topiramate and Acidosis

The use of topiramate, which is prescribed for the management of epilepsy, for migraine headache prophylaxis and as a weight-loss agent, has been associated with the development of metabolic acidosis, hypokalaemia and renal stone disease. We systematically reviewed all the literature.. The systematic review of the literature was realized using the principles underlying the UK Economic and Social Research Council guidance on the conduct of narrative synthesis and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement.. Fourty-seven reports published between 1996 and 2013 were retained for the final analysis. Five case-control studies and six longitudinal studies addressed the effect of topiramate on acid-base and potassium balance. A significant tendency towards mild-to-moderate hyperchloraemic metabolic acidosis (with bicarbonate ≤21.0 mmol l(-1) in approximately every third case) and mild hypokalaemia (with potassium ≤3.5 mmol l(-1) in 10% of the cases) was noted on treatment with topiramate, which was similar in children and adults. A single study observed that topiramate causes mild hyperuricaemia in male adults. A tendency towards hypocitraturia, a recognized promoter of renal stone formation, was noted in all patients on topiramate.. Increasing evidence supports the use of topiramate. Topiramate is generally well tolerated, and serious adverse events are rare. Nonetheless, the present systematic review of the literature indicates that its use is linked with the development of acidosis, hypokalaemia, hyperuricaemia and hypocitraturia.

Topics: Acidosis; Female; Fructose; Humans; Hypokalemia; Kidney Calculi; Male; Topiramate

Multiple new anticonvulsants have been introduced recently and they are supplanting the older medications. Whereas the older drugs have well-recognized side effects, both in typical therapeutic doses and in overdosage, the properties of the newer ones are unique and largely unknown to all but sub-specialists.. This article gives a concise overview of the potential complications of these new medications in both therapeutic use and overdose.. Clinically significant side effects of the new anticonvulsants, such as metabolic acidosis from topiramate, autoimmune reactions from lamotrigine, hyponatremia from oxcarbazepine, or psychosis from levitiracetam can cause serious morbidity and mortality if unrecognized. The effects of these medications in overdose are also largely unknown to most emergency physicians.. This article reviews the major potential side effects of the new seizure medications and the treatment of their overdoses for the practicing emergency physician.

Topics: Acidosis; Amines; Anticonvulsants; Carbamazepine; Cyclohexanecarboxylic Acids; Drug Overdose; Fructose; Gabapentin; gamma-Aminobutyric Acid; Humans; Lamotrigine; Levetiracetam; Nipecotic Acids; Oxcarbazepine; Piracetam; Psychoses, Substance-Induced; Seizures; Tiagabine; Topiramate; Triazines

Topiramate is a novel neuromodulatory agent commonly prescribed for the treatment of seizure disorders and for migraine headache prophylaxis. Calcium phosphate kidney stones have been observed with topiramate treatment, but a comprehensive elucidation of stone-risk profile was not reported previously. This study explores the relationship between topiramate treatment and propensity for kidney stone formation.. Thirty-two topiramate-treated subjects and 50 healthy volunteers participated in a cross-sectional study in which serum chemistry test and 24-hour urine collection results were evaluated for stone risk. Furthermore, a short-term longitudinal study was conducted in 7 patients to assess stone risk before and 3 months after topiramate treatment.. Serum bicarbonate levels were lower with topiramate treatment. Urinary pH, urinary bicarbonate excretion, and fractional excretion of bicarbonate increased, whereas urinary citrate excretion was significantly lower (737 +/- 329 versus 278 +/- 226 mg/d; P < 0.001). Net acid excretion did not change. The relative saturation ratio for brushite increased with topiramate treatment (3.14 +/- 1.69 versus 1.27 +/- 1.26; P < 0.001) because of urinary alkalinization and decreased urinary citrate levels. Urinary saturation of undissociated uric acid decreased (41 +/- 52 versus 76 +/- 60 mg/d; P < 0.001).. Treatment with topiramate causes systemic metabolic acidosis, markedly lower urinary citrate excretion, and increased urinary pH. These changes increase the propensity to form calcium phosphate stones.

Topics: Acid-Base Equilibrium; Acidosis; Adult; Bicarbonates; Calcium Phosphates; Citrates; Cross-Sectional Studies; Female; Fructose; Humans; Hydrogen-Ion Concentration; Kidney Calculi; Longitudinal Studies; Male; Middle Aged; Neuroprotective Agents; Topiramate

