topiramate and Vomiting

Although oral topiramate (TPM) products are widely prescribed for migraines and epilepsy, injectable TPM is not available for human use. We have developed a solubilized TPM formulation using a cyclodextrin matrix, Captisol with the long-term goal of evaluating its safety and efficacy in neonatal seizures. This study in healthy adult volunteers was performed as required by the U.S. Food and Drug Administration (FDA) to demonstrate the pharmacokinetics and safety prior to initiation of studies involving children. This study allowed investigation of absolute bioavailability, absolute clearance, and distribution volume of TPM, information that could not be obtained without using an intravenous TPM formulation.. This study was an open-label, two-way crossover of oral and intravenous TPM in 12 healthy adult volunteers. Initially two subjects received 50 mg, intravenously and orally. Following evidence of safety in the first two subjects, 10 individuals received 100 mg doses of intravenous and oral TPM randomly sequenced 2 weeks apart. Blood samples were taken just prior to drug administration and at intervals up to 120 h afterwards. TPM was measured using a validated liquid chromatography-mass spectrometry method. Concentration-time data were analyzed using a noncompartmental approach with WinNonlin 5.2.. All subjects completed the study. The mean (±standard deviation) absolute oral bioavailability was 109% (±10.8%). For intravenous and oral TPM the mean distribution volumes were 1.06 L/kg (±0.29) and 0.94 L/kg (±0.24). Clearances were 1.33 L/h (±0.26) and 1.22 L/h (±0.26). The half-life values were 42.3 h (±6.2) and 41.2 h (±7.5). No changes in heart rate, blood pressure, electrocardiography, or infusion site reactions were observed. Mild central nervous system cognitive adverse events and ataxia occurred between dosing and 2 h post dose with both intravenous and oral administration. With intravenous TPM, these adverse effects occurred as early as during the 15-min intravenous infusion.. In healthy adults, oral TPM is bioequivalent to intravenous TPM, and infusion of 50-100 mg over 15 min is safe. Neurologic effects occurred during the infusion, demonstrating that TPM rapidly diffuses into the brain, which supports its evaluation for neonatal seizures. Results from this pilot study will inform the design of subsequent studies in children and newborns, including controlled clinical trials intended to assess the efficacy and safety of intravenous TPM for neonatal seizures. In addition, our results provide support for the further development of intravenous TPM as bridge therapy for older children and adults in whom oral TPM therapy is interrupted.

Topics: Administration, Oral; Adult; Aged; Anticonvulsants; Blood Pressure; Cross-Over Studies; Female; Fructose; Heart Rate; Humans; Injections, Intravenous; Male; Middle Aged; Nausea; Paresthesia; Topiramate; Vomiting

To define yet more clearly the utility of topiramate in the treatment of chronic migraine, we evaluated prespecified secondary endpoints from a recent randomized, double-blind, placebo-controlled, multicenter clinical trial.. We previously reported that topiramate 100 mg per day produced a statistically significant reduction in mean monthly migraine/migrainous and migraine headache days compared with placebo treatment and that it was safe and generally well tolerated.. Variables analyzed included between-treatment group differences in percent responders, change in the mean monthly rate of total headache days and headache-free days, change in average and worst daily headache severity, change in the mean monthly use of acute headache medications, and absolute change and percent change in a headache index. Additional analyses included evaluation of changes in: the associated symptoms of photophobia, phonophobia, and nausea; Migraine-Specific Quality of Life Questionnaire scores; Migraine Disability Assessment Scale scores; and Physician's and Subjects Global Impression of Change.. The intent-to-treat population consisted of 306 patients (topiramate, n = 153; placebo, n = 153). Categorical responder rates of reductions in mean monthly migraine/migrainous days for topiramate- vs placebo-treated subjects were as follows: for > or =25% reduction: 68.6% vs 51.6% (P = .005); > or =50%: 37.3% vs 28.8% (P = .093); and > or =75%: 15.0% vs 9.2% (P = .061). The decrease in mean monthly total headache days and headache-free days for topiramate vs placebo treatment was 5.8 vs 4.7 days (P = .067). Compared with placebo, topiramate treatment resulted in statistically significant mean improvements in the Role Restrictive (P = .028) and Emotional Function (P = .036) domains of the Migraine-Specific Quality of Life Questionnaire, in the worst daily severity of migraine (P = .016), severity of photophobia (P = .032), frequency of vomiting (P = .018), photophobia (P = .038), phonophobia (P = .010), unilateral pain (P = .015), pulsatile pain (P = .023), and pain worsened because of physical activity (P = .047). In addition, there were trends observed (favoring topiramate) in average daily severity of migraine (P = .077), acute headache medication use (P = .127), severity of nausea (P = .098), frequency of nausea (P = .166), the Role Preventive domain of the Migraine-Specific Quality of Life Questionnaire (P = .061), and severity of phonophobia (P = .062).. In addition to significantly reducing mean monthly migraine/migrainous and migraine headache days, treatment of chronic migraine with topiramate was effective with regard to several traditionally important and clinically relevant secondary outcomes in migraine prevention trials. Treatment with topiramate was well tolerated and not associated with serious adverse events.

