tolfenamic-acid and Migraine-Disorders

Topics: Anti-Inflammatory Agents, Non-Steroidal; Diclofenac; Ergotamine; Humans; Ibuprofen; Indoles; Migraine Disorders; Naproxen; ortho-Aminobenzoates; Oxazolidinones; Piperidines; Pyrrolidines; Salicylates; Sumatriptan; Triazoles; Tryptamines

Topics: Acute Disease; Adult; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Child; Diclofenac; Drug Therapy, Combination; Ergotamine; Humans; Ibuprofen; Indoles; Migraine Disorders; Naproxen; ortho-Aminobenzoates; Oxazolidinones; Piperidines; Pyrrolidines; Salicylates; Serotonin Receptor Agonists; Sumatriptan; Triazoles; Tryptamines

The pharmacokinetics of tolfenamic acid is well described by a two-compartment model with relatively short half-lives (T/2 beta 1-2 hours) and tolfenamic acid is highly protein-bound with small volumes of distribution. It is cleared relatively fast (150-200 ml/min), mainly by hepatic metabolism and the metabolites are renally cleared as glucuronic acid conjugates. The peroral absorption is good and the peroral bioavailability is about 75%, as first pass metabolism accounts for about 20%. Tolfenamic acid shows linear pharmacokinetics and during multiple dosage regimen, i.e. thrice daily, no accumulation beyond the second dose is observed. The bioavailability in dependence of age and disease has been studied and only in the case of severe liver or kidney impairment, a change in dosage regimen seems warranted. The development of different formulations will be outlined, mainly on rectal delivery, on sustained release and rapid release oral formulations, on topical ointment, and on parenteral delivery. The problems with tolfenamic acid in pharmaceutical formulation caused mainly by poor solubility will be discussed. Formulations ready for the market now or very soon are Clotam capsules (tablets). Clotam retard tablets, Clotam suppositories, and Clotam oral suspension, whereas rapid tablets, topical ointments, and parenteral formulations need further development to be ready for marketing in the years to come.

Topics: Absorption; Aging; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Biological Availability; Dosage Forms; Drug Administration Routes; Half-Life; Humans; Liver Cirrhosis; Migraine Disorders; ortho-Aminobenzoates

Migraine is a paroxysmal disorder characterized by recurrent attacks of headache, with or without associated visual and gastrointestinal disturbances. Migraine can be classified in two main groups, common and classic. Theories trying to explain the pathogenesis of a migraine attack may emphasize either the central or peripheral aspects of the disease. The vascular theory may stress the importance of either central or peripheral blood flow or both. Cerebral vasoconstriction in the early phases of the attack is followed by vasodilatation and pain. Biochemical mediators of vascular responses are not exactly known, but platelets and 5-hydroxytryptamine and thromboxane released from them as well as noradrenaline are potent vasoconstrictors, while kinins and prostaglandins can explain the vasodilatory phase of migraine attacks. This review presents evidence for the role of arachidonic acid metabolites, prostaglandins and leukotrienes in migraine. The evidence comes from the measurements of eicosanoids in biological fluids during and after the attack, infusion studies where vasodilatory prostaglandins mimic the migraneous symptoms, and the good effect of non-steroidal anti-inflammatory drugs in the treatment and prophylaxis of migraine attacks. Additional data are based on experimental biochemical studies in which catecholamines and indolamines have been shown to increase the synthesis of vasodilatory prostaglandins. However, the final evidence still awaits its confirmation.

Topics: Humans; Leukotriene Antagonists; Leukotrienes; Migraine Disorders; ortho-Aminobenzoates; Prostaglandin Antagonists; Prostaglandins

The possible role of prostaglandins (PGs) in migraine has been the subject of increasing attention after the rather dramatic experiments done in man by Bergström and coworkers more than 25 years ago (1965). The role of PGs in migraine, however, is still hypothetical and not yet explained. PGs are known to sensitize nociceptors and produce hyperalgesia. PGs are involved in platelet aggregation thereby releasing serotonin. Vasodilatation, oedema and hyperalgesia in migraine have much in common with an inflammatory reaction. Tolfenamic acid (TA) inhibits PG biosynthesis and action and has an anti-aggregatory effect. TA is better than aspirin and as effective as ergotamine in treatment of acute migraine attacks. TA has fewer side effects than ergotamine. TA is as effective as propranolol in prophylactic treatment of migraine. The dose regimen of TA in acute treatment of migraine is 200 mg when the first symptoms of migraine appear. The treatment can be repeated after 2-3 hours if satisfactory effect is not obtained. The dose regimen of TA in prophylactic treatment of migraine is one sustained release tablet of 300 mg or 100 mg 3 times daily. After a treatment period of three months the regimen should be re-evaluated.

