DESCRIPTION
id: 5f1727c3-445b-43c7-b36a-02ba7fe4cc7e
displayName: DESCRIPTION SECTION
FDA Article Code: 34089-3
Gabapentin Capsules, USP are supplied as imprinted hard gelatin capsules containing 100 mg, 300 mg and 400 mg of gabapentin, USP.
The inactive ingredients are mannitol, pre-gelatinized starch and talc. The 100 mg capsule shell contains titanium dioxide. The 300 mg capsule contains FD&C Red 40, D&C Yellow 10 and titanium dioxide. The 400 mg capsule shell contains FD&C Red 40, D&C Yellow 10 and titanium dioxide.
Gabapentin, USP 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:
9
17
2
C H NO M.W. 171.24
9
17
2
Gabapentin, USP 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.
a1
a2
INDICATIONS AND USAGE
id: 061eb229-32d6-42b1-96e1-06c3c95f0482
displayName: INDICATIONS & USAGE SECTION
FDA Article Code: 34067-9
Postherpetic Neuralgia
Gabapentin is indicated for the management of postherpetic neuralgia in adults.
Epilepsy
Gabapentin is indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy. Gabapentin is also indicated as adjunctive therapy in the treatment of partial seizures in pediatric patients age 3 – 12 years.
CONTRAINDICATIONS
id: e113f511-f830-45d3-b5ad-ffa054193a3f
displayName: CONTRAINDICATIONS SECTION
FDA Article Code: 34070-3
Gabapentin is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.
WARNINGS
id: 1aa17d26-2fbc-4097-ad36-62c5c6a75e09
displayName: WARNINGS SECTION
FDA Article Code: 34071-1
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 (5-100 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 |
1.0 |
3.4 |
3.5 |
2.4 |
| Psychiatric |
5.7 |
8.5 |
1.5 |
2.9 |
| Other |
1.0 |
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.
Neuropsychiatric Adverse Events—Pediatric Patients 3-12 years of age
Gabapentin use in pediatric patients with epilepsy 3–12 years of age is associated with the occurrence of central nervous system related adverse events. The most significant of these can be classified into the following categories: 1) emotional lability (primarily behavioral problems), 2) hostility, including aggressive behaviors, 3) thought disorder, including concentration problems and change in school performance, and 4) hyperkinesia (primarily restlessness and hyperactivity). Among the gabapentin-treated patients, most of the events were mild to moderate in intensity.
In controlled trials in pediatric patients 3–12 years of age the incidence of these adverse events was: emotional lability 6% (gabapentin-treated patients) vs 1.3% (placebo-treated patients); hostility 5.2% vs 1.3%; hyperkinesia 4.7% vs 2.9%; and thought disorder 1.7% vs 0%. One of these events, a report of hostility, was considered serious. Discontinuation of gabapentin treatment occurred in 1.3% of patients reporting emotional lability and hyperkinesia and 0.9% of gabapentin-treated patients reporting hostility and thought disorder. One placebo-treated patient (0.4%) withdrew due to emotional lability.
Withdrawal Precipitated Seizure, Status Epilepticus
Antiepileptic drugs should not be abruptly discontinued because of the possibility of increasing seizure frequency.
In the placebo-controlled studies in patients >12 years of age, the incidence of status epilepticus in patients receiving gabapentin was 0.6% (3 of 543) versus 0.5% in patients receiving placebo (2 of 378). Among the 2074 patients >12 years of age treated with gabapentin across all studies (controlled and uncontrolled) 31 (1.5%) had status epilepticus. Of these, 14 patients had no prior history of status epilepticus either before treatment or while on other medications. Because adequate historical data are not available, it is impossible to say whether or not treatment with gabapentin is associated with a higher or lower rate of status epilepticus than would be expected to occur in a similar population not treated with gabapentin.
Tumorigenic Potential
In standard preclinical lifetime carcinogenicity studies, an unexpectedly high incidence of pancreatic acinar adenocarcinomas was identified in male, but not female, rats. (See .) 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 vivo
PRECAUTIONS: Carcinogenesis, Mutagenesis, Impairment of Fertility
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 ), 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.
in situ
Sudden and Unexplained Death in Patients With Epilepsy
During the course of premarketing development of gabapentin 8 sudden and unexplained deaths were recorded among a cohort of 2203 patients treated (2103 patient-years of exposure).
