DESCRIPTION

Gabapentin tablets, USP are supplied as film-coated tablets containing 600 mg and 800 mg of gabapentin USP.
 
The inactive ingredients for the tablets are copovidone, corn starch, crospovidone, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, and talc.
 
Gabapentin is described as 1-(aminomethyl)cyclohexaneacetic acid with a molecular formula of C9H17NO2 and a molecular weight of 171.24. The structural formula of gabapentin is:

Gabapentin USP is a white to off-white, crystalline solid with a pKa1 of 3.7 and a pKa2 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.

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 GABAA or GABAB 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 Cmax).

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 (Cmin) 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).

INDICATIONS AND USAGE

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 are also indicated as adjunctive therapy in the treatment of partial seizures in pediatric patients age 3 to 12 years.

CONTRAINDICATIONS

Gabapentin tablets 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	1	3.4	3.5	2.4
Psychiatric	5.7	8.5	1.5	2.9
Other	1	1.8	1.9	0.9
Total	2.4	4.3	1.8	1.9

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.

PRECAUTIONS

ADVERSE REACTIONS

Postherpetic Neuralgia
 
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 edema.
 
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 System/Preferred Term	Gabapentin N=336 %	Placebo N=227 %
a Reported as blurred vision
Body as a Whole
Asthenia	5.7	4.8
Infection	5.1	3.5
Headache	3.3	3.1
Accidental injury	3.3	1.3
Abdominal pain	2.7	2.6
Digestive System
Diarrhea	5.7	3.1
Dry mouth	4.8	1.3
Constipation	3.9	1.8
Nausea	3.9	3.1
Vomiting	3.3	1.8
Flatulence	2.1	1.8
Metabolic and Nutritional Disorders
Peripheral edema	8.3	2.2
Weight gain	1.8	0
Hyperglycemia	1.2	0.4
Nervous System
Dizziness	28	7.5
Somnolence	21.4	5.3
Ataxia	3.3	0
Thinking abnormal	2.7	0
Abnormal gait	1.5	0
Incoordination	1.5	0
Amnesia	1.2	0.9
Hypesthesia	1.2	0.9
Respiratory System
Pharyngitis	1.2	0.4
Skin and Appendages
Rash	1.2	0.9
Special Senses
Amblyopiaa	2.7	0.9
Conjunctivitis	1.2	0
Diplopia	1.2	0
Otitis media	1.2	0

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.

Epilepsy
 
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 , Neuropsychiatric 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 population studied.

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	Gabapentina N=543 %	Placeboa N=378 %
a Plus background antiepileptic drug therapy b Amblyopia was often described as blurred vision.
Body As A Whole
Fatigue	11	5
Weight Increase	2.9	1.6
Back Pain	1.8	0.5
Peripheral Edema	1.7	0.5
Cardiovascular
Vasodilatation	1.1	0.3
Digestive System
Dyspepsia	2.2	0.5
Mouth or Throat Dry	1.7	0.5
Constipation	1.5	0.8
Dental Abnormalities	1.5	0.3
Increased Appetite	1.1	0.8
Hematologic and Lymphatic Systems
Leukopenia	1.1	0.5
Musculoskeletal System
Myalgia	2	1.9
Fracture	1.1	0.8
Nervous System
Somnolence	19.3	8.7
Dizziness	17.1	6.9
Ataxia	12.5	5.6
Nystagmus	8.3	4
Tremor	6.8	3.2
Nervousness	2.4	1.9
Dysarthria	2.4	0.5
Amnesia	2.2	0
Depression	1.8	1.1
Thinking Abnormal	1.7	1.3
Twitching	1.3	0.5
Coordination Abnormal	1.1	0.3
Respiratory System
Rhinitis	4.1	3.7
Pharyngitis	2.8	1.6
Coughing	1.8	1.3
Skin and Appendages
Abrasion	1.3	0
Pruritus	1.3	0.5
Urogenital System
Impotence	1.5	1.1
Special Senses
Diplopia	5.9	1.9
Amblyopiab	4.2	1.1
Laboratory Deviations
WBC Decreased	1.1	0.5

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 intensity.

