Consumer medicine information

Noumed Lamotrigine

Lamotrigine

BRAND INFORMATION

Brand name

Noumed Lamotrigine

Active ingredient

Lamotrigine

Schedule

S4

 

Consumer medicine information (CMI) leaflet

Please read this leaflet carefully before you start using Noumed Lamotrigine.

What is in this leaflet

This leaflet answers some common questions about NOUMED LAMOTRIGINE.

It does not contain all of 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 taking NOUMED LAMOTRIGINE against the benefits it is expected to have for you or your child.

If your child is being treated with NOUMED LAMOTRIGINE, follow the same instructions in this leaflet as you would as the patient.

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 NOUMED LAMOTRIGINE is used for

NOUMED LAMOTRIGINE dispersible and chewable tablets contain the active ingredient lamotrigine.

Lamotrigine belongs to a group of medicines known as anti-epileptic medicines that are used to treat epilepsy in adults and children. NOUMED LAMOTRIGINE is used in partial or generalised seizures.

It may be used alone or in combination with other anti-epileptic medicines. In children, lamotrigine may be used only in combination with other antiepileptic medicines.

It is thought that NOUMED LAMOTRIGINE tablets work by controlling the levels of some brain chemicals that send signals to nerves.

Your doctor may have prescribed NOUMED LAMOTRIGINE for another reason.

Ask your doctor if you have any questions about why NOUMED LAMOTRIGINE has been prescribed for you or your child.

NOUMED LAMOTRIGINE is not recommended for use in children under 2 years of age.

There is no evidence that lamotrigine is addictive.

Before you take it

When you must not take it

Do not take NOUMED LAMOTRIGINE tablets if you are allergic to lamotrigine or any of the ingredients listed at the end of this leaflet. Some of the symptoms of an allergic reaction include shortness of breath; wheezing or difficulty in breathing; swelling of the face, lips tongue or other parts of the body; rash, itching or hives on the skin.

Do not take this medicine after the expiry date printed on the pack, or if the packaging is torn or shows signs of tampering. If you take it after the expiry date has passed, it may not work as well.

If it has expired or is damaged, return the pack to your pharmacist for disposal.

If you are not sure whether you should start talking this medicine, talk to your doctor.

Before you start to take it

Tell your doctor if you are taking any other medicines that contain lamotrigine.

Tell your doctor if you have allergies to any other medicines, foods, preservatives or dyes.

Tell your doctor if you are pregnant or intend to become pregnant. NOUMED LAMOTRIGINE may affect your unborn baby if you take it during pregnancy but it is still important that you control your fits while you are pregnant. Your doctor will discuss the risks and benefits of taking NOUMED LAMOTRIGINE during pregnancy and help you decide whether or not you should take it.

It is recommended that women on anti-epileptic medicines, such as NOUMED LAMOTRIGINE, receive pre-pregnancy counselling with regard to the possible risk on their unborn child.

Studies have shown a decrease in the levels of folic acid during pregnancy when lamotrigine is used. It is therefore recommended that you take a folate supplement, e.g. 5 mg daily, before becoming pregnant and during the first 12 weeks of your pregnancy.

Tell your doctor if you are breastfeeding or planning to breast-feed. Lamotrigine is thought to pass into breast milk. Your doctor will discuss the risks and benefits of taking NOUMED LAMOTRIGINE tablets while breast-feeding.

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

  • a history of allergy or rash to other anti-epileptic drugs.
  • liver or kidney problems
  • Parkinson’s disease, a slowly progressing "movement disorder" with symptoms such as trembling, rigid posture, slow movements and a shuffling, unbalanced walk. NOUMED LAMOTRIGINE may worsen these symptoms.
  • developed meningitis after taking lamotrigine.

Taking other medicines

Tell your doctor if you are taking any other medicines, including any that you get without a prescription from a pharmacy, supermarket or health food shop. Some medicines may interfere with the absorption or action of NOUMED LAMOTRIGINE tablets.

