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Topamax
Topamax is indicated as adjunctive therapy for adults and pediatric patients ages 2-16 years with partial onset seizures or primary generalized tonic-clonic seizures and in patients 2 years of age and older with seizures associated with lennox-gastaut syndrome.
Newer drugs which are also prescribed for epilepsy can include felbamate felbatol gabapentin neurontin lamotrigine lamictal levetiracetam keppra ; , oxcarbazepine trileptal tiagabine gabitril topiramate topamax ; and zonisamide zonagran.
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NDA 20-505 S-010, S-017, S-019 NDA 20-844 S-006, S-014, S-016 Approved Labeling Text dated 12 16 03 DRUG ABUSE AND DEPENDENCE The abuse and dependence potential of TOPAMAX has not been evaluated in human studies. OVERDOSAGE Overdoses of TOPAMAX have been reported. Signs and symptoms included convulsions, drowsiness, speech disturbance, blurred vision, diplopia, mentation impaired, lethargy, abnormal coordination, stupor, hypotension, abdominal pain, agitation, dizziness and depression. The clinical consequences were not severe in most cases, but deaths have been reported after poly-drug overdoses involving TOPAMAX. Topiramate overdose has resulted in severe metabolic acidosis see WARNINGS ; . A patient who ingested a dose between 96 and 110 g topiramate was admitted to hospital with coma lasting 20-24 hours followed by full recovery after 3 to 4 days. In acute TOPAMAX overdose, if the ingestion is recent, the stomach should be emptied immediately by lavage or by induction of emesis. Activated charcoal has been shown to adsorb topiramate in vitro. Treatment should be appropriately supportive. Hemodialysis is an effective means of removing topiramate from the body. DOSAGE AND ADMINISTRATION TOPAMAX has been shown to be effective in adults and pediatric patients ages 216 years with partial onset seizures or primary generalized tonic-clonic seizures, and in patient 2 years of age and older with seizures associated with Lennox-Gastaut syndrome. In the controlled add-on trials, no correlation has been demonstrated between trough plasma concentrations of topiramate and clinical efficacy. No evidence of tolerance has been demonstrated in humans. Doses above 400 mg day 600, 800, or 1, 000 mg day ; have not been shown to improve responses in doseresponse studies in adults with partial onset seizures. It is not necessary to monitor topiramate plasma concentrations to optimize TOPAMAX therapy. On occasion, the addition of TOPAMAX to phenytoin may require an adjustment of the dose of phenytoin to achieve optimal clinical outcome. Addition or withdrawal of phenytoin and or carbamazepine during adjunctive therapy.
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Vs. 13 percent of patients given placebo. In clinical trials, in combination with traditional AEDs, the most common side effects associated with TOPAMAX in pediatric patients included excessive drowsiness, loss of appetite, fatigue, nervousness, difficulty with concentration attention, weight decrease, aggressive reaction and difficulty with memory. The safety and effectiveness in patients younger than two have not been established. In adults, the most common types of side effects were somnolence, dizziness, coordination problems, speech disorders, psychomotor slowing, abnormal vision, difficulty with memory, sensory distortion and double vision. TOPAMAX is available as a tablet and in a capsule formulation that can be opened and sprinkled onto food for easy swallowing. The capsule also can be swallowed whole, offering patients greater flexibility. TOPAMAX was discovered and developed by the R.W. Johnson Pharmaceutical Research Institute, and is marketed in the United States by Ortho-McNeil Pharmaceutical, both Johnson & Johnson companies. Additional information about TOPAMAX is available by calling 1-800-682-6532 Please see Full U.S. Prescribing Information.
