CHLOROTHIAZIDE

Main information

  • Trade name:
  • CHLOROTHIAZIDE tablet
  • Composition:
  • CHLOROTHIAZIDE 250 mg
  • Prescription type:
  • PRESCRIPTION DRUG
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • CHLOROTHIAZIDE tablet
    United States
  • Language:
  • English

Status

  • Source:
  • DailyMed - NLM - National Library of Medicine
  • Authorization status:
  • Abbreviated New Drug Application
  • Last update:
  • 06-11-2017

Summary of Product characteristics: dosage, interactions, side effects

CHLOROTHIAZIDE- chlorothiazide tablet

Avera McKennan Hospital

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DESCRIPTION

Chlorothiazide is a diuretic and antihypertensive. It is 6- chloro-2H-1,2,4-benzothiadiazine-7-

sulfonamide 1, 1-dioxide. Its molecular formula is C H CIN O S and its structural formula is:

Chlorothiazide, USP is a white, or practically white crystalline compound with a molecular weight of

295.73 which is very slightly soluble in water, but readily soluble in dilute aqueous sodium hydroxide.

It is soluble in urine to the extent of about 150 mg per 100 mL at pH 7.

Each tablet for oral administration contains either 250 mg or 500 mg of chlorothiazide and the

following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium-Type A, magnesium

stearate, microcrystalline cellulose, sodium lauryl sulfate.

CLINICAL PHARMACOLOGY

The mechanism of the antihypertensive effect of thiazides is unknown. Chlorothiazide does not usually

affect normal blood pressure.

Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. At maximal

therapeutic dosages, all thiazides are approximately equal in their diuretic efficacy.

Chlorothiazide 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

Chlorothiazide is not metabolized but is eliminated rapidly by the kidney. The plasma half-life of

chlorothiazide is 45 to 120 minutes. After oral doses, 10 to 15 percent of the dose is excreted

unchanged in the urine. Chlorothiazide crosses the placental but not the blood-brain barrier and is

excreted in breast milk.

INDICATIONS AND USAGE

Chlorothiazide is indicated as adjunctive therapy in edema associated with congestive heart failure,

hepatic cirrhosis, and corticosteroid and estrogen therapy.

Chlorothiazide has also been found useful in edema due to various forms of renal dysfunction such as

nephrotic syndrome, acute glomerulonephritis, and chronic renal failure.

Chlorothiazide 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.

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

Anuria.

Hypersensitivity to this product or to other sulfonamide-derived drugs.

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 PRECAUTIONS: Drug Interactions).

PRECAUTIONS

General

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 arrhythmias 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.

Laboratory Tests

Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be done at

appropriate intervals.

Drug Interactions

When given concurrently the following drugs may interact with thiazide diuretics.

Alcohol, barbiturates, or narcotics: Potentiation of orthostatic hypotension may occur.

Antidiabetic drugs (oral agents and insulin): Dosage adjustment of the antidiabetic drug may be required.

Other antihypertensive drugs: Additive effect or potentiation.

Cholestyramine and colestipol resins: Both cholestyramine and colestipol resins have the potential of

binding thiazide diuretics and reducing diuretic absorption from the gastrointestinal tract.

Corticosteroids, ACTH: Intensified electrolyte depletion, particularly hypokalemia.

Pressor amines (e.g., norepinephrine): Possible decreased response to pressor amines but not sufficient

to preclude their use.

Skeletal muscle relaxants, nondepolarizing (e.g., tubocurarine): Possible increased responsiveness to the

muscle relaxant.

Lithium: Generally should not be given with diuretics. Diuretic agents reduce the renal clearance of

lithium and add a high risk of lithium toxicity. Refer to the package insert for lithium preparations

before use of such preparations with chlorothiazide.

Non-steroidal Anti-inflammatory Drugs: In some patients, the administration of a nonsteroidal anti-

inflammatory agent can reduce the diuretic, natriuretic, and antihypertensive effects of loop, potassium-

sparing and thiazide diuretics. Therefore, when chlorothiazide and non-steroidal anti-inflammatory

agents are used concomitantly, the patient should be observed closely to determine if the desired effect

of the diuretic is obtained.

Drug/Laboratory Test Interactions

Thiazides should be discontinued before carrying out tests for parathyroid function (see

PRECAUTIONS: General).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenicity studies have not been done with chlorothiazide.

Chlorothiazide was not mutagenic in vitro in the Ames microbial mutagen test (using a maximum

concentration of 5 mg/plate and Salmonella typhimurium strains TA98 and TA100) and was not

mutagenic and did not induce mitotic non-disjunction in diploid-strains of Aspergillus nidulans.

Chlorothiazide had no adverse effects on fertility in female rats at doses up to 60 mg/kg/day and no

adverse effects on fertility in male rats at doses up to 40 mg/kg/day. These doses are 1.5 and 1 times

(calculations based on a human body weight of 50 kg) the recommended maximum human dose,

respectively, when compared on a body weight basis.

