NUPENTIN TABS gabapentin 800 mg tablet blister pack

Australia - English - Department of Health (Therapeutic Goods Administration)

Buy It Now

Active ingredient:
gabapentin
Available from:
Alphapharm Pty Ltd
INN (International Name):
Gabapentin
Authorization status:
Registered
Authorization number:
174062

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Nupentin

gabapentin

CONSUMER MEDICINE INFORMATION

What is in this leaflet

This leaflet answers some common

questions about Nupentin.

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 Nupentin

against the benefits it is expected to

have for you.

If you have any concerns about

taking this medicine, ask your

doctor or pharmacist.

Keep this leaflet with the medicine.

You may need to read it again.

What Nupentin is used

for

What Nupentin does

Nupentin 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.

Nupentin is also used to treat

neuropathic pain, a type of pain

caused by damage to the nerves.

This medicine belongs to a group of

medicines called anticonvulsants.

How Nupentin works

This medicine is thought to work by

controlling brain chemicals which

send signals to nerves to help control

seizures or neuropathic pain.

Nupentin also has pain relieving

effects.

Your doctor may have prescribed

Nupentin 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

Nupentin for another reason.

Nupentin may lead to dependence on

this medicine.

Ask your doctor if you have any

questions about why Nupentin has

been prescribed for you.

This medicine is available only with

a doctor's prescription.

Use in children

There is not enough information to

recommend the use of this medicine

in children:

under the age of 3 years to control

epilepsy, or

under the age of 18 years to treat

neuropathic pain.

Before you take

Nupentin

When you must not take it

Do not take Nupentin if you have

an allergy to:

any medicine containing

gabapentin, the active ingredient

in Nupentin

any of the ingredients listed at the

end of this leaflet.

Some of the symptoms of an allergic

reaction may include:

shortness of breath

wheezing or difficulty breathing

swelling of the face, lips, tongue

or other parts of the body

rash, itching or hives on the skin.

Do not take Nupentin after the

expiry date printed on the pack or

if the packaging is torn or shows

signs of tampering.

If it has expired or is damaged, return

it to your pharmacist for disposal.

If you are not sure whether you

should start taking Nupentin, talk

to your doctor or pharmacist.

Before you start to take it

Tell your doctor or pharmacist if

you have allergies to:

any other medicines, especially

barbiturates or any other

anticonvulsant medicines

any other substances, such as

foods, preservatives or dyes.

Tell your doctor if you have or

have had any of the following

medical conditions:

kidney problems

mixed seizure disorders that

include absence seizures.

Tell your doctor if you are

pregnant or plan to become

pregnant.

Nupentin 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 Nupentin, your doctor can help

you decide whether or not to take it

during pregnancy.

Tell your doctor if you are breast-

feeding or plan to breast-feed.

NUPENTIN

Nupentin passes into breast milk. The

effect on your breast-fed baby is

unknown.

If you do breast-feed, watch your

baby carefully.

If your baby develops a skin rash,

becomes sleepy or has unusual

symptoms, don't breast-feed again

until you speak to your doctor.

Your doctor can discuss the risks and

benefits of breast-feeding with you.

If you have not told your doctor or

pharmacist about any of the above,

tell them before you start taking

Nupentin.

Taking other medicines

Tell your doctor or pharmacist if

you are taking any other

medicines, including:

all prescription medicines

all medicines, vitamins, herbal

supplements or natural therapies

you buy without a prescription

from a pharmacy, supermarket,

naturopath or health food shop.

Some medicines may be affected by

Nupentin or may affect how well it

works. You may need different

amounts of your medicines, or you

may need to take different medicines.

Your doctor or pharmacist will

advise you accordingly.

Tell your doctor or pharmacist if

you are taking any of the

following:

cimetidine, a medicine used to

treat stomach or duodenal ulcers

antacids, medicines used to treat

heartburn or reflux

opioids, medicines used to treat

severe pain e.g. morphine.

Your doctor and pharmacist have

more information on medicines to be

careful with or avoid while taking

Nupentin.

How to take Nupentin

Follow all directions given to you by

your doctor or pharmacist carefully.

They may differ from the

information contained in this leaflet.

If you do not understand the

instructions on the pack, ask your

doctor or pharmacist for help.

How much to take

Your doctor will tell you how many

capsules you need to take each day.

This may depend on your age, your

condition and whether or not you are

taking any other medicines.

Your doctor may recommend that

you start with a low dose of Nupentin

and slowly increase the dose to the

lowest amount needed to control

your epilepsy/convulsions or

neuropathic pain.

How to take it

Swallow Nupentin whole with a

full glass of water.

When to take it

Take Nupentin at about the same

time each day.

Taking Nupentin at the same time

each day will have the best effect. It

will also help you remember when to

take the capsules.

If you are taking Nupentin three

times a day, do not allow more than

12 hours between doses.

It does not matter if you take

Nupentin before or after food.

How long to take it

Continue taking your medicine for

as long as your doctor tells you to.

Nupentin 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 Nupentin, or

lower the dose, without checking

with your doctor. Do not let

yourself run out of medicine over

the weekend or holidays.

Stopping Nupentin suddenly may

cause unwanted side effects or make

your condition worse. Your doctor

will slowly reduce your dose before

you can stop taking it completely.

If you forget to take it

If it is almost time for your next

dose (within 4 hours), skip the dose

you missed and take your next dose

when you are meant to.

Otherwise, take it as soon as you

remember, and then go back to

taking Nupentin as you would

normally.

Do not take a double dose to make

up for the dose that you missed.

This may increase the chance of you

getting an unwanted side effect.

If you are not sure what to do, ask

your doctor or pharmacist.

If you have trouble remembering

to take Nupentin, ask your

pharmacist for help.

If you take too much

(overdose)

Immediately telephone your doctor

or Poisons Information Centre

(telephone Australia 13 11 26 or

New Zealand 0800 POISON or

0800 764 766) for advice, or go to

Accident and Emergency at the

nearest hospital, if you think that

you or anyone else may have taken

too much Nupentin.

Do this even if there are no signs of

discomfort or poisoning.

You may need urgent medical

attention.

Symptoms of an overdose may

include you falling unconscious,

feeling drowsy, weak, unsteady when

walking, having double vision,

slurred speech or diarrhoea.

