Naproxen - FDA prescribing information, side effects and uses

Nonsteroidal anti-inflammatory drug

renal adverse effects of nonsteroidal anti-inflammatory drugs

Caution is advised when high doses are required and some adjustment of dosage may be required in these patients. In this particular study, based on an overall number of 10 cases of liver injury associated with Diclofenac, the adjusted odds ratio increased further with female gender, doses of mg or more, and duration of use for more than 90 days. Naproxen is a potent inhibitor of prostaglandin synthesis in vitro. NSAIDs are used to treat pain and redness, swelling, and heat inflammation from medical conditions such as different types of arthritis, menstrual cramps and other types of short-term pain. No information is available from controlled clinical studies regarding the use of Diclofenac in patients with advanced renal disease. Diclofenac sodium Dosage Form: At these elevated levels, angiotensin II also constricts the afferent arteriole into the glomerulus in addition to the efferent arteriole it normally constricts.


NSAIDs have been studied in various assays to understand how they affect each of these enzymes. While these techniques may be effective, they are expensive for maintenance therapy. Gastrointestinal bleeding has occurred. The term nonsteroidal distinguishes these drugs from steroids , which while having a similar eicosanoid -depressing, anti-inflammatory action, have a broad range of other effects. When these drugs are administered concomitantly, patients should be adequately hydrated. Increased risk of a heart attack or stroke that can lead to death.

Prostaglandins and nonsteroidal anti-inflammatory drugs. American Journal of Medicine 80 Suppl. Nonsteroidal antiinflammatory drugs and renal function. Annual Review of Medicine Indomethacin as an analgesic after hysterectomy.

Acta Anaesthesiologica Scandinavica The morphine sparing effects of ketorolac tromethamine. A study of a new, parenteral non-steroidal anti-inflammatory agent after abdominal surgery. The morphine sparing effect of diclofenac sodium following upper abdominal surgery. Kehlet H, Dahl JB. Are perioperative prostaglandin synthetase inhibitors ulcerogenic in the short term?

Lindgren U, Djupso H. Diclofenac for pain after hip surgery. Postoperative nefopam and diclofenac. Evaluation of their morphine sparing effect after upper abdominal surgery. Adverse effects of non-steroidal drugs on renal function.

Annals of Internal Medicine Comparison of the car-diorespiratory effects of ketorolac and alfentanil during pro-pofol anaesthesia.

The effect of prostacyclin on asthma precipitated by aspirin. Allergy and Immunology Non-steroidal anti-inflammatory drugs and the kidney. The effects of ibuprofen and indomethacin on renal function in the presence and absence of frusemide in healthy volunteers on a restricted sodium diet.

British Journal of Clinical Pharmacology The molecular weight is The inactive ingredients in Diclofenac sodium delayed-release tablets include: Diclofenac is a potent inhibitor of prostaglandin synthesis in vitro. Diclofenac concentrations reached during therapy have produced in vivo effects. Prostaglandins sensitize afferent nerves and potentiate the action of bradykinin in inducing pain in animal models.

Prostaglandins are mediators of inflammation. Because Diclofenac is an inhibitor of prostaglandin synthesis, its mode of action may be due to a decrease of prostaglandins in peripheral tissues. Food has no significant effect on the extent of Diclofenac absorption. However, there is usually a delay in the onset of absorption of 1 to 4. Serum protein binding is constant over the concentration range 0.

Diclofenac diffuses into and out of the synovial fluid. Diffusion into the joint occurs when plasma levels are higher than those in the synovial fluid, after which the process reverses and synovial fluid levels are higher than plasma levels.

It is not known whether diffusion into the joint plays a role in the effectiveness of Diclofenac. Five Diclofenac metabolites have been identified in human plasma and urine. The metabolites include 4'-hydroxy-, 5-hydroxy-, 3'-hydroxy-, 4',5-dihydroxy- and 3'-hydroxy-4'-methoxy-Diclofenac.

The major Diclofenac metabolite, 4'-hydroxy-Diclofenac, has very weak pharmacologic activity. Both Diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy- and 3'-hydroxy-Diclofenac. Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion of the glucuronide and the sulfate conjugates of the metabolites.

