GABAPENTIN capsule

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

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Active ingredient:
GABAPENTIN (UNII: 6CW7F3G59X) (GABAPENTIN - UNII:6CW7F3G59X)
Available from:
Bryant Ranch Prepack
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Gabapentin is indicated for: •Adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and pediatric patients 3 years and older with epilepsy Gabapentin is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients. Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antiepileptic drugs (AEDs), such as gabapentin, during pregnancy. Encourage women who are taking gabapentin during pregnancy to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry by calling the toll free number 1-888-233-2334 or visiting http://www.aedpregnancyregistry.org/. Risk Summary There are no adequate data on the developmental risks associated with the use of gabapentin in pregnant women. In nonclinical studies in mice, rats, and rabbits, gabapentin was developmentally toxic (increased fetal skeletal and visceral abnormalities, and increased embryofeta
Product summary:
Product: 71335-1269 NDC: 71335-1269-1 90 CAPSULE in a BOTTLE NDC: 71335-1269-2 28 CAPSULE in a BOTTLE NDC: 71335-1269-3 58 CAPSULE in a BOTTLE NDC: 71335-1269-4 30 CAPSULE in a BOTTLE NDC: 71335-1269-5 60 CAPSULE in a BOTTLE NDC: 71335-1269-6 120 CAPSULE in a BOTTLE NDC: 71335-1269-7 180 CAPSULE in a BOTTLE Product: 71335-1496 NDC: 71335-1496-1 90 CAPSULE in a BOTTLE NDC: 71335-1496-2 28 CAPSULE in a BOTTLE NDC: 71335-1496-3 120 CAPSULE in a BOTTLE NDC: 71335-1496-4 30 CAPSULE in a BOTTLE NDC: 71335-1496-5 60 CAPSULE in a BOTTLE
Authorization status:
Abbreviated New Drug Application
Authorization number:
71335-1269-1, 71335-1269-2, 71335-1269-3, 71335-1269-4, 71335-1269-5, 71335-1269-6, 71335-1269-7, 71335-1496-1, 71335-1496-2, 71335-1496-3, 71335-1496-4, 71335-1496-5

GABAPENTIN - gabapentin capsule

Bryant Ranch Prepack

----------

Medication Guide

Gabapentin Capsules 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

· 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.

3. Gabapentin may cause a 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:

· skin rash

· hives

· difficulty breathing

· fever

· 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

· frequent infections

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:

· Partial seizures when taken together with other medicines in adults and children 3 years of age and older

with seizures.

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

· have diabetes

· 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.

o 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

take.

o Do not change your dose of gabapentin without talking to your healthcare provider.

o Take gabapentin capsules with water.

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 gabapentin?”

· sleepiness and dizziness, which could increase the occurrence of accidental injury, including falls

· The most common side effects of gabapentin include:

· lack of coordination

· feeling tired

· viral infection

· fever

· feeling drowsy

· jerky movements

· nausea and vomiting

· difficulty with coordination

· difficulty with speaking

· double vision

· tremor

· 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-FDA-

1088.

How should I store gabapentin?

· Store gabapentin Capsules between 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.

What are the ingredients in gabapentin?

Active ingredient: gabapentin USP

Inactive ingredients in the capsules: anhydrous lactose, cornstarch, and talc. The 100-mg capsule shell also

contains: gelatin, sodium lauryl sulfate, and titanium dioxide.

The 300-mg capsule shell also contains: gelatin, sodium lauryl sulfate, titanium dioxide, and yellow iron

oxide.

The 400-mg capsule shell also contains: gelatin, sodium lauryl sulfate, red iron oxide, titanium dioxide, and

yellow iron oxide. The imprinting ink contains shellac, dehydrated alcohol, isopropyl alcohol, butyl alcohol,

propyl glycol, strong ammonia solution, and titanium dioxide.

This Medication Guide has been approved by the U.S. Food and Drug Administration.