While you are taking

Nupentin

Things you must do

If you are about to be started on

any new medicine, remind your

NUPENTIN

doctor and pharmacist that you

are taking Nupentin.

Tell any other doctors, dentists,

and pharmacists who treat you

that you are taking Nupentin.

If you are going to have surgery or

emergency treatment, tell the

surgeon or anaesthetist that you

are taking Nupentin.

Tell your doctor immediately if

you have any thoughts of suicide or

self-harm, any unusual changes in

mood or behaviour, or show signs

of depression.

Some people being treated with anti-

epileptics, such as Nupentin, have

had thoughts of harming or killing

themselves.

Patients and caregivers should be

alert and monitor for signs and

symptoms of suicide, these include:

thoughts or talk of death or

suicide

thoughts or talk of self-harm or

harm to others

any recent attempts of self-harm

new or an increase in aggressive

behaviour, irritability or agitation

new onset of or worsening of

depression.

Mention of suicide or violence must

be taken seriously.

If you or someone you know is

demonstrating these warning signs

and symptoms of suicide while

taking Nupentin, contact your

doctor or a mental health

professional right away.

Tell your doctor if you feel

Nupentin is not helping your

condition.

Your doctor may need to change

your medicine.

Tell your doctor if, for any reason,

you have not taken Nupentin

exactly as prescribed.

Otherwise, your doctor may change

your treatment unnecessarily.

If you become pregnant while

taking Nupentin, tell your doctor

immediately.

If you need to have any medical

tests while you are taking

Nupentin, tell your doctor.

It may interfere with the results of

some tests.

If you are going to have any surgery

or procedure, including dental

surgery, tell your surgeon, doctor or

dentist that you are taking this

medicine.

Keep all of your doctor's

appointments so that your progress

can be checked.

Your doctor will check your progress

and may want to take some tests

from time to time. This helps to

prevent unwanted side effects.

Things you must not do

Do not take Nupentin to treat any

other complaints unless your

doctor tells you to.

Do not give Nupentin to anyone

else, even if their symptoms seem

similar to yours or they have the

same condition as you.

Do not stop taking Nupentin or

lower the dose without checking

with your doctor.

Stopping Nupentin suddenly, if you

have epilepsy, may cause unwanted

side effects or make your condition

worse. Your doctor will slowly

reduce your dose before you can stop

taking it completely.

Things to be careful of

Be careful driving or operating

machinery until you know how

Nupentin affects you.

As with other anticonvulsant

medicines, Nupentin may cause

drowsiness, dizziness, light-

headedness or sleepiness in some

people. Make sure you know how

you react to Nupentin before you

drive a car, operate machinery, or do

anything else that could be dangerous

if you are dizzy or light-headed. If

this occurs do not drive.

Children should not ride a bike,

climb trees or do anything else that

could be dangerous if they are

feeling drowsy or sleepy.

Be careful when drinking alcohol

while you are taking Nupentin.

Combining Nupentin and alcohol can

make you more sleepy, dizzy or

light-headed. Your doctor may

suggest you avoid alcohol while you

are being treated with Nupentin.

Side effects

Tell your doctor or pharmacist as

soon as possible if you do not feel

well while you are taking

Nupentin.

All medicines can have side effects.

Sometimes these are serious, but

most of the time these are not. You

may need medical attention if you get

some side effects.

It can be difficult to tell whether side

effects are the result of taking

Nupentin; of your condition; or side

effects of other medicines you may

be taking, for this reason it is

important to tell your doctor of any

change in your condition.

If you are over 65 years of age you

may have an increased chance of

getting side effects.

Ask your doctor or pharmacist to

answer any questions you may

have.

If you get any side effects, do not

stop taking Nupentin without first

talking to your doctor or

pharmacist.

Tell your doctor if...

Tell your doctor or pharmacist if

you notice any of the following and

they worry you:

dizziness* or light-headedness

feeling tired or drowsy*

unfriendliness*

unusually overactive*

forgetfulness, loss of

concentration or confusion

difficulty speaking

NUPENTIN

changes in your weight*

constipation, diarrhoea

nausea and/or vomiting*,

indigestion

dry mouth, red swollen gums

muscle pain or cramps, back pain

swelling of the hands or feet

runny or blocked nose

fever*

bronchitis*, lung infection*

sore throat and discomfort when

swallowing, coughing.

The above list includes the more

common side effects of Nupentin.

They are usually mild and short-

lived.

Tell your doctor as soon as

possible if...

Tell your doctor as soon as possible

if you notice any of the following:

weakness, unsteadiness when

walking including falling,

reduced co-ordination or slowed

reactions

unusual changes in mood* or

behaviour such as restlessness,

nervousness, or excitement

signs of new onset of, or

increased irritability or agitation

signs of depression

seeing or hearing things that are

not there, irrational thinking

blurred or double vision,

uncontrollable jerky eye

movements, difficulty seeing

signs of frequent infections such

as fever, severe chills, sore throat

or mouth ulcers.

trouble breathing or shallow

breaths (respiratory depression)

loss of consciousness

The side effects in the above lists

marked * have been specifically

reported in children taking Nupentin.

Go to hospital if...

Tell your doctor immediately or go

to Accident and Emergency at

your nearest hospital if you notice

any of the following:

more frequent or more severe

seizures (fits)

chest pain, a very fast heart rate

sudden signs of allergy such as

rash, itching or hives, fever,

swollen lymph glands, swelling

of the face, lips, tongue or other

parts of the body, shortness of

breath, wheezing or difficulty

breathing.

The above list includes very serious

side effects. You may need urgent

medical attention or hospitalisation.

These side effects are very rare.

Tell your doctor or pharmacist if

you notice anything else that is

making you feel unwell.

Other side effects not listed above

may also occur in some people.

Some of these side effects (for

example, changes in thyroid function,

structures of bones, high cholesterol,

levels of sugar in your blood or blood

pressure) can only be found when

your doctor does blood tests from

time to time to check your progress.

Do not be alarmed by the list of

possible side effects.

You may not experience any of them.

After taking Nupentin

Storage

Keep Nupentin where children

cannot reach it.

