Gabapentin

Gabapentin (gab-ah-PEN-tin) is the generic name (non-brand name) of the seizure medicine Neurontin (nur-ON-tin) used in the United States, Canada, the UK, and some other countries. Another commonly used name for Gabapentin is GBP.

As suggested by its name, gabapentin was purposely designed to be similar to GABA (gamma aminobutyric acid), the major inhibitory neurotransmitter in the human brain. As it turns out, however, gabapentin does not act like a GABA agonist in the brain. It was approved by the United States Food and Drug Administration (FDA) in 1993, and has been taken by over two million patients since then.

Gabapentin is manufactured in the United States by Pfizer Inc. through a subsidiary called Greenstone Ltd. It is also manufactured by IVAX and Alpharma. The name or appearance of gabapentin may be different in various countries but usually the dose (measured in milligrams, abbreviated "mg") will be the same.

Neurontin
Tablet
Neurotonin 100mg Capsule

Capsules

100-mg (white, hard-gelatin) Capsules with "PD" on one half and "Neurontin 100 mg" on the other.

Neurotonin 300mg Capsule

300-mg (yellow, hard-gelatin) Capsules with "PD" on one half and "Neurontin 300 mg" on the other.

Neurotonin 400mg Capsule

400-mg (orange, hard-gelatin) Capsules with "PD" on one half and "Neurontin 400 mg" on the other.

Tablets
600-mg (white, oval, coated)
Scored tablet marked with "NT" and "16" on one side

800-mg (white, oval, coated) 
Scored tablet marked with "NT" and "26" on one side

Liquid Solution

250 mg/5 mL (clear, colorless to slightly yellow)
Liquid with strawberry-anise flavor.

Indications

Gabapentin is approved as adjunctive therapy for partial seizures with or without secondary generalization in patients 12 years of age and older.

It does not prevent primary generalized seizures such as absence, myoclonic, or primary generalized tonic-clonic seizures.

Forms

Neurontin is marketed in the United States by Pfizer Inc. The name or appearance may differ in other places. These descriptions apply to the U.S. Versions:

Dosing

See package insert.

How to take and store Gabapentin?

Gabapentin can be taken either with food or without food. It has only a slight effect on the rate and extent of absorption. Antacids such as Maalox do affect the absorption of gabapentin, however, so they shouldn't be taken within 2 hours of a dose of gabapentin.

Capsules and tablets should be swallowed whole.

Patients should store the capsules or tablets at room temperature, away from dampness and direct light.

Missed Doses

In general, tell patients that if they forget a dose, they should take it as soon as they remember. If it is almost time for the next dose, they should delay that dose for a few hours, instead of taking two doses very close together.

Patients who often forget doses may benefit from using a special pillbox or watch with an alarm.

Mechanisms of actions of Gabapentin

Gabapentin was formed by the addition of a cyclohexyl group to gamma-aminobutyric acid (GABA), which allowed this form of GABA to cross the blood-brain barrier.

Despite its structural similarity to GABA, gabapentin does not bind to GABA receptors in the CNS. Its mechanism of action is unknown, but may involve enhanced neuronal GABA synthesis.

Clinical Pharmacology of Gabapentin

Absorption

The bioavailability of gabapentin is not dose-proportional; it decreases as the dose increases. When gabapentin is given in 3 divided doses, at 900 mg per day the bioavailability is approximately 60%, but at 2400 mg per day it drops to 34% and at 4800 mg per day it is only 27%.

Distribution and metabolism

Gabapentin is not metabolized, and does not induce or inhibit hepatic metabolism. It is not bound to plasma proteins and displays linear pharmacokinetics at usual dosages. Consequently, drug-drug interactions are not an issue with gabapentin.

The half-life of gabapentin in otherwise healthy patients with epilepsy is generally 4 to 9 hours; therefore, it is usually given three times a day.

Because the elimination of gabapentin is entirely renal, patients with renal insufficiency usually need lower dosages and less frequent dosing.

Steady state

In patients with normal renal function, steady state is reached after 1 to 2 days of taking a stable dose of gabapentin. The dose that a patient takes should not be increased until steady state has been reached (or some time later), so that the effects of the previous dosage can be assessed.

Efficacy of Gabapentin

Randomized, controlled studies comparing Neurontin (brand name version of gabapentin) and placebo used as add-on therapy have found that Neurontin reduces seizure frequency by at least half in about 12% more patients (Cramer et al. 2001). Side effects were only a little more troublesome than with the placebo and often went away without stopping the medication.

