Source:http://www4.wiwiss.fu-berlin.de/dailymed/resource/drugs/4032
| Predicate | Object |
|---|---|
| rdf:type | |
| rdfs:label |
Neurontin (Capsule)
|
| dailymed-instance:dosage |
Neurontin is 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 Neurontin 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).<br/>Postherpetic Neuralgia: In adults with postherpetic neuralgia, Neurontin 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.<br/>Epilepsy: Neurontin 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. Patients>12 years of age: The effective dose of Neurontin 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���12 years: 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 Neurontin 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) Neurontin 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 Neurontin therapy. Further, because there are no significant pharmacokinetic interactions among Neurontin and other commonly used antiepileptic drugs, the addition of Neurontin does not alter the plasma levels of these drugs appreciably. If Neurontin is discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of 1 week.<br/>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)] where age is in years, weight is in kilograms and Sis serum creatinine in mg/dL. Dosage adjustment in patients���12 years of age with compromised renal function or undergoing hemodialysis is recommended as follows (see dosing recommendations above for effective doses in each indication). The use of Neurontin in patients<12 years of age with compromised renal function has not been studied.<br/>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.
|
| dailymed-instance:descripti... |
Neurontin (gabapentin) Capsules, Neurontin (gabapentin) Tablets, and Neurontin (gabapentin) Oral Solution are supplied as imprinted hard shell capsules containing 100 mg, 300 mg, and 400 mg of gabapentin, elliptical film���coated tablets containing 600 mg and 800 mg of gabapentin or an oral solution containing 250 mg/5 mL of gabapentin. The inactive ingredients for the capsules are lactose, cornstarch, and talc. The 100 mg capsule shell contains gelatin and titanium dioxide. The 300 mg capsule shell contains gelatin, titanium dioxide, and yellow iron oxide. The 400 mg capsule shell contains gelatin, red iron oxide, titanium dioxide, and yellow iron oxide. The imprinting ink contains FD&C Blue No. 2 and titanium dioxide. The inactive ingredients for the tablets are poloxamer 407, copolyvidonum, cornstarch, magnesium stearate, hydroxypropyl cellulose, talc, candelilla wax and purified water. The inactive ingredients for the oral solution are glycerin, xylitol, purified water and artificial cool strawberry anise flavor. Gabapentin is described as 1-(aminomethyl)cyclohexaneacetic acid with a molecular formula of CHNOand a molecular weight of 171.24. The structural formula of gabapentin is: Gabapentin is a white to off-white crystalline solid with a pKof 3.7 and a pKof 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.
|
| dailymed-instance:clinicalP... |
Mechanism of Action: The mechanism by which gabapentin exerts its analgesic action is unknown, but in animal models of analgesia, gabapentin prevents allodynia (pain-related behavior in response to a normally innocuous stimulus) and hyperalgesia (exaggerated response to painful stimuli). In particular, gabapentin prevents pain-related responses in several models of neuropathic pain in rats or mice (e.g. spinal nerve ligation models, streptozocin-induced diabetes model, spinal cord injury model, acute herpes zoster infection model). Gabapentin also decreases pain-related responses after peripheral inflammation (carrageenan footpad test, late phase of formalin test). Gabapentin did not alter immediate pain-related behaviors (rat tail flick test, formalin footpad acute phase, acetic acid abdominal constriction test, footpad heat irradiation test). The relevance of these models to human pain is not known. The mechanism by which gabapentin exerts its anticonvulsant action is unknown, but in animal test systems designed to detect anticonvulsant activity, gabapentin prevents seizures as do other marketed anticonvulsants. Gabapentin exhibits antiseizure activity in mice and rats in both the maximal electroshock and pentylenetetrazole seizure models and other preclinical models (e.g., strains with genetic epilepsy, etc.). The relevance of these models to human epilepsy is not known. Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid) but it does not modify GABAor GABAradioligand binding, it is not converted metabolically into GABA or a GABA agonist, and it is not an inhibitor of GABA uptake or degradation. Gabapentin was tested in radioligand binding assays at concentrations up to 100��M and did not exhibit affinity for a number of other common receptor sites, including benzodiazepine, glutamate, N-methyl-D-aspartate (NMDA), quisqualate, kainate, strychnine-insensitive or strychnine-sensitive glycine, alpha 1, alpha 2, or beta adrenergic, adenosine A1 or A2, cholinergic muscarinic or nicotinic, dopamine D1 or D2, histamine H1, serotonin S1 or S2, opiate mu, delta or kappa, cannabinoid 1, voltage-sensitive calcium channel sites labeled with nitrendipine or diltiazem, or at voltage-sensitive sodium channel sites labeled with batrachotoxinin A 20-alpha-benzoate. Furthermore, gabapentin did not alter the cellular uptake of dopamine, noradrenaline, or serotonin. In vitro studies with radiolabeled gabapentin have revealed a gabapentin binding site in areas of rat brain including neocortex and hippocampus. A high-affinity binding protein in animal brain tissue has been identified as an auxiliary subunit of voltage-activated calcium channels. However, functional correlates of gabapentin binding, if any, remain to be elucidated.<br/>Pharmacokinetics and Drug Metabolism: All pharmacological actions following gabapentin administration are due to the activity of the parent compound; gabapentin is not appreciably metabolized in humans.<br/>Oral Bioavailability: Gabapentin bioavailability is not dose proportional; i.e., as dose is increased, bioavailability decreases. Bioavailability of gabapentin is approximately 60%, 47%, 34%, 33%, and 27% following 900, 1200, 2400, 3600, and 4800 mg/day given in 3 divided doses, respectively. Food has only a slight effect on the rate and extent of absorption of gabapentin (14% increase in AUC and C).<br/>Distribution: Less than 3% of gabapentin circulates bound to plasma protein. The apparent volume of distribution of gabapentin after 150 mg intravenous administration is 58��6 L (Mean��SD). In patients with epilepsy, steady-state predose (C) concentrations of gabapentin in cerebrospinal fluid were approximately 20% of the corresponding plasma concentrations.<br/>Elimination: Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug. Gabapentin is not appreciably metabolized in humans. Gabapentin elimination half-life is 5 to 7 hours and is unaltered by dose or following multiple dosing. Gabapentin elimination rate constant, plasma clearance, and renal clearance are directly proportional to creatinine clearance (see Special Populations: Patients With Renal Insufficiency, below). In elderly patients, and in patients with impaired renal function, gabapentin plasma clearance is reduced. Gabapentin can be removed from plasma by hemodialysis. Dosage adjustment in patients with compromised renal function or undergoing hemodialysis is recommended .<br/>Special Populations:<br/>Clinical Studies:<br/>Postherpetic Neuralgia: Neurontin was evaluated for the management of postherpetic neuralgia (PHN) in 2 randomized, double-blind, placebo-controlled, multicenter studies; N=563 patients in the intent-to-treat (ITT) population (Table 1). Patients were enrolled if they continued to have pain for more than 3 months after healing of the herpes zoster skin rash. Each study included a 1-week baseline during which patients were screened for eligibility and a 7- or 8-week double-blind phase (3 or 4 weeks of titration and 4 weeks of fixed dose). Patients initiated treatment with titration to a maximum of 900 mg/day gabapentin over 3 days. Dosages were then to be titrated in 600 to 1200 mg/day increments at 3- to 7-day intervals to target dose over 3 to 4 weeks. In Study 1, patients were continued on lower doses if not able to achieve the target dose. During baseline and treatment, patients recorded their pain in a daily diary using an 11-point numeric pain rating scale ranging from 0 (no pain) to 10 (worst possible pain). A mean pain score during baseline of at least 4 was required for randomization (baseline mean pain score for Studies 1 and 2 combined was 6.4). Analyses were conducted using the ITT population (all randomized patients who received at least one dose of study medication). Both studies showed significant differences from placebo at all doses tested. A significant reduction in weekly mean pain scores was seen by Week 1 in both studies, and significant differences were maintained to the end of treatment. Comparable treatment effects were observed in all active treatment arms. Pharmacokinetic/pharmacodynamic modeling provided confirmatory evidence of efficacy across all doses. Figures 1 and 2 show these changes for Studies 1 and 2. 