United States - English - NLM (National Library of Medicine)
GABAPENTIN- gabapentin tablet, film coated
St Marys Medical Park Pharmacy
GABAPENTIN TABLETS, USP
Gabapentin Tablets, USP are supplied as elliptical film-coated tablets containing 600 mg and 800 mg of
The inactive ingredients are: calcium stearate, crospovidone, hydroxypropyl cellulose, hypromellose,
polyethylene glycol and titanium dioxide. The 600 mg tablet also contains FD&C blue #2 aluminum lake
and synthetic yellow iron oxide. The 800 mg tablet also contains synthetic black iron oxide.
Gabapentin is described as 1-(aminomethyl) cyclohexane-acetic acid with a molecular formula of C
and a molecular weight of 171.24. The structural formula of gabapentin is:
Gabapentin is a white to off-white crystalline solid with a pKa
of 3.7 and a pKa
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.
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
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.
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 C
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.
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: Adult 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).
Adult Patients With Renal Insufficiency: Subjects (N=60) with renal insufficiency (mean creatinine
clearance ranging from 13-114 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.
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 subjects.
Dosage adjustment in patients undergoing hemodialysis is necessary (see DOSAGE AND
Because gabapentin is not metabolized, no study was performed in patients with hepatic impairment.
The effect of age was studied in subjects 20-80 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.)
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 groups
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 AND ADMINISTRATION).
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.
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
Given in 3 divided doses (TID)
7 weeks 1800, 2400
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.
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
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
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 25-35 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 AND USAGE
Gabapentin is indicated for the management of postherpetic neuralgia in adults.
Gabapentin is 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 is also indicated as adjunctive therapy in the treatment of partial seizures in pediatric patients
age 3-12 years.
Gabapentin is contraindicated in patients who have demonstrated hypersensitivity to the drug or its
Suicidal Behavior and Ideation
Antiepileptic drugs (AEDs), including gabapentin tablets, 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 (5-100 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
Events in Drug
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 tablets 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 3-12 years of age: Gabapentin use in
pediatric patients with epilepsy 3-12 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 3-12 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 frequency.
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
Tumorigenic Potential: 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 pre-existing 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
Sudden and Unexplained Death in Patients With Epilepsy: During the course of premarketing
development of gabapentin 8 sudden and unexplained deaths were recorded among a cohort of 2203
patients treated (2103 patient-years of exposure).
Some of these could represent seizure-related deaths in which the seizure was not observed, e.g., 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 (ranging from
0.0005 for the general population of epileptics to 0.003 for a clinical trial population similar to that in
the gabapentin program, to 0.005 for patients with refractory epilepsy). Consequently, whether these
figures 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.
Information for Patients
Patients should be instructed to take gabapentin only as prescribed.
Patients, their caregivers, and families should be counseled that AEDs, including gabapentin, may
increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the
emergence or worsening of 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
Patients should be advised that gabapentin tablets may cause dizziness, somnolence and other symptoms
and signs of CNS depression. Accordingly, they should be advised neither to drive a car nor to operate
other complex machinery until they have gained sufficient experience on gabapentin to gauge whether
or not it affects their mental and/or motor performance adversely.
Patients who require concomitant treatment with morphine may experience increases in gabapentin
concentrations. Patients should be carefully observed for signs of CNS depression, such as
somnolence, and the dose of gabapentin or morphine should be reduced appropriately (see Drug
Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy
Registry if they become pregnant. This registry is collecting information about the safety of
antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334
(see PRECAUTIONS: Pregnancy section).
Clinical trials data do not indicate that routine monitoring of clinical laboratory parameters is necessary
for the safe use of gabapentin. The value of monitoring gabapentin blood concentrations has not been
established. Gabapentin may be used in combination with other antiepileptic drugs without concern for
alteration of the blood concentrations of gabapentin or of other antiepileptic drugs.
In vitro studies were conducted to investigate the potential of gabapentin to inhibit the major cytochrome
P450 enzymes (CYP1A2, CYP2A6, CYP2C9, CYP2C19, CYP2D6, CYP2E1, and CYP3A4) that mediate
drug and xenobiotic metabolism using isoform selective marker substrates and human liver microsomal
preparations. Only at the highest concentration tested (171 μg/mL; 1 mM) was a slight degree of
inhibition (14%-30%) of isoform CYP2A6 observed. No inhibition of any of the other isoforms tested
was observed at gabapentin concentrations up to 171 μg/mL (approximately 15 times the C
Gabapentin is not appreciably metabolized nor does it interfere with the metabolism of commonly
coadministered antiepileptic drugs.
The drug interaction data described in this section were obtained from studies involving healthy adults
and adult patients with epilepsy.
Phenytoin: In a single (400 mg) and multiple dose (400 mg TID) study of gabapentin in epileptic patients
(N=8) maintained on phenytoin monotherapy for at least 2 months, gabapentin had no effect on the
steady-state trough plasma concentrations of phenytoin and phenytoin had no effect on gabapentin
Carbamazepine: Steady-state trough plasma carbamazepine and carbamazepine 10, 11 epoxide
concentrations were not affected by concomitant gabapentin (400 mg TID; N=12) administration.
Likewise, gabapentin pharmacokinetics were unaltered by carbamazepine administration.
