Reinin Special Precautions

Suicidal Behavior and Ideation: Antiepileptic drugs (AEDs), including gabapentin, increase the risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence of worsening of depression, suicidal thoughts or behavior, and/or any unusual changes in mood or behavior.
Pooled analysis of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDS showed that patients randomized to one of the AEDs had approximately twice the risk (adjusted Relative Risk 1.8, 95% CI: 1.2, 2.7) of suicidal thinking or behavior compared to patients randomized to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behavior or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behavior for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behavior with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behavior beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behavior was generally consistent among drugs in the data analyzed. The finding of increased risk with AEDs of varying mechanisms of action and across the range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age in the clinical trials analyzed.
The relative risk for suicidal thoughts or behavior was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing gabapentin or any other AED must balance this risk with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Should suicidal thoughts and behavior emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers and families should be informed that AEDs increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
Neuropsychiatric Adverse Events (Pediatric patients 3 to 12 years old): Gabapentin use in pediatric patients 3 to 12 years old with epilepsy is associated with mild to moderate central nervous system adverse events such as emotional lability (primarily behavioral problems), hostility (including aggressive behaviors), thought disorder (including concentration problems and change in school performance), and hyperkinesias (primarily restlessness and hyperactivity).
Withdrawal Precipitated Seizure, Status Epilepticus: Anticonvulsant drugs, including gabapentin, should not be discontinued suddenly because of the possibility of increased seizure frequency. Discontinuance of gabapentin and/or addition of an alternative anticonvulsant drug to current therapy should be done gradually over a minimum of one week.
Since adequate data are not available, it is impossible to say whether or not treatment with gabapentin is associated with a higher or lower rate of status epilepticus than would be expected to occur in a similar population not treated with gabapentin.
Use in ambulatory patients: Gabapentin may cause drowsiness, somnolence and other symptoms and signs of CNS depression. Patients should be cautioned that the drug may impair their ability to perform hazardous activities requiring mental alertness or physical coordination such as operating machinery or driving a motor vehicle.
Sudden and Unexplained Death in Patients with Epilepsy: During gabapentin's pre-marketing development, sudden and unexplained deaths were reported. Some of these could represent seizure-related deaths in which the seizure was not observed, such as at night. This represents an incidence of 0.0038 deaths per patient-year. Although this rate exceeds that expected in a healthy population matched for age and sex, it is within the range of estimates for the incidence of sudden unexplained deaths in patients with epilepsy not receiving gabapentin. Thus, whether these data are reassuring or raise further concern depends on comparability of the populations reported upon to the gabapentin cohort and the accuracy of the estimates provided.
Use in Children: There is no evidence of safety and efficacy of gabapentin in the management of postherpetic neuralgia in children. There is no evidence of efficacy of gabapentin as adjunctive therapy in the treatment of partial seizures in children below 3 years old.
Use in Elderly: The dose of gabapentin may need to be reduced in proportion to any reduction in creatinine clearance.