Esidrix (Hydrochlorothiazide) - Drug Interactions, Contraindications, Overdosage

DRUG INTERACTIONS

Drug/Laboratory Test Interactions

Thiazides may decrease serum PBI levels without signs of thyroid disturbance.

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

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 in vitro assays using strains TA 98, TA 100, TA 1535, TA 1537, and TA 1538 of Salmonella typhimurium (Ames assay) and in the Chinese Hamster Ovary (CHO) test for chromosomal aberrations, or in in vivo 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 nondisjunction 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/day, respectively, prior to mating 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/kg/day, 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.

OVERDOSAGE

Acute Toxicity

No deaths due to acute poisoning with Esidrix have been reported.

      Highest known doses ingested: children, 500 mg (14-year-old girl); young children, 125 mg (2 1/2-year-old child).

      Oral LD₅₀ in rats: >2750 mg/kg.

Signs and Symptoms

The most prominent feature of poisoning with Esidrix is acute loss of fluid and electrolytes.

      Cardiovascular: Tachycardia, hypotension, shock.

      Neuromuscula r: Weakness, confusion, dizziness, cramps of the calf muscles, paresthesia, fatigue, impairment of consciousness.

      Gastrointestinal: Nausea, vomiting, thirst.

      Renal: Polyuria, oliguria or anuria (due to hemoconcentration).

      Laboratory Findings: Hypokalemia, hyponatremia, hypochloremia, alkalosis, increased BUN (especially in patients with renal insufficiency).

      Combined Poisoning: Signs and symptoms may be aggravated or modified by concomitant intake of antihypertensive medication, barbiturates, curare, digitalis (hypokalemia), corticosteroids, narcotics, or alcohol.

Treatment

There is no specific antidote.

Elimination of the drug: Induction of vomiting, gastric lavage.

Measures to reduce absorption: Activated charcoal.

Hypotension, shock: The patient’s legs should be kept raised, and lost fluid and electrolytes (potassium, sodium) should be replaced.

Surveillance: Fluid and electrolyte balance (especially serum potassium) and renal function should be monitored until conditions become normal.

CONTRAINDICATIONS

Anuria; hypersensitivity to this or other sulfonamide-derived drugs.