Valproic Acid: The mean steady-state trough serum valproic acid concentrations prior to and during
concomitant gabapentin administration (400 mg TID; N=17) were not different and neither were
gabapentin pharmacokinetic parameters affected by valproic acid.
Phenobarbital: Estimates of steady-state pharmacokinetic parameters for phenobarbital or gabapentin
(300 mg TID; N=12) are identical whether the drugs are administered alone or together.
Naproxen: Coadministration (N=18) of naproxen sodium capsules (250 mg) with gabapentin (125 mg)
appears to increase the amount of gabapentin absorbed by 12% to 15%. Gabapentin had no effect on
naproxen pharmacokinetic parameters. These doses are lower than the therapeutic doses for both drugs.
The magnitude of interaction within the recommended dose ranges of either drug is not known.
Hydrocodone: Coadministration of gabapentin (125 to 500 mg; N=48) decreases hydrocodone (10 mg;
and AUC values in a dose-dependent manner relative to administration of hydrocodone
and AUC values are 3% to 4% lower, respectively, after administration of 125 mg
gabapentin and 21% to 22% lower, respectively, after administration of 500 mg gabapentin. The
mechanism for this interaction is unknown. Hydrocodone increases gabapentin AUC values by 14%.
The magnitude of interaction at other doses is not known.
Morphine: A literature article reported that when a 60-mg controlled release morphine capsule was
administered 2 hours prior to a 600-mg gabapentin capsule (N=12), mean gabapentin AUC increased by
44% compared to gabapentin administered without morphine (see PRECAUTIONS). Morphine
pharmacokinetic parameter values were not affected by administration of gabapentin 2 hours after
morphine. The magnitude of interaction at other doses is not known.
Cimetidine: In the presence of cimetidine at 300 mg QID (N=12) the mean apparent oral clearance of
gabapentin fell by 14% and creatinine clearance fell by 10%. Thus cimetidine appeared to alter the renal
excretion of both gabapentin and creatinine, an endogenous marker of renal function. This small
decrease in excretion of gabapentin by cimetidine is not expected to be of clinical importance. The
effect of gabapentin on cimetidine was not evaluated.
Oral Contraceptives: Based on AUC and half-life, multiple-dose pharmacokinetic profiles of
norethindrone and ethinyl estradiol following administration of tablets containing 2.5 mg of
norethindrone acetate and 50 mcg of ethinyl estradiol were similar with and without coadministration of
gabapentin (400 mg TID; N=13). The C
of norethindrone was 13% higher when it was
coadministered with gabapentin; this interaction is not expected to be of clinical importance.
Antacid Maalox® (Aluminum Hydroxide and Magnesium Hydroxide Suspension): Maalox® (Aluminum
Hydroxide and Magnesium Hydroxide Suspension) reduced the bioavailability of gabapentin (N=16) by
about 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours
after Maalox® (Aluminum Hydroxide and Magnesium Hydroxide Suspension). It is recommended that
gabapentin be taken at least 2 hours following Maalox® (Aluminum Hydroxide and Magnesium
Hydroxide Suspension) administration.
Effect Of Probenecid: Probenecid is a blocker of renal tubular secretion. Gabapentin pharmacokinetic
parameters without and with probenecid were comparable. This indicates that gabapentin does not
undergo renal tubular secretion by the pathway that is blocked by probenecid.
Drug/Laboratory Tests Interactions
Because false positive readings were reported with the Ames N-Multistix SG® dipstick test for urinary
protein when gabapentin was added to other antiepileptic drugs, the more specific sulfosalicylic acid
precipitation procedure is recommended to determine the presence of urine protein.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Gabapentin was given in the diet to mice at 200, 600, and 2000 mg/kg/day and to rats at 250, 1000, and
2000 mg/kg/day for 2 years. A statistically significant increase in the incidence of pancreatic acinar cell
adenomas and carcinomas was found in male rats receiving the high dose; the no-effect dose for the
occurrence of carcinomas was 1000 mg/kg/day. Peak plasma concentrations of gabapentin in rats
receiving the high dose of 2000 mg/kg were 10 times higher than plasma concentrations in humans
receiving 3600 mg per day, and in rats receiving 1000 mg/kg/day peak plasma concentrations were 6.5
times higher than in humans receiving 3600 mg/day. The pancreatic acinar cell carcinomas did not affect
survival, did not metastasize and were not locally invasive. The relevance of this finding to
carcinogenic risk in humans is unclear.
Studies designed to investigate the mechanism of gabapentin-induced pancreatic carcinogenesis in rats
indicate that gabapentin stimulates DNA synthesis in rat pancreatic acinar cells in vitro and, thus, may be
acting as a tumor promoter by enhancing mitogenic activity. It is not known whether gabapentin has the
ability to increase cell proliferation in other cell types or in other species, including humans.
Gabapentin did not demonstrate mutagenic or genotoxic potential in three in vitro and four in vivo assays.
It was negative in the Ames test and the in vitro HGPRT forward mutation assay in Chinese hamster lung
cells; it did not produce significant increases in chromosomal aberrations in the in vitro Chinese hamster
lung cell assay; it was negative in the in vivo chromosomal aberration assay and in the in vivo
micronucleus test in Chinese hamster bone marrow; it was negative in the in vivo mouse micronucleus
assay; and it did not induce unscheduled DNA synthesis in hepatocytes from rats given gabapentin.
