Consumer medicine information

Gabapentin Sandoz

Gabapentin

BRAND INFORMATION

Brand name

Gabapentin Sandoz

Active ingredient

Gabapentin

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Gabapentin Sandoz.

SUMMARY CMI

Gabapentin Sandoz®

Consumer Medicine Information (CMI) summary

The full CMI on the next page has more details. If you are worried about using this medicine, speak to your doctor or pharmacist.

WARNING: Important safety information is provided in a boxed warning in the full CMI. Read before using this medicine.

1. Why am I using Gabapentin Sandoz?

Gabapentin Sandoz contains the active ingredient gabapentin. Gabapentin Sandoz is used to control epilepsy and treat neuropathic pain. For more information, see Section 1. Why am I using Gabapentin Sandoz? in the full CMI.

2. What should I know before I use Gabapentin Sandoz?

Do not use if you have ever had an allergic reaction to gabapentin or any of the ingredients listed at the end of the CMI.

Talk to your doctor if you have any other medical conditions, take any other medicines, or are pregnant or plan to become pregnant or are breastfeeding. For more information, see Section 2. What should I know before I use Gabapentin Sandoz? in the full CMI.

3. What if I am taking other medicines?

Some medicines may interfere with Gabapentin Sandoz and affect how it works. A list of these medicines is in Section 3. What if I am taking other medicines? in the full CMI.

4. How do I use Gabapentin Sandoz?

  • Your doctor will tell you how many capsules you need to take each day. This may depend on your age, your condition and whether or not you are taking any other medicines.
  • Swallow the capsules whole with a full glass of water.

More instructions can be found in Section 4. How do I use Gabapentin Sandoz? in the full CMI.

5. What should I know while using Gabapentin Sandoz?

Things you should do
  • Remind any Remind any doctor, dentist or pharmacist, surgeon, or anaesthetist you visit that you are using Gabapentin Sandoz.
  • 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.
Things you should not do
  • Do not stop taking Gabapentin Sandoz or lower the dose without checking with your doctor.
Driving or using machines
  • Do not drive, operate machinery, ride a bike as Gabapentin Sandoz may cause drowsiness, dizziness, light-headedness or sleepiness in some people.
Drinking alcohol
  • Avoid alcohol as it can make you more sleepy, dizzy or light-headed.
Looking after your medicine
  • Keep your medicine in a cool dry place where the temperature stays below 30°C.
  • Keep your capsules in the pack until it is time to take them.

For more information, see Section 5. What should I know while using Gabapentin Sandoz? in the full CMI.

6. Are there any side effects?

Common side effects include dizziness, light-headedness, feeling tired, drowsy, unfriendliness, unusually overactive, forgetfulness, loss of concentration, confusion, difficulty speaking, weight change, constipation, diarrhoea, nausea, vomiting, indigestion, dry mouth, red swollen gums, muscle pain, cramps, back pain, swelling hand or feet, runny or blocked nose, fever, bronchitis, lung infection, sore throat, coughing. Serious side effects include unusual changes in mood or behaviour, increased irritability or agitation, depression, seeing or hearing things that are not there, blurred or double vision, uncontrollable jerky eye movements, difficulty seeing, fever, severe chills, sore throat or mouth ulcers, trouble breathing, loss of consciousness, severe seizures, chest pain, fast heart rate, sudden signs of allergy, severe skin rash, high body temperature enlarged lymph nodes. For more information, including what to do if you have any side effects, see Section 6. Are there any side effects? in the full CMI.

WARNING: Before taking Gabapentin Sandoz, tell your doctor if you have a history of drug abuse. Gabapentin Sandoz poses risks of abuse and dependence. Using Gabapentin Sandoz with other medicines that can make you feel drowsy such as sleeping tablets and other pain relievers (e.g. benzodiazepines and opioids), antihistamines, antidepressants, antipsychotics, cannabis, and alcohol may result in severe drowsiness, decreased awareness, breathing problems, coma and death. If you have any concern about taking this medicine, speak to your doctor.



FULL CMI

Gabapentin Sandoz®

Active ingredient(s): gabapentin

Consumer Medicine Information (CMI)

This leaflet provides important information about using Gabapentin Sandoz. You should also speak to your doctor or pharmacist if you would like further information or if you have any concerns or questions about using Gabapentin Sandoz.

