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Current Medical Research and Opinion Jul 2010Diclofenac is a proven, commonly prescribed nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory, and antipyretic properties, and has been... (Review)
Review
BACKGROUND
Diclofenac is a proven, commonly prescribed nonsteroidal anti-inflammatory drug (NSAID) that has analgesic, anti-inflammatory, and antipyretic properties, and has been shown to be effective in treating a variety of acute and chronic pain and inflammatory conditions. As with all NSAIDs, diclofenac exerts its action via inhibition of prostaglandin synthesis by inhibiting cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) with relative equipotency. However, extensive research shows the pharmacologic activity of diclofenac goes beyond COX inhibition, and includes multimodal and, in some instances, novel mechanisms of action (MOA).
DATA SOURCES
Literature retrieval was performed through PubMed/MEDLINE (through May 2009) using combinations of the terms diclofenac, NSAID, mechanism of action, COX-1, COX-2, and pharmacology. Reference citations resulting from publications identified in the literature search were reviewed when appropriate.
METHODS
This article reviews the established, putative, and emerging MOAs of diclofenac; compares the drug's pharmacologic and pharmacodynamic properties with other NSAIDs to delineate its potentially unique qualities; hypothesizes why it has been chosen for further recent formulation enhancement; and evaluates the potential effect of its MOA characteristics on safety.
DISCUSSION
Research suggests diclofenac can inhibit the thromboxane-prostanoid receptor, affect arachidonic acid release and uptake, inhibit lipoxygenase enzymes, and activate the nitric oxide-cGMP antinociceptive pathway. Other novel MOAs may include the inhibition of substrate P, inhibition of peroxisome proliferator activated receptor gamma (PPARgamma), blockage of acid-sensing ion channels, alteration of interleukin-6 production, and inhibition of N-methyl-D-aspartate (NMDA) receptor hyperalgesia. The review was not designed to compare MOAs of diclofenac with other NSAIDs. Additionally, as the highlighted putative and emerging MOAs do not have clinical data to demonstrate that these models are correct, further research is necessary to ascertain if the proposed pathways will translate into clinical benefits. The diversity in diclofenac's MOA may suggest the potential for a relatively more favorable profile compared with other NSAIDs.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Models, Biological; Pain; Signal Transduction
PubMed: 20470236
DOI: 10.1185/03007995.2010.486301 -
Journal of Pain & Palliative Care... Jun 2017Osteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which... (Review)
Review
Osteoarthritis (OA) is one of the most common causes of joint pain in the United States and non-steroidal anti-inflammatories (NSAIDs), such as Diclofenac sodium, which is currently available in two main routes of administration; oral and topical distribution have been established as one of the standard treatments for OA. Generally, oral NSAIDs are well tolerated; however our narrative review suggests that the topical solution had a better tolerability property than oral Diclofenac sodium, especially due to side effects of gastrointestinal bleeding with the utilization of the oral format. In addition, the topical route may be considered a reasonable selection by clinicians for management of musculoskeletal pain in those patients with a history of potential risk and adverse side effects. Most studies reviewed comparing oral versus topical solution of Diclofenac sodium revealed comparable efficacy, with minimal side effects utilizing the topical route. The key point of this narrative review is to help clinicians that currently must decide between very inexpensive diclofenac oral presentations and expensive topical presentations especially in the elderly population and the pros and cons of such decision-making process.
Topics: Administration, Cutaneous; Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Osteoarthritis
PubMed: 28388238
DOI: 10.1080/15360288.2017.1301616 -
Clinical Pharmacy Aug 1989The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of diclofenac sodium are reviewed. Diclofenac, the first nonsteroidal... (Review)
Review
The pharmacology, pharmacokinetics, clinical efficacy, adverse effects, and dosage of diclofenac sodium are reviewed. Diclofenac, the first nonsteroidal anti-inflammatory agent (NSAID) to be approved that is a phenylacetic acid derivative, competes with arachidonic acid for binding to cyclo-oxygenase, resulting in decreased formation of prostaglandins. The drug has both analgesic and antipyretic activities. Diclofenac is efficiently absorbed from the gastrointestinal tract; peak plasma concentrations occur 1.5 to 2.0 hours after ingestion in fasting subjects. Even though diclofenac has a relatively short elimination half-life in plasma (1.5 hours), it persists in synovial fluid. The drug is metabolized in the liver and is eliminated by urinary and biliary excretion. In clinical trials, diclofenac was as effective as aspirin, diflunisal, indomethacin, sulindac, ibuprofen, ketoprofen, and naproxen in improving function and reducing pain in patients with rheumatoid arthritis. For treatment of osteoarthritis, diclofenac was equivalent in efficacy to aspirin, diflunisal, indomethacin, sulindac, ibuprofen, ketoprofen, naproxen, flurbiprofen, mefenamic acid, and piroxicam. Diclofenac was as effective as indomethacin or sulindac in treating ankylosing spondylitis. The most frequent adverse effects reported for diclofenac were gastrointestinal, but these effects were fewer and less serious than occurred with aspirin or indomethacin; in addition, diclofenac caused fewer central nervous system reactions than indomethacin. Diclofenac is administered in divided doses with meals. The recommended total daily dosage is 100 to 150 mg (osteoarthritis and ankylosing spondylitis) or 150 to 200 mg (rheumatoid arthritis). Diclofenac is effective, but no more so than other NSAIDs. It is structurally distinct and offers another choice in the treatment of rheumatological conditions.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Diclofenac; Humans; Osteoarthritis
