farmacocinética, indicaciones y efectos colaterales
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.
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.
2: Mayo Clin
Proc 2000 Sep;75(9):967-70
linear IgA bullous dermatosis: case report and review.
Clowers-Webb HE, Davis JL, McEvoy MT, Davis MD.
Dermatology, Mayo Clinic, Rochester, Minn 55905, USA.
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
Balbir-Gurman A, Nahir AM.
Rheumatology, Rambam Medical Center and School of Medicine, Technion,
Israel Institute of Technology, Haifa.
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
Pharmacotherapy 1999 Jul;19(7):854-9
diclofenac, naproxen, and ibuprofen cohort study.
S, Garcia-Rodriguez LA, Duque-Oliart A, Varas-Lorenzo C.
Epidemiology, Clinical Development, Novartis Pharmaceuticals, S.A., Barcelona,
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
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.
(Oxford) 1999 May;38 Suppl 1:24-32
toxicity of non-steroidal anti-inflammatory drugs: the effect of
nimesulide compared with naproxen on the human gastrointestinal tract.
Medicine, Guy's, King's and St Thomas' School of Medicine, London, UK.
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.
Pharmacokinet 1997 Apr;32(4):268-93
pharmacokinetics of naproxen.
Medicine, Department of Pharmacology and Therapeutics, University of Calgary,
Alberta, Canada. firstname.lastname@example.org
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.
Immunopathol (Madr) 1996 Mar-Apr;24(2):89-92
reaction to naproxen.
MA, Bobadilla Gonzalez P.
Department, Infanta Cristina University Hospital, Badajoz, Spain.
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.
8: J Can Dent
Assoc 1992 May;58(5):401-5
pharmacology and dental therapeutics.
Dentistry, Dalhousie University, Dallas, Texas.
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.
9: Eur J
Rheumatol Inflamm 1992;12(2):9-20
gastrointestinal damage: methodological considerations and a review
of the experience with enteric coated naproxen.
Hospital, Medical Clinic, Department of gastroenterology, Oslo, Norway.
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.