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 with���50% reduction in pain score) at Endpoint: Controlled PHN Studies<br/>Epilepsy: The effectiveness of Neurontin 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, Neurontin or placebo was then added on to the existing therapy during a 12-week treatment period. Effectiveness was assessed primarily on the basis of the percent of patients with a 50% or greater reduction in seizure frequency from baseline to treatment (the "responder rate") and a derived measure called response ratio, a measure of change defined as (T���B)/(T + B), where B is the patient's baseline seizure frequency and T is the patient's seizure frequency during treatment. Response ratio is distributed within the range���1 to %1. A zero value indicates no change while complete elimination of seizures would give a value of���1; increased seizure rates would give positive values. A response ratio of���0.33 corresponds to a 50% reduction in seizure frequency. The results given below are for all partial seizures in the intent-to-treat (all patients who received any doses of treatment) population in each study, unless otherwise indicated. One study compared Neurontin 1200 mg/day divided TID with placebo. Responder rate was 23% (14/61) in the Neurontin group and 9% (6/66) in the placebo group; the difference between groups was statistically significant. Response ratio was also better in the Neurontin group (���0.199) than in the placebo group (���0.044), a difference that also achieved statistical significance. A second study compared primarily 1200 mg/day divided TID Neurontin (N=101) with placebo (N=98). Additional smaller Neurontin dosage groups (600 mg/day, N=53; 1800 mg/day, N=54) were also studied for information regarding dose response. Responder rate was higher in the Neurontin 1200 mg/day group (16%) than in the placebo group (8%), but the difference was not statistically significant. The responder rate at 600 mg (17%) was also not significantly higher than in the placebo, but the responder rate in the 1800 mg group (26%) was statistically significantly superior to the placebo rate. Response ratio was better in the Neurontin 1200 mg/day group (���0.103) than in the placebo group (���0.022); but this difference was also not statistically significant (p = 0.224). A better response was seen in the Neurontin 600 mg/day group (���0.105) and 1800 mg/day group (���0.222) than in the 1200 mg/day group, with the 1800 mg/day group achieving statistical significance compared to the placebo group. A third study compared Neurontin 900 mg/day divided TID (N=111) and placebo (N=109). An additional Neurontin 1200 mg/day dosage group (N=52) provided dose-response data. A statistically significant difference in responder rate was seen in the Neurontin 900 mg/day group (22%) compared to that in the placebo group (10%). Response ratio was also statistically significantly superior in the Neurontin 900 mg/day group (���0.119) compared to that in the placebo group (���0.027), as was response ratio in 1200 mg/day Neurontin (���0.184) compared to placebo. Analyses were also performed in each study to examine the effect of Neurontin 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 Neurontin compared to placebo and favorable trends for almost all comparisons. Analysis of responder rate using combined data from all three studies and all doses (N=162, Neurontin; N=89, placebo) also showed a significant advantage for Neurontin over placebo in reducing the frequency of secondarily generalized tonic-clonic seizures. In two of the three controlled studies, more than one dose of Neurontin 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 Neurontin Expressed as a Difference from Placebo by Dose and Study: Adjunctive Therapy Studies in Patients���12 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 Neurontin. 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���35 mg/kg/day Neurontin (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 Neurontin group (���0.146) than for the placebo group (���0.079). For the same population, the responder rate for Neurontin (21%) was not significantly different from placebo (18%). A study in pediatric patients age 1 month to 3 years compared 40 mg/kg/day Neurontin (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 torecord and count the occurrence of seizures. There were no statistically significant differences between treatments in either the response ratio or responder rate.
|
| dailymed-instance:activeIng... | |
| dailymed-instance:contraind... |
Neurontin is contraindicated in patients who have demonstrated hypersensitivity to the drug or its ingredients.
