Levetiracetam-associated hyponatremia

Hyponatremia has been associated with several antiepileptic drugs (AEDs), such as carbamazepine, oxcarbazepine, and occasionally with valproate and lamotrigine. 1,2 To date, there is only a report of hyponatremia associated with levetiracetam in a 65-year-old patient predisposed to the development of syndrome of inappropriate antidiuretic hormone secretion (SIADH). 3 We recently observed a patient developing hyponatremia following two challanges with levetiracetam in absence of any evident predisposition to SIADH. This 76-year-old man suffered from complex partial seizures, occasionally followed by secondarily generalization, started 4 months before. Initial treatment with phenobarbital (100 mg daily) was soon discontinued due to diurnal somnolence and replaced with levetiracetam (1000 mg twice daily). Six months later the man was admitted to our Neurology Clinic due to a tonic—clonic seizure. His previous medical history included hypertension and anxiety for which he was receiving amlodipine and lorazepam. At admission, an EEG revealed later-alized temporal epileptiform activity. Brain MRI and chest CT scan were unremarkable. Haematological tests showed serum sodium level of 127 mM (normal, 135—145) and osmolality of 290 mOsm/kg (normal, 280—300). Urine sodium and osmolality were 6 mM (normal, <10) and 190 Osm/kg (normal, 250—1200).tion were normal. Due to the poor clinical efficacy, levetiracetam was discontinued and valproic acid (600 mg daily) was initiated. A week later, his serum sodium level was 136 mM and the patient was discharged. However, at home his wife erroneously restarted levetiracetam treatment (500 mg twice daily). No further seizures did occur. A week later, serum sodium level were 130 mM, and osmolality of 290 mOsm/kg. Urine sodium and urine osmolality were within the normal limits. The patient was asymptomatic. Levetiracetam was discontinued, and the sodium level normalized after 4 days. Levetiracetam is an increasingly used AED with apparently low profile of toxicity. The most common adverse events mentioned in clinical trials include somnolence, asthenia, headache, dizziness, and nervousness. 4 This patient developed asymptomatic hyponatre-mia after two levetiracetam challenges, one of which in monotherapy. Amlodipine, which was a comedica-tion in our patient, has been previously associated with hyponatremia in a single case report. 5 However, it is unlikely that amlodipine induced low serum sodium as its dose remained stable during the two levetiracetam trials. Other causes of hyponatremia were excluded. There was a clear temporal association between the introduction and discontinuation of levetiracetam as previously reported, 3 likely due to the rapid (1 h after administration) peak effect of the drug …