Little or no free unchanged Diclofenac is excreted in the urine. Because renal elimination is not a significant pathway of elimination for unchanged Diclofenac, dosing adjustment in patients with mild to moderate renal dysfunction is not necessary.

The terminal half-life of unchanged Diclofenac is approximately 2 hours. The pharmacokinetics of Diclofenac has not been investigated in pediatric patients.

Pharmacokinetic differences due to race have not been identified. Diclofenac pharmacokinetics has been investigated in subjects with renal insufficiency. No differences in the pharmacokinetics of Diclofenac have been detected in studies of patients with renal impairment. The clinical significance of this interaction is not known.

Carefully consider the potential benefits and risks of Diclofenac sodium delayed-release tablets and other treatment options before deciding to use Diclofenac. Diclofenac sodium delayed-release tablets are contraindicated in the following patients:. Clinical trials of several COX-2 selective and nonselective NSAIDs of up to three years duration have shown an increased risk of serious cardiovascular CV thrombotic events, including myocardial infarction MI , and stroke, which can be fatal.

However, patients with known CV disease or risk factors had a higher absolute incidence of excess serious CV thrombotic events, due to their increased baseline rate. Some observational studies found that this increased risk of serious CV thrombotic events began as early as the first weeks of treatment. The increase in CV thrombotic risk has been observed most consistently at higher doses. To minimize the potential risk for an adverse CV event in NSAID-treated patients, use the lowest effective dose for the shortest duration possible.

Physicians and patients should remain alert for the development of such events, throughout the entire treatment course, even in the absence of previous CV symptoms. Patients should be informed about the symptoms of serious CV events and the steps to take if they occur. There is no consistent evidence that concurrent use of aspirin mitigates the increased risk of serious CV thrombotic events associated with NSAID use.

Observational studies conducted in the Danish National Registry have demonstrated that patients treated with NSAIDs in the post-MI period were at increased risk of reinfection, CV-related death, and all-cause mortality beginning in the first week of treatment.

Although the absolute rate of death declined somewhat after the first year post-MI, the increased relative risk of death in NSAID users persisted over at least the next four years of follow-up. Avoid the use of Diclofenac sodium delayed-release tablets in patients with a recent MI unless the benefits are expected to outweigh the risk of recurrent CV thrombotic events. If Diclofenac sodium delayed-release tablets are used in patients with a recent MI, monitor patients for signs of cardiac ischemia.

NSAIDs, including Diclofenac, cause serious gastrointestinal GI adverse events including inflammation, bleeding, ulceration, and perforation of the esophagus, stomach, small intestine, or large intestine, which can be fatal. These serious adverse events can occur at any time, with or without warning symptoms, in patients treated with NSAIDs.

However, even short-term therapy is not without risk. Most postmarketing reports of fatal GI events occurred in elderly or debilitated patients. In clinical trials of Diclofenac- containing products, meaningful elevations i.

In a large, open-label, controlled trial of 3, patients treated with oral Diclofenac sodium for months, patients were monitored first at 8 weeks and 1, patients were monitored again at 24 weeks. Elevations in transaminases were seen more frequently in patients with osteoarthritis than in those with rheumatoid arthritis.

Almost all meaningful elevations in transaminases were detected before patients became symptomatic. Abnormal tests occurred during the first 2 months of therapy with Diclofenac in 42 of the 51 patients in all trials who developed marked transaminase elevations. In postmarketing reports, cases of drug-induced hepatotoxicity have been reported in the first month, and in some cases, the first 2 months of therapy, but can occur at any time during treatment with Diclofenac.

Postmarketing surveillance has reported cases of severe hepatic reactions, including liver necrosis, jaundice, fulminant hepatitis with and without jaundice, and liver failure.

Some of these reported cases resulted in fatalities or liver transplantation. In a European retrospective population-based, case-controlled study, 10 cases of Diclofenac associated drug-induced liver injury with current use compared with non-use of Diclofenac were associated with a statistically significant 4-fold adjusted odds ratio of liver injury.

