tolfenamic-acid and Dysmenorrhea

This is an updated version of the original Cochrane review published in Issue 3, 2012. Caffeine has been added to common analgesics such as paracetamol, ibuprofen, and aspirin, in the belief that it enhances analgesic efficacy. Evidence to support this belief is limited and often based on invalid comparisons.. To assess the relative efficacy of a single dose of an analgesic plus caffeine against the same dose of the analgesic alone, without restriction on the analgesic used or the pain condition studied. We also assessed serious adverse events.. We searched CENTRAL, MEDLINE, and EMBASE from inception to 28 August 2014, the Oxford Pain Relief Database, and also carried out Internet searches and contacted pharmaceutical companies known to have carried out trials that have not been published.. We included randomised, double-blind studies that compared a single dose of analgesic plus caffeine with the same dose of the analgesic alone in the treatment of acute pain.. Two review authors independently assessed the eligibility and quality of studies, and extracted data. Any disagreements or uncertainties were settled by discussion with a third review author. We sought any validated measure of analgesic efficacy, but particularly the number of participants experiencing at least 50% of the maximum possible pain relief over four to six hours, participants reporting a global evaluation of treatment of very good or excellent, or headache relief after two hours. We pooled comparable data to look for a statistically significant difference, and calculated numbers needed to treat to benefit (NNT) with caffeine. We also looked for any numerical superiority associated with the addition of caffeine, and information about any serious adverse events.. We identified no new studies with available results for this update. The earlier review included 20 studies (7238 participants) in valid comparisons, but because we used different outcomes for some headache studies, the number of participants in the analyses of the effects of caffeine is now 4262 when previously it was 5243. The studies were generally of good methodological quality, using standard designs and mostly standard scales of pain measurement, although many of those treating postoperative pain were small.Most studies used paracetamol or ibuprofen, with 100 mg to 130 mg caffeine, and the most common pain conditions studied were postoperative dental pain, postpartum pain, and headache. There was a small but statistically significant benefit with caffeine used at doses of 100 mg or more, which was not dependent on the pain condition or type of analgesic. About 5% to 10% more participants achieve a good level of pain relief (at least 50% of the maximum over four to six hours) with the addition of caffeine, giving a NNT of about 14 (high quality evidence).Most comparisons individually demonstrated numerical superiority with caffeine, but not statistical superiority. One serious adverse event was reported with caffeine, but was considered unrelated to any study medication.We know of the existence of around 25 additional studies with almost 12,500 participants for which data for analysis were not obtainable. The additional analgesic effect of caffeine remained statistically significant but clinically less important even if all the known missing data had no effect; the bulk of the unobtainable data are reported to have similar results as this review.. The addition of caffeine (≥ 100 mg) to a standard dose of commonly used analgesics provides a small but important increase in the proportion of participants who experience a good level of pain relief.

Topics: Acetaminophen; Acute Pain; Adolescent; Adult; Aged; Analgesics; Caffeine; Chemotherapy, Adjuvant; Diclofenac; Drug Synergism; Dysmenorrhea; Female; Headache; Humans; Ibuprofen; Male; Middle Aged; ortho-Aminobenzoates; Pain, Postoperative; Postpartum Period; Pregnancy; Randomized Controlled Trials as Topic

The clinical efficacy of tolfenamic acid and mefenamic acid in the treatment of primary dysmenorrhoea was studied in a prospective, controlled, double-blind, cross-over study comprising 73 patients aged 13-39 with an average body weight of 56 kilos. The patients were randomized to receive either tolfenamic acid (200 mg t.i.d.) or mefenamic acid (500 mg t.i.d.) for 3 days, during 3 consecutive menstrual cycles each, in a sequential design A-B or B-A. At the beginning and at the end of each treatment period, 13 dysmenorrhoeic symptoms were evaluated on a visual analogue scale (lower back pain, interference with daily activities, nausea, vomiting, diarrhoea, headache, dizziness, fatigue, sweating, chills, hot flashes, depressant states, and mood swings). The data were analyzed by using two statistical models. The first one, for the 73 patients, by making paired comparisons regardless of treatment sequence. With respect to the initial values, the results showed that both drugs were statistically significant (P < 0.05) in reducing the intensity of the evaluated symptoms. When comparing both treatments, tolfenamic acid showed a significant difference as to interference with daily activities (P < 0.025) and hot flashes (P < 0.005). In the result analysis with the second model, the groups were divided according to the first assigned treatment and paired comparisons were made. It was observed that the group receiving tolfenamic acid in the last sequence reached a higher level of response and statistical significance was demonstrated in 8 of 13 evaluated symptoms.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adolescent; Adult; Anti-Inflammatory Agents, Non-Steroidal; Cross-Over Studies; Double-Blind Method; Drug Tolerance; Dysmenorrhea; Female; Humans; Mefenamic Acid; ortho-Aminobenzoates; Pain; Pain Measurement; Prospective Studies

Prostaglandins (PGs) may be involved in the development of the symptoms of endometriosis. Therefore 18 patients with pelvic endometriosis were treated in placebo controlled double-blind trial with different prostaglandin biosynthesis inhibitors. These drugs were: acetylsalicylic acid (0.5 g x 3) exerting a weak PG-synthetase inhibition, indomethacin (25 mg x 3) inhibiting PG-synthetase, and as a representative of fenamates, tolfenamic acid (200 mg x 3), which both inhibits PG-synthetase and antagonizes PGs at the target level. The therapeutic effect was evaluated using a specific endometriosis score separately during menstruation and in premenstrum. Prostaglandin biosynthesis inhibitors did not alleviate premenstrual complaints better than placebo. During menstruation tolfenamic acid relieved endometriotic symptoms more effectively than placebo while indomethacin and acetylsalicylic acid did not differ from placebo. A drug which inhibit both the synthesis and action of PGs can thus be used in the alleviation of secondary dysmenorrhea due to endometriosis.. The possible role of prostaglandins (PGs) in the biochemistry of endometriosis prompted this placebo-controlled double-blind trial evaluating the effect of PG-inhibitors on symptoms of endometriosis (especially pelvic pain). The 4 drugs used were: 1) placebo, 2) acetylsalicylic acid (ASA), 3) indomethacin, and 4) tolfenamic acid. Each drug was administered orally from Day 20 of the menstrual cycle until end of menstruation for 2 consecutive cycles. During menstruation, tolfenamic acid (P.01) and ASA (P.05) lowered the endometriosis score from the pretreatment level. Tolfenamic acid was more effective than placebo (P.05), whereas ASA and indomethacin did not differ from placebo. Each treatment, including placebo, lowered the endometriosis score (P.05) during the menstrual period, but none of the PG inhibitors was more effective than placebo (P.05). According to patient's subjective judgements, tolfenamic acid alleviated symptoms more effectively than other drugs tested. Pain symptoms occurred less often during tolfenamic acid and ASA than during placebo or indomethacin (P.05). Gastrointestinal side effects were more common with indomethacin and ASA (P.05). Indomethacin treatment raised the incidence of psychic complaints over those with ASA or placebo (P.05). Side effects were fairly evenly distributed among the therapies.

Topics: Aspirin; Double-Blind Method; Dysmenorrhea; Endometriosis; Female; Humans; Indomethacin; ortho-Aminobenzoates; Pelvic Neoplasms; Placebos; Prostaglandin Antagonists