FDA Approves Generic Version of AstraZeneca’s Prilosec

Pharmacology Watch

The FDA has approved the first generic version of AstraZeneca plc’s blockbuster drug, omeprazole (Prilosec). KUDCO, a subsidiary of Germany’s Schwartz Pharma was granted the approval in a court ruling in mid-October. The FDA has cleared a number of other generic versions of the drug; however, this is the first, in the eyes of the courts, that does not infringe on patents held by AstraZeneca. In a complicated set of deals, KUDCO is partnering with Andrix Pharmaceuticals and Genpharm Inc to bring the drug to market by early 2003. Prilosec, with worldwide sales of more than $4 billion a year, has been the focus of intense legal wrangling as AstraZeneca has pulled all the stops to prevent marketing of generic forms of the drug. Meanwhile, consumer groups hoping to bring down the cost of prescription medications have been urging the Bush administration to speed generics, such as omeprazole, to market. The FDA has approved omeprazole for over-the-counter use but is still working with AstraZeneca on labeling language. Consumers can expect OTC Prilosec in the second quarter of next year.

Pegasys Approved To Treat Hepatitis C

A second pegylated interferon has been approved for the treatment of chronic hepatitis C infection. F. Hoffmann-La Roche Ltd’s peginterferon alfa-2a (Pegasys) will compete with Schering-Plough’s peginterferon alfa 2-b (Peg-Intron) for this indication. It is estimated that nearly 4 million Americans have evidence of infection with hepatitis C, of which nearly 3 million have chronic hepatitis C infection. In the last few years, standard treatment has become interferon either standard or pegylated, alone or in combination with ribavirin. Standard interferon must be given 3 times a week. Adding polyethylene glycol (PEG) to the interferon molecule increases the elimination half-life, allowing for less-frequent dosing, generally once a week. Pegasys is approved only as monotherapy; however, Schering-Plough has applied for approval of combination therapy with Pegasys and ribavirin. The FDA has fast-tracked the application, with final approval expected before the end of year.

HRT Reduces Alzheimer’s Risk, Study Says

Yet another study has weighed in on the issue of hormone replacement therapy and the risk of Alzheimer’s disease (AD). This study of a population of older adults in Cache County, Utah showed that 10 years or more of HRT significantly reduced the risk of Alzheimer’s disease. Importantly, the study also showed that once women are in the early stages of Alzheimer’s disease, it is too late for HRT to have any benefit. The rate of AD was evaluated in 1357 men (median age, 73.2 years) and 1889 women (mean age, 74.5 years). After a 3-year follow-up, women who formerly used HRT or women who are currently using HRT for longer than 10 years had a statistically significant reduction in the rate of AD (HRT users represented 26 cases/1066 women, non HRT users represented 58 cases/800 women [adjusted HR, 0.59; 95% CI, 0.36-0.96]). Almost all the HRT-related reduction in the incidence of AD was among women who had formerly used HRT. A related editorial suggests that there may be a critical period soon after menopause, which is characterized by rapid estrogen depletion, where HRT may provide the most neuroprotective benefit for women (JAMA. 2002;288:2123-2129, 2170-2173). In mid-October officials from the National Institutes of Health announced that they would continue to study the effects of HRT or conditions such as osteoporosis and AD. This announcement was important in light of the early termination of the Women’s Health Initiative study on hormone replacement in July. Currently, the National Institute on Aging is funding 3 studies that will compare how well HRT combination therapy or estrogen alone helps prevent memory loss and loss of cognitive function in women older than 65.

Heparin Plus Alteplase More Effective

Patients with submassive pulmonary emboli (PE) will fare better treated with heparin plus alteplase compared to heparin alone, according to a new study. Alteplase, a thrombolytic agent, is commonly used in the treatment of massive PE. This study seeks to define the drug’s role in submassive PE in hemodynamically stable patients. Two hundred fifty-six patients with PE and pulmonary hypertension or RV dysfunction but without arterial hypertension or shock were evaluated. One hundred thirty-eight received heparin plus alteplase 100 mg and 118 received heparin plus placebo. The primary end point was in-hospital death or treatment escalation (pressors, repeat thrombolysis, intubation, CPR, or emergency embolectomy). The primary end point occurred nearly 3 times as often in the heparin plus placebo group, all due to treatment escalation. In-hospital death was nonsignificantly higher in the heparin group, 3.4%, vs 2.2% for the alteplase group (P = .71). However, 30-day event-free survival was higher with heparin vs alteplase (P = .005). The authors conclude that thrombolytic therapy with alteplase plus heparin should be considered in patients with submassive PE (N Engl J Med. 2002;347:1143-1150).

Digoxin Effects Differ By Sex

Digoxin should be used with caution in women with heart failure and may even be associated with an increase in mortality, according to a new study. The Digitalis Investigation Group looked at 6800 patients on digoxin therapy with the primary end point being mortality from any cause. While there was no increased mortality in men on digoxin, women on the drug had a higher rate of death compared to the placebo group (33.1% vs 28.9%, respectively; 95% CI,-0.5-8.8). The authors conclude that the effect of digoxin therapy differs between men and women. Women with congestive heart failure of a higher mortality rate associated with use of the drug, while the same is not seen with men (N Engl J Med. 2002;347:1403-1411).

McClellan Named FDA Commissioner

The Food and Drug Administration finally has a commissioner, after 2 years of vacancy in the position. The new commissioner, Mark McClellan, MD, was approved quickly and unanamously. He has a background in both medicine and economics, and has been an advisor to both Presidents Clinton and Bush. He has most recently been a professor of medicine and economics at Stanford University. Dr. McClellan joins the FDA at a time of unprecedented change and turmoil. There is high turnover at the agency, and criticism from consumer groups that drug approvals take too long on the one hand, and are too cursory on the other. President Bush has recently backed removing legal obstacles to the approval of generic drugs, a move meant to reduce prices for consumers, and a move that is not popular with Pharma.

FDA Actions

The FDA has approved 2 formulations of buprenorphine, a new schedule III narcotic for treatment of patients with narcotic addiction. Buprenorphine will be marketed as Subutrex by Reckitt Benckiser pharmaceuticals, while the second preparation, which combines buprenorphine with naloxone, will be marketed by the same company as Suboxone. The combination with naloxone is intended for maintenance therapy since naloxone will safeguard against intravenous abuse. The FDA took the unusual step of putting buprenorphine into the schedule III category rather than schedule II to allow easier prescribing in compliance with recent congressional legislation making maintenance narcotics more available to patients.

Bristol-Myers has received approval to market Metaglip, a new combination drug for treatment type 2 diabetes. Metaglip combines gliptizide and metformin in a single tablet for initial therapy of type 2 diabetes.


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.