Topiramate, which is increasingly being used to treat alcohol use disorder (AUD), is commonly associated with reduced serum bicarbonate concentrations. However, estimates of the prevalence and magnitude of this effect are from small samples and do not address whether topiramate's effects on acid-base balance differ in the presence of an AUD or by topiramate dosage.. Veterans Health Administration electronic health record (EHR) data were used to identify patients with a minimum of 180 days of topiramate prescription for any indication and a propensity score-matched control group. We differentiated patients into two subgroups based on the presence of a diagnosis of AUD in the EHR. Baseline alcohol consumption was determined using Alcohol Use Disorders Identification Test-Consumption (AUDIT-C) scores in the EHR. Analysis also included a three-level measure representing mean daily dosage. The topiramate-associated changes in serum bicarbonate concentration were estimated in difference-in-differences linear regression models. A serum bicarbonate concentration <17 mEq/L was considered to represent possible clinically significant metabolic acidosis.. The cohort comprised 4287 topiramate-treated patients and 5992 propensity score-matched controls with a mean follow-up period of 417 days. The mean topiramate-associated reductions in serum bicarbonate concentration were <2 mEq/L in the low (≤88.75), medium (>88.75 and ≤141.70), and high (>141.70) mg/day dosage tertiles, irrespective of AUD history. Concentrations <17 mEq/L occurred in 1.1% of topiramate-treated patients and 0.3% of controls and were not associated with alcohol consumption or an AUD diagnosis.. The excess prevalence of metabolic acidosis associated with topiramate treatment does not differ with dosage, alcohol consumption, or the presence of an AUD. Baseline and periodic serum bicarbonate concentration measurements are recommended during topiramate therapy. Patients prescribed topiramate should be educated about the symptoms of metabolic acidosis and urged to report their occurrence promptly to a healthcare provider.

Topics: Acidosis; Alcoholism; Bicarbonates; Humans; Topiramate; Veterans

Guidelines on the use of dialysis treatment in patients with chronic kidney disease (CKD) and TPM (Topiramate) intoxication are controversial. A 51-year-old man with epilepsy and CKD was carried to our emergency department for dysuria and sickness. He chronically assumed TPM 100 mg 3/day. Creatinine level was 2.1 mg/dL, blood urea nitrogen 70 mg/dL, and inflammation indexes were increased. We started empirical antibiotic therapy and rehydration. The day two he had diarrhea and an acute insurgence of dizziness, confusion, and bicarbonate levels reduction. Brain CT resulted negative for acute events. During the night his mental status worsened, and urinary output results were about 200 mL in 12h. EEG showed desynchronized brain bioelectric activity. Thereafter, there was an episode of seizure and then anuria, hemodynamic instability, and loss of consciousness. Creatinine value was 5.39 mg/dL with a serious metabolic acidosis non-anion gap. We decided to start 6-hours Sustained Low Efficiency Hemo-Dia-Filtration (SLE-HDF). We assisted in the recovery of consciousness and later in the improvement of kidney function after 4 hours of treatment. TPM levels before SLE-HDF resulted in 123.1 µg/mL. At the end of treatment resulted in 30 µg/mL. To our knowledge, this is the first report of TPM involuntary intoxication in a patient affected by CKD who survived such a high TPM concentration treated with renal replacement therapy. SLE-HDF resulted in moderate elimination of TPM and acidemia resolution, continuous monitoring patient's vital parameters in relation to his hemodynamic instability, since blood flow and dialysate flow are lower than conventional hemodialysis.

Topics: Acidosis; Creatinine; Humans; Hybrid Renal Replacement Therapy; Male; Middle Aged; Renal Dialysis; Renal Insufficiency, Chronic; Topiramate

The aim of this study is to present a case of 44 years old woman with topiramate induced metabolic acidosis and kidney stones.. The laboratory features of topiramate caused renal tubular acidosis in blood and urine during topiramate treatment, with correction of metabolic acidosis by potassium citrate, and after topiramate withdrawal are presented. Differential diagnosis of all possible causes of metabolic acidosis is discussed.. This study has shown that long-term topiramate administration could induce metabolic acidosis and consequently urholithiasis. Thus, we could recommend testing blood acid base balance, urinary pH and citrates in patients taking topiramate and suffering from kidney stones.

Topics: Acidosis; Adult; Anticonvulsants; Female; Fructose; Humans; Kidney Calculi; Migraine Disorders; Topiramate; Withholding Treatment

Topiramate is an anticonvulsant that is being increasingly used for a number of different off-label indications. Its inhibition of carbonic anhydrase isoenzymes can lead to metabolic acidosis, elevated urine pH, reduced urine citrate, and hypercalciuria, thereby creating a milieu that is ripe for calcium phosphate stone formation. In this review, we describe a case of topiramate-induced metabolic acidosis. We review the frequency of metabolic acidosis among children and adults, as well as the mechanism of hyperchloremic metabolic acidosis and renal tubular acidosis in topiramate users. Finally, we describe the long-term effects of topiramate-induced metabolic acidosis, including nephrolithiasis, nephrocalcinosis, and bone degradation. Patients who are prescribed topiramate should be carefully monitored for metabolic derangements, and they may benefit from alkali supplementation, or in extreme cases, discontinuation of the drug altogether.

Topics: Acidosis; Adult; Carbonic Anhydrase Inhibitors; Female; Fructose; Humans; Migraine Disorders; Topiramate

Objective We planned a cross-sectional analysis to determine the frequency and severity of metabolic acidosis in patients taking topiramate while awaiting craniotomy. Methods Eighty patients (18 - 65 years) taking topiramate to control seizures while awaiting elective craniotomy were enrolled. Any signs of metabolic acidosis or topiramate-related side effects were investigated. Blood chemistry levels and arterial blood gases, including lactate, were obtained. The severity of metabolic acidosis was defined according to base excess levels as mild or moderate. Results Blood gas analysis showed that 71% ( n = 57) of patients had metabolic acidosis. The frequency of moderate metabolic acidosis was 56% ( n = 45), while that of mild metabolic acidosis was 15% ( n = 12). A high respiratory rate was reported in only 10% of moderately acidotic patients. Conclusions In patients receiving topiramate, baseline blood gas analysis should be performed preoperatively to determine the presence and severity of metabolic acidosis.

