LA CONSULTA SEMANAL

CONSULTA

1: J Clin Pharmacol 2001 Feb;41(2):127-38

A look at the safety profile of over-the-counter naproxen sodium: a meta-analysis.

Bansal V, Dex T, Proskin H, Garreffa S.

Bayer Consumer Care, 36 Columbia Road, P.O. Box 1910, Morristown, NJ 07962-1910, USA.

As the trend for Americans to self-medicate continues to increase, it becomes important to review the safety of over-the-counter (OTC) medications. This article will review the safety of an OTC analgesic, Aleve (naproxen sodium). The objective of this meta-analysis is to evaluate the frequency of occurrence of all adverse events in subjects taking various doses of OTC naproxen sodium as compared to placebo. These varying doses and dosage regimens were studied individually and consisted of 220 to 880 mg administered in single, multiple, and PRN (as needed) doses of naproxen sodium. This meta-analysis confirmed the favorable safety profile of naproxen sodium at OTC doses and established that the overall occurrence of adverse events with naproxen sodium was comparable and in some cases significantly lower than placebo. These results indicate that treatment with naproxen sodium may be highly beneficial from a clinical and economical perspective and safe when adhering to labeled directions.

Publication Types:

Meta-Analysis

2: Mayo Clin Proc 2000 Sep;75(9):967-70

Naproxen-associated linear IgA bullous dermatosis: case report and review.

Bouldin MB, Clowers-Webb HE, Davis JL, McEvoy MT, Davis MD.

Department of Dermatology, Mayo Clinic, Rochester, Minn 55905, USA.

Linear IgA bullous dermatosis (LABD) is an acquired autoimmune subepidermal blistering disorder in which linear deposits of IgA are found along the basement membrane. Idiopathic, systemic disorder-related, and drug-induced forms of LABD have been described. Drug-induced LABD occurs in association with drug administration and resolves when the offending agent is discontinued. Other forms of LABD assume a more chronic course. The nonsteroidal anti-inflammatory drugs piroxicam and diclofenac have been previously reported to induce LABD. To our knowledge, this article describes the first documented case of LABD associated with naproxen administration, which resolved after discontinuation of the drug.

Publication Types:

Review

Review of Reported Cases

3: Clin Rheumatol 2000;19(3):242-4

Naproxen-induced leukocytoclastic vasculitis.

Schapira D, Balbir-Gurman A, Nahir AM.

Department of Rheumatology, Rambam Medical Center and School of Medicine, Technion, Israel Institute of Technology, Haifa.

Cutaneous reactions to non-steroidal anti-inflammatory drugs (NSAIDs) are rare in spite of their wide use. Only a few cases of hypersensitivity angiitis related to naproxen have been described. We report the case of a 62-year-old woman in whom leukocytoclastic skin vasculitis, peripheral neuropathy and nephritis developed after a short naproxen treatment, and gradually regressed after discontinuation of the drug and under glucocorticoid therapy. In the light of the relevant literature, the clinical and laboratory features of this reversible condition are described.

Publication Types:

Review

4: Pharmacotherapy 1999 Jul;19(7):854-9

Low-dose diclofenac, naproxen, and ibuprofen cohort study.

Perez-Gutthann S, Garcia-Rodriguez LA, Duque-Oliart A, Varas-Lorenzo C.

Global Epidemiology, Clinical Development, Novartis Pharmaceuticals, S.A., Barcelona, Spain.

The risk of a newly diagnosed episode of upper gastrointestinal bleeding, acute liver and renal failure, agranulocytosis, aplastic anemia, severe skin disorders, and anaphylaxis was examined within 30 days after the first prescription for a low dose of diclofenac, naproxen, or ibuprofen in a cohort in the United Kingdom. We identified 22,146 persons using diclofenac (< or = 75 mg), 46,919 using naproxen (< or = 750 mg), and 54,830 using ibuprofen (< or = 1200 mg). Age, gender, and comorbidity were similar in the three cohorts

Overall 64 potential cases were identified, and 20 were confirmed by medical record review. Incidence rates (95% CI) of upper gastrointestinal bleeding/10,000 people using diclofenac, naproxen, and ibuprofen were 1.8 (0.5-4.6), 2.3 (1.2-4.2), and 0.4 (0.04-1.3), respectively. There were three cases of hepatic injury, one with naproxen and two with ibuprofen. Although low, the incidence of gastrointestinal toxicity remains the main serious adverse event for all study drugs.

5: Rheumatology (Oxford) 1999 May;38 Suppl 1:24-32

Gastrointestinal toxicity of non-steroidal anti-inflammatory drugs: the effect of nimesulide compared with naproxen on the human gastrointestinal tract.

Bjarnason I, Thjodleifsson B.

Department of Medicine, Guy's, King's and St Thomas' School of Medicine, London, UK.

This overview includes theories and evaluation of non-steroidal anti-inflammatory drug (NSAID)-induced gastrointestinal toxicity. Factors in damage include microvascular aspects, neutrophil recruitment, mucosal prostaglandins, gastrointestinal secretions and bacteria. We have proposed an extensive simplified framework that includes an important local initiating effect which may involve NSAID accumulation, interaction with surface phospholipids, events that alter cellular ATP, and local/systemic effects of cyclooxygenase (COX) inhibition. COX-2-selective drugs are desirable not only because they spare COX-1 and so avoid gastrointestinal toxicity, but also because COX-2-selective agents are only weakly acidic and therefore avoid substantial accumulation in the gastric mucosa. Short-term endoscopy studies of NSAIDs are important initially to evaluate human gastroduodenal tolerability. They show that injury increases with the amount of NSAIDs even though the lowest therapeutic doses inhibit gastric COX almost completely, and that the more-acidic NSAIDs tend to cause greater gastric damage. Long-term endoscopy studies involve NSAID ingestion for at least 3 months. A main question is the extent to which the ulcers seen cause symptoms, substantial bleeding and/or perforation. Measurement of serious outcomes is thought by many to be the best assessment of gastrointestinal safety, but studies find marked variations even with the same drug. Damage to the small intestine by NSAIDs is even more frequent than to the upper gastrointestinal tract, but is difficult to evaluate. Conventional acidic NSAIDs increase the permeability of human small intestine, probably by a non-prostaglandin mechanism, but nimesulide does not do so, possibly because of its very weak acidity.