Topics: Acute Disease; Humans; Migraine Disorders; ortho-Aminobenzoates; Premedication; Prostaglandin Antagonists

Controlled studies of nonsteroidal antiinflammatory drugs (NSAIDs) for the management of migraine attacks or for the prophylactic long-term treatment of migraine are reviewed herein. A large number of NSAIDs have been tested against a placebo or reference drug, including aspirin, indomethacin, mefenamic acid, tolfenamic acid, flufenamic acid, ibuprofen, flurbiprofen, fenoprofen, naproxen and sodium naproxen, diclofenac and lornoxicam. For the treatment of acute attacks, published studies found that the NSAIDs were significantly more effective than the placebo and at least as effective as the reference drugs. Adverse effects were absent or mild in this indication. Studies of NSAIDs as prophylactic treatment of migraine attacks are less numerous but also point to the value of this approach. However, long-term use of NSAIDs is associated with side-effects, mainly involving the gastrointestinal tract.

Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Diclofenac; Ergotamine; Flufenamic Acid; Flurbiprofen; Humans; Metoclopramide; Migraine Disorders; Naproxen; ortho-Aminobenzoates; Randomized Controlled Trials as Topic

Rizatriptan is an effective and fast acting drug for the acute treatment of migraine. Some nonsteroidal anti-inflammatory drugs (NSAID) have also demonstrated efficacy in treating migraine attacks. There is evidence that the combination of a triptan and a NSAID decreases migraine recurrence in clinical practice. The primary aim of this randomized open label study was to assess the recurrence rates in migraine sufferers acutely treated with rizatriptan (RI) alone vs. rizatriptan plus a COX-2 enzyme inhibitor (rofecoxib, RO) vs. rizatriptan plus a traditional NSAID (tolfenamic acid, TO). We were also interested in comparing the efficacy rates within these three groups.. We assessed 45 patients from a headache clinic in Rio de Janeiro (35 women and 10 men, ages 18 to 65 years, mean 37 years). Patients with IHS migraine were randomized to one out of 3 groups, where they had to treat 6 consecutive moderate or severe attacks in counterbalanced order. In group 1, patients treated the first two attacks with 10 mg RI, the third and fourth attacks with RI + 50 mg RO and the last attacks with RI + 200 mg of TA. In group 2, we began with RI + TA, followed by RI, and RI + RO. Group 3 treated in the following order: RI + RO, RI + TA, RI alone. The presence of headache, nausea and photophobia at 1, 2 and 4 hours, as well as recurrence and side effects were compared.. A total of 33 patients finished the study, treating 184 attacks. The pain-free rates at 1 hour were: RI: 15.5%; RI + RO: 22.6%; RI + TA: 20.3%(NS). Pain-free rates at 2 h were: RI: 37.9%; RI + RO: 62.9%, and RI + TA: 40.6% (p = 0.008 for RI vs. RI + RO; p = 0.007 for RI + RO vs. RI + TA, NS for RI vs RI + TA). At 4 h, pain-free rates were: RI: 69%; RI + RO: 82.3%; RI + TA: 78.1% (NS for all comparisons). The combination of RI + RO was superior to RI and to RI + TA in regard of the absence of nausea and photophobia at 4 hours. Recurrence (after being pain-free at 2 h) was observed in 50% of patients treated with RI, in 15,4% of those treated with RI + RO, and in 7,7% of those treated with RI + TA.. Despite the methodological limitations of this study, the combination of RI and RO revealed a higher response rate at 2 hours. Recurrence was also clearly decreased with both combinations in relation to the use of RI alone. Controlled studies are necessary to provide additional evidence.

