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Treatment of juvenile migraine with subcutaneous sumatriptan.

An open, prospective study was undertaken to assess the efficacy and safety of subcutaneous sumatriptan in 17 children, ages 6 to 16 years, with severe, recurrent migraine. A 6-mg dose was used in 15 patients and relieved headache within 1 hour in six and by 2 hours in five others. Two smaller children received a 3-mg dose and both were headache-free within 2 hours. Most also reported marked improvement in associated symptoms such as nausea and photophobia. Four subjects had no clinical improvement after a 6-mg dose. Side effects, such as neck pressure, were brief and mild. These findings suggest that subcutaneous sumatriptan can be both effective and safe as an abortive agent in juvenile migraine, but the appropriate dose in smaller children will need further investigation.

Adolescent↗

Acetaminophen, aspirin, and caffeine versus sumatriptan succinate in the early treatment of migraine: results from the ASSET trial.

OBJECTIVE: To address the need for a rigorous, direct comparison of prescription and over-the-counter (OTC) migraine drugs and to expand the database on early treatment of migraine. BACKGROUND: Most people who experience migraine use OTC medications to treat their symptoms, but no head-to-head clinical trials comparing these agents with prescription migraine therapies have been published. In addition, even though most migraineurs treat early in the attack, few studies have been conducted to reflect this treatment pattern. METHODS: We compared a combination of nonprescription migraine medication (acetaminophen 500 mg, aspirin 500 mg, and caffeine 130 mg) with a prescription migraine product (50 mg sumatriptan) in a randomized, controlled clinical trial in which subjects treated at the first sign of a migraine attack. Subjects who reported vomiting during more than 20% of migraine episodes or who required bedrest during more than 50% of migraine episodes were excluded from the study. Of the 188 subjects randomized, 171 took study medication and were included in the analysis. CONCLUSION: The combination of acetaminophen, aspirin, and caffeine was significantly more effective (P > .05) than sumatriptan in the early treatment of migraine, as shown by superiority in summed pain intensity difference, pain relief, pain intensity difference, response, sustained response, relief of associated symptoms, use of rescue medication, disability relief, and global assessments of effectiveness. An additional, larger clinical trial is needed to confirm these results.

Acetaminophen↗

Co-administration of fluoxetine and sumatriptan: the Canadian experience.

Major depression and migraine are commonly comorbid. Therefore, there is considerable opportunity for serotonin reuptake inhibitors, which are commonly prescribed for the treatment of depression, to be used at the same time as sumatriptan, an anti-migraine treatment. As both of these drugs increase serotonin transmission, the potential for drug interaction is considerable. Adverse event reports were obtained from the post-marketing surveillance of fluoxetine in Canada. Of 22 adverse event reports obtained six showed varying degrees of evidence of a drug interaction between fluoxetine and sumatriptan, suggesting that this combination is not entirely free of side-effects and should be used with caution when indicated.

Canada↗

The clinical pharmacology, pharmacokinetics and metabolism of sumatriptan.

Clinical pharmacology studies were undertaken in young healthy volunteers, in a small number of elderly subjects and in migraine subjects during and between attacks. Absorption after subcutaneous and oral administration was rapid. Bioavailability was nearly 100% after subcutaneous administration and averaged 14% after oral administration. Elimination was predominantly by metabolism to a non-active indoleacetic acid analogue. The plasma half-lives of sumatriptan and the metabolite were about 2 h. Pharmacokinetic and pharmacodynamic variables were similar in all groups studied and were not altered by the presence of food, alcohol, dihydroergotamine or prophylactic migraine treatments. Sumatriptan produced a number of minor adverse events, but had no clinically significant effect on routine haematological or biochemical investigations using the intravenous, subcutaneous or oral routes. Transient rises in blood pressure were observed which were no greater than those that would be anticipated during moderate exercise. The physician-administered subcutaneous injection resulted in transient stinging at the site of injection in many subjects; administration using the auto-injector was better tolerated.

Aged↗

Methodology of clinical trials of sumatriptan in migraine and cluster headache.

