Naproxen adverse effects

Most NSAIDs (e.g., ibuprofen, naproxen, and others) inhibit both COX-1 and COX-2 isoforms. That is, they are nonselective inhibitors of the COX enzyme system. Whereas inhibition of COX-2 is responsible for beneficial effects, inhibition of COX-1 is responsible for the most common and important adverse effects of NSAIDs. COX-2-selective inhibitors have been produced and marketed in attempts to preserve the beneficial effects of COX-2 inhibition while avoiding the deleterious effects associated with inhibition of the COX-1 enzyme. This approach has not been entirely successful, as discussed below. 

Recent advances with other anti-inflammatory drugs, ibuprofen and naproxen, which only work by physically blocking the channel to arachidonic acid, mean that the adverse effect of stomach bleeding can be avoided. 

Meloxicam is an enolcarboxamide related to piroxicam that preferentially inhibits COX-2 over COX-1, particularly at its lowest therapeutic dose of 7.5 mg/d. It is not as selective as celecoxib and may be considered "preferentially" selective rather than "highly" selective. The drug is popular in Europe and many other countries for the treatment of most rheumatic diseases and approved for treatment of osteoarthritis in the USA. It is associated with fewer clinical gastrointestinal symptoms and complications than piroxicam, diclofenac, and naproxen. Similarly, while meloxicam is known to inhibit synthesis of thromboxane A2, even at supratherapeutic doses its blockade of thromboxane A2 does not reach levels that result in decreased in vivo platelet function (see common adverse effects above). 

Its properties are very similar to those of other NSAIDs, though it may be less damaging to the stomach than some other NSAIDs when given at a dosage of 1000 mg/d. Unfortunately, higher dosages (eg, 1500-2000 mg/d) are often needed, and this is a very expensive NSAID. Like naproxen, nabumetone has been reported to cause pseudoporphyria and photosensitivity in some patients. Other adverse effects mirror those of other NSAIDs. 

Naproxen Anaprox, Naprosyn, others Similar to ibuprofen in terms of benefits and adverse effects... 

Gastrointestinal adverse effects are particularly frequent, and affect some 14-25% of patients the incidence of the most serious, peptic ulcer and bleeding were 0.16-0.34% and 0.16-0.17%, respectively (1). A prospective 12-week endoscopic study documented better gastrointestinal tolerability with diclofenac than naproxen (SEDA-20, 92). Upper gastrointestinal hemorrhage has been associated with transdermal application of diclofenac, with massive bleeding in two of four patients (SEDA-21, 104). 

Flurbiprofen causes more gastrointestinal adverse effects than naproxen or ibuprofen. In a series of controlled double-bhnd studies, adverse reactions occurred in 27-42% of patients and were most commonly gastrointestinal in origin (18-28%) (SEDA-12, 85). 

Pseudoporphyria is an infrequent adverse effect of some NSAIDs, including naproxen (SEDA-12, 87), nabu-metone (SEDA-16, 111), and oxaprozin (SEDA-21,106). 

Nabumetone is a naproxen derivative, whose efficacy is related to its active metabolite, 6-methoxy-2-naphthyla-cetic acid. Not unexpectedly, a study in 2000 patients, mostly treated for more than 6 months, ehcited an adverse events pattern similar to the other derivatives of this class of NSAIDs (SEDA-13, 81). Adverse effects were reported in 18% of patients and 10% stopped taking the drug because of adverse reactions. Diarrhea was the most common problem (13%) followed by abdominal pain (9.9%), dyspepsia (9.3%), nausea (7.8%), and flatulence (4.7%). Ten ulcers were detected. Nervous system reactions, skin rashes, edema, unspecified eye disorders, and liver function test abnormahties aU occur (1). 

The adverse effects of naproxen resemble those of ibuprofen. Any minor differences in frequency cannot be assessed with certainty. In 881 patients who had been followed for more than 3 years, only 8.9% dropped out because of adverse effects. In shorter studies, doses of up to 1.5 g/day produced no more adverse effects than lower or standard doses of other NSAIDs (1). 

Piproxen is a piperazine derivative of naproxen its adverse effects profile is similar to that of naproxen (4). 

Local adverse effects of naproxen suppositories include edema, erythema, and bleeding, which are usually mild. 

The suspension and modified-release tablets produce the usual pattern of adverse effects (SEDA-15,101), although an enteric-coated formulation of naproxen in patients... 

In a prospective, randomized trial of the effect of eradication of H. pylori before the start of NSAID therapy on the subsequent risk of ulcer occurrence, patients who required new NSAID treatment and who had H. pylori infection but no pre-existing ulcers on baseline endoscopy were recruited (100). Of these patients, 100 were randomly allocated to naproxen for 8 weeks, either alone or preceded by a 1-week course of H. pylori eradication. Endoscopy was repeated after 8 weeks or if naproxen was withdrawn early because of adverse effects. The primary end-point of the study was the cumulative rate of gastric and duodenal endoscopic ulcers. At 8 weeks H. pylori was eradicated in 40 patients (89%) who took eradication therapy and in none of those who had no pretreatment. Twelve (26%) of those who had no... 

