In diabetic patients dosage adjustments of insulin or oral hypoglycemic agents may be required. Hyperglycemia may occur with thiazide diuretics. Thus latent diabetes mellitus may become manifest during thiazide therapy.
The antihypertensive effects of the drug may be enhanced in the post-sympathectomy patient.
If progressive renal impairment becomes evident, consider withholding or discontinuing diuretic therapy.
Thiazides have been shown to increase the urinary excretion of magnesium; this may result in hypomagnesemia.
Thiazides may decrease urinary calcium excretion. Thiazides may cause intermittent and slight elevation of serum calcium in the absence of known disorders of calcium metabolism. Marked hypercalcemia may be evidence of hidden hyperparathyroidism. Thiazides should be discontinued before carrying out tests for parathyroid function.
Increases in cholesterol and triglyceride levels may be associated with thiazide diuretic therapy.
When given concurrently the following drugs may interact with thiazide diuretics.
Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of Hydrochlorothiazide () in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice.
Hydrochlorothiazide () was not genotoxic in the Ames mutagenicity assay of strains TA 98, TA100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the sex-linked recessive lethal trait gene. Positive test results were obtained only in the CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of Hydrochlorothiazide () from 43 to 1300 μg/mL, and in the non-disjunction assay at an unspecified concentration.
Hydrochlorothiazide () had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to conception and throughout gestation.
Hydrochlorothiazide () Adverse Reactions
The following adverse reactions have been reported and, within each category, are listed in order of decreasing severity.
Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn.
Hydrochlorothiazide () Overdosage
The most common signs and symptoms observed are those caused by electrolyte depletion (hypokalemia, hypochloremia, hyponatremia) and dehydration resulting from excessive diuresis. If digitalis has also been administered, hypokalemia may accentuate cardiac arrhythmias.
In the event of overdosage, symptomatic and supportive measures should be employed. Emesis should be induced or gastric lavage performed. Correct dehydration, electrolyte imbalance, hepatic coma and hypotension by established procedures. If required, give oxygen or artificial respiration for respiratory impairment. The degree to which Hydrochlorothiazide () is removed by hemodialysis has not been established.
The oral LD of Hydrochlorothiazide () is greater than 10 g/kg in the mouse and rat.
Hydrochlorothiazide () Dosage And Administration
Therapy should be individualized according to patient response. Use the smallest dosage necessary to achieve the required response.
Hydrochlorothiazide () How Supplied
Hydrochlorothiazide () Tablets, USP 25 mg, are peach-colored, round,
scored tablets debossed "3571" and "V" on one side.
They are supplied as follows
Unit dose packages of 100 (10x10) NDC 68084-086-01
Hydrochlorothiazide ()
Hydrochlorothiazide () Package Label/principal Display Panel
