Consumer medicine information

Neurontin

Gabapentin

BRAND INFORMATION

Brand name

Neurontin

Active ingredient

Gabapentin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Neurontin.

What is in this leaflet

This leaflet answers some common questions about Neurontin.

It does not contain all the available information.

It does not take the place of talking to your doctor or pharmacist.

All medicines have risks and benefits. Your doctor has weighed the risks of you taking Neurontin against the benefits it is expected to have for you.

If you have any concerns about taking this medicine, ask your doctor or pharmacist.

Keep this leaflet with the medicine. You may need to read it again.

What Neurontin is used for

What Neurontin does

Neurontin is used to control epilepsy. Epilepsy is a condition where you have repeated seizures (fits). There are many different types of seizures, ranging from mild to severe.

Neurontin is also used to treat neuropathic pain, a type of pain caused by damage to the nerves.

This medicine belongs to a group of medicines called anticonvulsants.

How Neurontin works

This medicine is thought to work by controlling brain chemicals which send signals to nerves to help control seizures or neuropathic pain.

Neurontin also has pain relieving effects.

Your doctor may have prescribed Neurontin in addition to other medicines that you may be taking. This may be necessary if your current treatment is no longer working as well.

Your doctor may have prescribed Neurontin for another reason.

Neurontin may lead to dependence on this medicine.

Ask your doctor if you have any questions about why Neurontin has been prescribed for you.

This medicine is available only with a doctor's prescription.

Use in children

There is not enough information to recommend the use of this medicine in children:

  • under the age of 3 years to control epilepsy, or
  • under the age of 18 years to treat neuropathic pain.

Before you take Neurontin

When you must not take it

Do not take Neurontin if you have an allergy to:

  • any medicine containing gabapentin, the active ingredient in Neurontin
  • any of the ingredients listed at the end of this leaflet.

Some of the symptoms of an allergic reaction may include:

  • shortness of breath
  • wheezing or difficulty breathing
  • swelling of the face, lips, tongue or other parts of the body
  • rash, itching or hives on the skin.

Do not take Neurontin after the expiry date printed on the pack or if the packaging is torn or shows signs of tampering. If it has expired or is damaged, return it to your pharmacist for disposal.

If you are not sure whether you should start taking Neurontin, talk to your doctor or pharmacist.

Before you start to take it

Tell your doctor or pharmacist if you have allergies to:

  • any other medicines, especially barbiturates or any other anticonvulsant medicines
  • any other substances, such as foods, preservatives or dyes.

Tell your doctor if you have or have had any of the following medical conditions:

  • kidney problems
  • mixed seizure disorders that include absence seizures.

Tell your doctor if you are pregnant or plan to become pregnant. Neurontin may affect your developing baby if you take it during pregnancy. However, it is very important to control your fits while you are pregnant. If it is necessary for you to take Neurontin, your doctor can help you decide whether or not to take it during pregnancy.

Tell your doctor if you are breast-feeding or plan to breast-feed. Neurontin passes into breast milk. The effect on your breast-fed baby is unknown.

If you do breast-feed, watch your baby carefully. If your baby develops a skin rash, becomes sleepy or has unusual symptoms, don't breast-feed again until you speak to your doctor.

Your doctor can discuss the risks and benefits of breast-feeding with you.

If you have not told your doctor or pharmacist about any of the above, tell them before you start taking Neurontin.

Taking other medicines

Tell your doctor or pharmacist if you are taking any other medicines, including:

  • all prescription medicines
  • all medicines, vitamins, herbal supplements or natural therapies you buy without a prescription from a pharmacy, supermarket, naturopath or health food shop.

Some medicines may be affected by Neurontin or may affect how well it works. You may need different amounts of your medicines, or you may need to take different medicines. Your doctor or pharmacist will advise you accordingly.

Tell your doctor or pharmacist if you are taking any of the following:

  • cimetidine, a medicine used to treat stomach or duodenal ulcers
  • antacids, medicines used to treat heartburn or reflux
  • opioids, medicines used to treat severe pain e.g. morphine.

Your doctor and pharmacist have more information on medicines to be careful with or avoid while taking Neurontin.

How to take Neurontin

Follow all directions given to you by your doctor or pharmacist carefully. They may differ from the information contained in this leaflet.

If you do not understand the instructions on the pack, ask your doctor or pharmacist for help.

How much to take

Your doctor will tell you how many capsules/tablets you need to take each day. This may depend on your age, your condition and whether or not you are taking any other medicines.

Your doctor may recommend that you start with a low dose of Neurontin and slowly increase the dose to the lowest amount needed to control your epilepsy/convulsions or neuropathic pain.

How to take it

Swallow Neurontin whole with a full glass of water.

Neurontin tablets can be divided in half along the breakline, if advised by your doctor or pharmacist.

When to take it

Take Neurontin at about the same time each day. Taking Neurontin at the same time each day will have the best effect. It will also help you remember when to take the capsules/tablets.

If you are taking Neurontin three times a day, do not allow more than 12 hours between doses.

It does not matter if you take Neurontin before or after food.

How long to take it

Continue taking your medicine for as long as your doctor tells you to.

Neurontin helps control your condition, but does not cure it. Therefore you must take your medicine every day, even if you feel well.

Do not stop taking Neurontin, or lower the dose, without checking with your doctor. Do not let yourself run out of medicine over the weekend or holidays. Stopping Neurontin suddenly may cause unwanted side effects or make your condition worse. Your doctor will slowly reduce your dose before you can stop taking it completely.

If you forget to take it

If it is almost time for your next dose (within 4 hours), skip the dose you missed and take your next dose when you are meant to.

Otherwise, take it as soon as you remember, and then go back to taking Neurontin as you would normally.

Do not take a double dose to make up for the dose that you missed. This may increase the chance of you getting an unwanted side effect.

If you are not sure what to do, ask your doctor or pharmacist.

If you have trouble remembering to take Neurontin, ask your pharmacist for help.

If you take too much (overdose)

Immediately telephone your doctor or Poisons Information Centre (telephone Australia 13 11 26 or New Zealand 0800 POISON or 0800 764 766) for advice, or go to Accident and Emergency at the nearest hospital, if you think that you or anyone else may have taken too much Neurontin.

Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention.

Symptoms of an overdose may include you falling unconscious, feeling drowsy, weak, unsteady when walking, having double vision, slurred speech or diarrhoea.

While you are taking Neurontin

Things you must do

If you are about to be started on any new medicine, remind your doctor and pharmacist that you are taking Neurontin.

Tell any other doctors, dentists, and pharmacists who treat you that you are taking Neurontin.

If you are going to have surgery or emergency treatment, tell the surgeon or anaesthetist that you are taking Neurontin.

Tell your doctor immediately if you have any thoughts of suicide or self-harm, any unusual changes in mood or behaviour, or show signs of depression. Some people being treated with anti-epileptics, such as Neurontin, have had thoughts of harming or killing themselves.

Patients and caregivers should be alert and monitor for signs and symptoms of suicide, these include:

  • thoughts or talk of death or suicide
  • thoughts or talk of self-harm or harm to others
  • any recent attempts of self-harm
  • new or an increase in aggressive behaviour, irritability or agitation
  • new onset of or worsening of depression.

Mention of suicide or violence must be taken seriously.

If you or someone you know is demonstrating these warning signs and symptoms of suicide while taking Neurontin, contact your doctor or a mental health professional right away.

Tell your doctor if you feel Neurontin is not helping your condition. Your doctor may need to change your medicine.

Tell your doctor if, for any reason, you have not taken Neurontin exactly as prescribed. Otherwise, your doctor may change your treatment unnecessarily.

If you become pregnant while taking Neurontin, tell your doctor immediately.

If you need to have any medical tests while you are taking Neurontin, tell your doctor. It may interfere with the results of some tests.

If you are going to have any surgery or procedure, including dental surgery, tell your surgeon, doctor or dentist that you are taking this medicine.

Keep all of your doctor's appointments so that your progress can be checked. Your doctor will check your progress and may want to take some tests from time to time. This helps to prevent unwanted side effects.

Things you must not do

Do not take Neurontin to treat any other complaints unless your doctor tells you to.

Do not give Neurontin to anyone else, even if their symptoms seem similar to yours or they have the same condition as you.

Do not stop taking Neurontin or lower the dose without checking with your doctor. Stopping Neurontin suddenly, if you have epilepsy, may cause unwanted side effects or make your condition worse. Your doctor will slowly reduce your dose before you can stop taking it completely.

Things to be careful of

Be careful driving or operating machinery until you know how Neurontin affects you. As with other anticonvulsant medicines, Neurontin may cause drowsiness, dizziness, light-headedness or sleepiness in some people. Make sure you know how you react to Neurontin before you drive a car, operate machinery, or do anything else that could be dangerous if you are dizzy or light-headed. If this occurs do not drive.

Children should not ride a bike, climb trees or do anything else that could be dangerous if they are feeling drowsy or sleepy.

Be careful when drinking alcohol while you are taking Neurontin. Combining Neurontin and alcohol can make you more sleepy, dizzy or light-headed. Your doctor may suggest you avoid alcohol while you are being treated with Neurontin.

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking Neurontin.

All medicines can have side effects. Sometimes these are serious, but most of the time these are not. You may need medical attention if you get some side effects.

It can be difficult to tell whether side effects are the result of taking Neurontin; of your condition; or side effects of other medicines you may be taking, for this reason it is important to tell your doctor of any change in your condition.

If you are over 65 years of age you may have an increased chance of getting side effects.

Ask your doctor or pharmacist to answer any questions you may have.

If you get any side effects, do not stop taking Neurontin without first talking to your doctor or pharmacist.

Tell your doctor if...

Tell your doctor or pharmacist if you notice any of the following and they worry you:

  • dizziness* or light-headedness
  • feeling tired or drowsy*
  • unfriendliness*
  • unusually overactive*
  • forgetfulness, loss of concentration or confusion
  • difficulty speaking
  • changes in your weight*
  • constipation, diarrhoea
  • nausea and/or vomiting*, indigestion
  • dry mouth, red swollen gums
  • muscle pain or cramps, back pain
  • swelling of the hands or feet
  • runny or blocked nose
  • fever*
  • bronchitis*, lung infection*
  • sore throat and discomfort when swallowing, coughing.

The above list includes the more common side effects of Neurontin. They are usually mild and short-lived.

Tell your doctor as soon as possible if...

Tell your doctor as soon as possible if you notice any of the following:

  • weakness, unsteadiness when walking including falling, reduced co-ordination or slowed reactions
  • unusual changes in mood* or behaviour such as restlessness, nervousness, or excitement
  • signs of new onset of, or increased irritability or agitation
  • signs of depression
  • seeing or hearing things that are not there, irrational thinking
  • blurred or double vision, uncontrollable jerky eye movements, difficulty seeing
  • signs of frequent infections such as fever, severe chills, sore throat or mouth ulcers.
  • trouble breathing or shallow breaths (respiratory depression)
  • loss of consciousness

The side effects in the above lists marked * have been specifically reported in children taking Neurontin.

Go to hospital if...

Tell your doctor immediately or go to Accident and Emergency at your nearest hospital if you notice any of the following:

  • more frequent or more severe seizures (fits)
  • chest pain, a very fast heart rate
  • sudden signs of allergy such as rash, itching or hives, fever, swollen lymph glands, swelling of the face, lips, tongue or other parts of the body, shortness of breath, wheezing or difficulty breathing.

The above list includes very serious side effects. You may need urgent medical attention or hospitalisation. These side effects are very rare.

Tell your doctor or pharmacist if you notice anything else that is making you feel unwell. Other side effects not listed above may also occur in some people.

Some of these side effects (for example, changes in thyroid function, structures of bones, high cholesterol, levels of sugar in your blood or blood pressure) can only be found when your doctor does blood tests from time to time to check your progress.

Do not be alarmed by the list of possible side effects. You may not experience any of them.

After taking Neurontin

Storage

Keep your capsules/tablets in the pack until it is time to take them. If you take the capsules/tablets out of the pack they may not keep well.

Keep your capsules in a cool dry place where the temperature stays below 30°C.

