Journal Information
Vol. 32. Issue. 3.May 2012
Pages 275-418
Full text access
Topiramate-induced metabolic acidosis: a case study
Acidosis metabólica inducida por topiramato: a propósito de un caso.
Visits
12175
Lucía Fernández-de Oruetaa, Javier Esteban-Fernándeza, Harald F.J. Aichnera, Ángel Casillas-Villamora, Sergio Rodríguez-Álvareza
a Servicio de Medicina Interna, Hospital Universitario de Getafe, Getafe, Madrid,
This item has received
Article information
Full Text
Bibliography
Download PDF
Statistics
Full Text

We present the case of a 75 year-old male with hypertension and chronic obstructive pulmonary disease who was diagnosed with chronic delusional disorder and mixed personality disorder, along with partial epilepsy due to a left parietal haematoma from several years prior. The patient was under treatment with topiramate, levetiracetam, quetiapine, sertraline, clobazam, and bronchodilators. He sought treatment for a respiratory infection and functional deterioration consisting of apathy, drowsiness, and periods of aggressive behaviour. A physical examination revealed that the patient had no fever, although he did suffer from disorientation and slurred speech, and would drift off to sleep, but with no apparent focal loss of motor function. The patient also had shallow tachypnoea, widespread rhonchi, and crackles in the left base, with radiological images indicative of superinfection of the abnormally widened bronchial tubes. We performed a laboratory analysis, revealing mildly elevated chlorine (114mEq/l), with normal renal function and all other ion parameters (sodium: 138mEq/l; potassium: 4.2mEq/l), and baseline arterial gasses compatible with a diagnosis of metabolic acidosis (pH: 7.24; pCO2: 33mm Hg; pO2: 67mm Hg; bicarbonate: 17mmol/l; base excess [BE]: -9.1mmol/l). The anion GAP value (difference between serum sodium and the sum of chlorine and bicarbonate) was 7mEq/l. The patient received treatment with systemic steroids and quinolones, with rapid clinical improvement until reaching a normal baseline levels. However, later controls revealed persistent hyperchloremic metabolic acidosis; after ruling out other possibilities, we attributed this fact to the chronic treatment with topiramate, which was suspended and replaced with phenytoin, which completely resolved the altered laboratory values by the time the patient was discharged.

Topiramate is a sulphamate with anti-epileptic effects, and is indicated in preventative treatment of migrane,1,2 the treatment of neuropathic pain3, bipolar disorder,3 tobacco dependence, and bulimia nervosa,4 among other pathologies. Its most common secondary side effects2,5 are asthenia, dizziness, drowsiness, emotional lability, and weight loss. The development of urolithiasis and hyperchloremic metabolic acidosis with a normal anion GAP is much less common, but has been reported. Topiramate has a molecular structure very similar to acetazolamide2,6 and inhibits the carbonic anhydrase enzyme,3,6 especially the type II isoenzyme that predominates in human kidneys.1,2,6 This can lead to mixed renal tubular acidosis1 (type 3) as a result of ultrafiltration and reabsorption of bicarbonate in both proximal and distal tubules,4 thus altering urine acidification and provoking a decrease in serum bicarbonate and CO2 concentrations,4 which is usually mild and asymptomatic,7,8 although can produce hyperventilation,3,4 neurological symptoms,3 nephrolithiasis, osteoporosis, and osteomalacia in the long term. The circumstances that predispose patients to developing this complication are not well established, but patients are more likely to develop it if they have other conditions that cause acidosis, such as infections, diabetic ketoacidosis, chronic renal failure, or surgery.4,5 Certain genetic polymorphisms in the involved carbonic anhydrase isoenzymes may explain a greater or lesser susceptibility of certain patients to develop this complication.3,9 Some authors have suggested the possibility of monitoring bicarbonate1,6 or CO23,5 levels to predict these cases, although this is not a completely validated method. The development of metabolic acidosis during chronic treatment with topiramate is a reversible condition, regardless of the dosage3,9 and duration of treatment.9 The only treatment is to suspend the use of the drug10 (there is no antidote) and replace it with a substitute. When the withdrawal of the drug is not possible, and the patient maintains acceptable levels of pH and serum bicarbonate, with no symptoms, indefinite treatment with oral alkaline supplements can be administered (sodium citrate or citric acid1).

 

Conflicts of interest

The authors affirm that they have no conflicts of interest related to the content of this article.

Bibliography
[1]
1. Mirza N, Marson AG, Pirmohamed M. Effect of topiramate on acid-base balance: extent, mechanism and effects. Br J Clin Pharmacol 2009;68:655-61. [Pubmed]
[2]
Sacré A, Jouret F, Manicourt D, Devuyst O. Topiramate induces type 3 renal tubular acidosis by inhibiting renal carbonic anhydrase. Nephrol Dial Transplant 2006;21:2995-6. [Pubmed]
[3]
Burmeister JE, Pereira RR, Hartke EM, Kreuz M. Topiramate and severe metabolic acidosis: case report. Arq Neuropsiquiatr 2005;63:532-4. [Pubmed]
[4]
García Gil D, Pérez V, Asencio C, García-Torrejón J. Acute topiramete toxicity to suicidal attempt. Med Clin (Barc) 2009;133:766-7.
[5]
5. Montenegro MA, Guerreiro MM, Scotoni AE, Guerreiro CA. Predisposition to metabolic acidosis induced by topiramate. Arq Neuropsiquiatr 2000;58:1021-4. [Pubmed]
[6]
Sujan S, Torres de Rueda A, Montero L, Toledo R, Ros S, Martín Reyes G. Topiramate-induced renal tubular acidosis. A case report. Nefrologia. 2008;28(6):656-7.
[7]
Garris SS, Oles KS. Impact of topiramate on serum bicarbonate concentrations in adults. Ann Pharmacother 2005;39:424-6. [Pubmed]
[8]
Groeper K, McCann ME. Topiramate and metabolic acidosis: a case series and review of the literature. Paediatr Anaesth 2005;15:167-70. [Pubmed]
[9]
9. Mirza NS, Alfirevic A, Jorgensen A, Marson AG, Pirmohamed M. Metabolic acidosis with topiramate and zonisamide: an assessment of its severity and predictors. Pharmacogenet Genomics 2011;21:297-302. [Pubmed]
[10]
Shiber JR. Severe non-anion gap metabolic acidosis induced by topiramate: a case report. J Emerg Med 2010;38:494-6. [Pubmed]
Idiomas
Nefrología (English Edition)
Article options
Tools
es en

¿Es usted profesional sanitario apto para prescribir o dispensar medicamentos?

Are you a health professional able to prescribe or dispense drugs?