Consumer medicine information

GABARAN 600mg/800mg TABLETS; (GA-BA-RAN)

Gabapentin

BRAND INFORMATION

Brand name

Gabaran Tablets

Active ingredient

Gabapentin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using GABARAN 600mg/800mg TABLETS; (GA-BA-RAN).

What is in this leaflet

This leaflet answers some common questions aboutGABARAN tablets (gabapentin).

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 GABARAN against the benefits it is expected to have for you.

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

Keep this leaflet with this medicine.

You may need to read it again.

What GABARAN Tablets are used for

GABARAN contains gabapentin. Gabapentin belongs to a group of medicines used for treating epilepsy (antiepileptic medicines). These drugs are thought to work by controlling brain chemicals, which send signals to nerves so that convulsions do not happen.

Gabapentin also has analgesic effects. It may also be used for treating neuropathic pain (pain caused by damage to nerves).

Your doctor would have prescribed GABARAN tablets for one or more of the following:

  • To treat certain types of epilepsy (partial onset seizures) in combination with other antiepileptic medicines, when the condition is not controlled with other anti-epileptic medicines or there are unacceptable side effects.
  • To treat neuropathic pain (pain caused by damage to nerves). A variety of conditions can cause neuropathic pain, e.g., shingles, diabetes, trauma.

GABARAN 600 mg and 800 mg tablets will not be used to start your treatment. Your doctor will give you another brand of gabapentin when you begin your treatment. You will be givenGABARANtablets once your daily dose of gabapentin is 1800 mg (one 600 mg tablet three times a day) or more than 1800 mg.

Your doctor may have prescribed GABARAN tablets for another reason. Ask your doctor if you have any questions about why GABARAN tablets have been prescribed for you.

There is no evidence thatGABARAN tablets are addictive.

Gabapentin may make you sleepy or dizzy. This could affect your ability to drive a car or operate machinery.

Before you take GABARAN tablets

When you must not take it

Do not take GABARAN tablets if you are allergic to gabapentin or any of the inactive ingredients listed at the end of this leaflet. Symptoms of an allergic reaction may include skin rash, itchiness, shortness of breath, swelling of the tongue or face.

Do not take GABARAN tablets after the expiry date printed on the pack. If you take it after the expiry date has passed, it may not work as well. Do not take GABARAN if the tablets do not look quite right.

Do not take GABARAN tablets if the packaging is torn or shows signs of tampering.

Before you start to take it

Tell your doctor if you have any allergies to:

  • any other substances, such as foods, preservatives or dyes

Tell your doctor if you are pregnant or intend to become pregnant.

Like many other medicines, gabapentin 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 gabapentin, your doctor can help you decide whether or not to take it during pregnancy.

Tell your doctor if you are breast-feeding or planning to breast-feed

Your doctor will discuss the possible risks and benefits of using GABARAN during breast-feeding. 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.

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

  • You have mixed seizure and/or absence seizures disorder
  • You are pregnant, or planning to become pregnant, or are breast- feeding
  • You have had mental illness
  • You have problems with your kidneys

Your medicine also contains small amounts of an inactive ingredient called lactose monohydrate. If you have been told by your doctor that you have an intolerance to some sugars, contact your doctor before taking this medicine.

Tell your doctor if you plan to have blood/urine tests.

If you need a laboratory investigation such as blood test or urine test, do inform your doctor about the medicine you are taking.

If you have not told your doctor about any of the above, tell them before you take GABARAN tablets.

Taking other medicines

Tell your doctor if you are taking any other medicines, including medicines you buy without a prescription from a pharmacy, supermarket or health food shop.

GABARAN tablets are not expected to interact with other anti-epileptic medicines or the oral contraceptive pill.

Some medicines may interfere with the absorption or action of GABARAN tablets.

These include:

  • Antacids containing magnesium and aluminium (medicines for relieving symptoms of indigestion). These products can reduce the absorption of gabapentin.
  • Cimetidine (a medicine for indigestion)
  • Narcotic medicines (e.g. morphine)

These medicines may be affected byGABARAN tablets,or may affect how well it works. You may need to use different amounts of your medicine or you may need to take different medicines. Your doctor or pharmacist will be able to tell you what to do when taking/being given GABARAN tablets with other medicines.

Your doctor or pharmacist has more information on medicines to be careful with or avoid while takingGABARAN tablets.

