DICLOFENAC POTASSIUM- diclofenac potassium tablet, film coated
Ingenus Pharmaceuticals, LLC
Cardiovascular Thrombotic Events
- Nonsteroidal anti-inflammatory drugs (NSAIDs) cause an increased risk of serious cardiovascular thrombotic events, including myocardial infarction and stroke, which can be fatal. This risk may occur early in treatment and may increase with duration of use (see WARNINGS).
- Diclofenac potassium tablets are contraindicated in the setting of coronary artery bypass graft (CABG) surgery (see CONTRAINDICATIONS, WARNINGS).
Gastrointestinal Bleeding, Ulceration, and Perforation
- NSAIDs cause an increased risk of serious gastrointestinal (GI) adverse events, including 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 and patients with a prior history of peptic ulcer disease and/or GI bleeding are at greater risk for serious GI events (see WARNINGS).
Diclofenac potassium tablets, USP are a benzeneacetic acid derivative. Diclofenac potassium tablets are available as tablets of 50 mg (white) for oral administration. Diclofenac potassium, USP is a white or slightly yellowish crystalline powder and is sparingly soluble in water at 25ºC. The chemical name is 2-[(2,6-dichlorophenyl)amino] benzeneacetic acid, monopotassium salt. The molecular weight is 334.24 g/mol. Its molecular formula is C14 H10 Cl2 NKO2 , and it has the following structural formula:
The inactive ingredients in diclofenac potassium tablets include: anhydrous lactose, microcrystalline cellulose, croscarmellose sodium, sodium lauryl sulfate, colloidal silicon dioxide, magnesium stearate, titanium dioxide, polydextrose, hypromellose, triacetin, and polyethylene glycol.
Diclofenac has analgesic, anti-inflammatory, and antipyretic properties.
The mechanism of action of diclofenac potassium tablets, like that of other NSAIDs, is not completely understood but involves inhibition of cyclooxygenase (COX-1 and COX-2).
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.
Diclofenac is 100% absorbed after oral administration compared to intravenous (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). In some fasting volunteers, measurable plasma levels are observed within 10 minutes of dosing with diclofenac potassium tablets. Peak plasma levels are achieved approximately 1 hour in fasting normal volunteers, with a range of 0.33 to 2 hours. Food has no significant effect on the extent of diclofenac absorption. However, there is usually a delay in the onset of absorption and a reduction in peak plasma levels of approximately 30%.
|PK Parameter||Normal Healthy Adults (20 to 52 years)|
|Mean||Coefficient of Variation (%)|
|Absolute bioavailability (%) [N = 7]||55||40|
|Tmax (hr) [N = 65]||1.0||76|
|Oral clearance (CL/F; mL/min) [N = 61]||622||21|
|Renal clearance (% unchanged drug in urine) [N = 7]||< 1||–|
|Apparent volume of distribution (V/F; L/kg) [N = 61]||1.3||33|
|Terminal half-life (hr) [N = 48]||1.9||29|
The apparent volume of distribution (V/F) of diclofenac potassium is 1.3 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 to 105 mcg/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. The major diclofenac metabolite, 4′-hydroxy-diclofenac, has very weak pharmacologic activity. The formation of 4’-hydroxy-diclofenac is primarily mediated by CYP2C9. Both diclofenac and its oxidative metabolites undergo glucuronidation or sulfation followed by biliary excretion. Acylglucuronidation mediated by UGT2B7 and oxidation mediated by CYP2C8 may also play a role in diclofenac metabolism. CYP3A4 is responsible for the formation of minor metabolites, 5-hydroxy- and 3’-hydroxy-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.
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 potassium tablets have not been investigated in pediatric patients.
Race : Pharmacokinetic differences due to race have not been identified.
Hepatic Impairment : Hepatic metabolism accounts for almost 100% of diclofenac potassium tablets elimination, so patients with hepatic disease may require reduced doses of diclofenac potassium tablets compared to patients with normal hepatic function.
Renal Impairment: 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 to 90, 30 to 60, and less than 30 mL/min; N = 6 in each group), area under the curve (AUC) values and elimination rate were comparable to those in healthy subjects.
All MedLibrary.org resources are included in as near-original form as possible, meaning that the information from the original provider has been rendered here with only typographical or stylistic modifications and not with any substantive alterations of content, meaning or intent.