A locked cupboard at least one-and-

a-half metres above the ground is a

good place to store medicines.

Keep your capsules in the pack

until it is time to take them.

If you take the capsules out of the

pack they may not keep well.

Keep your capsules in a cool dry

place where the temperature stays

below 25°C.

Do not store Nupentin or any other

medicine in the bathroom or near a

sink.

Do not leave Nupentin in the car or

on window sills.

Heat and dampness can destroy some

medicines.

Disposal

If your doctor or pharmacist tells you

to stop taking Nupentin, or your

capsules have passed their expiry

date, ask your pharmacist what to do

with any that are left over.

Product description

What it looks like

Nupentin

Nupentin capsules are available in 3

strengths:

Nupentin 100 - white capsule,

with "GP100" printed on one half

and "G" on the other half

Nupentin 300 - yellow capsule,

with "GP300" printed on one half

and "G" on the other half

Nupentin 400 - orange capsule,

with "GP400" printed on one half

and "G" on the other half.

Nupentin capsules are marketed in

blister packs. Each pack contains 100

capsules.

Ingredients

Nupentin

The active ingredient in Nupentin is

gabapentin.

Each Nupentin 100 capsule

contains 100 mg of gabapentin.

Each Nupentin 300 capsule

contains 300 mg of gabapentin.

Each Nupentin 400 capsule

contains 400 mg of gabapentin.

The capsules also contain the

following inactive ingredients:

lactose monohydrate

maize starch

purified talc

gelatin

titanium dioxide (E171)

NUPENTIN

quinoline yellow CI47005 (E104)

[Nupentin 300 only]

allura red AC CI16035 (E129)

[Nupentin 300 only]

sunset yellow FCF CI15985

(E110) [Nupentin 400 only]

iron oxide red CI77491 (E172)

[Nupentin 400 only]

iron oxide yellow CI77492

(E172) [Nupentin 400 only]

Tek Print black ink.

Nupentin capsules also contain

sulfites (present in trace amounts).

The capsules are gluten free.

Manufacturer

Nupentin is made in Australia by:

Alphapharm Pty Limited

Level 1, 30 The Bond

30-34 Hickson Road

Millers Point NSW 2000

www.mylan.com.au

Australian registration numbers:

Nupentin 100 (100 mg capsule blister

pack): AUST R 101694

Nupentin 300 (300 mg capsule blister

pack): AUST R 101696

Nupentin 400 (400 mg capsule blister

pack): AUST R 101698

This leaflet was prepared in August

2019.

Nupentin_cmi\Aug19/00

NUPENTIN

Read the complete document

AUSTRALIAN PRODUCT INFORMATION

Nupentin

Gabapentin capsule

1

NAME OF THE MEDICINE

Gabapentin

2

QUALITATIVE AND QUANTITATIVE COMPOSITION

Gabapentin is a white to off-white crystalline solid. It is freely soluble in water and both basic and acidic

aqueous solutions.

Each NUPENTIN capsule contains gabapentin 100 mg, 300 mg or 400 mg as the active ingredient.

NUPENTIN also contains: lactose monohydrate and sulfites (present in trace amounts).

For the full list of excipients, see

Section 6.1 LIST OF EXCIPIENTS

3

PHARMACEUTICAL FORM

NUPENTIN 100:

Each 100 mg capsule contains gabapentin as the active ingredient, presented as a size 3

capsule with white body and white cap, “GP100” printed in black ink on the body and “G” on the cap.

NUPENTIN 300:

Each 300 mg capsule contains gabapentin as the active ingredient, presented as a

size 1 capsule with yellow body and yellow cap, “GP300” printed in black ink on the body and “G” on the

cap.

NUPENTIN 400:

Each 400 mg capsule contains gabapentin as the active ingredient, presented as a

size 0 capsule with orange body and orange cap, “GP400” printed in black ink on the body and “G” on the

cap.

4

CLINICAL PARTICULARS

4.1

THERAPEUTIC INDICATIONS

Gabapentin 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 anti-epileptic drugs.

Gabapentin is indicated for the treatment of neuropathic pain.

4.2

DOSE AND METHOD OF ADMINISTRATION

Epilepsy Dosage for Adults and Children Older than 12 Years of Age

Initiation of treatment should be as add-on therapy. Gabapentin can be given orally with or without food.

In controlled clinical trials, the effective dose range was 900 mg/day to 1800 mg/day given in divided

doses (three times a day).

Therapy may be initiated by administering 300 mg of Nupentin 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 Nupentin on Day 1, 300

mg Nupentin twice a day on Day 2, 300 mg Nupentin 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 antiepileptic

drugs and patients with multiple other medical problems.

NUPENTIN – PRODUCT INFORMATION

To minimise potential side effects, especially somnolence, dizziness, fatigue and ataxia, the first dose on Day

1 may be administered at bedtime. If necessary, the dose may be increased using 300 mg or 400 mg capsules

three times a day up to 2400 mg/day. Dosages up to 2400 mg/day have been well tolerated in long-term

open-label clinical studies. The maximum time between doses in the three times a day (TID) schedule should

not exceed 12 hours.

Neuropathic Pain in Adults Older than 18 Years of Age

The starting dose is 900 mg/day given in three daily divided doses, and titrated if necessary, based on response,

up to a maximum dose of 3600 mg/day.

Dose Adjustment in Impaired Renal Function in Patients with Neuropathic Pain or Epilepsy

Dose adjustment is recommended in patients with compromised renal function and/or those undergoing

haemodialysis (see

Table 1

Table 1. Maintenance Dosage of Gabapentin in Adults with Reduced Renal Function

Renal function Creatinine

Clearance (mL/min)

Total Daily Dose

a

(mg/day)

≥80

1200

2400

3600

50-79

1200

1800

30-49

15-29

<15

Total daily dose should be administered as a three times daily (tid) regimen. Doses used to treat patients with normal renal function

(creatinine clearance >80 mL/min) range from 900 to 3600 mg/day. Reduced dosages are for patients with renal impairment (creatinine

clearance <79 mL/min).

To be administered as 300 mg every other day.

For patients undergoing haemodialysis who have never received gabapentin, a loading dose of 300 mg to

400 mg is recommended, and then 200 mg to 300 mg of gabapentin following each 4 hours of haemodialysis.

