Corzide (Nadolol / Bendroflumethiazide) - Drug Interactions, Contraindications, Overdosage, etc

DRUG INTERACTIONS

Drug and Laboratory Test Interactions

Bendroflumethiazide may produce false-negative results with the phentolamine and tyramine tests; may interfere with the phenolsulfonphthalein test due to decreased excretion; and it may cause diagnostic interference of serum electrolyte levels, blood and urine glucose levels, and a decrease in serum PBI levels without signs of thyroid disturbance.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Nadolol

In chronic oral toxicologic studies (one to two years) in mice, rats, and dogs, nadolol did not produce any significant toxic effects. In two-year oral carcinogenicity studies in rats and mice, nadolol did not produce any neoplastic, preneoplastic, or nonneoplastic pathologic lesions. In fertility and general reproductive performance studies in rats, nadolol caused no adverse effect.

Bendroflumethiazide

Studies have not been performed to evaluate carcinogenic potential, mutagenesis, or whether this drug adversely affects fertility in males or females.

Pregnancy

Teratogenic Effects

Nadolol

Category C. In animal reproduction studies with nadolol, evidence of embryo- and fetotoxicity was found in rabbits, but not in rats or hamsters, at doses 5 to 10 times greater (on a mg/kg basis) than the maximum indicated human dose. No teratogenic potential was observed in any of these species.

There are no adequate and well-controlled studies in pregnant women. Nadolol should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Neonates whose mothers are receiving nadolol at parturition have exhibited bradycardia, hypoglycemia, and associated symptoms.

Bendroflumethiazide

Category C. Animal reproduction studies have not been conducted with bendroflumethiazide. It is also not known whether this drug can cause fetal harm when administered to a pregnant woman or can affect reproduction capacity. Bendroflumethiazide should be given to a pregnant woman only if clearly needed.

Nonteratogenic Effects

Thiazides cross the placental barrier and appear in cord blood. The use of thiazides in pregnant women requires that the anticipated benefit be weighed against possible hazards to the fetus. These hazards include fetal or neonatal jaundice, thrombocytopenia, and possibly other adverse reactions which have occurred in the adult.

Overdosage

In the event of overdosage, nadolol may cause excessive bradycardia, cardiac failure, hypotension, or bronchospasm.

In addition to the expected diuresis, overdosage of bendroflumethiazide may produce varying degrees of lethargy which may progress to coma with minimal depression of respiration and cardiovascular function and without significant serum electrolyte changes or dehydration. The mechanism of thiazide-induced CNS depression is unknown. Gastrointestinal irritation may occur. Transitory increase in BUN has been reported, and serum electrolyte changes may occur, especially in patients with impaired renal function.

Treatment

Nadolol can be removed from the general circulation by hemodialysis. In determining the duration of corrective therapy, note must be taken of the long duration of the effect of nadolol. In addition to gastric lavage, the following measures should be employed, as appropriate.

Excessive Bradycardia —Administer atropine (0.25 to 1.0 mg). If there is no response to vagal blockade, administer isoproterenol cautiously.

Cardiac Failure —Administer a digitalis glycoside and diuretic. It has been reported that glucagon may also be useful in this situation.

Hypotension —Administer vasopressors, e.g., epinephrine or levarterenol. (There is evidence that epinephrine may be the drug of choice.)

Bronchospasm —Administer a beta₂-stimulating agent and/or a theophylline derivative.

Stupor or Coma —Supportive therapy as warranted.

Gastrointestinal Effects —Symptomatic treatment as needed.

BUN and/or Serum Electrolyte Abnormalities —Institute supportive measures as required to maintain hydration, electrolyte balance, respiration, and cardiovascular and renal function.

Contraindications

Nadolol

Nadolol is contraindicated in bronchial asthma, sinus bradycardia and greater than first degree conduction block, cardiogenic shock, and overt cardiac failure (see WARNINGS).

Bendroflumethiazide

Bendroflumethiazide is contraindicated in anuria. It is also contraindicated in patients who have previously demonstrated hypersensitivity to bendroflumethiazide or other sulfonamide-derived drugs.