Oral (enalapril maleate, MSD)
RENITEC (enalapril maleate, MSD) is the maleate salt of enalapril, a
derivative of two amino-acids, Lalanine and L-proline. Following oral tablet
or wafer administration, enalapril is rapidly absorbed and then hydrolyzed
to enalaprilat, which is a highly specific, long-acting, non-sulphydryl
angiotensin converting enzyme inhibitor.
RENITEC is indicated in the treatment of all grades of essential
hypertension, and in renovascular hypertension. It may be used alone as
initial therapy or concomitantly with other anti hypertensive agents,
RENITEC is also indicated in the treatment and prevention of heart failure.
A multicenter, placebo-controlled, double-blind study of left ventricular
dysfunction (SOLVD) assessed the effects of RENITEC in 6,797 patients. 2,569
patients with all degrees of symptomatic heart failure (primarily mild to
moderate New York Heart Association Class II and III) were randomized into
the Treatment Arm, and 4,228 patients with asymptomatic left ventricular
dysfunction were randomized into the Prevention Arm. The combined results
demonstrated an overall reduced risk for the development of major ischemic
events. RENITEC decreased the incidence of myocardial infarction and reduced
the number of hospitalizations for unstable angina pectoris in patients with
left ventricular dysfunction.
In addition, in the Prevention Arm, RENITEC significantly prevented the
development of symptomatic heart failure and reduced the number of
hospitalizations for heart failure. In the Treatment Arm, RENITEC, as an
adjunct to conventional therapy, significantly reduced overall mortality and
hospitalization for heart failure and improved NYHA functional class.
In a similar study involving 253 patients with severe heart failure (New
York Heart Association Class IV), RENITEC was shown to improve symptoms and
reduce mortality significantly.
The cardioprotective properties of RENITEC were demonstrated in these
studies by the beneficial effects on survival and retardation of the
progression of heart failure in patients with symptomatic heart failure;
retardation of the development of symptomatic heart failure in asymptomatic
patients with left ventricular dysfunction; and prevention of coronary
ischemic events in patients with left ventricular dysfunction, specifically
reduction in the incidence of myocardial infarction and reduction in
hospitalization for unstable angina pectoris.
* All Grades of Essential Hypertension
* Renovascular Hypertension
* All Degrees of Heart Failure
In patients with symptomatic heart failure, RENITEC is also indicated to:
• Improve Survival
• Retard the Progression of Heart Failure
• Reduce Hospitalization for Heart Failure
* Prevention of Symptomatic Heart Failure
In asymptomatic patients with left ventricular dysfunction, RENITEC is
• Retard the Development of Symptomatic Heart Failure
• Reduce Hospitalization for Heart Failure
* Prevention of Coronary Ischemic Events in Patients with Left Ventricular
RENITEC is indicated to:
• Reduce the Incidence of Myocardial Infarction
• Reduce Hospitalization for Unstable Angina Pectoris
DOSAGE AND ADMINISTRATION
Since absorption of Tablets RENITEC is not affected by food, the tablets may
be administered before, during, or after meals.
The initial dose is 10 to 20 mg, depending on the degree of hypertension,
and is given once daily. In mild hypertension the recommended initial dose
is 10 mg daily. For other degrees of hypertension the initial dose is 20 mg
daily. The usual maintenance dose is one 20 mg tablet or wafer taken once
daily. The dosage should be adjusted according to the needs of the patient
to a maximum of 40 mg daily.
Since blood pressure and renal function in such patients may be particularly
sensitive to ACE inhibition, therapy should be initiated with a lower
starting dose (e.g. 5 mg or less). The dosage should then be adjusted
according to the needs of the patient. Most patients may be expected to
respond to one 20 mg tablet or
wafer taken once daily. For patients with hypertension who have been treated
recently with diuretics, caution is recommended (see next paragraph).
CONCOMITANT DIURETIC THERAPY IN HYPERTENSION
Symptomatic hypotension may occur following the initial dose of RENITEC;
this is more likely in patients who are being treated currently with
diuretics. Caution is recommended, therefore, since these patients may be
volume- or salt-depleted. The diuretic therapy should be discontinued for
2-3 days prior to initiation of therapy with RENITEC. If this is not
possible, the initial dose of RENITEC should be low (5 mg or less) to
determine the initial effect on the blood pressure. Dosage should then be
adjusted according to the needs of the patient.
DOSAGE IN RENAL INSUFFICIENCY
Generally, the intervals between the administration of enalapril should be
prolonged and/or the dosage reduced.
Creatinine Clearance mL/min
Initial Dose mg/day
<80 >30 mL/min.
5 - 10 mg
≤30 >10 mL/min.
2.5 - 5 mg
these patients will be on
2.5 mg on dialysis days**
* See PRECAUTIONS - Hemodialysis
** Enalaprilat is dialyzable.
Dosage on nondialysis days should be adjusted depending on the blood
HEART FAILURE / ASYMPTOMATIC
LEFT VENTRICULAR DYSFUNCTION
The initial dose of RENITEC in patients with symptomatic heart failure or
asymptomatic left ventricular dysfunction is 2.5 mg, and it should be
administered under close medical supervision to determine the initial effect
on the blood pressure. RENITEC may be used in the management of symptomatic
heart failure usually with diuretics and, where appropriate, digitalis. In
the absence of, or after effective management of, symptomatic hypotension
following initiation of therapy with RENITEC in heart failure, the dose
should be increased gradually to the usual maintenance dose of 20 mg, given
in a single dose or two divided doses, as tolerated by the patient. This
dose titration may be performed over a 2 to 4 week period, or more rapidly
if indicated by the presence of residual signs and symptoms of heart
failure. In patients with symptomatic heart failure, this dosage regimen was
effective in reducing mortality.
Blood pressure and renal function should be monitored closely both before
and after starting treatment with RENITEC (see PRECAUTIONS) because
hypotension and (more rarely) consequent renal failure have been reported.
In patients treated with diuretics, the dose should be reduced if possible
before beginning treatment with RENITEC. The appearance of hypotension after
the initial dose of RENITEC does not imply that hypotension will recur
during chronic therapy with RENITEC and does not preclude continued use of
the drug. Serum potassium also should be monitored (see DRUG INTERACTIONS).
RENITEC is contraindicated in patients who are hypersensitive to any
component of this product and in patients with a history of angioneurotic
edema relating to previous treatment with an angiotensin-converting enzyme
inhibitor and in patients with hereditary or idiopathic angioedema.