Keep your tablets in a cool dry place where the temperature stays below 25°C.

Do not store Neurontin or any other medicine in the bathroom or near a sink. Do not leave it on a window sill or in the car. Heat and dampness can destroy some medicines.

Keep it where children cannot reach it. A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Disposal

If your doctor or pharmacist tells you to stop taking Neurontin or the expiry date has passed, ask your pharmacist what to do with any medicine that is left over.

Product description

What it looks like

Capsules

100 mg - White capsule, marked Neurontin 100 mg, PD

300 mg - Yellow capsule, marked Neurontin 300 mg, PD

400 mg - Orange capsule, marked Neurontin 400 mg, PD

Tablets

600 mg - White, elliptical, film-coated tablet, with bisecting score on both sides and debossed with "NT" and "16" on one side.

800 mg - White, elliptical, film-coated tablet, with bisecting score on both sides and debossed with "NT" and "26" on one side.

Each pack contains 100 capsules/tablets.

Not all packs are available.

Ingredients

Active ingredient

  • Neurontin 100 mg - 100 mg gabapentin
  • Neurontin 300 mg - 300 mg gabapentin
  • Neurontin 400 mg - 400 mg gabapentin
  • Neurontin 600 mg - 600 mg gabapentin
  • Neurontin 800 mg - 800 mg gabapentin.

Other capsule ingredients:

  • Lactose monohydrate
  • talc-purified
  • starch maize
  • gelatin
  • titanium dioxide
  • Opacode Blue S-1-4118
  • iron oxide - yellow (300 mg / 400 mg)
  • iron oxide - red (400 mg).

Other tablet ingredients:

  • poloxamer
  • copovidone
  • starch-maize
  • magnesium stearate
  • candelilla wax
  • Opadry White YS-1-18111.

Neurontin does not contain sucrose, gluten, tartrazine or any other azo dyes.

Supplier

Neurontin is supplied in Australia by:

Pfizer Australia Pty Ltd
Sydney NSW
Toll Free Number: 1800 675 229

Australian Registration Numbers:

100 mg capsules: AUST R 74067

300 mg capsules: AUST R 66008

400 mg capsules: AUST R 66005

600 mg tablets: AUST R 71793

800 mg tablets: AUST R 71791

Neurontin is supplied in New Zealand by:

Pfizer New Zealand Ltd
PO Box 3998
Auckland
New Zealand
Toll Free Number: 0800 736 363

This leaflet was prepared in March 2020 ©

Pfizer Australia Pty Ltd ® Registered trademark.

pfcneuro10320

Published by MIMS May 2020

BRAND INFORMATION

Brand name

Neurontin

Active ingredient

Gabapentin

Schedule

S4

 

1 Name of Medicine

Gabapentin.

6.7 Physicochemical Properties

Gabapentin is a white to off white crystalline solid. It is freely soluble in water and both basic and acidic aqueous solutions.
The stuctural formula of gabapentin is shown below:

Chemical structure.


Chemical name: 1-(aminomethyl) cyclohexaneacetic acid.
Molecular formula: C9H17NO2.
Molecular weight: 171.24.

CAS number.

60142-96-3.

2 Qualitative and Quantitative Composition

Neurontin capsules: Each capsule contains 100 mg, 300 mg or 400 mg of gabapentin.
Neurontin tablets: Each tablet contains 600 mg or 800 mg of gabapentin.

Excipient(s) with known effect.

Neurontin capsules.

Sugars as lactose monohydrate.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

100 mg capsules.

Size C hard gelatin capsules with white opaque body and cap.

300 mg capsules.

Size B hard gelatin capsules with yellow opaque body and cap.

400 mg capsules.

Size A hard gelatin capsules with orange opaque body and cap.

600 mg tablets.

White, elliptical film-coated tablets with bisecting score on both sides and debossed with "NT" and "16" on one side.

800 mg tablets.

White, elliptical film-coated tablets with bisecting score on both sides and debossed with "NT" and "26" on one side.

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

The mechanism by which gabapentin exerts its anticonvulsant action is unknown. Gabapentin is structurally related to the neurotransmitter GABA (gamma-aminobutyric acid) but its mechanism of action is different from that of several other drugs that interact with GABA synapses, including valproate, barbiturates, benzodiazepines, GABA transaminase inhibitors, GABA uptake inhibitors, GABA agonists, and GABA prodrugs. In vitro studies with radiolabelled gabapentin have characterised a novel peptide binding site in rat brain tissues including neocortex and hippocampus that may relate to anticonvulsant activity of gabapentin and its structural derivatives. However, the identification and function of the gabapentin binding site remains to be elucidated. Gabapentin at relevant clinical concentrations does not bind to other common drug or neurotransmitter receptors of the brain including GABAA, GABAB, benzodiazepine, glutamate, glycine or N-methyl-d-aspartate receptors.
Gabapentin does not interact with sodium channels in vitro and so differs from phenytoin and carbamazepine. Several test systems ordinarily used to assess activity at the NMDA receptor complex have been examined. Results are contradictory. Accordingly, no general statement about the effects, if any, of gabapentin at the NMDA receptor can be made. Gabapentin slightly reduces the release of monoamine neurotransmitters in vitro. Gabapentin administration to rats increases GABA turnover in several brain regions in a manner similar to valproate sodium, although in different regions of brain. The relevance of these various actions of gabapentin to the anticonvulsant effects remains to be established. In animals, gabapentin readily enters the brain and shows efficacy in some, but not all, seizure models. These animal models included genetic models of seizures, and seizures induced by maximal electroshock, from chemical convulsants including inhibitors of GABA synthesis.

Clinical trials.

Partial seizures.

Adults.