Dosage for Children Aged 3 to 12 Years of Age

The effective dose of gabapentin is 25 mg/kg/day to 35 mg/kg/day given in three divided doses (3 times a

day). Titration to an effective dose can take place over 3 days by giving 10 mg/kg/day on Day 1, 20 mg/kg/day

on Day 2, and 30 mg/kg/day on Day 3. Dosages up to 40 mg/kg/day to 50 mg/kg/day have been well

tolerated in a longterm 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

alteration

plasma

concentrations

of gabapentin

serum concentrations

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 1 week.

4.3

CONTRAINDICATIONS

Hypersensitivity to gabapentin or the inactive ingredients.

4.4

SPECIAL WARNINGS AND PRECAUTIONS FOR USE

General

Although there is no evidence of rebound seizures with gabapentin, abrupt withdrawal of anticonvulsants

in epileptic patients may precipitate status epilepticus. When in the judgment 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.

NUPENTIN – PRODUCT INFORMATION

Gabapentin is generally not 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.

Gabapentin treatment

been

associated

with

dizziness

somnolence, which

could increase

occurrence of accidental injury (fall). There have also been post-marketing reports of confusion, loss of

consciousness and mental impairment. Therefore, patients should be advised to exercise caution until they

are familiar with the potential effects of the medication.

Central Nervous System Depression

Respiratory Depression

Gabapentin has been associated with central nervous system (CNS) depression including sedation,

somnolence, loss of consciousness as well as serious cases of respiratory depression. This may occur

without

concomitant

opioid

use.

Patients

with

compromised

respiratory

function,

respiratory or

neurological disease, renal impairment and the elderly are at higher risk of experiencing these severe

adverse effects. Concomitant use of CNS depressants with gabapentin increases the risk of respiratory

depression.

Concomitant Use with Opioids

Patients

require

concomitant

treatment

with

opioids

experience

increases

gabapentin

concentrations. Patients should be carefully observed for signs of central nervous system (CNS) depression;

such as somnolence, sedation and respiratory depression, and the dose of gabapentin or opioid should be

reduced appropriately (see

Section 4.1 INTERACTIONS WITH OTHER MEDICINES OTHER FORMS

OF INTERACTIONS

Suicidal Behaviour and Ideation

Antiepileptic drugs (AED), including gabapentin, increase the risk of suicidal thoughts or behaviour in

patients taking these drugs for any indication.

Patients treated with any AED for any indication should be

monitored for the emergence or worsening of depression, suicidal thoughts or behaviour, and/or any unusual

changes in mood or behaviour.

Pooled analyses of 199 placebo-controlled clinical trials (mono- and adjunctive therapy) of 11 different

AEDs showed that patients randomised to one of the AEDs had approximately twice the risk (adjusted

Relative Risk 1.8, 95% CI:1.2, 2.7) of suicidal thinking or behaviour compared to patients randomised to

placebo. In these trials, which had a median treatment duration of 12 weeks, the estimated incidence rate of

suicidal behaviour or ideation among 27,863 AED-treated patients was 0.43%, compared to 0.24% among

16,029 placebo-treated patients, representing an increase of approximately one case of suicidal thinking or

behaviour for every 530 patients treated. There were four suicides in drug-treated patients in the trials and

none in placebo-treated patients, but the number is too small to allow any conclusion about drug effect on

suicide.

The increased risk of suicidal thoughts or behaviour with AEDs was observed as early as one week after starting

drug treatment with AEDs and persisted for the duration of treatment assessed. Because most trials included

in the analysis did not extend beyond 24 weeks, the risk of suicidal thoughts or behaviour beyond 24 weeks

could not be assessed.

The risk of suicidal thoughts or behaviour was generally consistent among drugs in the data analysed.

The finding of increased risk with AEDs of varying mechanisms of action and across a range of indications

suggests that the risk applies to all AEDs used for any indication. The risk did not vary substantially by age (5-

100 years) in the clinical trials analysed.

Table 2 shows absolute and relative risk by indication for all

evaluated AEDs.

Table 2 Risk by Indication for Antiepileptic Drugs in the Pooled Analysis

Indication

Placebo

Patients

with

Drug Patients

with

Events /

1000

Patients

Relative Risk:

Incidence of

Events

in Drug

Risk Difference:

Additional Drug

Patients with

NUPENTIN – PRODUCT INFORMATION

Events / 1000

Patients

Patients/

Incidence in

Placebo Patients

Events

per 1000

Patients

Epilepsy

Psychiatric

Other

Total

The relative risk for suicidal thoughts or behaviour was higher in clinical trials for epilepsy than in clinical

trials for psychiatric or other conditions, but the absolute risk differences were similar for the epilepsy and

psychiatric indications.

Anyone considering prescribing gabapentin or any other AED must balance this risk with the risk of untreated

illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with

morbidity and mortality and an increased risk of suicidal thoughts and behaviour. Should suicidal thoughts

and behaviour emerge during treatment, the prescriber needs to consider whether the emergence of these

symptoms in any given patient may be related to the illness being treated.

Patients, their caregivers, and families should be informed that AEDs increase the risk of suicidal thoughts

and behaviour and should be advised of the need to be alert for the emergence or worsening of the signs and

symptoms of depression, any unusual changes in mood or behaviour, or the emergence of suicidal thoughts,

behaviour, or thoughts about self-harm. Behaviours of concern should be reported immediately to the treating

doctor.

Abuse and Dependence

Post-marketing cases of abuse and dependence have been reported with gabapentin. As with other CNS drugs,

patients should be carefully evaluated for a history of drug abuse and observed for possible signs of gabapentin

abuse.

Drug Rash with Eosinophilia and Systemic Symptoms (DRESS)

Severe, life-threatening, systemic hypersensitivity reactions such as drug rash with eosinophilia and systemic

symptoms (DRESS) have been reported in patients taking anti-epilepetic drugs including gabapentin.

It is important to note that early manifestations of hypersensitivity, such as fever or lymphadenopathy, may

be present even though rash is not evident. If such signs or symptoms are present, the patient should be

evaluated immediately. Gabapentin should be discontinued if an alternative aetiology for the signs or

symptoms cannot be established.