A study of add-on therapy in children aged 3 to 12 years had fairly similar results, with the greatest improvement reported for those with complex partial seizures and secondarily generalized seizures (Appleton et al. 1999).

No single combination of antiepileptic medications is perfect for everyone. Sometimes, a series of combinations must be tried before finding what is best for the individual patient. Because gabapentin generally does not interact with other medications, no adjustments are needed when it is used in combination with other seizure medicines. Gabapentin is a good choice for patients (such as many elderly people with epilepsy) who need to take medicine for other disorders.

Studies have also looked at the effectiveness of Neurontin (brand name version of gabapentin) used alone. In one study, patients with newly diagnosed partial seizures were treated with either Neurontin or carbamazepine (Tegretol, Carbatrol) (Beydoun, 1999). In this study, the two medications had a similar effect on the occurrence of seizures, but fewer patients taking Neurontin had to withdraw because of side effects.

Another study looked at patients who had been taking one or two other seizure medicines but continued to experience complex partial seizures or secondarily generalized seizures. These patients were gradually switched to Neurontin used alone at various doses. Each patient had to withdraw if seizures became more frequent. Overall, 20% completed 16 weeks of treatment with Gabapentin alone. This percentage was higher for those who had previously been taking only one medication, but it was lower for those who had been taking carbamazepine (Tegretol, Carbatrol).

Common side effects of Gabapentin

Dose-related side effects

Side effects of gabapentin are generally mild to moderate and transient. The most commonly reported dose-related side effects are:

  • drowsiness
  • ataxia
  • dizziness
  • nystagmus
  • fatigue

If these problems do not diminish within several days, a reduction in the dose of gabapentin often will solve the problem. Problems with sedation also may be helped by splitting the dose or giving the largest dose at bedtime.

Weight gain occurs in up to 5% of patients and is often accompanied by ankle edema.

The package insert for gabapentin warns that about 6% of children aged 3-12 years in clinical trials developed new behavioral problems (including hostility, aggressive behaviors, or hyperactivity) or trouble with thinking, especially concentration.

There are no known long-term side effects of gabapentin.

Idiosyncratic reactions

No idiosyncratic reactions or effects on bone marrow or hepatic function have been described.

Serious Side effects of Gabapentin

Most people who take gabapentin have mild side effects that go away without sequelae, or even no side effects at all. Gabapentin appears to be an exceptionally safe medicine. Indeed, no life-threatening reactions have been attributed to it. As with any medication, however, a very small number of people (well under 1%) have serious reactions, as described in the package insert.

In rare cases, gabapentin has made absence or myoclonic seizures worse.

On July 10, 2008, an advisory panel was convened by the Food and Drug Administration (FDA) to review data that the FDA had previously collected from drug studies showing an association between many of the antiepileptic drugs (AEDs) and suicidal ideation and behavior, which together are called suicidality. According to the FDA’s Alert, among the patients with epilepsy in these drug studies, 1 out of 1000 people taking the placebo (inactive substance) showed suicidality compared to approximately 3.5 out of 1000 people who took an AED. The FDA advisory panel voted to accept the FDA's data at its meeting on July 10.

Taking antiepileptic medicines may increase the risk of having suicidal thoughts or actions;

  • Do not make any changes to the medication regimen without first talking with the responsible healthcare professional;
  • Pay close attention to any day-to-day changes in mood, behavior and actions. These changes can happen very quickly so it is important to be mindful of any sudden differences.

Be aware of common warning signs that might be a signal for risk of suicide. Some of these are:

  •  Talking or thinking about wanting to hurt yourself or end your life
  •  Withdrawing from friends and family
  •  Becoming depressed or having your depression get worse
  •  Becoming preoccupied with death and dying
  •  Giving away prized possessions

We again urge patients and families to contact their doctor before stopping an epilepsy medication because this may possibly lead to seizures and worsening of mood.

Impact of Gabapentin on bone health

At this time there is no evidence to support that Gabapentin causes bone health problems.  Please see package insert.

Other Uses of Gabapentin

In the United States, gabapentin is approved by the FDA for the management of postherpetic neuralgia.

It is used off-label in a variety of other pain conditions such as diabetic and HIV neuropathy and migraine headaches. It is also used for affective disorders (primarily anxiety disorders).

Gabapentin Contraindications

Patients who are allergic to gabapentin or other ingredients should not take gabapentin.