PubMed: 2670397
DOI: No ID Found -
Marine Pollution Bulletin Jun 2018Interest in the presence and effects of diclofenac (DCF) and other pharmaceutical products (PPs) in the aquatic environment has been growing over the last 20 years.... (Review)
Review
Interest in the presence and effects of diclofenac (DCF) and other pharmaceutical products (PPs) in the aquatic environment has been growing over the last 20 years. DCF has been included in the First Watch List of the EU Water Framework Directive in order to gather monitoring data in surface waters. Despite PP input in water bodies, few studies have been conducted to determine the extent of DCF occurrence and effects on marine ecosystems, which is usually the final recipient of surface waters. The present article reviews available published data on DCF occurrence in marine water, sediment and organisms, and its effects on marine organisms. The findings highlight the scarcity of available data on the occurrence and effects of DCF in marine ecosystems, and the need for further data acquisition to assess the risks associated with the presence of this compound in the environment.
Topics: Aquatic Organisms; Diclofenac; Ecosystem; Geologic Sediments; Water Pollutants, Chemical
PubMed: 29886975
DOI: 10.1016/j.marpolbul.2018.04.053 -
Connecticut Medicine Oct 1989Diclofenac is the newest NSAID to be introduced to the United States. Extensive worldwide clinical studies with diclofenac have demonstrated its efficacy in the... (Clinical Trial)
Clinical Trial Randomized Controlled Trial
Diclofenac is the newest NSAID to be introduced to the United States. Extensive worldwide clinical studies with diclofenac have demonstrated its efficacy in the treatment of rheumatoid arthritis, osteoarthritis, and ankylosing spondylitis. Its overall safety and efficacy is comparable to other available NSAIDs. The potential advantage of diclofenac is its short serum half-life but long synovial fluid concentration which enables twice daily dosing.
Topics: Diclofenac; Double-Blind Method; Humans; Randomized Controlled Trials as Topic; Rheumatic Diseases
PubMed: 2684502
DOI: No ID Found -
The Medical Letter on Drugs and... Dec 1988
Clinical Trial
Topics: Arthritis; Clinical Trials as Topic; Diclofenac; Drug Interactions; Humans
PubMed: 3054450
DOI: No ID Found -
Clinical Drug Investigation 2009This review focuses on previously unpublished clinical and pharmacokinetic data with the diclofenac epolamine (diclofenac hydroxyethylpyrrolidine) patch supporting the... (Review)
Review
This review focuses on previously unpublished clinical and pharmacokinetic data with the diclofenac epolamine (diclofenac hydroxyethylpyrrolidine) patch supporting the hypothesis of a topical effect of this formulation. Previous studies have shown that 1 or 2 weeks of treatment with diclofenac epolamine provides pain relief for various localized musculoskeletal conditions such as ankle sprains, epicondylitis and knee osteoarthritis. The reduction in pain after application of the first patch in 155 patients with painful knee osteoarthritis was significant at the 1-hour time point and was superior to placebo at the 3-hour time point and at all time points thereafter. Comparable results were found in a study of 274 patients with acute ankle sprains, in which pain relief was also significantly superior to placebo at the 3-hour time point. Corresponding single-dose (patch) application for 12 hours in ten healthy volunteers demonstrated that diclofenac first appears in plasma at a mean of 4.5 hours after application (range 2-8 hours). Hence, the patch provided pain relief at a time point at which no diclofenac is assumed to be in plasma, which demonstrates local action in terms of tissue diclofenac accumulation under the patch. This is further supported by an apparent plasma diclofenac half-life of 9-12 hours after patch application, which implies the presence of a tissue reservoir, as the half-life after oral intake of diclofenac is 1-2 hours.Steady-state plasma diclofenac concentrations are present before 3 days' application (two patches/day) and are in the order of 1-3 ng/mL. The bioavailability in terms of systemic exposure from the patch compared with oral intake (75 mg/day) is in the order of 1%. Such low diclofenac concentrations are without systemic effects, as demonstrated by the fact that no drug-related gastrointestinal bleeding, ulcers or cutaneous events characteristic of Steven-Johnson syndrome have been reported during 15 years of diclofenac epolamine patch use.These data provide support for the notion that diclofenac epolamine patch provides pain relief through accumulation of diclofenac under the site of application, without any evidence of systemic effects.