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 and Dependence

Post-marketing cases of abuse and dependence have been reported with gabapentin. As with other CNS drugs,

patients should be carefully evaluated for a history of drug abuse and observed for possible signs of gabapentin

abuse.

Information for Patients

To assure safe and effective use of gabapentin, the following information and instructions should be given

to patients:

You should inform your physician about any prescription or non-prescription medications, alcohol

or drugs you are now taking or are planning to take during their treatment with gabapentin.

NUPENTIN – PRODUCT INFORMATION

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

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.

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.

You should not allow more than twelve 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 the following doses 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

Dosage

adjustment

patients

with

compromised

renal

function

undergoing

haemodialysis

recommended (see

Section 5.2

PHARMACOKINETIC PROPERTIES

Section 4.2 DOSE AND

METHOD OF ADMINISTRATION

Use in the Elderly

Reduction of gabapentin dosage may be required in patients with age related compromised renal function

(see

Section 5.2

PHARMACOKINETIC PROPERTIES

Paediatric Use

Epilepsy

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

Neuropathic Pain.

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

Effects on Laboratory Tests

False positive readings were reported with the Ames N-Multistix SG® dipstick test when gabapentin was added

to other anticonvulsant drugs. To determine urinary protein, the more specific sulfosalicylic acid precipitation

procedure is recommended.

4.5

INTERACTIONS

WITH

OTHER

MEDICINES

AND

OTHER

FORMS

OF

INTERACTIONS

There are spontaneous and literature case reports of respiratory depression and/or sedation associated

with gabapentin and opioid use. These effects would be of particular concern in elderly patients.

Anticonvulsants

In pharmacokinetic studies, no interactions were observed between gabapentin and phenobarbital (number

of subjects, N = 12), phenytoin (N = 8), valproic acid (N = 17) or carbamazepine (N = 12).

NUPENTIN – PRODUCT INFORMATION

Oral Contraceptives

Gabapentin did not influence the steady-state pharmacokinetics of norethindrone and ethynyl estradiol

when administered concomitantly with an oral contraceptive containing these two drugs (N = 13).

Antacid

Coadministration of gabapentin with large dose antacid (aluminium hydroxide 3600 mg,

magnesium

hydroxide 1800 mg) reduced gabapentin bioavailability (AUC) by about 20% (N = 16). Although the

difference was not expected to be clinically significant, it is recommended that gabapentin should be taken

about 2 hours following antacid administration, when the interaction has been shown to be diminished.

Cimetidine

In the presence of cimetidine at 300 mg four times a day (QID), the mean apparent oral clearance of gabapentin

fell by 14% and creatinine clearance by 10% (N = 12). Thus cimetidine appeared to alter the renal excretion

of both gabapentin and creatinine, an endogenous marker of renal function.

Probenecid

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

Morphine

A literature article reported that when a 60 mg controlled-release morphine capsule was administered 2

hours prior to a 600 mg gabapentin capsule (N = 12), mean gabapentin AUC increased by 44% compared to

gabapentin administered without morphine (see Precautions). 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.

4.6

FERTILITY, PREGNANCY AND LACTATION

Effects on Fertility

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

in the diet, with estimated exposure (plasma AUC) 14 times clinical exposure at the MRHD of 2400 mg/day.

Use in Pregnancy

Pregnancy 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

whether

gabapentin

casually

associated

with

increased

risk

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 of 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 fetus of uncontrolled epilepsy.

It is recommended that:

women on antiepileptic drugs (AEDs) receive pre-pregnancy counselling with regard to the risk of fetal

NUPENTIN – PRODUCT INFORMATION

abnormalities;

AEDs should be continued during pregnancy and monotherapy should be used if possible at the lowest

effective dose as risk of abnormality is greater in women taking combined medication;

folic acid supplementation (5 mg) should be commenced four weeks prior to and continue for twelve

weeks after conception;

specialist prenatal diagnosis including detailed mid-trimester ultrasound should be offered.

Studies in animals have shown reproductive toxicity. The potential risk for humans is unknown.

Embryofetal development studies with gabapentin in mice at oral doses up to 3000 mg/kg/day and in rats at

oral doses up to 1500 mg/kg/day revealed no evidence of fetal malformations. Delayed ossification in the

skull, vertebrae and limbs, indicative of fetal growth retardation, was reported in the offspring of mice

administered gabapentin

oral

doses

1000

3000

mg/kg/day

during

organogenesis,

and rats

administered gabapentin 2000 mg/kg/day in the diet during mating and throughout gestation. An increased

incidence of hydroureter and/or hydronephrosis was observed in rats treated with dietary gabapentin from

late

gestation

weaning

(see PRECAUTIONS

Lactation). In

these

studies,

exposure

gabapentin (based on areas under the concentration time curve) was up to 5 times higher in the mouse, and

up to 14 times higher in the rat, than in humans at the recommended maximum dose of 2400 mg/day.

In female rabbits given 60, 300 or 1500 mg/kg/day gabapentin orally during the period of organogenesis,

maternal toxicity and abortion were observed at the high dose, but at the low and mid doses, no evidence of

harm to the fetus was observed.

Use in Lactation

Gabapentin is excreted in human breast milk.

In a peri-natal/ postnatal study in rats administered gabapentin in the diet at doses of 500, 1000 and

2000 mg/kg/day from late

gestation to

weaning,

there

dose related reversible increase in the

incidence of hydroureter and hydronephrosis in 21 day-old pups.

Because the effect on the nursing infant is unknown, and because of the potential for serious adverse reactions

in nursing infants from gabapentin, a decision should be made whether to discontinue nursing or to discontinue

the drug, taking into account the importance of the drug to the mother. Gabapentin should be used in nursing

mothers only if the benefits clearly outweigh the risks.

4.7

EFFECTS ON ABILITY TO DRIVE AND USE MACHINES

Patients should be advised not to drive a car or operate potentially dangerous machinery until it is known

that this medication does not affect their ability to engage in these activities.

4.8

ADVERSE EFFECTS (UNDESIRABLE EFFECTS)

Adults and Children Older than 12 Years of Age with Epilepsy

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,

seen

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.

NUPENTIN – PRODUCT INFORMATION

Incidence in Controlled Epilepsy Clinical Trials

Table 3

lists 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.