Topics: Acidosis; Adolescent; Adult; Aged; Anticonvulsants; Blood Gas Analysis; Cross-Sectional Studies; Female; Fructose; Humans; Male; Middle Aged; Respiratory Rate; Seizures; Severity of Illness Index; Topiramate

To determine the frequency of metabolic acidosis and its related factors in outpatients taking topiramate in monotherapy or as an adjuvant for the treatment of epilepsy.. Cross-sectional analysis of arterial blood gas test of epileptic patients who received topiramate during 2010 in the Epilepsy Clinic at the National Medical Center '20 de Noviembre' in Mexico. Clinical data regarding epilepsy history and management and the common symptoms of metabolic acidosis were recorded.. We studied 32 adults with epilepsy at an outpatient epilepsy clinic who were treated with topiramate in monotherapy or in combination for at least one month. Metabolic acidosis was found in all patients (HCO3<22 Eq/L); nine were taking topiramate in monotherapy, and 23 were taking at least two antiepileptic drugs (AEDs). All of the patients were asymptomatic. We found no correlation between bicarbonate levels and the dose of the drug or the duration of treatment. The dose was significantly higher in the monotherapy group, and the bicarbonate level was lower in the patients taking more than one AEDs.. The use of concomitant AEDs increases the known effects of topiramate on serum bicarbonate levels and the presence of metabolic acidosis, and these effects appear to be independent of the number of AEDs used.. Topiramato en monoterapia o en combinacion como causa de acidosis metabolica en adultos con epilepsia.. Objetivo. Determinar la frecuencia de acidosis metabolica y sus factores relacionados en pacientes tratados con topiramato solo o como adyuvante para el tratamiento de epilepsia. Pacientes y metodos. Analisis transversal de la gasometria arterial de pacientes epilepticos que recibieron topiramato durante 2010 en la clinica de epilepsia del Centro Medico Nacional 20 de Noviembre en Mexico. Se registraron datos clinicos concernientes a la epilepsia y su tratamiento, asi como de los sintomas comunes de acidosis metabolica. Resultados. Se estudiaron 32 adultos con epilepsia, quienes recibieron topiramato en monoterapia o en combinacion por lo menos durante un mes. Se encontro acidosis metabolica en todos los pacientes (HCO3 < 22 Eq/L); nueve tomaron solo topiramato y 23 tomaron por lo menos dos farmacos antiepilepticos (FAE). Todos los pacientes fueron asintomaticos. No se encontro correlacion entre los niveles de bicarbonato y la dosis del medicamento o la duracion del tratamiento. La dosis fue significativamente mayor en el grupo de monoterapia y el nivel de bicarbonato fue mas bajo en los pacientes que tomaban mas de un FAE. Conclusiones. El uso concomitante de FAE incrementa los efectos conocidos del topiramato sobre los niveles sericos de bicarbonato y la presencia de acidosis metabolica; estos efectos parecen ser independientes del numero de FAE utilizados.

Topics: Acidosis; Adult; Anticonvulsants; Cross-Sectional Studies; Drug Therapy, Combination; Epilepsy; Female; Fructose; Humans; Male; Prospective Studies; Topiramate

Topiramate has been associated with metabolic acidosis secondary to decreased serum bicarbonate. Product labeling recommends serum bicarbonate monitoring at baseline and periodically thereafter.. The study objective was to assess changes in serum bicarbonate within the first year of topiramate use in an outpatient veteran population.. This was a single-center, retrospective study conducted at the Iowa City Veterans Affairs Health Care System. Inclusion criteria required a minimum of 1 topiramate outpatient prescription between October 1, 1999, and August 31, 2012, and at least 1 serum bicarbonate level within 12 months prior to topiramate initiation. Patients with topiramate nonadherence, concurrent use of sodium bicarbonate or oral carbonic anhydrase inhibitors, and individual serum bicarbonate values obtained during inpatient hospitalizations were excluded. Change in bicarbonate was evaluated using a paired t test. Decreases in bicarbonate of ≥5 mEq/L, values <20 mEq/L, days to lowest value, and correlation between adverse drug reactions (ADRs) and topiramate discontinuation were evaluated.. Of 546 patients reviewed, 350 were included in the analysis. There was a statistically significant decrease of 2.7 mEq/L in bicarbonate following initiation of topiramate. Only 1 patient had a bicarbonate value <17 mEq/L. There was no association between bicarbonate decrease ≥5 mEq/L and ADRs.. A statistically significant reduction in bicarbonate levels occurred with topiramate, which was clinically insignificant. ADR occurrence did not correlate with bicarbonate levels <17 mEq/L or a decrease ≥5 mEq/L. Our results indicate that serum bicarbonate levels should only be monitored before topiramate initiation and in patients presenting with symptoms suggestive of acidosis.