Topics: Acute Disease; Adolescent; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Cyclooxygenase Inhibitors; Drug Therapy, Combination; Female; Humans; Lactones; Male; Middle Aged; Migraine Disorders; ortho-Aminobenzoates; Secondary Prevention; Serotonin Receptor Agonists; Sulfones; Treatment Outcome; Triazoles; Tryptamines

The migraine prophylactic effect of tolfenamic acid 300 mg versus pizotifen 1.5 was evaluated in a prospective, randomized, double-blind, parallel group study. 192 patients were included with a frequency of 4-8 moderate to severe migraine attacks monthly, with or without aura, fulfilling the diagnostic criteria for migraine as defined by the International Headache Society. A four-week baseline period without medication was followed by 12 weeks of treatment with tolfenamic acid 300 mg or pizotifen 1.5 mg. In both periods patients were allowed to take escape medication (paracetamol and codeine) if the treatment was inefficient. All the patients had a headache diary before and during treatment. The primary criterion of efficacy was reduction in attack frequency per 4 weeks. Also reduction in intensity or duration of migraine attacks in hours at the end of 12 weeks treatment compared to the baseline period was measured. Both groups exhibited significant reduction in attack frequency (p < 0.001). Tolfenamic acid significantly reduced severity compared to the run-in period (p = 0.009). Patients treated with pizotifen needed more escape medication when compared to the run-in period (p < 0.01). Tolerance, especially weight gain, was a major drawback with pizotifen. Because of its high efficacy, excellent tolerability and low cost, tolfenamic acid is an interesting option for migraine prophylaxis.

Topics: Adolescent; Adult; Aged; Analgesics; Analgesics, Non-Narcotic; Anti-Inflammatory Agents, Non-Steroidal; Chi-Square Distribution; Costs and Cost Analysis; Data Interpretation, Statistical; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine Disorders; ortho-Aminobenzoates; Pizotyline; Prospective Studies; Prostaglandin Antagonists; Serotonin Antagonists; Time Factors

The efficacy and safety of tolfenamic acid and oral sumatriptan in the acute treatment of migraine was studied at five neurological centers in Finland. One hundred forty-one patients experiencing 289 migraine attacks, fulfilling the diagnostic criteria for migraine with or without aura as defined by the International Headache Society, were randomized. For first attacks, 77% of patients receiving tolfenamic acid experienced a reduction of the initial severe or moderate headache to mild or no headache after 2 hours, as compared to 79% in the sumatriptan group and 29% in the placebo group. No significant difference was found between active treatments (P = 0.85, 95% CI [-22%, 18%]), however, both active treatments were significantly better than placebo; P = 0.001, 95% CI (26%, 69%) for tolfenamic acid and P = 0.001, 95% CI (28%, 71%) for sumatriptan. For second attacks, results were similar with 70% of patients receiving tolfenamic acid experiencing relief, as compared to 64% in the sumatriptan group and 39% in the placebo group. No significant differences were observed in accompanying symptoms. Both drugs were well tolerated with the frequency of adverse events; 30% for tolfenamic acid and 41% for sumatriptan, a nonsignificant difference. In this study, tolfenamic acid and oral sumatriptan are comparably effective in the acute treatment of migraine. When comparably effective, factors like individual effect, tolerance, and cost of treatment should be considered when prescribing migraine medication.

Topics: Acute Disease; Adult; Dosage Forms; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine Disorders; ortho-Aminobenzoates; Prostaglandin Antagonists; Serotonin Receptor Agonists; Sumatriptan

320 cases of female migraine after menopause according to the diagnostic criteria were studied by using 1:1 matched analysis. It was found that the additional symptoms increased after menopause. Eighty cases available for follow-up were divided into two groups, on which the treatment tests were done. Each patient in group I took Nilestrioli 2 mg twice a month and Perphenazine 12 mg and Doxepin 75 mg per day, while each patient in group II took Tolfenamic acid 300 mg a day. Two months after treatment, the cure rates were 57.58% in group I and 27.78% in group II. Two monthes after the cessation of therapy, 2 cases had relapses in group I. These data indicate that the decrease of estrin disorder and the additional symptoms after monopause play important roles in the change of migraine physiology, and the corresponding treatment methods are rational.