Table 3: Adverse Events Reported in At Least 1% of Participants in Gabapentin Placebo-Controlled

Trials

Body System

Adverse Event

Gabapentin

a

N=543 (%)

Placebo

a

N=378 (%)

Body as a whole

Fatigue

11.0

Weight Increase

Back Pain

Peripheral Oedema

Viral Infection

Fever

Cardiovascular

Vasodilatation

Digestive System

Nausea and/or Vomiting

Dyspepsia

Abdominal Pain

Mouth or Throat Dry

Constipation

Dental Abnormalities

Diarrhoea

Increased Appetite

Haematologic and

Lymphatic Systems

Leukopenia

Musculoskeletal System

Myalgia

Fracture

Nervous System

Somnolence

19.3

Dizziness

17.1

Ataxia

12.5

Nystagmus

Headache

Tremor

Nervousness

Dysarthria

Amnesia

Depression

Thinking Abnormal

Confusion

Twitching

Coordination Abnormal

Insomnia

Emotional Lability

Respiratory System

Rhinitis

Pharyngitis

Coughing

Skin and Appendages

Rash

Abrasion

Pruritus

Acne

NUPENTIN – PRODUCT INFORMATION

Body System

Adverse Event

Gabapentin

a

N=543 (%)

Placebo

a

N=378 (%)

Urogenital System

Impotence

Special Senses

Diplopia

Amblyopia

Laboratory Deviations

WBC Decreased

Plus background antiepileptic medicine therapy

Amblyopia was often described as blurred vision.

Other Adverse Events Observed During All Epilepsy Clinical Studies

Those events that occurred in at least 1% of the study participants with epilepsy who received gabapentin

as adjunctive therapy in any clinical study and that are not described in the previous section as frequently

occurring treatment-emergent signs and symptoms during placebo-controlled studies are summarised below.

Body as a whole.

Asthenia, malaise, facial oedema.

Cardiovascular System

. Hypertension.

Digestive System.

Flatulence, anorexia, gingivitis.

Haematologic and Lymphatic System.

Purpura most often described as bruises resulting from physical trauma.

Musculoskeletal System.

Arthralgia

Nervous System.

Vertigo; hyperkinesia; increased, decreased or absent reflexes; paraesthesia, anxiety,

hostility.

Respiratory System.

Pneumonia.

Urogenital System.

Urinary tract infection.

Special Senses.

Abnormal vision, most often described as a visual disturbance.

Children from 3 to 12 Years of Age with Epilepsy

The most commonly observed adverse events reported with the use of 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.

Approximately 8% of the 292 children aged 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%) (see

Table 4

Table 4: Treatment Emergent Adverse Event Incidence in Children Age 3 to 12 Years in Controlled

AddOn Trials (Events in at least 2% of gabapentin patients and numerically more frequent than in

the placebo group)

Body System

Adverse Event

Gabapentin

a

N = 119 (%)

Placebo

a

N = 128 (%)

Body as a Whole

Viral Infection

10.9

Fever

10.1

Weight Increase

Fatigue

NUPENTIN – PRODUCT INFORMATION

Body System

Adverse Event

Gabapentin

a

N = 119 (%)

Placebo

a

N = 128 (%)

Digestive System

Nausea and/or Vomiting

Nervous System

Somnolence

Hostility

Emotional Lability

Dizziness

Hyperkinesia

Respiratory System

Bronchitis

Respiratory Infection

Plus background antiepileptic medicine therapy

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:

Body as a Whole.

Dehydration, infectious mononucleosis

Digestive System

. Hepatitis, oral moniliasis.

Haematologic and Lymphatic Systems.

Coagulation defect.

Nervous System.

Aura disappeared, occipital neuralgia.

Psychobiologic Function.

Sleepwalking.

Respiratory System.

Pseudo-croup, hoarseness.

Adults Older than 18 Years of Age with Neuropathic Pain

The most commonly observed adverse events reported with the use of gabapentin in adults older than 18

years of age with neuropathic pain, seen in at least twice the frequency among placebo treated patients, were dry

mouth,

peripheral

oedema,

weight

gain,

abnormal

gait,

amnesia,

ataxia,

confusion,

dizziness,

hypoaesthesia, somnolence, thinking abnormal, vertigo, rash and amblyopia.

Of the 821 adults who received 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

Table 5: Summary of Treatment-Emergent Signs and Symptoms in ≥1% of Gabapentin-Treated

Patients in Neuropathic Pain Placebo-Controlled Studies

COSTART

Body System

Adverse Event

Gabapentin

N = 821

Patients

Placebo

N = 537

Patient

Number

%

Number

%

Body as a Whole

Abdominal pain

Accidental injury

Asthenia

Back pain

Flu syndrome

Headache

Infection

NUPENTIN – PRODUCT INFORMATION

COSTART

Body System

Adverse Event

Gabapentin

N = 821

Patients

Placebo

N = 537

Patient

Number

%

Number

%

Pain

Digestive System

Constipation

Diarrhoea

Dry Mouth

Dyspepsia

Flatulence

Nausea

Vomiting

Metabolic and Nutritional

Peripheral oedema

Weight gain

Nervous System

Abnormal gait

Amnesia

Ataxia

Confusion

Dizziness

21.1

Hypoaesthesia

Somnolence

16.1

Thinking Abnormal

Tremor

Vertigo

Respiratory System

Dyspnoea

Pharyngitis

Skin and Appendages

Rash

Special Senses

Amblyopia

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

been

established.

Additional

post-marketing

adverse

events

reported

include

blood

creatine

phosphokinase increased, rhabdomyolysis, abnormal liver function, acute kidney failure, agitation, allergic

reaction including urticaria, alopecia, anaemia, anaphylaxis, angioedema, hyperglycemia and hypoglycaemia

(most often observed in patients with diabetes), breast hypertrophy, gynaecomastia, cardiac arrest, chest

pain,

convulsions, depersonalisation,

drug

rash

with

eosinophilia

systemic

symptoms,

erythema

multiforme,

fall,

hypersensitivity

including

systemic

reactions,

hyponatraemia,

jaundice,

loss

consciousness,

movement disorders

such

choreoathetosis,

dyskinesia

dystonia,

myoclonus,

palpitation, pancreatitis, renal impairment, speech disorder, sexual dysfunction (including changes in

libido, ejaculation disorders and anorgasmia), Stevens-Johnson syndrome, tachycardia, thrombocytopenia,

tinnitus,

urinary

incontinence

and symptoms of psychosis such as delusions, hallucinations, and thinking

abnormal.

