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DESCRIPTIONGabapentin tablets USP are an anticonvulsant for oral administration. Gabapentin USP is described as 1-(aminomethyl)cyclohexaneacetic acid. 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. The structural formula of gabapentin USP is:
C9H17NO2 M.W. 171.24
Each gabapentin tablet USP, for oral administration, contains 600 mg or 800 mg of gabapentin USP and contains the following inactive ingredients: lactose monohydrate, microcrystalline cellulose and polyethylene glycol.
CLINICAL PHARMACOLOGYMechanism 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 100and 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.
PHARMACOKINETICSPharmacokinetics and Drug Metabolism
Less than 3% of gabapentin circulates bound to plasma protein. The apparent volume of distribution of gabapentin after 150 mg intravenous administration is 586 L (MeanSD). In patients with epilepsy, steady-state predose (Cmin) concentrations of gabapentin in cerebrospinal fluid were approximately 20% of the corresponding plasma concentrations.
Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug. Gabapentin is not appreciably metabolized in humans.
Gabapentin elimination half-life is 5 to 7 hours and is unaltered by dose or following multiple dosing. Gabapentin elimination rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance (see Special Populations, Adult Patients With Renal Insufficiency, below). In elderly patients, and in patients with impaired renal function, gabapentin plasma clearance is reduced. Gabapentin can be removed from plasma by hemodialysis.
Dosage adjustment in patients with compromised renal function or undergoing hemodialysis is recommended (see DOSAGE AND ADMINISTRATION, Table 6).
Adult Patients With Renal Insufficiency
Subjects (n = 60) with renal insufficiency (mean creatinine clearance ranging from 13 to 114 mL/min) were administered single 400 mg oral doses of gabapentin. The mean gabapentin half-life ranged from about 6.5 hours (patients with creatinine clearance > 60 mL/min) to 52 hours (creatinine clearance < 30 mL/min) and gabapentin renal clearance from about 90 mL/min (> 60 mL/min group) to about 10 mL/min (< 30 mL/min). Mean plasma clearance (CL/F) decreased from approximately 190 mL/min to 20 mL/min.
Dosage adjustment in adult patients with compromised renal function is necessary (see DOSAGE AND ADMINISTRATION). Pediatric patients with renal insufficiency have not been studied.
Dosage adjustment in patients undergoing hemodialysis is necessary (see DOSAGE AND ADMINISTRATION).
Because gabapentin is not metabolized, no study was performed in patients with hepatic impairment.
Gabapentin pharmacokinetics were determined in 48 pediatric subjects between the ages of 1 month and 12 years following a dose of approximately 10 mg/kg. Peak plasma concentrations were similar across the entire age group and occurred 2 to 3 hours postdose. In general, pediatric subjects between 1 month and < 5 years of age achieved approximately 30% lower exposure (AUC) than that observed in those 5 years of age and older. Accordingly, oral clearance normalized per body weight was higher in the younger children. Apparent oral clearance of gabapentin was directly proportional to creatinine clearance. Gabapentin elimination half-life averaged 4.7 hours and was similar across the age groups studied.
A population pharmacokinetic analysis was performed in 253 pediatric subjects between 1 month and 13 years of age. Patients received 10 to 65 mg/kg/day given TID. Apparent oral clearance (CL/F) was directly proportional to creatinine clearance and this relationship was similar following a single dose and at steady state. Higher oral clearance values were observed in children < 5 years of age compared to those observed in children 5 years of age and older, when normalized per body weight. The clearance was highly variable in infants < 1 year of age. The normalized CL/F values observed in pediatric patients 5 years of age and older were consistent with values observed in adults after a single dose. The oral volume of distribution normalized per body weight was constant across the age range.
These pharmacokinetic data indicate that the effective daily dose in pediatric patients with epilepsy ages 3 and 4 years should be 40 mg/kg/day to achieve average plasma concentrations similar to those achieved in patients 5 years of age and older receiving gabapentin at 30 mg/kg/day (see DOSAGE AND ADMINISTRATION).
Although no formal study has been conducted to compare the pharmacokinetics of gabapentin in men and women, it appears that the pharmacokinetic parameters for males and females are similar and there are no significant gender differences.
Pharmacokinetic differences due to race have not been studied. Because gabapentin is primarily renally excreted and there are no important racial differences in creatinine clearance, pharmacokinetic differences due to race are not expected.
