Diclofenac sodium Dosage Form: Medically reviewed on July 1, Gastrointestinal Bleeding, Ulceration, And Perforation. Diclofenac sodium delayed-release tablets is a benzene-acetic acid derivative. The chemical name is 2-[ 2,6-dichlorophenyl amino] benzeneacetic acid, monosodium salt. 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, recent studies about diclofenac.
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 recent studies about diclofenac 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 recent studies about diclofenac and urine. Both Diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion.
Diclofenac is eliminated through metabolism and subsequent urinary and biliary excretion recent studies about diclofenac the glucuronide and the sulfate conjugates recent studies about diclofenac the recent studies about diclofenac. 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 recent studies about diclofenac 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, recent studies about diclofenac. 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, recent studies about diclofenac, including myocardial infarction MIand 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, recent studies about diclofenac. 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 recent studies about diclofenac. 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 recent studies about diclofenac 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 recent studies about diclofenac a recent MI unless the benefits recent studies about diclofenac expected to outweigh the risk of recurrent CV thrombotic events.
If Diclofenac sodium delayed-release tablets are used in patients with a recent studies about diclofenac 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, recent studies about diclofenac, 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.
NSAIDs, including Diclofenac, can lead to new onset of hypertension or worsening of preexisting hypertension, either of which may contribute to the increased incidence of CV events. Patients taking angiotensin converting enzyme ACE inhibitors, thiazides diuretics, or loop diuretics may have impaired response to these therapies when taking NSAIDs.
Use of Diclofenac may blunt the CV effects of several therapeutic agents used to treat these medical conditions [e. Avoid the use of Diclofenac in patients with severe heart failure unless the benefits are expected to outweigh the risk of worsening heart failure.
If Diclofenac is used in patients with severe heart failure, monitor patients for signs of worsening heart failure. Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, recent studies about diclofenac, administration of a NSAID may cause a dose-dependent reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation.
Patients at greatest risk of this reaction are those with impaired renal function, dehydration, hypovolemia, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors or ARBs, and the elderly.
No information is available from controlled clinical studies regarding the use of Diclofenac in patients with advanced renal disease, recent studies about diclofenac. The renal effects of Diclofenac may hasten the progression of renal dysfunction in recent studies about diclofenac with pre-existing renal disease, recent studies about diclofenac. Correct volume status in dehydrated or hypovolemic patients prior to initiating Diclofenac. Avoid the use of Diclofenac in patients with advanced renal disease unless the benefits are expected to outweigh the risk of worsening renal function.
If Diclofenac is used in patients with advanced renal disease, monitor patients for signs of worsening renal function. Increases in serum potassium concentration, including hyperkalemia, have been reported with use of NSAIDs, even in some patients without renal impairment. In patients with normal renal function, these effects have been attributed to a hyporeninemic-hypoaldosteronism state. When Diclofenac is used in patients with preexisting asthma without known aspirin sensitivitymonitor patients for changes in the signs and symptoms of asthma.
These serious events may occur without warning. Inform patients about the signs and symptoms of serious skin reactions and to discontinue the use of Diclofenac at the first appearance of skin rash or any other sign of hypersensitivity.
Diclofenac 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 Diclofenac, has any signs or symptoms of anemia, monitor hemoglobin or hematocrit. Co-morbid conditions such as coagulation disorders, concomitant use of warfarin, other anticoagulants, antiplatelet agents e. Diclofenac sodium delayed-release tablets 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.
The pharmacological activity of Diclofenac in reducing fever and inflammation may diminish the utility of these diagnostic signs in detecting complications of presumed noninfectious, painful conditions. 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 Diclofenac and periodically during the course of ongoing therapy.
Advise patients to be alert for the symptoms of cardiovascular thrombotic events, including chest pain, recent studies about diclofenac, 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, recent studies about diclofenac, 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. The pharmacological activity of Diclofenac in reducing inflammation, and possibly fever, may diminish the utility of diagnostic signs in detecting infections. See Table 2 for clinically significant drug interactions with Diclofenac, recent studies about diclofenac.