Topics: Administration, Topical; Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Humans; Musculoskeletal Diseases; Pain; Skin
PubMed: 19067470
DOI: 10.2165/0044011-200929010-00001 -
Drugs 2008*A new formulation of the nonselective NSAID diclofenac sodium suitable for intravenous bolus injection has been developed using hydroxypropyl beta-cyclodextrin as a... (Review)
Review
*A new formulation of the nonselective NSAID diclofenac sodium suitable for intravenous bolus injection has been developed using hydroxypropyl beta-cyclodextrin as a solubility enhancer (HPbetaCD diclofenac). * HPbetaCD diclofenac intravenous bolus injection was shown to be bioequivalent to the existing parenteral formulation of diclofenac containing propylene glycol and benzyl alcohol as solubilizers (PG-BA diclofenac), which is relatively insoluble and requires slow intravenous infusion over 30 minutes. * Single-dose HPbetaCD diclofenac 3.75, 9.4, 18.75, 25, 37.5, 50 and 75 mg administered by intravenous bolus injection produced significantly greater responses than placebo for total pain relief (TOTPAR) over 6 hours or pain intensity at 4 hours in the treatment of moderate or severe postoperative dental pain in randomized, double-blind trials. HPbetaCD diclofenac 37.5 and 75 mg were similar in efficacy to intravenous bolus ketorolac 30 mg. * In a well controlled trial, single-dose HPbetaCD diclofenac 75 mg intravenous bolus injection was shown to be superior to PG-BA diclofenac 75 mg intravenous infusion with respect to TOTPAR over 4 hours, indicating faster onset of analgesia in the treatment of moderate or severe postoperative dental pain. Both HPbetaCD diclofenac and PG-BA diclofenac were superior to placebo. * HPbetaCD diclofenac was generally well tolerated during single-dose treatment of postoperative pain. The tolerability profile was similar to that of PG-BA diclofenac, but with a lower incidence of thrombophlebitis.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Costs; Humans; Injections, Intravenous; Pain Measurement; Pain, Postoperative; Treatment Outcome
PubMed: 18081376
DOI: 10.2165/00003495-200868010-00008 -
CNS Drugs Aug 2014Diclofenac potassium powder for oral solution (Voltfast(®), Catafast(®), Cambia(®); hereafter referred to as diclofenac potassium powder) is a non-steroidal... (Review)
Review
Diclofenac potassium powder for oral solution (Voltfast(®), Catafast(®), Cambia(®); hereafter referred to as diclofenac potassium powder) is a non-steroidal anti-inflammatory drug (NSAID), and is indicated for the acute treatment of migraine. This article reviews the pharmacological properties of diclofenac potassium powder and its efficacy and tolerability in patients with acute migraine. Diclofenac potassium powder was clinically efficacious and generally well tolerated in placebo-controlled trials in patients with this indication; it was more effective than diclofenac potassium tablets with regard to the primary endpoint of 2-h pain relief as well as in several important secondary endpoints, such as time to onset of analgesic action. The oral powder-for-solution formulation of diclofenac potassium is a useful option in the acute treatment of migraine with or without aura.
Topics: Administration, Oral; Anti-Inflammatory Agents, Non-Steroidal; Controlled Clinical Trials as Topic; Diclofenac; Humans; Migraine Disorders; Powders
PubMed: 25034250
DOI: 10.1007/s40263-014-0186-y -
Drugs Mar 1988Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) advocated for use in painful and inflammatory rheumatic and certain non-rheumatic conditions. It is... (Clinical Trial)
Clinical Trial Review
Diclofenac is a non-steroidal anti-inflammatory drug (NSAID) advocated for use in painful and inflammatory rheumatic and certain non-rheumatic conditions. It is available in a number of administration forms which can be given orally, rectally or intramuscularly. Conveniently, dosage adjustments are not required in the elderly or in those patients with renal or hepatic impairment. The drug has a relatively short elimination half-life, which limits the potential for drug accumulation. In numerous clinical trials the efficacy of diclofenac is equivalent to that of the many newer and established NSAIDs with which it has been compared. As an analgesic it has a fast onset and long duration of action. When administered intramuscularly it is at least comparable to, and frequently superior to, many narcotic and spasmolytic combinations in renal and biliary colic. Extensive clinical experience has been gained with diclofenac, clearly establishing its safety profile. It is well tolerated compared with other NSAIDs and rarely produces gastrointestinal ulceration or other serious side effects. Thus, diclofenac can be considered as one of the few NSAIDs of 'first choice' in the treatment of acute and chronic painful and inflammatory conditions.
Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Arthritis; Clinical Trials as Topic; Diclofenac; Drug Combinations; Drug Evaluation, Preclinical; Fever; Humans; Pain; Rheumatic Diseases; Spondylitis, Ankylosing
PubMed: 3286213
DOI: 10.2165/00003495-198835030-00004