DESCRIPTION
id: 0e80dc51-e871-476e-9827-73e878e33efb
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Hydrochlorothiazide, USP 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 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 capsules, USP are for oral administration contains 12.5 mg of hydrochlorothiazide, USP. Each capsule contains the following inactive ingredients: lactose monohydrate, corn starch, pregelatinized starch, colloidal silicon dioxide, magnesium stearate, D&C Red #28, D&C Yellow #10, FD&C Blue #1, FD&C Blue #2, FD&C Red #40, titanium dioxide, gelatin, black iron oxide, propylene glycol and shellac.
CLINICAL PHARMACOLOGY
id: b0c2d3df-4a5f-434f-aeca-8422c4483447
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.
Pharmacokinetics and Metabolism
Hydrochlorothiazide is well absorbed (65% to 75%) following oral administration. Absorption of hydrochlorothiazide is reduced in patients with congestive heart failure.
Peak plasma concentrations are observed within 1 to 5 hours of dosing, and range from 70 to 490 ng/mL following oral doses of 12.5 to 100 mg. Plasma concentrations are linearly related to the administered dose. Concentrations of hydrochlorothiazide are 1.6 to 1.8 times higher in whole blood than in plasma. Binding to serum proteins has been reported to be approximately 40% to 68%. The plasma elimination half-life has been reported to be 6 to 15 hours. Hydrochlorothiazide is eliminated primarily by renal pathways. Following oral doses of 12.5 to 100 mg, 55% to 77% of the administered dose appears in urine and greater than 95% of the absorbed dose is excreted in urine as unchanged drug. In patients with renal disease, plasma concentrations of hydrochlorothiazide are increased and the elimination half-life is prolonged.
When hydrochlorothiazide is administered with food, its bioavailability is reduced by 10%, the maximum plasma concentration is reduced by 20%, and the time to maximum concentration increases from 1.6 to 2.9 hours.
Pharmacodynamics
Acute antihypertensive effects of thiazides are thought to result from a reduction in blood volume and cardiac output, secondary to a natriuretic effect, although a direct vasodilatory mechanism has also been proposed. With chronic administration, plasma volume returns toward normal, but peripheral vascular resistance is decreased. The exact mechanism of the antihypertensive effect of hydrochlorothiazide is not known.
Thiazides do not affect normal blood pressure. Onset of action occurs within 2 hours of dosing, peak effect is observed at about 4 hours, and activity persists for up to 24 hours.
Clinical Studies
In an 87 patient 4-week double-blind, placebo controlled, parallel group trial, patients who received hydrochlorothiazide had reductions in seated systolic and diastolic blood pressure that were significantly greater than those seen in patients who received placebo. In published placebo-controlled trials comparing 12.5 mg of hydrochlorothiazide to 25 mg, the 12.5 mg dose preserved most of the placebo-corrected blood pressure reduction seen with 25 mg.
INDICATIONS & USAGE
id: 407cc790-3084-4743-bdb1-3a2bffe68202
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
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.
Usage in Pregnancy
The routine use of diuretics in an otherwise healthy woman is inappropriate and exposes mother and fetus to unnecessary hazard. Diuretics do not prevent development of toxemia of pregnancy, and there is no satisfactory evidence that they are useful in the treatment of developed toxemia.
Edema during pregnancy may arise from pathological causes or from the physiologic and mechanical consequences of pregnancy. Diuretics are indicated in pregnancy when edema is due to pathologic causes, just as they are in the absence of pregnancy. Dependent edema in pregnancy resulting from restriction of venous return by the expanded uterus is properly treated through elevation of the lower extremities and use of support hose; use of diuretics to lower intravascular volume in this case is illogical and unnecessary. There is hypervolemia during normal pregnancy which is harmful to neither the fetus nor the mother (in the absence of cardiovascular disease), but which is associated with edema, including generalized edema in the majority of pregnant women. If this edema produces discomfort, increased recumbency will often provide relief. In rare instances this edema may cause extreme discomfort which is not relieved by rest. In these cases a short course of diuretics may provide relief and may be appropriate.
CONTRAINDICATIONS
id: e341018e-37e6-403b-944d-3df6feef938b
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
id: 36449b72-abab-4a9e-a112-66f44f21e761
displayName: WARNINGS SECTION
FDA Article Code: 34071-1
Acute Myopia and Secondary Angle-Closure Glaucoma
Hydrochlorothiazide, a sulfonamide, can cause an idiosyncratic reaction, resulting in acute transient myopia and acute angle-closure glaucoma. Symptoms include acute onset of decreased visual acuity or ocular pain and typically occur within hours to weeks of drug initiation. Untreated acute angle-closure glaucoma can lead to permanent vision loss. The primary treatment is to discontinue hydrochlorothiazide as rapidly as possible. Prompt medical or surgical treatments may need to be considered if the intraocular pressure remains uncontrolled. Risk factors for developing acute angle-closure glaucoma may include a history of sulfonamide or penicillin allergy.
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: 95311c42-b054-46f2-a0f6-63e27ad1cda0
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
id: eb891587-da70-40d6-a722-4decaec7c36a
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, thrombocytopenia.
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
id: 96a309b5-a5c8-448c-bee2-a7b9e8b29f07
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 & ADMINISTRATION
id: e2405091-450e-4e57-a928-0e4ff6beeca7
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: 1dea95fd-ad8b-4679-9ff9-1c7fd5e496a8
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Hydrochlorothiazide capsules, 12.5 mg are size #4 Teal Opaque/Teal Opaque colored hard gelatin capsules, imprinted with ‘195’ on both cap and body in black ink. They are available as follows:
Bottles of 100 NDC 57664-195-88
Bottles of 500 NDC 57664-195-13
Bottles of 1000 NDC 57664-195-18
Store at 20° to 25°C (68° to 77°F); excursions permitted 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].
Protect from light, moisture, freezing, -20°C (-4°F). Keep container tightly closed.
Distributed by:
Sun Pharmaceutical Industries, Inc.
Cranbury, NJ 08512
Revised: 10/2014
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
id: d691f1ce-09d9-4ebd-a778-e99d5c523eeb
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
Hydrochlorothiazide Capsules, USP 12.5 mg
NDC 57664-195-88
Rx Only
100 Capsules
ALKALOIDA Chemical Company Zrt.
Hydrochlorothiazide Capsules, USP 12.5 mg
NDC 57664-195-13
Rx Only
500 Capsules
ALKALOIDA Chemical Company Zrt.
Hydrochlorothiazide Capsules, USP 12.5 mg
NDC 57664-195-18
Rx Only
1000 Capsules
ALKALOIDA Chemical Company Zrt.