Manufactured by:

Alkem Laboratories Limited

ALKEM HOUSE, Lower Parel,

Mumbai – 400 013, INDIA

Distributed by:

Ascend Laboratories, LCC

Parsippany, NJ 07054

Revised : August, 2019

Revised: 7/2020

Document Id: fc1140a4-e0c6-4464-823a-b9ca085581ef

34391-3

Set id: 6670a64f-7f58-479f-b285-394abb753e2e

Version: 3

Effective Time: 20200706

Bryant Ranch Prepack

GABAPENTIN - gabapentin capsule

Bryant Ranch Prepack

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use GABAPENTIN CAPSULES safely and

effectively. See full prescribing information for GABAPENTIN CAPSULES.

GABAPENTIN capsules for oral use

Initial U.S. Approval: 1993

INDICATIONS AND USAGE

Gabapentin is indicated for:

· Adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization, in adults and

pediatric patients 3 years and older with epilepsy (1)

DOSAGE AND ADMINISTRATION

· Epilepsy with Partial Onset Seizures (2.2)

o Patients 12 years of age and older: starting dose is 300 mg three times daily; may be titrated up to 600 mg three times

daily

o Patients 3 to 11 years of age: starting dose range is 10 to 15 mg/kg/day, given in three divided doses; recommended

dose in patients 3 to 4 years of age is 40 mg/kg/day, given in three divided doses; the recommended dose in patients 5 to

11 years of age is 25 to 35 mg/kg/day, given in three divided doses. The recommended dose is reached by upward titration

over a period of approximately 3 days

· Dose should be adjusted in patients with reduced renal function (2.3, 2.4)

DOSAGE FORMS AND STRENGTHS

· Capsules: 100 mg, 300 mg, and 400 mg (3)

CONTRAINDICATIONS

Known hypersensitivity to gabapentin or its ingredients (4)

WARNINGS AND PRECAUTIONS

· Drug Reaction with Eosinophilia and Systemic Symptoms (Multiorgan hypersensitivity): Discontinue if alternative

etiology is not established (5.1)

· Anaphylaxis and Angioedema: Discontinue and evaluate patient immediately (5.2)

· Driving Impairment; Somnolence/Sedation and Dizziness: Warn patients not to drive until they have gained sufficient

experience to assess whether their ability to drive or operate heavy machinery will be impaired (5.3, 5.4)

· Increased seizure frequency may occur in patients with seizure disorders if gabapentin is abruptly discontinued (5.5)

· Suicidal Behavior and Ideation: Monitor for suicidal thoughts/behavior (5.6)

· Neuropsychiatric Adverse Reactions in Children 3-12 Years of Age: Monitor for such events (5.7)

ADVERSE REACTIONS

Most common adverse reactions (incidence ≥8% and at least twice that for placebo) were:

· Epilepsy in patients >12 years of age: Somnolence, dizziness, ataxia, fatigue, and nystagmus (6.1)

· Epilepsy in patients 3 to 12 years of age: Viral infection, fever, nausea and/or vomiting, somnolence, and hostility (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-

272-7901)or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch

DRUG INTERACTIONS

Concentrations increased by morphine; may need dose adjustment (5.4, 7.2)

USE IN SPECIFIC POPULATIONS

· Pregnancy: Based on animal data, may cause fetal harm (8.1)

See 17 for PATIENT COUNSELING INFORMATION and Medication Guide.

Revised: 7/2020

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS & USAGE

2 DOSAGE & ADMINISTRATION

2.2 Dosage for Epilepsy with Partial Onset Seizures

2.3 Dosage Adjustment in Patients with Renal Impairment

2.4 Dosage in Elderly

2.5 Administration Information

3 DOSAGE FORMS & STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity

5.2 Anaphylaxis and Angioedema

5.3 Effects on Driving and Operating Heavy Machinery

5.4 Somnolence/Sedation and Dizziness

5.5 Withdrawal Precipitated Seizure, Status Epilepticus

5.6 Suicidal Behavior and Ideation

5.7 Neuropsychiatric Adverse Reactions (Pediatric Patients 3 to 12 Years of Age)

5.8 Tumorigenic Potential

5.9 Sudden and Unexplained Death in Patients with Epilepsy

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Other Antiepileptic Drugs

7.2 Opioids

7.3 Maalox® (aluminum hydroxide, magnesium hydroxide)

7.4 Drug/Laboratory Test Interactions

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

9 DRUG ABUSE AND DEPENDENCE

9.1 Controlled Substance

9.2 Abuse

9.3 Dependence

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis & Mutagenesis & Impairment Of Fertility