Table 1. Controlled PHN Studies: Duration, Dosages, and Number of Patients
*Given in 3 divided doses (TID)StudyStudy DurationGabapentin (mg/day)*Target DosePatients Receiving GabapentinPatients Receiving Placebo18 weeks360011311627 weeks1800, 2400223111Total336227Each study included a 1 week baseline during which patients were screened for eligibility and a 7 or 8 week double-blind phase (3 or 4 weeks of titration and 4 weeks of fixed dose). Patients initiated treatment with titration to a maximum of 900 mg/day gabapentin over 3 days. Dosages were then to be titrated in 600 to 1200 mg/day increments at 3 to 7 day intervals to target dose over 3 to 4 weeks. In Study 1, patients were continued on lower doses if not able to achieve the target dose. During baseline and treatment, patients recorded their pain in a daily diary using an 11 point numeric pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). A mean pain score during baseline of at least 4 was required for randomization (baseline mean pain score for Studies 1 and 2 combined was 6.4). Analyses were conducted using the ITT population (all randomized patients who received at least one dose of study medication).
Both studies showed significant differences from placebo at all doses tested.
A significant reduction in weekly mean pain scores was seen by Week 1 in both studies, and significant differences were maintained to the end of treatment. Comparable treatment effects were observed in all active treatment arms. Pharmacokinetic/pharmacodynamic modeling provided confirmatory evidence of efficacy across all doses. Figures 1 and 2 show these changes for Studies 1 and 2.
Figure 1. Weekly Mean Pain Scores (Observed Cases in ITT Population): Study 1
Figure 2. Weekly Mean Pain Scores (Observed Cases in ITT Population): Study 2
The proportion of responders (those patients reporting at least 50% improvement in endpoint pain score compared with baseline) was calculated for each study ( Figure 3).
Figure 3. Proportion of Responders (patients with50% reduction in pain score) at Endpoint: Controlled PHN Studies
The effectiveness of gabapentin as adjunctive therapy (added to other antiepileptic drugs) was established in multicenter placebo-controlled, double-blind, parallel-group clinical trials in adult and pediatric patients (3 years and older) with refractory partial seizures.
Evidence of effectiveness was obtained in three trials conducted in 705 patients (age 12 years and above) and one trial conducted in 247 pediatric patients (3 to 12 years of age). The patients enrolled had a history of at least 4 partial seizures per month in spite of receiving one or more antiepileptic drugs at therapeutic levels and were observed on their established antiepileptic drug regimen during a 12 week baseline period (6 weeks in the study of pediatric patients). In patients continuing to have at least 2 (or 4 in some studies) seizures per month, gabapentin or placebo was then added on to the existing therapy during a 12 week treatment period. Effectiveness was assessed primarily on the basis of the percent of patients with a 50% or greater reduction in seizure frequency from baseline to treatment (the "responder rate") and a derived measure called response ratio, a measure of change defined as (T - B)/(T + B), where B is the patient's baseline seizure frequency and T is the patient
A third study compared gabapentin 900 mg/day divided TID (n = 111) and placebo (n = 109). An additional gabapentin 1200 mg/day dosage group (n = 52) provided dose-response data. A statistically significant difference in responder rate was seen in the gabapentin 900 mg/day group (22%) compared to that in the placebo group (10%). Response ratio was also statistically significantly superior in the gabapentin 900 mg/day group (-0.119) compared to that in the placebo group (-0.027), as was response ratio in 1200 mg/day gabapentin (-0.184) compared to placebo.
Analyses were also performed in each study to examine the effect of gabapentin on preventing secondarily generalized tonic-clonic seizures. Patients who experienced a secondarily generalized tonic-clonic seizure in either the baseline or in the treatment period in all three placebo-controlled studies were included in these analyses. There were several response ratio comparisons that showed a statistically significant advantage for gabapentin compared to placebo and favorable trends for almost all comparisons.
In two of the three controlled studies, more than one dose of gabapentin was used. Within each study the results did not show a consistently increased response to dose. However, looking across studies, a trend toward increasing efficacy with increasing dose is evident (see Figure 4).
Figure 4. Responder Rate in Patients Receiving Gabapentin Expressed as a Difference From Placebo by Dose and Study: Adjunctive Therapy Studies in Patients12 Years of Age With Partial Seizures
In the figure, treatment effect magnitude, measured on the Y axis in terms of the difference in the proportion of gabapentin and placebo assigned patients attaining a 50% or greater reduction in seizure frequency from baseline, is plotted against the daily dose of gabapentin administered (X axis).
