urticaria
Naproxen Contraindications and Precautions
Naproxen is contraindicated in patients with salicylate hypersensitivity or NSAID hypersensitivity who have experienced asthma, urticaria, or other allergic reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactoid reactions to naproxen have been reported in such patients. Naproxen should not be used in patients with aspirin-sensitive asthma or the aspirin triad because of the approximate 5% cross-sensitivity that occurs between aspirin and NSAIDs. The triad typically occurs in patients with asthma who experience rhinitis with or without nasal polyps, or who experience severe, potentially fatal, acute bronchospasm after taking aspirin or other NSAIDs. The use of NSAIDs, including naproxen, may cause serious and potentially fatal skin reactions including exfoliative dermatitis, Stevens-Johnson syndrome, and toxic epidermal necrolysis. Patients should be instructed to discontinue the medication and contact their health care provider if erythema, rash, blisters, or related skin reactions develop.
Chronic use of naproxen can result in gastritis, ulceration with or without perforation, and/or GI bleeding, which can occur at any time, often without preceding symptoms. Therefore, naproxen is relatively contraindicated in patients with a history of or active GI disease including peptic ulcer disease, ulcerative colitis, or GI bleeding. Older patients seem to tolerate GI ulceration or bleeding less well than younger patients. Most fatal GI events occur in older or debilitated patients. Patients at increased risk for NSAID-induced GI bleeding include the elderly, those receiving concurrent myelosuppressive chemotherapy, corticosteroid therapy, or anticoagulant therapy, tobacco smoking patients, and patients with alcoholism. Patients should not self-medicate with naproxen if they consume 3 or more alcoholic beverages per day. It is recommended not to initiate therapy with maximum doses in these patients due to the likely increased frequency of adverse reactions. All patients receiving prolonged treatment should be routinely monitored for potential GI ulceration and bleeding (see Adverse Reactions).
Naproxen should be used with caution in patients with hepatic disease. Naproxen is highly bound to plasma proteins, especially albumin. Severe hepatic reactions have occurred during treatment with naproxen, and patients with hepatic impairment are at an increased risk for developing these complications. Elevations in liver function tests also can occur. Naproxen should be discontinued if elevated hepatic enzymes persist or worsen, or if signs or symptoms of hepatic disease, such as jaundice, develop (see Adverse Reactions).
An extensive review of the available literature was recently conducted by Advisory Committees for the Center for Drug Evaluation and Research (CDER) addressing the potential association between cardiovascular (CV) risk (e.g., thrombotic events, myocardial infarction, and stroke) and nonsteroidal anti-inflammatory drug (NSAID) usage. Subsequently, it was concluded that, pending additional information, NSAIDS as a group (excluding aspirin) carry an increased CV risk compared to placebo. Clinicians should be particularly cautious when prescribing NSAIDs on a chronic basis. A retrospective review by the CDER Advisory Committees of short-term efficacy trials of non-prescription strength naproxen indicated that an increase in CV events was not apparent during the studies. Therefore, a boxed warning in non-prescription product labeling (e.g., Aleve®, Midol® Extended Relief) is not required at this time. However, it is important to note that CV risk was not the focus of the studies and further information is needed to determine if a cause and effect relationship exists between non-prescription strength NSAID use and adverse cardiovascular outcomes. Meta-analyses have demonstrated that the effect of NSAIDs on blood pressure is the greatest in hypertensive individuals receiving antihypertensive medication. In addition, normotensive subjects receiving antihypertensive therapy had higher increases in blood pressure than subjects with uncontrolled hypertension or normotensive subjects receiving no hypertensive therapy. Chronic use of naproxen should be avoided if possible in patients with cardiac disease or at risk for cardiac disease to include uncontrolled or severe hypertension, cardiac arrhythmias (tachycardia), cerebrovascular disease (e.g., stroke, transient ischemic attack), or significant coronary artery disease (including acute myocardial infarction, angina, or history of myocardial infarction). Considerable caution should be used in patients with controlled or mild hypertension, heart failure, cardiomyopathy, ischemic heart disease, and peripheral vascular disease.