Topics: Acidosis; Adult; Aged; Bicarbonates; Female; Fructose; Hospitalization; Humans; Iowa; Male; Middle Aged; Retrospective Studies; Topiramate; Veterans

A 42-year old woman was referred for a metabolic evaluation after two episodes of kidney stones. Her laboratory results revealed a normal anion-gap metabolic acidosis, a marked hypocitraturia (0,6 mmol/24h; norm 1,6-4,5) and a urinary pH of 7,0 confirming renal tubular acidosis (RTA). We identified topiramate, our patient's medication for migraine, as the cause of the RTA. Topiramate, a carboanhydrase inhibitor leads to RTA of a mixed (proximal and distal) type and thus significantly increases the risk for kidney stones.

Topics: Acidosis; Acidosis, Renal Tubular; Adult; Anticonvulsants; Citric Acid; Diagnosis, Differential; Female; Fructose; Humans; Kidney Calculi; Migraine Disorders; Renal Colic; Topiramate

Topics: Acidosis; Acidosis, Renal Tubular; Aged; Anticonvulsants; Cerebral Hemorrhage, Traumatic; Comorbidity; Drug Substitution; Epilepsies, Partial; Fructose; Humans; Male; Phenytoin; Polypharmacy; Schizophrenia, Paranoid; Topiramate

Topics: Acidosis; Alkalosis, Respiratory; Bicarbonates; Brain; Carbon Dioxide; Carbonic Anhydrase Inhibitors; Causality; Fructose; Humans; Hyperventilation; Partial Pressure; Topiramate

A non-anion gap acidosis can be induced by topiramate, causing symptomatic dyspnea and confusion.. Discuss the pathophysiology of the hyperchloremic metabolic acidosis caused by topiramate, the typical clinical presentation, and the recommended treatment.. This case presents a young woman with a clinically significant non-anion gap metabolic acidosis believed to be caused by topiramate. She had been taking the medication for several months without prior adverse effects. Once she began having dyspnea as a respiratory response to the renal tubule acidosis, she had decreased oral intake of food and fluids, which induced a pre-renal acute renal failure that worsened her acidemia. In the Emergency Department, she received intravenous fluids and sodium bicarbonate, and later was intubated for mechanical ventilation due to respiratory fatigue. With the topiramate withdrawn, the patient had a full recovery of her renal function and metabolic acid-base status over the next 72 h. This case serves to increase awareness of this possible adverse effect and the recommended treatment as topiramate becomes more widely used.. Topiramate can induce a renal tubule acidosis resulting in a hyperchloremic metabolic acidosis. Recognition of the underlying cause is crucial so that the drug can be withdrawn while supportive care is provided.

Topics: Acid-Base Equilibrium; Acidosis; Adult; Female; Fructose; Humans; Neuroprotective Agents; Topiramate

Topiramate, which is commonly prescribed for seizure disorders and migraine prophylaxis, sometimes causes metabolic acidosis and hypokalemia. Since the effects of topiramate on acid-base balance and potassium levels have not been well explored in children, acid-base balance, anion gap and potassium were assessed in 24 patients (8 females and 16 males) aged between 4.6 and 19 years on topiramate for more than 12 months and in an age-matched control group. Plasma bicarbonate (21.7 versus 23.4 mmol/L; P<0.03), carbon dioxide pressure (39.7 versus 43.2mm Hg; P<0.05), and potassium (3.7 versus 4.0 mmol/L; P<0.03) were on the average lower and chloride (109 versus 107 mmol/L; P<0.03) higher in patients treated with topiramate than in controls. Blood pH, plasma sodium and the anion gap were similar in patients on topiramate and in controls. In patients on topiramate no significant correlation was observed between the dosage of this agent and plasma bicarbonate or potassium as well as between topiramate blood level and the mentioned electrolytes. In conclusion long-term topiramate treatment is associated with a mild, statistically significant tendency towards compensated normal anion gap metabolic acidosis and hypokalemia.

Topics: Acid-Base Equilibrium; Acidosis; Adolescent; Anticonvulsants; Bicarbonates; Child; Child, Preschool; Chlorides; Dose-Response Relationship, Drug; Electrolytes; Epilepsy; Female; Fructose; Humans; Hypokalemia; Male; Potassium; Topiramate; Young Adult

Topiramate is used to treat a variety of neurologic and psychiatric diseases due to its benign safety profile. Data regarding the toxicity and toxicokinetics of topiramate in acute overdose are limited. A case of massive, acute ingestion resulting in the highest reported topiramate level is presented, including toxicokinetic evaluation. A 37-year-old woman presented with coma unresponsive to naloxone following topiramate ingestion. She had normal vital signs without respiratory depression. She was intubated for airway protection, given 3.5 mg lorazepam IV for facial and neck muscle twitching, and transferred to our facility. No additional sedation was required for 18 h on the ventilator. Following mental status improvement, the patient was extubated. Confusion, dysarthria, and imbalance resolved over the next 2 days. Nonanion gap metabolic acidosis persisted for 3 days. Peak serum topiramate level was 356.6 microg/ml (reference range, 5-20 microg/ml). Massive topiramate ingestion led to prolonged coma with normal vital signs and nonanion gap metabolic acidosis. Coma of this severity has not been previously reported. Serum half-life, which has not been studied after overdose, was 16 h. Despite the large ingestion and significant presenting symptoms, the patient recovered fully with supportive intensive care alone. Massive acute topiramate ingestion may lead to nonanion gap metabolic acidosis and prolonged coma which resolves with intensive supportive care. Toxicokinetic data following large, suicidal ingestion of topiramate were similar to previously published pharmacokinetic information.