Although no formal analysis by gender has been performed, estimates of response (Response Ratio) derived from clinical trials (398 men, 307 women) indicate no important gender differences exist. There was no consistent pattern indicating that age had any effect on the response to gabapentin. There were insufficient numbers of patients of races other than Caucasian to permit a comparison of efficacy among racial groups.
A fourth study in pediatric patients age 3 to 12 years compared 25 to 35 mg/kg/day gabapentin (n = 118) with placebo (n = 127). For all partial seizures in the intent-to-treat population, the response ratio was statistically significantly better for the gabapentin group (-0.146) than for the placebo group (-0.079). For the same population, the responder rate for gabapentin (21%) was not significantly different from placebo (18%).
A study in pediatric patients age 1 month to 3 years compared 40 mg/kg/day gabapentin (n = 38) with placebo (n = 38) in patients who were receiving at least one marketed antiepileptic drug and had at least one partial seizure during the screening period (within 2 weeks prior to baseline). Patients had up to 48 hours of baseline and up to 72 hours of double-blind video EEG monitoring to record and count the occurrence of seizures. There were no statistically significant differences between treatments in either the response ratio or responder rate.
INDICATIONS & USAGEPostherpetic Neuralgia
Gabapentin tablets USP are indicated for the management of postherpetic neuralgia in adults.
Gabapentin tablets USP are indicated as adjunctive therapy in the treatment of partial seizures with and without secondary generalization in patients over 12 years of age with epilepsy. Gabapentin tablets USP are also indicated as adjunctive therapy in the treatment of partial seizures in pediatric patients age 3 to 12 years.
CONTRAINDICATIONSGabapentin tablets USP are contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.
WARNINGSSuicidal 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
IndicationPlacebo Patients with Events Per 1000 PatientsDrug Patients with Events Per 1000 PatientsRelative Risk: Incidence of Events in Drug Patients/Incidence in Placebo PatientsRisk Difference: Additional Drug Patients with Events Per 1000 PatientsEpilepsy22.214.171.124Psychiatric126.96.36.199.9Other188.8.131.52Total184.108.40.206.9The 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 EventsPediatric Patients 3 to 12 Years of Age
Gabapentin use in pediatric patients with epilepsy 3 to 12 years of age is associated with the occurrence of central nervous system related adverse events. The most significant of these can be classified into the following categories: 1) emotional lability (primarily behavioral problems), 2) hostility, including aggressive behaviors, 3) thought disorder, including concentration problems and change in school performance, and 4) hyperkinesia (primarily restlessness and hyperactivity). Among the gabapentin-treated patients, most of the events were mild to moderate in intensity.
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.
In standard preclinical in vivo lifetime carcinogenicity studies, an unexpectedly high incidence of pancreatic acinar adenocarcinomas was identified in male, but not female, rats (see PRECAUTIONS, Carcinogenesis,Mutagenesis,Impairment of Fertility). The clinical significance of this finding is unknown. Clinical experience during gabapentin's premarketing development provides no direct means to assess its potential for inducing tumors in humans.
In clinical studies in adjunctive therapy in epilepsy comprising 2085 patient-years of exposure in patients > 12 years of age, new tumors were reported in 10 patients (2 breast, 3 brain, 2 lung, 1 adrenal, 1 non-Hodgkin's lymphoma, 1 endometrial carcinoma in situ), and preexisting tumors worsened in 11 patients (9 brain, 1 breast, 1 prostate) during or up to 2 years following discontinuation of gabapentin. Without knowledge of the background incidence and recurrence in a similar population not treated with gabapentin, it is impossible to know whether the incidence seen in this cohort is or is not affected by treatment.
Sudden and Unexplained Death in Patients with Epilepsy
During the course of premarketing development of gabapentin 8 sudden and unexplained deaths were recorded among a cohort of 2203 patients treated (2103 patient-years of exposure).
