Bleeding naproxen

Although extraordinary in its powers, aspirin is also more dangerous than commonly believed. Only about 15 g can be fatal to a small child, and aspirin can cause stomach bleeding and allergic reactions in long-term users. Even more serious is a condition called Reye s syndrome, a potentially fatal reaction to aspirin sometimes seen in children recovering from the flu. As a result of these problems, numerous other NSAIDs have been developed in the last several decades, most notably ibuprofen and naproxen. 

Use with caution in patients with renal failure (dehydration) and bleeding Ibuprofen children 10 mg/kg every 6-8 hours adult 200-400 mg/dose Naproxen 5 mg/kg every 12 hours adult 250-500 mg/dose... 

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. 

COX-1 is found in healthy individuals and is important in maintaining a balanced physiological role in kidneys and stomach. COX-2, on the other hand, is induced in the case of inflammation where it mediates the inflammation process. Aspirin, ibuprofen, and naproxen inhibit both COX-1 and COX-2 indiscriminately. While this reduces the production of PGE2 through the inhibition of COX-2, it upsets the hemostasis function of COX-1, which has a protective function for the mucosal lining, and leads to bleeding and ulcer formation. 

Other- Gastritis (etodolac) pyrosis (meclofenamate) heartburn (naproxen, meclofenamate, ibuprofen, mefenamic acid, piroxicam) Gl distress (tolmetin) epigastric pain (ibuprofen) indigestion (ibuprofen) Gl tract fullness (ibuprofen) Gl pain (sulindac) gross bleeding (mefenamic acid). 

Miscellaneous Edema (flurbiprofen, naproxen, meloxicam) thirst pyrexia (fever and chills) sweating breast changes gynecomastia muscle cramps facial edema menstrual disorders impotence vaginal bleeding influenza-like disease/symptoms (meloxicam). 

Naproxen (Naprosyn) also has pharmacological properties and clinical uses similar to those of ibuprofen. It exhibits approximately equal selectivity for COX-1 and COX-2 and is better tolerated than certain NSAIDs, such as indomethacin. Adverse reactions related to the GI tract occur in about 14% of all patients, and severe GI bleeding has been reported. CNS complaints (headache, dizziness, drowsiness), dermatological effects (pruritus, skin eruptions, echinoses), tinnitus, edema, and dyspnea also occur. 

Aspirin (now a generic name) is one of a number of nonsteroidal antiinflammatory drugs (NSAIDs) others include ibuprofen and naproxen (see Fig. 21-15), all now sold over the counter. Unfortunately, aspirin reduces but does not eliminate the side effects of salicylates. In some patients, aspirin itself can produce stomach bleeding, kidney failure, and, in extreme cases, death. New NSAIDs with the beneficial effects of aspirin but without its side effects would be medically valuable. 

Cyclooxygenase (COX) forms prostanoids that are active throughout the body. Beyond pain and inflammation, prostanoids also play a role in maintaining the mucosal lining of the stomach. Long-term use of NSAIDs like aspirin, ibuprofen, and naproxen can lead to increased incidence of ulcers and stomach bleeding in patients. 

In the VIGOR study, 8076 patients with rheumatoid arthritis were randomly assigned to receive rofecoxib 50 mg/day or naproxen 500 mg bd. The primary endpoint was a confirmed clinical upper gastrointestinal event (gastroduodenal perforation or obstruction, upper gastrointestinal bleeding, and symptomatic gastroduodenal ulcer). 

Overall, confirmed upper gastrointestinal events occurred in 177 patients, 56 with rofecoxib n — 4047), and 121 in those taking naproxen n — 4029). In 53 of these patients (16 taking rofecoxib and 37 taking naproxen) the event was complicated. That means that during a median follow-up of 9.0 months, there were 2.1 confirmed gastrointestinal events per 100 patient-years with rofecoxib compared with 4.5 per 100 patient-years with naproxen (RR = 0.5 95% Cl = 0.2, 0.8). The respective rates of complicated ulcers (perforation, obstruction, and bleeding) were 0.6 per 100 patient-years and 1.4 per 100 patient-years (RR = 0.4 95% Cl = 0.2, 0.8). 

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). 

There were no differences in the incidence of middle and distal duodenum lesions (14). Esophageal ulceration with bleeding was reported in an elderly woman with esophageal dysmotility (SEDA-17, 112). Esophageal symptoms and esophageal ulcers were reported with naproxen sodium tablets (as opposed to capsules) for over-the-counter use (SEDA-22, 111). Naproxen did not cause reflux and had no significant effect on motility in healthy subjects (15). 

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

Strom BL, Schinnar R, Bilker WB, Feldman H, Farrar JT, Carson JL. Gastrointestinal tract bleeding associated with naproxen sodium vs ibuprofen. Arch Intern Med 1997 157(22) 2626-31. 

This study has therefore shown that in patients infected with H. pylori who take low-dose aspirin, eradication of H. pylori is as effective as prophylactic therapy with omeprazole in preventing recurrent upper gastrointestinal bleeding. Therefore, patients taking aspirin for cardiovascular prophylaxis could be tested for H. pylori infection and treated for it if infection is confirmed. In contrast, omeprazole is superior to eradication of H. pylori for the secondary prevention of upper gastrointestinal bleeding in H. py/on-infected users of naproxen and presumably other non-aspirin NSAIDs. 

E Naproxen would be the reasonable choice because of the relatively infrequent (twice to three times daily) dosing regimen and more tolerable side effect profile compared with aspirin and indomethacin. Celecoxib and rofecoxib would be alternatives if the patient could not tolerate naproxen. These agents should be reserved for patients with known Gl bleeding disorders or intolerance to the other nonspecific NSAIDs. COX-2 inhibitors are still second-line therapy due to high cost and not well studied for the treatment of OA. 

Oral anticoagulants + naproxen Increased anticoagulant effect and risk of Gl bleeding Naproxen has ulcerogenic potential. Displacement from protein Best to avoid concurrent administration. Monitor patient... 

Chan PKI, Chung SCS, Suen BY, et al. Preventing recurrence of upper gastrointestinal bleeding in patients with Helicobacter pylori infection who are taking low-dose aspirin or naproxen. N Engl J Med 2001 344 967-973. 

---