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Mission Statement The Southern Pain Society is a regional section of the American Pain Society and endorses and supports the mission and goals of the American Pain Society. The Southern Pain Society's missions are to serve people with pain by advancing research and treatment and to increase the knowledge and skill of the regional professional community. SPS Board of Directors President: Benjamin Johnson, M.D., MBA President Elect: Daniel M. Doleys, Ph.D. Immediate Past President: Angela J. Koestler, Ph.D. Treasurer: John Satterthwaite, M.D. Secretary: Mary Alice Yoham, MSN, ARNP At-Large Directors Sunil Dogra, M.D. B. Todd Sitzman, M.D., MPH Jonathan Cole, Ph.D. Ike Eriator, M.D. Executive Director: Lori H. Postal, RNC, MS Committees and Chairs Awards: Joseph Holtman, M.D. By-Laws: Joe Jacobson, P.T. Districting: Daniel M. Doleys, Ph.D. District Presidents: Benjamin Johnson, M.D., MBA E Communications: Stanley Chapman, Ph.D. Finance: John Satterthwaite, M.D. Membership: Mary Paris, ARNP Newsletter: Kenneth L. Kirsh, PhD Nominating: Angela J. Koestler, Ph.D. Public Affairs: Eric Pearson, M.D. Professional Education: Janice Livengood, Ph.D. Program: Daniel M. Doleys, Ph.D. SPS News Editorial Board Editor: Kenneth L. Kirsh, PhD SPS News is the official publication of the SPS, provided quarterly to its members. SPS may publish material dealing with controversial issues. The views expressed are those of the authors and may not reflect those of the SPS. No endorsement of those views should be inferred unless specifically identified as the official policy of the SPS. Submissions are welcomed. Publication is based on editorial judgment as to quality of material, timeliness, and potential interest to members.
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The tablet and capsule formulations of TOPAMAX are bioequivalent at equivalent doses. The pharmacokinetic profile of topiramate compared to other antiepileptic drugs shows a long plasma elimination half-life, linear pharmacokinetics, predominantly renal clearance, absence of significant protein binding and lack of clinically relevant active metabolites. Topiramate is not a potent inducer of drug metabolising enzymes. It can be administered without regard to meals and routine monitoring of plasma topiramate concentrations is not necessary. In clinical studies, there was no consistent relationship between plasma concentrations and efficacy or adverse events. Topiramate was rapidly and well absorbed and distributed in total body water following oral administration in animals. The same metabolic and elimination pathways were present as in human subjects. Cmax values were similar to those obtained in human subjects but topiramate was more rapidly cleared in animals resulting in lower overall systemic exposure. Absorption: Based on recovery of radioactivity from urine in humans, the mean extent of absorption of a 100 mg dose of 14C-topiramate was at least 81%. Following oral administration of 100 mg topiramate to healthy subjects, a mean peak plasma concentration Cmax ; of approximately 2 micrograms ml was achieved within 2 or 3 hours Tmax ; . The bioavailability of topiramate is not significantly affected by food. Distribution: Generally 13-17% of topiramate is bound to plasma proteins. A low capacity binding site for topiramate in on erythrocytes that is saturated at steady-state has been observed. Following single dose administration, the volume of distribution varies inversely with dose. The mean apparent volume of distribution has been measured as 0.8 - 0.55 L kg for a single dose range of 100 mg to 1200 mg. There is an effect of gender on the volume of distribution. Values for females are about 50% lower than those for males. This is attributed to the higher percent body fat in females and is of no clinical consequence. Metabolism: Topiramate is not extensively metabolised ~20% ; in healthy volunteers. It is metabolised up to 50% in patients receiving concomitant antiepileptic therapy with known inducers of drug-metabolising enzymes. Six metabolites formed through hydroxylation, hydrolysis and glucuronidation, have been isolated, characterised and identified from plasma, urine and faeces of humans. Each metabolite represents less than 3% of the total radioactivity excreted following administration of 14C-topiramate. Two metabolites, which retained most of the structure of topiramate, were tested and found to have little or no anticonvulsant activity. Elimination: In humans, the major route of elimination of unchanged topiramate and its metabolites is via the kidney at least 81% of the dose ; . Approximately 66% of a dose of 14C-topiramate was excreted unchanged in the urine within four days. Following twice a day dosing with 50 mg and 100 mg of topiramate, the mean renal clearance was approximately 18 ml min and 17 ml min, respectively. There is evidence of renal tubular reabsorption of.
