Jewish World Review May 3, 2002 / 21 Iyar, 5762

Risk of adverse drug reactions from newly released medications

By Robert A. Wascher, M.D., F.A.C.S. | Prior to being approved for public use, the FDA requires all new drugs to undergo extensive safety testing in both animals and humans. It therefore stands to reason that the incidence of subsequent adverse reactions to these new medications should be a very rare event.

However, a study in this week's Journal of the American Medical Association (JAMA) suggests otherwise. A review of new drugs approved between 1975 and 1999 revealed that 548 chemically distinct new drugs became available for public use during this timeframe.

Following FDA approval, slightly more than 1 out of 10 new drugs were subsequently found to be associated with adverse effects severe enough to require special "black box" warnings or withdrawal from the market. When these results were used to statistically predict the likelihood of a black box warning or withdrawal from the market over a period of 25 years, the probability of a newly introduced drug requiring either of these actions rose to 20%.

This study strongly suggests that, despite a rigorous program of FDA-sanctioned pre-approval safety testing, 1 in 5 newly introduced drugs will eventually require either strict warnings for prescribing physicians and their patients or/and removal from the market.

At the same time, it should be acknowledged that the FDA has recently tightened its standards for drug safety testing prior to granting expedited approval. Moreover, many black box warnings have been used to identify extremely rare or merely suspected potential adverse reactions, all in the interest of improved patient safety.


A recent FDA advisory warned of the potential risk of severe liver injury in people taking the widely used herbal supplement Kava. Now, the Annals of Internal Medicine is reporting that the dietary weight loss supplement LipoKinetix (manufactured by Syntrax Corporation) may also be associated with severe liver injury in some cases.

A review of the FDA adverse event database revealed 7 patients who were taking LipoKinetix when the acute onset of severe liver injury occurred. All 7 patients had onset of liver impairment within 3 months of starting the supplement, and all patients recovered their liver function after discontinuing LipoKinetix.

While these 7 cases represent a small number of patients, the association of recent intake of LipoKinetix with liver failure, and which subsequently resolved after discontinuation of the supplement, strongly suggests that, in at least some people, this substance may be very toxic to the liver. Until further information becomes available, it might be prudent to discontinue taking this supplement at the present time.


The journal Science is reporting on a new class of experimental sutures and implantable surgical prosthetic devices. These new compounds can be compressed into small shapes, and then "re-sized" by the body's heat after implantation.

Relatively large sheets of these materials could be inserted into body cavities through tiny laparoscopic incisions, and then be sutured or stapled into place, after they expand, to repair weakened tissues (to repair hernias, for example). The concept is somewhat similar to those tiny toy animals that swell up to a much larger size after being placed in a container of water. Sutures made from such materials could also be loosely applied within the body, only to "tighten-up" after exposure to body temperatures.

These revolutionary bioplastic materials are then gradually degraded and absorbed by the body as it heals. Such shape-shifting prosthetic materials could have a very significant impact in surgery, and particularly on many "minimally invasive" surgical procedures, including laparoscopic surgery of the abdominal and chest cavities.


Recent research has shown that patients with significant risk factors for coronary artery disease who undergo surgery with a general anesthetic are less likely to die of heart-related causes if they are given beta-blocking drugs before surgery.

This class of drugs blocks receptors for some of the hormones in the body that are produced during the "fight or flight" response. In general, these hormones increase heart rate as well as the force of the heart's contractions.

In patients with significant underlying heart disease, these stress hormone effects on the heart can deprive the already damaged organ of vital blood flow and oxygen, increasing the risk of heart attack. During surgery, the body also pumps out these same stress-related hormones, increasing the risk of heart attack in patients with already diseased hearts.

In this week's JAMA, the preoperative use of beta-blocking drugs has also now been shown to reduce the risk of death associated with coronary artery bypass surgery. Clearly, patients undergoing bypass surgery already have, by definition, significant coronary artery disease. This new study found that the mortality rate of bypass surgery was reduced by 20% in patients who received beta blockers prior to being put to sleep for their heart surgery.

Although the actual reduction in risk of mortality went only from 3.4% in patients not receiving beta-blockers to 2.8% for those patients who did get the drug, nearly a million coronary artery bypass operations are done around the world each year. Thus, the routine use of beta-blockers prior to starting this operation could potentially result in 6,000 lives being saved each year.

JWR contributor Dr. Robert A. Wascher is a senior research fellow in molecular & surgical oncology at the John Wayne Cancer Institute in Santa Monica, CA. Comment by clicking here.