Due to the role of prostaglandins in renal function and hemodynamics, patients with renal disease or at risk for renal disease should be closely observed during therapy with naproxen due to an increased risk for reduced renal blood flow or volume. Naproxen and its metabolites are renally excreted. Accumulation of parent drug and metabolites can occur in patients with renal disease, renal impairment or renal failure, increasing the risk of potential toxicity. Dosage adjustment may be necessary (see Dosage, renal impairment). Conditions such as congestive heart failure, edema, or hypertension can be exacerbated by the fluid retention cause by suboptimal renal perfusion. Naproxen should be used cautiously in patients with any of these conditions or other diseases that predispose to fluid retention. Patients with renal impairment, renal failure, hepatic disease, diabetes mellitus, systemic lupus erythematosus (SLE), or congestive heart failure, rheumatoid arthritis, edema, extracellular volume depletion (i.e., hypovolemia or dehydration), sepsis; those taking diuretics or nephrotoxic drugs; and the elderly are at the highest risk for complications related to suboptimal renal perfusion. Also, the elderly have an increased free plasma fraction of naproxen relative to younger adult patients, which may be associated with a greater risk of adverse effects at a given dosage (see Pharmacokinetics).
Naproxen should be used cautiously in patients with preexisting hematological disease (e.g., coagulopathy or hemophilia) or thrombocytopenia due to the effect of the drug on platelet function and vascular response to bleeding. Naproxen should also be used with caution in patients undergoing surgery when a high degree of hemostasis is required. NSAIDs should be used with caution in patients with immunosuppression or neutropenia. NSAIDs may mask the signs of infection such as fever or pain in patients with bone marrow suppression.
Anemia may be exacerbated with the use of systemic NSAIDs, such as naproxen. This may be due to fluid retention, GI blood loss, or an incompletely described effect upon erythrogenesis. Patients who have initial hemoglobin values of 10 g/dl or less and who are to receive long-term NSAID therapy should have hemoglobin values determined periodically.
Intramuscular injections should be administered cautiously to patients receiving naproxen. The risk of bleeding, bruising, or hematomas from IM injections may be increased due to the platelet effects of naproxen therapy.
Use of naproxen may cause increased bleeding in patients with dental disease. Patients should inform their dentist they are taking naproxen prior to any dental work due to a potential increased risk of bleeding. Patients should be instructed on proper oral hygiene.
Naproxen should be used with caution in children. There is a greater incidence of naproxen-induced skin rash and increase in bleeding times in children. Safety and effectiveness in children less than 2 years of age has not been established.
Naproxen is classified as FDA pregnancy risk category B drug; no studies have linked naproxen use during pregnancy and congenital defects. However, there are no adequate and well-controlled studies of naproxen in pregnant women; use of naproxen should be avoided unless the potential therapeutic benefits justify its use during pregnancy. Naproxen is classified as a FDA pregnancy risk category D drug if used during the third trimester, due to the potential for prostaglandin synthetase inhibitors to cause in utero constriction of the fetal ductus arteriosus. Of 40 babies born with persistent pulmonary hypertension of the newborn (PPHN), 87.5% had the presence of an NSAID in their meconium versus 24.6% of 61 children born without PPHN; the presence of only 4 NSAIDs was examined. In addition to meconium aspiration, asphyxia, respiratory distress syndrome, and group B streptococcal pneumonia, ductus arteriosus constriction by an NSAID appears to be another predisposing factor for PPHN development, as a patent ductus arteriosus was absent in 18 of the 40 infants. Naproxen given to delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction, and abnormal prostaglandin E concentrations in preterm infants. Prostaglandin synthetase inhibitors also have the potential to prolong pregnancy and inhibit labor if taken during the third trimester. There may be an increased risk of neonatal complications, such as necrotizing enterocolitis, patent ductus arteriosus, and intracranial hemorrhage when prostaglandin synthetase inhibitors are used to delay preterm labor.
Naproxen is not recommended for breast-feeding mothers due to potential adverse effects to the nursing infant from NSAID-induced prostaglandin inhibition. Naproxen is excreted into breast milk in concentrations of 1% of maternal plasma concentrations.
Naproxen is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft surgery (CABG). An increased incidence of myocardial infarction and stroke was found through analysis of data regarding the use of a COX-2 selective NSAID for the treatment of pain in the first 10 - 14 days after CABG surgery. This warning is not currently applicable to non-prescription strength products (e.g., Aleve®, Midol® Extended Relief); however the precaution has been added voluntarily by some manufacturers.
[ Last revised: 2/24/2006 9:20:00 PM ]
References
. Frishman WH. Effects of nonsteroidal anti-inflammatory drug therapy on blood pressure and peripheral edema. Am J Cardiol 2002;89(suppl):18D - 25D.
. Alano MA, Ngougmna E, Ostrea EM, et al. Analysis of nonsteroidal antiinflammatory drugs in meconium and its relation to persistent pulmonary hypertension of the newborn. Pediatrics 2001;107:519 - 23.
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