Some of these could represent seizure-related deaths in which the seizure was not observed, e.g., at night. This represents an incidence of 0.0038 deaths per patient-year. Although this rate exceeds that expected in a healthy population matched for age and sex, it is within the range of estimates for the incidence of sudden unexplained deaths in patients with epilepsy not receiving gabapentin (ranging from 0.0005 for the general population of epileptics to 0.003 for a clinical trial population similar to that in the gabapentin program, to 0.005 for patients with refractory epilepsy). Consequently, whether these figures are reassuring or raise further concern depends on comparability of the populations reported upon to the gabapentin cohort and the accuracy of the estimates provided.
ADVERSE REACTIONS
id: 6d36d123-bb2b-45e9-ab52-aa87773c8994
displayName: ADVERSE REACTIONS SECTION
FDA Article Code: 34084-4
Postherptic 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/ |
Gabapentin |
Placebo |
| Preferred Term |
N=336 |
N=227 |
|
% |
% |
Reported as blurred vision
a
|
|
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 |
0.0 |
| Hyperglycemia |
1.2 |
0.4 |
|
Nervous System
|
|
|
| Dizziness |
28.0 |
7.5 |
| Somnolence |
21.4 |
5.3 |
| Ataxia |
3.3 |
0.0 |
| Thinking abnormal |
2.7 |
0.0 |
| Abnormal gait |
1.5 |
0.0 |
| Incoordination |
1.5 |
0.0 |
| 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
|
|
|
Amblyopia
a
|
2.7 |
0.9 |
| Conjunctivitis |
1.2 |
0.0 |
| Diplopia |
1.2 |
0.0 |
| Otitis media |
1.2 |
0.0 |
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 hyperkinesias (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/ |
Gabapentin
a
|
Placebo
a
|
| Adverse Event |
N=543 |
N=378 |
|
% |
% |
Plus background antiepileptic drug therapy
a
|
Amblyopia was often described as blurred vision.
b
|
|
Body As A Whole
|
|
|
| Fatigue |
11.0 |
5.0 |
| 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 |
2.0 |
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 |
4.0 |
| Tremor |
6.8 |
3.2 |
| Nervousness |
2.4 |
1.9 |
| Dysarthria |
2.4 |
0.5 |
| Amnesia |
2.2 |
0.0 |
| 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 |
0.0 |
| Pruritus |
1.3 |
0.5 |
|
Urogenital System
|
|
|
| Impotence |
1.5 |
1.1 |
|
Special Senses
|
|
|
| Diplopia |
5.9 |
1.9 |
Amblyopia
b
|
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/ |
Gabapentin
a
|
Placebo
a
|
| Adverse Event |
N=119 |
N=128 |
|
% |
% |
Plus background antiepileptic drug therapy
a
|
|
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 |
7.0 |
|
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.
: asthenia, malaise, face edema; : allergy, generalized edema, weight decrease, chill; : strange feelings, lassitude, alcohol intolerance, hangover effect.
Body As A Whole:
Frequent
Infrequent
Rare
: hypertension; : hypotension, angina pectoris, peripheral vascular disorder, palpitation, tachycardia, migraine, murmur; : 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.
Cardiovascular System:
Frequent
Infrequent
Rare
: anorexia, flatulence, gingivitis; : glossitis, gum hemorrhage, thirst, stomatitis, increased salivation, gastroenteritis, hemorrhoids, bloody stools, fecal incontinence, hepatomegaly; : 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.
Digestive System:
Frequent
Infrequent
Rare
: hyperthyroid, hypothyroid, goiter, hypoestrogen, ovarian failure, epididymitis, swollen testicle, cushingoid appearance.
Endocrine System:
Rare
: purpura most often described as bruises resulting from physical trauma; : anemia, thrombocytopenia, lymphadenopathy; : WBC count increased, lymphocytosis, non-Hodgkin’s lymphoma, bleeding time increased.