Topics: Analgesics; Anti-Anxiety Agents; Antipsychotic Agents; Case-Control Studies; Doxepin; Estradiol Congeners; Female; Follow-Up Studies; Humans; Migraine Disorders; ortho-Aminobenzoates; Perphenazine; Postmenopause; Quinestrol

The prophylactic effect of tolfenamic acid and propranolol was studied in a randomized double-blind cross-over trial of 76 patients with migraine with or without aura. After a 4-week run-in period patients were randomly allocated to treatment with either tolfenamic acid 100 mg three times daily or propranolol 40 mg three times daily for 12 weeks. After a placebo wash-out period of 4 weeks the patients got the alternative drug for 12 weeks; 56 patients completed the study. Both drugs significantly reduced migraine attacks as judged from the reduction in the efficacy parameters (migraine hours, migraine days, and migraine intensity) in the treatment periods compared with the run-in period. No statistical significant difference in any efficacy parameter was found between the two drugs (level 2 alpha = 0.05, alpha = 0.10). The adverse effects showed no statistical difference in frequency between the 2 treatments. Twenty patients discontinued the study: 12 patients on propranolol and 8 patients on tolfenamic acid. Side effects were the cause of premature discontinuation of study medicine in 9 patients during propranolol treatment (dizziness, fatigue, and fall in blood pressure) and in 5 patients during tolfenamic acid treatment (gastrointestinal symptoms).

Topics: Adult; Aged; Cross-Over Studies; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine Disorders; ortho-Aminobenzoates; Propranolol; Severity of Illness Index

Controlled studies of nonsteroidal antiinflammatory drugs (NSAIDs) for the management of migraine attacks or for the prophylactic long-term treatment of migraine are reviewed herein. A large number of NSAIDs have been tested against a placebo or reference drug, including aspirin, indomethacin, mefenamic acid, tolfenamic acid, flufenamic acid, ibuprofen, flurbiprofen, fenoprofen, naproxen and sodium naproxen, diclofenac and lornoxicam. For the treatment of acute attacks, published studies found that the NSAIDs were significantly more effective than the placebo and at least as effective as the reference drugs. Adverse effects were absent or mild in this indication. Studies of NSAIDs as prophylactic treatment of migraine attacks are less numerous but also point to the value of this approach. However, long-term use of NSAIDs is associated with side-effects, mainly involving the gastrointestinal tract.

Topics: Acetaminophen; Anti-Inflammatory Agents, Non-Steroidal; Aspirin; Diclofenac; Ergotamine; Flufenamic Acid; Flurbiprofen; Humans; Metoclopramide; Migraine Disorders; Naproxen; ortho-Aminobenzoates; Randomized Controlled Trials as Topic

In a double-blind cross-over study we compared tolfenamic acid with paracetamol in out-patients with common migraine (migraine without aura). Each patient was treated during (at least) 4 attacks with one of the following alternatives: tolfenamic acid 200 mg, tolfenamic acid 400 mg, paracetamol 500 mg or paracetamol 1000 mg in a randomized sequence. The same sequence of treatments was applied to (preferably) 4 more attacks. Dosage was repeated after 2 h if the attack had not abated. Escape medication was allowed after 4 h if the treatment was inefficient. A total of 83 patients were admitted to the study, but 3 dropped out, while 10 completed less than 4 attacks. Seventy completed 4 attacks, and 58 completed all 8. The total number of attacks treated was 545. We found a significant superiority of tolfenamic acid over paracetamol with regard to effect on pain after 2 h (p less than 0.01), patients' global evaluation (p less than 0.001), and use of escape medication (p less than 0.02). The trend was the same for duration of attacks, confinement to bed during attack and nausea, but the results were not statistically significant. There was no significant difference between the smaller and the larger dose of either drug nor between the need for escape medication, although the trend favoured tolfenamic acid. Side effects were few. Tolfenamic acid is evidently valuable in treatment of migraine.

Topics: Acetaminophen; Adult; Aged; Analgesics; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine Disorders; ortho-Aminobenzoates; Random Allocation

To compare the effect of tolfenamic acid and paracetamol in acute migraine, 149 patients participated in a double-blind controlled, multipractice study. 116 patients completed both treatments. The patients were asked to evaluate the two drugs in terms of the following parametres: 1) intensity of headache after three hours: as usual or less, 2) necessity of further medicine after three hours, 3) assessment of test medicine regarding the effect on strength, duration, and other inconveniences connected with the headache, 4) possible side effect connected with test medicine, and how these were experienced. After both forms of treatment, the patients were asked to give an overall judgement of the medicine, which had the best effect. No statistically significant difference was observed between the effect of 400 mg tolfenamic acid and 1 g paracetamol as to the five test parametres when using parametric or non-parametric statistics with a significance level of 5%. However, tolfenamic acid was numerically better than paracetamol with regard to headache after three hours, necessity of further medicine, judgement of attacks, and preference.

