Hydrochlorothiazide Capsules USP, Rx only

DESCRIPTION

id: f5126867-9a28-45eb-a07f-c70ded667ddc
displayName: Description Section
FDA Article Code: 34089-3

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 molecular formula is C₇H₈ClN₃O₄S₂; its molecular weight is 297.74; and its structural formula is:

CLINICAL PHARMACOLOGY

id: 832c5d75-3119-4921-923f-32e115c389ad
displayName: Clinical Pharmacology Section
FDA Article Code: 34090-1

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.

INDICATIONS AND USAGE

id: f16a5d39-67ae-4535-8d23-fb6fb0509db9
displayName: Indications & Usage Section
FDA Article Code: 34067-9

Hydrochloro­thiazide capsules USP 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 capsules USP may be used in those patients in whom the development of hyperkalemia cannot be risked, including patients taking ACE inhibitors.

CONTRAINDICATIONS

id: 4269c08b-8fa1-45d2-abf2-89879f60702a
displayName: Contraindications Section
FDA Article Code: 34070-3

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

WARNINGS

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displayName: Warnings Section
FDA Article Code: 34071-1

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.

PRECAUTIONS

id: dc783ba6-df8f-4dc5-a560-fd28169087a0
displayName: Precautions Section
FDA Article Code: 42232-9

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.

ADVERSE REACTIONS

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displayName: Adverse Reactions Section
FDA Article Code: 34084-4

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.

OVERDOSAGE

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displayName: Overdosage Section
FDA Article Code: 34088-5

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.

DOSAGE AND ADMINISTRATION

id: bac023f4-ffaa-49c5-8819-97cf780b33d1
displayName: Dosage & Administration Section
FDA Article Code: 34068-7

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.

HOW SUPPLIED

id: 77a5cd9a-633d-4a6c-89dc-7ff5f2accf60
displayName: How Supplied Section
FDA Article Code: 34069-5

Hydrochlorothiazide Capsules USP 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.

         Bottles of 100               NDC 65862-113-01
         Bottles of 300               NDC 65862-113-33
         Bottles of  500              NDC 65862-113-05
         Bottles of 1,000             NDC 65862-113-99

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–500 090, India

Revised: 06/2015

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL – 12.5 mg (100 Capsule Bottle)

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displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4

NDC 65862-113-01

Hydrochlorothiazide Capsules USP

12.5 mg

Rx only                  100 Capsules

AUROBINDO