Hematologic And Lymphatic System:
Frequent
Infrequent
Rare
: arthralgia; : tendinitis, arthritis, joint stiffness, joint swelling, positive Romberg test; : costochondritis, osteoporosis, bursitis, contracture.
Musculoskeletal System:
Frequent
Infrequent
Rare
: vertigo, hyperkinesia, paresthesia, decreased or absent reflexes, increased reflexes, anxiety, hostility; : 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, suicide attempt, psychosis; : 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, suicide.
Nervous System:
Frequent
Infrequent
Rare
: pneumonia; : epistaxis, dyspnea, apnea; : mucositis, aspiration pneumonia, hyperventilation, hiccup, laryngitis, nasal obstruction, snoring, bronchospasm, hypoventilation, lung edema.
Respiratory System:
Frequent
Infrequent
Rare
: alopecia, eczema, dry skin, increased sweating, urticaria, hirsutism, seborrhea, cyst, herpes simplex; : herpes zoster, skin discolor, skin papules, photosensitive reaction, leg ulcer, scalp seborrhea, psoriasis, desquamation, maceration, skin nodules, subcutaneous nodule, melanosis, skin necrosis, local swelling.
Dermatological:
Infrequent
Rare
: hematuria, dysuria, urination frequency, cystitis, urinary retention, urinary incontinence, vaginal hemorrhage, amenorrhea, dysmenorrhea, menorrhagia, breast cancer, unable to climax, ejaculation abnormal; : kidney pain, leukorrhea, pruritus genital, renal stone, acute renal failure, anuria, glycosuria, nephrosis, nocturia, pyuria, urination urgency, vaginal pain, breast pain, testicle pain.
Urogenital System:
Infrequent
Rare
: abnormal vision; : 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; : 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.
Special Senses:
Frequent
Infrequent
Rare
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:
dehydration, infectious mononucleosis
Body As A Whole:
hepatitis
Digestive System:
coagulation defect
Hemic And Lymphatic System:
aura disappeared, occipital neuralgia
Nervous System:
sleepwalking
Psychobiologic Function:
pseudocroup, hoarseness
Respiratory System:
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.
chest pain, cellulitis, malaise, neck pain, face edema, allergic reaction, abscess, chills, chills and fever, mucous membrane disorder; body odor, cyst, fever, hernia, abnormal BUN value, lump in neck, pelvic pain, sepsis, viral infection.
Body as A Whole:
Infrequent:
Rare:
hypertension, syncope, palpitation, migraine, hypotension, peripheral vascular disorder, cardiovascular disorder, cerebrovascular accident, congestive heart failure, myocardial infarction, vasodilatation; angina pectoris, heart failure, increased capillary fragility, phlebitis, thrombophlebitis, varicose vein.
Cardiovascular System:
Infrequent:
Rare:
gastroenteritis, increased appetite, gastrointestinal disorder, oral moniliasis, gastritis, tongue disorder, thirst, tooth disorder, abnormal stools, anorexia, liver function tests abnormal, periodontal abscess; cholecystitis, cholelithiasis, duodenal ulcer, fecal incontinence, gamma glutamyl transpeptidase increased, gingivitis, intestinal obstruction, intestinal ulcer, melena, mouth ulceration, rectal disorder, rectal hemorrhage, stomatitis.
Digestive System:
Infrequent:
Rare:
diabetes mellitus.
Endocrine System:
Infrequent:
ecchymosis, anemia; lymphadenopathy, lymphoma-like reaction, prothrombin decreased.
Hemic And Lymphatic System:
Infrequent:
Rare:
edema, gout, hypoglycemia, weight loss; alkaline phosphatase increased, diabetic ketoacidosis, lactic dehydrogenase increased.
Metabolic And Nutritional:
Infrequent:
Rare:
arthritis, arthralgia, myalgia, arthrosis, leg cramps, myasthenia; shin bone pain, joint disorder, tendon disorder.
Musculoskeletal:
Infrequent:
Rare:
confusion, depression; 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, suicide attempt; agitation, hypertonia, libido increased, movement disorder, myoclonus, vestibular disorder.
Nervous System:
Frequent:
Infrequent:
Rare:
cough increased, bronchitis, rhinitis, sinusitis, pneumonia, asthma, lung disorder, epistaxis; hemoptysis, voice alteration.