Topics: Acetaminophen; Adolescent; Adult; Aged; Analgesics; Clinical Trials as Topic; Double-Blind Method; Humans; Middle Aged; Migraine Disorders; ortho-Aminobenzoates; Random Allocation

In 31 patients with at least 3 migraine attacks per month the prophylactic effect of tolfenamic acid 300 mg/day, propranolol 120 mg/day, and placebo was compared in a randomized double-blind cross-over study. The patients were treated for 12 weeks with each drug, but only the last 11 weeks were used for evaluation. Both tolfenamic acid and propranolol significantly reduced the number of attacks, the total duration of attacks and additional drugs taken when compared with placebo. Tolfenamic acid, but not propranolol, significantly reduced the median intensity of pain and the number of attacks confining the patients to their beds when compared with placebo. Only mild adverse reactions occurred with no significant difference between the drugs. It was concluded that the prophylactic effect of tolfenamic acid 300 mg/day in migraine was at least as good as propranolol 120 mg/day.

Topics: Adolescent; Adult; Aged; Double-Blind Method; Female; Humans; Male; Middle Aged; Migraine Disorders; ortho-Aminobenzoates; Pain; Propranolol; Random Allocation; Time Factors; Work Capacity Evaluation

Tolfenamic acid is an anti-inflammatory analgesic which is used in the treatment of migraine attacks. Because caffeine is used in certain analgesic combinations, its effects on the absorption of tolfenamic acid was studied in a crossover study in migraine patients. Caffeine did not significantly change the absorption of tolfenamic acid during migraine attacks. The extent of absorption following oral administration of tolfenamic acid is decreased during migraine attacks, irrespectively if the volunteers received caffeine or placebo in combination with the drug. The reasons are discussed. It seems obvious that the migraine itself is responsible for the lack of absorption that cannot be counteracted with caffeine. Pain relief within a five-hour testing period was not influenced by concomitant administration of caffeine. It is concluded that tolfenamic acid alone is sufficient in treating migraines.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Caffeine; Drug Therapy, Combination; Female; Humans; Intestinal Absorption; Kinetics; Middle Aged; Migraine Disorders; ortho-Aminobenzoates

Tolfenamic acid is a fenamate which inhibits prostaglandin (PG) biosynthesis and may act as a PG antagonist as well. Caffeine and metoclopramide are used in combination with analgesics and ergotamine in the treatment of migraine attacks, but controlled clinical studies on fixed combinations with analgesics are rare. The effects of orally given tolfenamic acid (200 mg), caffeine (100 mg), metoclopramide (10 mg), tolfenamic acid + caffeine (200 mg + 100 mg), tolfenamic acid + metoclopramide (200 mg + 10 mg) and placebo were studied in 49 migraine patients (3 men, 46 women) in a double-blind randomized cross-over study comprising 482 migraine attacks. The patients were allowed to take either one or two capsules of each preparation for an attack. Additional drugs were allowed after 3 h. Parameters characterizing the effects and side-effects of the drugs were registered. Tolfenamic acid and its combinations were found to be effective in the treatment of acute migraine, but caffeine and metoclopramide alone did not differ from placebo. Combination with metoclopramide was better than tolfenamic acid alone as judged by the smaller dose needed and the intensity of attack. Between tolfenamic acid alone and its caffeine combination there were no statistically significant differences.

Topics: Adult; Analgesics; Caffeine; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Male; Metoclopramide; Middle Aged; Migraine Disorders; ortho-Aminobenzoates

Tolfenamic acid is a potent inhibitor of prostaglandin biosynthesis, which has been proved effective in the treatment of acute migraine attacks. The usefulness of caffeine, metoclopramide and pyridoxine as adjuncts to tolfenamic acid was tested in acute migraine attacks in ten patients. A combination of tolfenamic acid (200 mg) with either caffeine (100 mg), metoclopramide (10 mg) or pyridoxine (300 mg) was given twice to each patient in random order. Thus 60 attacks were treated. The tolfenamic acid-caffeine combination proved the most effective as judged by duration and intensity of attacks, working ability, vigilance, and overall evaluation of the drugs by the patients. Metoclopramide was somewhat better than pyridoxine as an additive.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Caffeine; Drug Combinations; Female; Humans; Metoclopramide; Middle Aged; Migraine Disorders; ortho-Aminobenzoates; Prostaglandin Antagonists; Pyridoxine; Random Allocation

