|
Reduction in systemic blood pressure appears to have been mediated by a decrease in peripheral vascular resistance without reflex cardiac effects. Similarly, renal, splanchnic, cerebral, and skeletal muscle blood flow were unchanged compared to baseline, as was glomerular filtration rate.
Heart Failure In a randomized, double-blind, placebo-controlled trial, 179 patients with heart fail-ure, all receiving diuretics and some receiving digoxin, were administered single doses of 1, 20, or 40 mg of MONOPRIL or placebo. Doses of 20 and 40 mg of MONOPRIL resulted in acute decreases in pulmonary capillary wedge pressure (pre-load) and mean arterial blood pressure and systemic vascular resistance (afterload). One hundred fifty-five of these patients were re-randomized to once-daily therapy with MONOPRIL (1, 20, or 40 mg) for an additional 10 weeks. Hemodynamic mea-surements made 24 hours after dosing showed (relative to baseline) continued reduction in pulmonary capillary wedge pressure, mean arterial blood pressure, right atrial pressure and an increase in cardiac index and stroke volume for the 20 and 40 mg dose groups. No tachyphylaxis was seen. MONOPRIL was studied in 3 double-blind, placebo-controlled, 12-24 week trials including a total of 734 patients with heart failure, with MONOPRIL doses from 10 to 40 mg daily. Concomitant therapy in 2 of these 3 trials included diuretics and digi-talis; in the third trial patients were receiving only diuretics. All 3 trials showed statis-tically significant benefits of MONOPRIL therapy, compared to placebo, in one or more of the following: exercise tolerance (one study), symptoms of dyspnea, orthop-nea and paroxysmal nocturnal dyspnea (2 studies), NYHA classification (2 studies), hospitalization for heart failure (2 studies), study withdrawals for worsening heart fail-ure (2 studies), and/ or need for supplemental diuretics (2 studies). Favorable effects were maintained for up to two years. Text Continues Below
Effects of MONOPRIL on long-term mortality in heart failure have not been evaluated. The once-daily dosage for the treatment of congestive heart failure was the only dosage regimen used during clinical trial devel-opment and was determined by the measurement of hemodynamic responses. INDICATIONS AND USAGE MONOPRIL is indicated for the treatment of hypertension. It may be used alone or in combination with thiazide diuretics. MONOPRIL is indicated in the management of heart failure as adjunctive therapy when added to conventional therapy including diuretics with or without digitalis (see DOSAGE AND ADMINISTRATION). In using MONOPRIL (consideration should be given to the fact that another angiotensin-converting enzyme inhibitor, captopril, has caused agranulocytosis, particularly in patients with renal impairment or collagen-vascular disease. Available data are insufficient to show that MONOPRIL does not have a similar risk (see WARNINGS). In considering use of MONOPRIL, it should be noted that in controlled trials ACE inhibitors have an effect on blood pressure that is less in black patients than in non-blacks. In addition, ACE inhibitors (for which adequate data are available) cause a high-er rate of angioedema in black than in non-black patients (see WARNINGS: Head and Neck Angioedema and Intestinal Angioedema). USE IN PREGNANCY When used in pregnancy during the second and third trimesters, ACE inhibitors can cause injury and even death to the developing fetus. When pregnancy is detected, MONOPRIL should be discontinued as soon as pos-sible. See WARNINGS: Fetal/ Neonatal Morbidity and Mortality.
Page: << Prev | 1 | 2 | 3 | 4 | 5
|
.gif)
