Gabapentin

REMEDYREPACK INC.

FULL PRESCRIBING INFORMATION: CONTENTS*

• GABAPENTIN DESCRIPTION
• CLINICAL PHARMACOLOGY
• PHARMACOKINETICS
• CLINICAL STUDIES
• INDICATIONS & USAGE
• GABAPENTIN CONTRAINDICATIONS
• WARNINGS
• PRECAUTIONS
• INFORMATION FOR PATIENTS
• LABORATORY TESTS
• DRUG INTERACTIONS
• DRUG & OR LABORATORY TEST INTERACTIONS
• CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY
• PREGNANCY
• NURSING MOTHERS
• PEDIATRIC USE
• GERIATRIC USE
• GABAPENTIN ADVERSE REACTIONS
• DRUG ABUSE AND DEPENDENCE
• OVERDOSAGE
• DOSAGE & ADMINISTRATION
• HOW SUPPLIED
• SPL MEDGUIDE
• PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION

FULL PRESCRIBING INFORMATION

GABAPENTIN DESCRIPTION

CLINICAL PHARMACOLOGY

PHARMACOKINETICS

CLINICAL STUDIES

Postherpetic Neuralgia


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

Epilepsy
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 & USAGE

GABAPENTIN CONTRAINDICATIONS

WARNINGS

PRECAUTIONS

INFORMATION FOR PATIENTS

LABORATORY TESTS

DRUG INTERACTIONS

DRUG & OR LABORATORY TEST INTERACTIONS

CARCINOGENESIS & MUTAGENESIS & IMPAIRMENT OF FERTILITY

PREGNANCY

NURSING MOTHERS

PEDIATRIC USE

GERIATRIC USE

GABAPENTIN ADVERSE REACTIONS

DRUG ABUSE AND DEPENDENCE

OVERDOSAGE

DOSAGE & ADMINISTRATION

HOW SUPPLIED

SPL MEDGUIDE

• ●thoughts about suicide or dying

• ●attempts to commit suicide

• ●new or worse depression

• ●new or worse anxiety

• ●feeling agitated or restless

• ●panic attacks

• ●trouble sleeping (insomnia)

• ●new or worse irritability

• ●acting aggressive, being angry, or violent

• ●acting on dangerous impulses

• ●an extreme increase in activity and talking (mania)

• ●other unusual changes in behavior or mood

• ●How can I watch for early symptoms of suicidal thoughts and actions?

• ●Keep all follow-up visits with your healthcare provider as scheduled.

• ●Call your healthcare provider between visits as needed, especially if you are worried about symptoms.

• ●Suicidal thoughts or actions can be caused by things other than medicines. If you have suicidal thoughts or actions, your healthcare provider may check for other causes.

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

• ●Who should not take gabapentin?

• ●have or have had depression, mood problems, or suicidal thoughts or behavior

• ●are pregnant or plan to become pregnant. It is not known if gabapentin can harm your unborn baby. Tell your healthcare provider right away if you become pregnant while taking gabapentin. You and your healthcare provider will decide if you should take gabapentin while you are pregnant.

• ●o If you become pregnant while taking gabapentin, talk to your healthcare provider about registering with the North American Antiepileptic Drug (NAAED) Pregnancy Registry. The purpose of this registry is to collect information about the safety of antiepileptic drugs during pregnancy. You can enroll in this registry by calling 1-888-233-2334.

• ●Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

• ●-Do not change your dose of gabapentin without talking to your healthcare provider. If you break a tablet in half the unused half of the tablet should be taken at your next scheduled dose. Half tablets not used within several days of breaking should be thrown away.

• ●If you take too much gabapentin, call your healthcare provider or your local Poison Control Center right away.

• ●What should I avoid while taking gabapentin?

• ●Do not drive, operate heavy machinery, or do other dangerous activities until you know how gabapentin affects you. Gabapentin can slow your thinking and motor skills.

• ●What are the possible side effects of gabapentin

• ●The most common side effects of gabapentin include:

• ●dizziness

• ●lack of coordination

• ●viral infection

• ●feeling drowsy

• ●feeling tired

• ●fever

• ●jerky movements

• ●difficulty with speaking

• ●temporary loss of memory (amnesia)

• ●tremor

• ●difficulty with coordination

• ●double vision

• ●unusual eye movement

• ●Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

• ●Keep gabapentin and all medicines out of the reach of children.

PACKAGE LABEL.PRINCIPAL DISPLAY PANEL SECTION