Some of these could represent seizure-related deaths in which the seizure was not observed, e.g., at night. This represents an incidence of 0.0038 deaths per patient-year. Although this rate exceeds that expected in a healthy population matched for age and sex, it is within the range of estimates for the incidence of sudden unexplained deaths in patients with epilepsy not receiving gabapentin (ranging from 0.0005 for the general population of epileptics to 0.003 for a clinical trial population similar to that in the gabapentin program, to 0.005 for patients with refractory epilepsy). Consequently, whether these figures are reassuring or raise further concern depends on comparability of the populations reported upon to the gabapentin cohort and the accuracy of the estimates provided.
INFORMATION FOR PATIENTSInform patients of the availability of a Medication Guide, and instruct them to read the Medication Guide prior to taking gabapentin. Instruct patients to take gabapentin only as prescribed.
Patients, their caregivers, and families should be counseled that AEDs, including gabapentin, may increase the risk of suicidal thoughts and behavior and should be advised of the need to be alert for the emergence or worsening of symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts, behavior, or thoughts about self-harm. Behaviors of concern should be reported immediately to healthcare providers.
Patients should be advised that gabapentin may cause dizziness, somnolence and other symptoms and signs of CNS depression. Accordingly, they should be advised neither to drive a car nor to operate other complex machinery until they have gained sufficient experience on gabapentin to gauge whether or not it affects their mental and/or motor performance adversely.
Patients who require concomitant treatment with morphine may experience increases in gabapentin concentrations. Patients should be carefully observed for signs of CNS depression, such as somnolence, and the dose of gabapentin or morphine should be reduced appropriately (see Drug Interactions).
Patients should be encouraged to enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry if they become pregnant. This registry is collecting information about the safety of antiepileptic drugs during pregnancy. To enroll, patients can call the toll free number 1-888-233-2334 (see PRECAUTIONS, Pregnancy section).
LABORATORY TESTSClinical trials data do not indicate that routine monitoring of clinical laboratory parameters is necessary for the safe use of gabapentin. The value of monitoring gabapentin blood concentrations has not been established. Gabapentin may be used in combination with other antiepileptic drugs without concern for alteration of the blood concentrations of gabapentin or of other antiepileptic drugs.
Gabapentin is not appreciably metabolized nor does it interfere with the metabolism of commonly coadministered antiepileptic drugs.
The drug interaction data described in this section were obtained from studies involving healthy adults and adult patients with epilepsy.
In a single (400 mg) and multiple dose (400 mg TID) study of gabapentin in epileptic patients (n = 8) maintained on phenytoin monotherapy for at least 2 months, gabapentin had no effect on the steady-state trough plasma concentrations of phenytoin and phenytoin had no effect on gabapentin pharmacokinetics.
Coadministration (n = 18) of naproxen sodium capsules (250 mg) with gabapentin (125 mg) appears to increase the amount of gabapentin absorbed by 12% to 15%. Gabapentin had no effect on naproxen pharmacokinetic parameters. These doses are lower than the therapeutic doses for both drugs. The magnitude of interaction within the recommended dose ranges of either drug is not known.
A literature article reported that when a 60 mg controlled-release morphine capsule was administered 2 hours prior to a 600 mg gabapentin capsule (n = 12), mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine (see PRECAUTIONS). Morphine pharmacokinetic parameter values were not affected by administration of gabapentin 2 hours after morphine. The magnitude of interaction at other doses is not known.
In the presence of cimetidine at 300 mg QID (n = 12) the mean apparent oral clearance of gabapentin fell by 14% and creatinine clearance fell by 10%. Thus cimetidine appeared to alter the renal excretion of both gabapentin and creatinine, an endogenous marker of renal function. This small decrease in excretion of gabapentin by cimetidine is not expected to be of clinical importance. The effect of gabapentin on cimetidine was not evaluated.
Antacid (Aluminum Hydroxide and Magnesium Hydroxide)
Aluminum hydroxide and magnesium hydroxide reduced the bioavailability of gabapentin (n = 16) by about 20%. This decrease in bioavailability was about 5% when gabapentin was administered 2 hours after aluminum hydroxide and magnesium hydroxide. It is recommended that gabapentin be taken at least 2 hours following aluminum hydroxide and magnesium hydroxide administration.
Effect of Probenecid
Probenecid is a blocker of renal tubular secretion. Gabapentin pharmacokinetic parameters without and with probenecid were comparable. This indicates that gabapentin does not undergo renal tubular secretion by the pathway that is blocked by probenecid.
