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Cochrane Database Syst Rev. 2004;(2):CD004768. BACKGROUND: Diclofenac is a benzene-acetic acid derivative that acts, like other NSAIDs, by inhibiting cyclo-oxygenase isoforms that mediate the body's production of the prostaglandins implicated in pain and inflammation. Diclofenac is widely available as a sodium or potassium salt. Diclofenac potassium tablets are known as 'immediate-release' diclofenac as absorption takes place in the gastrointestinal tract whereas 'delayed-release' (enteric-coated) diclofenac tablets resist dissolution until reaching the duodenum. An existing review showed that diclofenac was an effective treatment for acute postoperative pain but did not address the distinction between potassium and sodium salts due to lack of data. The aim of this update is to gather and add appropriate information published subsequently and, data permitting, examine any potential differences between the two different diclofenac formulations. OBJECTIVES: To assess single dose oral diclofenac for the treatment of acute postoperative pain and determine whether there are differences between the different formulations. SEARCH STRATEGY: We searched the Cochrane Library (Issue 2, 2003), MEDLINE (1966 to May 1996), EMBASE (1980 to 1996), Biological Abstracts (1985 to 2003), the Oxford Pain Relief Database (1950 to 1994), PubMed (1996 to 2003) and reference lists of articles. SELECTION CRITERIA: Randomised, double-blind, placebo-controlled clinical trials of single dose, oral diclofenac sodium or diclofenac potassium for acute postoperative pain in adults. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trials for inclusion in the review, quality and extracted data. The area under the pain relief versus time curve was used to derive the proportion of patients prescribed diclofenac or placebo with at least 50% pain relief over four to six hours using validated equations. The number needed to treat (NNT) was calculated. Information on adverse effects was also collected. MAIN RESULTS: One additional trial was included and added to the six trials included in the original review. All seven trials provided data for quantitative analysis: 581 patients were treated with diclofenac and 364 were treated with placebo. The NNT for at least 50% relief over four to six hours with diclofenac 25 mg, 50 mg and 100 mg compared with placebo was 2.8 (95% CI 2.1 to 4.3), 2.3 (2.0 to 2.7) and 1.9 (1.6 to 2.2) respectively. Though higher doses produced lower (better) NNTs, statistical significance was not achieved. There was no significant difference between diclofenac 50 mg and placebo in the proportion of patients experiencing dizziness, headache, nausea or vomiting. The weighted median duration of analgesia was 2 hours for placebo, 6.7 hours for diclofenac 50 mg and 7.2 hours for diclofenac 100 mg. Sensitivity analyses for drug formulation, pain model, trial size and quality did not reveal any statistically significant differences. REVIEWERS' CONCLUSIONS: Oral diclofenac is an effective single-dose treatment for moderate to severe postoperative pain. There was no significant difference between diclofenac and placebo in the incidence of adverse effects, or between diclofenac sodium and potassium, different pain models, smaller and larger trials and trials of higher and lower quality. Rheumatology (Oxford). 2003 Oct;42(10):1207-15. OBJECTIVE: To compare the efficacy and upper gastrointestinal (GI) safety of valdecoxib 20 and 40 mg daily with those of diclofenac 75 mg slow release (SR) twice daily in treating rheumatoid arthritis (RA). METHODS: Seven hundred and twenty-two patients with adult-onset RA were enrolled into this 26-week, randomized, multicentre, double-blind, parallel-group study (246 in the valdecoxib 20 mg daily arm, 237 in the valdecoxib 40 mg daily arm and 239 in the diclofenac 75 mg SR daily arm). Acetylsalicylic acid use (< or =325 mg per day) was similar across all groups: 5.4% in the diclofenac group, 5.7% in the valdecoxib 20 mg group and 5.9% in the valdecoxib 40 mg group. Efficacy was measured by the Patient's Assessment of Arthritis Pain [visual analogue scale (VAS)] and the modified Health Assessment Questionnaire (mHAQ) at baseline and at weeks 2, 6, 8, 12, 18 and 26 of treatment, or at early termination. Upper