United States - English - NLM (National Library of Medicine)
Aphena Pharma Solutions - Tennessee, LLC
Gabapentin Tablets, USP
Read the Medication Guide before you start taking gabapentin and each time you get a refill. There may be
new information. This information does not take the place of talking to your healthcare provider about your
medical condition or treatment.
What is the most important information I should know about gabapentin?
Do not stop taking gabapentin without first talking to your healthcare provider.
Stopping gabapentin suddenly can cause serious problems.
Gabapentin can cause serious side effects including:
1. Like other antiepileptic drugs, gabapentin may cause suicidal thoughts or actions in a very small number of
people, about 1 in 500.
Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse,
or worry you:
thoughts about suicide or dying
attempts to commit suicide
new or worse depression
new or worse anxiety
feeling agitated or restless
trouble sleeping (insomnia)
new or worse irritability
acting aggressive, being angry, or violent
acting on dangerous impulses
an extreme increase in activity and talking (mania)
other unusual changes in behavior or mood
How can I watch for early symptoms of suicidal thoughts and actions?
Pay attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or feelings.
Keep all follow-up visits with your healthcare provider as scheduled.
Call your healthcare provider between visits as needed, especially if you are worried about symptoms.
Do not stop taking gabapentin without first talking to a healthcare provider.
Stopping gabapentin suddenly can cause serious problems. Stopping a seizure medicine suddenly in a
patient who has epilepsy can cause seizures that will not stop (status epilepticus).
Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or
actions, your healthcare provider may check for other causes.
2. Changes in behavior and thinking - Using gabapentin in children 3 to 12 years of age can cause emotional
changes, aggressive behavior, problems with concentration, restlessness, changes in school performance, and
What is gabapentin?
Gabapentin is a prescription medicine used to treat:
Pain from damaged nerves (postherpetic pain) that follows healing of shingles (a painful rash that
comes after a herpes zoster infection) in adults.
Partial seizures when taken together with other medicines in adults and children 3 years of age and
Who should not take gabapentin?
Do not take gabapentin if you are allergic to gabapentin or any of the other ingredients in gabapentin. See the
end of this Medication Guide for a complete list of ingredients in gabapentin.
What should I tell my healthcare provider before taking gabapentin?
Before taking gabapentin, tell your healthcare provider if you:
have or have had kidney problems or are on hemodialysis
have or have had depression, mood problems, or suicidal thoughts or behavior
are pregnant or plan to become pregnant. It is not known if gabapentin can harm your unborn baby.
Tell your healthcare provider right away if you become pregnant while taking gabapentin. You and
your healthcare provider will decide if you should take gabapentin while you are pregnant.
If you become pregnant while taking gabapentin, talk to your healthcare provider about registering
with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The purpose of this
registry is to collect information about the safety of antiepileptic drugs during pregnancy. You can
enroll in this registry by calling 1-888-233-2334.
are breastfeeding or plan to breastfeed. Gabapentin can pass into breast milk. You and your healthcare
provider should decide how you will feed your baby while you take gabapentin.
Tell your healthcare provider about all the medicines you take, including prescription and non-prescription
medicines, vitamins, and herbal supplements.
Taking gabapentin with certain other medicines can cause side effects or affect how well they work. Do not
start or stop other medicines without talking to your healthcare provider.
Know the medicines you take. Keep a list of them and show it to your healthcare provider and pharmacist
when you get a new medicine.
How should I take gabapentin?
Take gabapentin exactly as prescribed. Your healthcare provider will tell you how much gabapentin
Do not change your dose of gabapentin without talking to your healthcare provider. If you break a
tablet in half the unused half of the tablet should be taken at your next scheduled dose. Half tablets
not used within several days of breaking should be thrown away.
Gabapentin can be taken with or without food. If you take an antacid containing aluminum and
magnesium, such as Maalox®, Mylanta®, Gelusil®, Gaviscon®, or Di-Gel®, you should wait at least
2 hours before taking your next dose of gabapentin.
If you take too much gabapentin, call your healthcare provider or your local Poison Control Center
What should I avoid while taking gabapentin?
Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking gabapentin
without first talking with your healthcare provider. Taking gabapentin with alcohol or drugs that
cause sleepiness or dizziness may make your sleepiness or dizziness worse.
Do not drive, operate heavy machinery, or do other dangerous activities until you know how
gabapentin affects you. Gabapentin can slow your thinking and motor skills.