How GABARAN tablets are given

How much to take

Your doctor will tell you how many tablets you will 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 ofGABARAN and slowly increase the dose to the lowest amount needed to control your epilepsy/convulsions or neuropathic pain.

Take your medicine as instructed by your doctor. Do not take more than the doctor told you to. Check the label carefully for how much to take and how often to take. Your pharmacist or doctor can help if you are not sure.

How to take it

Note: GABARAN tablets are available as 600 mg and 800 mg tablets . GABARAN 600 mg and 800 mg tablets may be used for administering gabapentin in the dose range of 1800 to 3600 mg/day. Lower strengths of gabapentin are available in other dose forms (e.g. gabapentin 300 and 400 mg capsules). GABARAN 600 mg and800 mg tablets should not be broken into two halves to administer lower doses.

Swallow the tablet whole with a full glass of water. GABARAN tablets may be taken with or without food. If you are taking antacids containing magnesium and aluminium, it is recommended that you take GABARAN tablets at least 2 hours after taking your indigestion medicine.

Adults

Epilepsy (adults and children aged over 12 years)

Your doctor would usually start your treatment with 300 mg gabapentin taken once a day on the first day, followed by 300 mg gabapentin taken twice a day on the second day, and 300 mg gabapentin taken three times a day on the third day. Your doctor may also advise you to take 300 mg gabapentin three times daily on the first day. Your doctor will use another brand of gabapentin to start your treatment.

Thereafter, your doctor may increase your dose over the next few days to a maximum of 800 mg of gabapentin, taken three times a day. GABARAN 600 mg and 800 mg tablets may be used by your doctor to give you 600 to 800 mg of gabapentin, three times a day, as a maintenance dose.

Neuropathic pain (adults over the age of 18 years)

Your doctor would usually start your treatment with 300 mg gabapentin taken three times a day. Thereafter, your doctor may increase your dose over the next few days to a maximum of 1200 mg of gabapentin, taken three times a day. GABARAN 600 mg and 800 mg tablets may be used by your doctor to give you 600 to 1200 mg of gabapentin, three times a day, as a maintenance dose.

If you are elderly or have kidney problems, your doctor may prescribe a lower dose for you.

If gabapentin treatment is to be discontinued or another anti-epileptic medicine is to be added, this would be done gradually over a period of at least one week.

Children

Epilepsy (children aged between 3 to 12 years)

The dose that is right for your child would be decided by the doctor, based on your child’s weight.

Children below 3 years of age

The safety of GABARAN in the treatment of epilepsy has not been established in children below 3 years of age.

The safety of GABARAN in the treatment of neuropathic pain has not been established in children and adolescents below 18 years of age.

When to take it

Take your GABARAN tablets at about the same time. Take the first days dose at bedtime for best results. Taking your tablets at the same time will have the best effect. It will also help you to remember when to take the tablets.

How long to take it

Continue taking GABARAN tablets until your doctor tells you to stop. GABARAN 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 GABARAN, or lower the dosage, without checking with your doctor. Do not let yourself run out of medicine over the weekend or on holidays.

StoppingGABARANsuddenly may cause unwanted 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, skip the dose you missed and take your next dose when you are meant to.

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

Do not double a dose to make up for the dose you have missed.

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

If you have trouble remembering when to take your medicine, ask your pharmacist for some hints.

If you take too much (Overdose)

Immediately telephone your doctor or the Poisons Information Centre (Telephone No: 13  11  26), or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else has taken too much of GABARAN tablets. Do this even if there are no signs of discomfort or poisoning.

You may need urgent medical attention. If you take too many GABARAN tablets, you may feel drowsy, weak, unsteady when walking, have double vision, slurred speech or diarrhoea. Keep this telephone number handy.

While you are using GABARAN tablets

Things you must remember

Take GABARAN tablets exactly as your doctor tells you to.

Try not to miss any doses and take the medicine even if you feel well.

Visit your doctor regularly for check-ups.

Tell all doctors, dentists and pharmacists who are treating you that you are taking GABARAN tablets.

If you are about to be started on any new medicine, tell your doctor or pharmacist that you are taking GABARAN tablets.

Tell your doctor if you are to undergo any blood or urine test.

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

Tell your doctor immediately if you have any suicidal thoughts or mood changes

Persons taking antiepileptic medicines, including gabapentin, may be more likely to think about killing themselves or actually doing so.