The clinical development of sumatriptan has involved large international multicentre trials. To allow comparison of results obtained in a variety of clinical settings, great emphasis was placed on the use of consistent methodology across the programme. This applied to selection of patients, trial design, symptom evaluation and statistical analysis. Patients were selected for the major trials if they fulfilled the International Headache Society's diagnostic criteria for migraine or cluster headache. Relief of the headache was used as the main efficacy measure and this was assessed using standardized self-rating scales. All major controlled trials in migraine employed a parallel group design to avoid carryover effects and to ensure blinding was not compromised; however, because of the rarity of cluster headache, a crossover trial was performed in this indication. Appropriate statistical analyses were then performed on the data. The rationale for the methodology adopted is discussed. Strict adherence to these principles has allowed us to compare the results of sumatriptan treatment across a wide range of countries and treatment settings, and a selection of different administration routes.

Cluster Headache↗

The clinical profile of sumatriptan: safety and tolerability.

The safety and tolerability of sumatriptan have been extensively studied. The majority of adverse events (defined as any medical event irrespective of possible causal relationship to treatment) were mild to moderate in intensity, transient and resolved spontaneously. In short-term studies, the most frequently reported adverse events were nausea, vomiting, dizziness, vertigo, malaise, fatigue, injection-site reactions, heaviness, pressure, feelings of warmth and headache. The adverse event profile was unchanged during long-term open treatment and was unaffected by frequency of treatment with sumatriptan. In 3-5% of patients, the symptoms of pressure and warmth were experienced in the chest, but extensive investigations, including ECG monitoring, have indicated that these symptoms are not normally associated with cardiac dysfunction.

Administration, Oral↗

Zolmitriptan: differences from sumatriptan.

Zolmitriptan is a potent 5-HT(1B/1D) agonist whose targets include the peripheral and central components of the trigeminovascular system. It is generally well-tolerated and has dose-dependent efficacy in the treatment of migraine. The 2.5 mg dose is felt to provide the best balance between efficacy and adverse events. In a direct comparative study, the 2 h headache response rate for zolmitriptan 2.5 mg was statistically superior to sumatriptan 25 and 50 mg, although at 3.3% not clinically significant. Two comparative studies have found no difference in adverse event frequency between zolmitriptan and sumatriptan.

Cluster Headache↗

Thermoreversible-mucoadhesive gel for nasal delivery of sumatriptan.

The purpose of the present study was to develop intranasal delivery systems of sumatriptan using thermoreversible polymer Pluronic F127 (PF127) and mucoadhesive polymer Carbopol 934P (C934P). Formulations were modulated so as to have gelation temperature below 34 degrees C to ensure gelation at physiological temperature after intranasal administration. Gelation temperature was determined by physical appearance as well as by rheological measurement. The gelation temperatures of the formulations decreased by addition of increasing concentrations of Carbopol (ie, from 29 degrees C for 18% PF127 to 23.9 degrees C for 18% PF127, 0.5% Carbopol). The mucoadhesive force in terms of detachment stress, determined using sheep nasal mucosal membrane, increased with increasing concentration of Carbopol. The results of in vitro drug permeation studies across sheep nasal mucosa indicate that effective permeation coefficient could be significantly increased by using in situ gelling formulation with Carbopol concentration 0.3% or greater. Finally, histopathological examination did not detect any damage during in vitro permeation studies. In conclusion, the PF127 gel formulation of sumatriptan with in situ gelling and mucoadhesive properties with increased permeation rate is promising for prolonging nasal residence time and thereby nasal absorption.

Adhesives↗

Chronopharmacokinetics of sumatriptan in healthy human subjects.