What are the possible side effects of gabapentin?
See "What is the most important information I should know about gabapentin?"
The most common side effects of gabapentin include:
lack of coordination
difficulty with speaking
temporary loss of memory (amnesia)
difficulty with coordination
unusual eye movement
Tell your healthcare provider if you have any side effect that bothers you or that does not go away.
These are not all the possible side effects of gabapentin. For more information, ask your healthcare provider
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-
How should I store gabapentin?
Store gabapentin tablets at 20° to 25°C (68° to 77°F). [See USP controlled room temperature].
Keep gabapentin and all medicines out of the reach of children.
General information about the safe and effective use of gabapentin
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use
gabapentin for a condition for which it was not prescribed. Do not give gabapentin to other people, even if
they have the same symptoms that you have. It may harm them.
This Medication Guide summarizes the most important information about gabapentin. If you would like more
information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for
information about gabapentin that was written for healthcare professionals.
For more information about gabapentin tablets, or to report side effects regarding gabapentin tablets, please
call Exelan Pharmaceuticals Inc. at 1-855-295-7455.
What are the ingredients in gabapentin Tablets?
Active ingredient: Gabapentin, USP
Inactive ingredients: Mannitol, Hydroxypropyl Cellulose, Crospovidone, Talc, Magnesium Stearate and
Aquarius® BP18114 Cool Vanilla.
InvaGen Pharmaceuticals, Inc.
Hauppauge, NY, 11788
Exelan Pharmaceuticals, Inc.
Lawrenceville, GA 30046
Document Id: 3d72b0b2-b4b3-4643-96ab-de4106a5320b
Set id: 11da2692-fb0a-4519-b8a4-323c7a6eeb4d
Effective Time: 20200603
Aphena Pharma Solutions - Tennessee, LLC
GABAPENTIN - gabapentin tablet, film coated
Aphena Pharma Solutions - Tennessee, LLC
Gabapentin Tablets, USP
Gabapentin tablets, USP are white colored film coated, modified capsule shaped biconvex tablets
containing 600 mg and 800 mg of gabapentin, USP.
Each tablet for oral administration contains the following inactive ingredients: Mannitol, Hydroxypropyl
Cellulose, Crospovidone, Talc, Magnesium Stearate and Aquarius
BP18114 Cool Vanilla.
Gabapentin is described as 1-(aminomethyl)cyclohexaneacetic acid with a molecular formula of
C H NO and a molecular weight of 171.24. The structural formula of gabapentin is:
Gabapentin is a white to off-white crystalline solid with a pK of 3.7 and a pK of 10.7. It is freely
soluble in water and both basic and acidic aqueous solutions. The log of the partition coefficient (n-
octanol/0.05M phosphate buffer) at pH 7.4 is -1.25.
This product(Gabapentin Tablets, USP 600 mg and 800 mg) meets the USP Dissolution Test 1.
Mechanism of Action
The mechanism by which gabapentin exerts its analgesic action is unknown, but in animal models of
analgesia, gabapentin prevents allodynia (pain-related behavior in response to a normally innocuous
stimulus) and hyperalgesia (exaggerated response to painful stimuli). In particular, gabapentin prevents
pain-related responses in several models of neuropathic pain in rats or mice (e.g., spinal nerve ligation
models, streptozocin-induced diabetes model, spinal cord injury model, acute herpes zoster infection
model). Gabapentin also decreases pain-related responses after peripheral inflammation (carrageenan
footpad test, late phase of formalin test). Gabapentin did not alter immediate pain-related behaviors (rat
tail flick test, formalin footpad acute phase, acetic acid abdominal constriction test, footpad heat
irradiation test). The relevance of these models to human pain is not known.
The mechanism by which gabapentin exerts its anticonvulsant action is unknown, but in animal test
systems designed to detect anticonvulsant activity, gabapentin prevents seizures as do other marketed
anticonvulsants. Gabapentin exhibits antiseizure activity in mice and rats in both the maximal
electroshock and pentylenetetrazole seizure models and other preclinical models (e.g., strains with
genetic epilepsy, etc.). The relevance of these models to human epilepsy is not known.
Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid) but it does
not modify GABA or GABA radioligand binding, it is not converted metabolically into GABA or a
GABA agonist, and it is not an inhibitor of GABA uptake or degradation. Gabapentin was tested in
radioligand binding assays at concentrations up to 100 µM and did not exhibit affinity for a number of
other common receptor sites, including benzodiazepine, glutamate, N-methyl-D-aspartate (NMDA),
quisqualate, kainate, strychnine-insensitive or strychnine-sensitive glycine, alpha 1, alpha 2, or beta
adrenergic, adenosine A1 or A2, cholinergic muscarinic or nicotinic, dopamine D1 or D2, histamine
H1, serotonin S1 or S2, opiate mu, delta or kappa, cannabinoid 1, voltage-sensitive calcium channel sites
labeled with nitrendipine or diltiazem, or at voltage-sensitive sodium channel sites labeled with
batrachotoxinin A 20-alpha-benzoate. Furthermore, gabapentin did not alter the cellular uptake of
dopamine, noradrenaline, or serotonin.
In vitro studies with radiolabeled gabapentin have revealed a gabapentin binding site in areas of rat brain
including neocortex and hippocampus. A high-affinity binding protein in animal brain tissue has been
identified as an auxiliary subunit of voltage-activated calcium channels. However, functional correlates
of gabapentin binding, if any, remain to be elucidated.
Pharmacokinetics and Drug Metabolism
All pharmacological actions following gabapentin administration are due to the activity of the parent
compound; gabapentin is not appreciably metabolized in humans.
Oral Bioavailability: Gabapentin bioavailability is not dose proportional; i.e., as dose is increased,
bioavailability decreases. Bioavailability of gabapentin is approximately 60%, 47%, 34%, 33%, and
27% following 900, 1200, 2400, 3600, and 4800 mg/day given in 3 divided doses, respectively. Food
has only a slight effect on the rate and extent of absorption of gabapentin (14% increase in AUC and
Distribution: Less than 3% of gabapentin circulates bound to plasma protein. The apparent volume of
distribution of gabapentin after 150 mg intravenous administration is 58±6 L (Mean ±SD). In patients
with epilepsy, steady-state predose (C
) concentrations of gabapentin in cerebrospinal fluid were
approximately 20% of the corresponding plasma concentrations.
Elimination: Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged
drug. Gabapentin is not appreciably metabolized in humans.
Gabapentin elimination half-life is 5 to 7 hours and is unaltered by dose or following multiple dosing.
Gabapentin elimination rate constant, plasma clearance, and renal clearance are directly proportional to
creatinine clearance (see Special Populations: Patients With Renal Insufficiency , below). In elderly
patients, and in patients with impaired renal function, gabapentin plasma clearance is reduced. Gabapentin
can be removed from plasma by hemodialysis.
Dosage adjustment in patients with compromised renal function or undergoing hemodialysis is
recommended (see DOSAGE AND ADMINISTRATION, Table 6).
Special Populations: Adult Patients With Renal Insufficiency: Subjects (N=60) with renal insufficiency
(mean creatinine clearance ranging from 13 to 114 mL/min) were administered single 400 mg oral doses
of gabapentin. The mean gabapentin half-life ranged from about 6.5 hours (patients with creatinine
clearance >60 mL/min) to 52 hours (creatinine clearance <30 mL/min) and gabapentin renal clearance
from about 90 mL/min (>60 mL/min group) to about 10 mL/min (<30 mL/min). Mean plasma clearance
(CL/F) decreased from approximately 190 mL/min to 20 mL/min.
Dosage adjustment in adult patients with compromised renal function is necessary (see DOSAGE AND
ADMINISTRATION). Pediatric patients with renal insufficiency have not been studied.
Hemodialysis: In a study in anuric adult subjects (N=11), the apparent elimination half-life of gabapentin
on nondialysis days was about 132 hours; during dialysis the apparent half-life of gabapentin was
reduced to 3.8 hours. Hemodialysis thus has a significant effect on gabapentin elimination in anuric
Dosage adjustment in patients undergoing hemodialysis is necessary (see DOSAGE AND
Hepatic Disease: Because gabapentin is not metabolized, no study was performed in patients with hepatic
Age: The effect of age was studied in subjects 20 to 80 years of age. Apparent oral clearance (CL/F) of
gabapentin decreased as age increased, from about 225 mL/min in those under 30 years of age to about
125 mL/min in those over 70 years of age. Renal clearance (CLr) and CLr adjusted for body surface
area also declined with age; however, the decline in the renal clearance of gabapentin with age can
largely be explained by the decline in renal function. Reduction of gabapentin dose may be required in
patients who have age related compromised renal function. (See PRECAUTIONS, Geriatric Use, and
DOSAGE AND ADMINISTRATION.)