14 CLINICAL STUDIES

14.2 Epilepsy for Partial Onset Seizures (Adjunctive Therapy)

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

Sections or subsections omitted from the full prescribing information are not listed.

1 INDICATIONS & USAGE

Gabapentin is indicated for:

Adjunctive therapy in the treatment of partial onset seizures, with and without secondary generalization,

in adults and pediatric patients 3 years and older with epilepsy

2 DOSAGE & ADMINISTRATION

2.2 Dosage for Epilepsy with Partial Onset Seizures

Patients 12 years of age and above

The starting dose is 300 mg three times a day. The recommended maintenance dose of gabapentin is 300

mg to 600 mg three times a 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. Administer gabapentin three times a day using

300 mg or 400 mg capsules. The maximum time between doses should not exceed 12 hours.

Pediatric Patients Age 3 to 11 years

The starting dose range is 10 mg/kg/day to 15 mg/kg/day, given in three divided doses, and the

recommended maintenance dose reached by upward titration over a period of approximately 3 days. The

recommended maintenance dose of gabapentin in patients 3 to 4 years of age is 40 mg/kg/day, given in

three divided doses. The recommended maintenance dose of gabapentin in patients 5 to 11 years of age

is 25 mg/kg/day to 35 mg/kg/day, given in three divided doses. Gabapentin may be administered as the

oral capsule. 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 hour.

2.3 Dosage Adjustment in Patients with Renal Impairment

Dosage adjustment in patients 12 years of age and older with renal impairment or undergoing

hemodialysis is recommended, as follows (see dosing recommendations above for effective doses in

each indication):

TABLE 1. Gabapentin Dosage Based on Renal Function

Renal Function

Creatinine Clearance

(mL/min)

Total Daily

Dose Range

(mg/day)

Dose Regimen (mg)

≥ 60

900 to 3600

300 TID 400 TID 600 TID

800 TID 1200 TID

> 30 to 59

400 to 1400

200 BID 300 BID 400 BID

500 BID 700 BID

> 15 to 29

200 to 700

200 QD 300 QD 400 QD

500 QD 700 QD

100 to 300

100 QD 125 QD 150 QD

200 QD 300 QD

Post-Hemodialysis Supplemental Dose (mg)

Hemodialysis

125 150

TID = Three times a day; BID = Two times a day; QD = Single daily dose

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 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.

Creatinine clearance (CLCr) is difficult to measure in outpatients. In patients with stable renal function,

creatinine clearance can be reasonably well estimated using the equation of Cockcroft and Gault:

The use of gabapentin in patients less than 12 years of age with compromised renal function has not

been studied.

2.4 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.

2.5 Administration Information

Administer gabapentin orally with or without food.

Gabapentin capsules should be swallowed whole with water.

If the 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

prescriber).

3 DOSAGE FORMS & STRENGTHS

Capsules:

· 100 mg: White hard gelatin capsules imprinted “216” on body with blue ink.

· 300 mg: Yellow hard gelatin capsules imprinted “215” on body with blue ink.

· 400 mg: Orange hard gelatin capsules imprinted “214” on body with blue ink.

4 CONTRAINDICATIONS

Gabapentin is contraindicated in patients who have demonstrated hypersensitivity to the drug or its

ingredients.

5 WARNINGS AND PRECAUTIONS

5.1 Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan

Hypers ens itivity

Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS), also known as multiorgan

hypersensitivity, has occurred with gabapentin. Some of these reactions have been fatal or life-

threatening. DRESS typically, although not exclusively, presents with fever, rash, and/or

lymphadenopathy, in association with other organ system involvement, such as hepatitis, nephritis,

hematological abnormalities, myocarditis, or myositis sometimes resembling an acute viral infection.

