Polypharmacy%u2014the good, the bad, and the ugly

In this era of an aging population, drug—drug and drug–disease interactions, and increasing numbers of medical therapies, polypharmacy is the rule, not the exception. As pointed out in the excellent review by Berensen and Weart (page 27), polypharmacy can be associated with adverse reactions, decreased efficacy, decreased adherence, and greater cost. Of course, when appropriate, polypharmacy may also improve a patient’s quality of life and adherence to treatment, and thereby improve morbidity and mortality.

So how can one enhance the good and reduce the bad? Berensen and Weart provide a number of recommendations, including keeping medication regimens simple and partnering with a pharmacist. One other recommendation I might add is to insist that patients bring with them to each visit all medications: pills and liquids, prescription and nonprescription, bought in either

a pharmacy, food market, or health food store. The physician or staff should then record these in the patient’s chart on each visit and address possible drug interactions.

One approach to simplifying polypharmacy is the use of combination tablets, an approach criticized years ago and still (although less so) controversial today. The problem with combination tablets 10 or more years ago included the fact that most medications had many titration steps, and it was difficult to come up with combination tablets that had the necessary doses for a specific patient; another issue was that older drugs were associated with more adverse effects, and it was difficult to determine which medication in the combination tablet was causing a problem. SerApEs was a classic example of one of the older combination tablets. It contained three separate drugs—reserpine, apresoline, and esidrex—and it was a very effective antihypertensive medication. Modern-day medications have a narrower titration range and fewer side effects. There are a number of examples of two medications in one tablet. For hypertension, for example, there are a number of agents, eg, beta blocking agents, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, etc, combined with a diuretic. The combination of amlodipine besylate and benazepril hydrochloride (Lotrel®) is an example of two antihypertensive agents, other than a diuretic, in a combination pill. Another approach is the use of a combination pill that addresses two distinct diseases that commonly occur together. The recent release of a combination tablet containing amlodipine besylate and atorvastatin calcium (Caduet®), in recognition of the frequent association of dyslipidemia with hypertension, is one example. This recent entry may represent the beginning of the “polypill” era. Indeed, there has been a recent flurry of editorials regarding the concept of a polypill—a proposed tablet that would contain an HMG-CoA reductase inhibitor (statin), three antihypertensive agents at half dose, aspirin (75 mg), and folic acid; this combination of six medications in one tablet could be indicated for most patients with hypertension. Then, instead of six pills, polypharmacy would be achieved with one tablet in which the prospect for drug—drug interactions would be minimal.