In 31 patients with more than 2 migraine attacks per month the prophylactic effect of tolfenamic acid and placebo was compared in a double-blind crossover study. The patients were treated for 10 weeks with each preparation, with a 2-week break in treatment between the preparations. Tolfenamic acid had a significantly better effect in relation to the preferences of the patients, the number of attacks, the total duration of the attacks, the degree of severity, the number of episodes of vomiting, and work capacity. Mild symptoms and complaints occurred in both treatment periods, but they were qualitatively and quantitatively similar. Laboratory investigations of blood, liver function, and kidney function showed no changes whilst on treatment with either preparation. It is therefore concluded that tolfenamic acid can be used in the prophylactic treatment of migraine.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Female; Humans; Male; Middle Aged; Migraine Disorders; ortho-Aminobenzoates; Placebos

Topics: Aspirin; Clinical Trials as Topic; Double-Blind Method; Ergotamine; Gastric Emptying; Humans; Migraine Disorders; ortho-Aminobenzoates; Prostaglandin Antagonists

Tolfenamic acid (a potent inhibitor of prostaglandin biosynthesis), ergotamine tartrate, acetylsalicylic acid, or placebo was administered during 160 migraine attacks in twenty women in a double-blind, cross-over study. Tolfenamic acid and ergotamine were equally effective in reducing the duration and intensity of attacks, but side-effects, especially nausea, were less common with tolfenamic acid. This probably accounted for the patients' preference for tolfenamic acid. The effectiveness of tolfenamic acid in acute migraine attacks accords with the postulated role of prostaglandins in migraine.

Topics: Adolescent; Adult; Aspirin; Chemical Phenomena; Chemistry; Clinical Trials as Topic; Consumer Behavior; Double-Blind Method; Drug Evaluation; Ergotamine; Female; Humans; Middle Aged; Migraine Disorders; Nausea; ortho-Aminobenzoates; Placebos; Prostaglandin Antagonists; Vasoconstrictor Agents

Triptans are effective drugs for the acute treatment of migraine. However, 30-40% of the patients commonly present recurrence before 24 hours therefore requiring another dose. Nonsteroidal anti-inflammatory drugs (NSAID) such as tolfenamic acid and naproxen sodium combined with sumatriptan have demonstrated efficacy in reducing recurrence observed with the single use of this drug. Steroids also have been suggested to treat refractory migraine and status migranosus. The aim of this study was to evaluate whether patients presenting frequent recurrence with the combination triptan plus NSAID, would decrease it with the association of dexamethasone.. Twenty three patients, 17 women and 6 men with migraine according to IHS criteria were prospectively studied. All patients presented frequent recurrence (> or= 60%, mean recurrence rate 74,8%) with the single use of sumatritpan 100 mg or zolmitriptan 2,5 mg or rizatriptan 10mg in at least 5 consecutive attacks, and didn't present a reduction of the recurrence rate superior than 20% with the combination of tolfenamic acid 200 mg or rofecoxib 25 mg in at least 5 other consecutive attacks (mean recurrence rate 60%). The patients had to treat 6 consecutive moderate or severe migraine attacks with their usual combination plus 4 mg of dexamathasone with a maximum of twice a week, and fill out a diary reporting headache parameters.. Twenty patients, 16 women and 4 men completed the study. Of those who completed the study, 11 took rizatriptan plus rofecoxib, 4 rizatriptan plus tolfenamic acid, 3 zolmitriptan plus rofecoxib, 1 zolmitriptan plus tolfenamic acid and 1 patient took sumatriptan plus tolfenamic acid, having the 20 patients taken as a third medication, a single tablet of 4 mg of dexamethasone. All patients took oral formulations and none presented vomiting after that. Among all 20 patients, one female and one male patient presented recurrence in 3 out of the 6 attacks (50%) while the remaining 18 patients revealed recurrence in 1 or 2 treated attacks (mean 23,4%) (p<0,001).. We concluded that the judicious use of oral dexamethasone might be useful for a limited population of migraine patients still presenting recurrence with the combination of a triptan and a NSAID. Case-control studies and studies with a randomized double-blind design are necessary to confirm these observations.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Dexamethasone; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Migraine Disorders; Naproxen; ortho-Aminobenzoates; Prospective Studies; Secondary Prevention; Serotonin Receptor Agonists; Sumatriptan

