Gabapentin

1. Gabapentin
Class: Anticonvulsants, Miscellaneous
VA Class: CN400
Chemical Name: 1-(Aminomethyl)-cyclohexaneacetic acid
Molecular Formula: C9H17NO2
CAS Number: 60142-96-3
Introduction
Anticonvulsant; structurally related to the inhibitory CNS neurotransmitter GABA.
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Uses for Gabapentin
Pending revision, the material in this section should be considered in light of more recently
available information in the MedWatch notification at the beginning of this monograph.
Seizure Disorders
Management (in combination with other anticonvulsants) of partial seizures with or without
secondary generalization in adults and children >12 years of age.
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Management (in combination with other anticonvulsants) of partial seizures in children 3–12
years of age.
1

Neuropathic Pain
Management of postherpetic neuralgia in adults.
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Treatment of pain associated with diabetic neuropathy†.
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40% of
patients who receive gabapentin for pain associated with diabetic neuropathy obtain good pain
relief.
40

Some evidence of benefit for the relief of chronic neurogenic pain† in a variety of conditions
including trigeminal neuralgia†,
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47
pain and control of paroxysmal symptoms of multiple
sclerosis†,
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49
complex regional pain syndromes†,
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53
HIV-related peripheral
neuropathy†,
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50
and neuropathic pain associated with cancer†.
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51
Also has been used in
the treatment of restless legs syndrome†.
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Additional study needed to further elucidate
precise role in the management of these conditions.
Vasomotor Symptoms
Has been used for the management of vasomotor symptoms (e.g., hot flashes) in women with
breast cancer†.
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2. Has been used for the management of vasomotor symptoms (e.g., hot flashes) associated with
menopause†.
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Gabapentin Dosage and Administration
General
Seizure Disorders
Monitoring of plasma gabapentin concentrations is not necessary to optimize therapy.
1

Because addition of gabapentin to existing anticonvulsant therapy does not appreciably
alter steady-state plasma concentrations of concomitantly administered anticonvulsants,
additional monitoring of plasma concentrations of anticonvulsants generally is not
necessary.
1
(See Specific Drugs under Interactions.)
Discontinuance of gabapentin and/or addition of an alternative anticonvulsant drug to
therapy should be done gradually over ≥1 week.
1

Administration
Oral Administration
Administer orally without regard to meals.
1

If Neurontin film-coated scored tablets containing 600 or 800 mg of gabapentin are to be used in
patients requiring a 300- or 400-mg dose, divide the tablet in half to allow administration of the
appropriate dose.
1
Instruct patients to take one-half tablet and to use the remaining half-tablet for
the next dose.
1
Half-tablets that are not used within several days should be discarded.
1

Seizure Disorders
Administer orally 3 times daily.
1
The interval between doses in this schedule should not exceed
12 hours.
1

Dosage
Pending revision, the material in this section should be considered in light of more recently
available information in the MedWatch notification at the beginning of this monograph.
Pediatric Patients
Seizure Disorders
Partial Seizures
Oral

3. Children 3–12 years of age: Initially, 10–15 mg/kg daily in 3 divided doses.
1
Maintenance
dosage of 40 mg/kg daily in 3 divided doses for children 3 or 4 years of age and 25–35 mg/kg
daily in 3 divided doses for children 5–12 years of age.
1

Children >12 years of age: Initially, 300 mg 3 times daily.
1
Maintenance dosage of 900 mg to 1.8
g daily in 3 divided doses.
1

Adults
Seizure Disorders
Partial Seizures
Oral
Initially, 300 mg 3 times daily.
1
Maintenance dosage of 900 mg to 1.8 g daily in 3 divided
doses.
1