If you or someone you know demonstrate any of the following warning signs of suicide-related behaviour while taking GABARAN, contact a healthcare provider immediately, or even go to the nearest hospital for treatment:

  • thoughts or talk of death or suicide, or self-harm or harm to others
  • any recent attempts of self-harm
  • increase in aggressive behaviour, irritability or agitation

Things you must not do

Do not give this medicine to anyone else, even if they have the same condition as you.

Do not use GABARAN tablets to treat any other complaints unless your doctor tells you to.

Do not stop taking GABARAN tablets, or lower the dose, without first checking with your doctor.

Things to be careful of

Be careful driving or operating machinery until you know how GABARAN affects you.

Gabapentin may make you dizzy. This may affect your ability to drive or operate machinery. Make sure you know how you react to GABARAN tablets before you drive a car, operate machinery, or do anything else that could be dangerous if you are not alert.

Your doctor may suggest you avoid alcohol while you are being treated with GABARAN tablets.

Side effects

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

Ask your doctor or pharmacist any questions you may have.

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

  • Uncontrolled shaking (tremors), memory loss, abnormal thinking, confusion, dizziness, sleep disturbances, anxiety, nervousness, depressed mood, emotional lability, hostile behaviour, hallucinations, difficulty in speech, uncontrolled jerking of facial muscles (twitching), reduced co-ordination or slowed reactions, gait disturbances, irregular involuntary contraction of a muscle
  • Double vision, reduced vision, unusual jerky eye movements
  • Hoarseness of voice
  • Accidental injury, headache, unsteadiness, tiredness, decreased sensitivity to touch, weight gain, generalised weakness
  • Feeling sick (nausea), being sick (vomiting), constipation, diarrhoea (loose stools), pain in the belly, indigestion, wind (flatulence), increased or decreased appetite, dryness of mouth, white patches inside the mouth or on the tongue (oral thrush)
  • Chest infection, difficulty in breathing, sore throat
  • Ringing in the ears
  • Fast and irregular heart beat
  • Dizziness and/or light-headedness
  • Sweating
  • Pins and needles sensation, numbness
  • Joint pains, muscle aches, back ache
  • Loss of hair
  • Runny nose, cough
  • Easy fracture and dislocation of bones
  • Sexual inability in men (impotence)
  • Inability to hold urine
  • Fever, flu-like illness
  • Distorted teeth
  • Swelling of the hands or feet
  • High blood pressure
  • Excessive development of the breast in the male and female

These are the more common side effects of GABARAN tablets. These side effects are usually mild and occur at the start of treatment.

Tell your doctor immediately if you notice any of the following

  • Unusual bleeding or increased tendency to bleed, persistent sore throat and frequent infections, and/or anaemia
  • Sudden onset of severe abdominal pain associated with feeling sick (nausea) and being sick (vomiting) (manifestations of a condition called pancreatitis)
  • Swelling of face, ankles or other parts of the body, with decrease in the amount of urine passed
  • Yellowing of skin and whites of eyes with decreased appetite, abdominal pain
  • More frequent or more severe seizures (fits)
  • Myocardial Infarction (chest pain is more severe and prolonged than angina pain described above and may be associated with nausea (feeling sick), vomiting (being sick) and excessive sweating (occurs due to a complete blockade in one or more of the blood vessels, which supply the muscles of the heart, and the resulting failure to deliver oxygen for normal functioning of the heart)

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

  • Thoughts of suicide or self-harm
  • Symptoms of an allergic reaction may include rashes, hives, itching, chest constriction, shortness of breath or swelling of face, lips, tongue, hands/feet, fainting, fever.
  • Severe skin reactions with blisters, sores or ulceration
  • Rashes and hives with muscle and joint pains, and fever

These are very serious side effects. You may need urgent medical attention or hospitalisation. All these side effects are very rare.

Changes in laboratory tests

  • Increased blood sugar in diabetic patients
  • Abnormal liver function tests

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

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

After using it

Storage

Keep this medicine where young children cannot reach it.

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

Keep your GABARAN in a cool, dry place where it stays below 25°C. Do not store it, or any other medicine, in the bathroom or near a sink.

Do not leave it in the car on hot days.

Disposal

If your doctor tells you to stop taking GABARAN tablets or you find that they have passed their expiry date, ask your pharmacist what to do with any tablets that are left over.

Product description

What it looks like

GABARAN 600 mg are white to off-white, oval-shaped, biconvex film-coated tablets imprinted with 'G 600' in black ink on one side and plain on the other side. Available in packs of 100 tablets.