Generalised oedema, hepatitis, hypotension, neuropathy/peripheral neuropathy and syncope have been rarely

reported.

Adverse events following the abrupt discontinuation of gabapentin have also been reported.

The most

frequently reported events were anxiety, insomnia, nausea, pain, and sweating.

Some cases of hypomania have been reported after commencement of gabapentin.

each

case,

other anticonvulsants had been used concurrently, and symptoms of hypomania resolved following a

reduction in dosage or cessation of the medicine.

NUPENTIN – PRODUCT INFORMATION

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.

Overdoses as high as 108 g have been reported with full recovery following symptomatic therapy. Reduced

absorption of gabapentin at higher doses may limit drug absorption at the time of overdosing and, hence,

minimise toxicity from overdoses.

Treatment of Overdosage

There is no specific antidote for gabapentin; treatment is symptomatic. The patient should be monitored

closely and given supportive care where necessary to maintain vital functions. Overdoses may involve other

concurrent medications and should be treated accordingly.

Activated charcoal may reduce absorption of the drug if given within one hour after ingestion. In patients

who are not fully conscious or have impaired gag reflex, consideration should be given to administering

activated charcoal via nasogastric tube once the airway is protected.

Gabapentin can be removed by haemodialysis. Although haemodialysis has not been performed in the

few overdose cases reported, it may be indicated by the patient's clinical state or in patients with

significant renal impairment.

Ipecac-induced emesis is not recommended because of the potential for CNS depression.

For information on the management of overdose, contact the Poisons Information Centre on 13 11 26

(Australia).

5

PHARMACOLOGICAL PROPERTIES

5.1

PHARMACODYNAMIC PROPERTIES

Mechanism of Action

The mechanism by which gabapentin exerts its anticonvulsant action is unknown. Gabapentin is structurally

related to the neurotransmitter GABA (gamma-aminobutyric acid) but its mechanism of action is different

from that of several other drugs that interact with GABA synapses, including valproate, barbiturates,

benzodiazepines, GABA transaminase inhibitors, GABA uptake inhibitors, GABA agonists, and GABA

prodrugs.

In vitro

studies with radiolabelled gabapentin have characterised a novel peptide binding site in

rat brain tissues including neocortex and hippocampus that may relate to 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 GABA

, GABA

, 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

NUPENTIN – PRODUCT INFORMATION

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 4 partial seizures per month in spite of receiving one or more

antiepileptic drugs at therapeutic levels and were observed on their established antiepileptic drug regimen

during a 12-week baseline period. In patients continuing to have at least 2 (or 4 in some studies) seizures per

month, gabapentin or placebo was then added on to the existing therapy during a 12-week treatment

period. Effectiveness

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, 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 compared primarily 1200 mg/day three times daily 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, given as three divided doses (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

NUPENTIN – PRODUCT INFORMATION

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,

placebocontrolled, multicentre clinical studies. The studies were conducted in 247 children who had refractory

partial seizures and were receiving 1 to 3 standard antiepileptic drugs. After a 6-week baseline phase, during

which patients received their prescribed antiepileptic medicines, 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 nonnormality 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 older than 18 years of

age were assessed in two randomised, double-blind, parallel-group, placebo-controlled, multi-centre 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/day, 2400 mg/day and 3600 mg/day divided into three times a day dosing consecutively

over the first four weeks of the study. Patients were then maintained at the maximum dose that was tolerated

for the remaining four weeks. The primary efficacy measure used in both studies was change from baseline

to the final week in mean pain score obtained from daily pain diaries (pain was measured using an 11-point

Likert scale). Several secondary

outcomes

were also

assessed

including:

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.

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

All pharmacological actions following gabapentin administration are due to the activity of the parent

compound; as gabapentin is not appreciably metabolised in humans.

Absorption

Gabapentin bioavailability is not dose proportional, i.e. as the dose is increased, the bioavailability decreases.

A 400 mg dose, for example is about 25% less bioavailable than a 100 mg dose. Over the recommended dose

range of 300 mg to 600 mg three times a day, however, the differences in bioavailability are not large, and

bioavailability is about 60%. The bioavailability of the 800 mg dose was found to be approximately 35%

in single and multiple dose studies. The absolute bioavailability of gabapentin following daily doses of

1200 mg/day, 2400 mg/day, 3600 mg/day, and 4800 mg/day averaged 47%, 34%, 33%, and 27% respectively.

NUPENTIN – PRODUCT INFORMATION

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,

steadystate

pre-dose

concentrations

gabapentin

cerebrospinal

fluid

were

approximately 20% of

the corresponding plasma concentrations.

Metabolism

Gabapentin is eliminated from the systemic circulation by renal excretion as unchanged drug. Gabapentin is

not appreciably metabolised in humans.

Excretion

The elimination half-life of gabapentin is 5 to 7 hours and is unaltered by dose or following multiple dosing.

Gabapentin elimination rate constant, plasma clearance, and renal clearance are directly proportional to

creatinine clearance. In elderly patients, and in patients with impaired renal function, gabapentin plasma

clearance is reduced. Gabapentin can be removed by haemodialysis.

Dose adjustment in patients with compromised renal function or in those undergoing haemodialysis

is recommended (see

Section 4.2

DOSE AND METHOD OF ADMINISTRATION

Special Populations

Patients with Renal Insufficiency

Subjects with renal insufficiency (mean creatinine clearance ranging from 13 mL/min to 114 mL/minute)

were administered 400 mg oral dose of gabapentin. The mean gabapentin half-life ranged from about 6.5

hours

(patients with creatinine clearance (CL

> 60 mL/min) to 52 hours (CL

< 30 mL/min) and gabapentin

renal

clearance

ranged

from

about

mL/min

>

mL/min)

about

mL/min

<

mL/min).

