The Latest Information on New Drugs and New Indications
By William T. Elliott, MD, FACP
Sales of pfizer's sildenafil (viagra) have been staggering. physicians and pharmacists around the country are reporting unprecedented requests for the drug to the tune of 15,000-20,000 new prescriptions per day. Many pharmacies are having difficulty keeping the drug in stock-all of this before the company has even launched an advertising campaign for the medication. There is also word that the drug is being tested for use in women, although no results are available yet. In the meantime, Pfizer's stock is soaring. (See article on page 74.)
Is there an optimal LDL level for those treated with statins? A linear relationship between LDL lowering and coronary events has been shown in a number of trials. A recent issue of Circulation contains a review of data from the CARE Trial, which used pravastatin. The analysis reaffirmed the expected reduction in coronary events with cholesterol lowering from 174 to 125, but no further benefit was seen from 125 to 71. This suggests a threshold effect for cholesterol lowering, with a questionable benefit for lowering LDL below 125 (Circulation 1998;97:1446-1452). Other studies have not shown a threshold effect, and most experts still recommend a target LDL of 100 for all patients with CAD.
The generic drug industry has come under scrutiny because of questionable pricing practices and charges of cornering the market for certain drugs. At the forefront of the controversy is the generic drug manufacturer Mylan, which makes nearly 100 different entities. One of their best sellers, lorazepam, was subject to a more than 300% increase in price on March 3, from $17 to nearly $65/100 pills. At the same time, other generic manufacturers of lorazepam raised their prices to similar levels. Rumors have circulated in the industry that Mylan has stockpiled certain raw materials for the drug, forcing some companies to discontinue the product altogether. Mylan denies these allegations, claiming that it needs to increase the price of lorazepam and several other of its generic products, to stay competitive and avoid losing money in the low margin generic market.
The FDA has mandated that all enriched grains, including breakfast cereals, be fortified with folic acid as of January 1, 1998. Folic acid in the diet of women during their childbearing years has been shown to reduce the incidence of neural tube birth defects, but there may be another benefit. A recent study (N Engl J Med 1998;338(15):1009-1015) suggests that folate supplements lower homocysteine levels, a risk factor for coronary disease in some patients.
Daily doses of aspirin may be nearly as effective as warfarin in preventing stroke in certain low-risk patients with atrial fibrillation. Part of the ongoing Stroke Prevention in Atrial Fibrillation trial (SPAF), the most recent study (JAMA 1998;279(16):1273-1277) looked at patients with atrial fibrillation who were treated with aspirin alone. The authors considered patients high-risk if they had congestive heart failure, previous thromboembolism, systolic BP greater than 160, or female gender older than 75 years. In the absence of these risk factors, patients treated with aspirin alone had about a 1% per year risk of stroke, about the same as the general population. The authors conclude that aspirin may be a reasonable alternative to anticoagulation with warfarin in low-risk patients with atrial fibrillation.
A tiff has developed between drug maker Glaxo Wellcome and Chelsea Laboratories, a generic drug company, over the secret recipe for buproprion, Glaxo's new stop-smoking drug. Glaxo claims that former employees of Burroughs Wellcome gave the recipe for the drug to Chelsea when Glaxo took over Burroughs Wellcome in 1995. The patent for buproprion expired in 1994, but no generics have been developed yet. A court battle is developing.
The FDA has given preliminary approval to medical glue for wound closure. A non-absorbable cyanoacrylate derivative similar to "Super Glue," the product has been tested on more than 800 subjects, including children as young as age 1. The glue works best for superficial wounds that need closure or as a epidermal closure agent after subcutaneous absorbable suture has been used. The cosmetic outcome is good, and a return visit for suture removal is not needed. Application takes less than a minute and is painless, making the glue ideal for pediatric use in the emergency setting.
Many pharmaceutical manufacturers are eyeing the lucrative over-the-counter (OTC) market in the wake of such successful prescription to OTC switches such as the H2 antagonists and NSAIDS. Consideration is even being given to anti-herpes drugs such as acyclovir, antifungals such as terbinafine, and statins such as fluvastatin. All of these drugs face uphill battles in the FDA and from specialty groups who are concerned about inappropriate usage.
Researchers have leaked results of a study to be presented this month concerning raloxifene and breast cancer. The results, published in the Wall Street Journal and The New York Times, apparently show a 45% reduction in the risk of breast cancer-not as effective as tamoxiphen-but unlike tamoxiphen, the drug is not associated with an increased risk of endometrial cancer. Early sales of raloxifene have been disappointing to Lilly, perhaps because the drug causes hot flashes for many women.
Still counter-intuitive to most primary care doctors, a recent study has again shown benefit for the use of beta blockers in patients with dilated cardiomyopathy. The Italian study (Heart 1998;79:337-334) looked at more than 600 patients with cardiomyopathy. Those treated with metoprolol along with standard CHF regimens (ACEIs and diuretics) had a seven-year, 30% reduction in all-cause mortality. This confirms the theory that excessive neuroendocrine activation may be detrimental to the failing heart.