Gabapentin 300mg and 400mg capsules
Gabapentin exhibits antiseizure activity in mice and rats both in the
maximal electroshock and in the pentylenetetrazol seizure models. Gabapentin
is structurally related to the neurotransmitter GABA (gammaaminobutyric
acid) but does not interact with GABA receptors, it is not metabolized to
GABA or to GABA agonists, and it is not an inhibitor of GABA uptake or
degradation. Gabapentin at concentrations up to 100 µM did not demonstrate
affinity for other receptor sites such as benzodiazepine, glutamate, glycine
or N-methyl-D-aspartate receptors nor does it interact with neuronal sodium
channels or L-type calcium channels.
The mechanism of action of gabapentin has not yet been established, however,
it is unlike that of the commonly used anticonvulsant drugs. The mechanism
of the anticonvulsant action of gabapentin appears to be distinctly
different from that of other antiepileptic drugs. Although structurally
similar to GABA (gamma-aminobutyric acid), gabapentin at concentrations up
to 1000 µM, did not bind to GABA receptors, it was not metabolized to GABA or
a GABA agonist, and it did inhibit the uptake of GABA or its degradation by
GABA-transaminase. Therefore, it does not appear to act through any known
GABA mechanism, in contrast to the benzodiazepines, barbiturates, sodium
valproate and other similar agents. Gabapentin (0.01 to 100 µM) did not
interact with neuronal sodium channels or L-type calcium channels, in
contrast to phenytoin, carbamazepine and sodium valproate which interact
with these to promote the stability of excitable membranes. Finally,
gabapentin (0.01 to 100 µM) did not interact with glutamate, glycine or
N-methyl-D-aspartate (NMDA) receptors, in contrast to other drugs that have
demonstrated anticonvulsant activity in animal models following interaction
with these receptors. These neurophysiological findings indicate that
gabapentin has a mechanism of action different from that of commonly used
Pharmacokinetics: Adults: Following oral administration of gabapentin. peak
plasma concentrations are observed within 2 to 3 hours. Absolute
bioavailability of a 300 mg dose of gabapentin capsules is approximately
59%. At doses of 300 and 400 mg, gabapentin bioavailability is unchanged
following multiple dose administration.
Gabapentin elimination from plasma is best described by linear
pharmacokinetics. The elimination half-life of gabapentin is independent of
dose and averages 5 to 7 hours in subjects with normal renal function.
Plasma gabapentin concentrations are dose-proportional at doses of 300 to
400 mg q8h, ranging between 1 and 10 µg/mL, but are less than
doseproportional above the clinical range (>600 mg q8h). There is no
correlation between plasma levels and efficacy. Gabapentin pharmacokinetics
are not affected by repeated administration, and steady-state plasma
concentrations are predictable from single dose data.
Gabapentin is not
appreciably metabolized in humans, is eliminated solely by renal excretion,
and can be removed from plasma by hemodialysis. Gabapentin does not induce
or inhibit hepatic mixed function oxidase enzymes responsible for drug
metabolism, does not interfere with the metabolism of commonly
co-administered antiepileptic drugs, and is minimally bound to plasma
Food has no effect on the rate or extent of absorption of gabapentin.
In patients of epilepsy, gabapentin concentrations in cerebrospinal fluid
are approximately 20% of corresponding steady-state trough plasma
Apo-Gabapentin is indicated for the treatment of neuropathic pain.
Apo-Gabapentin is indicated as adjunctive therapy in the treatment of
partial seizures with or without secondary generalization in adults with
Dosage and Administration
Adults (over the age of 18)
Apo-Gabapentin should be titrated to a maximum dose of 1800 mg per day.
Titration to an effective dose can progress rapidly and can be accomplished
over a few days by administering 300 mg once a day on day 1, 300 mg twice a
day on day 2 and 300 mg three times a day on day 3. as described in Table 1.
|Table 1: DOSING CHART - INITIAL TITRATION
||300 mg once a day
||300 mg two times a day
||300 mg three times a day
Thereafter, the dose can be increased using increments of 300 mg per day
given in three divided doses to a maximum of 1800 mg per day. It is not
necessary to divide the doses equally when titrating Apo-Gabapentin.
maximum time between doses in a three times daily schedule should not exceed
12 hours. Gabapentin may be given orally with or without food.
If Apo-Gabapentin is discontinued, or the dose reduced or substituted with
an alternative medication, this should be done gradually over a minimum of
Elderly patients may require dosage adjustment because of declining renal
function with age (see Table 2).
Apo-Gabapentin is recommended for add-on therapy in patients > 12 years. The
effective dosage range was 900 to 1800 mg/day given in divided doses (3
times a day) using 300 or 400 mg capsules. Therapy may be initiated by
titrating the dose as described below (see Table 1). Thereafter, the dose
can be increased in three equally divided doses up to a clinically effective
and tolerated dose. The first dose on Day 1 may be administered at bedtime
to minimize potential side effects, especially somnolence, ataxia, fatigue
and dizziness. Doses up to 2400 mg/day have been well tolerated in long-term
open-label 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. APO-GABAPENTIN (gabapentin) is given orally
with or without food.
Table 1. Titration schedule
||300 mg OD
||300 mg BID
||300 mg TID
||400 mg OD
||400 mg BID
||400 mg TID
Daily maintenance doses should be given in three equally divided doses (see
Table 2), and the maximum time between doses in a three times daily schedule
should not exceed 12 hours. It is not necessary to monitor gabapentin plasma
concentrations in order to optimize APO-GABAPENTIN therapy.
Further, as there are no drug interactions with commonly used antiepileptic
drugs, APO-GABAPENTIN may be used in combination with these drugs without
concern for alteration of plasma concentrations of either gabapentin or
other antiepileptic drugs.
Dosage adjustment in elderly patients due to declining renal function and in
patients with renal impairment or undergoing hemodialysis is recommended as
follows (see Table 2).
Table 2: Maintenance dosage of APO-GABAPENTIN in adults with reduced renal
Renal Function Creatinine
Total Daily Dose (mg/day)
Dose regimen (mg)
30 to 60
15 to 30
400 three times a day
300 twice a day
300 once a day
300 once daily every
200 to 300**
* Loading dose of 300 to 400 mg
Maintenance dose of 200 to 300 mg APO-GABAPENTIN following each 4 hours of