Where to find information in this leaflet:

1. Why am I using Gabapentin Sandoz?
2. What should I know before I use Gabapentin Sandoz?
3. What if I am taking other medicines?
4. How do I use Gabapentin Sandoz?
5. What should I know while using Gabapentin Sandoz?
6. Are there any side effects?
7. Product details

1. Why am I using Gabapentin Sandoz?

Gabapentin Sandoz contains the active ingredient gabapentin. Gabapentin Sandoz belongs to a group of medicines called anticonvulsants.

Gabapentin Sandoz 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.

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

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

Gabapentin Sandoz also has pain relieving effects.

Your doctor may have prescribed Gabapentin Sandoz 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 Gabapentin Sandoz for another reason.

Gabapentin Sandoz may lead to dependence on this medicine. Ask your doctor if you have any questions about why Gabapentin Sandoz has been prescribed for you.

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.

2. What should I know before I use Gabapentin Sandoz?

Warnings

When you must not take Gabapentin Sandoz

Do not use Gabapentin Sandoz if:

  • you are allergic to gabapentin, or 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.
    Always check the ingredients to make sure you can use this medicine.
  • the expiry date printed on the pack has passed or if the packaging is torn or shows signs of tampering.

Check with your doctor if you:

  • have allergies to any other medicines, especially barbiturates or any other anticonvulsant medicines or any other substances, such as foods, preservatives or dyes.
  • have any other medical conditions:
    - kidney problems
    - mixed seizure disorders that include absence seizures.
  • take any medicines for any other condition.
  • have a history of drug abuse and/or psychiatric disorders.
    - Gabapentin Sandoz poses risks of abuse and dependence. Your body may become used to you taking Gabapentin Sandoz and this may result in physical dependence. It means that you may experience withdrawal symptoms if you stop taking Gabapentin Sandoz suddenly. So it is important to strictly follow the directions given by your doctor.
  • are pregnant or plan to become pregnant.
  • are breast-feeding or plan to breast-feed.
  • if you notice any of the symptoms related to these serious skin reactions described in section 6 under table titled "Serious side effects", stop using gabapentin and seek medical attention immediately.
    - Serious skin rashes including Stevens-Johnson syndrome, toxic epidermal necrolysis and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported in association with gabapentin.

During treatment, you may be at risk of developing certain side effects. It is important you understand these risks and how to monitor for them. See additional information under Section 6. Are there any side effects?

Pregnancy and breastfeeding

Check with your doctor if you are pregnant or intend to become pregnant.

Gabapentin Sandoz 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 this medicine, your doctor can help you decide whether or not to take it during pregnancy.

Gabapentin Sandoz passes into breast milk. The effect on your breast-fed baby is unknown.

Talk to your doctor if you are breastfeeding or intend to breastfeed.

If you do breastfeed, watch your baby carefully.

If your baby develops a skin rash, becomes sleepy or has unusual symptoms, don't breastfeed again until you speak to your doctor.

Your doctor will discuss the risks and benefits of breastfeeding with you.

If you have not told your doctor about any of the above, tell them before you start taking Gabapentin Sandoz.

3. What if I am taking other medicines?

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

Some medicines may interfere with Gabapentin Sandoz and affect how it works.

Some medicines may be affected by Gabapentin Sandoz 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.

Gabapentin Sandoz and certain other medicines may influence each other.

Using Gabapentin Sandoz with other medicines that can make you feel drowsy, such as sleeping tablets and other pain relievers (e.g. benzodiazepines and opioids), antihistamines, antidepressants, antipsychotics, cannabis, and alcohol may result in severe drowsiness, decreased awareness, breathing problems, coma and death.

Your doctor will minimise the dose and duration of use; and monitor you for signs and symptoms of breathing difficulties and sedation.

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.

Check with your doctor or pharmacist if you are not sure about what medicines, vitamins or supplements you are taking and if these affect Gabapentin Sandoz.

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

4. How do I use Gabapentin Sandoz?

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, ask your doctor or pharmacist for help.

How much to take

  • Your doctor will tell you how many capsules 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 of Gabapentin Sandoz and slowly increase the dose to the lowest amount needed to control your epilepsy/convulsions or neuropathic pain.
  • Follow the instructions provided and use Gabapentin Sandoz until your doctor tells you to stop.

When to take Gabapentin Sandoz

  • Gabapentin Sandoz should be used at about the same time each day.
  • Taking it at the same time each day will have the best effect. It will also help you remember when to take it.
  • If you are taking Gabapentin Sandoz three times a day, do not allow more than 12 hours between doses.
  • It does not matter if you take this medicine before or after food.