Topics: Analgesics; Anticonvulsants; Disability Evaluation; Double-Blind Method; Fructose; Humans; Migraine Disorders; Outcome Assessment, Health Care; Photophobia; Placebos; Quality of Life; Severity of Illness Index; Surveys and Questionnaires; Time Factors; Topiramate; Treatment Outcome; Vomiting

Practice guidelines recommend topiramate as second-line treatment for the prevention of moderate-severe cyclic vomiting syndrome (CVS) in adults. However, data are limited to small studies in children.. To characterise the response to topiramate as prophylactic therapy in adults with CVS.. We conducted a retrospective review of patients with CVS. Clinical characteristics, number of CVS episodes, emergency department (ED) visits, and hospitalisations the year before and after initiating topiramate were recorded. Response was defined as a global improvement in symptoms or >50% reduction in the number of CVS episodes, ED visits or hospitalisations.. Sixty-five percent (88/136) of patients responded to topiramate in an intent-to-treat analysis. There was a significant decrease in the annual number of CVS episodes (18.1 vs 6.2, P < 0.0001), CVS-related ED visits (4.3 vs 1.6, P = 0.0029), and CVS-related hospitalisations (2.0 vs 1.0, P = 0.035). Logistic regression revealed that higher doses of topiramate, longer use of topiramate (≥12 months) and topiramate as monotherapy were associated with a response to treatment. Anxiety was associated with non-response to topiramate. Fifty-five percent of patients experienced side effects, and 32% discontinued the medication as a result. The most common side effects were cognitive impairment (13%), fatigue (11%) and paresthesia (10%). This represented a refractory group with topiramate being initiated in patients (92%) who had failed treatment with tricyclic antidepressants (TCAs).. Topiramate may be an effective second-line prophylaxis for patients with moderate-severe CVS, but its use is limited by side effects. Efforts to develop better-tolerated therapies for CVS are warranted.

Topics: Adult; Child; Hospitalization; Humans; Retrospective Studies; Topiramate; Vomiting

Topics: Anticonvulsants; Humans; Topiramate; Vomiting

Topics: Humans; Topiramate; Vomiting

Cyclic vomiting syndrome is a disorder characterized by recurrent attacks of vomiting and intervals of normal health between vomiting episodes averaging 2-4 weeks. It has been described by a variety of names such as abdominal migraine, abdominal epilepsy, and periodic syndrome but now has been classified in the subgroup of childhood periodic syndromes that are commonly precursors of migraine. Topiramate is an antiepileptic drug used both in the treatment of epilepsy and in migraine prophylaxis. This report presents a child with cyclic vomiting syndrome with generalized epileptiform discharges who responded to topiramate therapy. The common features of epilepsy, migraine, and cyclic vomiting syndrome are discussed.

Topics: Anticonvulsants; Brain; Child; Electroencephalography; Female; Fructose; Humans; Periodicity; Syndrome; Topiramate; Vomiting

Subacute sclerosing panencephalitis can show variations in clinical course, and some ophthalmologic abnormalities can be seen as cortical blindness and optic atrophy. A 4-year-old girl was referred to our hospital with a complaint of diplopia, vomiting, and ataxia. On physical examination, she was found to have stage IV papilledema with retinal hemorrhage. She was diagnosed as having idiopathic intracranial high pressure until magnetic resonance imaging demonstrated T2-weighted hyperintense lesions. After observation of head drop attacks and detection of elevated antimeasles antibodies in cerebrospinal fluid, the diagnosis of subacute sclerosing panencephalitis was established, and isoprinosine and carbamazepine were started for treatment. However, because carbamazepine failed to control the head drop attacks, topiramate was also included, and the attacks were kept under control with topiramate. The case presented in this article is a good example of subacute sclerosing panencephalitis in which, at early stages, some of the signs and symptoms can lead to an erroneous diagnosis. In addition, we have demonstrated that topiramate might be a good choice for treatment for the persistent myoclonus seen in this type of patient.

Topics: Anticonvulsants; Brain; Carbamazepine; Child, Preschool; Diplopia; Female; Fructose; Humans; Intracranial Pressure; Magnetic Resonance Imaging; Papilledema; Seizures; Subacute Sclerosing Panencephalitis; Topiramate; Vomiting

Topics: Adult; Anticonvulsants; Epilepsy; Fructose; Humans; Intellectual Disability; Male; Topiramate; Vomiting