Neuropathic Pain
Postherpetic Neuralgia
Oral
300 mg on the first day, 300 mg twice daily on the second day, and 300 mg 3 times daily on the
third day.
1
Increase dosage as needed for relief of pain up to a total daily dosage of 1.8 g in 3
divided doses.
1
No evidence of additional benefit with dosages >1.8 g daily.
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Diabetic Neuropathy
Oral
Dosages of 900 mg to 3.6 g daily have been used; however, pain relief generally observed in
patients receiving dosages >1.8 g daily.
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Vasomotor Symptoms†
Oral
300 mg 3 times daily has been effective; higher dosages may provide additional benefit.
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Prescribing Limits
Pediatric Patients
Children 3–12 years of age: Dosages up to 50 mg/kg daily in divided doses have been tolerated
as adjunctive therapy in the management of partial seizures.
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4. Children >12 years of age: Dosage of 3.6 g daily has been tolerated as adjunctive therapy in the
management of partial seizures.
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Adults
Dosage of 3.6 g daily has been tolerated as adjunctive therapy in the management of partial
seizures.
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Special Populations
Renal Impairment
Not studied in children <12 years of age with renal impairment.
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In adults and children ≥12 years of age, base dosage on measured or estimated Clcr:
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a
In patients with Clcr <15 mL/min, reduce dosage proportionally (e.g., a patient with a Clcr of 7.5
mL/min should receive one-half the dosage that a patient with a Clcr of 15 mL/min should
receive).
b
Give maintenance doses based on Clcr, with supplemental doses (125–350 mg) given after each
4-hour hemodialysis session.
1

Dosage for Adults and Children ≤12 Years of Age with Renal Impairment
Clcr (mL/min)
Total Daily Dosage
(mg/day)
Dosage Regimen
≥60 900–3600
300 –1200 mg 3 times
daily
30–59 400–1400 200 –700 mg twice daily
15–29 200–700 200 –700 mg once daily
15
a
100–300 100 –300 mg once daily
ESRD patients undergoing
hemodialysis
— 125–350 mg
b

Geriatric Patients
Select dosage carefully, usually initiating therapy at the low end of the dosage range.
1
Adjust
dosage based on Clcr.
1

Cautions for Gabapentin
Contraindications
Known hypersensitivity to gabapentin or any ingredient in the formulation.
1

5. Warnings/Precautions
Warnings
Pending revision, the material in this section should be considered in light of more recently
available information in the MedWatch notification at the beginning of this monograph.
Cognitive/Neuropsychiatric Effects
Pending revision, the material in this section should be considered in light of more recently
available information in the MedWatch notification at the beginning of this monograph.
Emotional lability (primarily behavioral problems), hostility (including aggressive behaviors),
thought disorders (including concentration and school performance changes), and hyperkinesia
(primarily restlessness and hyperactivity) associated with use in children 3–12 years of age with
epilepsy.
1

Withdrawal Seizures
Abrupt withdrawal may result in increased seizure frequency; withdraw gabapentin gradually
and reduce dosage slowly over ≥1 week.
1

Status Epilepticus
Not established whether incidence of status epilepticus (1.5% in controlled and uncontrolled
trials of gabapentin) is higher or lower than would be expected in patients with epilepsy not
treated with the drug.
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Tumorigenic Potential
Unexpectedly high incidence of pancreatic acinar adenocarcinomas in male but not female rats.
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Clinical relevance unknown.
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Sudden, Unexplained Deaths in Epilepsy
Higher incidence of sudden and unexplained deaths than would be expected in a healthy
(nonepileptic) population; however, incidence is within range of estimates for patients with
epilepsy or refractory epilepsy.
1

Specific Populations
Pregnancy
Category C.
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Lactation

6. Distributed into milk; use only if potential benefits outweigh the risks.
1

Pediatric Use
Safety and efficacy as adjunctive therapy in the management of partial seizures not established in
children <3 years of age.
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Safety and efficacy for the management of postherpetic neuralgia not established in children.
1

Geriatric Use
Insufficient experience with gabapentin for the management of partial seizures in patients ≥65
years of age to determine whether they respond differently than younger adults.
1
Select dosage
carefully.
1
(See Geriatric Patients under Dosage and Administration.)
Appeared to be more effective for the management of postherpetic neuralgia in patients >75
years of age than in younger patients; apparent difference in efficacy may be related to decreased
renal function in older patients.
1

Adverse effects in older patients with postherpetic neuralgia generally similar to those in
younger adults; however, the incidence of peripheral edema and ataxia appears to increase with
age.
1

Geriatric patients may have decreased hepatic, renal, or cardiac function, with increased risk of
adverse effects.
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Use with caution; renal function monitoring may be useful.
1

Renal Impairment
Clearance decreased; adjust dosage in adults and children ≥12 years of age with renal
impairment.
1
(See Renal Impairment under Dosage and Administration.)
Use in children <12 years of age with renal impairment has not been studied.
1

Common Adverse Effects
Children 3–12 years of age receiving gabapentin as adjunctive therapy for partial seizures: viral
infection, fever, nausea and/or vomiting, somnolence, hostility.
1