Pediatric: Gabapentin pharmacokinetics were determined in 48 pediatric subjects between the ages of 1
month and 12 years following a dose of approximately 10 mg/kg. Peak plasma concentrations were
similar across the entire age group and occurred 2 to 3 hours postdose. In general, pediatric subjects
between 1 month and <5 years of age achieved approximately 30% lower exposure (AUC) than that
observed in those 5 years of age and older. Accordingly, oral clearance normalized per body weight
was higher in the younger children. Apparent oral clearance of gabapentin was directly proportional to
creatinine clearance. Gabapentin elimination half-life averaged 4.7 hours and was similar across the age
A population pharmacokinetic analysis was performed in 253 pediatric subjects between 1 month and 13
years of age. Patients received 10 to 65 mg/kg/day given TID. Apparent oral clearance (CL/F) was
directly proportional to creatinine clearance and this relationship was similar following a single dose
and at steady state. Higher oral clearance values were observed in children <5 years of age compared
to those observed in children 5 years of age and older, when normalized per body weight. The
clearance was highly variable in infants <1 year of age. The normalized CL/F values observed in
pediatric patients 5 years of age and older were consistent with values observed in adults after a single
dose. The oral volume of distribution normalized per body weight was constant across the age range.
These pharmacokinetic data indicate that the effective daily dose in pediatric patients with epilepsy ages
3 and 4 years should be 40 mg/kg/day to achieve average plasma concentrations similar to those
achieved in patients 5 years of age and older receiving gabapentin at 30 mg/kg/day. (see DOSAGE
Gender: Although no formal study has been conducted to compare the pharmacokinetics of gabapentin in
men and women, it appears that the pharmacokinetic parameters for males and females are similar and
there are no significant gender differences.
Race: Pharmacokinetic differences due to race have not been studied. Because gabapentin is primarily
renally excreted and there are no important racial differences in creatinine clearance, pharmacokinetic
differences due to race are not expected.
Gabapentin was evaluated for the management of postherpetic neuralgia (PHN) in 2 randomized, double-
blind, placebo-controlled, multicenter studies; N=563 patients in the intent-to-treat (ITT) population
(Table 1). Patients were enrolled if they continued to have pain for more than 3 months after healing of
the herpes zoster skin rash.
TABLE 1. Controlled PHN Studies: Duration, Dosages, and
Number of Patients
Each study included a 1 week baseline during which patients were screened for eligibility and a 7- or 8-
week double-blind phase (3 or 4 weeks of titration and 4 weeks of fixed dose). Patients initiated
treatment with titration to a maximum of 900 mg/day gabapentin over 3 days. Dosages were then to be
titrated in 600 to 1200 mg/day increments at 3- to 7-day intervals to target dose over 3 to 4 weeks. In
Study 1, patients were continued on lower doses if not able to achieve the target dose. During baseline
and treatment, patients recorded their pain in a daily diary using an 11-point numeric pain rating scale
ranging from 0 (no pain) to 10 (worst possible pain). A mean pain score during baseline of at least 4 was
required for randomization (baseline mean pain score for Studies 1 and 2 combined was 6.4). Analyses
were conducted using the ITT population (all randomized patients who received at least one dose of
Both studies showed significant differences from placebo at all doses tested.
A significant reduction in weekly mean pain scores was seen by Week 1 in both studies, and significant
differences were maintained to the end of treatment. Comparable treatment effects were observed in all
active treatment arms. Pharmacokinetic/pharmacodynamic modeling provided confirmatory evidence of
efficacy across all doses. Figures 1 and 2 show these changes for Studies 1 and 2.
Given in 3 divided doses (TID)
The proportion of responders (those patients reporting at least 50% improvement in endpoint pain score
compared with baseline) was calculated for each study (Figure 3).
The effectiveness of gabapentin as adjunctive therapy (added to other antiepileptic drugs) was
established in multicenter placebo-controlled, double-blind, parallel-group clinical trials in adult and
pediatric patients (3 years and older) with refractory partial seizures.
