Approaches to meeting the criteria for fixed dose antihypertensive combinations. Focus on metoprolol.

Fixed dose antihypertensive combinations are being used increasingly in the management of hypertension. There are advantages and disadvantages of this form of therapy. The key aims are to: (i) achieve increased efficacy by using drugs that complement each other's actions; (ii) use low doses to minimise adverse effects; and (iii) provide a simple once daily regimen. Fixed dose combinations containing metoprolol have the advantage that beta-blockers are drugs for which there is most evidence that they are cardioprotective; metoprolol is the best documented beta-blocker in this context. The early combination of conventional release metoprolol and hydrochlorothiazide was inadequately investigated by modern standards, but proved well tolerated and effective in clinical practice. The introduction of the long acting metoprolol CR/ZOK (controlled release/zero order kinetics) produced a very satisfactory once daily preparation with no major pharmacokinetic interactions. The fixed dose combination of felodipine and metoprolol CR/ZOK has been well investigated. The two agents complement each other's actions and together provide very effective blood pressure control, cardioprotection and very good tolerability. A case can be made that this preparation more closely meets the requirements of an ideal antihypertensive than a single agent given alone.