cataflam
Manufacturer: Novartis
The following prescribing information is based on official labeling in effectAugust 2003 cataflam.
DESCRIPTION
Cataflam ® (diclofenac potassium immediate-release tablets), is a benzeneaceticacid derivative cataflam. Cataflam is available as immediate-release Tablets of 50 mg(light brown) for oral administration cataflam. The chemical name is 2-[(2,6-dichlorophenyl)amino]benzeneacetic acid, monopotassium salt cataflam. The molecular weight is 334.25 cataflam. Itsmolecular formula is C 14 H 10 Cl 2 NKO 2 , and it has the following structuralformula The inactive ingredients in Cataflam include: calcium phosphate, colloidalsilicon dioxide, iron oxides, magnesium stearate, microcrystalline cellulose,polyethylene glycol, povidone, sodium starch glycolate, maize starch, sucrose,talc, titanium dioxide cataflam. CLINICAL PHARMACOLOGY
Pharmacodynamics
Cataflam ® (diclofenac potassium immediate-release tablets) is a nonsteroidalanti-inflammatory drug (NSAID) that exhibits anti-inflammatory, analgesic, andantipyretic activities in animal models cataflam. The mechanism of action of Cataflam,like that of other NSAIDs, is not completely understood but may be related toprostaglandin synthetase inhibition cataflam. Pharmacokinetics
Absorption
Diclofenac is 100% absorbed after oral administration compared to IV administrationas measured by urine recovery cataflam. However, due to first-pass metabolism, only about50% of the absorbed dose is systemically available (see Table 1) cataflam. In some fastingvolunteers, measurable plasma levels are observed within 10 minutes of dosingwith Cataflam cataflam. Peak plasma levels are achieved approximately 1 hour in fastingnormal volunteers, with a range of .33 to 2 hours cataflam. Food has no significant effecton the extent of diclofenac absorption cataflam. However, there is usually a delay inthe onset of absorption and a reduction in peak plasma levels of approximately30% cataflam. Table 1 cataflam. Pharmacokinetic Parameters for Diclofenac PK Parameter Normal HealthyAdults
(20-52 yrs.)
Mean Coefficient of Variation (%)
Absolute Bioavailability (%) [N = 7] 55 40
T max (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
Distribution
The apparent volume of distribution (V/F) of diclofenac potassium is 1.3 L/kg cataflam.
Diclofenac is more than 99% bound to human serum proteins, primarily to albumin cataflam. Serum protein binding is constant over the concentration range (0.15-105 µg/mL)achieved with recommended doses cataflam. Diclofenac diffuses into and out of the synovial fluid cataflam. Diffusion into thejoint occurs when plasma levels are higher than those in the synovial fluid,after which the process reverses and synovial fluid levels are higher than plasmalevels cataflam. It is not known whether diffusion into the joint plays a role in theeffectiveness of diclofenac cataflam. Metabolism
Five diclofenac metabolites have been identified in human plasma and urine cataflam. The metabolites include 4'-hydroxy-, 5-hydroxy-, 3'-hydroxy-, 4',5-dihydroxy-and 3'-hydroxy-4'-methoxy diclofenac cataflam. In patients with renal dysfunction, peakconcentrations of metabolites 4'-hydroxy-and 5-hydroxy-diclofenac were approximately50% and 4% of the parent compound after single oral dosing compared to 27% and1% in normal healthy subjects cataflam. However, diclofenac metabolites undergo furtherglucuronidation and sulfation followed by biliary excretion cataflam. One diclofenac metabolite 4'-hydroxy-diclofenac has very weak pharmacologicactivity cataflam. Excretion
Diclofenac is eliminated through metabolism and subsequent urinary and biliaryexcretion of the glucuronide and the sulfate conjugates of the metabolites cataflam. Little or no free unchanged diclofenac is excreted in the urine cataflam. Approximately65% of the dose is excreted in the urine and approximately 35% in the bile asconjugates of unchanged diclofenac plus metabolites cataflam. Because renal eliminationis not a significant pathway of elimination for unchanged diclofenac, dosingadjustment in patients with mild to moderate renal dysfunction is not necessary cataflam. The terminal half-life of unchanged diclofenac is approximately 2 hours cataflam. Special Populations
Pediatric: The pharmacokinetics of Cataflam has not been investigated in pediatricpatients cataflam. Race: Pharmacokinetics differences due to race have not been identified cataflam. Hepatic Insufficiency: Hepatic metabolism accounts for almost 100% of Cataflamelimination, so patients with hepatic disease may require reduced doses of Cataflamcompared to patients with normal hepatic function cataflam. Renal Insufficiency: Diclofenac pharmacokinetics has been investigated in subjectswith renal insufficiency cataflam. No differences in the pharmacokinetics of diclofenachave been detected in studies of patients with renal impairment cataflam. In patientswith renal impairment (inulin clearance 60-90, 30-60, and <30 mL/min; N=6in each group), AUC values and elimination rate were comparable to those inhealthy subjects cataflam.