These include:

  • other medicines used to treat seizures or mental health problems including phenytoin, phenobarbitone, primidone, sodium valproate, carbamazepine, risperidone, zonisamide
  • rifampicin (an antibiotic used to treat certain bacterial infections)
  • lopinavir/ritonavir (used to treat HIV)
  • organic cationic transporter 2 (OCT2) substrates such as dofetilide
  • any form of hormonal contraceptives (e.g. oral contraceptive pills) or hormone replacement therapies (HRT)

These medicines may be affected by NOUMED LAMOTRIGINE or may affect how well it works. You may need to use different amounts of your medicine or you may need to take different medicines. Your doctor will be able to tell you what to do when taking NOUMED LAMOTRIGINE with other medicines.

Your doctor or pharmacist has more information on medicines to be careful with or avoid while taking NOUMED LAMOTRIGINE.

How to take NOUMED LAMOTRIGINE

Using it for the first time

You may notice that you feel dizzy, tired or unsteady in the first few weeks of treatment with NOUMED LAMOTRIGINE. During this period, you may also notice that you have slight problems with your vision. As your reactions may be slower during this period, you should not operate any machinery or appliances and you should not drive a vehicle. If any of these effects do not go away or are troublesome, you should see your doctor.

If you develop any skin rash (e.g. spots or hives) during NOUMED LAMOTRIGINE treatment, contact your doctor immediately. There are reports of severe, potentially life-threatening skin rashes associated with lamotrigine treatment, particularly in children.

Treatment with lamotrigine will be discontinued unless the rash is not drug-related.

Tell your doctor if you have thoughts of suicide or self-harm at any time while being treated with NOUMED LAMOTRIGINE.

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

How much to take

Take NOUMED LAMOTRIGINE tablets as directed by your doctor or pharmacist. Never change the dose yourself. Do not increase the dose more quickly than you have been told.

Your doctor and pharmacist will give you instructions on:

  • how many tablets to take at each time (dose)
  • how many doses to take each day
  • when to take each of your doses

Your doctor may also advise you to start or stop taking other medications depending on what conditions you are being treated for and the way you respond to treatment.

If your doctor has prescribed NOUMED LAMOTRIGINE to your child for epilepsy, their weight will be checked and the dose reviewed as their weight changes.

If there is something that you do not understand ask either your doctor or pharmacist.

It is usual for the dose of NOUMED LAMOTRIGINE to start at quite a low level and be slowly increased during the first few weeks of treatment. The doses that your doctor prescribes will generally depend on your age and weight, any other medications you are taking, and your response to NOUMED LAMOTRIGINE.

Your dose may be different if:

  • you have problems with your liver/kidney(s)
  • you have been taking other antiepileptic medicines
  • you start or stop taking hormonal contraceptive pills (oral pills)

Tell your doctor if there are any changes in your menstrual pattern, such as breakthrough bleeding. Your doctor may need to adjust the dose of NOUMED LAMOTRIGINE as the contraceptive may not work as effectively.

Talk to your doctor as soon as possible if you become pregnant or if you are planning to become pregnant. Your doctor may need to change the dose of NOUMED LAMOTRIGINE during your pregnancy.

How to take it

NOUMED LAMOTRIGINE may be taken with or without food.

The tablets may be swallowed whole, chewed or dispersed in a small volume of water (at least enough to cover the whole tablet).

When to take it

Take your NOUMED LAMOTRIGINE tablets at about the same time each day. Taking your tablets at the same time each day will have the best effect. It will also help you to remember when to take the tablets.

How long to take it

Continue taking NOUMED LAMOTRIGINE until your doctor tells you to stop. Most people will need to take NOUMED LAMOTRIGINE for a long time. If you stop taking NOUMED LAMOTRIGINE, your symptoms may return.

Your doctor will advise you if you need to stop taking NOUMED LAMOTRIGINE, and how to gradually reduce your dose over a period of two weeks.

If you forget to take it

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

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

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

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

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

If you take too much (overdose)

Immediately telephone your doctor or the Poisons Information Centre (13 11 26), or go to Accident and Emergency at your nearest hospital, if you think that you or anyone else has taken too many NOUMED LAMOTRIGINE tablets. Do this even if there are no signs of discomfort or poisoning. You may need urgent medical attention. Keep this telephone number handy.