How to take Gabapentin Sandoz

  • Swallow the capsules whole with a full glass of water.

How to long to take Gabapentin Sandoz

  • Continue taking your medicine for as long as your doctor tells you.
  • This medicine 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 Gabapentin Sandoz, or lower the dose, without checking with your doctor. Do not let yourself run out of medicine over the weekend or holidays.
  • Stopping Gabapentin Sandoz suddenly may worsen your condition or increase your chance of experiencing withdrawal symptoms, such as sleeplessness, headache, nausea (feeling sick), anxiety, excessive sweating or diarrhoea (runny stools). If appropriate, your doctor will slowly reduce your dose before you can stop taking it completely.

If you forget to use Gabapentin Sandoz

Gabapentin Sandoz should be used regularly at the same time each day. If you miss your dose at the usual time, take it as soon as you remember, and then go back to taking Gabapentin Sandoz as you would normally.

Otherwise 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.

Do not take a double dose to make up for the dose 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 when to take your medicine, ask your pharmacist for help.

If you use too much Gabapentin Sandoz

If you think that you have used too much Gabapentin Sandoz, you may need urgent medical attention.

You should immediately:

  • phone the Poisons Information Centre
    (by calling 13 11 26), or
  • contact your doctor, or
  • go to the Emergency Department at your nearest hospital.

You should 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.

5. What should I know while using Gabapentin Sandoz?

Things you must do

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

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

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

If you feel Gabapentin Sandoz is not helping your condition, tell your doctor. Your doctor may need to change your medicine.

If, for any reason, you have not taken Gabapentin Sandoz exactly as prescribed, tell your doctor. Otherwise, your doctor may change your treatment unnecessarily.

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

Call your doctor straight away 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 Gabapentin Sandoz, 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.
    Any mention of suicide or violence must be taken seriously.
  • you or someone you know is demonstrating these warning signs and symptoms of suicide while taking Gabapentin Sandoz, contact your doctor or a mental health professional right away.
  • you become pregnant while taking Gabapentin Sandoz.

Remind any doctor, dentist or pharmacist, surgeon you visit that you are using Gabapentin Sandoz, if you are going to have any surgery or procedure (including dental surgery).

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 Gabapentin Sandoz to treat any other complaints unless your doctor tells you to.
  • Do not give your medicine to anyone else, even if their symptoms seem similar to yours or they have the same condition as you.
  • Do not stop taking your medicine or lower the dose without checking with your doctor.

Stopping Gabapentin Sandoz 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.

Driving or using machines

Be careful before you drive or use any machines or tools until you know how Gabapentin Sandoz affects you.

As with other anticonvulsant medicines, Gabapentin Sandoz may cause drowsiness, dizziness, light-headedness or sleepiness in some people. Make sure you know how you react to this medicine 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.

Drinking alcohol

Tell your doctor if you drink alcohol.

Be careful when drinking alcohol while you are taking this medicine.

Combining Gabapentin Sandoz and alcohol can make you more sleepy, dizzy or light headed. Your doctor may suggest you avoid alcohol while you are being treated with Gabapentin Sandoz.

Looking after your medicine

  • Keep your medicine in a cool dry place where the temperature stays below 30°C.
  • If you take the capsules out of its original container it may not keep well.

Follow the instructions in the carton on how to take care of your medicine properly.

Store it in a cool dry place away from moisture, heat or sunlight; for example, do not store it:

  • in the bathroom or near a sink, or
  • in the car or on window sills.

Keep it where young children cannot reach it.

A locked cupboard at least one-and-a-half metres above the ground is a good place to store medicines.

Getting rid of any unwanted medicine

If you no longer need to use this medicine, your doctor or pharmacist tells you to stop taking, it is out of date or damaged, take it to any pharmacy for safe disposal.

Do not use this medicine after the expiry date.

6. Are there any side effects?

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

All medicines can have side effects. If you do experience any side effects, most of them are minor and temporary. However, some side effects may need medical attention.

It can be difficult to tell whether side effects are the result of taking this medicine; 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.

See the information below and, if you need to, ask your doctor or pharmacist if you have any further questions about side effects.

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

Less serious side effects

The below list includes the more common side effects of Gabapentin Sandoz. They are usually mild and short-lived.

