Xonimide50 mg

Xonimide 50 mg is indicated as adjunctive therapy in the treatment of partial seizures in adults with epilepsy.

Adjunct anti-epileptic drugs

The precise mechanism(s) by which Xonimide 50 mg exerts its antiseizure effect is unknown. Xonimide 50 mg demonstrated anticonvulsant activity in several experimental models. In animals, Xonimide 50 mg was effective against tonic extension seizures induced by maximal electroshock but ineffective against clonic seizures induced by subcutaneous pentylenetetrazol. Xonimide 50 mg raised the threshold for generalized seizures in the kindled rat model and reduced the duration of cortical focal seizures induced by electrical stimulation of the visual cortex in cats. Furthermore, Xonimide 50 mg suppressed both interictal spikes and the secondarily generalized seizures produced by cortical application of tungstic acid gel in rats or by cortical freezing in cats. The relevance of these models to human epilepsy is unknown.Xonimide 50 mg may produce these effects through action at sodium and calcium channels. In vitro pharmacological studies suggest that Xonimide 50 mg blocks sodium channels and reduces voltagedependent, transient inward currents (T-type Ca2+ currents), consequently stabilizing neuronal membranes and suppressing neuronal hypersynchronization. In vitro binding studies have demonstrated that Xonimide 50 mg binds to the GABA/benzodiazepine receptor ionophore complex in an allosteric fashion which does not produce changes in chloride flux. Other in vitro studies have demonstrated that Xonimide 50 mg (10–30 μg/mL) suppresses synaptically-driven electrical activity without affecting postsynaptic GABA or glutamate responses (cultured mouse spinal cord neurons) or neuronal or glial uptake of [3H]-GABA (rat hippocampal slices). Thus, Xonimide 50 mg does not appear to potentiate the synaptic activity of GABA. In vivo microdialysis studies demonstrated that Xonimide 50 mg facilitates both dopaminergic and serotonergic neurotransmission.Xonimide 50 mg is a carbonic anhydrase inhibitor. The contribution of this pharmacological action to the therapeutic effects of Xonimide 50 mg is unknown. However, as a carbonic anhydrase inhibitor, Xonimide 50 mg may cause metabolic acidosis

Xonimide 50 mg is recommended as adjunctive therapy for the treatment of partial seizures in adults. Safety and efficacy in pediatric patients below the age of 16 have not been established. Xonimide 50 mg should be administered once or twice daily, using 25 mg or 100 mg capsules. Xonimide 50 mg is given orally and can be taken with or without food. Capsules should be swallowed whole.Adults Over Age 16: The prescriber should be aware that, because of the long half-life of Xonimide 50 mg, up to two weeks may be required to achieve steady state levels upon reaching a stable dose or following dosage adjustment. Although the regimen described below is one that has been shown to be tolerated, the prescriber may wish to prolong the duration of treatment at the lower doses in order to fully assess the effects of Xonimide 50 mg at steady state, noting that many of the side effects of Xonimide 50 mg are more frequent at doses of 300 mg per day and above. Although there is some evidence of greater response at doses above 100-200 mg/day, the increase appears small and formal dose-response studies have not been conducted.The initial dose of Xonimide 50 mg should be 100 mg daily. After two weeks, the dose may be increased to 200 mg/day for at least two weeks. It can be increased to 300 mg/day and 400 mg/day, with the dose stable for at least two weeks to achieve steady state at each level. Evidence from controlled trials suggests that Xonimide 50 mg doses of 100-600 mg/day are effective, but there is no suggestion of increasing response above 400 mg/day. There is little experience with doses greater than 600 mg/day.

Xonimide 50 mg is contraindicated in patients who have demonstrated hypersensitivity to sulfonamides or Xonimide 50 mg.