|
| dailymed-instance:supply |
Neurontin (gabapentin) capsules, tablets and oral solution are supplied as follows: 100 mg capsules; White hard gelatin capsules printed with "PD" on one side and "Neurontin/100 mg" on the other; available in:Bottles of 100: N 0071-0803-24Unit dose 50's: N 0071-0803-40 300 mg capsules; Yellow hard gelatin capsules printed with "PD" on one side and "Neurontin/300 mg" on the other; available in:Bottles of 100: N 0071-0805-24Unit dose 50's: N 0071-0805-40 400 mg capsules; Orange hard gelatin capsules printed with "PD" on one side and "Neurontin/400 mg" on the other; available in:Bottles of 100: N 0071-0806-24Unit dose 50's: N 0071-0806-40 600 mg tablets; White elliptical film-coated scored tablets debossed with "NT" and "16" on one side; available in:Bottles of 100: N 0071-0513-24 800 mg tablets; White elliptical film-coated scored tablets debossed with "NT" and"26" on one side; available in:Bottles of 100: N 0071-0401-24 250 mg/5 mL oral solution; Clear colorless to slightly yellow solution; each 5 mL of oral solution contains 250 mg of gabapentin; available in:Bottles containing 470 mL: N0071-2012-23 Storage (Capsules) Store at 25��C (77��F); excursions permitted to 15�����30��C (59�����86��F) [see USP Controlled Room Temperature]. Storage (Tablets) Store at 25��C (77��F); excursions permitted to 15�����30��C (59�����86��F) [see USP Controlled Room Temperature]. Storage (Oral Solution) Store refrigerated, 2�����8��C (36�����46��F)
|
| dailymed-instance:genericDr... | |
| dailymed-instance:activeMoi... | |
| dailymed-instance:inactiveI... | |
| dailymed-instance:overdosag... |
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 Neurontin 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.
|
| dailymed-instance:genericMe... |
gabapentin
|
| dailymed-instance:fullName |
Neurontin (Capsule)
|
| dailymed-instance:adverseRe... |
Postherpetic Neuralgia: The most commonly observed adverse events associated with the use of Neurontin 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 Neurontin 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 Neurontin-treated patients were dizziness, somnolence, and nausea.<br/>Incidence in Controlled Clinical Trials: Table 2 lists treatment-emergent signs and symptoms that occurred in at least 1% of Neurontin-treated patients with postherpetic neuralgia participating in placebo-controlled trials and that were numerically more frequent in the Neurontin group than in the placebo group. Adverse events were usually mild to moderate in intensity. 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.<br/>Epilepsy: The most commonly observed adverse events associated with the use of Neurontin 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 Neurontin 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 . 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 Neurontin 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%).<br/>Incidence in Controlled Clinical Trials: Table 3 lists treatment-emergent signs and symptoms that occurred in at least 1% of Neurontin-treated patients>12 years of age with epilepsy participating in placebo-controlled trials and were numerically more common in the Neurontin group. In these studies, either Neurontin 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 Neurontin 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 inspectionof 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. 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 Neurontin-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 Neurontin. The incidence of adverse events increased slightly with increasing age in patients treated with either Neurontin 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 4 lists treatment-emergent signs and symptoms that occurred in at least 2% of Neurontin-treated patients age 3 to 12 years of age with epilepsy participating in placebo-controlled trials and were numerically more common in the Neurontin group. Adverse events were usually mild to moderate in intensity. 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.<br/>Other Adverse Events Observed During All Clinical Trials:<br/>Postmarketing and Other Experience: In addition to the adverse experiences reported during clinical testing of Neurontin, the following adverse experiences have been reported in patients receiving marketed Neurontin. 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 hypertrophy, 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.
|
| dailymed-instance:warning |
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.<br/>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 Neurontin 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 Neurontin 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 Neurontin is associated with a higher or lower rate of status epilepticus than would be expected to occur in a similar population not treated with Neurontin.<br/>Tumorigenic Potential: In standard preclinical in vivo lifetime carcinogenicity studies, an unexpectedly high incidence of pancreatic acinar adenocarcinomas was identified in male, but not female, rats. 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 Neurontin. Without knowledge of the background incidence and recurrence in a similar population not treated with Neurontin, it is impossible to know whether the incidence seen in this cohort is or is not affected by treatment.<br/>Sudden and Unexplained Death in Patients With Epilepsy: During the course of premarketing development of Neurontin 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 Neurontin (ranging from 0.0005 for the general population of epileptics to 0.003 for a clinical trial population similar to that in the Neurontin 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 Neurontin cohort and the accuracy of the estimates provided.
|
| dailymed-instance:indicatio... |
Postherpetic Neuralgia: Neurontin (gabapentin) is indicated for the management of postherpetic neuralgia in adults.<br/>Epilepsy: Neurontin (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. Neurontin is also indicated as adjunctive therapy in the treatment of partial seizures in pediatric patients age 3���12 years.
|
| dailymed-instance:represent... | |
| dailymed-instance:routeOfAd... | |
| dailymed-instance:name |
Neurontin
|