Less serious side effectsWhat to do
  • dizziness* or light-headedness
  • feeling tired or drowsy*
  • unfriendliness*
  • being unusually overactive*
  • forgetfulness, loss of concentration or confusion
  • difficulty speaking
  • changes in your weight*
  • constipation or diarrhoea
  • nausea and/or vomiting*, indigestion
  • dry mouth, red swollen gums
  • muscle pain or cramps, back pain
  • swelling of hands or feet
  • runny or blocked nose
  • fever*
  • bronchitis*, lung infection*
  • sore throat and discomfort when swallowing, coughing.
Speak to your doctor if you have any of these less serious side effects and they worry you.

Serious side effects

Serious side effectsWhat to do
  • 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
  • reddish non-elevated, target-like or circular patches on the trunk, often with central blisters, skin peeling, ulcers of mouth, throat, nose, genitals and eyes. These serious skin rashes can be preceded by fever and flu-like symptoms (Stevens-Johnson syndrome, toxic epidermal necrolysis).
  • widespread rash, high body temperature and enlarged lymph nodes (DRESS syndrome or drug hypersensitivity syndrome).
Tell your doctor as soon as possible and seek medical attention immediately if you notice any of the serious side effects.

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

Very serious side effects

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

Very serious side effectsWhat to do
  • 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.
Call your doctor straight away, or go straight to the Emergency Department at your nearest hospital if you notice any of these very serious side effects.

Tell your doctor or pharmacist if you notice anything else that may be making you feel unwell.

Other side effects not listed here may 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.

Reporting side effects

After you have received medical advice for any side effects you experience, you can report side effects to the Therapeutic Goods Administration online at www.tga.gov.au/reporting-problems. By reporting side effects, you can help provide more information on the safety of this medicine.

Always make sure you speak to your doctor or pharmacist before you decide to stop taking any of your medicines.

7. Product details

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

What Gabapentin Sandoz contains

Active ingredient
(main ingredient)		gabapentin
Other ingredients
(inactive ingredients)		pregelatinised maize starch
maize starch
purified talc
colloidal anhydrous silica
titanium dioxide
sodium lauryl sulfate
gelatin
iron oxide yellow
iron oxide red (400 mg capsule only)
Potential allergensThis medicine does not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Do not take this medicine if you are allergic to any of these ingredients.

What Gabapentin Sandoz looks like

Gabapentin Sandoz 300 mg– yellow capsules, available in blister packs of 100 capsules (Aust R 157197).

Gabapentin Sandoz 400 mg– brown capsules, available in blister packs of 100 capsules (Aust R 157195).

Who distributes Gabapentin Sandoz

Sandoz Pty Ltd
100 Pacific Highway
North Sydney, NSW 2060
Australia
Tel 1800 726 369

This leaflet was prepared in January 2024.

® Registered Trade Mark. The trade marks mentioned in this material are the property of their respective owners.

Published by MIMS March 2024

BRAND INFORMATION

Brand name

Gabapentin Sandoz

Active ingredient

Gabapentin

Schedule

S4

 

1 Name of Medicine

Gabapentin.

2 Qualitative and Quantitative Composition

Each Gabapentin Sandoz 100 mg capsule contains 100 mg of gabapentin.
Each Gabapentin Sandoz 300 mg capsule contains 300 mg of gabapentin.
Each Gabapentin Sandoz 400 mg capsule contains 400 mg of gabapentin.
For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Gabapentin Sandoz 100 mg* capsules.

Size 3 hard gelatin capsules with white body and cap.

Gabapentin Sandoz 300 mg capsules.

Size 1 hard gelatin capsules with yellow body and cap.

Gabapentin Sandoz 400 mg capsules.

Size 0 hard gelatin capsules with brown body and cap.
* Gabapentin Sandoz 100 mg capsules are not marketed in Australia.

4 Clinical Particulars

4.1 Therapeutic Indications

Gabapentin Sandoz 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 medicines.
Gabapentin Sandoz is indicated for the treatment of neuropathic pain.

4.2 Dose and Method of Administration

Dosage.

Epilepsy.

Adults and children over 12 years of age.

Initiation of treatment should be as add-on therapy.
In controlled clinical trials, the effective dose range was 900 to 1,800 mg/day given in divided doses (three times a day).
Therapy may be initiated by administering gabapentin 300 mg three times daily 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 gabapentin 300 mg on day 1, gabapentin 300 mg twice a day on day 2 and gabapentin 300 mg three times a day on day 3. Titration may be preferable for patients with renal impairment, patients with encephalopathy, patients on more than two other antiepileptic medicines 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 or 400 mg capsules three times a day up to 2,400 mg/day. Dosages up to 2,400 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.