Topics: Acidosis; Adult; Anticonvulsants; Bipolar Disorder; Blood Gas Analysis; Coma; Critical Care; Drug Overdose; Female; Fructose; Gas Chromatography-Mass Spectrometry; Humans; Hypnotics and Sedatives; Lorazepam; Respiration, Artificial; Topiramate

Topics: Acidosis; Acute Kidney Injury; Female; Fructose; Humans; Hydronephrosis; Middle Aged; Neuroprotective Agents; Tomography, X-Ray Computed; Topiramate; Ureteral Calculi; Ureteral Obstruction

The clinical manifestations of acute topiramate toxicity are described.. Seven cases of acute and acute-on-chronic topiramate toxicity observed in two clinical units of Polish Poison Control Centers in 2004-2005 were analyzed.. The patients were 4 women and 2 men aged between 16 and 38 (mean 21.0 +/- 8.4) years. The doses of topiramate ranged from 10.7 to 218 mg/kg. The most frequent symptom was somnolence (66.7%) and, vertigo, agitation, and mydriasis were less common (33.4%). One patient who was not previously treated with topiramate experienced three secondarily generalized tonic-clonic seizures. Metabolic acidosis, lasting for 3-7 days, was observed in four cases, and did not influence the outcome.. The clinical manifestations of acute poisonings with topiramate ranged from asymptomatic to severe, but no distant sequelae or fatalities were observed. The course of acute poisoning seems to be more severe in patients who were not previously treated with topiramate.

Topics: Acidosis; Adolescent; Adult; Anticonvulsants; Drug Overdose; Epilepsy, Tonic-Clonic; Female; Fructose; Humans; Male; Poison Control Centers; Poland; Severity of Illness Index; Sleep Stages; Suicide, Attempted; Topiramate; Young Adult

A rare adverse effect observed after dose escalation of topiramate therapy is discussed. A review of published cases, monitoring recommendations, and important counseling information for patients who are prescribed topiramate are described.. A 37-year-old man hospitalized for mental status changes and possible seizure developed hyperchloremic, normal anion-gap, metabolic acidosis. His medical history was significant for AIDS, progressive multifocal leukoencephalopathy, a cerebrovascular accident, a seizure disorder for the past three years, and a pulmonary embolism five months before being admitted to the hospital. The patient was also taking topiramate for two months before being hospitalized for his seizure disorder. His dosage was increased after admission, but no changes were made to his other medications. The only new medication initiated was cefotaxime for 14 days to treat pneumonia. During the following 8 days, the patient continued to receive increased dosages of topiramate. His serum chloride concentration increased daily and his serum bicarbonate decreased. Topiramate was identified as the cause and was discontinued the next day. Six other cases of metabolic acidosis in adults are reviewed, as well as risk factors for metabolic acidosis.. After receiving increased dosages of topiramate, a 37-year-old man developed hyperchloremic, normal anion-gap, metabolic acidosis, which resolved after discontinuation of the drug.

Topics: Acidosis; Adult; Anions; Anticonvulsants; Chlorides; Fructose; Humans; Male; Topiramate

Topics: Acidosis; Anesthesia, General; Anticonvulsants; Blood Gas Analysis; Fructose; Humans; Intraoperative Complications; Neurosurgical Procedures; Topiramate

To report a case of hyperventilation caused by topiramate therapy and propose a pathophysiologic mechanism for this disorder.. A 52-year-old woman with refractory seizure disorder was admitted to the burn care unit with burns over 10% of her body. Her seizure medications, unchanged and well tolerated for several months, included carbamazepine 1200 mg, lamotrigine 500 mg, phenobarbital 80 mg, and topiramate 150 mg per day. During hospitalization, despite a relatively normal arterial pH, the woman developed persistent hyperventilation, with respiratory rates up to 50 breaths/min. Alkalinization did not reduce the hyperventilation. Thoracic contrast-enhanced computed tomographic scan ruled out pulmonary embolism and persistent pneumonia. Salicylate and biguanide screening were negative; results of repeated thyroid and liver function tests were normal. Cerebral magnetic resonance imaging excluded a cerebral pathology. After cerebrospinal fluid (CSF) analysis showed acidosis (pH 7.14), topiramate was withdrawn and the patient's general condition rapidly improved. Forty-eight hours later, the CSF pH had increased to 7.26. The woman was discharged from the burn care unit on the 42nd hospital day.. Hyperchloremic normal anion gap metabolic acidosis, which can lead to hyperventilation, has been reported as an adverse effect of topiramate treatment. However, our patient had respiratory alkalosis. Concurrent etiologies of peripheral hyperventilation were excluded, leaving central neurogenic hyperventilation as the remaining etiology. Such central neurogenic hyperventilation associated with topiramate has previously been reported in intensive care. Our case report demonstrates CSF acidosis. Withdrawing topiramate reduced both CSF acidosis and hyperventilation. The mechanism of topiramate-induced CSF acidosis remains unclear. According to the Naranjo probability scale, the relationship of hyperventilation to administration of topiramate in our patient was probable.. Normal doses of topiramate may provoke central neurogenic hyperventilation, as a result of CSF acidosis. The acid-base status of critically ill patients receiving topiramate should be monitored carefully.

