be made whether to discontinue breast-feeding or discontinue levetiracetam. Other experts suggest that breast-feeding may be continued during levetiracetam therapy in some cases. In one small case series, foremilk samples were taken 3—5 days postpartum from 7 women who were taking levetiracetam 1,500—3,500 mg/day PO. The mean milk:maternal serum concentration ratio was 1 (range 0.76—1.33); however, six of the infant corresponding serum concentrations were very low or below the level of quantification. The remaining infant did not have a serum concentration measured at 3—5 days of age. Milk concentrations were measured again from one or more women at 2 weeks, 4 weeks, 6—8 weeks, 4 months, and 10 months postpartum, and the maternal milk:serum ratios were similar to those at 3—5 days postpartum. No infant-related adverse effects were noted. In another case series including 11 mother-infant pairs, levetiracetam was excreted into breast milk at a concentration similar to that in maternal plasma; the mean milk:plasma ratio was 1.05 (range 0.78—1.55). Assuming a daily milk intake of 150 ml/kg/day, the infant dose was estimated to be approximately 2.4 mg/kg/day. Although no safe dosage range has been established in the neonatal population, initial doses of 14 mg/kg/day PO are FDA approved for patients as young as one month of age (see Dosage). NOTE: In this study, milk concentrations were single, morning trough concentrations collected between day 4 and 23 after delivery; therefore, total infant exposure over a 24-hour period may differ from this estimate. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated seizure disorder. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.
Driving or operating machinery
Levetiracetam commonly causes somnolence, fatigue, and dizziness. Somnolence occurs most frequently within the first 4 weeks of treatment. Patients should be advised to use caution when driving or operating machinery, or performing other tasks that require mental alertness until they are aware of whether levetiracetam adversely affects their mental and/or motor performance. Levetiracetam has been associated with somnolence, fatigue, and behavioral abnormalities.
Depression, suicidal ideation
In January 2008, the FDA alerted healthcare professionals of an increased risk of suicidal ideation and behavior in patients receiving anticonvulsants to treat epilepsy, psychiatric disorders, or other conditions (e.g., migraine, neuropathic pain). This alert followed an initial request by the FDA in March 2005 for manufacturers of marketed anticonvulsants to provide data from existing controlled clinical trials for analysis. Prior to this request, preliminary evidence had suggested a possible link between anticonvulsant use and suicidality. The primary analysis consisted of 199 placebo-controlled clinical studies with a total of 27,863 patients in drug treatment groups and 16,029 patients in placebo groups (>= 5 years of age). There were 4 completed suicides among patients in drug treatment groups versus none in the placebo groups. Patients receiving anticonvulsants had approximately twice the risk of suicidal behavior or ideation as patients receiving placebo (0.43% vs. 0.24%, respectively; RR 1.8, 9 |
