Prpms-HYDROCHLOROTHIAZIDE (Hydrochlorothiazide Tablets USP) 12.5, 25, 50 & 100 mg
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6111 Royalmount Avenue, Suite 100 March 21, 2003 Montreal, Quebec H4P 2T4 Date of Revision:
SUMMARY PRODUCT INFORMATION 3 INDICATIONS AND CLINICAL USE 3 CONTRAINDICATIONS 4 WARNINGS AND PRECAUTIONS 4 ADVERSE REACTIONS 7 DRUG INTERACTIONS 8 DOSAGE AND ADMINISTRATION 8 OVERDOSAGE 10 ACTION AND CLINICAL PHARMACOLOGY 10 STORAGE AND STABILITY 11 DOSAGE FORMS, COMPOSITION AND PACKAGING 11
PHARMACEUTICAL INFORMATION 13 DETAILED PHARMACOLOGY 13 TOXICOLOGY 14 REFERENCES 15
Prpms-HYDROCHLOROTHIAZIDE (Hydrochlorothiazide Tablets, USP) 12.5 mg, 25 mg, 50 mg and 30 mg Tablets Diuretic - Antihypertensive
| Route of Administration | Dosage Form/ Strength | Clinically Relevant Nonmedicinal Ingredients |
| Oral | tablet 12.5 mg, 25 mg, 50 mg & 100 mg | None. For a complete listing see Dosage Forms, Composition and Packaging section. |
pms-HYDROCHLOROTHIAZIDE (Hydrochlorothiazide) is indicated for the treatment of:
C
Edema
C
Hypertension
C
Toxemia of Pregnancy
Edema
pms-HYDROCHLOROTHIAZIDE (hydrochlorothiazide) is indicated in edema associated with congestive heart failure, hepatic cirrhosis, corticosteroid and estrogen therapy, premenstrual tension with edema and in edema of renal origin (i.e. nephrotic syndrome, acute glomerulonephritis and chronic renal disease). In obese patients in whom fluid retention is a complicating factor, it may help to initiate a loss of fluid and, thus of weight.
Hypertension
pms-HYDROCHLOROTHIAZIDE may be used alone or as an adjunct to other antihypertensive drugs. Since it enhances the action of these agents, their dosage must be reduced to avoid an excessive drop in pressure and other unwanted side effects.
Toxemia of Pregnancy
pms-HYDROCHLOROTHIAZIDE may be effective in the treatment of toxemia of pregnancy (including eclampsia).
Geriatrics (> 65 years of age):
No data is available.
Pediatrics (0 to 16 years of age):
No data is available.
pms-HYDROCHLOROTHIAZIDE (Hydrochlorothiazide Tablets, USP), as all diuretics, is contraindicated in anuria. pms-HYDROCHLOROTHIAZIDE should be discontinued if increasing azotemia and oliguria occur during treatment of severe progressive renal disease. pms-HYDROCHLOROTHIAZIDE is contraindicated in persons known to be sensitive to hydrochlorothiazide or to other sulfonamide-derived drugs. Patients who are hypersensitive to any ingredient in the formulation of pms- HYDROCHLOROTHIAZIDE or component of the container. For a complete listing, see the Dosage Forms, Composition and Packaging section of the product monograph.
General
Patients on long therapy with hydrochlorothiazide are required to be on potassium rich diet. Periodic determinations of serum electrolytes to detect possible electrolyte imbalance should be performed. The antihypertensive effects of the drug may be enhanced in the postsympathectomy patient.
Carcinogenesis and Mutagenesis
No data available.
Cardiovascular
No data available.
Ear/Nose/Throat
No data available.
Endocrine and Metabolism
Calcium excretion is decreased by thiazides.
Chloride deficiency is generally mild and does not require specific treatment except under special conditions such as renal or/and hepatic disease.
Dilutional hyponatremia may occur in edematous patients in hot
weather; appropriate therapy is water restriction rather than administration of salt except when hyponatremia is life threatening. In actual salt depletion, appropriate replacement is the therapy of choice.
All patients receiving thiazide should be observed for clinical signs 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 of serum electrolyte imbalance, irrespective of cause are: 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. Serum electrolytes may also be influenced by medication such as digitalis.
Hyperuricemia may occur or frank gout may be precipitated in certain patients receiving thiazide therapy.
Hypokalemia may develop, especially with rapid diuresis, when severe cirrhosis is present or during concomitant use of corticosteroids or ACTH. Deficient oral electrolyte intake will also contribute to hypokalemia. Hypokalemia may 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 the use of potassium supplements.
Insulin requirements in diabetic patients may be increased, decreased, or remain unchanged. Latent diabetes mellitus may become manifest during thiazide therapy. Concomitant therapy with lithium is not recommended with diuretics because of the reduction of renal clearance of lithium and therefore an added risk of lithium toxicity.
Pathological changes in the parathyroid gland with hypercalcemia and hypophosphatemia have been observed in a few patients on prolonged thiazide therapy. The common complications of hyperparathyroidism such as renal lithiasis, bone resorption, and peptic ulceration have not been reported. Use of thiazides should be discontinued before carrying out tests for parathyroid function.