No adverse effects on fertility or reproduction were observed in rats at doses up to 2000 mg/kg
(approximately 5 times the maximum recommended human dose on a mg/m
Pregnancy Category C: Gabapentin has been shown to be fetotoxic in rodents, causing delayed
ossification of several bones in the skull, vertebrae, forelimbs, and hindlimbs. These effects occurred
when pregnant mice received oral doses of 1000 or 3000 mg/kg/day during the period of
organogenesis, or approximately 1 to 4 times the maximum dose of 3600 mg/day given to epileptic
patients on a mg/m
basis. The no-effect level was 500 mg/kg/day or approximately ½ of the human
dose on a mg/m
When rats were dosed prior to and during mating, and throughout gestation, pups from all dose groups
(500, 1000 and 2000 mg/kg/day) were affected. These doses are equivalent to less than approximately 1
to 5 times the maximum human dose on a mg/m
basis. There was an increased incidence of hydroureter
and/or hydronephrosis in rats in a study of fertility and general reproductive performance at 2000
mg/kg/day with no effect at 1000 mg/kg/day, in a teratology study at 1500 mg/kg/day with no effect at
300 mg/kg/day, and in a perinatal and postnatal study at all doses studied (500, 1000 and 2000
mg/kg/day). The doses at which the effects occurred are approximately 1 to 5 times the maximum human
dose of 3600 mg/day on a mg/m
basis; the no-effect doses were approximately 3 times (Fertility and
General Reproductive Performance study) and approximately equal to (Teratogenicity study) the
maximum human dose on a mg/m
basis. Other than hydroureter and hydronephrosis, the etiologies of
which are unclear, the incidence of malformations was not increased compared to controls in offspring
of mice, rats, or rabbits given doses up to 50 times (mice), 30 times (rats), and 25 times (rabbits) the
human daily dose on a mg/kg basis, or 4 times (mice), 5 times (rats), or 8 times (rabbits) the human daily
dose on a mg/m
In a teratology study in rabbits, an increased incidence of post implantation fetal loss occurred in dams
exposed to 60, 300 and 1500 mg/kg/day, or less than approximately ¼ to 8 times the maximum human
dose on a mg/m
basis. There are no adequate and well-controlled studies in pregnant women. This
drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
To provide information regarding the effects of in utero exposure to gabapentin, physicians are advised
to recommend that pregnant patients taking gabapentin enroll in the North American Antiepileptic Drug
(NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and
must be done by patients themselves. Information on the registry can also be found at the website
Use In Nursing Mothers:
Gabapentin is secreted into human milk following oral administration. A nursed infant could be exposed
to a maximum dose of approximately 1 mg/kg/day of gabapentin. Because the effect on the nursing infant
is unknown, gabapentin should be used in women who are nursing only if the benefits clearly outweigh
Safety and effectiveness of gabapentin in the management of postherpetic neuralgia in pediatric patients
have not been established. Effectiveness as adjunctive therapy in the treatment of partial seizures in
pediatric patients below the age of 3 years has not been established. (see CLINICAL
PHARMACOLOGY, Clinical Studies).
The total number of patients treated with gabapentin in controlled clinical trials in patients with
postherpetic neuralgia was 336, of which 102 (30%) were 65 to 74 years of age, and 168 (50%) were
75 years of age and older. There was a larger treatment effect in patients 75 years of age and older
compared with younger patients who received the same dosage. Since gabapentin is almost exclusively
eliminated by renal excretion, the larger treatment effect observed in patients >75 years may be a
consequence of increased gabapentin exposure for a given dose that results from an age-related
decrease in renal function. However, other factors cannot be excluded. The types and incidence of
adverse events were similar across age groups except for peripheral edema and ataxia, which tended to
increase in incidence with age.
Clinical studies of gabapentin in epilepsy did not include sufficient numbers of subjects aged 65 and
over to determine whether they responded differently from younger subjects. Other reported clinical
experience has not identified differences in responses between the elderly and younger patients. In
general, dose selection for an elderly patient should be cautious, usually starting at the low end of the
dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of
concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug
may be greater in patients with impaired renal function. Because elderly patients are more likely to have
decreased renal function, care should be taken in dose selection, and dose should be adjusted based on
creatinine clearance values in these patients (see CLINICAL PHARMACOLOGY, ADVERSE
REACTIONS, and DOSAGE AND ADMINISTRATION).
The most commonly observed adverse events associated with the use of gabapentin in adults, not seen at
an equivalent frequency among placebo-treated patients, were dizziness, somnolence, and peripheral
In the 2 controlled studies in postherpetic neuralgia, 16% of the 336 patients who received gabapentin
and 9% of the 227 patients who received placebo discontinued treatment because of an adverse event.
The adverse events that most frequently led to withdrawal in gabapentin-treated patients were dizziness,
somnolence, and nausea.
Incidence In Controlled Clinical Trials:
Table 3 lists treatment-emergent signs and symptoms that occurred in at least 1% of gabapentin treated
patients with postherpetic neuralgia participating in placebo-controlled trials and that were numerically
more frequent in the gabapentin group than in the placebo group. Adverse events were usually mild to
moderate in intensity.
TABLE 3. Treatment-Emergent Adverse Event
Incidence in Controlled Trials in Postherpetic
Neuralgia (Events in at least 1% of Gabapentin-
Treated Patients and Numerically More Frequent
Than in the Placebo Group)
Body as a Whole
Reported as blurred vision
Metabolic and Nutritional Disorders
Skin and Appendages
Other events in more than 1% of patients but equally or more frequent in the placebo group included
pain, tremor, neuralgia, back pain, dyspepsia, dyspnea, and flu syndrome.
