Renal effects topiramate

Hemodialysis Topiramate is cleared by hemodialysis 4 to 6 times greater than in a healthy individual a prolonged period of dialysis may cause topiramate levels to fall below that required to maintain an antiseizure effect. To avoid rapid drops in topiramate plasma concentration during hemodialysis, a supplemental dose of topiramate may be required. The actual adjustment should take into account 1) the duration of the dialysis period, 2) the clearance rate of the dialysis system being used, and 3) the effective renal clearance of topiramate in the patient being dialyzed. 

Metabolic acidosis Hyperchloremic, nonanion gap, metabolic acidosis is associated with topiramate treatment. This metabolic acidosis is caused by renal bicarbonate loss because of the inhibitory effect of topiramate on carbonic anhydrase. Generally, topiramate-induced metabolic acidosis occurs early in treatment, although cases can occur at any time during treatment. Bicarbonate decrements usually are mild to moderate rarely, patients can experience severe decrements to values below 10 mEq/L. Conditions or therapies that predispose to acidosis may be additive to the bicarbonate lowering effects of topiramate. If metabolic acidosis develops and persists, consider reducing the dose or discontinuing topiramate. 

Adverse effects These are primarily related to CNS and Gl disturbances. They include impaired concentration, dizziness, ataxia, diplopia, somnolence, nervousness, and confusion, as well as nausea and weight loss. Renal stones have been reported in 1.5 percent of patients. Topiramate is teratogenic in animals, and should be avoided during pregnancy. Inducers of drug metabolism such as phenytoin and carbamazepine decrease topiramate serum concentrations by approximately 50 percent. Topiramate decreases ethinyl estradiol concentrations of oral contraceptive preparations, and individuals should supplement the amount of ethinyl estradiol. 

The efficacy and tolerability of topiramate have been studied in 170 patients with refractory epilepsy (7). The most common adverse effects resulting in withdrawal were fatigue, weight loss, irritability, paresthesia, depression, and headache. Three patients developed renal calculi but continued therapy. 

The results of six double-blind, placebo-controlled trials with topiramate in adults with treatment-resistant partial-onset seizures with or without secondary generalization have been analysed (14). Seizures were reduced by at least 50% in 43% of topiramate-treated patients and in 12% of placebo-treated patients. The most common treatment-related adverse events were dizziness, somnolence, fatigue, psychomotor slowing, nervousness, paresthesia, ataxia, memory difficulty, and speech problems. These effects were generally mild to moderate, usually occurred early in treatment, often during titration, and resolved with continued treatment. Other adverse effects were weight loss and, in a few patients, renal calculi. 

Topiramate Blocks glutamate (AMPA) receptors T GABA effects Partial seizures Sedation, ataxia, j weight loss, j word-finding s difficulty, j renal stones i 1... 

Topiramate is well tolerated. The most common adverse effects are somnolence, fatigne, weight loss, and nervousness. It can precipitate renal calculi, which is most likely due to inhibition of carbonic anhydrase. Topiramate has been associated with cognitive impairment and patients may complain abont a change in the taste of carbonated beverages. 

The anticonvulsant topiramate has also been reported to be effective in reducing binge and purge frequencies in comparison with placebo. However, bothersome side-effects such as paresthesias, impaired cognition, and renal calculi may lessen its usefulness. Naltrexone is a possible adjunct in patients who are refractory to SSRIs, especially those with comorbid alcoholism and/or self-injurious behavior. ... 

The reasons for these reactions are not known, but topiramate is mainly eliminated by renal excretion and high doses of topiramate may competitively interfere with lithium excretion. Similarly, lithium may affect topiramate clearance. Some of the toxicity could have been due to the adverse effects of either drug, with the weight loss in the first case possibly disturbing the sodium excretion, which could have affected the loss of lithium in the urine. 

All the available evidence for the use of topiramate as monotherapy in patients with newly or recently diagnosed epilepsy has been examined in a systematic review of three randomized, double-bUnd, controlled trials which recruited more than 1000 patients [302 ]. The most common adverse events associated with topiramate 50-500 mg/day generally occurred early in the course of treatment and were nervous system-related effects headache (15-25%), dizziness (12-19%), fatigue (11-23%), somnolence (10-17%), anorexia (8-10%), insomnia (7—10%), and hyperesthesia (5— 10%). Adverse events that were likely to have been related to the carbonic-anhy-drase activity of topiramate (e.g. paresthesia, changes in serum bicarbonate) were frequent (13-35%) but were not usually considered clinically relevant Renal calculi occurred infrequently (1%). The most frequent adverse events during maintenance therapy were headache (20%), reduced appetite (11%), and weight loss (11%). 

Add-base balance In some patients topiramate can cause metabolic acidosis, whose susceptibility factors, underlying mechanisms, and clinical effects have been reviewed [318 ]. Topiramate impairs both the normal reabsorption of filtered HCO by the proximal renal tubule and the excretion of by the distal renal tubule. This combination of defects is termed mixed renal tubular acidosis. The mechanism involves inhibition of carbonic anhydrase. This mechanism can make patients acutely ill, and chronically can lead to nephrolithiasis, osteoporosis, and in children growth retardation. The usefulness of monitoring HCO concentrations has not been proven and is not routine. Hence, there is no proven method for predicting or preventing the effect of topiramate on acid-base balance. However, patients with a history of renal calculi or known mixed renal tubular acidosis should not receive topiramate. 

---