Although sumatriptan is an effective drug for the treatment of acute migraine attacks, recurrence has been cited as an important limitation for its use. Tolfenamic acid is also effective in the acute treatment of migraine attacks. We studied the recurrence rate of migraine attacks with the use of sumatriptan plus tolfenamic acid among patients who presented frequent recurrence with sumatriptan. Fifty migraineurs were retrospectively studied, all having treated at least 10 attacks with 100 mg P.O.; sumatriptan was effective in at least eight of them. The patients also presented recurrence in less than 24 h in at least five of the treated attacks. We then used sumatriptan 100 mg plus tolfenamic acid 200 mg P.O. during the first 60 min of the attack; 240 attacks were treated and there was recurrence in 57 (23.8%). With sumatriptan alone, 5 out of 8 attacks (62.5%) presented recurrence. We therefore conclude that the combination sumatritpan plus tolfenamic acid is effective in reducing the recurrence rate from 5 of 8 (62.5%) to 1.19 of 5 (23.8%). Further prospective studies with a double-blind design and a higher number of treated attacks are necessary to confirm these initial observations.

Topics: Adult; Analgesics; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Migraine Disorders; ortho-Aminobenzoates; Recurrence; Sumatriptan

Topics: Aged; Female; Humans; Male; Middle Aged; Migraine Disorders; ortho-Aminobenzoates; Prostaglandin Antagonists; Pulmonary Fibrosis; Radiography

The relative importance of neural and humoral components in the pathogenesis of migraine has yet to be determined, but there is circumstantial evidence that implicates noradrenaline and serotonin as neural or humoral mediators in the recurrent headache, neurological and gastrointestinal symptoms that comprise the migraine syndrome. The treatment of migraine includes the avoidance of precipitating factors when possible, psychological counselling and relaxation training. Pharmacotherapy can be considered rationally in terms of agents acting on receptors that may possibly play a part in the mechanism of migraine.

Topics: Adrenergic alpha-Agonists; Adrenergic beta-Agonists; Calcium Channel Blockers; Cerebrovascular Circulation; Ergotamine; Ergotamines; Female; Humans; Menstruation; Methysergide; Migraine Disorders; ortho-Aminobenzoates; Pizotyline; Pregnancy; Propranolol

Topics: Cerebrovascular Circulation; Humans; Leukotriene B4; Lipoxygenase; Migraine Disorders; ortho-Aminobenzoates; Prostaglandin Antagonists; Prostaglandins; SRS-A; Thromboxanes; Vasodilation

The effect of acute migraine attack and rectally given metoclopramide on the absorption of orally given tolfenamic acid (300 mg) was investigated in seven female patients in a crossover study consisting of four phases, two without migraine and two during migraine. Metoclopramide hydrochloride (20 mg) or placebo was given double-blind. Migraine attacks delayed the absorption of tolfenamic acid. Serum concentrations of tolfenamic acid 1.5 and 2 h after drug administration remained smaller, the peak serum concentration (tmax) occurred later and the area under the serum concentration-time curve between zero and 2 h (AUC0-2 h) remained decreased during migraine. Metoclopramide pretreatment in migraine attacks increased the serum concentration of tolfenamic acid at 1.5 h, but its peak concentration, time to peak concentration and the AUC0-5 h remained unchanged as compared with the values obtained with tolfenamic acid alone. Between the absorption of tolfenamic acid without migraine and after metoclopramide pretreatment during migraine no significant differences existed. When the patients were studied without migraine the serum concentrations of tolfenamic acid 45 min and 60 min after its administration were higher after metoclopramide than after placebo pretreatment. During migraine attacks the serum concentrations and the AUC0-5.5 h of metoclopramide were slightly lowered. The impairment of drug absorption by migraine was not related to the duration or severity of the attack. The observed changes in drug absorption during migraine attacks are obviously due to the delay in gastric emptying. Rectally administered metoclopramide accelerates the absorption of orally given tolfenamic acid.

Topics: Absorption; Administration, Oral; Adult; Digestive System; Double-Blind Method; Drug Therapy, Combination; Female; Humans; Kinetics; Metoclopramide; Migraine Disorders; ortho-Aminobenzoates; Random Allocation

Topics: Adult; Ergotamine; Female; Headache; Humans; Male; Middle Aged; Migraine Disorders; ortho-Aminobenzoates; Substance Withdrawal Syndrome; Substance-Related Disorders