INDICATIONS AND USAGE
Cataflam ® (diclofenac potassium immediate-release tablets) is indicated:
For treatment of primary dysmenorrhea
For relief of mild to moderate pain
For relief of signs and symptoms of osteoarthritis
For relief of signs and symptoms of rheumatoid arthritis
CONTRAINDICATIONS
Cataflam ® (diclofenac potassium immediate-release tablets) is contraindicatedin patients with known hypersensitivity to diclofenac cataflam. Cataflam should not begiven to patients who have experienced asthma, urticaria, or allergic-type reactionsafter taking aspirin or other NSAIDs cataflam. Severe, rarely fatal, anaphylactic-likereactions to NSAIDs have been reported in such patients (see WARNINGS - AnaphylactoidReactions , and PRECAUTIONS - Preexisting Asthma ) cataflam.
WARNINGS
Gastrointestinal (GI) Effects - Risk of GI Ulceration, Bleeding, and Perforation:
Serious gastrointestinal toxicity such as inflammation, bleeding, ulceration,and perforation of the stomach, small intestine or large intestine, can occurat any time, with or without warning symptoms, in patients treated with nonsteroidalanti-inflammatory drugs (NSAIDs) cataflam. Minor upper gastrointestinal problems, suchas dyspepsia, are common and may also occur at any time during NSAID therapy cataflam. Therefore, physicians and patients should remain alert for ulceration and bleedingeven in the absence of previous GI tract symptoms cataflam. Patients should be informedabout the signs and/or symptoms of serious GI toxicity and the steps to takeif they occur cataflam. The utility of periodic laboratory monitoring has not been demonstrated,nor has it been adequately assessed cataflam. Only one in five patients, who developa serious upper GI adverse event on NSAID therapy, is symptomatic cataflam. It has beendemonstrated that upper GI ulcers, gross bleeding or perforation, caused byNSAIDs, appear to occur in approximately 1% of patients treated for 3-6 months,and in about 2%-4% of patients treated for one year cataflam. These trends continue thus,increasing the likelihood of developing a serious GI event at some time duringthe course of therapy cataflam. However, even short term therapy is not without risk cataflam.
NSAIDs should be prescribed with extreme caution in those with a prior historyof ulcer disease or gastrointestinal bleeding cataflam. Most spontaneous reports of fatalGI events are in elderly or debilitated patients and therefore special careshould be taken in treating this population cataflam. To minimize the potential riskfor an adverse GI event, the lowest effective dose should be used for the shortestpossible duration cataflam. For high risk patients, alternate therapies that do not involveNSAIDs should be considered cataflam. Studies have shown that patients with a prior history of peptic ulcer diseaseand/or gastrointestinal bleeding and who use NSAIDs, have a greater than 10-foldrisk for developing a GI bleed than patients with neither of these risk factors cataflam. In addition to a past history of ulcer disease, pharmacoepidemiological studieshave identified several other co-therapies or co-morbid conditions that mayincrease the risk for GI bleeding such as: treatment with oral corticosteroids,treatment with anticoagulants, longer duration of NSAID therapy, smoking, alcoholism,older age, and poor general health status cataflam. Anaphylactoid Reactions
As with other NSAIDs, anaphylactoid reactions may occur in patients withoutknown prior exposure to Cataflam ® (diclofenac potassium immediate-releasetablets) cataflam. Cataflam should not be given to patients with the aspirin triad cataflam. Thissymptom complex typically occurs in asthmatic patients who experience rhinitiswith or without nasal polyps, or who exhibit severe, potentially fatal bronchospasmafter taking aspirin or other NSAIDs cataflam. (See CONTRAINDICATIONS and PRECAUTIONS- Preexisting Asthma .) Emergency help should be sought in cases where an anaphylactoidreaction occurs cataflam.
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