The problems and pitfalls of NSAID therapy in the elderly (Part I)

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most commonly prescribed drugs worldwide when grouped by generic categories and account for 3 to 9% of total prescription numbers in various countries. While NSAIDs are responsible for approximately 25% of all reported adverse drug reactions, aging may substantially increase the risk of NSAID-induced reactions. Several factors may contribute to NSAID-related toxicity in the elderly. The increase in morbidity associated with aging may result in consumption of a wide range of potent drugs, while inappropriate drug therapy and aberrant compliance are also capable of contributing to adverse drug reactions in geriatric patients. Age-related alterations in pharmacokinetics may influence the handling of NSAIDs in the elderly; in particular, dosage reduction is appropriate for azapropazone (apazone), naproxen, ketoprofen and salicylates administered to healthy aged patients, whereas the presence of renal disease may also necessitate dosage reduction of diflunisal, indomethacin, sulindac and mefenamic acid. Changes in NSAID pharmacodynamics with aging, such as increased CNS sensitivity to NSAIDs and impaired homeostasis, also predispose the elderly to NSAID-related adverse effects. It is undisputed that gastrointestinal toxicity due to NSAID therapy is a class effect. A significant association has been found between aspirin and uncomplicated gastric, but not uncomplicated duodenal ulcer, while nonaspirin NSAIDs are significantly associated with both uncomplicated gastric and duodenal ulceration. The use of NSAIDs is accompanied by a 2- to 5-fold risk of serious complications of peptic ulcer disease, i.e. haemorrhage or perforation, which increases in the elderly, particularly women. A broad range of renal side effects has been ascribed to NSAIDs, of which acute renal impairment is the most common in the elderly. Although most NSAIDs have been reported to cause hepatotoxicity, serious abnormalities of liver function are rare and are largely unpredictable. Other adverse effects due to NSAIDs have also been described, some of which (e.g. cardiovascular, CNS and haematological effects) may be more common in the elderly.