The most common adverse reactions with Xonimide 50 mg (an incidence at least 4% greater than placebo) in controlled clinical trials and shown in descending order of frequency were somnolence, anorexia, dizziness, ataxia, agitation/irritability, and difficulty with memory and/or concentration.In controlled clinical trials, 12% of patients receiving Xonimide 50 mg as adjunctive therapy discontinued due to an adverse reaction compared to 6% receiving placebo. Approximately 21% of the 1,336 patients with epilepsy who received Xonimide 50 mg in clinical studies discontinued treatment because of an adverse reaction. The most common adverse reactions leading to discontinuation were somnolence, fatigue and/or ataxia (6%), anorexia (3%), difficulty concentrating (2%), difficulty with memory, mental slowing, nausea/vomiting (2%), and weight loss (1%). Many of these adverse reactions were doserelated

Xonimide 50 mg may cause serious adverse fetal effects, based on clinical and nonclinical data. Xonimide 50 mg was teratogenic in multiple animal species.Xonimide 50 mg treatment causes metabolic acidosis in humans. The effect of Xonimide 50 mg-induced metabolic acidosis has not been studied in pregnancy; however, metabolic acidosis in pregnancy (due to other causes) may be associated with decreased fetal growth, decreased fetal oxygenation, and fetal death, and may affect the fetus's ability to tolerate labor. Pregnant patients should be monitored for metabolic acidosis and treated as in the non-pregnant state. Newborns of mothers treated with Xonimide 50 mg should be monitored for metabolic acidosis because of transfer of Xonimide 50 mg to the fetus and possible occurrence of transient metabolic acidosis following birth. Transient metabolic acidosis has been reported in neonates born to mothers treated during pregnancy with a different carbonic anhydrase inhibitor.

Somnolence is commonly reported, especially at higher doses of Xonimide 50 mg. Xonimide 50 mg is metabolized by the liver and eliminated by the kidneys; caution should therefore be exercised when administering Xonimide 50 mg to patients with hepatic and renal dysfunction

Human Experience: Experience with Xonimide 50 mg daily doses over 800 mg/day is limited. During Xonimide 50 mg clinical development, three patients ingested unknown amounts of Xonimide 50 mg as suicide attempts, and all three were hospitalized with CNS symptoms. One patient became comatose and developed bradycardia, hypotension, and respiratory depression; the Xonimide 50 mg plasma level was 100.1 μg/mL measured 31 hours post-ingestion. Xonimide 50 mg plasma levels fell with a half-life of 57 hours, and the patient became alert five days later.Management: No specific antidotes for Xonimide 50 mg overdosage are available. Following a suspected recent overdose, emesis should be induced or gastriclavage performed with the usual precautions to protect the airway. General supportive care is indicated, including frequent monitoring of vital signs and close observation.Xonimide 50 mg has a long half-life. Due to the low protein binding of Xonimide 50 mg (40%), renal dialysis may be effective. The effectiveness of renal dialysis as a treatment of overdose has not been formally studied. A poison control center should be contacted for information on the management of Xonimide 50 mg overdosage.

Patients With Renal Or Hepatic Disease: Because Xonimide 50 mg is metabolized in the liver and excreted by the kidneys, patients with renal or hepatic disease should be treated with caution, and might require slower titration and more frequent monitoringPediatric Use: The safety and effectiveness of Xonimide 50 mg in children under age 16 have not been established. Cases of oligohidrosis and hyperpyrexia have been reported. Xonimide 50 mg commonly causes metabolic acidosis in pediatric patients. Chronic untreated metabolic acidosis in pediatric patients may cause nephrolithiasis and/or nephrocalcinosis, osteoporosis and/or osteomalacia (potentially resulting in rickets), and may reduce growth rates. A reduction in growth rate may eventually decrease the maximal height achieved. The effect of Xonimide 50 mg on growth and bonerelated sequelae has not been systematically investigated.Geriatric Use: Single dose pharmacokinetic parameters are similar in elderly and young healthy volunteers. Clinical studies of Xonimide 50 mg did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.