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An explanation for the association of TOPAMAX and kidney stones may lie in the fact that topiramate is a weak carbonic anhydrase inhibitor. Carbonic anhydrase inhibitors, e.g., acetazolamide or dichlorphenamide, promote stone formation by reducing urinary citrate excretion and by increasing urinary pH. The concomitant use of TOPAMAX with other carbonic anhydrase inhibitors or potentially in patients on a ketogenic diet may create a physiological environment that increases the risk of kidney stone formation, and should therefore be avoided. Increased fluid intake increases the urinary output, lowering the concentration of substances involved in stone formation. Hydration is recommended to reduce new stone formation. Paresthesia Paresthesia, an effect associated with the use of other carbonic anhydrase inhibitors, appears to be a common effect of TOPAMAX. Adjustment of Dose in Renal Failure The major route of elimination of unchanged topiramate and its metabolites is via the kidney. Dosage adjustment may be required see DOSAGE AND ADMINISTRATION ; . Decreased Hepatic Function In hepatically impaired patients, topiramate should be administered with caution as the clearance of topiramate may be decreased. Information for Patients Patients taking TOPAMAX should be told to seek immediate medical attention if they experience blurred vision or periorbital pain. Patients, particularly those with predisposing factors, should be instructed to maintain an adequate fluid intake in order to minimize the risk of renal stone formation [See PRECAUTIONS: General, for support regarding hydration as a preventative measure]. Patients should be warned about the potential for somnolence, dizziness, confusion, and difficulty concentrating and advised not to drive or operate machinery until they have gained sufficient experience on topiramate to gauge whether it adversely affects their mental and or motor performance. Additional food intake may be considered if the patient is losing weight while on this medication. Please refer to the end of the product labeling for important information on how to take TOPAMAX topiramate capsules ; Sprinkle Capsules. Drug Interactions: Antiepileptic Drugs Potential interactions between topiramate and standard AEDs were assessed in controlled clinical pharmacokinetic studies in patients with epilepsy. The effects of these interactions on mean plasma AUCs are summarized in the following table: In Table 3, the second column AED concentration ; describes what happens to the concentration of the AED listed in the first column when topiramate is added. The third column topiramate concentration ; describes how the coadministration of a drug listed in the first column modifies the concentration of topiramate in experimental settings when TOPAMAX was given alone.
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For a given stensosis the former giving a "tighter" estimate ; , it is neceassary for any centre to standardise its measurements according to either ECST, NASCET, or the "common carotid" method7. Carotid endarterectomy should be performed by a surgeon with a sufficiently large practice to enable continuing technical proficiency in the procedure, and operative complications must be open to prospective audit. Once complication rates exceed those of ECST 7.5% ; and NASCET 5.8% ; all benefit is rapidly lost and harm results. "Best medical therapy" must persist throughout the assessment period and after surgery. Lifelong antiplatelet therapy, anticoagulation for atrial fibrillation, control of hypertension, hypercholesterolaemia and diabetes, and advice regarding smoking is crucial. Since the publication of the final results of ECST4 and NASCET8 there have been many further analyses of either subgroups from the individual trials or using data pooled from these and other studies: 30-70% disease Patients with symptomatic ICA stenosis of 30-50% do not benefit from surgery. Males with 50-69% stensosis and ipsilateral cortical cerebral ischaemic probably do benefit from surgery absolute risk reduction of any stroke or death 9% ; .Women with 50-69% stensosis or males with 50-69% stenosis who have suffered lacunar or retinal ischaemic events do not benefit9 and diamox.
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Anorgasmia developed with topiramate Topakax ; therapy in 7 patients who had not experienced prior sexual dysfunction. The 7 patients, 2 men and 5 women, were treated at 3 headache clinics, and all reported their adverse experiences spontaneously. Patients ranged in age from 40 to 62 years. Topiramate dosages ranged from 45 to 200 mg day. Anorgasmia resolved after topiramate was stopped in 4 patients and with a dosage reduction in 3 patients. The pathophysiology is not understood, but topiramate appeared to produce new-onset, dose-related anorgasmia in these patients. It is likely that a central effect involving several neurotransmitter systems modulated by the drug underlies development of the anorgasmia. Topiramate is also a carbonic anhydrase inhibitor, a drug class that has been associated with erectile dysfunction.
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Antiseizure medications such as divalproex sodium depakote ; , valproate valproic acid ; , or topiramate topamax ; , which may be tried if other treatments are not effective and arava!