There were no clinically important differences between men and women in the types and incidence of
adverse events. Because there were few patients whose race was reported as other than white, there are
insufficient data to support a statement regarding the distribution of adverse events by race.
The most commonly observed adverse events associated with the use of gabapentin in combination with
other antiepileptic drugs in patients >12 years of age, not seen at an equivalent frequency among
placebo-treated patients, were somnolence, dizziness, ataxia, fatigue, and nystagmus. The most
commonly observed adverse events reported with the use of gabapentin in combination with other
antiepileptic drugs in pediatric patients 3 to 12 years of age, not seen at an equal frequency among
placebo-treated patients, were viral infection, fever, nausea and/or vomiting, somnolence, and hostility
(see WARNINGS, Neurospychiatric Adverse Events).
Approximately 7% of the 2074 patients >12 years of age and approximately 7% of the 449 pediatric
patients 3 to 12 years of age who received gabapentin in premarketing clinical trials discontinued
treatment because of an adverse event. The adverse events most commonly associated with withdrawal
in patients >12 years of age were somnolence (1.2%), ataxia (0.8%), fatigue (0.6%), nausea and/or
vomiting (0.6%), and dizziness (0.6%). The adverse events most commonly associated with withdrawal
in pediatric patients were emotional lability (1.6%), hostility (1.3%), and hyperkinesia (1.1%).
Incidence In Controlled Clinical Trials: Table 4 lists treatment-emergent signs and symptoms that
occurred in at least 1% of gabapentin-treated patients >12 years of age with epilepsy participating in
placebo-controlled trials and were numerically more common in the gabapentin group. In these studies,
either gabapentin or placebo was added to the patient’s current antiepileptic drug therapy. Adverse
events were usually mild to moderate in intensity.
The prescriber should be aware that these figures, obtained when gabapentin was added to concurrent
antiepileptic drug therapy, cannot be used to predict the frequency of adverse events in the course of
usual medical practice where patient characteristics and other factors may differ from those prevailing
during clinical studies. Similarly, the cited frequencies cannot be directly compared with figures
obtained from other clinical investigations involving different treatments, uses, or investigators. An
inspection of these frequencies, however, does provide the prescribing physician with one basis to
estimate the relative contribution of drug and nondrug factors to the adverse event incidences in the
Table 4. Treatment-Emergent Adverse Event Incidence
in Controlled Add-On Trials in Patients >12 Years of
Age (Events in at Least 1% of Gabapentin Patients and
Numerically More Frequent Than in the Placebo Group)
Body System/ Adverse Event
N = 543
N = 378
Body As A Whole
Mouth or Throat Dry
Hematologic and Lymphatic Systems
Plus background antiepileptic drug therapy
Amblyopia was often described as blurred vision.
Skin and Appendages
Other events in more than 1% of patients >12 years of age but equally or more frequent in the placebo
group included: headache, viral infection, fever, nausea and/or vomiting, abdominal pain, diarrhea,
convulsions, confusion, insomnia, emotional lability, rash, acne.
Among the treatment-emergent adverse events occurring at an incidence of at least 10% of gabapentin
treated patients, somnolence and ataxia appeared to exhibit a positive dose-response relationship.
The overall incidence of adverse events and the types of adverse events seen were similar among men
and women treated with gabapentin. The incidence of adverse events increased slightly with increasing
age in patients treated with either gabapentin or placebo. Because only 3% of patients (28/921) in
placebo-controlled studies were identified as nonwhite (black or other), there are insufficient data to
support a statement regarding the distribution of adverse events by race.
Table 5 lists treatment-emergent signs and symptoms that occurred in at least 2% of gabapentin-treated
patients age 3 to 12 years of age with epilepsy participating in placebo-controlled trials and were
numerically more common in the gabapentin group. Adverse events were usually mild to moderate in
Table 5. Treatment-Emergent Adverse Event
Incidence in Pediatric Patients Age 3 to 12 Years
in a Controlled Add-On Trial (Events in at Least
2% of Gabapentin Patients and Numerically
More Frequent Than in the Placebo Group)
Body System/Adverse EventGabapentin
N = 119
N = 128
Body As A Whole
Plus background antiepileptic drug therapy
Nausea and/or Vomiting
Other events in more than 2% of pediatric patients 3 to 12 years of age but equally or more frequent in
the placebo group included: pharyngitis, upper respiratory infection, headache, rhinitis, convulsions,
diarrhea, anorexia, coughing, and otitis media.
Other Adverse Events Observed During All Clinical Trials In Adults And Adolescents (Except Clinical
Trials In Neuropathic Pain):
Gabapentin has been administered to 4717 patients >12 years of age during all adjunctive therapy
clinical trials (except clinical trials in patients with neuropathic pain), only some of which were
placebo-controlled. During these trials, all adverse events were recorded by the clinical investigators
using terminology of their own choosing. To provide a meaningful estimate of the proportion of
individuals having adverse events, similar types of events were grouped into a smaller number of
standardized categories using modified COSTART dictionary terminology. These categories are used
in the listing below. The frequencies presented represent the proportion of the 4717 patients >12 years
of age exposed to gabapentin who experienced an event of the type cited on at least one occasion while
receiving gabapentin. All reported events are included except those already listed in Table 4, those too
general to be informative, and those not reasonably associated with the use of the drug.