DRUG & OR LABORATORY TEST INTERACTIONSBecause false positive readings were reported with the Ames N-Multistix SGdipstick test for urinary protein when gabapentin was added to other antiepileptic drugs, the more specific sulfosalicylic acid precipitation procedure is recommended to determine the presence of urine protein.
CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY
Studies designed to investigate the mechanism of gabapentin-induced pancreatic carcinogenesis in rats indicate that gabapentin stimulates DNA synthesis in rat pancreatic acinar cells in vitro and, thus, may be acting as a tumor promoter by enhancing mitogenic activity. It is not known whether gabapentin has the ability to increase cell proliferation in other cell types or in other species, including humans.
No adverse effects on fertility or reproduction were observed in rats at doses up to 2000 mg/kg (approximately 5 times the maximum recommended human dose on a mg/m2 basis).
Pregnancy Category C
Gabapentin has been shown to be fetotoxic in rodents, causing delayed ossification of several bones in the skull, vertebrae, forelimbs, and hindlimbs. These effects occurred when pregnant mice received oral doses of 1000 or 3000 mg/kg/day during the period of organogenesis, or approximately 1 to 4 times the maximum dose of 3600 mg/day given to epileptic patients on a mg/m2 basis. The no-effect level was 500 mg/kg/day or approximatelyof the human dose on a mg/m2 basis.
In a teratology study in rabbits, an increased incidence of postimplantation fetal loss occurred in dams exposed to 60, 300, and 1500 mg/kg/day, or less than approximatelyto 8 times the maximum human dose on a mg/m2 basis. There are no adequate and well-controlled studies in pregnant women. This drug should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.
To provide information regarding the effects of in utero exposure to gabapentin, physicians are advised to recommend that pregnant patients taking gabapentin enroll in the North American Antiepileptic Drug (NAAED) Pregnancy Registry. This can be done by calling the toll free number 1-888-233-2334, and must be done by patients themselves. Information on the registry can also be found at the website http://www.aedpregnancyregistry.org/.
NURSING MOTHERSGabapentin is secreted into human milk following oral administration. A nursed infant could be exposed to a maximum dose of approximately 1 mg/kg/day of gabapentin. Because the effect on the nursing infant is unknown, gabapentin should be used in women who are nursing only if the benefits clearly outweigh the risks.
PEDIATRIC USESafety and effectiveness of gabapentin in the management of postherpetic neuralgia in pediatric patients have not been established.
Effectiveness as adjunctive therapy in the treatment of partial seizures in pediatric patients below the age of 3 years has not been established (see CLINICALPHARMACOLOGY, Clinical Studies).
GERIATRIC USEThe total number of patients treated with gabapentin in controlled clinical trials in patients with postherpetic neuralgia was 336, of which 102 (30%) were 65 to 74 years of age, and 168 (50%) were 75 years of age and older. There was a larger treatment effect in patients 75 years of age and older compared with younger patients who received the same dosage. Since gabapentin is almost exclusively eliminated by renal excretion, the larger treatment effect observed in patients75 years may be a consequence of increased gabapentin exposure for a given dose that results from an age-related decrease in renal function. However, other factors cannot be excluded. The types and incidence of adverse events were similar across age groups except for peripheral edema and ataxia, which tended to increase in incidence with age.
Clinical studies of gabapentin in epilepsy did not include sufficient numbers of subjects aged 65 and over to determine whether they responded differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.
This drug is known to be substantially excreted by the kidney, and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. Because elderly patients are more likely to have decreased renal function, care should be taken in dose selection, and dose should be adjusted based on creatinine clearance values in these patients (see CLINICALPHARMACOLOGY, ADVERSE REACTIONS, and DOSAGE AND ADMINISTRATION sections).
ADVERSE REACTIONSPostherpetic 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)
*Reported as blurred visionBody System/Preferred TermGabapentinPlacebon = 336n = 227%%Body as a WholeAsthenia5.74.8Infection5.13.5Headache3.33.1Accidental injury3.31.3Abdominal pain2.72.6Digestive SystemDiarrhea5.73.1Dry mouth4.81.3Constipation3.91.8Nausea3.93.1Vomiting3.31.8Flatulence2.11.8Metabolic and Nutritional DisordersPeripheral edema8.32.2Weight gain1.80Hyperglycemia1.20.4Nervous SystemDizziness287.5Somnolence21.45.3Ataxia3.30Thinking abnormal2.70Abnormal gait1.50Incoordination1.50Amnesia1.20.9Hypesthesia1.20.9Respiratory SystemPharyngitis1.20.4Skin and AppendagesRash1.20.9Special SensesAmblyopia*2.70.9Conjunctivitis1.20Diplopia1.20Otitis media1.20Other events in more than 1% of patients but equally or more frequent in the placebo group included pain, tremor, neuralgia, back pain, dyspepsia, dyspnea, and flu syndrome.