GABARAN 800 mg are white to off-white, oval-shaped, biconvex film-coated tablets imprinted with 'G 800' in black ink on one side and plain on the other side. Available in packs of 100 tablets.

Ingredients

Active ingredient

GABARAN 600 mg tablets - 600 mg of gabapentin

GABARAN 800 mg tablets - 800 mg of gabapentin

Inactive ingredients

Hydroxypropylcellulose, mannitol, crospovidone, purified talc, magnesium stearate, poloxamer, Opadry 20A59015, Opacode S-1-17823

Australian Registration Numbers

GABARAN 600 mg tablets blister pack – AUST R 121833

GABARAN 800 mg tablets blister pack – AUST R 121843

Sponsor

GABARAN Tablets are supplied in Australia by:

Ranbaxy Australia Pty Ltd.
Suite 4.02, Level 4, Building D
12 – 24 Talavera Rd
North Ryde, NSW 2113

GABARAN® is a registered trade mark owned by Ranbaxy Laboratories Limited.

This leaflet was prepared in May 2010.

BRAND INFORMATION

Brand name

Gabaran Tablets

Active ingredient

Gabapentin

Schedule

S4

 

Name of the medicine

Gabapentin.

Excipients.

Hydroxypropylcellulose, mannitol, crospovidone, purified talc, magnesium stearate, poloxamer, Opadry 20A59015, Opacode S-1-17823.

Description

CAS Number: 60142-96-3. Gabaran tablets contain gabapentin, which is chemically designated as 1-(aminomethyl) cyclohexaneacetic acid, with a molecular formula of C9H17NO2 and a molecular weight of 171.24. Gabapentin is a white to off-white crystalline solid with a pKa1 of 3.7 and a pKa2 of 10.7. It is freely soluble in water and both basic and acidic aqueous solutions. The log of the partition coefficient (n-octanol/0.05 M phosphate buffer) at pH 7.4 is -1.25.
Gabaran tablets contain following inactive ingredients: hydroxypropylcellulose, mannitol, crospovidone, purified talc, magnesium stearate, poloxamer, Opadry 20A59015, Opacode S-117823.

Pharmacology

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.

Pharmacokinetics.

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 decreased. A 400 mg dose, for example, is about 25% less bioavailability than a 100 mg dose. Over the recommended dose range of 300 to 600 mg three times a day, however, the difference in bioavailability is 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, 2400, 3600, 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 cerebrospinal fluid were approximately 20% of the corresponding plasma concentrations.

Elimination.

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.
Dosage adjustment in patients with compromised renal function or undergoing haemodialysis is recommended (see Dosage and Administration).

Special populations.

Paediatric patients.

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

Elderly patients.

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 under 30 years of age to about 125 mL/min in those over 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 aged related compromised renal function.

Patients with renal insufficiency.

Subjects with renal insufficiency (mean creatinine clearance ranging from 13-114 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.

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 Dosage and Administration).

Clinical Trials

The effectiveness of gabapentin as adjunctive therapy was established in three multi-centre, 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 of 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, gabapentin or placebo was then added on to the existing therapy during a 12-week treatment period. Effectiveness was assessed primarily on the basis of the percent of patients with a 50% or greater reduction in seizure frequency from baseline to treatment (the responder rate) and a derived measure called response ratio, a measure of change defined as (T - B)/ (T + B), where B is the patient's baseline seizure frequency and T is the patient'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 gabapentin 1200 mg/day three times a day with placebo. Responder rate was 23% (14/61) in the gabapentin group and 9% (6/66) in the placebo group; the difference between groups was statistically significant. Response ratio was also better in the gabapentin 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 three times a day. Gabapentin (N = 101) with placebo (N = 98). Additional smaller gabapentin 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 gabapentin 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 gabapentin 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 gabapentin 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 gabapentin 900 mg/day three times a day. (N = 111) and placebo (N = 109). An additional gabapentin 1200 mg/day dosage group (N = 52) provided dose-response data. A statistically significant difference in responder rate was seen in the gabapentin 900 mg/day group (22%) compared to that in the placebo group (10%). Response ratio was also statistically significantly superior in the gabapentin 900 mg/day group (-0.119) compared to that in the placebo group (-0.027), as was response ratio in 1200 mg/day gabapentin (-0.184) compared to placebo.
A one week, prospective, multi-centre, randomised, double-blind, placebo lead-in, parallel-group study compared the tolerability of gabapentin 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, non titrated = 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 non titrated group reporting the higher incidence, however, it did not lead to increased discontinuation in this group.
The safety and efficacy of gabapentin 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, multicentric 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 gabapentin (25 to 35 mg/kg/day) or placebo added to their baseline AEDs. The primary analysis of RRatio (MITT population) demonstrated that gabapentin 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.
The efficacy and safety of gabapentin for the treatment of neuropathic pain in adults over 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 gabapentin in the treatment of painful diabetic peripheral neuropathy and the other study was conducted in patients with post-herpetic neuralgia. The studies were of a similar design. Following a baseline screening week and randomisation, gabapentin was titrated from 900 mg/day to 1800 mg, 2400 mg 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 gabapentin 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 gabapentin and 1.4 in patients receiving placebo (p < 0.001). In the post-herpetic neuralgia study, mean pain score decreased by 2.1 in patients receiving gabapentin and 0.5 in patients receiving placebo (p < 0.001). Gabapentin 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 gabapentin.