Respiratory System:
Infrequent:
Rare:
pruritus, skin ulcer, dry skin, herpes zoster, skin disorder, fungal dermatitis, furunculosis, herpes simplex, psoriasis, sweating, urticaria, vesiculobullous rash; acne, hair disorder, maculopapular rash, nail disorder, skin carcinoma, skin discoloration, skin hypertrophy.
Skin And Appendages:
Infrequent:
Rare:
abnormal vision, ear pain, eye disorder, taste perversion, deafness; conjunctival hyperemia, diabetic retinopathy, eye pain, fundi with microhemorrhage, retinal vein thrombosis, taste loss.
Special Senses:
Infrequent:
Rare:
urinary tract infection, dysuria, impotence, urinary incontinence, vaginal moniliasis, breast pain, menstrual disorder, polyuria, urinary retention; cystitis, ejaculation abnormal, swollen penis, gynecomastia, nocturia, pyelonephritis, swollen scrotum, urinary frequency, urinary urgency, urine abnormality.
Urogenital System:
Infrequent:
Rare:
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, 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
id: 6d50af40-e286-47a5-aa2f-848b45cfa5dc
displayName: DRUG ABUSE AND DEPENDENCE SECTION
FDA Article Code: 42227-9
The abuse and dependence potential of gabapentin has not been evaluated in human studies.
OVERDOSAGE
id: 51c490be-a225-4a41-ab64-427d267037fd
displayName: OVERDOSAGE SECTION
FDA Article Code: 34088-5
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
id: 3a9e0fa3-95dc-4940-b91e-f5cd23667e59
displayName: DOSAGE & ADMINISTRATION SECTION
FDA Article Code: 34068-7
Gabapentin Capsules, USP are given orally with or without food.
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 is recommended for add-on therapy in patients 3 years of age and older. Effectiveness in pediatric patients below the age of 3 years has not been established.
The effective dose of gabapentin is 900 to 1800 mg/day and given in divided doses (three times a day) using 300 or 400 mg capsules, or 600 or 800 mg tablets. The starting dose is 300 mg three times a day. If necessary, the dose may be increased using 300 or 400 mg capsules, or 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.
Patients >12 years of age:
The starting dose should range from 10-15 mg/kg/day in 3 divided doses, and the effective dose reached by upward titration over a period of approximately 3 days. The effective dose of gabapentin in patients 5 years of age and older is 25–35 mg/kg/day and given in divided doses (three times a day). The effective dose in pediatric patients ages 3 and 4 years is 40 mg/kg/day and given in divided doses (three times a day) (see .) Gabapentin may be administered as the oral solution, capsule, or tablet, or using combinations of these formulations. 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.
Pediatric Patients Age 3–12 years:
CLINICAL PHARMACOLOGY, Pediatrics
It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin therapy. Further, because there are no significant pharmacokinetic interactions among gabapentin and other commonly used antiepileptic drugs, the addition of gabapentin does not alter the plasma levels of these drugs appreciably.
If gabapentin is discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of 1 week.
Dosage in Renal Impairment
Creatinine clearance is difficult to measure in outpatients. In patients with stable renal function, creatinine clearance (C ) can be reasonably well estimated using the equation of Cockcroft and Gault: for females C =(0. 85)( 140-age)(weight)/[(72)(S )] for males C =(140-age)(weight)/[(72)(S )]
Cr
Cr
Cr
Cr
Cr
where age is in years, weight is in kilograms and S is serum creatinine in mg/dL.
Cr
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)
|
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).
a
|
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.
b
|
| ≥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 |
15
a
|
100-300 |
100 QD |
125 QD |
150 QD |
200 QD |
300 QD |
Post-Hemodialysis Supplemental Dose (mg)
b
|
| Hemodialysis |
125
b
|
150
b
|
200
b
|
250
b
|
350
b
|
The use of gabapentin 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
id: 5ca74dcf-4e54-47e2-a4d3-c66e63e54cb3
displayName: HOW SUPPLIED SECTION
FDA Article Code: 34069-5
NDC:64725-0221-1 in a BOTTLE of 100 CAPSULES
