Counterfeit Procrit Uncovered by FDA Surveillance

Pharmacology Watch

In one of the more bizarre stories of the year, the FDA has uncovered files of counterfeit Procrit (epoetin alfa—Johnson & Johnson) in routine surveillance. To make matters worse, the fake vials have been contaminated with bacteria and many contain no active ingredient. Johnson & Johnson is sending out a "Dear Doctor" letter to warn health care professionals about the counterfeit vials including the lot numbers of the suspected counterfeits. Fake Procrit was also discovered last summer in United States. At that time, counterfeiters apparently purchased 2000 U/mL vials and labeled them as the higher priced 40,000 U/mL vials. More information is available at the Johnson & Johnson/Ortho Biotech web site including pictures of the counterfeit vials.

Pharmaceutical Marketing Campaigns in Full Swing

Love em or hate em, direct-to-consumer (DTC) advertisements of pharmaceuticals are big business. The Kaiser Family foundation reports that spending on DTC ads increased nearly 10- fold in 10 years, from $260 million to $2.5 billion in 2000. More than 80% of respondents report seeing or hearing a drug ad in the last 3 months according to an FDA survey, and the Kaiser study reports that one third of patients have asked their doctor about an ad they saw on TV or in print. Unfortunately, drug ads are increasingly unregulated. The FDA is tasked with reviewing DTC ads for false or misleading statements, but according to a recent review in Consumer Reports, the agency has only 30 reviewers to handle 30,000 submissions each year. By the time false or misleading ads are pulled from the airways, they have often run their lifespan, with new ads appearing in their place. But are the pharmaceutical companies getting $2.5 billion of value from these ads? Apparently. A recent FDA survey of physicians revealed that when patients initiate a discussion about a prescription drug they’ve seen advertised, they asked for a prescription more than 50% of the time. Some 66% of physicians said they were not pressured to prescribe a drug in that situation. However, when a specific brand name drug was requested, physicians felt pressured to prescribe it more than 50% of the time. Despite this, physicians are split on the effect of DTC ads on their patients and practice, with 32% feeling negative about the ads, 40% feeling positive, and 28% feeling that DTC advertising has no effect on the practice (www.fda.gov/cder/ddmac/presentations.htm).

Ambulatory Antibiotic Reduction: Take the Good with the Bad

The national campaign to reduce antibiotic use in ambulatory practice seems to be working, but there is good news and bad news. Researchers from UCSF and Harvard reviewed the rates of overall antibiotic use in the National Ambulatory Medical Care Survey between 1991-1992, and compared those rates to usage between 1998-1999. The use of antibiotics decreased in the latter time period especially for the treatment of respiratory tract infections such as the common cold and pharyngitis (visits with a prescription decreased from 13% to 10% in adults, and from 33% to 22% among children). The use of broad-spectrum antibiotics increased over the same time span; however, including the macrolides azithromycin and clarithromycin, quinolones, amoxicillin-clavulanate, and second- and third-generation cephalosporins. The use of these antibiotics increased from 24% to 48% of all antibiotic prescriptions among adults and from 23% to 40% among children. An accompanying editorial reiterates the CDC’s Campaign for Appropriate Antibiotic Use in the Community, which encourages prescribing antimicrobials only when they are likely to be beneficial to the patient, selecting agents that will target the likely pathogen, and using these agents in the correct dose and for the proper duration. The editorial suggests that we have been effective at decreasing the overall use of antibiotics, but less successful at promoting targeted therapy, ie, using narrow spectrum antibiotics whenever appropriate to reduce the likelihood of resistance in a population (Ann Intern Med. 2003;138:525-533,605-606).

Nefazodone Under Attack Once Again

Public Citizen, the national nonprofit watchdog organization, has petitioned the FDA to remove the antidepressant nefazodone (Serzone—Bristol-Myers Squibb) from the US market. The petition is based on evidence of liver toxicity associated with the drug including liver failure and death. Nefazodone was recently pulled from the European market after reports of a worldwide total of 28 cases of liver failure of which 18 patients died. The move in Europe was voluntary on the part of Bristol-Myers Squibb because of the call for increased liver enzyme monitoring requirements in several European countries. In this country, the FDA has required a black box warning on nefazodone since January 2002. Despite these concerns, nefazodone, which is a SSRI antidepressant, continues to be relatively popular, with more than 4 million prescriptions written last year. Bristol-Myers Squibb has no plans to withdraw the drug in this country at present.

Lindane Receives Black Box Warning

The FDA has issued a Public Health Advisory concerning the use of lindane for the treatment of scabies and lice. The boxed warning is the result of concern of potential neurotoxicity especially in children. The new advisory states that lindane is a second-line treatment and updates information about its potential risk in children and adults who weigh less than 110 pounds. The advisory also states that reapplication of lindane lotion or shampoo is not appropriate even if itching continues after the single treatment. The FDA is also requiring package sizes to be limited to 1 and 2 oz in order to minimize the potential for product access in a single treatment. Lindane, also known as gamma benzene hexachloride, is an industrial pesticide, has been in use for decades, and has been banned in several countries. Neurologic side effects include dizziness, seizures, and even death. The drug is currently approved for the treatment of lice and scabies in patients who have failed or are intolerant of other therapies. First-line agents for scabies include permethrin cream (Nix, Elimite, Acticin) and malathion lotion (Ovide) and for lice pyrethrum with piperonyl butoxide shampoo and cream rinse permethrin cream rinse (Nix and Rid).

Aspirin Could Help Reduce Colorectal Adenomas

Two different studies in the same issue of the New England Journal of Medicine suggest that daily doses of aspirin reduce the risk of colorectal adenomas. In the first study, 635 patients with previous colorectal cancer were randomized to receive either 325 mg of aspirin per day or placebo. The study was terminated early when a significant reduction in colorectal adenomas was shown during the planned interim analysis. After an average of 12.8 months of follow-up, 1 or more adenomas were found in 17% of patients in the aspirin group and 27% patients in the placebo group (P = 0.004). The mean number of adenomas was lower in the aspirin group (P = 0.003) and the time to detection of the first adenoma was longer in the aspirin group than in the placebo group (P = 0.022). In the second study, 1121 patients with a recent history of adenomas were randomized to placebo (372 patients), 81 mg of aspirin (377 patients), or 325 mg of aspirin (372 patients). Follow-up colonoscopy was done approximately 3 years after randomization. The incidence of 1 or more adenomas was 47% placebo group, 38% in the 81 mg aspirin group, and 45% in the 325 mg aspirin group (global P = 0.04). The risk of larger polyps including adenomas measuring > 1 cm or with tubulovillous or villous, or severe dysplasia was also lowest in the 81 mg aspirin group. An accompanying editorial suggests that inhibition of COX-2 may prevent inflammation, increased cell proliferation and angiogenesis. The author also cautions that prophylactic aspirin is not a substitute for colorectal cancer screening (N Engl J Med. 2003; 348:883-890, 891-899,879-880).


This supplement was written by William T. Elliott, MD, FACP, Chair, Formulary Committee, Kaiser Permanente, California Division; Assistant Clinical Professor of Medicine, University of California-San Francisco. Telephone: (404) 262-5517. E-mail: robin.mason@ahcpub.com. In order to reveal any potential bias in this publication, we disclose that Dr. Elliott reports no consultant, stockholder, speaker’s bureau, research, or other financial relationships with companies having ties to this field of study.