GABAPENTIN tablet, film coated

United States - English - NLM (National Library of Medicine)

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Active ingredient:
Gabapentin (UNII: 6CW7F3G59X) (Gabapentin - UNII:6CW7F3G59X)
Available from:
Aphena Pharma Solutions - Tennessee, LLC
INN (International Name):
Gabapentin
Composition:
Gabapentin 800 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Postherpetic Neuralgia Gabapentin tablets USP are indicated for the management of postherpetic neuralgia in adults. Epilepsy 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 12 years. Gabapentin tablets USP are contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients. The abuse and dependence potential of gabapentin has not been evaluated in human studies.
Product summary:
Gabapentin Tablets, USP 600 mg: White colored film coated, Modified Capsule shaped, biconvex tablets de-bossed with '1' on the left side of the bisect and '2' on the right side of the bisect on one side and bisect on other; supplied in bottles of 90's count (NDC 76282-405-90), 100's count (NDC 76282-405-01) and 500’s count (NDC 76282-405-05). Gabapentin Tablets, USP 800 mg: White colored film coated, Modified Capsule shaped, biconvex tablets de-bossed with '1' on the left side of the bisect and '3' on the right side of the bisect on one side and bisect on other; supplied in bottles of 90's count (NDC 76282-406-90), 100's count (NDC 76282-406-01) and 500’s count (NDC 76282-406-05). Store at 20° to 25°C (68° to 77°F). [See USP controlled room temperature]. Rev: 10/12.
Authorization status:
Abbreviated New Drug Application
Authorization number:
43353-190-45, 43353-190-53, 43353-190-70, 43353-190-92

Aphena Pharma Solutions - Tennessee, LLC

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SPL MEDGUIDE

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

panic attacks

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.

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.

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

to take.

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

right away.

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:

dizziness

lack of coordination

viral infection

feeling drowsy

feeling tired

fever

jerky movements

difficulty with speaking

temporary loss of memory (amnesia)

tremor

difficulty with coordination

double vision

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

or pharmacist.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-

1088.

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.

Manufactured by:

InvaGen Pharmaceuticals, Inc.

Hauppauge, NY, 11788

Manufactured for:

Exelan Pharmaceuticals, Inc.

Lawrenceville, GA 30046

Rev: 10/12

Barcode: 406-10-2012

Revised: 6/2020

Document Id: 3d72b0b2-b4b3-4643-96ab-de4106a5320b

34391-3

Set id: 11da2692-fb0a-4519-b8a4-323c7a6eeb4d

Version: 5

Effective Time: 20200603

Aphena Pharma Solutions - Tennessee, LLC

GABAPENTIN - gabapentin tablet, film coated

Aphena Pharma Solutions - Tennessee, LLC

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Gabapentin Tablets, USP

Rx Only

DESCRIPTION

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.

CLINICAL PHARMACOLOGY

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

subjects.

Dosage adjustment in patients undergoing hemodialysis is necessary (see DOSAGE AND

ADMINISTRATION).

Hepatic Disease: Because gabapentin is not metabolized, no study was performed in patients with hepatic

impairment.

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

groups studied.

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).

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.

Clinical Studies

Postherpetic Neuralgia

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

Study

Study

Duration

Gabapentin

(mg/day)

Target

Patients

Receiving

Gabapentin

Patients

Receiving

Placebo

*

Dos e

Gabapentin

Placebo

8 weeks

3600

7 weeks

1800, 2400

Total

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

study medication).

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).

Epileps y

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

all comparisons.

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

racial groups.

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

placebo (18%).

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

Postherpetic Neuralgia

Gabapentin tablets USP are indicated for the management of postherpetic neuralgia in adults.

Epileps y

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

12 years.

CONTRAINDICATIONS

Gabapentin tablets USP are contraindicated in patients who have demonstrated hypersensitivity to the

drug or its ingredients.

WARNINGS

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

Indication

Placebo Patients

with Events Per

1000 Patients

Drug Patients with

Events Per 1000

Patients

Relative Risk:

Incidence of Events

in Drug

Patients /Incidence

in Placebo Patients

Risk Difference:

Additional Drug

Patients with Events

Per 1000 Patients

Epilepsy

Psychiatric

Other

Total

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

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

with gabapentin.

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 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

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