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JPET #128207 described during treatment with the anti-epileptic and mood-stabilizing drug valproate Depakote ; Ruedrich et al., 1999 ; and preliminary trials with the anti-epileptic topiramate Topamxa ; have been promising Shapira et al., 2002 ; . However, it should be noted that these three compounds have not been studied as extensively as the older drug classes have. Furthermore, interpretation of these clinical trials and those of the older drugs ; is hampered by the fact that most trials are conducted with uncontrolled open label designs, owing to the severe nature of the disorder. In addition, the effects of concomitant behavior therapy are generally not reported, and interactions with additional ongoing drug interventions may obscure the treatment outcomes. Precise monitoring of specific behaviors may also be difficult throughout the daily lives of patients, so many trials have relied upon more global impressions of the patients' progress, rather than specific counts of SIB e.g. Caicedo and Williams, 2002 ; . In light of these difficulties in the design and interpretation of clinical drug trials for SIB, it would be useful to have an animal model with good predictive validity for pharmacotherapeutic effects. The availability of such a model could benefit patient populations by helping to prescreen potential pharmacotherapies under controlled laboratory conditions, with precisely defined and quantifiable dependent measures. In one animal model of SIB, rodents exhibit self-biting behavior after administration of high doses of the indirect monoamine agonist pemoline 2-amino-5-phenyl-1, 3-oxazol-4-one ; Mueller and Hsiao, 1980; Kies and Devine, 2004 ; . The pemoline-induced SIB occurs in a doseorderly and stereotyped manner after 3-5 daily injections Kies and Devine, 2004 ; , and it can be blocked by co-administration of haloperidol, pimozide, or naltrexone Mueller and Nyhan, 1982; King et al., 1993 ; . Accordingly, the model seems to be responsive to classical interventions that.
Pentin Neurontin ; , lamotrigine Lamictal ; , oxcarbazepine Trileptal ; , levetiracetam Keppra ; , pregabalin Lyrica ; , tiagabine Gabitril ; , and topiramate Topqmax ; are generally recommended over the older AEDs.8 Despite these recommendations, older AEDS such as phenytoin Dilantin ; , valproate Depakote ; , and carbamazepine Tegretol ; are the most commonly prescribed treatment options.9, 10 The specific risks and challenges of these drugs, especially when used in older adults, are related to drug metabolism changes that occur with increasing age, increased likelihood of drug-drug interactions among patients who take multiple other drugs, and serum drug level limits that do not necessarily apply in older adults because they were developed in younger individuals.1 Drug choices and potential side effects are shown in Table 1. For institutionalized older adults, diazepam Valium ; , administered as a buccal squirt or rectal suppository, provides immediate treatment of seizures. Decisions on drug use must be made based on individual needs and side-effect profiles. The guideline for drug dosing is to start low and monitor drug effectiveness in preventing seizures. Extendedrelease formulations may be helpful in improving drug adherence. Consideration can be given to stopping medication if the patient is free of seizures for 2 to 5 years. Overall, the evaluation and treatment of seizures in older adults should be geared toward helping these individuals obtain and maintain optimal quality of life through seizure elimination, balanced with tolerance of the medication. MPM.
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Case Summary Delbert Hill "Husband" ; appeals the trial court's property division in his dissolution proceedings with Sarah Hill "Wife" ; . Husband argues that the trial court abused its discretion in failing to award him a greater share of the marital property. Finding that the trial court acted within its discretion in dividing the marital property, we affirm. Facts and Procedural History Husband and Wife were married on November 22, 1989. During the marriage, Husband worked as a truck driver, and Wife largely stayed at home as a housewife and a mother of the couple's two children. Wife has a history of mental illness. She says that she has been diagnosed with bipolar disorder, and she takes Lexapro, Zyprexa, and Topamax for a "Recurrent, Major Depressive Disorder." Appellant's App. p. 129. She was institutionalized once before she married Husband and at least three times while she was married to Husband. Most recently, Wife lived in a group home for approximately two-and-a-half years, from November 2002 until May 2005. According to Husband, the longest period Wife ever worked during the marriage was three weeks. On April 15, 2004, Wife filed a petition for dissolution of the marriage. At the final hearing, held on March 2 and June 20, 2005, there was extensive testimony regarding Wife's past struggles with mental illness from Husband's brother, Ira Hill, from Wife's friend, Donna Bratcher, and from Husband and Wife themselves. There was also testimony that outside of two short periods of employment in December 2004 and June 2005, Wife has remained unemployed. At the time of the final hearing, Husband, 2.
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