Symptoms of lamotrigine overdose can include:

  • rapid, uncontrollable movements of the eyes
  • clumsiness and lack of co-ordination affecting your balance or when walking
  • dizziness, headache
  • drowsiness
  • blurred vision
  • vomiting
  • increased seizures, fits, convulsions
  • loss of consciousness, coma

Taking very high doses of lamotrigine can be fatal.

While you are taking it

Your doctor or pharmacist will give you special instructions while you or your child are being treated with NOUMED LAMOTRIGINE.

Things you must do

Take NOUMED LAMOTRIGINE exactly as your doctor tells you to.

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

Visit your doctor regularly for check-ups.

Tell any doctor, dentist or pharmacist who is treating you that you are taking NOUMED LAMOTRIGINE, especially if you are about to be started on any new medicine.

If you are to undergo a laboratory test, tell the doctor, nurse or hospital that you are taking NOUMED LAMOTRIGINE. Lamotrigine may interfere with some tests to detect other drugs.

Tell your doctor immediately if you become pregnant or are trying to become pregnant while taking NOUMED LAMOTRIGINE. Your doctor will discuss the risks and benefits of taking this medicine during pregnancy.

Talk to your doctor if you are breastfeeding or planning to breastfeed. Lamotrigine can pass into breast milk and may affect your baby. Your doctor will discuss the risks and benefits of breastfeeding while taking NOUMED LAMOTRIGINE.

Contact your doctor immediately if you develop any skin rash (e.g. spots or hives) during treatment with NOUMED LAMOTRIGINE. Treatment with lamotrigine will be discontinued unless the rash is not drug-related since the effects can be severe and potentially life-threatening.

Tell your doctor immediately if you have any suicidal thoughts or mood changes. Anti-epileptic medicines, including lamotrigine, may increase the risk of having suicidal thoughts and making suicide attempts. All mentions suicide or violence must be taken seriously.

If you or someone you know have any of the following warning signs of suicide-related behaviour while being treated with NOUMED LAMOTRIGINE, contact your doctor immediately, helpline or Accident and Emergency at your nearest hospital:

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

Tell your doctor if, for any reason, you have not taken your medicine exactly as directed. Otherwise, your doctor may think that it was not working as it should and change your treatment unnecessarily.

Things you must not do

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

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

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

Do not stop taking NOUMED LAMOTRIGINE, or lower the dose, without first checking with your doctor. If you stop taking NOUMED LAMOTRIGINE suddenly, your epilepsy may come back or become worse. This is known as rebound seizures. Your doctor will advise you if you need to stop taking NOUMED LAMOTRIGINE tablets and how.

Things to be careful of

Be careful driving or operating machinery until you know how NOUMED LAMOTRIGINE affects you. NOUMED LAMOTRIGINE may make you feel drowsy, dizzy, or cause blurring of vision, which could affect your ability to drive or operate machinery. If this occurs do not drive.

If you drink alcohol, the drowsiness, dizziness or light-headedness may be worse.

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

Side effects

Tell your doctor or pharmacist as soon as possible if you do not feel well while you are taking NOUMED LAMOTRIGINE, even if the effect is not listed below.

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

The most commonly reported side effects are:

  • dizziness or motion problems such as tics, unsteadiness and jerkiness
  • tremor
  • skin rashes
  • headache
  • feeling sick (nausea)
  • vomiting
  • feeling drowsy, tired or weak
  • blurred or double vision
  • rapid, uncontrollable eye movements
  • trouble sleeping
  • irritability, aggression or agitation
  • hallucinations, confusion
  • increased activity in children
  • joint, back or stomach pain
  • respiratory or lung problems
  • depression
  • loss of memory
  • liver problems
  • diarrhoea
  • dry mouth

In general, these side effects usually happen only during the first few weeks of treatment with NOUMED LAMOTRIGINE.

If any of these side effects persist, or are troublesome, see your doctor.

Other very rare but serious side effects may need urgent medical attention or hospitalisation.

“Lupus-like reactions” may present as a collection of symptoms consisting of fever, pain in the joints and general ill-health.

Meningitis may present as a group of symptoms consisting of fever, nausea, vomiting, headache, stiff neck and extreme sensitivity to bright light. These may be caused by an inflammation of the membranes that cover the brain and spinal cord.

