Felodipine/Metoprolol - A review of the fixed dose controlled release formulation in the management of essential hypertension

The main objective of fixed dose combination therapy For hypertension is to improve blood pressure (BP) control with lower, better tolerated dosages o f 2 antihypertensives rather than higher dosages of a single agent. Felodip ine and metoprolol lower BP via different, but complementary, mechanisms an d 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 administrated at the same dosages. Mean BP was reduced to <155/90mm Hg in patients treated with combination therapy and controlled in approximate to 70% of patients. In one study that titrated dosages to effect, fewer felodi pine/metoprolol than felodipine or metoprolol monotherapy recipients requir ed dosage increases to achieve BP control (45 vs 60 and 67%, respectively), Data from double blind comparative studies show that the antihypertensive e fficacy of felodipine/metoprolol 5 to 10/50 to 100 mg/day is significantly greater than that of enalapril monotherapy or captopril plus hydrochlorothi azide and equivalent to nifedipine/atenolol and amlodipine. In comparisons with enalapril, fewer felodipine/metoprolol than enalapril r ecipients required dosage titration to achieve BP control. Compared with amlodipine, felodipine/metoprolol significantly reduced mean 24-hour average BP (8.9/5.5 vs 14.4/9.5mm Hg after 6 weeks; p < 0.001). Bot h treatments preserved diurnal rhythm. Long term follow-up studies show that the antihypertensive effect of felodi pine/metoprolol occurs mostly during the first month of treatment with smal l 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 simi lar during 12 weeks treatment with felodipine/metoprolol, enalapril or plac ebo. In a retrospective pharmacoeconomic analysis conducted in Sweden, felodipin e/metoprolol was more cost effective than enalapril as initial treatment fo r hypertension. Peripheral oedema, headache and flushing were the most commonly reported ad verse 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 m ay 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 experie nce greater control of BP, with less need for dosage titration, than those treated with felodipine, metoprolol or enalapril monotherapy. Importantly t his greater efficacy does not appear to be associated with a higher inciden ce of adverse events relative to monotherapy. Additionally, in short term s tudies felodipine/metoprolol had a similar (minimal) effect on QOL to enala pril monotherapy but was more cost effective.