CHLOROTHIAZIDE- chlorothiazide tablet
Avera McKennan Hospital
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.
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.
Hypersensitivity to this product or to other sulfonamide-derived drugs.
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).
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
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
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
Thiazides have been shown to increase the urinary excretion of magnesium; this may result in
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.
Periodic determination of serum electrolytes to detect possible electrolyte imbalance should be done at
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
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
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.
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).
Chlorothiazide may cause fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse
reactions which have occurred in the adult.
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.
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
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).
The following adverse reactions have been reported and, within each category, are listed in order of
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,
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.
Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy
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
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.
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
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.)
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
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:
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
Chlorothiazide 250 mg tablet label
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
Active Ingredient/Active Moiety
Basis of Strength
Stre ng th
CHLO RO THIAZIDE (UNII: 77W477J15H) (CHLOROTHIAZIDE - UNII:77W477J15H)
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)
S hap e
S iz e
Avera McKennan Hospital
Marketing Start Date
Marketing End Date
NDC:6 9 18 9 -0 151-1
1 in 1 DOSE PACK; Type 0 : No t a Co mbinatio n Pro duct
Marke ting Cate gory
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Marke ting End Date
ANDA0 8 4217
0 3/0 1/20 15
Avera McKennan Hospital (068647668)
Ad d re s s
Busine ss Ope rations
Avera McKennan Ho spital
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relabel(6 9 18 9 -0 151) , repack(6 9 18 9 -0 151)