GI safety was evaluated by endoscopy at the end of treatment, which took place no more than 2 days after the last dose of study medication or at early termination. RESULTS: Valdecoxib 20 and 40 mg daily were comparable to diclofenac 75 mg SR twice daily in treating the signs and symptoms of RA. No significant differences were observed between treatment groups with respect to mean changes from baseline in the Patient's Assessment of Arthritis Pain (VAS) or mHAQ. The incidence of gastroduodenal ulcers in patients receiving valdecoxib 20 mg daily (6%) and valdecoxib 40 mg daily (4%) was significantly lower (P < 0.001) than in patients receiving diclofenac 75 mg SR twice daily (16%). Valdecoxib 20 mg daily was also associated with significantly improved GI tolerability (P = 0.035) compared with diclofenac. CONCLUSIONS: Single daily doses of valdecoxib 20 and 40 mg provided efficacy comparable to that of diclofenac, with a superior upper GI safety profile in the long-term treatment of RA patients. Can J Anaesth 2000 Mar;47(3):220-4 PURPOSE: To compare the postoperative analgesic effects of 50 mg diclofenac p.o. before surgery and intra-articular ropivacaine injected after diagnostic day-case knee arthroscopy performed under spinal anesthesia. METHODS: In a randomized, double-blind investigation, 200 ASA physical status 1-2 outpatients, age 18-60 yr, received either 50 mg diclofenac p.o. or placebo one hour before operation (100 patients per group), and intraarticular injections of either 20 ml of ropivacaine 0.5% or 20 ml of saline 0.9% (50 patients in each premedication groups). Patients received 50 mg diclofenac p.o. prn and, if needed, 0.1 mg x kg(-1) oxycodone im for postoperative pain relief. Patients were discharged home with a supply of 50 mg diclofenac tablets and were given a sheet of paper with knee pain VAS scales and a questionnaire of analgesics taken. Patients rated their VAS scores eight hours after surgery and in the moming and at the end of the first and the second postoperative days, respectively. RESULTS: The only statistically significant difference was found when the diclofenac groups were combined and compared with the combined placebo premedication groups. The VAS scores of knee pain at eight hours after the operation were 19+/-22 in the two diclofenac premedication groups and 32+/-28 in the two placebo groups (P = 0.001). CONCLUSIONS: Diclofenac premedication p.o. reduced the VAS scores at eight hours postoperatively while intra-articular ropivacaine did not. Eur J Obstet Gynecol Reprod Biol 2000 Feb;88(2):143-6 OBJECTIVE: Pain relief of good quality after caesarean section (CS) results in early mobilization and good early mother-child interaction. Patient-controlled analgesia (PCA), with systemic opioids, gives a very high level of patient satisfaction. However, opioids have well documented side-effects i.e. sedation, nausea and respiratory depression. To minimize the risk of such negative effects we studied how far the required dose of opioid could be decreased with a multimodal strategy adding diclofenac. STUDY DESIGN: In a randomized double-blind study, 50 parturients scheduled for elective CS under spinal anaesthesia, received rectally either diclofenac (Suppositorium diclofenac) 50 mgx3 or placebo 1x3 during the first 24 h postoperatively. All patients had PCA with the possibility of self-administered doses of ketobemidone 1 mg/6 min. RESULTS: In the group receiving diclofenac rectally the consumption of ketobemidone was reduced with 39% compared to the placebo group. CONCLUSION: A multimodal analgetic strategy with the addition of 150 mg diclofenac during the first 24 h after CS reduces the need for opioids significantly with maintained or improved analgetic effect. This is expected to reduce the risk of negative side-effects of systemic opioids. Tumori 1999 Mar-Apr;85(2):96-100 AIM: To compare the analgesic efficacy and toxicity of the nonsteroidal anti-inflammatory analgesic drug, ketorolac (Toradol, Recordati spa, Milan) 10 mg p.o. (t.i.d.) with diclofenac (Voltaren, Novartis Farma, Origglo, VA) 50 mg p.o. (t.i.d.) in cancer patients with moderate to severe chronic pain. METHODS AND STUDY DESIGN: The study was a multicenter randomized double-blind cross-over trial. Each treatment lasted 7 days, after which the patients