Gabapentin may worsen absence and myoclonic seizures, so caution should be observed if the patient might have these seizure types.

Gabapentin Interactions with other medications

There are no known interactions of gabapentin with other medications, herbs, or dietary supplements.

Gabapentin effects on Children

Gabapentin has been used for many years to treat children with partial seizures. It is not effective for absence seizures.

Children usually start with a dose of 10-15 mg/kg per day. This is usually given in 3 equal doses.

Most children do best at about 25-60 mg/kg per day, split into 3 doses.

The package insert for Gabapentin warns that about 6% of children aged 3-12 years in clinical trials developed new behavioral problems (including hostility, aggressive behaviors, or hyperactivity) or trouble with thinking, especially concentration.

Gabapentin and Pregnancy

The FDA lists gabapentin in Pregnancy Category C. Studies in animals have shown some harm to the fetus. There have not been enough well-controlled studies in women. Caution is advised, but the benefits of the medication may outweigh the potential risks.

The risk of defects generally is higher for women who take more than one AED and for women with a family history of birth defects. Whether this applies to gabapentin is not yet known.

Advise women who are capable of becoming pregnant to take at least 400 mcg (0.4 mg) of folic acid (folate) daily to help prevent neural tube defects. Women at high risk, such as those with a history of a neural tube defect in a previous pregnancy, should take 4000 mcg (4 mg) daily, beginning before they become pregnant. The effectiveness of prophylactic folic acid use in preventing defects related to Neurontin has not been proven, however, so diagnostic ultrasonography at the 18th to 20th week is recommended, especially if pregnancy termination is an option.

About 20% to 35% of women have seizures more often during pregnancy because of changes in hormones or changes in how their seizure medicine is metabolized. This does not appear to be an issue with gabapentin.

Breast-feeding by mothers taking gabapentin is likely to be safe for healthy, full-term newborns. A small amount of the medication will appear in the milk; one estimate is that the baby may receive up to about 1 mg/kg per day in the milk. The effect of this amount on an infant is unknown.

Gabapentin effects on Seniors

Older patients eliminate gabapentin more slowly than younger adults and they are often more susceptible to side effects. Therefore, lower initial doses, slower titration, and lower maintenance doses are advised.

Some common side effects of gabapentin, such as ataxia, may exacerbate pre-existing problems of seniors, putting them at greater risk of injury from falls.

Because gabapentin generally does not interact with other medications, it can be a good choice for patients (such as many elderly people with epilepsy) who also are being treated for other disorders.

Gabapentin Dosing and titration

Dosing in patients with normal renal function should be initiated at 300 mg a day and increased by 300 mg (in 3 or 4 divided doses) every 1 to 3 days to the maximum tolerated dose.

The recommended dosage as add-on therapy ranges from 900 to 1800 mg daily, but many patients need higher dosages for efficacy. Doses are generally given three times a day, with no more than 12 hours between doses.

A therapeutic serum concentration range has not been established.

Special Concerns for Gabapentin

See package insert.

Gabapentin Package insert

In the United States, companies that manufacture medicines are required to publish certain kinds of information about each product. This document is commonly known as a “package insert” because it is usually included with each package of the medicine.

You can also read these documents (also called "prescribing information") online. The U.S. package insert for Neurontin (gabapentin) is found at:

Some of the information may differ in other countries.

 

To learn how to read and understand a package insert, see How to read a package insert.

 

Gabapentin References for Professionals

Abstracts of articles relevant to this topic are available through PubMed, a service of the National Library of Medicine:

Here are links to some articles relevant to this subject:

Cramer JA, Ben Menachem E, French J. Review of treatment options for refractory epilepsy: new medications and vagal nerve stimulation. Epilepsy Res 2001 Nov;47(1-2):17-25. PMID: 11673017.

Appleton R, Fichtner K, LaMoreaux, et al. Gabapentin as add-on therapy in children with refractory partial seizures: a 12-week, multicentre, double-blind, placebo-controlled study. Gabapentin Paediatric Study Group. Epilepsia 1999 Aug;40(8):1147-54. PMID 10448830.

Beydoun A. Monotherapy trials with gabapentin for partial epilepsy. Epilepsia 1999;40 Suppl 6:S13-6. PMID: 10530677.

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The mission of the Epilepsy Foundation is to lead the fight to overcome the challenges of living with epilepsy and to accelerate therapies to stop seizures, find cures, and save lives.

 
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