DESCRIPTION
id: e0d88da4-966e-4f0b-add5-6602ac1cb09f
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Hydrochlorothiazide is a diuretic and antihypertensive. It is the 3, 4-dihydro derivative of chlorothiazide. It is chemically designated as 6-chloro-3, 4-dihydro-2H-1, 2, 4- benzothiadiazine-7-sulfonamide 1, 1-dioxide and has the following structural formula:
C7H8ClN3O4S2 M.W. 297.74
Hydrochlorothiazide is a white, or practically white, crystalline powder which is slightly soluble in water, but freely soluble in sodium hydroxide solution. Each tablet for oral administration contains 25mg hydrochlorothiazide. In addition, each tablet contains the following inactive ingredients: corn starch, FD&C Yellow #6, dibasic calcium phosphate, pregelatinized starch, colloidal silicon dioxide, lactose monohydrate and magnesium stearate.
CLINICAL PHARMACOLOGY
id: 0c5bbf36-2fb1-493b-b172-bfaf49ded7db
displayName: CLINICAL PHARMACOLOGY SECTION
FDA Article Code: 34090-1
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.
Pharmacokinetics and Metabolism
id: ea6a7437-56a8-4ed2-a7f6-819e00dd8a00
displayName: SPL UNCLASSIFIED SECTION
FDA Article Code: 42229-5
Hydrochlorothiazide is not metabolized but is eliminated rapidly by the kidney. When plasma levels have been followed for at least 24 hours, the plasma half-life has been observed to vary between 5.6 and 14.8 hours. At least 61 percent of the oral dose is eliminated unchanged within 24 hours. Hydrochlorothiazide crosses the placental but not the blood-brain barrier and is excreted in breast milk.
INDICATIONS AND USAGE
id: c6343f24-76e2-4114-8004-da6c136b17ca
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Hydrochlorothiazide tablets are indicated as adjunctive therapy in edema associated with congestive heart failure, hepatic cirrhosis, and corticosteroid and estrogen therapy.
Hydrochlorothiazide tablets have also been found useful in edema due to various forms of renal dysfunction such as nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.
Hydrochlorothiazide tablets are 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.
Use in Pregnancy
Routine use of diuretics during normal pregnancy 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 toxemia.
Edema during pregnancy may arise from pathologic causes or from the physiologic and mechanical consequences of pregnancy. Thiazides are indicated in pregnancy when edema is due to pathologic causes, just as they are in the absence of pregnancy (see
PRECAUTIONS
,
Pregnancy
). Dependent edema in pregnancy, resulting from restriction of venous return by the gravid uterus, is properly treated through elevation of the lower extremities and use of support stockings. Use of diuretics to lower intravascular volume in this instance is illogical and unnecessary. During normal pregnancy there is hypervolemia which is not harmful to the fetus or the mother in the absence of cardiovascular disease. However, it may be associated with edema, rarely generalized edema. If such edema causes discomfort, increased recumbency will often provide relief. Rarely this edema may cause extreme discomfort which is not relieved by rest. In these instances, a short course of diuretic therapy may provide relief and be appropriate.
CONTRAINDICATIONS
id: 010419a8-f82b-403f-bc65-cc4e013c48f0
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Anuria.
Hypersensitivity to this product or to other sulfonamide-derived drugs.
WARNINGS
id: e0a50420-b049-481e-bfc4-30c7965acaac
displayName: WARNINGS SECTION
FDA Article Code: 34071-1
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
PRECAUTIONS, Drug Interactions
).
ADVERSE REACTIONS
id: b0181abd-3f5a-4f05-b394-8dae9911cc1c
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
The following adverse reactions have been reported and within each category, are listed in 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, paresthesias, 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: 90330577-0ccd-4705-863f-f003d18d32b7
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: 4db01a9f-aa3f-4bfe-a343-beb57fa47c21
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
Therapy should be individualized according to patient response. Use the smallest dosage necessary to achieve the required response.
Adults
For Edema
The usual adult dosage is 25 to 100 mg daily as a single or divided dose. Many patients with edema respond to intermittent therapy, i.e., administration on alternate days or on three to five days each week. With an intermittent schedule, excessive response and the resulting undesirable electrolyte imbalance are less likely to occur.
For Control of Hypertension
The usual initial dose in adults is 25 mg daily given as a single dose. The dose may be increased to 50 mg daily, given as a single or two divided doses. Doses above 50 mg are often associated with marked reductions in serum potassium (see also
PRECAUTIONS
).
Patients usually do not require doses in excess of 50 mg of hydrochlorothiazide daily when used concomitantly with other antihypertensive agents.
HOW SUPPLIED
id: 9f1a1e61-61f7-401e-9db0-d773fb362dcf
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
Hydrochlorothiazide Tablets USP are available as light orange, circular, flat, beveled, uncoated tablets, with score line having “U” and “128” debossed across the score line on one side and plain on other side containing 25 mg of hydrochlorothiazide USP.
Bottles of 30 : NDC 0179-0065-30
Bottles of 50 : NDC 0179-0065-50
STORAGE AND HANDLING
id: d48f7580-3df5-4a56-a40d-d797ab6faf43
displayName: STORAGE AND HANDLING SECTION
FDA Article Code: 44425-7
PHARMACIST: Dispense in a well-closed container as defined in the USP. Use child-resistant closure (as required)
Store at 20° – 25° C (68°-77° F) [See USP Controlled Room Temperature].
Package Label – Bottle of 30’s
id: 74e6a908-a155-47f9-839e-c725f0301105
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
Package Label – Bottle of 50’s
id: 7c14c904-3da5-41be-aa1c-3a7fcbc94494
displayName: PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
FDA Article Code: 51945-4