Pregnancy

Teratogenic Effects. Pregnancy Category C

Although reproduction studies performed with chlorothiazide doses of 50 mg/kg/day in rabbits, 60

mg/kg/day in rats and 500 mg/kg/day in mice revealed no external abnormalities of the fetus or

impairment of growth and survival of the fetus due to chlorothiazide, such studies did not include

complete examinations for visceral and skeletal abnormalities. It is not known whether chlorothiazide

can cause fetal harm when administered to a pregnant woman; however, thiazides cross the placental

barrier and appear in cord blood. Chlorothiazide should be used during pregnancy only if clearly

needed (see INDICATIONS AND USAGE).

Nonteratogenic Effects

Chlorothiazide may cause fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse

reactions which have occurred in the adult.

Nursing Mothers

Because of the potential for serious adverse reactions in nursing infants from chlorothiazide, a decision

should be made whether to discontinue nursing or to discontinue the drug, taking into account the

importance of the drug to the mother.

Pediatric Use

There are no well-controlled clinical trials in pediatric patients. Information on dosing in this age group

is supported by evidence from empiric use in pediatric patients and published literature regarding the

treatment of hypertension in such patients. (See DOSAGE AND ADMINISTRATION: Infants and

Children.)

Geriatric Use

Clinical studies of chlorothiazide did not include sufficient numbers of subjects aged 65 and over to

determine whether they respond differently from younger subjects. Other reported clinical experience

has not identified differences in responses between the elderly and younger patients. In general, dose

selection for an elderly patient should be cautious, usually starting at the low end of the dosing range,

reflecting the greater frequency of decreased hepatic, renal or cardiac function, and of concomitant

disease or other drug therapy.

This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug

may be greater in patients with impaired renal function. Because elderly patients are more likely to have

decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal

function (see WARNINGS).

ADVERSE REACTIONS

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

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 chlorothiazide sodium is removed by hemodialysis has not been established.

The oral LD of chlorothiazide is 8.5 g/kg, greater than 10 g/kg, and greater than 1 g/kg, in the mouse,

rat and dog respectively.

DOSAGE AND ADMINISTRATION

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 0.5 g to 1 g once or twice a day. 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 adult starting dosage is 0.5 g or 1 g a day as a single or divided dose. Dosage is increased or

decreased according to blood pressure response. Rarely some patients may require up to 2 g a day in

divided doses.

Infants and Children

For Diuresis and For Control of Hypertension

The usual pediatric dosage is 5 to 10 mg per pound (10 to 20 mg/kg) per day in single or two divided

doses, not to exceed 375 mg per day in infants up to 2 years of age or 1 g per day in children 2 to 12

years of age. In infants less than 6 months of age, doses up to 15 mg per pound (30 mg/kg) per day in

two divided doses may be required. (See PRECAUTIONS: Pediatric Use.)

HOW SUPPLIED

Chlorothiazide tablets, USP are available containing 250 mg or 500 mg of Chlorothiazide, USP.

The 250 mg tablets are white, round, scored tablets debossed with M to the left of the score and 50 to

the right of the score on one side of the tablet and blank on the other side. They are available as

follows:

NDC 0378-0150-01

bottles of 100 tablets

The 500 mg tablets are white, round, scored tablets debossed with MYLAN above the score and 162

below the score on one side of the tablet and blank on the other side. They are available as follows:

NDC 0378-0162-01

bottles of 100 tablets

Store at 20?? to 25??C (68?? to 77??F). [See USP for Controlled Room Temperature.]

Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505

REVISED MARCH 2006

CTZ:R13

Chlorothiazide 250 mg tablet label

CHLOROTHIAZIDE

chlorothiazide tablet

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 9 18 9 -0 151(NDC:0 378 -0 150 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

CHLO RO THIAZIDE (UNII: 77W477J15H) (CHLOROTHIAZIDE - UNII:77W477J15H)

CHLOROTHIAZIDE

250 mg

Inactive Ingredients

Ingredient Name

Stre ng th

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

CRO SCARMELLO SE SO DIUM (UNII: M28 OL1HH48 )

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

CELLULO SE, MICRO CRYSTALLINE (UNII: OP1R32D6 1U)

SO DIUM LAURYL SULFATE (UNII: 36 8 GB5141J)

Product Characteristics

Color

WHITE

S core

2 pieces

S hap e

ROUND

S iz e

10 mm

Flavor

Imprint Code

M;50

Avera McKennan Hospital

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 9 18 9 -0 151-1

1 in 1 DOSE PACK; Type 0 : No t a Co mbinatio n Pro duct

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 8 4217

0 3/0 1/20 15

Labeler -

Avera McKennan Hospital (068647668)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Avera McKennan Ho spital

0 6 8 6 476 6 8

relabel(6 9 18 9 -0 151) , repack(6 9 18 9 -0 151)

Revised: 11/2015