Use Of Common OTC Drugs In Pregnancy Linked To Abdominal Birth Defect

WESTPORT, Dec 12 (Reuters) - In utero exposure to "...aspirin, ibuprofen or decongestants during the first trimester of pregnancy appears to significantly increase the risk of gastroschisis," according to the December 11 Los Angeles Times. The Times reports on a study by Dr. Claudine P. Torfs for the California Birth Defects Monitoring Program that is published in the current issue of Teratology.

Evidently, exposure to organic solvents also increases the risk of the birth defect "...in which a tear in the abdomen allows the intestines to protrude." The Times reports that gastroschisis is most prevalent in infants born to women younger than 25 years, and "...occurs in about one out of every 4,500 births." Early treatment, though "complex and costly," will generally correct the defect with "...no permanent repercussions."

Dr. Torfs comments that although a stronger risk of gastroschisis is associated with exposure to cocaine, cigarette smoke and X-rays, exposures to OTC drugs "...are more widespread." She also points out that many exposures to organic solvents come from household use of such products as hair dyes, nail polish, furniture paints and fabric dyes "...without the use of protective gear.". "In the workplace, there are rules and regulations about exposures," Dr. Torfs comments in the Times article. "It may be that people should worry also about their hobbies."

"There is an epidemic of adverse drug reactions to NSAIDs. The Food and Drug Administration believes anywhere from 10,000 to 20,000 deaths each year are the result of severe bleeding caused by NSAIDs. It is a big problem.".
Dr. James F. Fries. Professor of Medicine at Stanford University School of Medicine. in Marsa L. "America's Other Drug Problem," Los Angeles Times Magazine, September 29, 1996.

The best evidence indicates that cervical manipulation for neck pain is much safer than the use of NSAIDs, by as much as a factor of several hundred times. There is no evidence that indicates NSAID use is any more effective than cervical manipulation for neck pain.
Dabbs V; Lauretti WJ; A Risk Assessment Of Cervical Manipulation vs. NSAID's For The Treatment Of Neck Pain. J Manipulative Physio Ther 1995; 18(8):530-6

Less is better in aspirin therapy

UTRECHT, HOLLAND. Stroke patients have an increased risk of dying from another stroke or from heart failure. This risk can be reduced by 20 to 25 percent by taking a regular aspirin (300 mg) every day. Researchers in Holland have now concluded that a daily dosage of 30 mg of aspirin is just as effective in preventing death from vascular diseases as are the higher dosages commonly recommended. The lower dosage also reduces the chance of internal bleeding
and gastric discomfort. The New England Journal of Medicine, October 31, 1991, pp. 1261-65

Anti-inflammatory drugs implicated in ulcers

GLASGOW, SCOTLAND. Researchers at the Royal Infirmary in Glasgow have concluded that long term use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin and ibuprofen may lead to inflammation of the small intestine with associated blood and protein loss. The researchers performed autopsies on 713 patients and found that 8.4% of users of NSAIDs had ulcerations in the small intestine as compared to only 0.6% of non users. Similarly, ulcers of the stomach or duodenum were found in 21.7% of NSAID users but in only 12.3% of non users. The authors conclude that people who take NSAIDs regularly have an increased risk of developing potentially life-threatening ulcers in the small intestine.
The New England Journal of Medicine, September 10, 1992, pp. 749-54

Aspirin usage linked to ulcers

ATLANTA, GEORGIA. Doctors at the Grady Memorial Hospital in Atlanta warn that even short term (<1 week) use of aspirin and other nonsteroidal anti- inflammatory drugs (NSAIDs) can precipitate ulcer-related bleeding. During a two-year study period they investigated the use of NSAIDs by 421 patients admitted to the hospital with upper gastrointestinal hemorrhage. The most common causes of bleeding were gastric ulcers (31 per cent) and duodenal ulcers (26 per cent). The researchers found a very high usage of NSAIDs among the patients in the week prior to hospital admission. Thus about 35 per cent of the patients had taken over-the-counter aspirin while another six per cent had taken prescription aspirin. Another 20 per cent of the patients had taken NSAIDs other than aspirin either by prescription or bought over-the-counter. The doctors conclude that the use of NSAIDs may be a more important cause of gastrointestinal bleeding than previously thought.