Publication Types:

Review

6: Clin Pharmacokinet 1997 Apr;32(4):268-93

Clinical pharmacokinetics of naproxen.

Davies NM, Anderson KE.

Faculty of Medicine, Department of Pharmacology and Therapeutics, University of Calgary, Alberta, Canada. ndavies@acs.ucalgary.ca

Naproxen is a stereochemically pure nonsteroidal anti-inflammatory drug of the 2-arylpropionic acid class. The absorption of naproxen is rapid and complete when given orally. Naproxen binds extensively, in a concentration-dependent manner, to plasma albumin. The area under the plasma concentration-time curve (AUC) of naproxen is linearly proportional to the dose for oral doses up to a total dose of 500 mg. At doses greater than 500 mg there is an increase in the unbound fraction of drug, leading to an increased renal clearance of total naproxen while unbound renal clearance remains unchanged. Substantial concentrations of the drug are attained in synovial fluid, which is a proposed site of action for nonsteroidal anti-inflammatory drugs. Relationships between the total and unbound plasma concentration, unbound synovial fluid concentration and therapeutic effect have been established. Naproxen is eliminated following biotransformation to glucuroconjugated and sulphate metabolites which are excreted in urine, with only a small amount of the drug being eliminated unchanged. The excretion of the 6-O-desmethylnaproxen metabolite conjugate may be tied to renal function, as accumulation occurs in end-stage renal disease but does not appear to be influenced by age. Hepatic disease and rheumatoid arthritis can also significantly alter the disposition kinetics of naproxen. Although naproxen is excreted into breast milk the amount of drug transferred comprises only a small fraction of the maternal exposure. Significant drug interactions have been demonstrated for probenecid, lithium and methotrexate.

Publication Types:

Review

7: Allergol Immunopathol (Madr) 1996 Mar-Apr;24(2):89-92

Cutaneous reaction to naproxen.

Gonzalo Garijo MA, Bobadilla Gonzalez P.

Allergology Department, Infanta Cristina University Hospital, Badajoz, Spain.

A 28-year-old woman with a previous atopic history had been complaining of itching and burning erythematous plaques or blister eruptions on her face and neck for the last 2 years. These lesions became red-brown and then disappeared in 1-2 weeks. However, the site of two of them had remained heavily pigmented after resolution. Sometimes, vesicular lesions affected the oral mucosa causing a burning sensation. She had noticed that these eruptions reappeared in the same location and related to menstruation (when she used to take naproxen sodium because of dysmenorrhea). Furthermore, pigmented sites became red-brown, elevated and itchy. These findings suggested a fixed drug eruption (FDE) due to naproxen, a sporadic clinical event previously reported only once. Patch tests were performed on the back (normal skin) with a series of NSAIDs, and with naproxen both on the back and on previous FDE sites. The test were negative on the back, and on previous FDE sites the skin got dark. The value of this result as a diagnostic tool was unclear so we performed an oral challenge test with naproxen which proved the diagnosis definitely.

Publication Types:

Review

8: J Can Dent Assoc 1992 May;58(5):401-5

Naproxen: pharmacology and dental therapeutics.

Roda RS.

Faculty of Dentistry, Dalhousie University, Dallas, Texas.

Naproxen and naproxen sodium are very commonly used and effective non-steroidal anti-inflammatory analgesics. In this paper, they are described and compared, and their pharmacokinetics and indications are discussed. Adverse reactions to these drugs and the mechanism of action of these effects on the gastrointestinal tract, central nervous system, kidneys, liver, and blood are described. A discussion of the effects of the drugs on the elderly and during pregnancy and lactation is included. Also, the allergenicity, miscellaneous rare complications and acute toxicity of the naproxen anion are described, followed by a description of the more common drug interactions. The results of several recent studies that may call into question the current recommendations on using these pharmaceuticals are cited. Until this controversy can be resolved, the practitioner should rely on the principle of "first do no harm" in choosing a course of drug treatment.

Publication Types:

Review

9: Eur J Rheumatol Inflamm 1992;12(2):9-20

NSAID-associated gastrointestinal damage: methodological considerations and a review of the experience with enteric coated naproxen.

Aabakken L.

Ulleval Hospital, Medical Clinic, Department of gastroenterology, Oslo, Norway.

Various methods are available for investigating gastrointestinal adverse effects of NSAIDs. Upper endoscopy is regarded a gold standard for controlled studies, but the grading and categorization of the visual impression of mucosal changes is complicated. Faecal blood loss represents another aspect of the toxicity, but quantitative measurements require the cumbersome procedure of 51Cr-labelling of red blood cells. For monitoring distal gut effects, permeability tests can be applied, and combination of tracer substances may further enhance the method. Measurements of electrical potential differences over the gastric mucosa are also available to monitor functional aspects of the gastric mucosal integrity. Controlled endoscopic trials have indicated an advantage of enteric coated naproxen tablets over plain tablets. Distal transfer of the toxicity by small bowel release of the active substance, has not been confirmed by permeability tests.

Publication Types:

Review