Thiazides may decrease serum PBI levels without signs of thyroid disturbance.
Gastrointestinal
Non-specific small bowel lesions consisting of stenosis with or without ulceration, may occur in association with the administration of enteric coated potassium salts, alone or with oral diuretics. These small bowel lesions have caused obstruction, hemorrhage and perforation. Surgery was frequently required and deaths have occurred. Available information tends to implicate enteric coated potassium salts, although lesions of this type also occur spontaneously. Such preparations should be used only when adequate dietary supplementation is not practical, and should be discontinued immediately if abdominal pain, distention, nausea, vomiting or gastrointestinal bleeding occur.
Genitourinary
No data available.
Hematologic
No data available.
Hepatic/biliary/Pancreatic
Hydrochlorothiazide should be used with caution in patients with impaired hepatic function or progressive liver disease, since minor alterations of fluid and electrolyte balance or of serum ammonia may precipitate hepatic coma.
Immune
The possibility of exacerbation or activation of systemic lupus erythematosus has been reported. Sensitivity reactions may occur in patients with or without a history of allergy or bronchial asthma.
Neurologic
No data available.
Ophthalmologic
No data available.
Peri-Operative Considerations
No data available.
Psychiatric
No data available.
Renal
In progressive renal impairment, therapy with hydrochlorothiazide should be withheld or discontinued. Hydrochlorothiazide may commence or precipitate azotemia. It should be used with caution in patients with severely impaired renal function to avoid toxic or cumulative effect. If azotemia becomes more severe and oliguria occurs during treatment of patients with severe renal disease, administration of the diuretic must be stopped.
Respiratory
No data available.
Sensitivity/Resistance
No data available.
Sexual Function/Reproduction
No data available.
Skin
No data available.
Special Population
Thiazides cross the placental barrier and appear in cord blood. When hydrochlorothiazide is used in pregnancy or in women of child-bearing age, the potential benefits of the drug should be weighed against the possible hazards to the fetus. These hazards include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have occurred in the adult. The routine use of diuretics in otherwise healthy pregnant women with or without mild edema is not indicated.
Since thiazides appear in breast milk, hydrochlorothiazide is contraindicated in nursing mothers. If use of the drug is deemed essential, the patient should stop nursing.
Safety and effectiveness in children under 18 years of age have not been established.
Safety and effectiveness in adults over 65 years of age have not been established.
Whenever adverse reactions are moderate or severe, thiazide dosage should be reduced or therapy withdrawn. Cardiovascular: Orthostatic hypotension (may be aggravated by alcohol, barbiturates, or narcotics). Central nervous system: Dizziness, vertigo, paresthesias, headache, xanthopsia. Gastrointestinal system: Anorexia, gastric irritation, nausea, vomiting, cramps, diarrhea, constipation, jaundice (intrahepatic cholestatic jaundice), pancreatitis, sialadenitis. Hematologic: Leukopenia, agranulocytosis, thrombocytopenia, aplastic anemia. Hypersensitivity: Purpura, photosensitivity, rash, urticaria, necrotizing angitis (vasculitis), fever, respiratory distress including pneumonitis, anaphylactic reactions. Other: Hyperglycemia, glycosuria, hyperuricemia, muscle spasm, weakness, restlessness, transient blurred vision.
Hydrochlorothiazide adds to or potentiates the action of other antihypertensive drugs. Potentiation occurs especially with ganglionic or peripheral adrenergic blocking drugs.
Drug-Drug Interactions
Orthostatic hypotension may occur and may be potentiated by alcohol, barbiturates, or narcotics.
Concomitant therapy with lithium is not recommended with diuretics because of the reduction of renal clearance of lithium and therefore an added risk of lithium toxicity.
Thiazides may decrease arterial responsiveness to norepinephrine. This diminution is not sufficient to preclude effectiveness of the pressor agent for therapeutic use.
The rate of elimination of hydrochlorothiazide is decreased some what by the coadministration of probenecid without, however, an accompanying reduction in diuresis.
Thiazide drugs may increase the responsiveness to tubocurarine.
Drug-Food Interactions
Interactions with food have not been established.
Drug-Herb Interactions
Interactions with herbal products have not been established.
Drug-Laboratory Test Interactions
There are no known interactions of Hydrochlorothiazide with commonly used laboratory tests.
Therapy should be individualized according to the patients requirement. Use the smallest dosage necessary to achieve the required response.
Dosing Considerations
Diuresis Toxemia of pregnancy Premenstrual tension with edema Control of Hypertension
Adult patients
Diuresis
The recommended adult dosage is 50 to 100 mg once or twice a day. Many patients 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.
the recommended dosage is 100 mg daily or, in severe cases and for brief periods, 200 mg daily (in divided doses). Frequency of administration may range from once every four days to daily.
The recommended dosage is 25 to 50 mg once or twice a day from the first appearance of symptoms until onset of the menses.