Adults (over 18 years of age).

The starting dose is 900 mg/day given as three daily divided doses, and titrated if necessary, based on response, up to a maximum dose of 3,600 mg/day.

Children aged 3 to 12 years of age.

The effective dose of gabapentin is 25 to 35 mg/kg/day given in divided doses (three times a day). Titration to an effective dose can take place over three 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.

Method of administration.

Gabapentin can be given orally with or without food.

Dosage adjustment.

Renal impairment.

Dosage adjustment is recommended in patients with neuropathic pain or epilepsy who have compromised renal function or who are undergoing haemodialysis. (See Table 1.)
For patients undergoing haemodialysis who have never received gabapentin, a loading dose of 300 to 400 mg is recommended, then gabapentin 200 to 300 mg following each four hours of haemodialysis.
Unlike other agents in this class, it is not necessary to monitor gabapentin plasma concentrations to optimise Gabapentin Sandoz therapy. Further, Gabapentin Sandoz may be used in combination with other anti-epileptic drugs without concern for alteration of the plasma concentration of gabapentin or serum concentrations of other anti-epileptic drugs.

Discontinuation of Gabapentin Sandoz.

If Gabapentin Sandoz is discontinued and/or an alternate anticonvulsant medication is added to the therapy, this should be done gradually over a minimum of 1 week (see Section 4.4 Special Warnings and Precautions for Use, Discontinuation).

4.3 Contraindications

Gabapentin Sandoz is contraindicated in patients who have demonstrated hypersensitivity to gabapentin or the inactive ingredients in the capsules.

4.4 Special Warnings and Precautions for Use

Although there is no evidence of rebound seizures with gabapentin, abrupt withdrawal of anticonvulsants in epileptic patients may precipitate status epilepticus. When in the judgment of the doctor 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.
As with other antiepileptic medicinal products, some patients may experience an increase in seizure frequency or the onset of new types of seizures with gabapentin.
As with other antiepileptics, attempts to withdraw concomitant anti-epileptics in treatment refractory patients on more than one anti-epileptic, in order to reach gabapentin monotherapy have a low success rate.
Gabapentin is not generally considered effective against primary generalised seizures such as 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.
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 including opioids with gabapentin increases the risk of respiratory depression.

Concomitant use with opioids and other CNS depressants.

Patients who require concomitant treatment with opioids may experience increases in gabapentin concentrations. Concomitant use of opioids may result in severe sedation, respiratory depression, coma and death. Limit dosages and durations of gabapentin to the minimum required to achieve desired therapeutic effect. Patients who require concomitant treatment with CNS depressants, including opioids should be carefully observed for signs of CNS depression, such as somnolence, sedation and respiratory depression; and the dose of gabapentin or concomitant treatment with CNS depressants including opioids should be reduced appropriately (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions, Concomitant use with opioids and other CNS depressants).
Caution is advised when prescribing gabapentin concomitantly with opioids due to risk of CNS depression. In a population-based, observational, nested case-control study of opioid users, co-prescription of opioids and gabapentin was associated with an increased risk for opioid-related death compared to opioid prescription use alone (adjusted odds ratio [aOR], 1.49 [95% CI, 1.18 to 1.88, p < 0.001]).

Suicidal behaviour and ideation.

Antiepileptic drugs, including gabapentin, increase the risk of suicidal thoughts or behaviours 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% Cl: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 of worsening of the signs and symptoms of depression, any unusual changes in mood or behaviour, or emergence of suicidal thoughts, behaviour, or thoughts about self-harm. Behaviours of concern should be reported immediately to the treating doctor.

Severe cutaneous adverse reactions (SCARs).

SCARs including Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug rash with eosinophilia and systemic symptoms (DRESS), which can be life-threatening or fatal, have been reported rarely in association with gabapentin treatment. At the time of prescribing, patients should be advised of the signs and symptoms and monitored closely for skin reactions. If signs and symptoms suggestive of these reactions appear, gabapentin should be withdrawn immediately, and an alternative treatment considered (as appropriate).
If the patient has developed a serious reaction such as SJS, TEN or DRESS with the use of gabapentin, treatment with gabapentin must not be restarted at any time.