The effectiveness of Neurontin as adjunctive therapy was established in three multicentre, placebo controlled, double blind, parallel group clinical trials in 705 adults with refractory partial seizures. 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. 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, given as three divided doses (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 Neurontin (n = 101), given as three divided doses, 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, given as three divided doses (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.
A one week, prospective, multicentre, randomised, double blind, placebo lead in, parallel group study compared the tolerability of Neurontin administered as an initial dosage of 900 mg/day versus a dosage titrated to 900 mg/day over three days (i.e. 300 mg on day 1, 600 mg on day 2, 900 mg on day 3). 781 patients (titrated = 383, nontitrated = 388) involved in the study had partial seizures which were not adequately controlled with one or two other antiepileptic drugs. For the MITT population, on both the first day of active medication, and all 5 days of active medication, there were no clinically meaningful treatment group differences in the incidences of fatigue, ataxia and somnolence (i.e. the upper 95% confidence limit for the difference < 7.5%). Only the difference in dizziness exceeded this upper confidence limit (upper confidence limit = 10.7% for the first day and 11.3% for all 5 days), with the nontitrated group reporting the higher incidence, however it did not lead to increased discontinuation in this group.

Paediatric patients.

The safety and efficacy of Neurontin administered as adjunctive therapy for the treatment of partial seizures in paediatric patients aged 3 to 12 years were assessed in two randomised, double blind, parallel group, placebo controlled, multicentre clinical studies. The studies were conducted in 247 children who had refractory partial seizures and were receiving 1 to 3 standard antiepileptic drugs. After a 6 week baseline phase, during which patients received their prescribed antiepileptic drugs, there was a 12 week double blind treatment phase. Patients who had experienced a minimum of 4 seizures during baseline were randomised and had either Neurontin (25 to 35 mg/kg/day) or placebo added to their baseline AEDs. The primary analysis of RRatio (MITT population) demonstrated that Neurontin was significantly better than placebo in controlling partial seizures (p = 0.04). Results for the ITT population did not show a significant difference in RRatio between the treatment groups. Further analysis using rank transformed data was performed as the data showed evidence of non-normality of distribution. Results of this analysis showed that mean RRatio was significantly lower (better) for the gabapentin treatment group than for the placebo group in both the MITT (p = 0.01) and ITT (p = 0.03) populations.

Neuropathic pain.

Adults.

The efficacy and safety of Neurontin for the treatment of neuropathic pain in adults older than 18 years of age were assessed in two randomised, double blind, parallel group, placebo controlled, multicentre studies. One study examined the efficacy and safety of Neurontin in the treatment of painful diabetic peripheral neuropathy and the other study was conducted in patients with postherpetic neuralgia. The studies were of a similar design. Following a baseline screening week and randomisation, Neurontin was titrated from 900 mg/day to 1800 mg/day, 2400 mg/day and 3600 mg/day divided into three times a day dosing consecutively over the first four weeks of the study. Patients were then maintained at the maximum dose that was tolerated for the remaining four weeks. The primary efficacy measure used in both studies was change from baseline to the final week in mean pain score obtained from daily pain diaries (pain was measured using an 11 point Likert scale). Several secondary outcomes were also assessed, including the Short Form McGill Pain Questionnaire (SF-MPQ) (sensory, affective and total pain scores), SF-MPQ visual analogue scale (VAS) and present pain intensity scale (PPI), mean sleep interference score, Patient and Clinical Global Impression of Change (PGIC and CGIC) and the quality of life measures SF-36 Quality of Life Questionnaire (QOL) and Profile of Mood States (POMS).
Results from both studies demonstrated that Neurontin provided statistically significantly greater improvement in relief of neuropathic pain than placebo. In patients with painful diabetic peripheral neuropathy, mean pain score decreased by 2.6 in patients receiving Neurontin and 1.4 in patients receiving placebo (p < 0.001). In the postherpetic neuralgia study, mean pain score decreased by 2.1 in patients receiving Neurontin and 0.5 in patients receiving placebo (p < 0.001). Neurontin was significantly better than placebo in controlling pain from week two of both studies (p < 0.001). Sleep interference scores, Short Form McGill sensory, affective and total pain scores, VAS and PPI scale as well as PGIC, CGIC and some of the quality of life measures showed significant differences in favour of Neurontin.

5.2 Pharmacokinetic Properties

All pharmacological actions following gabapentin administration are due to the activity of the parent compound; gabapentin is not appreciably metabolised in humans.

Absorption.

Gabapentin bioavailability is not dose proportional, i.e. as dose is increased, bioavailability decreases. A 400 mg dose, for example, is about 25% less bioavailable than a 100 mg dose. Over the recommended dose range of 300 mg to 600 mg three times a day, however, the differences in bioavailability are not large, and bioavailability is about 60%. The bioavailability of the 800 mg dose was found to be approximately 35% in single and multiple dose studies. The absolute bioavailability of gabapentin following daily doses of 1200 mg/day, 2400 mg/day, 3600 mg/day, and 4800 mg/day averaged 47%, 34%, 33% and 27%, respectively. Food has no effect on the rate and extent of absorption of gabapentin.

Distribution.

Gabapentin circulates largely unbound (< 3%) to plasma proteins. 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 (Cmin) concentrations of gabapentin in the cerebrospinal fluid were approximately 20% of the corresponding plasma concentrations.

Metabolism and excretion.

Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug. Gabapentin is not appreciably metabolised in humans.
The elimination half-life of gabapentin 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. In elderly patients and in patients with impaired renal function, gabapentin plasma clearance is reduced. Gabapentin can be removed by haemodialysis.
Dose adjustment in patients with compromised renal function or in those undergoing haemodialysis is recommended (see Section 4.2 Dose and Method of Administration).

Special populations.

Patients with renal insufficiency.

Subjects with renal insufficiency (mean creatinine clearance ranging from 13 mL/min to 114 mL/min) were administered 400 mg oral dose of gabapentin. The mean gabapentin half-life ranged from about 6.5 hours (patients with creatinine clearance (ClCr) > 60 mL/min) to 52 hours (ClCr < 30 mL/min) and gabapentin renal clearance ranged from about 90 mL/min (ClCr > 60 mL/min) to about 10 mL/min (ClCr < 30 mL/min). Gabapentin dosage should be adjusted in patients with compromised renal function (see Section 4.2 Dose and Method of Administration).

Patients on haemodialysis.

In a study in anuric patients, the elimination half-life of gabapentin on nondialysis day was about 132 hours. Dialysis three times a week (4 hour duration) lowered the apparent half-life of gabapentin by about 60%, from 132 hours to 51 hours. Gabapentin dosage should be adjusted in patients undergoing haemodialysis (see Section 4.2 Dose and Method of Administration).