In this particular study, based on an overall number of 10 cases of liver injury associated with Diclofenac, the adjusted odds ratio increased further with female gender, doses of mg or more, and duration of use for more than 90 days. Physicians should measure transaminases at baseline and periodically in patients receiving long-term therapy with Diclofenac, because severe hepatotoxicity may develop without a prodrome of distinguishing symptoms.

The optimum times for making the first and subsequent transaminase measurements are not known. Based on clinical trial data and postmarketing experiences, transaminases should be monitored within 4 to 8 weeks after initiating treatment with Diclofenac. However, severe hepatic reactions can occur at any time during treatment with Diclofenac. Inform patients of the warning signs and symptoms of hepatotoxicity e.

If clinical signs and symptoms consistent with liver disease develop, or if systemic manifestations occur e. To minimize the potential risk for an adverse liver related event in patients treated with Diclofenac, use the lowest effective dose for the shortest duration possible.

Exercise caution when prescribing Diclofenac with concomitant drugs that are known to be potentially hepatotoxic e. Inform patients about the signs and symptoms of serious skin reactions and to discontinue use of Naproxen Suspension at the first appearance of skin rash or any other sign of hypersensitivity. Naproxen may cause premature closure of the fetal ductus arteriosus. This may be due to occult or gross blood loss, fluid retention, or an incompletely described effect on erythropoiesis.

If a patient treated with Naproxen Suspension has any signs or symptoms of anemia, monitor hemoglobin or hematocrit. Co-morbid conditions such as coagulation disorders, or concomitant use of warfarin, other anticoagulants, antiplatelet agents e. Naproxen Suspension should not be used concomitantly with other Naproxen-containing products since they all circulate in the plasma as the Naproxen anion.

Naproxen Suspension cannot be expected to substitute for corticosteroids or to treat corticosteroid insufficiency. Abrupt discontinuation of corticosteroids may lead to disease exacerbation. Patients on prolonged corticosteroid therapy should have their therapy tapered slowly if a decision is made to discontinue corticosteroids and the patient should be observed closely for any evidence of adverse effects, including adrenal insufficiency and exacerbation of symptoms of arthritis.

Patients with initial hemoglobin values of 10 g or less who are to receive long-term therapy should have hemoglobin values determined periodically. Because of adverse eye findings in animal studies with drugs of this class, it is recommended that ophthalmic studies be carried out if any change or disturbance in vision occurs.

Advise the patient to read the FDA-approved patient labeling Medication Guide that accompanies each prescription dispensed. Inform patients, families, or their caregivers of the following information before initiating therapy with Naproxen Suspension and periodically during the course of ongoing therapy. Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, shortness of breath, weakness, or slurring of speech, and to report any of these symptoms to their healthcare provider immediately see WARNINGS; Cardiovascular Thrombotic Events.

Advise patients to report symptoms of ulcerations and bleeding, including epigastric pain, dyspepsia, melena, and hematemesis to their health care provider. Advise patients to be alert for the symptoms of congestive heart failure including shortness of breath, unexplained weight gain, or edema and to contact their healthcare provider if such symptoms occur see WARNINGS; Heart Failure and Edema.

Inform patients of the signs of an anaphylactic reaction e. Alert patients that NSAIDs may be present in "over the counter" medications for treatment of colds, fever, or insomnia.

Caution should be exercised by patients whose activities require alertness if they experience drowsiness, dizziness, vertigo or depression during therapy with Naproxen. The pharmacological activity of Naproxen in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections.

See Table 1 for clinically significant drug interactions with Naproxen. No evidence of tumorigenicity was found. Studies to evaluate the mutagenic potential of Naproxen Suspension have not been completed. Studies to evaluate the impact of Naproxen on male or female fertility have not been completed. Use of NSAIDs, including Naproxen Suspension, during the third trimester of pregnancy increases the risk of premature closure of the fetal ductus arteriosus.