04/26/02: Angry young men & risk of premature cardiovascular disease; stay-at-home dads & risk of cardiovascular disease; more on the effects of statins; dairy consumption and the risk of pre-diabetes; smallpox vaccine: good to the last drop?
04/19/02: Change your sex by drinking water?; Anti-inflammatory RXs may reduce growth of breast cancer cells; radiation treatment reduces repeat narrowing of bypass grafts
04/05/02: Fish & Omega-3 fatty acid consumption and cardiac health; news briefs
04/05/02: Can coffee reduce your risk of tooth decay?; exercise & blood pressure; a single high-fat meal reduces coronary artery function
04/01/02: Pre-diabetes: a newly defined category of health risk; teen television viewing and subsequent aggressive behavior; the benefits of strength training in the elderly; more ...
03/22/02: Bacteria, antibiotics & heart disease; mammograms: the debate continues; calcium & the risk of colon cancer ... and more
03/15/02: Mammography debate continues; statins & fracture risk; physical fitness & the risk of death; other intriguing findings
03/08/02: Blows to the chest & sudden cardiac death; air quality & the risk of lung cancer; tomatoes and your prostate
03/01/02: Diet & the risk of ovarian cancer; lifetime risk of developing high blood pressure; Osteoporosis prevention with a once-a-year injection?
02/26/02: The continuing controversy regarding screening mammography
02/22/02: Lowering body temperature after heart attack improves outcome; A silver lining for the chronically sleep-deprived?
02/15/02: Hormone replacement therapy & the risk of breast cancer; use it or lose it: Alzheimer's disease & cognitive stimulation; stress, divorce & death; child daycare, infections & parental guilt
02/08/02: Possible breakthrough in early cancer diagnosis; mammography: the controversy continues; CPR techniques revisited
02/01/02: Antibiotics in livestock feed & human disease; genetic detection of early colon cancer in the stool; genetic analysis of breast cancers may help decide treatment
01/25/02: Drug increases lifespan (if you're a fly...); workplace attitudes and smoking cessation; effects of inadequate sleep on surgeons
01/18/02: Lifelong effects of premature birth; smokers under the knife; aspirin and cardiovascular health
01/11/02: Estrogen levels in the blood & breast cancer risk; Heart attack: sex and survival; dangerous lettuce invaders
01/09/02: Cancer & aging: Two sides of the same coin?
01/04/02: Vitamin a & the risk of hip fracture in postmenopausal women; ovarian cancer risk and oral contraceptives
12/28/01: Magnetic Resonance Imaging (MRI) detects coronary artery disease; new development in obesity research; adverse childhood experiences & the risk of suicide attempts
12/21/01: Vaccination of children controls hepatitis a in the community; a possible cure for sickle cell disease; leptin and the risk of heart attacks
12/14/01: Chernobyl and the Risk of Thyroid Cancer in hildren; children & obesity; gastroesophageal reflux disease update
12/07/01: Update on school shootings; new implantable heart-assist device approved for further evaluation; prevention of fungal infections in pre-term babies
11/30/01: Flu vaccination in asthmatics; low-tar cigarettes are not less harmful; beans and your heart
11/21/01: Modified smallpox vaccine may reduce risk of cervical cancer; New approach to breast cancer diagnosis; New non-invasive prenatal diagnostic test for down's syndrome
11/16/01: Cholesterol-lowering drugs reduce risk of heart attack; supplemental radiation therapy reduces risk of breast cancer recurrence; brains of women may answer age-old questions
11/09/01: Bio-warfare (redux); my gray matter is bigger than yours; mad elk disease?
11/02/01: Making sense of bio-warfare
10/26/01: The impact of mammography on deaths due to breast cancer; diet & exercise may slow cancer cell growth; antidepressants and the risk of heart disease
10/19/01: New insights into autism; the wiley appendix
10/12/01: More bad news about obesity links to other diseases…Hey dad, can I borrow the car keys?
10/05/01: California leads nation in reduction of tobacco-related disease; exercise as an antidepressant?
09/25/01: Advances in the detection of breast cancer; primary care physician awareness of peripheral arterial disease; arsenic in the water
09/17/01: In perspective
09/12/01: Genes may hold secret to long life; men and women: cognitive function in the elderly; physical activity, obesity and the risk of pancreatic cancer
09/05/01: English milk cows prefer Beethoven and Simon & Garfunkel over Bananarama; new prostate cancer prevention study: looking for a few good men; exercise & diet can help prevent diabetes
08/28/01: Arthritis drugs may be linked with increased risk of heart disease; errors in blood clotting tests can be fatal; infant soy formula not associated with reproductive side effects

© 2002, Dr. Robert A. Wascher