Elderly (≥ 65 years).

In a study examining the effect of age on the elimination of gabapentin, apparent oral clearance (CL/F) of gabapentin decreased as age increased, from about 225 mL/min in those younger than 30 years of age to about 125 mL/min in those older than 70 years of age. Renal clearance also declined with age, however the decline in the renal clearance of gabapentin can largely be explained by the decline in renal function. Reduction of gabapentin dose may be required in patients who have age related compromised renal function.

Children and adolescents.

Gabapentin pharmacokinetics were determined in 24 healthy paediatric subjects between the ages of 4 and 12 years. In general, gabapentin plasma concentrations in these children are similar to those in adults.

5.3 Preclinical Safety Data

Genotoxicity.

There is no evidence that gabapentin has genotoxic potential. It was not mutagenic in vitro in standard assays using bacterial or mammalian cells. Gabapentin did not induce structural chromosome aberrations in mammalian cells in vitro or in vivo, and did not induce micronucleus formation in the bone marrow of hamsters.

Carcinogenicity.

Gabapentin was given in the diet to mice at 200, 600, and 2000 mg/kg/day and to rats at 250, 1000 and 2000 mg/kg/day for 2 years. A statistically significant increase in the incidence of pancreatic acinar cell adenoma and carcinoma was found only in male rats at the highest dose. Peak plasma gabapentin concentrations and areas under the concentration time curve in rats at 2000 mg/kg/day were 14 times higher than plasma concentrations in humans given the recommended maximum tolerated dose of 2400 mg/day. The pancreatic acinar cell tumours in male rats were low grade malignancies which did not metastasise or invade surrounding tissue, and were similar to those seen in concurrent controls. The relevance of these pancreatic acinar cell tumours in male rats to carcinogenic risk in human is unclear.

4 Clinical Particulars

4.1 Therapeutic Indications

Neurontin is indicated for the treatment of partial seizures, including secondarily generalised tonic-clonic seizures, initially as add-on therapy in adults and children age 3 years and above who have not achieved adequate control with standard antiepileptic drugs.
Neurontin is indicated for the treatment of neuropathic pain.

4.3 Contraindications

Neurontin is contraindicated in patients who have demonstrated hypersensitivity to gabapentin or the inactive ingredients in the capsules and tablets.

4.4 Special Warnings and Precautions for Use

General.

Although there is no evidence of rebound seizures with gabapentin, abrupt withdrawal of anticonvulsants in epileptic patients may precipitate status epilepticus. When in the judgement of the clinician, there is a need for dose reduction, discontinuation or substitution of alternative anticonvulsant medication, this should be done gradually over a minimum of one week.
Gabapentin is generally not considered effective in the treatment of absence seizures and may exacerbate these seizures in some patients. Consequently, Neurontin should be used with caution in patients who have mixed seizure disorders that include absence seizures.
Gabapentin treatment has been associated with dizziness and somnolence, which could increase the occurrence of accidental injury (fall). There have also been post-marketing reports of confusion, loss of consciousness and mental impairment. Therefore, patients should be advised to exercise caution until they are familiar with the potential effects of the medication.

Central nervous system depression.

Respiratory depression.

Gabapentin has been associated with central nervous system (CNS) depression including sedation, somnolence, loss of consciousness as well as serious cases of respiratory depression. This may occur without concomitant opioid use. Patients with compromised respiratory function, respiratory or neurological disease, renal impairment and the elderly are at higher risk of experiencing these severe adverse effects. Concomitant use of CNS depressants with gabapentin increases the risk of respiratory depression.

Concomitant use with opioids.

Patients who require concomitant treatment with opioids may experience increases in gabapentin concentrations. Patients should be carefully observed for signs of central nervous system (CNS) depression, such as somnolence, sedation and respiratory depression; and the dose of Neurontin or opioid should be reduced appropriately (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Suicidal behaviour and ideation.

Antiepileptic drugs (AED), including gabapentin, increase the risk of suicidal thoughts or behaviour in patients taking these drugs for any indication. Patients treated with any AED for any indication should be monitored for the emergence or worsening of depression, suicidal thoughts or behaviour, and/or any unusual changes in mood or behaviour.
Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different AEDs showed that patients randomised to one of the AEDs had approximately twice the risk (adjusted relative risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behaviour compared to patients randomised to placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of suicidal behaviour or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among 16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or behaviour for every 530 patients treated. There were four suicides in drug-treated patients in the trials and none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on suicide.
The increased risk of suicidal thoughts or behaviour with AEDs was observed as early as one week after starting drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behaviour beyond 24 weeks could not be assessed.
The risk of suicidal thoughts or behaviour was generally consistent among drugs in the data analysed. The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-100 years) in the clinical trials analysed. Table 2 shows absolute and relative risk by indication for all evaluated AEDs.
The relative risk for suicidal thoughts or behaviour was higher in clinical trials for epilepsy than in clinical trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and psychiatric indications.
Anyone considering prescribing gabapentin or any other AED must balance this risk with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behaviour. Should suicidal thoughts and behaviour emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts and behaviour and should be advised of the need to be alert for the emergence or worsening of the signs and symptoms of depression, any unusual changes in mood or behaviour, or the emergence of suicidal thoughts, behaviour, or thoughts about self-harm. Behaviours of concern should be reported immediately to the treating doctor.

Drug rash with eosinophilia and systemic symptoms.

Severe, life-threatening, systemic hypersensitivity reactions such as drug rash with eosinophilia and systemic symptoms (DRESS) have been reported in patients taking antiepileptic drugs including Neurontin.
It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may be present even though rash is not evident. If such signs or symptoms are present, the patient should be evaluated immediately. Neurontin should be discontinued if an alternative aetiology for the signs or symptoms cannot be established.

Anaphylaxis.

Neurontin can cause anaphylaxis. Signs and symptoms in reported cases have included difficulty breathing, swelling of the lips, throat, and tongue, and hypotension requiring emergency treatment. Patients should be instructed to discontinue Neurontin and seek immediate medical care should they experience signs or symptoms of anaphylaxis.

