The main objective of fixed dose combination
therapy for
hypertension is to improve blood pressure (BP) control with lower, better tolerated dosages of 2
antihypertensives rather than higher dosages of a single agent.
Felodipine and
metoprolol lower BP via different, but complementary, mechanisms and
controlled release formulations of these 2 drugs are available as a fixed dose combination,
felodipine/
metoprolol. In clinical trials in patients with
hypertension,
felodipine/
metoprolol was significantly more effective than placebo and the respective monotherapies administered at the same dosages. Mean BP was reduced to < 155/90 mm Hg in patients treated with combination
therapy and controlled in approximately 70% of patients. In one study that titrated dosages to effect, fewer
felodipine/
metoprolol than
felodipine or
metoprolol monotherapy recipients required dosage increases to achieve BP control (45 vs 60 and 67%, respectively). Data from double blind comparative studies show that the
antihypertensive efficacy of
felodipine/
metoprolol 5 to 10/50 to 100 mg/day is significantly greater than that of
enalapril monotherapy or
captopril plus
hydrochlorothiazide and equivalent to
nifedipine/
atenolol and
amlodipine. In comparisons with
enalapril, fewer
felodipine/
metoprolol than
enalapril recipients required dosage titration to achieve BP control. Compared with
amlodipine,
felodipine/
metoprolol significantly reduced mean 24-hour average BP (8.9/5.5 vs 14.4/9.5 mm Hg after 6 weeks; p < 0.001). Both treatments preserved diurnal rhythm. Long term follow-up studies show that the
antihypertensive effect of
felodipine/
metoprolol occurs mostly during the first month of treatment with small additional decreases in BP being observed in the second and third months, and a relatively constant effect thereafter. According to a validated questionnaire, quality of life was relatively similar during 12 weeks treatment with
felodipine/
metoprolol,
enalapril or placebo. In a retrospective pharmacoeconomic analysis conducted in Sweden,
felodipine/
metoprolol was more cost effective than
enalapril as initial treatment for
hypertension. Peripheral oedema,
headache and
flushing were the most commonly reported adverse events with
felodipine/
metoprolol and
felodipine monotherapy, whereas
dizziness,
fatigue,
headache and respiratory
infection were more frequent with
metoprolol monotherapy. Dose-dependent adverse events such as oedema may occur less often in patients taking lower dosages in combination than in those taking higher dosages of
felodipine monotherapy. Thus, patients with
hypertension treated with
felodipine/
metoprolol experience greater control of BP, with less need for dosage titration, than those treated with
felodipine,
metoprolol or
enalapril monotherapy. Importantly this greater efficacy does not appear to be associated with a higher incidence of adverse events relative to monotherapy. Additionally, in short term studies
felodipine/
metoprolol had a similar (minimal) effect on QOL to
enalapril monotherapy but was more cost effective.