Prinivil or Zestril (Lisinopril)
The following drug information is obtained from various newswires, published
medical journal articles, and medical conference presentations.
Approved November 24, 1995
hypertension, heart failure, acute myocardial infarction
This drug is being marketed by both Merck and Zeneca. The Merck
product is called Prinivil; Zeneca's product is called
Prinivil is indicated for the treatment of hypertension, heart
failure, and acute myocardial infarction. It may be used alone as
initial therapy or concomitantly with other classes of
antihypertensive agents. It is indicated as adjunctive therapy in
the management of heart failure in subjects who are not responding
adequately to diuretics and digitalis. It is also indicated for the
treatment of hemodynamically stable subjects within 24 hours of
acute myocardial infarction, to improve survival.
In most hypertensive subjects studied, onset of antihypertensive
activity was seen at one hour after oral administration of an
individual dose of Prinivil, with peak reduction of blood pressure
achieved by six hours. Although an antihypertensive effect was
observed 24 hours after dosing with recommended single daily doses,
the effect was more consistent and the mean effect was considerably
larger in doses of 20 mg or more than with lower doses. However, at
all doses studied, the mean antihypertensive effect was
substantially smaller 24 hours after dosing than it was six hours
During baseline-controlled clinical trials in subjects receiving
digitalis and diuretics, single doses of Prinivil resulted in
decreases in pulmonary capillary wedge pressure, systemic vascular
resistance, and blood pressure accompanied by an increase in
cardiac output and no change in heart rate.
A multicenter, controlled, randomized, unblinded clinical trial
was conducted in 19,394 subjects with acute myocardial infarction
admitted to a coronary care unit. The trial was designed to examine
the effects of short-term (6-week) treatment with Prinivil,
nitrates, their combination, or no therapy. Subjects receiving
Prinivil alone or with nitrates had an 11% lower risk of death
compared to patients receiving no Prinivil at 6 weeks.
Prinivil was found to be generally well tolerated in controlled
clinical trials. For the most part, the following adverse effects
were mild and transient: fatigue, diarrhea, nausea, headache, and
Mechanism of Action
The effects of Prinivil in hypertension and heart failure appear
to result primarily from suppression of the
renin-angiotensin-aldosterone system. Inhibition of ACE results in
decreased plasma angiotensin II, which leads to decreased
vasopressor activity and to decreased aldosterone secretion.
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, Prinivil should be discontinued
as soon as possible.