crossed over to the other drug. Pain intensity was evaluated by the visual analogue scale (VAS) after the first dose and by the 5-point verbal rating scale (VRS) by the patient and by the physician following the 7-day treatment. RESULTS AND CONCLUSIONS: A total of 138 advanced cancer patients were enrolled in the study. Overall 251 single-dose administrations (117 cross-over observations) and 257 multiple treatments (127 cross-over experiments) were assessable. After a single administration of ketorolac and diclofenac, no significant difference could be observed in analgesic activity, as indicated by the area under the pain-intensity time curve (AUC0-8), in the maximum efficacy, or the duration of efficacy of the two drugs. The Westlake confidence intervals of the AUC0-8 ratio (ketorolac: diclofenac) (1.07; 90% CI, 0.94-1.19), of the maximum efficacy ratio (1.03; 90% CI, 0.92-1.14), and the duration of efficacy ratio (1.05; 90% CI, 0.97-1.11) showed the bioequivalence of the two drugs. Satisfactory pain relief was reported for multiple 7-day treatments, with no significant differences between the two therapies: according to the physician's evaluation, in 93/128 (73%; 95% CI, 65-80%) ketorolac treatments and 91/129 (71%; 95% CI, 63-78%) diclofenac treatments; according to the patient's evaluation, in 83/128 cases (65%; 95% CI, 57-73%) after ketorolac and in 74/129 cases (57%; 95% CI, 49-66%) after diclofenac. Adverse symptoms were acceptable with both drugs. Interestingly, a pronounced sequence effect was found: gastric disturbances after ketorolac were observed mainly (10 out of 15 observed events) when the drug was given to patients pretreated with diclofenac. Anesth Analg 1999 Jan;88(1):149-54 Nonsteroidal antiinflammatory drugs (NSAIDs) have become increasingly popular in the treatment of perioperative pain. Due to concerns that cyclooxygenase inhibition may adversely affect renal function, these drugs are often not used in geriatric surgical patients. However, the perioperative effect of NSAIDs on renal blood flow (RBF) and glomerular filtration rate (GFR) has not been assessed. Therefore, using a prospective, controlled, double-blinded study design, we evaluated the effect of diclofenac on RBF and GFR in 20 patients (>65 yr) undergoing open reduction and internal fixation of the femur. All patients were normovolemic before the study. A standardized general anesthetic was administered. On induction of anesthesia, patients in the diclofenac group received an IV bolus of diclofenac (0.7 mg/kg) followed by a constant infusion (0.15 mg x kg(-1) x h(-1)) until the end of surgery. In the saline group, an equal volume of saline was administered. During four time periods (equilibration, anesthesia, surgical, recovery), GFR and effective renal plasma flow (ERPF) were measured by inulin and para-aminohippurate clearance, respectively. After the induction of anesthesia and throughout the surgical period, ERPF and GFR were significantly decreased compared with preoperative baseline values. However, no difference was demonstrated between the groups. These results suggest that, in geriatric surgical patients, the adjuvant administration of NSAIDs does not adversely affect renal function. IMPLICATIONS: As determined by inulin and paraaminohippurate clearance, the intraoperative administration of diclofenac does not decrease glomerular filtration rate or effective renal plasma flow in normovolemic geriatric patients. Therefore, diclofenac may be administered during the perioperative period. Cleft Palate Craniofac J 1998 Nov;35(6):544-5 OBJECTIVE: This prospective study looked at the postoperative hemorrhage risk associated with the use of diclofenac following cleft palate repair. PATIENTS: Twenty consecutive children (6 months to 9 years of age) requiring repair of the hard or soft palate were included. DESIGN AND METHODS: Single per rectum doses of diclofenac were given at 1 mg/kg following cleft palate repair, with additional doses every 12 hours. RESULTS AND CONCLUSIONS: The use of the nonsteroidal anti-inflammatory drug, diclofenac, for postoperative analgesia is well established for many types of surgery. The authors find that twice daily diclofenac rectal suppositories provide very good analgesia postcleft palate repair. This, combined with supplemental oral