Hydrochloro­thiazide is the 3,4-dihydro derivative of chlorothiazide. Its chemical name is 6-Chloro-3,4-dihydro-2H-1,2,4-benzothiadiazine-7-sulfonamide 1,1-dioxide. Its empirical formula is C7H8ClN3O4S2; its molecular weight is 297.74; and its structural formula is:

It is a white, or practically white, crystalline powder which is slightly soluble in water, but freely soluble in sodium hydroxide solution.
 
Hydrochloro­thiazide is supplied as 12.5 mg capsules for oral use. Each capsule contains the following inactive ingredients: colloidal silicon dioxide, corn starch, lactose monohydrate, and magnesium stearate. The hard gelatin shell consists of gelatin, titanium dioxide, sodium lauryl sulphate, FD&C Blue #1, D&C Red #28, D&C Yellow #10, black iron oxide and shellac.

Hydrochlorothiazide blocks the reabsorption of sodium and chloride ions, and it thereby increases the quantity of sodi­um traversing the distal tubule and the volume of water excret­ed. A portion of the additional sodium presented to the distal tubule is exchanged there for potassium and hydrogen ions. With continued use of hydro­chlorothiazide and depletion of sodium, compensatory mecha­nisms tend to increase this exchange and may produce excessive loss of potassium, hydrogen and chloride ions. Hydrochlorothiazide also decreases the excretion of cal­cium and uric acid, may increase the excretion of iodide and may reduce glomerular fil­tration rate. Metabolic toxicities associated with excessive elec­trolyte changes caused by hydrochlorothiazide have been shown to be dose-related.

Hydrochloro­thiazide capsules are indicated in the management of hypertension either as the sole therapeutic agent, or in combination with other antihypertensives. Unlike potassium sparing combina­tion diuretic products, hydrochloro­thiazide may be used in those patients in whom the development of hyperkalemia cannot be risked, including patients taking ACE inhibitors.

Hydrochlorothiazide capsules are con­traindicated in patients with anuria. Hypersensitivity to this product or other sulfonamide derived drugs is also con­traindicated.

Diabetes and Hypoglycemia: Latent diabetes mellitus may become manifest and diabetic patients given thiazides may require adjustment of their insulin dose. 
 
Renal Disease: Cumulative effects of the thiazides may develop in patients with impaired renal function. In such patients, thiazides may precipitate azotemia.

Electrolyte and Fluid Balance Status: In published studies, clinically significant hypokalemia has been consistently less common in patients who received 12.5 mg of hydro­chlorothiazide than in patients who received higher doses. Nevertheless, periodic determi­nation of serum electrolytes should be performed in patients who may be at risk for the development of hypo­kalemia. Patients should be observed for signs of fluid or electrolyte disturbances, i.e., hyponatremia, hypochloremic alkalosis, and hypokalemia and hypomagnesemia.
 
Warning signs or symptoms of fluid and electrolyte imbalance include dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, 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, during concomitant use of corticosteroid or adrenocorti­cotropic hormone (ACTH) or after prolonged therapy. Interference with adequate oral electrolyte intake will also con­tribute to hypokalemia. Hypo­kalemia and hypomagnesemia can provoke ventricular arrhythmias or sensitize or exaggerate the response of the heart to the toxic effects of dig­italis. Hypokalemia may be avoided or treated by potas­sium supplementation or increased intake of potassium rich foods.
 
Dilutional hyponatremia is life-threatening and may occur in edematous patients in hot weather; appropriate therapy is water restriction rather than salt administration, except in rare instances when the hypo­natremia is life-threatening. In actual salt depletion, appropri­ate replacement is the therapy of choice.
 
Hyperuricemia: Hyperuricemia or acute gout may be precipi­tated in certain patients receiv­ing thiazide diuretics.
 
Impaired Hepatic Function: Thiazides should be used with caution in patients with impaired hepatic function. They can precipitate hepatic coma in patients with severe liver dis­ease. 

Parathyroid Disease: Calcium excretion is decreased by thi­azides, and pathologic changes in the parathyroid glands, with hypercalcemia and hypophos­phatemia, have been observed in a few patients on prolonged thiazide therapy.

The adverse reactions associated with hydrochlorothiazide have been shown to be dose related.  In controlled clinical trials, the adverse events reported with doses of 12.5 mg hydrochlorothiazide once daily were comparable to placebo. The following adverse reactions have been reported for doses of hydrochlorothiazide 25 mg and greater and, within each category, are listed in the order of decreasing severity.
 
Body as a whole: Weakness.
 
Cardiovascular:  Hypotension including orthostatic Hypotension (may be aggravated by alcohol, barbiturates, narcotics or antihypertensive drugs).
 
Digestive: Pancreatitis, jaundice (intrahepatic cholestatic jaundice), diarrhea, vomiting, sialadenitis, cramping, constipation, gastric irritation, nausea, anorexia.
 
Hematologic: Aplastic anemia, agranulocytosis, leukopenia, hemolytic anemia, thrombo-cytopenia.
 
Hypersensitivity:Anaphylactic reactions, necrotizing angiitis (vasculitis and cutaneous vasculitis), respiratory distress including pneumonitis and pulmonary edema, photosensitivity, fever, urticaria, rash, purpura.
 
Metabolic:  Electrolyte imbalance (see PRECAUTIONS), hyperglycemia, glycosuria, hyperuricemia.
 
Musculoskeletal:  Muscle Spasm.
 
Nervous System/Psychiatric: Vertigo, paresthesia, dizziness, headache, restlessness.
 
Renal:  Renal failure, renal dysfunction, interstitial nephritis (see WARNINGS).
 
Skin: Erythema multiforme including Stevens-Johnson syndrome, exfoliative dermatitis including toxic epidermal necrolysis, alopecia.
 
Special Senses:  Transient blurred vision, xanthopsia.
 
Urogenital:  Impotence.
 
Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn.

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 LD50 of hydrochlorothiazide is greater than 10 g/kg in the mouse and rat.

For Control of Hypertension: The adult initial dose of hydrochloro­thiazide is one capsule given once daily whether given alone or in combination with other antihypertensives. Total daily doses greater than 50 mg are not recommended.

Hydrochlorothiazide Capsules 12.5 mg are blue/blue size ‘4’ hard gelatin capsules, imprinted with ‘D’ on blue cap and ‘26’ on blue body with black edible ink, filled with white to off-white powder.

They are supplied by State of Florida DOH Central Pharmacy as follows:

Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light, moisture, freezing, -20°C  (-4°F).
 
Manufactured for:
Aurobindo Pharma USA, Inc.
2400 Route 130 North
Dayton, NJ 08810
 
Manufactured by:
Aurobindo Pharma Limited
Hyderabad–500 072, India

This Product was Repackaged By:

State of Florida DOH Central Pharmacy
104-2 Hamilton Park Drive
Tallahassee, FL 32304
United States

NDC 53808-0265-1
Hydrochlorothiazide Capsules
12.5 mg
Rx only                  30 Capsules
AUROBINDO