Topics: Acidosis; Anticonvulsants; Drug Therapy, Combination; Female; Fructose; Humans; Hyperventilation; Middle Aged; Seizures; Topiramate

Topics: Acidosis; Adverse Drug Reaction Reporting Systems; Anticonvulsants; Carbamazepine; Communication; Cooperative Behavior; Drug Monitoring; Drug-Related Side Effects and Adverse Reactions; Fructose; Humans; Hyponatremia; Topiramate

Ongoing refinements in pharmacology continue to provide new medications for the treatment of seizure disorders and other neurologic conditions. The authors present the cases of two children who developed relatively uncommon adverse effects to new anticonvulsant medications, including metabolic acidosis with topiramate and hyponatremia with oxcarbazepine. In one of our two patients, intraoperative acidosis related to topiramate was noted. Appropriate investigation with documentation of normal serum lactate resulted in the exclusion of other potentially serious causes of acidosis and in the identification of topiramate as the causative agent. In our second patient, hyponatremia and status epilepticus resulted from therapy with oxcarbazepine. Prompt recognition of hyponatremia, fluid restriction, and cessation of oxcarbazepine therapy resulted in prompt correction of the hyponatremia. We review previous reports of these adverse effects with topiramate and oxcarbazepine, describe the pathophysiology of these metabolic alterations, provide treatment strategies, and make suggestions for monitoring patients during therapy with these anticonvulsant medications.

Topics: Acidosis; Anticonvulsants; Blood Gas Analysis; Carbamazepine; Child; Child, Preschool; Female; Fructose; Humans; Hyponatremia; Intraoperative Complications; Lactic Acid; Male; Topiramate

This paper examines the relative effectiveness of sulfamate and sulfamide groups for the inhibition of carbonic anhydrase-II (CA-II). Topiramate (1) and its sulfamide analogue 4, and 4,5-cyclic sulfate 6 and its sulfamide analogue 5, were compared for inhibition of human CA-II. A colorimetric assay, based on the pH shift that accompanies hydration of carbon dioxide, and an esterase assay were used. For these bioisosteric pairs, 1/4 and 6/5, the sulfamate compound was markedly more potent than its sulfamide counterpart. A similar, large difference in potency was also observed for the sulfamate/sulfamide pairs 14/15 and 16/17. These results indicate that the sulfamide moiety is not particularly suitable for obtaining potent carbonic anhydrase inhibition. A discussion of this structure-activity relationship with respect to the interactions of 1 and 6 with CA-II from published X-ray data is presented. A metabolic acidosis study was performed in rats with 1, 4, 6, and 2, and the results are discussed with respect to the degree of inhibition of CA-II in vivo.

Topics: Acidosis; Animals; Anticonvulsants; Carbonic Anhydrase II; Carbonic Anhydrase Inhibitors; Fructose; Humans; Male; Models, Molecular; Molecular Structure; Protein Binding; Rats; Rats, Sprague-Dawley; Structure-Activity Relationship; Sulfonamides; Sulfonic Acids; Topiramate

Topiramate is a new anticonvulsant drug recommended for treatment of partial and generalized seizures in children and adults. It has been found to cause a nonanion gap metabolic acidosis in some patients, which is related to carbonic anhydrase inhibition. This adverse reaction is more common in children than adults and is rarely symptomatic. Clinicians need to be aware of this potential side effect especially in children undergoing major surgery. Children who are treated with topiramate should have a careful history taken preoperatively looking for signs of a metabolic acidosis and baseline blood chemistries should be measured prior to surgery to detect an asymptomatic metabolic acidosis.

Topics: Acidosis; Adolescent; Anticonvulsants; Blood Gas Analysis; Child; Child, Preschool; Electrodiagnosis; Epilepsy; Female; Fructose; Humans; Male; Retrospective Studies; Spinal Fusion; Topiramate

Topiramate is an antiepileptic medication with multiple pharmacologic effects, including inhibition of carbonic anhydrase activity. It is associated with metabolic acidosis in both children and adults.. To evaluate the incidence and magnitude of the effect of topiramate on serum bicarbonate concentrations in an adult population.. This was a retrospective cohort study. Data were evaluated to assess the relationship between serum bicarbonate concentrations before and during topiramate therapy.. Fifty-four patients (40 females) with a mean age of 47.6 years (range 19-89) were included in the study. Mean +/- SD serum bicarbonate concentrations before and during topiramate therapy were 26.8 +/- 2.9 mEq/L (range 21-36) and 21.7 +/- 3.6 mEq/L (range 13-29), respectively, with a mean difference of 5.1 (95% CI 3.7 to 6.5; p < 0.001). Twenty-six patients (48%) had low serum bicarbonate concentrations while on topiramate, with a mean concentration of 18.8 mEq/L (range 13-21).. Topiramate was associated with metabolic acidosis in 48% of the patients studied, which did not result in clinically significant problems.