Abuse and dependence.

Post-marketing cases of abuse and dependence have been reported with gabapentin. As with other CNS drugs, patients should be carefully evaluated for a history of drug abuse and observed for possible signs of gabapentin abuse.

Information for patients.

To ensure safe and effective use of Neurontin, the following information and instructions should be given to patients.
1. You should inform your physician about any prescription or non-prescription medications, alcohol or drugs you are now taking or are planning to take during your treatment with gabapentin.
2. No teratogenic effects have been found in animals. However, the risk to the human fetus cannot be dismissed. Therefore you should inform your physician if you are pregnant, or if you are planning to become pregnant, or if you become pregnant while you are taking gabapentin.
3. Gabapentin is excreted in human milk, and the effect on the nursing infant is unknown. You should inform your physician if you are breast-feeding an infant.
4. Neurontin may impair your ability to drive a car or operate potentially dangerous machinery. Until it is known that this medication does not affect your ability to engage in these activities, do not drive a car or operate potentially dangerous machinery.
5. You should not allow more than 12 hours between Neurontin doses. If you have missed a dose by not more than 4 hours, take the dose as soon as you remember. However, if you have missed a dose by more than 4 hours, you should skip the dose and continue taking following doses as usual.
6. Prior to initiation of treatment with Neurontin, the patient should be instructed that a rash or other signs or symptoms of hypersensitivity such as fever or lymphadenopathy may herald a serious medical event and that the patient should report any such occurrence to a physician immediately.

Use in renal impairment.

See Section 5.2 Pharmacokinetic Properties; Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use, Central nervous system depression.

Use in the elderly.

See Section 5.2 Pharmacokinetic Properties; Section 4.4 Special Warnings and Precautions for Use, Central nervous system depression.

Paediatric use.

Epilepsy.

Safety and effectiveness in children below the age of 3 years have not been established.

Neuropathic pain.

Safety and effectiveness in children below the age of 18 years have not been established.

Effects on laboratory tests.

False positive readings were reported with the Ames N-Multistix SG dipstick test when gabapentin was added to other anticonvulsant drugs. To determine urinary protein, the more specific sulfosalicylic acid precipitation procedure is recommended.

4.5 Interactions with Other Medicines and Other Forms of Interactions

There are spontaneous and literature case reports of respiratory depression and/or sedation associated with gabapentin and opioid use. These effects would be of particular concern in elderly patients.

Anticonvulsants.

In pharmacokinetic studies, no interactions were observed between gabapentin and phenobarbital (number of subjects, N = 12), phenytoin (N = 8), valproic acid (N = 17), or carbamazepine (N = 12).

Oral contraceptives.

Gabapentin did not influence the steady-state pharmacokinetics of norethindrone and ethinyl estradiol when administered concomitantly with an oral contraceptive containing these two drugs (N = 13).

Antacid.

Coadministration of gabapentin with large dose antacid (aluminium hydroxide 3600 mg, magnesium hydroxide 1800 mg) reduced gabapentin bioavailability (AUC) by about 20% (N = 16). Although the difference was not expected to be clinically significant, it is recommended that gabapentin should be taken about 2 hours following antacid administration, when the interaction has been shown to be diminished.

Cimetidine.

In the presence of cimetidine at 300 mg four times a day (QID), the mean apparent oral clearance of gabapentin fell by 14% and creatinine clearance by 10% (N = 12). Thus cimetidine appeared to alter the renal excretion of both gabapentin and creatinine, an endogenous marker of renal function.

Probenecid.

Renal excretion of gabapentin was unaltered by probenecid, a blocker of renal tubular secretion.

Morphine.

A literature article reported that when a 60 mg controlled release morphine capsule was administered 2 hours prior to a 600 mg Neurontin capsule (N = 12), mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine (see Section 4.4 Special Warnings and Precautions for Use). Morphine pharmacokinetic parameter values were not affected by administration of Neurontin 2 hours after morphine. The magnitude of interaction at other doses is not known.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

No adverse effects on fertility or reproduction were observed in rats at doses up to 2000 mg/kg/day administered in the diet, with estimated exposure (plasma AUC) 14 times clinical exposure at the MRHD of 2400 mg/day.
(Category B3)
Gabapentin crosses the human placenta.
Congenital malformations and adverse pregnancy outcomes have been reported with gabapentin use, however there are no adequate and well-controlled studies in pregnant women and no definite conclusions can be made as to whether gabapentin is causally associated with an increased risk of congenital malformations or other adverse developmental outcomes when taken during pregnancy. The risk of birth defects is increased by a factor of 2-3 in the offspring of mothers treated with an antiepileptic medicinal product.
Gabapentin should be used during pregnancy only if the potential benefit to the mother clearly outweighs the potential risk to the fetus.
The risk of having a child with a congenital defect as a result of antiepileptic medication is far outweighed by the dangers to the mother and fetus of uncontrolled epilepsy.
It is recommended that:
women on antiepileptic drugs (AEDs) receive pre-pregnancy counselling with regard to the risk of fetal abnormalities;
AEDs should be continued during pregnancy and monotherapy should be used if possible at the lowest effective dose as risk of abnormality is greater in women taking combined medication;
folic acid supplementation (5 mg) should be commenced four weeks prior to and continue for twelve weeks after conception;
specialist prenatal diagnosis including detailed mid-trimester ultrasound should be offered.
Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown.
Embryofetal development studies with gabapentin in mice at oral doses up to 3000 mg/kg/day and in rats at oral doses up to 1500 mg/kg/day revealed no evidence of fetal malformations. Delayed ossification in the skull, vertebrae and limbs, indicative of fetal growth retardation, was reported in the offspring of mice administered gabapentin at oral doses of 1000 and 3000 mg/kg/day during organogenesis, and rats administered gabapentin 2000 mg/kg/day in the diet during mating and throughout gestation. An increased incidence of hydroureter and/or hydronephrosis was observed in rats treated with dietary gabapentin from late gestation to weaning (see Section 4.6 Fertility, Pregnancy and Lactation, Use in lactation). In these studies, exposure to gabapentin (based on areas under the concentration time curve) was up to 5 times higher in the mouse, and up to 14 times higher in the rat, than in humans at the recommended maximum dose of 2400 mg/day.
In female rabbits given 60, 300 or 1500 mg/kg/day gabapentin orally during the period of organogenesis, maternal toxicity and abortion were observed at the high dose, but at the low and mid doses, no evidence of harm to the fetus was observed.
Gabapentin is excreted in human milk. In a peri-postnatal study in rats administered gabapentin in the diet at doses of 500, 1000 and 2000 mg/kg/day from late gestation to weaning, there was a dose related reversible increase in the incidence of hydroureter and hydronephrosis in 21 day-old pups.
Because the effect on the nursing infant is unknown, and because of the potential for serious adverse reactions in nursing infants from gabapentin, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother. Neurontin should be used in nursing mothers only if the benefits clearly outweigh the risks.