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 Event	Gabapentina N=119 %	Placeboa N=128 %
a Plus background antiepileptic drug therapy
Body As A Whole
Viral Infection	10.9	3.1
Fever	10.1	3.1
Weight Increase	3.4	0.8
Fatigue	3.4	1.6
Digestive System
Nausea and/or Vomiting	8.4	7
Nervous System
Somnolence	8.4	4.7
Hostility	7.6	2.3
Emotional Lability	4.2	1.6
Dizziness	2.5	1.6
Hyperkinesia	2.5	0.8
Respiratory System
Bronchitis	3.4	0.8
Respiratory Infection	2.5	0.8

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
 
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, 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, antisocial reaction.

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, testicle 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 hypertrophy.

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 enlargement, 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.

OVERDOSAGE

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 supportive care.

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 renal impairment.

DOSAGE AND ADMINISTRATION

Gabapentin tablets are 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 discarded. 
 
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 prescriber).

Postherpetic Neuralgia
 
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.

Epilepsy
 
Gabapentin tablets are 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 tablets 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 to 12 years
 
The starting dose should range from 10 to 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 tablets in patients 5 years of age and older is 25 to 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 tablets and other commonly used antiepileptic drugs, the addition of gabapentin tablets does not alter the plasma levels of these drugs appreciably.
 
If gabapentin tablets are 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 (CCr) can be reasonably well estimated using the equation of Cockcroft and Gault:
 
      for females CCr=(0.85)[(140-age)(weight)/(72)(SCr)]
      for males CCr=(140-age)(weight)/(72)(SCr)
 
where age is in years, weight is in kilograms and SCr 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 each indication).

TABLE 6. Gabapentin Dosage Based on Renal Function

Renal Function Creatinine Clearance (mL/min)	Total Daily Dose Range (mg/day)	Dose Regimen (mg)
a 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). b 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.
≥60	900-3600	300 TID	400 TID	600 TID	800 TID	1200 TID
>30-59	400-1400	200 BID	300 BID	400 BID	500 BID	700 BID
>15-29	200-700	200 QD	300 QD	400 QD	500 QD	700 QD
15a	100-300	100 QD	125 QD	150 QD	200 QD	300 QD
Post-Hemodialysis Supplemental Dose (mg)b
Hemodialysis		125b	150b	200b	250b	350b

The use of gabapentin tablets in patients <12 years of age with compromised renal function has not been studied.

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.

HOW SUPPLIED

Gabapentin Tablets USP, 600 mg are white, biconvex, elliptical, film-coated tablets, with deep break line on both sides and debossed with ‘D’ and ‘24’ on either side of the break line on one side and plain on other side.
 
Bottles of 10     NDC 33261-051-10
Bottles of 20     NDC 33261-051-20
Bottles of 21     NDC 33261-051-21
Bottles of 30     NDC 33261-051-30
Bottles of 42     NDC 33261-051-42
Bottles of 45     NDC 33261-051-45
Bottles of 60     NDC 33261-051-60
Bottles of 81     NDC 33261-051-81
Bottles of 90     NDC 33261-051-90
Bottles of 100   NDC 33261-051-00
Bottles of 120   NDC 33261-051-02
Bottles of 126   NDC 33261-051-97
Bottles of 180   NDC 33261-051-99


 
Gabapentin Tablets USP, 800 mg are white, biconvex, elliptical, film-coated tablets, with deep break line on both sides and debossed with ‘D’ and ‘25’ on either side of the break line on one side and plain on other side.
 
Bottles of 10 NDC 33261-116-10
Bottles of 20 NDC 33261-116-20
Bottles of 21 NDC 33261-116-21
Bottles of 30 NDC 33261-116-30
Bottles of 42 NDC 33261-116-42
Bottles of 45 NDC 33261-116-45
Bottles of 60 NDC 33261-116-60
Bottles of 81 NDC 33261-116-81
Bottles of 90 NDC 33261-116-90
Bottles of 100 NDC 33261-116-00
Bottles of 120 NDC 33261-116-02
Bottles of 126 NDC 33261-116-97
Bottles of 180 NDC 33261-116-99
 
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]
 
Maalox® is a registered trademark of Novartis Consumer Health, Inc. 
 