Topics: Acidosis; Adult; Aged; Aged, 80 and over; Anticonvulsants; Bicarbonates; Cohort Studies; Epilepsy; Female; Fructose; Humans; Male; Middle Aged; Retrospective Studies; Topiramate

Topics: Acidosis; Anticonvulsants; Fructose; Humans; Male; Middle Aged; Topiramate

Topiramate (TPM) is widely used as add-on therapy for epilepsy. TPM inhibits carbonic anhydrase, which may result in metabolic acidosis from decreased serum bicarbonate. The ketogenic diet (KGD) predisposes patients to metabolic acidosis, especially during induction. In children with refractory epilepsy, cotreatment with TPM and KGD may be considered, but special attention should be paid to the combined risks for metabolic acidosis and nephrolithiasis. We report our experience in 14 children cotreated with TPM and the KGD.. Medical records of 14 children cotreated with the KGD and TPM for medically refractory epilepsy were reviewed retrospectively. Bicarbonate levels were analyzed and correlated with clinical profiles, including duration of cotreatment, TPM dose, KGD ratio, and seizure control.. Nine children had a <20% decrease in bicarbonate levels, from 5.3 to 12.3 mEq/L (mean, 7.6 mEq/L). Cotreatment was continued in all patients for duration of 33 to 544 days (seven had remained on cotreatment at the end of the study period), although two children required bicarbonate supplements to continue the KGD. No patient had nephrolithiasis.. Although a large decrease in bicarbonate level occurred in the majority of children, the decrease appeared mostly at the time of KGD induction when added to prior TPM therapy. Bicarbonate levels should be monitored carefully with TPM and KGD cotreatment, and bicarbonate supplements given when symptomatic.

Topics: Acidosis; Adolescent; Age Factors; Anticonvulsants; Bicarbonates; Child; Child, Preschool; Combined Modality Therapy; Epilepsy; Female; Fructose; Humans; Infant; Ketosis; Male; Retrospective Studies; Topiramate; Treatment Outcome; Urinary Calculi

Topiramate (TPM) inhibits carbonic anhydrase, with metabolic acidosis as a possible side effect, although this has been reported in only two adult cases. We investigated the acid-base metabolism in infants and toddlers treated with TPM.. Nine infants and toddlers aged 5 months to 2.3 years (median, 6 months) were treated with TPM at maximal doses of 8.2-26 mg/kg/day (median, 11 mg/kg/day). The maximal TPM dose was achieved after 8-35 days (median, 17 days). TPM was given in addition to other antiepileptic drugs (AEDs) in five cases and as a sole AED in four patients with refractory epilepsy resistant to multiple AEDs. The diagnoses were infantile spasms (n = 5), epilepsia partialis continua (n = 1), infantile epileptic encephalopathy (n = 1), and Lennox-Gastaut syndrome (n = 2).. The blood gases were normal before treatment with TPM in all nine children. Metabolic acidosis developed in eight children after 8-26 days (median, 14 days) of TPM treatment with a minimum of serum bicarbonate between 15 to 18 mM (median, 17 mM), a minimal base excess between -6.2 and -11.2 mM (median, -7.9 mM), and pH between 7.22 and 7.40 (median, 7.35). Four of nine children showed clinical signs of hyperventilation and received oral sodium bicarbonate (1-2 mmol/kg), while TPM was still effective.. Because metabolic acidosis developed in eight of the nine infants and toddlers taking TPM, we would suggest that the acid-base metabolism be monitored in young children who receive TPM.

Topics: Acid-Base Equilibrium; Acidosis; Age Factors; Anticonvulsants; Bicarbonates; Blood Gas Analysis; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Epilepsy; Follow-Up Studies; Fructose; Humans; Hydrogen-Ion Concentration; Infant; Topiramate; Treatment Outcome

Topiramate (TPM) has been widely used as an adjunctive therapy for treating epilepsy. TPM is reported to have multiple mechanisms of action, including inhibition of carbonic anhydrase, which may result in metabolic acidosis from decreased serum bicarbonate (HCO3-).. Clinical data from 30 children who received TPM as adjunctive therapy for medically refractory epilepsy were reviewed at Children's Hospital, Boston. Serum HCO3- levels were assessed before, during, and after discontinuing TPM (n = 9). When multiple data were available, mean values were used for analysis.. Of the 30 patients, 21 had a >10% decrease in HCO3- levels. The mean decrease in HCO3- among the 21 patients was 4.7 mEq/L, and maximum was 10 mEq/L. No clinical symptoms occurred, and HCO3- supplement was not needed, except for one patient who developed tachypnea from worsened acidosis after prolonged status epilepticus during a suspected viral illness. Among the 21 patients, TPM was discontinued in seven children because of a lack of efficacy, and in two because of anorexia. After discontinuing TPM, the serum HCO3- returned to the previous level before starting TPM in all nine.. Decreased HCO3- levels occurred in the majority of patients reviewed, usually only to a small to moderate extent, but by 8 and 10 mEq/L in two cases. In patients at risk for acidosis, the decrease in HCO3- may cause significant consequences, such as severe acidosis or renal calculi. Monitoring HCO3- levels before and during TPM therapy may be indicated, especially with conditions that predispose to acidosis.