Evidence of effectiveness was obtained in three trials conducted in 705 patients (age 12 years and
above) and one trial conducted in 247 pediatric patients (3 to 12 years of age). The patients enrolled had
a history of at least 4 partial seizures per month in spite of receiving one or more antiepileptic drugs at
therapeutic levels and were observed on their established antiepileptic drug regimen during a 12 week
baseline period (6 weeks in the study of pediatric patients). In patients continuing to have at least 2 (or 4
in some studies) seizures per month, gabapentin or placebo was then added on to the existing therapy
during a 12 week treatment period. Effectiveness was assessed primarily on the basis of the percent of
patients with a 50% or greater reduction in seizure frequency from baseline to treatment (the "responder
rate" ) and a derived measure called response ratio, a measure of change defined as (T - B)/(T + B),
where B is the patient’s baseline seizure frequency and T is the patient’s seizure frequency during
treatment. Response ratio is distributed within the range -1 to +1. A zero value indicates no change
while complete elimination of seizures would give a value of -1; increased seizure rates would give
positive values. A response ratio of -0.33 corresponds to a 50% reduction in seizure frequency. The
results given below are for all partial seizures in the intent-to-treat (all patients who received any
doses of treatment) population in each study, unless otherwise indicated.
One study compared gabapentin 1200 mg/day divided TID with placebo. Responder rate was 23%
(14/61) in the gabapentin group and 9% (6/66) in the placebo group; the difference between groups was
statistically significant. Response ratio was also better in the gabapentin group (-0.199) than in the
placebo group (-0.044), a difference that also achieved statistical significance.
A second study compared primarily 1200 mg/day divided TID gabapentin (N=101) with placebo (N
=98). Additional smaller gabapentin dosage groups (600 mg/day, N=53; 1800 mg/day, N=54) were also
studied for information regarding dose response. Responder rate was higher in the gabapentin 1200
mg/day group (16%) than in the placebo group (8%), but the difference was not statistically significant.
The responder rate at 600 mg (17%) was also not significantly higher than in the placebo, but the
responder rate in the 1800 mg group (26%) was statistically significantly superior to the placebo rate.
Response ratio was better in the gabapentin 1200 mg/day group (-0.103) than in the placebo group (-
0.022); but this difference was also not statistically significant (p = 0.224). A better response was seen
in the gabapentin 600 mg/day group (-0.105) and 1800 mg/day group (-0.222) than in the 1200 mg/day
group, with the 1800 mg/day group achieving statistical significance compared to the placebo group.
A third study compared gabapentin 900 mg/day divided TID (N=111) and placebo (N=109). An
additional gabapentin 1200 mg/day dosage group (N=52) provided dose-response data. A statistically
significant difference in responder rate was seen in the gabapentin 900 mg/day group (22%) compared
to that in the placebo group (10%). Response ratio was also statistically significantly superior in the
gabapentin 900 mg/day group (-0.119) compared to that in the placebo group (-0.027), as was response
ratio in 1200 mg/day gabapentin (-0.184) compared to placebo.
Analyses were also performed in each study to examine the effect of gabapentin on preventing
secondarily generalized tonic-clonic seizures. Patients who experienced a secondarily generalized
tonic-clonic seizure in either the baseline or in the treatment period in all three placebo-controlled
studies were included in these analyses. There were several response ratio comparisons that showed a
statistically significant advantage for gabapentin compared to placebo and favorable trends for almost
Analysis of responder rate using combined data from all three studies and all doses (N=162, gabapentin;
N=89, placebo) also showed a significant advantage for gabapentin over placebo in reducing the
frequency of secondarily generalized tonic-clonic seizures.
In two of the three controlled studies, more than one dose of gabapentin was used. Within each study the
results did not show a consistently increased response to dose. However, looking across studies, a
trend toward increasing efficacy with increasing dose is evident (see Figure 4 ).
In the figure, treatment effect magnitude, measured on the Y axis in terms of the difference in the
proportion of gabapentin and placebo assigned patients attaining a 50% or greater reduction in seizure
frequency from baseline, is plotted against the daily dose of gabapentin administered (X axis).
Although no formal analysis by gender has been performed, estimates of response (Response Ratio)
derived from clinical trials (398 men, 307 women) indicate no important gender differences exist. There
was no consistent pattern indicating that age had any effect on the response to gabapentin. There were
insufficient numbers of patients of races other than Caucasian to permit a comparison of efficacy among
A fourth study in pediatric patients age 3 to 12 years compared 25 to 35 mg/kg/day gabapentin (N=118)
with placebo (N = 127). For all partial seizures in the intent-to-treat population, the response ratio was
statistically significantly better for the gabapentin group (-0.146) than for the placebo group (-0.079).