4.8 Adverse Effects (Undesirable Effects)

Adults and children older than 12 years of age with epilepsy.

Neurontin has been evaluated for safety in approximately 2000 subjects and patients and was well tolerated. Of these, 543 patients participated in controlled clinical trials.
The most commonly observed adverse events associated with the use of Neurontin in combination with other antiepileptic drugs, not seen in an equivalent frequency among placebo treated patients, were somnolence, dizziness, ataxia, fatigue and nystagmus.
Approximately 7% of the 2074 individuals who received Neurontin in the premarketing clinical trials discontinued treatment because of an adverse event. The adverse events most commonly associated with withdrawal were somnolence, ataxia, fatigue, nausea and/or vomiting and dizziness.

Incidence in controlled epilepsy clinical trials.

Table 3 lists the treatment emergent signs and symptoms that occurred in at least 1% of Neurontin treated patients with epilepsy participating in Neurontin placebo controlled trials. 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.

Other adverse events observed during all epilepsy clinical studies.

Those events that occurred in at least 1% of the study participants with epilepsy who received gabapentin as adjunctive therapy in any clinical study and that are not described in the previous section as frequently occurring treatment emergent signs and symptoms during placebo controlled studies are summarised below.

Body as a whole.

Asthenia, malaise, facial oedema.

Cardiovascular system.

Hypertension.

Digestive system.

Flatulence, anorexia, gingivitis.

Haematologic and lymphatic systems.

Purpura most often described as bruises resulting from physical trauma.

Musculoskeletal system.

Arthralgia.

Nervous system.

Vertigo, hyperkinesia, increased/ decreased or absent reflexes, paraesthesia, anxiety, hostility.

Respiratory system.

Pneumonia.

Urogenital system.

Urinary tract infection.

Special senses.

Abnormal vision, most often described as a visual disturbance.

Children from 3 to 12 years of age with epilepsy.

The most commonly observed adverse events reported with the use of Neurontin in combination with other antiepileptic drugs in children 3 to 12 years of age, not seen in equal frequency among placebo treated patients, were viral infection, fever, nausea and/or vomiting and somnolence.
Approximately 8% of the 292 children aged 3 to 12 years who received Neurontin in pre-approval clinical trials discontinued treatment because of an adverse event. The adverse events most commonly associated with withdrawal in children were somnolence (1.4%), hyperkinesia (1.0%) and hostility (1.0%). See Table 4.
Other events in more than 2% of children but equally or more frequent in the placebo group included pharyngitis, upper respiratory infection, headache, rhinitis, convulsions, diarrhoea, anorexia, coughing and otitis media.
Adverse events occurring during clinical trials in children treated with gabapentin that were not reported in adjunctive therapy trials in adults are as follows.

Body as a whole.

Dehydration, infectious mononucleosis.

Digestive system.

Hepatitis, oral moniliasis.

Haematologic and lymphatic systems.

Coagulation defect.

Nervous system.

Aura disappeared, occipital neuralgia.

Psychobiologic function.

Sleepwalking.

Respiratory system.

Pseudocroup, hoarseness.

Adults older than 18 years of age with neuropathic pain.

The most commonly observed adverse events reported with the use of Neurontin in adults older than 18 years of age with neuropathic pain, seen in at least twice the frequency among placebo treated patients, were dry mouth, peripheral oedema, weight gain, abnormal gait, amnesia, ataxia, confusion, dizziness, hypoaesthesia, somnolence, thinking abnormal, vertigo, rash and amblyopia.
Of the 821 adults who received Neurontin in the painful diabetic peripheral neuropathy and postherpetic neuralgia trials, 13.2% discontinued treatment because of an adverse event. The adverse events most commonly associated with withdrawal were dizziness (4.4%), somnolence (2.9%) and nausea (1.3%). See Table 5.

Post-marketing experience.

The following adverse events have been reported in patients receiving gabapentin post-marketing, however the data are insufficient to support an estimate of their incidence or to establish causation.
Sudden, unexplained deaths have been reported where a causal relationship to treatment with gabapentin has not been established. Additional post-marketing adverse events reported include blood creatine phosphokinase increased, rhabdomyolysis, abnormal liver function, acute kidney failure, agitation, allergic reaction including urticaria, alopecia, anaphylaxis, anaemia, angioedema, hyperglycemia and hypoglycemia (most often observed in patients with diabetes), breast hypertrophy, gynaecomastia, cardiac arrest, chest pain, convulsions, depersonalisation, drug rash with eosinophilia and systemic symptoms, erythema multiforme, fall, hypersensitivity including systemic reactions, hyponatraemia, jaundice, loss of consciousness, movement disorders such as choreoathetosis, dyskinesia and dystonia, myoclonus, palpitation, pancreatitis, renal impairment, speech disorder, sexual dysfunction (including changes in libido, ejaculation disorders and anorgasmia), Stevens-Johnson syndrome, tachycardia, thrombocytopenia, tinnitus, urinary incontinence and symptoms of psychosis such as delusions, hallucinations, and thinking abnormal.
Generalised oedema, hepatitis, hypotension, neuropathy/ peripheral neuropathy and syncope have been rarely reported.
Adverse events following the abrupt discontinuation of gabapentin have also been reported. The most frequently reported events were anxiety, insomnia, nausea, pain and sweating.
Some cases of hypomania have been reported after commencement of gabapentin. In each case, other anticonvulsants had been used concurrently, and symptoms of hypomania resolved following a reduction in dosage or cessation of the drug.