paracetamol, obviates the need for opiates, resulting in alert infants who feed well and are suitable for early discharge. Hum Reprod 1998 Sep;13(9):2480-3 The aim was to evaluate the effect of diclofenac on uterine artery blood flow resistance during the first day of menstruation. A total of 28 regularly menstruating women were examined longitudinally with and without a copper intrauterine contraceptive device (IUD) by transvaginal colour Doppler ultrasonography. The uterine artery pulsatility index (PI) was first measured, after which 50 mg of diclofenac was infused i.v. After 15 min the PI was measured again. The patients evaluated their menstrual pain with a scoring system before and after the diclofenac infusion. The mean PI (SD) during menstruation was significantly lower with the IUD [2.13 (0.43)] than without [2.39 (0.62)], P = 0.05. The mean PI in nine patients who experienced advanced menstrual pain was also lower in the presence of the IUD [2.16 (0.42)] than without it [2.83 (0.78); P < 0.05]. Diclofenac was effective in revealing menstrual pain both with and without the IUD, and reduced the PI in the absence of an IUD [pre-treatment 2.39 (0.62) versus post-treatment 2.12 (0.45); P < 0.001], but had no effect when the IUD was present [pre-treatment 2.13 (0.43) versus post-treatment 2.10 (0.41)]. The results indicate that by inhibiting prostaglandin synthesis one can reduce the resistance to blood flow in the uterine arteries during menstruation. This does not hold true when an IUD is present, however, suggesting that the device might induce the production of vasoactive agents other than prostaglandins in the surrounding tissue. Pharmacotherapy 1998 May-Jun;18(3):504-8 STUDY OBJECTIVE: To compare the analgesic efficacy and safety of two single doses of ketorolac with diclofenac in acute cancer pain. DESIGN: Double-blind, randomized, clinical study. SETTING: Hospital-based clinical research center. SUBJECTS: One hundred eighty patients suffering acute, moderate, or severe cancer pain. INTERVENTIONS: A single intramuscular injection of ketorolac 10 or 30 mg or diclofenac 75 mg. MEASUREMENTS AND MAIN RESULTS: Pain intensity was assessed 30 minutes and 1, 2, 3, 4, 5, and 6 hours after injection or until rescue drug administration. In approximately 70% of patients all treatments provided prompt sustained pain relief throughout the 6-hour observation period. There were no statistically significant differences in any of the analyzed efficacy measures among the three groups. CONCLUSION: Intramuscular ketorolac 10 mg is adequate to relieve cancer pain, and is equivalent to ketorolac 30 mg and to diclofenac 75 mg. Pain. 1998 Feb;74(2-3):133-7. J Pain Symptom Manage 1997 Jul;14(1):15-20 BACKGROUND & AIMS: Nonsteroidal anti-inflammatory drugs (NSAIDs)
have been used to relieve biliary colic. Follow-up was limited in previous
studies, and the role of NSAIDs in the natural history of biliary colic has not
been clarified. The purpose of this study was to evaluate the efficacy of
diclofenac, a potent NSAID, in the the immediate symptomatic relief of biliary
colic and the prevention of cholelithiasis-related complications. METHODS:
Fifty-three patients with cholelithiasis and biliary colic were enrolled in this
randomized, double-blind, placebo-controlled study. They received a single 75-mg
(3 mL) intramuscular injection of diclofenac (n = 27) or similarly administered
3 mL of saline (n = 26). All patients were followed up for at least 3 days. The
effect of either treatment was assessed by changes in the severity of pain and
the development of cholelithiasis-related complications. RESULTS: Complete
relief of pain was obtained in 21 diclofenac and in 7 placebo patients;
progression to acute cholecystitis was observed in 4 and 11 patients,
respectively. Fewer overall complications were observed in the diclofenac group.
CONCLUSIONS: In patients with cholelithiasis who present with biliary colic, a
single 75-mg intramuscular dose of diclofenac can provide satisfactory pain
relief and decrease substantially the rate of progression to acute cholecystitis. J Refract Surg 1996 Nov-Dec;12(7):792-4 Clin Pharm. 1989 Aug;8(8):545-58. 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. Drug Intell Clin Pharm. 1988 Nov;22(11):850-9.
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