Anaphylaxis.

Gabapentin 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 gabapentin and seek immediate medical care should they experience signs or symptoms of anaphylaxis.

Abuse potential or dependence.

Gabapentin is a potential drug of abuse and dependence.
There have been post-market reports of overdose and deaths among users of gabapentin, particularly with concomitant use of other sedating medicines, such as opioids and/or benzodiazepines.
The risk of abuse of gabapentin should particularly be monitored among current or past opioids and/or benzodiazepine users.
Patients should be carefully evaluated for a history of substance abuse and/or psychiatric disorders prior to being prescribed gabapentin and observed for signs of gabapentin abuse (e.g. development of tolerance, increase in dose, drug seeking behaviour).

Discontinuation.

Withdrawal symptoms have been observed in some patients after discontinuation of gabapentin, including severe symptoms in patients taking high doses. Withdrawal symptoms after discontinuation of both short-term and long-term treatment with gabapentin have been observed in some patients. The following events have been mentioned: insomnia, headache, nausea, anxiety, hyperhidrosis and diarrhoea. Discontinuation should be done gradually over a minimum of one week (see Section 4.2 Dose and Method of Administration, Discontinuation of Gabapentin Sandoz).

Pancreatitis.

If a patient develops acute pancreatitis under treatment with gabapentin, discontinuation of gabapentin should be considered.

Information for patients.

To assure safe and effective use of gabapentin, the following information and instructions should be given to patients.
Patients should inform their physician about any prescription or non-prescription medications, alcohol or medicines they are now taking or plan to take during their treatment with gabapentin.
No teratogenic effects have been found in animals. However the risk to the human foetus cannot be dismissed. Therefore, female patients should inform their doctor if they are pregnant, are planning to become pregnant, or become pregnant while taking gabapentin.
Gabapentin is excreted in human milk, and the effect on the breastfed infant is unknown. Women should inform their doctor if they are breastfeeding an infant.
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.
More than 12 hours should not be allowed between gabapentin doses. If a dose is missed by not more than four hours, the dose should be taken as soon as it is remembered. However, if a dose is missed by more than four hours, the dose should be skipped and the following doses taken as usual.
Prior to initiation of treatment with gabapentin, 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.

No systematic studies in patients 65 years or older have been conducted with gabapentin. In one double-blind study in patients with neuropathic pain, somnolence, peripheral oedema and asthenia occurred in a somewhat higher percentage in patients aged 65 years or above, than in younger patients. Apart from these findings, clinical investigations in this age group do not indicate an adverse event profile different from that observed in younger patients.
See Section 5.2 Pharmacokinetic Properties; Section 4.4 Special Warnings and Precautions for Use, Central nervous system depression; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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.
The effects of long-term (greater than 36 weeks) gabapentin therapy on learning, intelligence and development in children and adolescents have not been adequately studied. The benefits of prolonged therapy must therefore be weighed against the potential risks of such therapy.

Effects on laboratory tests.

False positive readings were reported with the Ames N-Multistix SG dipstick test when gabapentin was added to other anticonvulsant medicines. 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, sedation, and death associated with gabapentin when co-administered with CNS depressants, including opioids. In some of these reports, the authors considered the combination of gabapentin with opioids to be a particular concern in frail patients, in the elderly, in patients with serious underlying respiratory disease, with polypharmacy, and in those patients with substance abuse disorders.

Anticonvulsants.

In pharmacokinetic studies, no interactions were observed between gabapentin and phenobarbital (phenobarbitone) (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 (norethisterone) and ethinyloestradiol when administered concomitantly with an oral contraceptive containing these two medicines (n = 13).

Antacid.

Co-administration of gabapentin with large dose antacid (aluminium hydroxide 3,600 mg, magnesium hydroxide 1,800 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 300 mg four times daily, 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.

Concomitant use with opioids and other CNS depressants.

In post-marketing experience, there are reports of respiratory failure, coma and deaths in patients taking gabapentin and other CNS depressant medications including opioids, and in patients who have a history of substance abuse (see Section 4.4 Special Warnings and Precautions for Use, Concomitant use with opioids and other CNS depressants).

Morphine.