There were no clinically important differences between men and women in the types and incidence of adverse events. Because there were few patients whose race was reported as other than white, there are insufficient data to support a statement regarding the distribution of adverse events by race.
The most commonly observed adverse events associated with the use of gabapentin in combination with other antiepileptic drugs in patients > 12 years of age, not seen at an equivalent frequency among placebo-treated patients, were somnolence, dizziness, ataxia, fatigue, and nystagmus. The most commonly observed adverse events reported with the use of gabapentin in combination with other antiepileptic drugs in pediatric patients 3 to 12 years of age, not seen at an equal frequency among placebo-treated patients, were viral infection, fever, nausea and/or vomiting, somnolence, and hostility (see WARNINGS, 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)
*Plus background antiepileptic drug therapyAmblyopia was often described as blurred visionBody System/Adverse EventGabapentin*Placebo*n = 543n = 378%%Body as a WholeFatigue115Weight increase2.91.6Back pain1.80.5Peripheral edema1.70.5CardiovascularVasodilation1.10.3Digestive SystemDyspepsia2.20.5Mouth or throat dry1.70.5Constipation1.50.8Dental abnormalities1.50.3Increased appetite1.10.8Hematologic and Lymphatic SystemsLeukopenia1.10.5Musculoskeletal SystemMyalgia21.9Fracture1.10.8Nervous SystemSomnolence19.38.7Dizziness17.16.9Ataxia12.55.6Nystagmus8.34Tremor6.83.2Nervousness2.41.9Dysarthria2.40.5Amnesia2.20Depression1.81.1Thinking abnormal1.71.3Twitching1.30.5Coordination abnormal1.10.3Respiratory SystemRhinitis4.13.7Pharyngitis2.81.6Coughing1.81.3Skin and AppendagesAbrasion1.30Pruritus1.30.5Urogenital SystemImpotence1.51.1Special SensesDiplopia5.91.9Amblyopia4.21.1Laboratory DeviationsWBC decreased1.10.5Other 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)
*Plus background antiepileptic drug therapyBody System/Adverse EventGabapentin*Placebo*n = 119n = 128%%Body as a WholeViral infection10.93.1Fever10.13.1Weight increase3.40.8Fatigue3.41.6Digestive SystemNausea and/or vomiting8.47Nervous SystemSomnolence8.44.7Hostility7.62.3Emotional lability4.21.6Dizziness2.51.6Hyperkinesia2.50.8Respiratory SystemBronchitis3.40.8Respiratory infection2.50.8Other 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.
Body as a Whole
Frequent: asthenia, malaise, face edema
Infrequent: allergy, generalized edema, weight decrease, chill
Rare: strange feelings, lassitude, alcohol intolerance, hangover effect
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
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, perleche, salivary gland enlarged, lip hemorrhage, esophagitis, hiatal hernia, hematemesis, proctitis, irritable bowel syndrome, rectal hemorrhage, esophageal spasm
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
Infrequent: tendinitis, arthritis, joint stiffness, joint swelling, positive Romberg test
Rare: costochondritis, osteoporosis, bursitis, contracture
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
Infrequent: epistaxis, dyspnea, apnea
Rare: mucositis, aspiration pneumonia, hyperventilation, hiccup, laryngitis, nasal obstruction, snoring, bronchospasm, hypoventilation, lung edema
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
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
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
Hemic and Lymphatic System
Aura disappeared, occipital neuralgia
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.
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
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
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
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
Infrequent: arthritis, arthralgia, myalgia, arthrosis, leg cramps, myasthenia
Rare: shin bone pain, joint disorder, tendon disorder
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
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
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
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 DEPENDENCEThe abuse and dependence potential of gabapentin has not been evaluated in human studies.
OVERDOSAGEA 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 & ADMINISTRATIONGabapentin tablets USP 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 tablets USP 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).
