DICLOFENAC SODIUM- diclofenac sodium tablet, delayed release
McKesson Packaging Services a business unit of McKesson Corporation
- NSAIDs may cause an increased risk of serious cardiovascular thrombotic events, myocardial infarction, and stroke, which can be fatal. This risk may increase with duration of use. Patients with cardiovascular disease or risk factors for cardiovascular disease may be at greater risk (See WARNINGS).
- Diclofenac sodium delayed-release tablets are contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
- NSAIDs cause an increased risk of serious gastrointestinal adverse events including inflammation, bleeding, ulceration, and perforation of the stomach or intestines, which can be fatal. These events can occur at any time during use and without warning symptoms. Elderly patients are at greater risk for serious gastrointestinal events (See WARNINGS).
Diclofenac sodium delayed-release is a benzene-acetic acid derivative. The chemical name is 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, monosodium salt. The molecular weight is 318.13. Its molecular formula is C14 H10 Cl2 NNaO2 , and it has the following structural formula
Each enteric-coated tablet for oral administration contains 50 mg or 75 mg of diclofenac sodium. In addition, each tablet contains the following inactive ingredients: aluminum hydrate, colloidal silicon dioxide, hypromellose, lactose monohydrate, magnesium stearate, microcrystalline cellulose, polyethylene glycol, polysorbate 80, polyvinyl acetate phthalate, propylene glycol, silica, sodium alginate, sodium starch glycolate (Type A), stearic acid, synthetic black iron oxide, talc, and titanium dioxide.
Diclofenac sodium delayed-release tablets are a nonsteroidal anti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, and antipyretic activities in animal models. The mechanism of action of diclofenac sodium delayed-release, like that of other NSAIDs, is not completely understood but may be related to prostaglandin synthetase inhibition.
Diclofenac is 100% absorbed after oral administration compared to IV administration as measured by urine recovery. However, due to first-pass metabolism, only about 50% of the absorbed dose is systemically available (see Table 1). 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 4.5 hours and a reduction in peak plasma levels of <20%.
|PK Parameter||Normal Healthy Adults (20-48 yrs.)|
|Mean||Coefficient of Variation (%)|
|Absolute Bioavailability (%) [N = 7]||55||40|
|Tmax (hr) [N = 56]||2.3||69|
|Oral Clearance (CL/F; mL/min) [N = 56]||582||23|
|Renal Clearance (% unchanged drug in urine) [N = 7]||<1||–|
|Apparent Volume of Distribution (V/F; L/kg) [N = 56]||1.4||58|
|Terminal Half-life (hr)[N = 56]||2.3||48|
The apparent volume of distribution (V/F) of diclofenac sodium is 1.4 L/kg.
Diclofenac is more than 99% bound to human serum proteins, primarily to albumin. Serum protein binding is constant over the concentration range (0.15-105 µg/mL) achieved with recommended doses.
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. In patients with renal dysfunction, peak concentrations of metabolites 4′-hydroxy- and 5-hydroxy-diclofenac were approximately 50% and 4% of the parent compound after single oral dosing compared to 27% and 1% in normal healthy subjects. However, diclofenac metabolites undergo further glucuronidation and sulfation followed by biliary excretion.
One diclofenac metabolite 4′-hydroxy- diclofenac has very weak pharmacologic activity.
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. Approximately 65% of the dose is excreted in the urine and approximately 35% in the bile as conjugates of unchanged diclofenac plus metabolites. 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.
Pediatric: The pharmacokinetics of diclofenac sodium delayed-release has not been investigated in pediatric patients.
Race:Pharmacokinetics differences due to race have not been identified.
Hepatic Insufficiency:Hepatic metabolism accounts for almost 100% of diclofenac sodium delayed-release elimination, so patients with hepatic disease may require reduced doses of diclofenac sodium delayed-release compared to patients with normal hepatic function.
Renal Insufficiency: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. In patients with renal impairment (inulin clearance 60-90, 30-60, and <30 mL/min; N=6 in each group), AUC values and elimination rate were comparable to those in healthy subjects.
Carefully consider the potential benefits and risks of diclofenac sodium delayed-release and other treatment options before deciding to use diclofenac sodium delayed-release. Use the lowest effective dose for the shortest duration consistent with individual patient treatment goals (see WARNINGS).
Diclofenac sodium delayed-release tablets are indicated:
• For relief of signs and symptoms of osteoarthritis
• For relief of signs and symptoms of rheumatoid arthritis
• For acute or long-term use in the relief of signs and symptoms of ankylosing spondylitis
Diclofenac sodium delayed-release tablets are contraindicated in patients with known hypersensitivity to diclofenac. Diclofenac sodium delayed-release should not be given to patients who have experienced asthma, urticaria, or other allergic-type reactions after taking aspirin or other NSAIDs. Severe, rarely fatal, anaphylactic-like reactions to NSAIDs have been reported in such patients (see WARNINGS, Anaphylactoid Reactions, and PRECAUTIONS, Preexisting Asthma).
Diclofenac sodium delayed-release is contraindicated for the treatment of peri-operative pain in the setting of coronary artery bypass graft (CABG) surgery (see WARNINGS).
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