Eosinophilia is often present. This disorder is variable in its expression, and other organ systems not

noted here may be involved.

It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy,

may be present even though rash is not evident. If such signs or symptoms are present, the patient should

be evaluated immediately. Gabapentin should be discontinued if an alternative etiology for the signs or

symptoms cannot be established.

5.2 Anaphylaxis and Angioedema

Gabapentin can cause anaphylaxis and angioedema after the first dose or at any time during treatment.

Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat,

and tongue, and hypotension requiring emergency treatment. Patients should be instructed to discontinue

gabapentin and seek immediate medical care should they experience signs or symptoms of anaphylaxis

or angioedema.

5.3 Effects on Driving and Operating Heavy Machinery

Patients taking gabapentin should not drive until they have gained sufficient experience to assess

whether gabapentin impairs their ability to drive. Driving performance studies conducted with a prodrug

of gabapentin (gabapentin enacarbil tablet, extended release) indicate that gabapentin may cause

significant driving impairment. Prescribers and patients should be aware that patients’ ability to assess

their own driving competence, as well as their ability to assess the degree of somnolence caused by

gabapentin, can be imperfect. The duration of driving impairment after starting therapy with gabapentin

is unknown. Whether the impairment is related to somnolence [see Warnings and Precautions (5.4 ) ] or

other effects of gabapentin is unknown.

Moreover, because gabapentin causes somnolence and dizziness [see Warnings and Precautions (5.4)],

patients should be advised not to operate complex machinery until they have gained sufficient

experience on gabapentin to assess whether gabapentin impairs their ability to perform such tasks

5.4 Somnolence/Sedation and Dizziness

During the controlled epilepsy trials in patients older than 12 years of age receiving doses of

gabapentin up to 1800 mg daily, somnolence, dizziness, and ataxia were reported at a greater rate in

patients receiving gabapentin compared to placebo: i.e., 19% in drug versus 9% in placebo for

somnolence, 17% in drug versus 7% in placebo for dizziness, and 13% in drug versus 6% in placebo

for ataxia. In these trials somnolence, ataxia and fatigue were common adverse reactions leading to

discontinuation of gabapentin in patients older than 12 years of age, with 1.2%, 0.8% and 0.6%

discontinuing for these events, respectively.

Patients should be carefully observed for signs of central nervous system (CNS) depression, such as

somnolence and sedation, when gabapentin is used with other drugs with sedative properties because of

potential synergy. In addition, patients who require concomitant treatment with morphine may experience

increases in gabapentin concentrations and may require dose adjustment.[see Drug Interactions (7.2)].

5.5 Withdrawal Precipitated Seizure, Status Epilepticus

Antiepileptic drugs should not be abruptly discontinued because of the possibility of increasing seizure

frequency.

In the placebo-controlled epilepsy 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

epilepsy 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.

5.6 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

1,000 Patients

Drug

Patients

with

Events

1,000 Patients

Relative

Risk:

Incidence

Events

Drug

Patients/Incidence

Placebo

Patients

Risk

Difference:

Additional Drug

Patients

with

Events Per 1,000

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.

5.7 Neuropsychiatric Adverse Reactions (Pediatric Patients 3 to 12 Years of Age)

Gabapentin use in pediatric patients with epilepsy 3 to12 years of age is associated with the occurrence

of CNS related adverse reactions. 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 reactions were mild to moderate in intensity.

In controlled clinical epilepsy trials in pediatric patients 3 to 12 years of age, the incidence of these

adverse reactions was: emotional lability 6% (gabapentin-treated patients) versus 1.3% (placebo-treated

patients); hostility 5.2% versus 1.3%; hyperkinesia 4.7% versus 2.9%; and thought disorder 1.7% versus

0%. One of these reactions, 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.