Data from observational studies regarding potential embryofetal risks of NSAID use in women in the first or second trimesters of pregnancy are inconclusive. In the general U. In animal reproduction studies in rats, rabbit, and mice no evidence of teratogenicity or fetal harm when Naproxen was administered during the period of organogenesis at doses 0. Based on animal data, prostaglandins have been shown to have an important role in endometrial vascular permeability, blastocyst implantation, and decidualization.

In animal studies, administration of prostaglandin synthesis inhibitors such as Naproxen, resulted in increased pre- and post-implantation loss. There is some evidence to suggest that when inhibitors of prostaglandin synthesis are used to delay preterm labor there is an increased risk of neonatal complications such as necrotizing enterocolitis, patent ductus arteriosus and intracranial hemorrhage.

Naproxen treatment given in late pregnancy to delay parturition has been associated with persistent pulmonary hypertension, renal dysfunction and abnormal prostaglandin E levels in preterm infants. Because of the known effects of nonsteroidal antiinflammatory drugs on the fetal cardiovascular system closure of ductus arteriosus , use during pregnancy particularly starting at 30 weeks of gestation, or third trimester should be avoided.

In animal studies, administration of prostaglandin synthesis inhibitors such as Naproxen, resulted in increased preand post-implantation loss. There are no studies on the effects of Naproxen Suspension during labor or delivery.

In animal studies, NSAIDS, including Naproxen, inhibit prostaglandin synthesis, cause delayed parturition, and increase the incidence of stillbirth. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Naproxen Suspension and any potential adverse effects on the breastfed infant from the Naproxen Suspension or from the underlying maternal condition.

Based on the mechanism of action, the use of prostaglandin-mediated NSAIDs, including Naproxen Suspension, may delay or prevent rupture of ovarian follicles, which has been associated with reversible infertility in some women. Published animal studies have shown that administration of prostaglandin synthesis inhibitors has the potential to disrupt prostaglandin- mediated follicular rupture required for ovulation.

Consider withdrawal of NSAIDs, including Naproxen Suspension, in women who have difficulties conceiving or who are undergoing investigation of infertility.. Safety and effectiveness in pediatric patients below the age of 2 years have not been established. There are no adequate effectiveness or dose-response data for other pediatric conditions, but the experience in juvenile arthritis and other use experience have established that single doses of 2.

Studies indicate that although total plasma concentration of Naproxen is unchanged, the unbound plasma fraction of Naproxen is increased in the elderly. Caution is advised when high doses are required and some adjustment of dosage may be required in elderly patients.

As with other drugs used in the elderly, it is prudent to use the lowest effective dose. Experience indicates that geriatric patients may be particularly sensitive to certain adverse effects of nonsteroidal anti-inflammatory drugs.

Elderly or debilitated patients seem to tolerate peptic ulceration or bleeding less well when these events do occur. Naproxen is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and it may be useful to monitor renal function.

Geriatric patients may be at a greater risk for the development of a form of renal toxicity precipitated by reduced prostaglandin formation during administration of nonsteroidal anti-inflammatory drugs see WARNINGS; Renal Toxicity and Hyperkalemia. The following adverse reactions are discussed in greater detail in other sections of the labeling:. Adverse reactions reported in controlled clinical trials in patients treated for rheumatoid arthritis or osteoarthritis are listed below.

In general, reactions in patients treated chronically were reported 2 to 10 times more frequently than they were in short-term studies in the patients treated for mild to moderate pain or for dysmenorrhea. The most frequent complaints reported related to the gastrointestinal tract.

In controlled clinical trials with about 80 pediatric patients and in well-monitored, open-label studies with about pediatric patients with juvenile arthritis treated with Naproxen, the incidence of rash and prolonged bleeding times were increased, the incidence of gastrointestinal and central nervous system reactions were about the same, and the incidence of other reactions were lower in pediatric patients than in adults.

Gastrointestinal GI Experiences, including: Those adverse reactions observed through postmarketing reports are italicized. Body as a Whole: Esophagitis, stomatitis, hematemesis, pancreatitis, vomiting, colitis, exacerbation of inflammatory bowel disease ulcerative colitis, Crohn's disease. If skin fragility, blistering or other symptoms suggestive of pseudoporphyria occur, treatment should be discontinued and the patient monitored. Symptoms following acute NSAID overdosages have been typically limited to lethargy, drowsiness, epigastric pain, nausea and vomiting, which have been generally reversible with supportive care.