A literature article reported that when a controlled-release morphine 60 mg capsule was administered two hours prior to a gabapentin 600 mg capsule (n = 12), mean gabapentin area under the concentration time curve (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 gabapentin two 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 2,000 mg/kg/day administered in the diet, with estimated exposure (plasma AUC) 14 times clinical exposure at the MRHD of 2,400 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 foetus.
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 foetus of uncontrolled epilepsy. Most frequently reported are cleft lip, cardiovascular malformations and neural tube defects.
It is recommended that women on antiepileptic drugs (AEDs) receive pre-pregnancy counselling with regard to the risk of foetal 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 12 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.
Multiple antiepileptic drug therapy may be associated with a higher risk of congenital malformations than monotherapy, therefore it is important that monotherapy is practiced whenever possible. No sudden discontinuation of antiepileptic therapy should be undertaken as this may lead to breakthrough seizures, which could have serious consequences for both mother and child. Developmental delay in children of mothers with epilepsy has been observed rarely. It is not possible to differentiate if the developmental delay is caused by genetic, social factors, maternal epilepsy or the antiepileptic therapy.
Embryo foetal development studies with gabapentin in mice at oral doses up to 3,000 mg/kg/day and in rats at oral doses up to 1,500 mg/kg/day revealed no evidence of foetal malformations. Delayed ossification in the skull, vertebrae and limbs, indicative of foetal growth retardation, was reported in the offspring of mice administered gabapentin at oral doses of 1,000 and 3,000 mg/kg/day during organogenesis, and rats administered gabapentin 2,000 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 five times higher in the mouse and up to 14 times higher in the rat than in humans at the recommended maximum tolerated dose of 2,400 mg/day.
In female rabbits given gabapentin 60, 300 or 1,500 mg/kg/day 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 foetus was observed.
 Gabapentin is excreted in human milk.
In a peri-postnatal study in rats administered gabapentin in the diet at doses of 500, 1,000 and 2,000 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 breastfed infant is unknown, and because of the potential for serious adverse reactions in breastfed infants from gabapentin, a decision should be made whether to discontinue breastfeeding or to discontinue the medicine, taking into account the importance of the medicine to the mother. Gabapentin should be used in breastfeeding mothers only if the benefits clearly outweigh the risks.

4.7 Effects on Ability to Drive and Use Machines

Gabapentin may have some influence on the ability to drive and use machines. Gabapentin acts on the CNS and may cause somnolence and dizziness or other related symptoms. Even, if they were only of mild or moderate degree, these undesirable effects could be potentially dangerous in patients driving or operating machinery. This is especially true at the beginning of the treatment and after an increase in dose. 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.

4.8 Adverse Effects (Undesirable Effects)

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

Gabapentin has been evaluated for safety in approximately 2,000 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 medicines, not seen in an equivalent frequency among placebo-treated patients, were somnolence, dizziness, ataxia, fatigue and nystagmus.
Approximately 7% of the 2,074 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.

Listed in Table 3 are the 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 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.

Hypertension.

Digestive system.

Flatulence, anorexia, gingivitis.

Haematological, lymphatic systems.

Purpura (most often described as bruises resulting from physical trauma).

Musculoskeletal.

Arthralgia.

Nervous system.

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

Respiratory.

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 gabapentin in combination with other antiepileptic medicines 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 gabapentin in preapproval 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.

Haematological and lymphatic system.

Coagulation defect.

Nervous system.

Aura disappeared, occipital neuralgia.

Psychobiological function.

Sleepwalking.

Respiratory system.

Pseudocroup, 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.
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%). See Table 5.
The adverse events observed during clinical studies conducted in patients with epilepsy (gabapentin as adjunctive therapy and monotherapy) and patients with neuropathic pain not mentioned above include: hyperglycaemia and hypoglycaemia (≥ 1/100 to < 1/10), mental impairment (≥ 1/1,000 to < 1/100), and loss of consciousness (≥ 1/10,000 to < 1/1,000).

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, allergic reaction including urticaria, alopecia, anaphylaxis, agitation, anaemia, angioedema, hyperglycaemia and hypoglycaemia (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, toxic epidermal necrolysis, hypersensitivity including systemic reactions, jaundice, 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), fall, hyponatraemia, loss of consciousness, 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 medicine.

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.

4.9 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.
Overdose 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.

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. Overdose may involve other concurrent medication and should be treated accordingly.
Activated charcoal may reduce absorption of the drug if given within one hour of 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 131126 (Australia).

5 Pharmacological Properties

5.1 Pharmacodynamic Properties

Mechanism of action.

