OVERDOSAGE

No specific information is available on the treatment of overdosage with VASERETIC. Treatment is symptomatic and supportive. Therapy with VASERETIC should be discontinued and the patient observed closely. Suggested measures include induction of emesis and/or gastric lavage, and correction of dehydration, electrolyte imbalance and hypotension by established procedures.

Enalapril Maleate – Single oral doses of enalapril above 1,000 mg/kg and ≥ 1,775 mg/kg were associated with lethality in mice and rats, respectively. The most likely manifestation of overdosage would be hypotension, for which the usual treatment would be intravenous infusion of normal saline solution. Enalaprilat may be removed from general circulation by hemodialysis and has been removed from neonatal circulation by peritoneal dialysis (seeWARNINGS, Anaphylactoid Reactions During Membrane Exposure).

Hydrochlorothiazide – Lethality was not observed after administration of an oral dose of 10 g/kg to mice and rats. 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.

DOSAGE AND ADMINISTRATION

Enalapril and hydrochlorothiazide are effective treatments for hypertension. The usual dosage range of enalapril is 10 to 40 mg per day administered in a single or two divided doses; hydrochlorothiazide is effective in doses of 12.5 to 50 mg daily. The side effects (seeWARNINGS) of enalapril are generally rare and apparently independent of dose; those of hydrochlorothiazide are a mixture of dose-dependent phenomena (primarily hypokalemia) and dose- independent phenomena (e.g., pancreatitis), the former much more common than the latter. Therapy with any combination of enalapril and hydrochlorothiazide will be associated with both sets of dose-independent side effects but the addition of enalapril in clinical trials blunted the hypokalemia normally seen with diuretics. To minimize dose-independent side effects, it is usually appropriate to begin combination therapy only after a patient has failed to achieve the desired effect with monotherapy.

Dose Titration Guided by Clinical Effect: A patient whose blood pressure is not adequately controlled with either enalapril or hydrochlorothiazide monotherapy may be given VASERETIC 10-25 mg. Further increases of enalapril, hydrochlorothiazide or both depend on clinical response. The hydrochlorothiazide dose should generally not be increased until 2-3 weeks have elapsed. In general, patients do not require doses in excess of 20 mg of enalapril or 50 mg of hydrochlorothiazide. The daily dosage should not exceed two tablets of VASERETIC 10-25 mg.

Replacement Therapy: The combination may be substituted for the titrated components.

Use in Renal Impairment: The usual regimens of therapy with VASERETIC need not be adjusted as long as the patient's creatinine clearance is greater than 30 mL/min/1.73 m2 (serum creatinine approximately less than or equal to 3 mg/dL or 265 µmol/L). In patients with more severe renal impairment, loop diuretics are preferred to thiazides, so enalapril maleate and hydrochlorothiazide is not recommended (seeWARNINGS, Anaphylactoid Reactions During Membrane Exposure).

HOW SUPPLIED

VASERETIC Tablets 10-25 mg are rust-colored, oval-shaped tablets with one side imprinted with “VASE 10-25” and both sides scored. Each tablet contains 10 mg of enalapril maleate and 25 mg of hydrochlorothiazide. They are supplied as follows:

NDC 0187-0146-01 bottles of 100 (with desiccant).

Storage: Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Keep container tightly closed.

Protect from moisture.

Dispense in a tight container as per USP, if product package is subdivided.