Rhythms in the onset and symptoms of several diseases are well established. Migraine is a disorder that exhibits periodicity in its symptoms and so chronotherapy may be beneficial in treating the problem. Designing a chronotherapeutic schedule requires chronopharmacokinetic and chronopharmacodynamic data of the drugs prescribed. We have studied the chronopharmacokinetics of sumatriptan, a drug of choice in migraine treatment. Twelve healthy male volunteers were treated with 100 mg sumatriptan orally at 0700, 1300, 1900 and 0100 h in a randomized 4 x 4 Latin square crossover design, with a wash-out period of one week. Serum samples were analysed by high performance liquid chromatography with an electrochemical detector. Pharmacokinetic parameters were calculated using noncompartmental methods. The pharmacokinetic parameters were analysed using analysis of variance and a two-tailed paired t-test at the probability of 95%. The mean peak serum concentration following the 0700 h administration (Cmax; 59.09 +/- 10.53 ng mL(-1)) was significantly (P < 0.05; n = 12) higher than after the 1900 h administration (Cmax 41.88 +/- 12.21 ngmL(-1)). The mean area under the serum concentration-time curve from time zero to the last time-point (AUCo-t), the area under the serum concentration-time curve from zero to infinity (AUC 0-infinity), and the area under the first moment curve (AUMC) were significantly (P < 0.05; n = 12) higher following the 0700 and 0100 h administrations than after the 1900 h administration. Following administration at 0700 h, the mean oral clearance (CLs/f; 781 +/- 186 mL h(- 1) kg(-1)) and the apparent volume of distribution (Vd/f; 2,379 +/- 684) were significantly lower (P < 0.05; n = 12) than after the 1900 h administration (CLs/f 1,208 +/- 458 mL h(-1) kg(-1), Vd/f 4,655 +/- 2,096 mL kg(-1)). The mean Vd/f value was again lower after the 1300h administration than after the 1900 h administration (2,763 +/- 1,417 vs 4,655 +/- 2,096 mL kg(-1); P < 0.05; n = 12). The variations may be due to the time dependent changes in the extent of absorption and/or circadian variations in hepatic blood flow.

Adult↗

Oral sumatriptan-associated transmural myocardial infarction.

A 43-year-old healthy man developed transmural myocardial infarction shortly after ingesting sumatriptan succinate 100 mg for migraine. Coronary arteriography revealed only minor irregularities in the left anterior descending artery. Oral sumatriptan should be used with caution in any patient with vascular risk factors and avoided in those with coronary artery disease or vasospasm.

Administration, Oral↗

A pilot study of oral sumatriptan as intermittent prophylaxis of menstruation-related migraine.

Headaches associated with menstruation are often resistant to abortive and preventative medications. We performed an open-label study in 20 female migraineurs, employing oral sumatriptan perimenstrually as short-term prophylaxis of menstrual migraine. In 126 sumatriptan-treated cycles, headache was absent in 52.4% and reduced in severity by 50% or greater in 42%. Breakthrough headaches were rare and significantly reduced in severity compared with baseline headaches.

Adult↗

Pregnancy outcome following first trimester exposure to sumatriptan.

We prospectively compared pregnancy outcome after exposure to sumatriptan with that of disease-matched controls and nonteratogen controls. There were no differences in the rates of live births, spontaneous abortions, therapeutic abortions, or major birth defects among the three groups. This first prospective report suggests that the use of sumatriptan during organogenesis is not associated with an apparent increased risk of major birth defects.

Adult↗

Sumatriptan: a decade of use and experience in the treatment of migraine.

The migraine-specific triptans have revolutionized the treatment of migraine and are usually the drugs of choice to treat a migraine attack in progress. Sumatriptan (Imitrex) has been available for the longest time within the class, is most flexible in form and has been given successfully to the most number of patients. It is useful for the full range of attacks experienced by a migraine suffer. The aim of this review is to provide an overview of the first 10 years of the use of sumatriptan.

Clinical Trials as Topic↗

Sumatriptan-associated myocardial infarction: report of case with attention to potential risk factors.

Vascular headaches are a relatively common phenomenon. Increasing numbers of patients with headache are being considered for treatment with the selective serotonin-receptor agonist sumatriptan succinate because of its potential for pronounced therapeutic efficacy in selected patients. Sumatriptan-associated myocardial infarction occurred in a 50-year-old woman with a history of migraine headaches. Cardiac risk factors that must be considered in all patients with migraine before initiation of therapy include concomitant ergotamine use, postmenopausal state, male gender older than 40 years, family history of heart disease, cigarette smoking, hypertension, diabetes mellitus, as reviewed in this report.

