Norvasc - Clinical Pharmacology

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With chronic once daily oral administration, antihypertensive effectiveness is maintained for at least 24 hours. Plasma concentrations correlate with effect in both young and elderly patients. The magnitude of reduction in blood pressure with NORVASC is also correlated with the height of pretreatment elevation; thus, individuals with moderate hypertension (diastolic pressure 105-114 mmHg) had about a 50% greater response than patients with mild hypertension (diastolic pressure 90-104 mmHg).

Normotensive subjects experienced no clinically significant change in blood pressures (+ 1/– 2 mmHg). In hypertensive patients with normal renal function, therapeutic doses of NORVASC resulted in a decrease in renal vascular resistance and an increase in glomerular filtration rate and effective renal plasma flow without change in filtration fraction or proteinuria. As with other calcium channel blockers, hemodynamic measurements of cardiac function at rest and during exercise (or pacing) in patients with normal ventricular function treated with NORVASC have generally demonstrated a small increase in cardiac index without significant influence on dP/ dt or on left ventricular end diastolic pressure or volume.

In hemodynamic studies, NORVASC has not been associated with a negative inotropic effect when administered in the therapeutic dose range to intact animals and man, even when co-administered with beta-blockers to man. Similar findings, however, have been observed in normals or well-compensated patients with heart failure with agents possessing significant negative inotropic effects.

Studies in Patients with Congestive Heart Failure:

NORVASC has been compared to placebo in four 8-12 week studies of patients with NYHA class II/ III heart failure, involving a total of 697 patients. In these studies, there was no evidence of worsened heart failure based on measures of exercise tolerance, NYHA classification, symptoms, or LVEF. In a long-term (follow-up at least 6 months, mean 13.8 months) placebo-controlled mortality/ morbidity study of NORVASC 5-10 mg in 1153 patients with NYHA classes III (n= 931) or IV (n= 222) heart failure on stable doses of diuretics, digoxin, and ACE inhibitors, NORVASC had no effect on the primary endpoint of the study which was the combined endpoint of all-cause mortality and cardiac morbidity (as defined by life-threatening arrhythmia, acute myocardial infarction, or hospitalization for worsened heart failure), or on NYHA classification, or symptoms of heart failure. Total combined all-cause mortality and cardiac morbidity events were 222/ 571 (39%) for patients on NORVASC and 246/ 583 (42%) for patients on placebo; the cardiac morbid events represented about 25% of the endpoints in the study.