Manufactured for:
Aurobindo Pharma USA, Inc.
2400 Route 130 North
Dayton, NJ 08810
 
Manufactured by:
Aurobindo Pharma Limited
Unit-VII (SEZ)
Mahaboob Nagar (Dt)
AP-509302, INDIA

Repackaged By:
Aidarex Pharmaceuticals, LLC.
Corona, CA 92880
 
Issued: August 2011

MEDICATION GUIDE

Gabapentin Tablets, USP
Rx only
 
Read the Medication Guide before you start taking gabapentin tablets 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 tablets?

Do not stop taking gabapentin tablets without first talking to your healthcare provider. Stopping gabapentin tablets suddenly can cause serious problems.

Gabapentin tablets can cause serious side effects including:
 
1. Like other antiepileptic drugs, gabapentin tablets 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 tablets without first talking to a healthcare provider.
  

• Stopping gabapentin tablets 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 tablets 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 tablets may cause a serious or life-threatening allergic reaction that may affect your skin or other parts of your body such as your liver or blood cells. You may or may not have rash when you get this type of reaction. It may cause you to be hospitalized or to stop gabapentin tablets. Call a healthcare provider right away if you have any of the following symptoms:
 

• skin rash
• hives
• fever
• swollen glands that do not go away
• swelling of your lip and 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 tablets.

What are gabapentin tablets?
 
Gabapentin tablets are 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 tablets?
 
Do not take gabapentin tablets if you are allergic to gabapentin or any of the other ingredients in gabapentin tablets. See the end of this Medication Guide for a complete list of ingredients in gabapentin tablets. 

What should I tell my healthcare provider before taking gabapentin tablets?
 
Before taking gabapentin tablets, 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 tablets can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking gabapentin tablets. You and your healthcare provider will decide if you should take gabapentin tablets while you are pregnant.
  • If you become pregnant while taking gabapentin tablets, 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 tablets.

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.
 
Taking gabapentin tablets 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 tablets?
 

• Take gabapentin tablets exactly as prescribed. Your healthcare provider will tell you how much gabapentin tablets to take.
  • Do not change your dose of gabapentin tablets 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 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 tablets.
• If you take too much gabapentin tablets, call your healthcare provider or your local Poison Control Center right away.

What should I avoid while taking gabapentin tablets?
 

• Do not drink alcohol or take other medicines that make you sleepy or dizzy while taking gabapentin tablets without first talking with your healthcare provider. Taking gabapentin tablets 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 tablets affect you. Gabapentin tablets can slow your thinking and motor skills.

What are the possible side effects of gabapentin tablets?
 

• See “What is the most important information I should know about gabapentin tablets?”
• The most common side effects of gabapentin tablets include:
  • dizziness
  • difficulty with speaking
  • lack of coordination
  • temporary loss of memory (amnesia)
  • viral infection
  • tremor
  • feeling drowsy
  • difficulty with coordination
  • feeling tired
  • double vision
  • fever
  • unusual eye movement
  • jerky movements

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 tablets. 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 tablets?
 

• Store gabapentin tablets between 20° to 25°C (68° to 77°F).  

Keep gabapentin tablets and all medicines out of the reach of children.
 
General information about the safe and effective use of gabapentin tablets
 
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use gabapentin tablets for a condition for which it was not prescribed. Do not give gabapentin tablets to other people, even if they have the same symptoms that you have. They may harm them. 
 
This Medication Guide summarizes the most important information about gabapentin tablets. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about gabapentin tablets that was written for healthcare professionals. 
 
For more information about gabapentin tablets and for medical inquiries or to report side effects regarding gabapentin tablets, please call 1-866-850-2876.
 
What are the ingredients in gabapentin tablets?
 
Active ingredient: gabapentin 
 
Inactive ingredients: copovidone, corn starch, crospovidone, hydroxypropyl cellulose, magnesium stearate, microcrystalline cellulose, and talc.
 
This Medication Guide has been approved by the U.S. Food and Drug Administration.
 
* All brands listed are the trademarks of their respective owners and are not trademarks of Aurobindo Pharma Limited.
 
Manufactured for:
Aurobindo Pharma USA, Inc.
2400 Route 130 North
Dayton, NJ 08810
 
Manufactured by:
Aurobindo Pharma Limited
Unit-VII (SEZ)
Mahaboob Nagar (Dt)
AP-509302, INDIA

Issued: August 2011

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 600 mg (100 Tablet Bottle)

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 800 mg (100 Tablet Bottle)