Female↗

Effect of sumatriptan on health care resource use among patients with migraine.

Previous investigations examining health care resource utilization in patient populations have shown patients with migraine to consume significantly higher health care resources compared with individuals without migraine. The purpose of this study was to compare health care resource and narcotic use in migraineurs prescribed sumatriptan (oral, subcutaneous, or nasal) with those not prescribed sumatriptan.

Adult↗

Upregulated expression of peripheral serotonergic receptors in migraine and cluster headache by sumatriptan.

The double-label flow cytometric analysis of peripheral serotonergic pathways of migraine and cluster headache on a monocyte model has been used to evaluate the activity of drugs with a selective activity on central vascular 5-HT1D receptors, such as sumatriptan, ergotamine and ondansetron. The results indicated that sumatriptan and ergotamine progressively increase the peripheral expression of 5-HT (5-hydroxytryptamine, serotonin). The increase obtained in migraine after ergotamine is more evident than that obtained in cases of cluster headache. Ondansetron produced a moderate increase in serotonergic expression only in cluster headache. The events that occur at intracranic neural and vascular level may cause the described changes of 5-HT expression on the monocyte model as an indirect, reflective, peripheral registration of central serotonergic variations during headache attack as well as during the drug-sustained recovery phase.

Adult↗

Differential expression of sumatriptan-sensitive 5-hydroxytryptamine receptors in human trigeminal ganglia and cerebral blood vessels.

The efficacy of sumatriptan in migraine relief has been attributed to its interaction with 5-hydroxytryptamine1D (5-HT1D) receptors in cerebral blood vessels and/or on nerve endings of the trigeminovascular system in the dura mater. Using the high sensitivity of polymerase chain reaction (PCR) amplification, we investigated the expression of the sumatriptan-sensitive 5-HT receptors, namely, the 5-HT1D alpha, 5-HT1D beta, and 5-HT1F subtypes in human trigeminal ganglia (10 experiments) and cerebral blood vessels (seven experiments) obtained postmortem. Messages for the 5-HT1D alpha and 5-HT1D beta receptors were expressed in all except one of the 10 trigeminal ganglia studied. Expression of the 5-HT1F receptor was detected by gel electrophoresis of the PCR products in six ganglia and by Southern blot hybridization in two additional cases. In human brain vessels, message for the 5-HT1D beta receptor was present in all samples, whereas specific PCR products corresponding to the 5-HT1D alpha receptor could hardly be detected in only two preparations. PCR products indicative of the 5-HT1F receptor message were detected by gel electrophoresis in three brain vessel preparations and confirmed in the other four by Southern blot hybridization. Restriction mapping and sequence analysis of all PCR products identified the expected human 5-HT receptor DNA sequences. The data confirm that the 5-HT1D beta receptor is the dominant species in human cerebral blood vessels and further show that this receptor and the 5-HT1F are expressed in both neural and vascular tissues. In contrast, the data point to a preferential expression of 5-HT1D alpha receptors in neural versus vascular tissues and strongly reemphasize the need for selective 5-HT1D alpha agonists in the identification of the target tissue(s) for antimigraine drugs. Moreover, the data stress the importance to better understand the role of 5-HT1F receptors in cerebrovascular functions and dural inflammation and further raise interest regarding their possible involvement in migraine therapy.

Adult↗

-The evaluation of the effectiveness and tolerance of sumatriptan in abortive treatment of migraine attacks (open multicenter trial).

The authors review data on sumatriptan obtained in the results of their own studies performed on 78 patients in 10 Polish neurological centres. In all 154 migraine attacks were treated with 6 mg of subcutaneous sumatriptan. Significant decrease of pain intensity was achieved in 30% of cases after 15 min and 60%--after 30 min. According to the patient's own opinion, 62% of them evaluated the drug as very efficient, 23% of patients--as efficient. Adverse effects were reported by 11 patients (15%), but they were mild and transient. Headache recurred in 16% of patients.

Adult↗