In adults with postherpetic neuralgia, gabapentin tablets USP therapy may be initiated as a single 300 mg dose on Day 1, 600 mg/day on Day 2 (divided BID), and 900 mg/day on Day 3 (divided TID). The dose can subsequently be titrated up as needed for pain relief to a daily dose of 1800 mg (divided TID). In clinical studies, efficacy was demonstrated over a range of doses from 1800 mg/day to 3600 mg/day with comparable effects across the dose range. Additional benefit of using doses greater than 1800 mg/day was not demonstrated.
Gabapentin tablets USP 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 USP 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.
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 USP 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). Gabapentin tablets USP 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.
It is not necessary to monitor gabapentin plasma concentrations to optimize gabapentin tablets USP therapy. Further, because there are no significant pharmacokinetic interactions among gabapentin tablets USP and other commonly used antiepileptic drugs, the addition of gabapentin tablets USP does not alter the plasma levels of these drugs appreciably.
If gabapentin tablets USP 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 patients12 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 Tablets USP Dosage Based on Renal Function
*For patients with creatinine clearance < 15 mL/min, reduce daily dose in proportion to creatinine clearance (e.g., patients with a creatinine clearance of 7.5 mL/min should receive one-half the daily dose that patients with a creatinine clearance of 15 mL/min receive).Patients on hemodialysis should receive maintenance doses based on 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.Renal Function Creatinine ClearanceTotal Daily Dose RangeDose Regimen(mL/min)(mg/day)(mg)60900 to 3600300 TID400 TID600 TID800 TID1200 TID> 30 to 59400 to 1400200 BID300 BID400 BID500 BID700 BID> 15 to 29200 to 700200 QD300 QD400 QD500 QD700 QD15*100 to 300100 QD125 QD150 QD200 QD300 QDPost-Hemodialysis Supplemental Dose (mg)Hemodialysis125150200250350The use of gabapentin tablets USP 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 SUPPLIEDGabapentin Tablets USP, 600 mg are available as white, oval shaped tablets, debossed "X" 4443, with a partial score on one side and600on the other side containing 600 mg gabapentin USP packaged in bottles of 100, 500 and 1000 tablets and unit-dose boxes of 100 tablets.
Gabapentin Tablets USP, 800 mg are available as white, oval shaped tablets, debossed "X" 4444, with a partial score on one side and800on the other side containing 800 mg gabapentin USP packaged in bottles of 100 and 500 tablets and unit-dose boxes of 100 tablets.
Dispense in a tight container as defined in the USP, with a child-resistant closure (as required).
Store at 20to 25(68to 77[See USP Controlled Room Temperature].
KEEP THIS AND ALL MEDICATIONS OUT OF THE REACH OF CHILDREN.
SPL MEDGUIDEGABAPENTIN (GA-ba-PEN'-tin) TABLETS USP
Read the Medication Guide before you start taking gabapentin and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or treatment.
What is the most important information I should know about gabapentin?
Do not stop taking gabapentin without first talking to your healthcare provider.
Stopping gabapentin suddenly can cause serious problems.
Gabapentin can cause serious side effects including:
1.Like other antiepileptic drugs, gabapentin may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.
Call a healthcare provider right away if you have any of these symptoms, especially if they are new, worse, or worry you:
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).
What is gabapentin?
Gabapentin is a prescription medicine used to treat:
Pain from damaged nerves (postherpetic pain) that follows healing of shingles (a painful rash that comes after a herpes zoster infection) in adults.
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
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.
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.
How should I store gabapentin?
Store gabapentin tablets between 59to 86(15to 30
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use gabapentin for a condition for which it was not prescribed. Do not give gabapentin to other people, even if they have the same symptoms that you have. It may harm them.
This Medication Guide summarizes the most important information about gabapentin. If you would like more information, talk with your healthcare provider. You can ask your healthcare provider or pharmacist for information about gabapentin that was written for healthcare professionals.
For more information about gabapentin, or to report side effects regarding gabapentin, please call Teva Pharmaceuticals Medical Affairs at 1-888-838-2872.
What are the ingredients in gabapentin?
Active ingredient: gabapentin USP
Inactive ingredients: lactose monohydrate, microcrystalline cellulose and polyethylene glycol.
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTIONDRUG: Gabapentin
SCORE: Two even pieces
SIZE: 18 mm
Revised: 06/2011 REMEDYREPACK INC.
Reproduced with permission of U.S. National Library of Medicine
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