Events are further classified within body system categories and enumerated in order of decreasing
frequency using the following definitions: frequent adverse events are defined as those occurring in at
least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare
events are those occurring in fewer than 1/1000 patients.
Body as a whole: Frequent: asthenia, malaise, face edema; Infrequent: allergy, generalized edema, weight
decrease, chill; Rare: strange feelings, lassitude, alcohol intolerance, hangover effect.
Cardiovascular system: Frequent: hypertension; Infrequent: hypotension, angina pectoris, peripheral
vascular disorder, palpitation, tachycardia, migraine, murmur; Rare: atrial fibrillation, heart failure,
thrombophlebitis, deep thrombophlebitis, myocardial infarction, cerebrovascular accident, pulmonary
thrombosis, ventricular extrasystoles, bradycardia, premature atrial contraction, pericardial rub, heart
block, pulmonary embolus, hyperlipidemia, hypercholesterolemia, pericardial effusion, pericarditis.
Digestive system: Frequent: anorexia, flatulence, gingivitis; Infrequent: glossitis, gum hemorrhage, thirst,
stomatitis, increased salivation, gastroenteritis, hemorrhoids, bloody stools, fecal incontinence,
hepatomegaly; Rare: dysphagia, eructation, pancreatitis, peptic ulcer, colitis, blisters in mouth, tooth
discolor, perlèche, salivary gland enlarged, lip hemorrhage, esophagitis, hiatal hernia, hematemesis,
proctitis, irritable bowel syndrome, rectal hemorrhage, esophageal spasm.
Endocrine system: Rare: hyperthyroid, hypothyroid, goiter, hypoestrogen, ovarian failure, epididymitis,
swollen testicle, cushingoid appearance.
Hematologic and lymphatic system: Frequent: purpura most often described as bruises resulting from
physical trauma; Infrequent: anemia, thrombocytopenia, lymphadenopathy; Rare: WBC count increased,
lymphocytosis, non-Hodgkin’s lymphoma, bleeding time increased.
Musculoskeletal system: Frequent: arthralgia; Infrequent: tendinitis, arthritis, joint stiffness, joint swelling,
positive Romberg test; Rare: costochondritis, osteoporosis, bursitis, contracture.
Nervous system: Frequent: vertigo, hyperkinesia, paresthesia, decreased or absent reflexes, increased
reflexes, anxiety, hostility; Infrequent: CNS tumors, syncope, dreaming abnormal, aphasia, hypesthesia,
intracranial hemorrhage, hypotonia, dysesthesia, paresis, dystonia, hemiplegia, facial paralysis, stupor,
cerebellar dysfunction, positive Babinski sign, decreased position sense, subdural hematoma, apathy,
hallucination, decrease or loss of libido, agitation, paranoia, depersonalization, euphoria, feeling high,
doped-up sensation, suicidal, psychosis; Rare: choreoathetosis, orofacial dyskinesia, encephalopathy,
nerve palsy, personality disorder, increased libido, subdued temperament, apraxia, fine motor control
disorder, meningismus, local myoclonus, hyperesthesia, hypokinesia, mania, neurosis, hysteria,
Respiratory system: Frequent: pneumonia; Infrequent: epistaxis, dyspnea, apnea; Rare: mucositis,
aspiration pneumonia, hyperventilation, hiccup, laryngitis, nasal obstruction, snoring, bronchospasm,
hypoventilation, lung edema.
Dermatological: Infrequent: alopecia, eczema, dry skin, increased sweating, urticaria, hirsutism,
seborrhea, cyst, herpes simplex; Rare: herpes zoster, skin discolor, skin papules, photosensitive
reaction, leg ulcer, scalp seborrhea, psoriasis, desquamation, maceration, skin nodules, subcutaneous
nodule, melanosis, skin necrosis, local swelling.
Urogenital system: Infrequent: hematuria, dysuria, urination frequency, cystitis, urinary retention, urinary
incontinence, vaginal hemorrhage, amenorrhea, dysmenorrhea, menorrhagia, breast cancer, unable to
climax, ejaculation abnormal; Rare: kidney pain, leukorrhea, pruritus genital, renal stone, acute renal
failure, anuria, glycosuria, nephrosis, nocturia, pyuria, urination urgency, vaginal pain, breast pain,
Special senses: Frequent: abnormal vision; Infrequent: cataract, conjunctivitis, eyes dry, eye pain, visual
field defect, photophobia, bilateral or unilateral ptosis, eye hemorrhage, hordeolum, hearing loss,
earache, tinnitus, inner ear infection, otitis, taste loss, unusual taste, eye twitching, ear fullness; Rare:
eye itching, abnormal accommodation, perforated ear drum, sensitivity to noise, eye focusing problem,
watery eyes, retinopathy, glaucoma, iritis, corneal disorders, lacrimal dysfunction, degenerative eye
changes, blindness, retinal degeneration, miosis, chorioretinitis, strabismus, eustachian tube
dysfunction, labyrinthitis, otitis externa, odd smell.