Topics: Acidosis; Adolescent; Adult; Age Factors; Anticonvulsants; Bicarbonates; Carbonic Anhydrase Inhibitors; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Epilepsy; Fructose; Humans; Infant; Topiramate

Two children who presented with symptomatic metabolic acidosis after being put on topiramate (TPM) are reported. The first patient was an 11-year-old male with refractory complex partial epilepsy who was put on TPM for 13 months. He developed hyperventilation 1 week after increasing the dose to 300 mg/day. Arterial blood gas revealed hyperchloraemic metabolic acidosis with partial respiratory compensation: pH 7.36, PCO2 27.2 mmHg, bicarbonate 14.9 mEq/L, base excess -8.9 mmol/L. Hyperventilation and acidosis resolved after administration of sodium bicarbonate and reduction of the dose of TPM. The second patient was a female who developed increasing irritability at age 16 months and 21 months, each time associated with introduction of TPM and resolved promptly upon withdrawal of the drug. Venous blood gas taken during the second episode revealed pH 7.34, PCO2 37.4 mmHg, bicarbonate 20.4 mEq/L, base excess -4.2 mmol/L. The predominant mechanism of TPM-induced hyperventilation involves inhibition of carbonic anhydrase at the proximal renal tubule, resulting in impaired proximal bicarbonate reabsorption. The occurrence of hyperpnoea or mental status change in any patient who is on TPM should prompt an urgent blood gas sampling, with correction of the acid-base disturbances accordingly.

Topics: Acidosis; Anticonvulsants; Bicarbonates; Blood Gas Analysis; Child; Dose-Response Relationship, Drug; Epilepsy; Female; Fructose; Humans; Hyperventilation; Infant; Male; Topiramate

Mental status changes and metabolic acidosis may occur with topiramate therapy. These adverse events were reported during dosage titration and with high dosages of the drug. A 20-year-old man receiving topiramate, valproic acid, and phenytoin experienced acute-onset mental status changes with hyperchloremic metabolic acidosis. He had been receiving a modest dose of topiramate for 9 months. He was weaned off topiramate over 5 days, and his mental status returned to baseline within 48 hours of discontinuing the agent. This case illustrates the need for close evaluation of patients who experience acute-onset mental status changes during topiramate therapy.

Topics: Acidosis; Acute Disease; Adult; Anticonvulsants; Chlorides; Confusion; Fructose; Humans; Male; Seizures; Topiramate

Metabolic acidosis induced by topiramate is a well documented but infrequent adverse event. The objective was to demonstrate the lowering of carbon dioxide serum levels, which is usually asymptomatic but may facilitate the occurrence of metabolic acidosis in patients using topiramate.. We evaluated, prospectively, the carbon dioxide serum levels of 18 patients seen at the epilepsy clinic of our university hospital, before and 3 months after introducing topiramate.. Five patients were female and 13 were male, age ranging from 2 to 16 years old (mean=9. 3). Carbon dioxide mean serum levels were 25 and 21.2 mmol/L (normal = 22 to 30), before and 3 months after introducing topiramate, respectively. Dose ranged from 2.08 to 11.76 mg/kg/day (mean=6. 7mg/kg/day). Adverse events were anorexia, nausea and somnolence.. We conclude that the lowering of carbon dioxide serum levels induced by topiramate is mostly asymptomatic, but may facilitate the occurrence of metabolic acidosis. Since patients in use of topiramate have refractory epilepsy, they may need epilepsy surgery, and must be carefully monitored for the risk of metabolic acidosis during surgery.

Topics: Acidosis; Adolescent; Anticonvulsants; Carbon Dioxide; Child; Child, Preschool; Disease Susceptibility; Epilepsy; Female; Fructose; Humans; Infant; Male; Prospective Studies; Topiramate

Topiramate (TPM) is a novel antiepileptic medication (AED) with at least three mechanisms of action. A possible fourth mechanism, that of a carbonic anhydrase inhibitor, also may contribute to its antiepileptic properties. We report a patient with intractable epilepsy and normal renal function who developed a normal anion gap metabolic acidosis, which worsened during elective surgery for temporal lobectomy. We believe this side effect of TPM can become clinically significant during surgery, concomitant use of another carbonic anhydrase inhibitor, and potentially with the ketogenic diet.

Topics: Acidosis; Anticonvulsants; Carbonic Anhydrase Inhibitors; Epilepsy; Epilepsy, Temporal Lobe; Fructose; Humans; Male; Middle Aged; Temporal Lobe; Topiramate