Actions: Anticonvulsant.
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 medicines 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, which may relate to the 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 (NMDA) 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 the 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 gabapentin 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 four partial seizures per month in spite of receiving one or more antiepileptic medicines at therapeutic levels and were observed on their established antiepileptic medicine regimen during a 12 week baseline period. In patients continuing to have at least two (or four 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 1,200 mg/day, given as three divided doses (divided TID) 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 primarily compared gabapentin 1,200 mg/day, given as three divided doses (n = 101) with placebo (n = 98). Additional smaller gabapentin dosage groups (600 mg/day, n = 53; 1,800 mg/day, n = 54) were also studied for information regarding dose response. Responder rate was higher in the gabapentin 1,200 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 1,800 mg group (26%) was statistically significantly superior to the placebo rate. Response ratio was better in the gabapentin 1,200 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 1,800 mg/day group (-0.222) than in the 1,200 mg/day group, with the 1,800 mg/day group achieving statistical significance compared to the placebo group.
A third study compared gabapentin 900 mg/day, given as three divided doses (n = 111) and placebo (n = 109). An additional gabapentin 1,200 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 gabapentin 1,200 mg/day (-0.184) compared to placebo.
A one week, prospective, multicentre, 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, nontitrated = 388) involved in the study had partial seizures which were not adequately controlled with one or two other antiepileptic medicines. For the MITT population, on both the first day of active medication, and all five 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 five 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 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, multicentre clinical studies. The studies were conducted in 247 children who had refractory partial seizures and were receiving one to three standard antiepileptic medicines. After a six week baseline phase, during which patients received their prescribed antiepileptic medicines, there was a 12 week double blind treatment phase. Patients who had experienced a minimum of four 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.
Neuropathic pain.

Adults.

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 1,800 mg/day, 2,400 mg/day and 3,600 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 eleven 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 2 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.

5.2 Pharmacokinetic Properties

Absorption.

Gabapentin bioavailability is not dose proportional, i.e. as the dose is increased, the bioavailability is decreased. A 400 mg dose, for example, has 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 1,200 mg/day, 2,400 mg/day, 3,600 mg/day and 4,800 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 ± standard deviation). In patients with epilepsy, steady-state pre-dose (Cmin) concentrations of gabapentin in the cerebrospinal fluid were approximately 20% of the corresponding plasma concentrations.

Metabolism.

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

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 five to seven 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 is recommended in patients with compromised renal function or in those undergoing haemodialysis (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 to 114 mL/minute) were administered an oral dose of gabapentin 400 mg. The mean gabapentin half-life ranged from about 6.5 hours (patients with creatinine clearance > 60 mL/minute) to 52 hours (creatinine clearance < 30 mL/minute) and gabapentin renal clearance ranged from about 90 mL/minute (creatinine clearance > 60 mL/minute) to about 10 mL/minute (creatinine clearance < 30 mL/minute). 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 non-dialysis day was about 132 hours. Dialysis three times a week (four 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 patients (≥ 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/minute in those under 30 years of age to about 125 mL/minute 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 age related compromised renal function.

Paediatric patients.

Gabapentin pharmacokinetics were determined in 24 healthy paediatric subjects between the ages of 4 and 12 years. In general, plasma gabapentin 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 2,000 mg/kg/day and to rats at 250, 1,000 and 2,000 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 2,000 mg/kg/day are 14 times higher than plasma concentrations in humans given the recommended maximum tolerated dose of 2,400 mg/day. The pancreatic acinar cell tumours in male rats were 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 humans is unclear.

6 Pharmaceutical Particulars

6.1 List of Excipients

Pregelatinised maize starch, maize starch, purified talc, colloidal anhydrous silica, titanium dioxide, sodium lauryl sulfate, gelatin, iron oxide yellow (300 mg and 400 mg capsules), iron oxide red (400 mg capsules only).

6.2 Incompatibilities

Incompatibilities were either not assessed or not identified as part of the registration of this medicine.
For information on interactions with other medicines and other forms of interactions, see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions.

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

Store below 30°C.

6.5 Nature and Contents of Container

Gabapentin Sandoz 100*, 300, 400 mg capsules are available in blister packs (PV/PVDC/PE/Al) of 100 capsules.
* Gabapentin Sandoz 100 mg capsules are not marketed in Australia.

6.6 Special Precautions for Disposal

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

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.

Chemical structure.


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

CAS number.

60142-96-3.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes