Defining the opportunity for pharmacogenetic intervention in primary care.

UNLABELLED: Pharmacogenetics (PG), the study of human genome function and its effects on drug response, represents an exciting approach for reducing adverse drug events and increasing therapeutic efficacy. However, there is no clear information of the potential impact of PG in the primary care setting. Therefore, a study was conducted to determine the frequency of use of medications under PG influence, including 16 PG adverse drug reaction (ADR)-associated medications, in the primary care setting. PATIENTS AND METHODS: A cohort of 607 consecutive patients was accrued over a 3-month period from three primary care practices. Patients were asked to answer a verbal survey of demographics and medication use during the past 12 months. The survey specifically evaluated 16 drugs known to commonly cause ADRs and undergo metabolism by polymorphic enzymes. Patients also disclosed information on all other medication use in the last year. Medication use was verified by chart review. The primary outcome was the frequency of medication use. RESULTS: Among the 16 ADR-associated medications, patients used analgesics (88.5%), antihypertensives (14.3%) and antidepressants (9.6%) most commonly. Overall, 28.6% of patients took more than one of the PG ADR-associated medications. Neither gender nor race appeared to influence the frequency of use of these medications (p=0.5 and p=0.08, respectively). Patients taking one or more of the drugs were older (p<0.001). More patients seen for a chronic visit took one or more of the ADR-associated drugs than patients seen for an acute visit (35.8 versus 18.5%, p<0.001). DISCUSSION: This is the first attempt to describe the potential role of pharmacogenetics in the primary care setting. The findings indicate that at least one in four primary care patients take at least one medication that commonly causes adverse drug reactions due to genetic variability in drug metabolism, indicating that there is a potential role of pharmacogenomics in primary care. Nearly every patient was on a medication with putative PG association. CONCLUSIONS: Studies of the ability of PG should not be limited to medical subspecialties, as there is a great potential impact of PG on the primary care setting.

Entecavir: a new nucleoside analog for the treatment of chronic hepatitis B infection.

BACKGROUND: Chronic hepatitis B infection carries considerable risk for the development of cirrhosis and hepatocellular carcinoma. Treatment options are increasing but are limited to interferon alfa-2b, pegylated interferon alfa-2a, lamivudine, adefovir dipivoxil, and entecavir. Entecavir, a nucleoside analog, is the newest oral antiviral approved in the United States for treatment of chronic hepatitis B. OBJECTIVE: To review the available data for entecavir regarding its pharmacology, pharmacokinetics, safety, efficacy, and clinical use. METHODS: A MEDLINE, EMBASE, and Cochrane search of the English-language literature from January 1997-May 2006 was performed. Preapproval studies provided by the manufacturer and abstracts from recent scientific meetings on infectious disease and hepatology were also reviewed. RESULTS: Three phase III clinical trials representing more than 1600 subjects established the superior efficacy and equivalent safety of entecavir compared with lamivudine for treating patients who are hepatitis B early antigen (HBeAg) positive, HBeAg negative, or refractory to lamivudine. Entecavir resistance has not occurred in nucleoside-naïve patients but may develop in those who already possess lamivudine resistance mutations. CONCLUSION: Trial results, along with previously published response rates for adefovir dipivoxil and interferon monotherapy, make entecavir the preferred first-line treatment option for patients with chronic hepatitis B who are nucleoside naïve, HBeAg positive or negative, and have compensated liver disease. Both entecavir and adefovir dipivoxil maintain activity against hepatitis B virus in patients with chronic hepatitis B who are refractory to lamivudine, and both agents are reasonable first-line treatment options. Longer trials involving nucleoside-naïve, lamivudine-refractory patients are needed to determine entecavir's optimal treatment duration, long-term safety, and durability of response, including rate of resistance.