5.8 Tumorigenic Potential

In an oral carcinogenicity study, gabapentin increased the incidence of pancreatic acinar cell tumors in

rats [see Nonclinical Toxicology (13.1)]. 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 2,085 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

treatment.

5.9 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 epilepsy patients treated (2103 patient-years of exposure) with

gabapentin.

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.

6 ADVERSE REACTIONS

The following serious adverse reactions are discussed in greater detail in other sections:

· Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS)/Multiorgan Hypersensitivity [see

Warnings and Precautions (5.1)]

· Anaphylaxis and Angioedema [see Warnings and Precautions (5.2)]

· Somnolence/Sedation and Dizziness [seeWarnings and Precautions (5.4)]

· Withdrawal Precipitated Seizure, Status Epilepticus [see Warnings and Precautions (5.5)]

· Suicidal Behavior and Ideation [see Warnings and Precautions (5.6)]

· Neuropsychiatric Adverse Reactions (Pediatric Patients 3 to 12 Years of Age) [see Warnings and

Precautions (5.7]

· Sudden and Unexplained Death in Patients with Epilepsy [see Warnings and Precautions (5.9)]

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed

in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug

and may not reflect the rates observed in practice.

Epilepsy with Partial Onset Seizures (Adjunctive Therapy)

The most common adverse reactions with 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 common adverse reactions with 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 and

Precautions (5.7)].

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 reaction. The adverse reactions 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 reactions most commonly associated with

withdrawal in pediatric patients were emotional lability (1.6%), hostility (1.3%), and hyperkinesia

(1.1%).

Table 4 lists adverse reactions 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.

TABLE 4. Adverse Reactions in Pooled Placebo-Controlled Add-On Trials In Epilepsy Patients

>12 years of age

Gabapentin

N=543

Placebo

N=378 %

Body as a Whole

Fatigue

Increased Weight

Back Pain

Peripheral Edema

Cardiovascular

Vasodilatation

Digestive System

Dyspepsia

Dry Mouth or Throat

Constipation

Dental Abnormalities

Nervous System

Somnolence

Dizziness

Ataxia

Nystagmus

Tremor

Dysarthria

Amnesia

Depression

Abnormal thinking

Abnormal coordination

Respiratory System

Pharyngitis

Coughing

Skin and Appendages

Abrasion

Urogenital System

Impotence

Special Senses

Diplopia

Amblyopia

Plus background antiepileptic drug therapy

Amblyopia was often described as blurred vision.

Among the adverse reactions occurring at an incidence of at least 10% in gabapentin-treated patients,

somnolence and ataxia appeared to exhibit a positive dose-response relationship.

The overall incidence of adverse reactions and the types of adverse reactions seen were similar among

men and women treated with gabapentin. The incidence of adverse reactions 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 reactions by race.

Table 5 lists adverse reactions 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 which were numerically more

common in the gabapentin group.

TABLE 5. Adverse Reactions in a Placebo-Controlled Add-On Trial in Pediatric Epilepsy

Patients Age 3 to 12 Years

Gabapentin

N=119 %

Placebo

N=128 %

Body as a Whole

Viral Infection

Fever

Increased Weight

Fatigue

Digestive System

Nausea and/or Vomiting

Nervous System

Somnolence

Hostility

Emotional Lability

Dizziness

Hyperkinesia

Respiratory System

Bronchitis

Respiratory Infection

Plus background antiepileptic drug therapy

Other reactions 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.

6.2 Postmarketing Experience

The following adverse reactions have been identified during postmarketing use of gabapentin. Because

these reactions are reported voluntarily from a population of uncertain size, it is not always possible to

reliably estimate their frequency or establish a causal relationship to drug exposure.

Hepatobiliary disorders: jaundice

Investigations: elevated creatine kinase, elevated liver function tests

Metabolism and nutrition disorders: hyponatremia

Musculoskeletal and connective tissue disorder: rhabdomyolysis

Nervous system disorders: movement disorder

Psychiatric disorders: agitation

Reproductive system and breast disorders: breast enlargement, changes in libido, ejaculation disorders

and anorgasmia

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