Clinical Trials In Pediatric Patients With Epilepsy: Adverse events occurring during epilepsy clinical
trials in 449 pediatric patients 3 to 12 years of age treated with gabapentin that were not reported in
adjunctive trials in adults are:
Body as a whole: dehydration, infectious mononucleosis
Digestive system: hepatitis
Hemic and lymphatic system: coagulation defect
Nervous system: aura disappeared, occipital neuralgia
Psychobiologic function: sleepwalking
Respiratory system: pseudocroup, hoarseness
Clinical Trials In Adults With Neuropathic Pain Of Various Etiologies: Safety information was
obtained in 1173 patients during double-blind and open-label clinical trials including neuropathic pain
conditions for which efficacy has not been demonstrated. Adverse events reported by investigators
were grouped into standardized categories using modified COSTART IV terminology. Listed below
are all reported events except those already listed in Table 3 and those not reasonably associated with
the use of the drug.
Events are further classified within body system categories and enumerated in order of decreasing
frequency using the following definitions: frequent adverse events are defined as those occurring in at
least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients, rare
events are those occurring in fewer than 1/1000 patients.
Body as a whole: Infrequent: chest pain, cellulitis, malaise, neck pain, face edema, allergic reaction,
abscess, chills, chills and fever, mucous membrane disorder; Rare: body odor, cyst, fever, hernia,
abnormal BUN value, lump in neck, pelvic pain, sepsis, viral infection.
Cardiovascular system: Infrequent: hypertension, syncope, palpitation, migraine, hypotension, peripheral
vascular disorder, cardiovascular disorder, cerebrovascular accident, congestive heart failure,
myocardial infarction, vasodilatation; Rare: angina pectoris, heart failure increased capillary fragility,
phlebitis, thrombophlebitis, varicose vein.
Digestive system: Infrequent: gastroenteritis, increased appetite, gastrointestinal disorder, oral moniliasis,
gastritis, tongue disorder, thirst, tooth disorder, abnormal stools, anorexia, liver function tests abnormal,
periodontal abscess; Rare: cholecystitis, cholelithiasis, duodenal ulcer, fecal incontinence, gamma
glutamyl transpeptidase increased, gingivitis, intestinal obstruction, intestinal ulcer, melena, mouth
ulceration, rectal disorder, rectal hemorrhage, stomatitis.
Endocrine system: Infrequent: diabetes mellitus.
Hemic and lymphatic system: Infrequent: ecchymosis, anemia; Rare: lymphadenopathy, lymphoma-like
reaction, prothrombin decreased.
Metabolic and nutritional: Infrequent: edema, gout, hypoglycemia, weight loss; Rare: alkaline
phosphatase increased, diabetic ketoacidosis, lactic dehydrogenase increased.
Musculoskeletal:Infrequent: arthritis, arthralgia, myalgia, arthrosis, leg cramps, myasthenia; Rare: shin
bone pain, joint disorder, tendon disorder.
Nervous system: Frequent: confusion, depression; Infrequent: vertigo, nervousness, paresthesia,
insomnia, neuropathy, libido decreased, anxiety, depersonalization, reflexes decreased, speech
disorder, abnormal dreams, dysarthria, emotional lability, nystagmus, stupor, circumoral paresthesia,
euphoria, hyperesthesia, hypokinesia; Rare: agitation, hypertonia, libido increased, movement disorder,
myoclonus, vestibular disorder.
Respiratory system: Infrequent: cough increased, bronchitis, rhinitis, sinusitis, pneumonia, asthma, lung
disorder, epistaxis; Rare: hemoptysis, voice alteration.
Skin and appendages: Infrequent: pruritus, skin ulcer, dry skin, herpes zoster, skin disorder, fungal
dermatitis, furunculosis, herpes simplex, psoriasis, sweating, urticaria, vesiculobullous rash; Rare:
acne, hair disorder, maculopapular rash, nail disorder, skin carcinoma, skin discoloration, skin
Special senses:Infrequent: abnormal vision, ear pain, eye disorder, taste perversion, deafness; Rare:
conjunctival hyperemia, diabetic retinopathy, eye pain, fundi with microhemorrhage, retinal vein
thrombosis, taste loss.
Urogenital system:Infrequent: urinary tract infection, dysuria, impotence, urinary incontinence, vaginal
moniliasis, breast pain, menstrual disorder, polyuria, urinary retention: Rare: cystitis, ejaculation
abnormal, swollen penis, gynecomastia, nocturia, pyelonephritis, swollen scrotum, urinary frequency,
urinary urgency, urine abnormality.
Postmarketing And Other Experience:
In addition to the adverse experiences reported during clinical testing of gabapentin, the following
adverse experiences have been reported in patients receiving marketed gabapentin. These adverse
experiences have not been listed above and data are insufficient to support an estimate of their incidence
or to establish causation. The listing is alphabetized: angioedema, blood glucose fluctuation, breast
hypertrophy, erythema multiforme, elevated liver function tests, fever, hyponatremia, jaundice,
movement disorder, Stevens-Johnson syndrome. Adverse events following the abrupt discontinuation of
gabapentin have also been reported. The most frequently reported events were anxiety, insomnia,
nausea, pain and sweating.
DRUG ABUSE AND DEPENDENCE
The abuse and dependence potential of gabapentin has not been evaluated in human studies.
A lethal dose of gabapentin was not identified in mice and rats receiving single oral doses as high as
8000 mg/kg. Signs of acute toxicity in animals included ataxia, labored breathing, ptosis, sedation,
hypoactivity, or excitation.
