Hydrochlorothiazide (Page 2 of 3)

Drug/Laboratory Test Interactions

Thiazides should be discontinued before carrying out tests for parathyroid function (see PRECAUTIONS, General).

Carcinogenesis, Mutagenesis, Impairment of Fertility

Two-year feeding studies in mice and rats conducted under the auspices of the National Toxicology Program (NTP) uncovered no evidence of a carcinogenic potential of hydrochlorothiazide in female mice (at doses of up to approximately 600 mg/kg/day) or in male and female rats (at doses of up to approximately 100 mg/kg/day). The NTP, however, found equivocal evidence for hepatocarcinogenicity in male mice.

Hydrochlorothiazide was not genotoxic in vitro in the Ames mutagenicity assay of Salmonella typhimurium strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in vivo in assays using mouse germinal cell chromosomes, Chinese hamster bone marrow chromosomes, and the Drosophila sex-linked recessive lethal trait gene. Positive test results were obtained only in the in vitro CHO Sister Chromatid Exchange (clastogenicity) and in the Mouse Lymphoma Cell (mutagenicity) assays, using concentrations of hydrochlorothiazide from 43 to 1300 µg/ml, and in the Aspergillus nidulans non-disjunction assay at an unspecified concentration.

Hydrochlorothiazide had no adverse effects on the fertility of mice and rats of either sex in studies wherein these species were exposed, via their diet, to doses of up to 100 and 4 mg/kg, respectively, prior to conception and throughout gestation.

Pregnancy

Teratogenic Effects-Pregnancy Category B

Studies in which hydrochlorothiazide was orally administered to pregnant mice and rats during their respective periods of major organogenesis at doses up to 3000 and 1000 mg hydrochlorothiazide/kg, respectively, provided no evidence of harm to the fetus.

There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nonteratogenic Effects

Thiazides cross the placental barrier and appear in cord blood. There is a risk of fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions that have occurred in adults.

Nursing Mothers

Thiazides are excreted in breast milk. Because of the potential for serious adverse reactions in nursing infants, a decision should be made whether to discontinue nursing or to discontinue hydrochlorothiazide, 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).

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 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

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 3 to 5 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.

Infants and Children

For Diuresis and for Control of Hypertension

The usual pediatric dosage is 0.5 to 1 mg per pound (1 to 2 mg/kg) per day in single or two divided doses, not to exceed 37.5 mg per day in infants up to 2 years of age or 100 mg per day in children 2 to 12 years of age. In infants less than 6 months of age, doses up to 1.5 mg per pound (3 mg/kg) per day in two divided doses may be required. (See PRECAUTIONS, Pediatric Use).

HOW SUPPLIED

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 100 : NDC 29300-128-01

Bottles of 500 : NDC 29300-128-05

Bottles of 1,000 : NDC 29300-128-10

Bottles of 5,000 : NDC 29300-128-50

Hydrochlorothiazide Tablets, USP are available as light orange, circular, flat, beveled, uncoated tablets, with score line having “U” and “129″ debossed across the score line on one side and plain on other side containing 50 mg of hydrochlorothiazide, USP.

Bottles of 100 : NDC 29300-129-01

Bottles of 500 : NDC 29300-129-05

Bottles of 1,000 : NDC 29300-129-10

Bottles of 5,000 : NDC 29300-129-50

PHARMACIST: Dispense in a well-closed container as defined in the USP. Use child-resistant closure (as required)

Store at 20° to 25°C (68° to 77°F)

[see USP Controlled Room Temperature].

Please address medical inquiries to Unichem’s toll free # 1-866-562-4616.

Manufactured by:

UNICHEM LABORATORIES LTD.

Pilerne Ind. Estate, Pilerne, Bardez, Goa 403 511, India

Manufactured for:

Company Logo

East Brunswick, NJ 08816

06-R-05/2019

13011531

Page 2 of 3 1 2 3

All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.

This site is provided for educational and informational purposes only, in accordance with our Terms of Use, and is not intended as a substitute for the advice of a medical doctor, nurse, nurse practitioner or other qualified health professional.

Privacy Policy | Copyright © 2019. All Rights Reserved.