Adults and children >12 years of age receiving gabapentin as adjunctive therapy for partial
seizures with or without secondary generalization: somnolence, dizziness, ataxia, fatigue,
nystagmus.
1

Adults receiving gabapentin for management of postherpetic neuralgia: dizziness, somnolence,
peripheral edema.
1

Interactions for Gabapentin

7. Not metabolized by CYP isoenzymes.
1
Does not inhibit CYP isoenzymes 1A2, 2C9, 2C19, 2D6,
2E1, or 3A4 in vitro; causes slight inhibition of CYP2A6 at high concentrations.
1

Specific Drugs
Drug Interaction Comments
Antacids Reduced bioavailability of gabapentin
1

Administer gabapentin at least
2 hours after antacid
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Anticonvulsants
Plasma concentrations of carbamazepine,
phenytoin, valproic acid, phenobarbital, and
diazepam in existing treatment regimens not
affected by gabapentin;
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pharmacokinetics of gabapentin not affected by
these drugs
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Cimetidine Possible decrease in gabapentin clearance
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Not likely to be clinically
important
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Hydrocodone
Possible dose-dependent decrease in plasma
concentrations of hydrocodone; possible
increase in plasma concentrations of gabapentin
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Morphine
Increase in plasma concentrations of
gabapentin
1

Decrease in dosage of
morphine or gabapentin may
be required in patients with
symptoms of CNS depression
(e.g., somnolence)
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Naproxen
Increased bioavailability of gabapentin at
subtherapeutic dosages of both drugs
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Extent of interaction at usual
therapeutic dosages is
unknown
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Oral
Contraceptives
Possible increase in peak plasma concentrations
of norethindrone
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Not likely to be clinically
important
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Probenecid No pharmacokinetic interaction observed
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Gabapentin Pharmacokinetics
Absorption
Bioavailability
Bioavailability of 60–27% for doses ranging from 900 mg to 4.8 g daily.
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Bioavailability is not
dose proportional.
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Food
Food increases extent of absorption and peak plasma concentration by 14%.
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8. Distribution
Extent
Readily crosses the blood-brain barrier and concentrates in brain tissue.
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Distributed into breast
milk.
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Not known whether gabapentin crosses the placenta.
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Plasma Protein Binding
<3%.
1

Elimination
Metabolism
Not appreciably metabolized.
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Elimination Route
Excreted renally as unchanged drug.
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Half-life
5–7 hours.
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Special Populations
In children <5 years of age, clearance normalized for weight is higher than in adults and children
≥5 years of age.
1

In patients with renal impairment, plasma clearance is decreased and half-life is prolonged.
1
In
patients with Clcr <30 mL/minute, half-life of 52 hours reported.
1
In anuric patients, half-life
reported to be 132 hours on nondialysis days and 3.8 hours during hemodialysis.
1

Stability
Storage
Oral
Capsules and Tablets : 25°C (may be exposed to 15–30°C).
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Oral Solution : 2–8°C.
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9. Actions
Mechanism of anticonvulsant action is unknown.
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Does not bind to GABA
receptors,
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affect GABA reuptake or metabolism,
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or act as a precursor of
GABA or other substances active at GABA receptors.
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Mechanism of analgesic action is unknown.
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Prevents allodynia (pain-related
behavior in response to normally innocuous stimuli) and hyperalgesia (exaggerated
response to painful stimuli) in several animal models of neuropathic pain.
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Decreases
pain-related responses after peripheral inflammation in animals; however, has not altered
immediate pain-related behaviors.
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Clinical relevance of these findings is not known.
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Advice to Patients
Pending revision, the material in this section should be considered in light of more recently
available information in the MedWatch notification at the beginning of this monograph.
Importance of taking gabapentin exactly as prescribed.
1
Importance of not abruptly
discontinuing therapy.
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Potential for drug to impair mental alertness or physical coordination; avoid driving or
operating machinery until effects on individual are known.
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Importance of women informing clinicians if they are or plan to become pregnant or plan
to breast-feed.
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Importance of informing clinicians of existing or contemplated concomitant therapy,
including prescription and OTC drugs.
1

Importance of informing patients of other important precautionary information. (See
Cautions.)
1

Preparations
Routes Dosage Forms Strengths

Oral Capsules 100 mg*


300 mg*


400 mg*


Solution 250 mg/5 mL


Tablets 100 mg*


300 mg*


400 mg*


600 mg


800 mg

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