Acute oral overdoses of gabapentin up to 49 grams have been reported. In these cases, double vision,
slurred speech, drowsiness, lethargy and diarrhea were observed. All patients recovered with
Gabapentin can be removed by hemodialysis. Although hemodialysis has not been performed in the few
overdose cases reported, it may be indicated by the patient’s clinical state or in patients with significant
DOSAGE AND ADMINISTRATION
Gabapentin is given orally with or without food. Patients should be informed that, should they break the
scored 600 or 800 mg tablet in order to administer a half-tablet, they should take the unused half-tablet
as the next dose. Half-tablets not used within several days of breaking the scored tablet should be
If gabapentin dose is reduced, discontinued or substituted with an alternative medication, this should be
done gradually over a minimum of 1 week (a longer period may be needed at the discretion of the
In adults with postherpetic neuralgia, gabapentin therapy may be initiated as a single 300-mg dose on
Day 1, 600 mg/day on Day 2 (divided BID), and 900 mg/day on Day 3 (divided TID). The dose can
subsequently be titrated up as needed for pain relief to a daily dose of 1800 mg (divided TID). In
clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day
with comparable effects across the dose range. Additional benefit of using doses greater than 1800
mg/day was not demonstrated.
Gabapentin is recommended for add-on therapy in patients 3 years of age and older. Effectiveness in
pediatric patients below the age of 3 years has not been established.
Patients >12 Years Of Age
The effective dose of gabapentin is 900 to 1800 mg/day and given in divided doses (three times a day)
using 600 or 800 mg tablets. The starting dose is
300 mg three times a day. If necessary, the dose may be increased using 600 or 800 mg tablets three
times a day up to 1800 mg/day. Dosages up to 2400 mg/day have been well tolerated in long-term
clinical studies. Doses of 3600 mg/day have also been administered to a small number of patients for a
relatively short duration, and have been well tolerated. The maximum time between doses in the TID
schedule should not exceed 12 hours.
Pediatric Patients Age 3-12 Years
The starting dose should range from 10-15 mg/kg/day in 3 divided doses, and the effective dose
reached by upward titration over a period of approximately 3 days. The effective dose of gabapentin in
patients 5 years of age and older is 25-35 mg/kg/day and given in divided doses (three times a day). The
effective dose in pediatric patients ages 3 and 4 years is 40 mg/kg/day and given in divided doses (three
times a day). (See CLINICAL PHARMACOLOGY, Pediatrics.) Dosages up to 50 mg/kg/day have been
well tolerated in a long-term clinical study. The maximum time interval between doses should not
exceed 12 hours.
It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy. Further,
because there are no significant pharmacokinetic interactions among gabapentin and other commonly
used antiepileptic drugs, the addition of gabapentin does not alter the plasma levels of these drugs
If gabapentin is discontinued and/or an alternate anticonvulsant medication is added to the therapy, this
should be done gradually over a minimum of 1 week.
Dosage In Renal Impairment
Creatinine clearance is difficult to measure in outpatients. In patients with stable renal function,
creatinine clearance (C
) can be reasonably well estimated using the equation of Cockcroft and Gault:
for females C
= (0.85) (140-age) (weight)/[(72)(S
for males C
= (140-age) (weight)/[(72)(S
where age is in years, weight is in kilograms and S
is serum creatinine in mg/dL.
Dosage adjustment in patients ≥ 12 years of age with compromised renal function or undergoing
hemodialysis is recommended as follows (see dosing recommendations above for effective doses in
Table 6. Gabapentin Dosage Based on Renal Function
For patients with creatinine clearance <15 mL/min, reduce daily dose in
proportion to creatinine clearance (e.g., patients with a creatinine clearance
of 7.5 mL/min should receive one-half the daily dose that patients with a
creatinine clearance of 15 mL/min receive).
Patients on hemodialysis should receive maintenance doses based on
200-700 200 QD 300 QD
500 QD 700 QD
100-300 100 QD 125 QD
200 QD 300 QD
Post-Hemodialysis Supplemental Dose
estimates of creatinine clearance as indicated in the upper portion of the table
and a supplemental post-hemodialysis dose administered after each 4 hours
of hemodialysis as indicated in the lower portion of the table.
The use of gabapentin in patients <12 years of age with compromised renal function has not been
Dosage In Elderly:
Because elderly patients are more likely to have decreased renal function, care should be taken in dose
selection, and dose should be adjusted based on creatinine clearance values in these patients.
800 mg tablets:
White to off white, biconvex, oval shape, coated tablet scored on both sides and debossed with "204"
on one side, available in:
NDC: 60760-0038-60 BOTTLE OF 60
60760-0038-90 BOTTLE OF 90
60760-0038-30 BOTTLE OF 30
Store at 25 degrees C (77 degrees F); excursions permitted to 15 degrees to 30 degrees C (59 degrees
to 86 degrees F) See USP Controlled Room Temperature
The following are registered trademarks of their respective manufacturers: Maalox Alovartis
Consumer Health Canada Inc.; Ames N-Multistix SG Miles Laboratories, Inc.
Sun Pharmaceutical Industries Ltd.
Acme Plaza, Andheri-Kurla Road,
Andheri (East), Mumbai - 400 059, India.
Caraco Pharmaceutical Laboratories, Ltd.