For the same population, the responder rate for gabapentin (21 %) was not significantly different from
A study in pediatric patients age 1 month to 3 years compared 40 mg/kg/day gabapentin (N=38) with
placebo (N=38) in patients who were receiving at least one marketed antiepileptic drug and had at least
one partial seizure during the screening period (within 2 weeks prior to baseline). Patients had up to 48
hours of baseline and up to 72 hours of double-blind video EEG monitoring to record and count the
occurrence of seizures. There were no statistically significant differences between treatments in either
the response ratio or responder rate.
INDICATIONS & USAGE
Gabapentin tablets USP are indicated for the management of postherpetic neuralgia in adults.
Gabapentin tablets USP are indicated as adjunctive therapy in the treatment of partial seizures with and
without secondary generalization in patients over 12 years of age with epilepsy. Gabapentin tablets USP
are also indicated as adjunctive therapy in the treatment of partial seizures in pediatric patients age 3 to
Gabapentin tablets USP are contraindicated in patients who have demonstrated hypersensitivity to the
drug or its ingredients.
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 or worsening of depression, suicidal thoughts or behavior, and/or any
unusual changes in mood or behavior.
Pooled analyses 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 a range of
indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary
substantially by age (5 to 100 years) in the clinical trials analyzed. Table 2 shows absolute and relative
risk by indication for all evaluated AEDs.
TABLE 2 Risk by indication for antiepileptic drugs in the pooled analysis
with Events Per
Drug Patients with
Events Per 1000
Incidence of Events
in Placebo Patients
Patients with Events
Per 1000 Patients
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 the risk of suicidal thoughts
or behavior 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 of Age
Gabapentin use in pediatric patients with epilepsy 3 to 12 years of age is associated with the occurrence
of central nervous system related adverse events. The most significant of these can be classified into
the following categories: 1) emotional lability (primarily behavioral problems), 2) hostility, including
aggressive behaviors, 3) thought disorder, including concentration problems and change in school
performance, and 4) hyperkinesia (primarily restlessness and hyperactivity). Among the gabapentin-
treated patients, most of the events were mild to moderate in intensity.
In controlled trials in pediatric patients 3 to 12 years of age, the incidence of these adverse events was:
emotional lability 6% (gabapentin-treated patients) vs 1.3% (placebo-treated patients); hostility 5.2% vs
1.3%; hyperkinesia 4.7% vs 2.9%; and thought disorder 1.7% vs 0%. One of these events, a report of
hostility, was considered serious. Discontinuation of gabapentin treatment occurred in 1.3% of patients
reporting emotional lability and hyperkinesia and 0.9% of gabapentin-treated patients reporting hostility
and thought disorder. One placebo-treated patient (0.4%) withdrew due to emotional lability.
Withdrawal Precipitated Seizure, Status Epilepticus
Antiepileptic drugs should not be abruptly discontinued because of the possibility of increasing seizure
In the placebo-controlled studies in patients > 12 years of age, the incidence of status epilepticus in
patients receiving gabapentin was 0.6% (3 of 543) versus 0.5% in patients receiving placebo (2 of 378).
Among the 2074 patients > 12 years of age treated with gabapentin across all studies (controlled and
uncontrolled) 31 (1.5%) had status epilepticus. Of these, 14 patients had no prior history of status
epilepticus either before treatment or while on other medications. Because adequate historical 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
In standard preclinical in vivo lifetime carcinogenicity studies, an unexpectedly high incidence of
pancreatic acinar adenocarcinomas was identified in male, but not female, rats (See PRECAUTIONS ,
Carcinogenesis, Mutagenesis, Impairment of Fertility). The clinical significance of this finding is
unknown. Clinical experience during gabapentin's premarketing development provides no direct means
to assess its potential for inducing tumors in humans.
In clinical studies in adjunctive therapy in epilepsy comprising 2085 patient-years of exposure in
patients > 12 years of age, new tumors were reported in 10 patients (2 breast, 3 brain, 2 lung, 1 adrenal, 1
non-Hodgkin's lymphoma, 1 endometrial carcinoma in situ), and preexisting tumors worsened in 11
patients (9 brain, 1 breast, 1 prostate) during or up to 2 years following discontinuation of gabapentin.
Without knowledge of the background incidence and recurrence in a similar population not treated with
gabapentin, it is impossible to know whether the incidence seen in this cohort is or is not affected by