Widespread use of naproxen, sulindac, diclofenac, and diflunisal probably explains why they were the most frequently rmphcated, rather than because they have a greater tendency to cause these adverse effects. NSAIDs differ in their ability to cause adverse skin reactions in terms of both frequency and severity pyrazolones, butazones, and oxicams are most often blamed, and among the arylalkanoic acid derivatives fenbufen and carprofen are most often incriminated. 

Even rectal and enteric-coated formulations can cause adverse reactions in the upper gastrointestinal tract. In one double-blind, crossover trial, plain naproxen caused fewer gastrointestinal adverse effects than enteric-coated phenylbutazone (Butacote) (24). 

In 32 207 patients taking part in a short (1-4 weeks) postmarketing study of tolmetin, adverse effects occurred in 12%, and led to withdrawal in 3.6% (1). Tolerability was similar to that of naproxen, indometacin (SEDA-7, 114), and ibuprofen (SED-9, 152) (2). In another retrospective study in patients treated for 1 year or more with tolmetin, 64% reported generally mild transitory adverse effects. In controlled studies, about 10% of patients withdrew owing to adverse effects (3). In another study of 25 000 prescription records (4), tolmetin caused adverse... 

In one of the cases reviewed by Sheikh and colleagues, a patient developed a generalized urticarial rash, nausea, and abdominal pain after ingestion of chaparral, but had been taking chaparral for 1 yr, had a history of allergies, and was also taking naproxen and ketorolac. Miscellaneous adverse effects associated with chaparral use include sudden unilateral loss of vision, tachycardia, electrolyte abnormalities with cardiac arrest, and syncopal episodes (Sheikh et al., 1997). 

In the recent 8000-patient celecoxib long-term arthritis safety study [123], significantly more patients receiving traditional NSAlDs (ibuprofen or diclofenac) experienced clinically significant elevations in serum creatinine and/or serum urea nitrogen levels when compared to celecoxib. In an equally large gastrointestinal safety trial with rofecoxib, the incidence of adverse effects related to renal function for rofecoxib was similar to naproxen (1.2% versus 0.9%, respectively) [124]. When rofecoxib and celecoxib were directly evaluated in elderly hypertensive OA patients who manifested "normal" serum creatinine at the time of study recruitment, the overall incidence of clinically... 

Typical gastrointestinal adverse effects with naproxen occur at approximately the same frequency as with indomethacin, but perhaps with less severity. CNS side effects range from drowsiness, headache, dizziness, and sweating, to fatigue, depression, and ototoxicity. Less common reactions include pruritus and a variety of dermatological problems. A few instances of jaundice, impairment of renal function, angioedema, thrombocytopenia and agranulocytosis have been reported. 

Typical Gl adverse effects with naproxen occur at approximately the same frequency as with indomethacin, but perhaps with less severity. CNS side effects range from drowsiness, headache,... 

Adverse effects of naproxen is similar to that of ibuprofen. The most frequent adverse effects occuring are gastrointestinal disturbances. Peptric ulceration and gastro-intestinal bleeding have been reported, other side effects include headache, dizziness, nervousness, skin rash, pruritus, tinnitus, oedema, depression, drowsiness, insomnia, and blurred vision and other occular reactions. Hypersensitivity reactions, abnormalities of liver function tests, impairment of renal function including interstitial nephritis or the nephrotic-syndrome, agranulocytosis, and thrombocytopenia have occasionally been observed (5). 

Naproxen is comparable to aspirin in controlling disease symptoms, but with lesser frequency and severity of nervous system and milder gastrointestinal adverse effects (2). 

Misoprostol increases the incidence of abdominal pain and diarrhoea when used with diclofenac or indometacin. Isolated cases of neurological adverse effects have been seen with naproxen or phenylbutazone given with misoprostol. However, no important pharmacokinetic interactions seem to occur between aspirin, diclofenac, ibuprofen or indometacin and misoprostol. NSAIDs are reported not to affect the abortive effects of intravaginal misoprostol. 

A higher incidence of abdominal pain, diarrhoea, nausea and dyspepsia occurred when diclofenac was combined with misoprostol. Concurrent use of indometacin and misoprostol also resulted in an increase in frequency and severity of abdominal symptoms, frequency of bowel movements and a decrease in faecal consistency. The most frequent adverse effect of misoprostol alone is diarrhoea, and this may limit the dose tolerated. When using misoprostol with NSAIDs, warn patients about the possibility of increased stomach pain and diarrhoea. Preparations combining diclofenac or naproxen with misoprostol are available. 

Huq M. Neurological adverse effects of naproxen and misoprostol combination. BrJ Gen Pract (1990) 40,432. 

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