Indications

Gabaran is indicated for the maintenance 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 anti-epileptic drugs.
Gabaran is also indicated for the maintenance treatment of neuropathic pain.

Contraindications

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

Precautions

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 not generally considered effective in the treatment of absence seizures and may exacerbate these seizures in some patients. Consequently, gabapentin should be used with caution in patients who have mixed seizure disorders that include absence seizures.
Patients who require concomitant treatment with morphine may experience increases in gabapentin concentrations. Patients should be carefully observed for signs of CNS depression, such as somnolence, and the dose of gabapentin or morphine should be reduced appropriately.

Information for patients.

To assure safe and effective use of gabapentin, the following information and instructions should be given to patients:
1. Inform your physician about any prescription or non-prescription medications, alcohol, or drugs you are now taking or plan to take during your treatment with gabapentin.
2. No teratogenic effects have been found in animals. However, the risk to the human foetus 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. Gabapentin 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 gabapentin 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.

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.

Effect on driving and operating machinery.

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.

Use in children.

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.

Use in pregnancy.

(Category B1)
The risk of having an abnormal child 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 prepregnancy 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.
Reproduction studies in mice at doses up to 3000 mg/kg/day and in rats at doses up to 2000 mg/kg/day revealed no evidence of impaired fertility or harm to the foetus due to gabapentin administration. 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 tolerated dose of 2400 mg/day. In rabbits given 60, 300 or 1500 mg/kg/day gabapentin 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 impaired fertility or harm to the foetus was observed. There are, however, no adequate and well-controlled studies in pregnant women. Therefore, this drug should be used during pregnancy only if clearly needed.

Use in lactation.

Gabapentin is excreted in human milk. In a peri-postnatal study in rats at doses of 500, 1000 and 2000 mg/kg/day, there was a dose related increase in the incidence of hydroureter 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. Gabapentin should be used in nursing mothers only if the benefits clearly outweigh the risks.

Suicidal behaviour and ideation.

Antiepileptic drugs, 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 1 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 of 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.

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 two 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 drug concentrations and areas under the concentration time curve in rats at 2000 mg/kg/day are 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 are low grade malignancies, 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.

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.

Effect on fertility.

No adverse effects on fertility or reproduction were observed in rats at doses up to 2000 mg/kg/day.

Interactions

In pharmacokinetic studies, no interactions were observed between gabapentin and phenobarbital, phenytoin, valproic acid, or carbamazepine.
Gabapentin did not influence the steady-state pharmacokinetics of norethindrone and ethinyl estradiol when administered concomitantly with an oral contraceptive containing these two drugs.

Antacid.

Coadministration of gabapentin with antacid reduced gabapentin bioavailability by about 20%.

Cimetidine.

In the presence of cimetidine at 300 mg QID, the mean apparent oral clearance of gabapentin fell by 14% and creatinine clearance by 10%. Thus cimetidine appeared to alter the renal excretion of both gabapentin and creatinine, an endogenous marker of renal function. 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 gabapentin capsule, mean gabapentin AUC increased by 44% compared to gabapentin administered without morphine. Morphine pharmacokinetic parameter values were not affected by administration of gabapentin 2 hours after morphine. The magnitude of interaction at other doses is not known.

Adverse Effects

Adults and children over 12 years of age.

Gabapentin 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 gabapentin 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 gabapentin 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 clinical trials.