Gastrointestinal bleeding has occurred. Hypertension, acute renal failure, respiratory depression, and coma have occurred, but were rare. A few patients have experienced convulsions, but it is not clear whether or not these were drug-related.

There are no specific antidotes. Hemodialysis does not decrease the plasma concentration of Naproxen because of the high degree of its protein binding. Forced diuresis, alkalinization of urine or hemodialysis, or hemoperfusion may not be useful due to high protein binding. For additional information about overdosage treatment contact a poison control center After observing the response to initial therapy with Naproxen Suspension, the dose and frequency should be adjusted to suit an individual patient's needs.

Different dose strengths and formulations ie, tablets, suspension of the drug are not necessarily bioequivalent. This difference should be taken into consideration when changing formulation.

Although Naproxen Suspension and other formulations of Naproxen and Naproxen sodium all circulate in the plasma as Naproxen, they have pharmacokinetic differences that may affect onset of action. During long-term administration, the dose of Naproxen may be adjusted up or down depending on the clinical response of the patient. A lower daily dose may suffice for long-term administration. The morning and evening doses do not have to be equal in size and the administration of the drug more frequently than twice daily is not necessary.

The use of Naproxen Suspension is recommended for juvenile arthritis in children 2 years or older because it allows for more flexible dose titration based on the child's weight. The following table may be used as a guide for dosing of Naproxen Suspension.

The recommended starting dose of Naproxen Suspension is mg 20 mL , followed by mg 10 mL every 6 to 8 hours as required. Available as light orange colored, pineapple-orange flavored suspension in 1 pint mL light-resistant bottles NDC Nonsteroidal anti-inflammatory drugs meloxicam , ibuprofen , diclofenac , Voltaren , Aleve , Mobic. Back Pain tramadol , Cymbalta , aspirin , ibuprofen , duloxetine , More Ankylosing Spondylitis prednisone , Humira , aspirin , triamcinolone , diclofenac , Voltaren , More Bursitis prednisone , triamcinolone , Aleve , dexamethasone , betamethasone , indomethacin , More The easiest way to lookup drug information, identify pills, check interactions and set up your own personal medication records.

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Iamges: renal adverse effects of nonsteroidal anti-inflammatory drugs

renal adverse effects of nonsteroidal anti-inflammatory drugs

Drugs That Interfere with Hemostasis. This mechanism of action was elucidated by John Vane — , who received a Nobel Prize for his work see Mechanism of action of aspirin.

renal adverse effects of nonsteroidal anti-inflammatory drugs

By the German chemist Felix Hoffmann and the Bayer company prompted a new age of pharmacology by converting salicylic acid into acetylsalicylic acid—named aspirin by Heinrich Dreser. Non-steroidal anti-inflammatory drugs NSAIDs are used chronically to reduce pain and inflammation in patients with arthritic conditions, and also acutely as analgesics by many patients.

renal adverse effects of nonsteroidal anti-inflammatory drugs

NSAIDs may aggravate hypertension high blood pressure and thereby antagonize the effect of antihypertensives[70] such as ACE inhibitors. This is particularly important in kidney failure where the kidney is trying to maintain renal perfusion pressure by elevated angiotensin II levels. Other factors that increase the risk of GI bleeding in patients treated with NSAIDs include longer duration of NSAID therapy; concomitant use of oral corticosteroids, aspirin, anticoagulants, or selective serotonin reuptake inhibitors SSRIssmoking, use of alcohol, older age, and poor general renal adverse effects of nonsteroidal anti-inflammatory drugs rena. During concomitant use of Diclofenac with diuretics, observe patients for signs of worsening renal function, in addition to assuring diuretic efficacy including antihypertensive effects see WARNINGS; Renal Toxicity and Hyperkalemia. Prostaglandins are mediators of inflammation. Diclofenac is a potent inhibitor of prostaglandin synthesis in oxys steroids review.