Misoprostol and Nonsteroidal Anti-inflammatory Drugs: A Tale of Effects, Outcomes, and Costs

Nonsteroidal anti-inflammatory drugs (NSAIDs) injure the mucosal lining of the stomach, causing a “gastroduodenopathy” of superficial erosions in the antrum and duodenum with occult gastrointestinal bleeding [1]. Dyspeptic symptoms are of little value in discriminating between patients with and without this gastropathy. Many epidemiologic studies have also documented an increased risk for perforation, obstruction, and overt gastrointestinal bleeding from larger chronic ulcers associated with NSAID use [2]. Physicians have had to balance these known unfavorable consequences of NSAIDs with their utility in treating painful inflammatory conditions.

Casual observation suggests that many physicians and patients have concluded that the adverse outcomes are less important than the clinical benefits. Despite a flurry of media “revelations,” NSAIDs continue to be one of the most commonly prescribed classes of drugs in the United States [3], and the Food and Drug Administration (FDA) has decided that ibuprofen, naproxen, and aspirin can be safely sold over the counter to be used at the patient's discretion.

Because cumulative knowledge showed that the gastropathy was associated with depletion of tissue prostaglandins and that the damage could be prevented by pretreatment with prostaglandins, the oral prostaglandin congener misoprostol (Cytotec; G.D. Searle and Co., Chicago, Illinois) was submitted for FDA approval. Despite initial concerns about misoprostol's abortifacient property, the drug was approved as “indicated for the prevention of NSAID-induced gastric ulcers in patients at high risk …