The following Table 2 lists treatment-emergent signs and symptoms that occurred in at least 1% of gabapentin-treated patients with epilepsy participating in gabapentin placebo-controlled trials. In these studies, either gabapentin 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 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 summarized below.

Body as a whole.

Asthenia, malaise, facial edema.

Cardiovascular system.

Hypertension.

Digestive system.

Flatulence, anorexia, gingivitis.

Haemic, 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.

Children from 3 to 12 years of age.

The most commonly observed adverse events reported with the use of gabapentin 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 (Table 3).
Approximately 8% of the 292 children age 3 to 12 years who received gabapentin 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%).
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, diarrhea, 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:

Body as a whole.

Dehydration, infectious mononucleosis.

Digestive system.

Hepatitis, oral moniliasis.

Haemic and lymphatic system.

Coagulation defect.

Nervous system.

Aura disappeared, occipital neuralgia.

Psychobiologic function.

Sleepwalking.

Respiratory system.

Pseudo-croup, hoarseness.

Adults over 18 years of age with neuropathic pain.

The most commonly observed adverse events reported with the use of gabapentin in adults over 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, abnormal thinking, vertigo, rash, and amblyopia (Table 4).
Of the 821 adults who received gabapentin, in the painful diabetic peripheral neuropathy and post-herpetic 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%).

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 abnormal liver function, acute kidney failure, allergic reaction including urticaria, alopecia, anaemia, angioedema, blood glucose fluctuations in patients with diabetes, breast hypertrophy, gynaecomastia, cardiac arrest, chest pain, convulsions, depersonalisation, erythema multiforme, jaundice, movement disorders such as choreoathetosis, dyskinesia and dystonia, myoclonus, palpitation, pancreatitis, renal impairment, speech disorder, sexual dysfunction, 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.

Dosage and Administration

Note.

Gabaran tablets are available as 600 mg and 800 mg unscored tablets and should not be broken into half. They are not intended as a substitute for gabapentin 300 mg and 400 mg capsules which are used for dose titration or in lower daily dose regimens. Gabaran 600 mg and 800 mg Tablets may be used for administering gabapentin in the dose range of 1800 to 3600 mg/day. Other brands of gabapentin should be used for administering doses below 1800 mg/day.

Epilepsy.

Gabapentin dosage for adults and children over 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 to 1800 mg/day given in divided doses (three times a day).
Therapy may be initiated by administering 300 mg of gabapentin three times a day on Day 1, or by titrating the dose as described below: Titration to an effective dose can take place rapidly, over a few days, giving 300 mg gabapentin on Day 1, 300 mg gabapentin twice a day on Day 2, 300 mg gabapentin three times a day on Day 3. Titration may be preferable for patients with renal impairment, patients with encephalopathy, patients on more than 2 other anti-epileptic 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 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 (over 18 years of age).

The starting dose is 900 mg/day given as three daily divided doses of gabapentin 300 mg, and titrated if necessary, based on response, up to a maximum dose of 3600 mg/day.

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

Dosage adjustment is recommended in patients with compromised renal function or those undergoing haemodialysis (see Table 5).
For patients undergoing hemodialysis who have never received gabapentin, a loading dose of 300 to 400 mg is recommended, then 200 to 300 mg of gabapentin following each 4 hours of hemodialysis.

Dosage for children aged 3 to 12 years of age.

The effective dose of gabapentin is 25 to 35 mg/kg/day given in 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 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.
Unlike other agents in this class, it is not necessary to monitor gabapentin plasma concentrations to optimise gabapentin therapy. Further, gabapentin 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 gabapentin is discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of one week.

Overdosage

Symptoms.

Symptoms of an overdose included somnolence, ataxia, dizziness, double vision, nystagmus, slurred speech, drowsiness, 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.

Management.

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.
Contact the Poisons Information Centre for advice on the management of an overdose.

Presentation

Gabaran White to off-white, oval shaped, biconvex film-coated tablets imprinted with 'G 600' in black ink on one side and plain on the other side, containing 600 mg of gabapentin.
Gabaran White to off-white, oval shaped, biconvex film-coated tablets imprinted with 'G 800' in black ink on one side and plain on the other side, containing 800 mg of gabapentin.
The tablets are supplied in blister pack and HDPE bottle pack containing 50 and 100 tablets.

Storage

Store below 25°C.

Poison Schedule

S4.