Gabapentin dosage should be adjusted in patients with compromised renal function (see

Section 4.2

DOSE AND METHOD OF ADMINISTRATION

Patients on Haemodialysis

In a study in anuric patients, the elimination half-life of gabapentin on non-dialysis 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).

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/min in those younger than 30 years of age to

about 125 mL/min in those older than 70 years of age. Renal clearance also declined with age; however, the

decline in the renal clearance of gabapentin can largely be explained by the decline in renal function.

Reduction of gabapentin dose may be required in patients who have age-related compromised renal function.

Paediatric patients

Gabapentin pharmacokinetics were determined in 24 healthy paediatric subjects between the ages of four

and twelve 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

NUPENTIN – PRODUCT INFORMATION

using bacterial or mammalian cells.

Gabapentin did not induce structural chromosome aberrations in

mammalian cells

in vitro

in vivo

, and did not induce micronucleus formation in the bone marrow of hamsters.

Carcinogenicity

Gabapentin was given in the diet to mice at 200, 600, and 2000 mg/kg/day and to rats at 250, 1000 and

2000 mg/kg/day for 2 years.

A statistically significant increase in the incidence of pancreatic acinar cell

adenoma and carcinoma

was found only in

male rats

at the highest dose.

Peak plasma

gabapentin

concentrations and areas under the concentration time curve in rats at 2000 mg/kg/day were 14 times higher

than plasma concentrations in humans given the recommended maximum tolerated dose of 2400 mg/day. The

pancreatic acinar cell tumours in male rats were low grade malignancies, which did not metastasise or invade

surrounding tissue, and were similar to those seen in concurrent controls. The relevance of these pancreatic

acinar cell tumours in male rats to carcinogenic risk in humans is unclear.

6

PHARMACEUTICAL PARTICULARS

6.1

LIST OF EXCIPIENTS

NUPENTIN also contains the following excipients: maize starch, purified talc, gelatin and titanium dioxide.

NUPENTIN 300 also contains Allura red AC CI16035 and Quinoline yellow CI47005.

NUPENTIN 400 also contains Sunset yellow FCF CI15985, Iron oxide red CI77491 and Iron oxide yellow

CI77192. TekPrint SW-9009 Black Ink and TekPrint SW-9008 Black Ink are used as printing inks.

6.2

INCOMPATIBILITIES

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 25

This medicinal product does not require any special storage conditions.

6.5

NATURE AND CONTENTS OF CONTAINER

Container closure details: PVC/PE/PVDC/Al blister packs and HDPE bottles* with PP caps

Pack sizes:

NUPENTIN 100

NUPENTIN 300

NUPENTIN 400:

Available in blister packs and bottles* each

containing 100 capsules.

* Not marketed in Australia.

6.6

SPECIAL PRECAUTIONS FOR DISPOSAL

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

6.7

PHYSICOCHEMICAL PROPERTIES

Chemical Structure

NUPENTIN – PRODUCT INFORMATION

Chemical name: 1-(aminomethyl) cyclohexaneacetic acid

Molecular formula:

Molecular weight: 171.24

CAS Number

60142-96-3

7

MEDICINE SCHEDULE (POISONS STANDARD)

Schedule 4 - Prescription Only Medicine

8

SPONSOR

Alphapharm Pty Limited

Level 1, 30 The Bond

30 – 34 Hickson Road

Millers Point NSW 2000

www.mylan.com.au

9

DATE OF FIRST APPROVAL

23/07/2004

10 DATE OF REVISION

06/08/2019

Summary Table of Changes

Section Changed

Summary of New Information

All

PI reformat

All

Removed reference to gabapentin tablets (discontinued)

2

Addition of ingredients with known effects in line with TGO 91 labelling

requirements

6.5

Addition of container closure details for gabapentin capsules

Nupentin_pi\Aug19/00

Read the complete document

Public Summary

Summary for ARTG Entry:

174062

NUPENTIN TABS gabapentin 800 mg tablet blister pack

ARTG entry for

Medicine Registered

Sponsor

Alphapharm Pty Ltd

Postal Address

PO Box R1462,ROYAL EXCHANGE, NSW, 1225

Australia

ARTG Start Date

18/10/2011

Product category

Medicine

Status

Active

Approval area

Drug Safety Evaluation Branch

Conditions

Conditions applicable to all therapeutic goods as specified in the document "Standard Conditions Applying to Registered or Listed Therapeutic Goods

Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Conditions applicable to the relevant category and class of therapeutic goods as specified in the document "Standard Conditions Applying to Registered

or Listed Therapeutic Goods Under Section 28 of the Therapeutic Goods Act 1989" effective 1 July 1995.

Products

1. NUPENTIN TABS

Product Type

Single Medicine Product

Effective date

16/10/2017

Warnings

See Product Information and Consumer Medicine Information for this product

Standard Indications

Specific Indications

Gabapentin is indicated for the treatment of partial seizures, including secondarily generalised tonic-clonic seizures, initially as add-on therapy in adults

and children age 3 years and above who have not achieved adequate control with standard antiepileptic drugs.,Gabapentin is indicated for the treatment

of neuropathic pain.

Additional Product information

Container information

Type

Material

Life Time

Temperature

Closure

Conditions

Blister Pack

PA/Al/PVC/Al -

polyamide-aluminium

foil-polyvinylchloride/al

uminium foil

24 Months

Store below 25

degrees Celsius

Not recorded

Store in Original

Container

Pack Size/Poison information

Pack Size

Poison Schedule

(S4) Prescription Only Medicine

(S4) Prescription Only Medicine

Components

1.

Dosage Form

Tablet

Route of Administration

Oral

Visual Identification

White to off-white, oval, biconvex, uncoated, beveled edged tablets

debossed with "MYLAN" on one side and "G / 25" on the other side.

Active Ingredients

Gabapentin

800 mg

© Commonwealth of Australia.This work is copyright.You are not permitted to re-transmit, distribute or commercialise the material without obtaining prior

written approval from the Commonwealth.Further details can be found at http://www.tga.gov.au/about/website-copyright.htm.

Public Summary

Page 1 of

Produced at 29.11.2017 at 03:39:33 AEDT

This is not an ARTG Certificate document.

The onus is on the reader to verify the current accuracy of the information on the document subsequent to the date shown.

Visit www.tga.gov.au for contact information

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