Wilcox, C. Mel, et al. Striking prevalence of over-the-counter nonsteroidal anti-inflammatory drug use in patients with upper gastrointestinal hemorrhage. Archives of Internal Medicine, Vol. 154, January 10, 1994, pp. 42-6

Drug dependency starts in childhood

HYATTSVILLE, MARYLAND. Researchers at the Centers for Disease Control and Prevention have completed a study of the use of over-the-counter (OTC) medications among children in the United States. The study involved interviews with the mothers of 8145 three-year-old children. The results were startling. During the 30 days prior to the interview more than half (53.7 per cent) of the children had been given OTC medications. The most common medications were Tylenol (66.7 per cent) and cough or cold medicines (66.7 per cent). About 40 per cent of the children receiving OTC medications were given two medications while 5 per cent were given three or four different kinds at the same time. The use of OTC medications was substantially higher among children whose mothers were white, had a high school education or college degree, and a higher than average household income. About one-third of the OTC medications were "cold" medicines; this despite the fact that there is ample evidence that these medications are ineffective and may, in some circumstances, have adverse side effects. It is also of concern that almost 15 per cent of the children were given anti-diarrheal agents even though these medicines are not recommended for young children due to potential side effects.

Kogan, Michael D., et al. Over-the-counter medication use among US preschool- age children. Journal of the American Medical Association, Vol. 272, No. 13, October 5, 1994, pp. 1025-30

NSAIDs implicated in common kidney disease

ROCHESTER, MINNESOTA. Membranous nephropathy (MN) is a common cause of nephrotic syndrome. Nephrotic syndrome is characterized by edema and loss of protein through the urine. MN is most common in men aged 40 to 50 years and can lead to end-stage renal disease and death. The cause of MN is unknown in the majority of cases, but certain drugs such as gold, penicillamin and captopril have been implicated. Now researchers at the Mayo Clinic report that the use of nonsteroidal anti-inflammatory drugs (NSAIDs) can cause membranous nephropathy. Their survey involved 125 patients with MN who had been patients at the Clinic between 1975 and 1995. Twenty-nine of the patients had been taking NSAIDs when their symptoms developed. The researchers concluded that the MN was directly caused by the NSAIDs in 13 of the patients. These patients were instructed to discontinue the use of NSAIDs and within a few weeks their MN symptoms disappeared. There has been no relapse for follow-up periods ranging from five months to 13 years. The following NSAIDs were implicated in the development of MN: diclofenac, fenoprofen, ibuprofen, nabumetone, naproxen, and tolmetin. Aspirin and acetaminophen (Paracetemol, Tylenol) have been implicated in the development of other forms of kidney disease. The researchers conclude that the use of NSAIDs should always be investigated in patients diagnosed with MN as their withdrawal may result in prompt and complete recovery.

Radford, M. Gene, et al. Reversible membranous nephropathy associated with the use of nonsteroidal anti-inflammatory drugs. Journal of the American Medical Association, Vol. 276, No. 6, August 14, 1996, pp. 466-69

Aspirin Causes Gastroinestinal Perforations

BACKGROUND & AIMS: Current studies lack appropriate data on aspirin and other risk factors for gastrointestinalperforation. The aim of this study was to obtain the best estimate on aspirin and nonaspirin nonsteroidal anti-inflammatory drug (NSAID) use in these patients.

METHODS: In 76 consecutive patients with gastrointestinal perforation and 152 matched controls, a detailed clinical history supplemented with an objective test of current aspirin use (platelet cyclooxygenase activity) was obtained.

RESULTS: Of the 76 cases, 78.9% were upper and 21% lower gastrointestinal perforations. Evidence of NSAID use was found in 71% of cases (70% upper, 75% lower) vs. 26.9% of controls (odds ratio, 6.64; 95% confidence interval, 3.6-12.2; P < 0.0001). The objective test showed 12.7% more aspirin users than clinical history alone. NSAID use was aspirin (alone or combined) in 66.6% of cases, and 59.25% was nonprescription. Other independent risk factors were smoking, alcohol, and a history of arthritis or peptic ulcer but not a positive Helicobacter pylori serology. Age, but not NSAID use, affected perforation-associated mortality.