Reporting suspected adverse effects.

Reporting suspected adverse reactions after registration of the medicinal product is important. It allows continued monitoring of the benefit-risk balance of the medicinal product. Healthcare professionals are asked to report any suspected adverse reactions at www.tga.gov.au/reporting-problems.

4.2 Dose and Method of Administration

Dosage.

Epilepsy dosage for adults and children older than 12 years of age.

Initiation of treatment should be as add-on therapy. Gabapentin can be given orally with or without food.
In controlled clinical trials, the effective dose range was 900 mg/day to 1800 mg/day given in divided doses (three times a day).
Therapy may be initiated by administering 300 mg of Neurontin three times a day on day 1, as 300 mg capsules or half 600 mg tablets, or by titrating the dose as described below.
Titration to an effective dose can take place rapidly, over a few days, giving 300 mg Neurontin on day 1, 300 mg Neurontin twice a day on day 2, 300 mg Neurontin three times a day on day 3, as 300 mg capsules or half 600 mg tablets. Titration may be preferable for patients with renal impairment, patients with encephalopathy, patients on more than 2 other antiepileptic drugs and patients with multiple other medical problems.
To minimise potential side effects, especially somnolence, dizziness, fatigue and ataxia, the first dose on day 1 may be administered at bedtime. If necessary, the dose may be increased using 300 mg or 400 mg capsules or 600 mg or 800 mg tablets three times a day up to 2400 mg/day. Dosages up to 2400 mg/day have been well tolerated in long-term, open label clinical studies. The maximum time between doses in the three times a day schedule should not exceed 12 hours.

Neuropathic pain in adults older than 18 years of age.

The starting dose is 900 mg/day given in three daily divided doses, and titrated if necessary, based on response, up to a maximum dose of 3600 mg/day.

Dosage for children aged 3 to 12 years of age.

The effective dose of Neurontin is 25 mg/kg/day to 35 mg/kg/day given in three divided doses (3 times a day). Titration to an effective dose can take place over 3 days by giving 10 mg/kg/day on day 1, 20 mg/kg/day on day 2 and 30 mg/kg/day on day 3. Dosages up to 40 mg/kg/day to 50 mg/kg/day have been well tolerated in a long-term clinical study. Doses of 60 mg/kg/day have also been administered to a small number of children.

Dosage adjustment.

Dose adjustment in impaired renal function in patients with neuropathic pain or epilepsy.

Dose adjustment is recommended in patients with compromised renal function and/or in those undergoing haemodialysis (see Table 1).
For patients undergoing haemodialysis who have never received gabapentin, a loading dose of 300 mg to 400 mg is recommended, and then 200 mg to 300 mg of Neurontin following each 4 hours of haemodialysis.
Unlike other agents in this class, it is not necessary to monitor gabapentin plasma concentrations to optimise Neurontin therapy. Further, Neurontin may be used in combination with other antiepileptic drugs without concern for alteration of the plasma concentrations of gabapentin or serum concentrations of other antiepileptic drugs. 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.

4.7 Effects on Ability to Drive and Use Machines

Patients should be advised not to drive a car or operate potentially dangerous machinery until it is known that this medication does not affect their ability to engage in these activities.

4.9 Overdose

Signs and symptoms.

Symptoms of an overdose included somnolence, ataxia, dizziness, double vision, nystagmus, slurred speech, drowsiness, loss of consciousness, lethargy, mild hypotension and gastrointestinal symptoms including diarrhoea. Gabapentin overdose alone has not been reported to produce significant cardiotoxicity.
Overdoses as high as 108 g have been reported with full recovery following symptomatic therapy. Reduced absorption of gabapentin at higher doses may limit drug absorption at the time of overdosing and, hence, minimise toxicity from overdoses.

Treatment of overdosage.

There is no specific antidote for gabapentin; treatment is symptomatic. The patient should be monitored closely and given supportive care where necessary to maintain vital functions. Overdoses may involve other concurrent medications and should be treated accordingly.
Activated charcoal may reduce absorption of the drug if given within one hour after ingestion. In patients who are not fully conscious or have impaired gag reflex, consideration should be given to administering activated charcoal via nasogastric tube once the airway is protected.
Gabapentin can be removed by haemodialysis. Although haemodialysis 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.
Ipecac induced emesis is not recommended because of the potential for CNS depression.
For information on the management of overdose, contact the Poisons Information Centre on 13 11 26 (Australia).

7 Medicine Schedule (Poisons Standard)

S4.

6 Pharmaceutical Particulars

6.1 List of Excipients

Neurontin capsules.

Lactose monohydrate, purified talc, maize starch, gelatin, titanium dioxide, Opacode Blue S-1-4118.
300 mg capsule also contains: iron oxide yellow.
400 mg capsule also contains: iron oxide yellow, iron oxide red.

Neurontin tablets.

Poloxamer, copovidone, maize starch, magnesium stearate, candelilla wax, Opadry White YS-1-18111.

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.

6.3 Shelf Life

In Australia, information on the shelf life can be found on the public summary of the Australian Register of Therapeutic Goods (ARTG). The expiry date can be found on the packaging.

6.4 Special Precautions for Storage

Capsules: Store below 30°C.
Tablets: Store below 25°C.

6.5 Nature and Contents of Container

100 mg capsules: Available in PVC/PVDC/aluminium foil blister packs of 100 capsules.
300 mg capsules: Available in PVC/PVDC/aluminium foil blister packs of 4, 20 and 100 capsules.
400 mg capsules: Available in PVC/PVDC/aluminium foil blister packs of 100 capsules.
600 mg tablets: Available in PVC/PE/PVDC/aluminium foil or PVC/PVDC/aluminium foil blister packs of 20 and 100 tablets.
800 mg tablets: Available in PVC/PE/PVDC/aluminium foil or PVC/PVDC/aluminium foil blister packs of 100 tablets.
Not all presentations are available.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of by taking to your local pharmacy.

Summary Table of Changes