Editorial: Overdosing the American Public? Compounding to the Rescue!
In a recent issue of Consumer Reports on Health, the author begins with a statement that "The best dose of any medication is the lowest one that works". However, determining the lowest dose that works is difficult because it varies from person to person. Few doctors have the knowledge or the willingness to spend the necessary time "customizing drug doses", the author states. The adage of "start low and go slow" requires extra monitoring of the patient initially to ensure that the dose is working adequately; however, over time, this process can yield more efficient care as side effects decline and patient compliance and outcomes improve. This is interesting because in this weeks PTcommunity.com Newsletter, the announcement was made that the USP's National Adverse Drug Event Database reached 1,000,000 entries (the program started in 1998); this is amazing as only 900 health care facilities have contributed data; so there are actually many, many more occurring.
It has been estimated in the Consumer Reports on Health article that each year an estimated 75,000 deaths in the U.S. may be caused by Food and Drug Administration-approved drug doses that are too high for these individuals. These high doses may also cause patients to stop taking crucial medication because of side effects and this generates extra costs for consumers, insurers and the government.
Why the overdosing? The pharmaceutical industry recommends starting doses that apply to all adults, even though sometimes evidence is to the contrary. A single dose makes it easier for doctors to prescribe and makes it easier for the company to market.
What does this do for therapeutic drug monitoring and pharmacokinetics? It makes it extremely difficult to use a single dose product to adjust dosages unless the drug is converted into alternative dosage forms.
The author states that the industry tends to use higher doses in initial clinical studies submitted to the FDA to demonstrate the drug's effectiveness in most people. The agency typically approves the drug at those levels. As more people use the drug and further studies emerge, the recommended starting doses may drop, but the industry does not generally make these smaller doses commercially available.
Standardized dosing may help market drugs but it is not the best approach for the patients, especially the elderly who take a disproportionate amount of medications in the U.S. A geriatrician from the University of Massachusetts states "a little medicine often goes a long way in the elderly".
Many drugs in the following list have "lower effective daily dosages" as compared to the "usual recommended daily dosage"; however, these drugs may not be commercially available in lower dosages. These drugs include diclofenac, atorvastatin, lovastatin, pravastatin, simvastatin, bupropion, fluoxetine, nortriptyline, sertraline, trazodone, venlafaxine, amlodipine, atenolol, bisoprolol, captopril, chlorthalidone, enlapril, felodipine, hydrochlorothiazide, lisinopril, losartan, propranolol, ramipril, zolpidem, omeprazole and ranitidine.
What is the answer? There are three options: (1) manufacturers can market multiple strengths of their products, (2) patients can subdivide their dosage forms, (3) pharmacists can compound the exact dosage they need. The first option is not likely. The second option is not advisable due to variability in breaking tablets into multiple pieces (Note: Pharmacists should not split or break these tablets as there is no assurance that the individual pieces will meet the FDA or USP standards of content and content uniformity��also, will the patient be willing to pay for "spoiled pieces that did not break correctly"? Obviously, the best option is compounding the appropriate dosage strength.
In summary, I would like to quote from an article in the American Journal of Health-System Pharmacy in June of this year; written by DHHS Secretary Michael O. Leavit where he quotes Felix Frueh, Associate Director of Genomics in FDA's Office of Clinical Pharmacology and Biopharmaceutics who states, "The paradigm of one-size-fits-all approach to prescribing a medication, which has been used by most physicians for the past century, is 'clearly outdated".
Yes, the era of individualized patient medications (customized dosages for patients) is being recognized as very important and economical. However, it is going to take a lot more work to make it a total reality.
Loyd V. Allen, Jr., Ph.D., R.Ph
Editor-in-Chief |