CONCLUSIONS: NSAID use is strongly associated with an increased risk of both upper and lower gastrointestinal perforation. The high prevalence of aspirin (over-the-counter) use suggests that future introduction of new NSAIDs may not have a major impact on decreasing gastrointestinal complications if other measures are not taken. Concomitant NSAID use, smoking, and alcohol use is a pervasive association.

Lanas A, Serrano P, Bajador E, Esteva F, Benito R, Sainz R. Evidence of aspirin use in both upper and lower gastrointestinal perforation. Gastroenterology 112: 683-689 (1997)

Aspirin Use Increases Risk Of Ulcers

OBJECTIVE--To determine the risks of hospitalisation for bleeding peptic ulcer with the current prophylactic aspirin regimens of 300 mg daily or less.

DESIGN--A case-control study with hospital and community controls.

SETTING--Hospitals in Glasgow, Newcastle, Nottingham, Oxford, and Portsmouth.

SUBJECTS--1121 patients with gastric or duodenal ulcer bleeding matched with hospital and community controls.

RESULTS--144 (12.8%) cases had been regular users of aspirin (taken at least five days a week for at least the previous month) compared with 101 (9.0%) hospital and 77 (7.8%) community controls. Odds ratios were raised for all doses of aspirin taken, whether compared with hospital or community controls (compared with combined controls: 75 mg, 2.3 (95% confidence interval 1.2 to 4.4); 150 mg, 3.2 (1.7 to 6.5); 300 mg, 3.9 (2.5 to 6.3)). Results were not explained by confounding influences of age, sex, prior ulcer history or dyspepsia, or concurrent non-aspirin non-steroidal anti-inflammatory drug use. Risks seemed particularly high in patients who took non-aspirin non-steroidal anti-inflammatory drugs concurrently.

CONCLUSION--No conventionally used prophylactic aspirin regimen seems free of the risk of peptic ulcer complications.

Weil J, Colin-Jones D, Langman M, Lawson D, Logan R, Murphy M, Rawlins M, Vessey M, Wainwright P. Prophylactic aspirin and risk of peptic ulcer bleeding.BMJ 1995 Apr 1;310(6983):827-830

NSAIDs Can Increase Blood Pressure

Although evidence of a link between the use of nonsteroidal anti-inflammatory drugs (NSAIDs) and elevated blood pressure (BP) has been inconsistent, an analysis finds that the drugs are associated with a clinically important increase in BP. The effect is most pronounced in patients on antihypertensive therapy.

Dr. Anthony G. Johnson of Princess Alexandra Hospital in Queensland, Australia, reviewed the data on the effects of NSAIDs on BP. He concludes that "Pooled data drawn from published reports of randomised trials of younger adults reveal that NSAID usage produces a clinically significant increment in mean blood pressure of approximately 5 mm Hg."

When sustained over several years of NSAID use, this elevation could "...be associated with a substantial increase in the risk of stroke and coronary heart disease events," according to Johnson's report in the November issue of Drug Safety.

Johnson found that the most marked increases in BP occurred in patients who were also taking antihypertensive medication. This finding is of concern since "...12% to 15% of older individuals receive an NSAID and an antihypertensive agent concurrently."

Since piroxicam, naproxen, and indomethacin appear to have the strongest effects on BP, physicians prescribing NSAIDs for hypertensive patients may want to try other alternatives. Sulindac, for example, has the smallest pressor effect.

Johnson stresses the importance of the "rational use of NSAIDs," and points out that when other alternatives cannot be identified, patients prescribed these drugs "...should be monitored carefully by regular blood pressure checks particularly during the period of initiation."