The usual recommended starting dosage is 50 or 100 mg a day as a single or divided dose. Dosage is increased or decreased according to the blood pressure response of the patient. Some patients may require doses of 200 mg a day in divided doses. Careful observation for changes in blood pressure must be made when pms- HYDROCHLOROTHIAZIDE (Hydrochlorothiazide Tablets, USP) is used with other antihypertensive drugs, especially during initial therapy. The dosage of other agents must be reduced by at least 50%, as soon as it is added to the regimen, to prevent excessive drop in blood pressure. As the blood pressure falls under the potentiating effect of this agent, a further reduction in dosage, or discontinuation of other antihypertensive drugs may be necessary. A single daily dose as low as12.5 mg of Hydrochlorothiazide could be used in combination with another antihypertensive. In the case of hypertension monotherapy, doses as low as a single daily dose 12.5 mg may be effective (especially in the elderly or as a starting dose), as well as a daily dose of 25 mg given in two divided doses.
Infants and Children
The usual recommended pediatric dosage is based on 1.0 mg of pms- HYDROCHLOROTHIAZIDE per pound of body weight per day in two doses. Infants under 6 months of age may require up to 1.5 mg per pound per day in two doses. On this basis, infants up to 2 years of age may be given 12.5 to 37.5 mg daily in two doses. Children from 2 to 12 years of age may be given 37.5 to 100 mg daily in two doses. Dosage in both age groups should be based on body weight.
Symptoms
Overdosage of hydrochlorothiazide may produce diuresis accompanied with electrolyte imbalance (hypokalemia, hyponatremia and hypochloremic alkalosis) and dehydration. The symptoms are as follows: dryness of mouth, thirst, weakness, lethargy, drowsiness, restlessness, muscle pains or cramps, muscular fatigue, hypotension, oliguria, tachycardia, gastrointestinal disturbances, menta1 confusion, delirium, convulsions, shock, coma. Hypokalemia can sensitize or exaggerate the response of the heart to the toxic effects of digitalis (e.g. increased ventricular irritability). Hydrochlorothiazide may precipitate hepatic coma in patients with cirrhosis; increase the effect of other antihypertensive agents and decrease arterial responsiveness to norepinephrine.
Treatment
No specific antidote is available. Treatment is symptomatic and supportive. Induce emesis or perform gastric lavage. Correct dehydration, electrolyte imbalance, hepatic coma, and hypotension by established procedures. Administer oxygen or artificial respiration for respiratory impairment.
Mechanism of Action
Hydrochlorothiazide is a diuretic and an antihypertensive agent. The exact mechanism of the antihypertensive effect is unknown. Hydrochlorothiazide has no effect on normal blood pressure. Hydrochlorothiazide affects the renal tubular mechanism of electrolyte reabsorption. It increases excretion of sodium and chloride in approximately equivalent amounts and reduces the rate of formation of solute-free water. Natriuresis causes a secondary loss of potassium and bicarbonate.
Pharmacokinetics
Hydrochlorothiazide is rapidly absorbed from the gastrointestinal tract. Onset of action after oral administration occurs in 2 hours and the peak effect at approximately 4 hours. Duration of action persists for approximately 6 to 12 hours.
The drug is distributed throughout the extracellular space and does not accumulate in tissues other than the kidney. It passes readily through the placental barrier to the fetus.
Hydrochlorothiazide is not metabolized.
Hydrochlorothiazide is eliminated rapidly by the kidney.
pms-HYDROCHLOROTHIAZIDE (Hydrochlorothiazide Tablets, USP) Tablets should be stored at controlled room temperature (15degto 30degC).
pms-HYDROCHLOROTHIAZIDE (Hydrochlorothiazide Tablets, USP) tablets are available for oral use in four dosage strengths of 12.5 mg, 25 mg, 50 mg and 100 mg hydrochlorothiazide, USP.
Availability of Dosage Forms
pms-HYDROCHLOROTHIAZIDE (Hydrochlorothiazide Tablets, USP) Tablets are supplied as: 12.5 mg tablets: Round, peach-colored, flat-faced, beveledged tablets, with debossed "P" logo on one side and plain on the other side. Supplied in bottles of 500 and 1000 tablets. 25 mg tablets: Peach-colored, flat, and scored compressed tablets, imprinted 25 over "p". Supplied in bottles of 100 and 1000 tablets. 50 mg tablets: Peach-colored, flat, and scored compressed tablets, imprinted 50 over "p". Supplied in bottles of 100, 1000 and 5000 tablets. 100 mg tablets: Peach-colored, flat, and scored compressed tablets, imprinted 100 over "p". Supplied in bottles of 100 tablets.
Composition
pms-HYDROCHLOROTHIAZIDE (Hydrochlorothiazde Tablets, USP) 12.5 mg, 25 mg, 50 mg and 100 mg tablets contains 12.5 mg, 25 mg, 50 mg and 100 mg of Hydrochlorothiazide, respectively. Non medicinal ingredients (alphabetical): alginic acid, FD&C Yellow No. 6 Aluminum Lake, silicon dioxide, magnesium stearate, microcrystalline cellulose and sodium carboxymethylcellulose. Product Monograph available upon request. Biomed 2002 Inc. Montreal, Quebec H4P 2T4