1150 Elijah McCoy Drive, Detroit MI 48202
GABAPENTIN - gabapentin capsule
GABAPENTIN - gabapentin tablet, film coated
Sun Pharmaceutical Industries Limited
Gabapentin Capsules, USP
Gabapentin Tablets, USP
(GA ba PEN tin)
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. Suicidal Thoughts. 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 hyperactivity.
3. Gabapentin may cause serious or life-threatening allergic reactions that may affect your skin or other
parts of your body such as your liver or blood cells. This may cause you to be hospitalized or to stop
gabapentin. You may or may not have a rash with an allergic reaction caused by gabapentin. Call a
healthcare provider right away if you have any of the following symptoms:
swollen glands that do not go away
swelling of your face, lips, throat, or tongue
yellowing of your skin or of the whites of the eyes
unusual bruising or bleeding
severe fatigue or weakness
unexpected muscle pain
These symptoms may be the first signs of a serious reaction. A healthcare provider should examine you
to decide if you should continue taking gabapentin.
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 older
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.
Pregnancy Registry: 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 breast-feeding or plan to breast-feed. 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 over-the-
counter 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 to
Do not change your dose of gabapentin without talking to your healthcare provider.
If you take gabapentin tablets and break a tablet in half, the unused half of the tablet should be taken at
your next scheduled dose. Half tablets not used within 28 days of breaking should be thrown away.
Take gabapentin capsules with water.
Gabapentin tablets 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
right away at 1-800-222-1222.
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?
Gabapentin may cause serious side effects including:
See “What is the most important information I should know about gabapentin?”
problems driving while using gabapentin. See “What I should avoid while taking Neurontin?”
sleepiness and dizziness, which could increase the occurrence of accidental injury, including falls
The most common side effects of gabapentin include:
lack of coordination
nausea and vomiting
difficulty with coordination
difficulty with speaking
unusual eye movement
swelling, usually of legs and feet
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 or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-
How should I store gabapentin?
Store gabapentin capsules and tablets at 20° to 25°C (68 to 77°F)
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, call 1-800-818-4555.
What are the ingredients in gabapentin?
Active ingredient: gabapentin
Inactive ingredients in the capsules: calcium carbonate, calcium sulfate dihydrate, glyceryl behenate,
and pregelatinized maize starch. The capsule shell contains gelatin, titanium dioxide, sodium lauryl
sulfate, yellow iron oxide (300 mg and 400 mg) and red iron oxide (400 mg). The imprinting ink
contains shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol, propylene glycol, strong
ammonia solution, black iron oxide, potassium hydroxide, and purified water.
Inactive ingredients in the tablets: glyceryl behenate, hydroxypropyl cellulose, low substituted
hydroxypropyl cellulose, magnesium stearate, mannitol, talc, pregelatinized maize starch and Opadry
YS-1-7003 (hypromellose, titanium dioxide, polyethylene glycol, and polysorbate 80).
This Medication Guide has been approved by the U.S. Food and Drug Administration.
* All trademark names are the property of their respective owners.
Sun Pharmaceutical Industries, Inc.
Cranbury, NJ 08512
Sun Pharmaceutical Industries Ltd.
Halol-389 350, Gujarat, India.
Document Id: 55e62f9c-ff35-494d-aa1b-ed759bc59512
Set id: c9a05f0c-b5f0-422c-9d67-6d0efc921a74
Effective Time: 20171118
Sun Pharmaceutical Industries Limited
PACKAGE DISPLAY PANEL
gabapentin tablet, film coated
Product T ype
HUMAN PRESCRIPTION DRUG
Ite m Code (Source )
NDC:6 0 76 0 -0 38 (NDC:6 2756 -20 4)
Route of Administration
Active Ingredient/Active Moiety
Basis of Strength
Stre ng th
GABAPENTIN (UNII: 6 CW7F3G59 X) (GABAPENTIN - UNII:6 CW7F3G59 X)
8 0 0 mg
Stre ng th
CALCIUM STEARATE (UNII: 776 XM70 47L)
CRO SPO VIDO NE (UNII: 6 8 40 19 6 0 MK)
HYDRO XYPRO PYL CELLULO SE (UNII: RFW2ET6 71P)
HYPRO MELLO SES (UNII: 3NXW29 V3WO)
PO LYETHYLENE GLYCO L (UNII: 3WJQ0 SDW1A)
TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)
FERRIC O XIDE YELLO W (UNII: EX438 O2MRT)
white (o ff white)
S hap e
OVAL (20 4)
S iz e
Marketing Start Date
Marketing End Date
NDC:6 0 76 0 -0 38 -30
30 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct
12/0 3/20 10
NDC:6 0 76 0 -0 38 -6 0
6 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct
12/0 3/20 10
NDC:6 0 76 0 -0 38 -9 0
9 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct
12/0 3/20 10
Marke ting Cate gory
Application Numbe r or Monograph Citation
Marke ting Start Date
Marke ting End Date
12/0 3/20 10
St Marys Medical Park Pharmacy (063050751)
Ad d re s s
Busine ss Ope rations
St Marys Medical Park Pharmacy
0 6 30 50 751
repack(6 0 76 0 -0 38 ) , relabel(6 0 76 0 -0 38 )
St Marys Medical Park Pharmacy
Ad d re s s
Busine ss Ope rations
Sun Pharmaceutical Ind Ltd.
7259 59 238
ma nufa c ture (6 0 76 0 -0 38 )