Drug Safety (1997;17:277-289)


MONTREAL, CANADA. Nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most prescribed drugs in the world today. It is estimated that 70 million prescriptions are filled each year in the United States for these drugs. Corresponding figures for Great Britain and Canada are 20 million and 10 million respectively. Numerous studies have shown that the use of NSAIDs increases the risk of hospitalization or death from gastrointestinal bleeding. In Canada 365 people die and 3900 people are hospitalized every year from taking NSAIDs. The corresponding numbers for the United States are 7600 deaths and 76,000 hospitalizations. It has also been estimated that one third of the cost of treating arthritis patients relates to treatment of the side-effects of NSAIDs. In the mid-1980s physicians were advised against prescribing NSAIDs to elderly people and people with a history of peptic (gastric and duodenal) ulcers. However, a recent survey carried out by a team of American and Canadian researchers clearly shows that this warning has largely gone unheeded.

The blinded study involved 112 practicing physicians in Montreal. Each physician was visited by one or more of eight elderly, "standardized" patients - four of which had osteoarthritis in the hip and a history of peptic ulcer while the other four had current stomach (midepigastric) pain and pain and stiffness in the right hip. The diagnoses and prescription patterns of the participating physicians were evaluated by an expert panel. The panel concluded that unnecessary prescriptions for NSAIDs and other drugs were written during 41.7 per cent of all visits. Naproxen was the most commonly prescribed NSAID with diclofenac a close second. The physicians did correctly diagnose gastropathy (disease involving the stomach) in 93.4 per cent of the visits by the stomach pain patients, but managed it incorrectly in 23 per cent of the cases. The hip patients were diagnosed correctly (osteoarthritis) in 90.6 per cent of cases and were prescribed acceptable treatment in 58.3 per cent of the cases while the suggested treatment for the remaining 41.7 per cent of the patients was deemed to be either suboptimal or clearly unsafe (22.3 per cent). The researchers conducting the study found that physicians were more likely to mismanage a case the less time they spent with the patient. Studies have shown that elderly patients and patients with peptic ulcers have a greatly increased risk of serious complications if taking NSAIDs. It was therefore particularly disturbing that the patients' risk factors were not assessed at all during 19 of the 57 visits during which NSAIDs were prescribed. The researchers conclude that unnecessary prescription of NSAIDs and incorrect management of NSAID-related side-effects are common and may contribute significantly to avoidable gastrointestinal disease in elderly people.

Tamblyn, Robyn, et al. Unnecessary prescribing of NSAIDs and the management of NSAID-related gastropathy in medical practice. Annals of Internal Medicine, Vol. 127, September 15, 1997, pp. 429-38

NSAID Related Deaths

Conservative calculations estimate that approximately 107,000 patients are hospitalized annually for nonsteroidal anti-inflammatory drug (NSAID)-related gastrointestinal (GI) complications and at least 16,500 NSAID-related deaths occur each year among arthritis patients alone. The figures for all NSAID users would be overwhelming, yet the scope of this problem is generally under-appreciated. The Arthritis, Rheumatism, and Aging Medical Information System (ARAMIS) Post-Marketing Surveillance Program (PMS) has prospectively followed patient status and outcomes, drug side effects, and the economic impact of illness for >11,000 arthritis patients at 8 participating institutions in the United States and Canada. Analysis of these data indicates that: (1) osteoarthritis (OA) and rheumatoid arthritis (RA) patients are 2.5-5.5 times more likely than the general population to be hospitalized for NSAID-related GI events; (2) the absolute risk for serious NSAID-related GI toxicity remains constant and the cumulative risk increases over time; (3) there are no reliable warning signals- >80% of patients with serious GI complications had no prior GI symptoms; (4) independent risk factors for serious GI events were age, prednisone use, NSAID dose, disability level, and previous NSAID-induced GI symptoms; and (5) antacids and H2 antagonists do not prevent NSAID-induced gastric ulcers, and high-risk NSAID users who take gastro-protective drugs are more likely to have serious GI complications than patients not taking such medications. Currently, limiting NSAID use is the only way to decrease the risk of NSAID-related GI events. Ongoing ARAMIS research is aimed at developing a simple point-score system for estimating individual risks of developing serious NSAID-related GI complications.

Singh G. Recent considerations in nonsteroidal anti-inflammatory drug gastropathy.Am J Med 1998 Jul 27;105(1B):31S-38S