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

  • thoughts of suicide or self-harm
  • allergic reactions
  • severe skin reactions with blisters, sores or ulceration
  • fainting
  • high temperature, swelling of the face, enlarged lymph glands in neck, armpits or groin
  • unusual bleeding or increased tendency to bleed, persistent sore throat and frequent infections and/or anaemia
  • sore mouth or sore eyes
  • sudden onset of severe abdominal pain associated with feeling sick (nausea) and being sick (vomiting)
  • yellowing of skin and whites of eyes (jaundice) with decreased appetite and/or abdominal pain
  • an increase in the frequency of seizures or convulsions
  • unusual movements that you cannot control such as irregular jerking or shaking of arms and legs
  • unsteadiness or loss of coordination while walking
  • worsening of your symptoms if you already have Parkinson’s Disease
  • temporary paralysis or weakness of muscles

Other side effects not listed above may also occur in some patients. Some of these side effects (for example, changes in your liver function) can only be found when your doctor does tests from time to time to check your progress.

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

Tell your doctor if you notice anything else that is making you feel unwell, if your seizures get worse or experience new types of seizures.

After taking it

Storage

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

Keep your medicine in a cool, dry place, protected from light, where the temperature stays below 25°C. Do not store it, or any other medicine, in the bathroom or near a sink. Do not leave it in the car on hot days.

Heat and dampness can destroy some medicines.

Keep this medicine 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.

Disposal

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

Product description

What it looks like

NOUMED LAMOTRIGINE dispersible and chewable tablets are available in 4 strengths.

All tablets are white to off-white, uncoated, circular, flat and bevel-edged with a characteristic fruity odour. One side is plain while the other side is debossed to indicate the strength:

25 mg: LI2
50 mg: LI3
100 mg: LI4
200 mg: LI5

The tablets are packaged in blister packs (either Alu/PA-Alu/PVC or PVC/PvDC-Alu) of 56 tablets.

Ingredients

Active ingredient

NOUMED LAMOTRIGINE tablets contain 25 mg, 50 mg, 100 mg or 200 mg of lamotrigine.

Inactive ingredients

  • microcrystalline cellulose
  • crospovidone
  • calcium carbonate
  • aspartame
  • povidone
  • hyprolose
  • magnesium stearate
  • maltodextrin
  • purified talc
  • colloidal anhydrous silica
  • mixed berries flavour

NOUMED LAMOTRIGINE tablets contain aspartame, but do not contain lactose, sucrose, gluten, tartrazine or any other azo dyes.

Sponsor

Avallon Pharmaceuticals Pty Ltd
Level 5, 7 Eden Park Drive
Macquarie Park NSW 2113
Telephone 1800 930 999
www.avallon-pharma.com.au

Australian Registration numbers

25 mg: AUST R 324705
50 mg: AUST R 324706
100 mg: AUST R 324707
200 mg: AUST R 324708

This leaflet was revised in February 2021.

Published by MIMS April 2021

BRAND INFORMATION

Brand name

Noumed Lamotrigine

Active ingredient

Lamotrigine

Schedule

S4

 

1 Name of Medicine

Lamotrigine.

2 Qualitative and Quantitative Composition

Noumed Lamotrigine chewable and dispersible tablets contain 25 mg, 50 mg, 100 mg or 200 mg of lamotrigine.

Excipients with known effect.

Contains aspartame. For the full list of excipients, see Section 6.1 List of Excipients.

3 Pharmaceutical Form

Noumed Lamotrigine chewable and dispersible tablets are white to off-white, uncoated, circular flat beveled tablets with a characteristic fruity odour.
The 25 mg tablet is debossed with "LI2" on one side and plain on the other side.
The 50 mg tablet is debossed with "LI3" on one side and plain on the other side.
The 100 mg tablet is debossed with "LI4" on one side and plain on the other side.
The 200 mg tablet is debossed with "LI5" on one side and plain on the other side.

4 Clinical Particulars

4.1 Therapeutic Indications

Noumed Lamotrigine is an antiepileptic drug for the treatment of partial and generalised seizures in adults and children.
There is extensive experience with lamotrigine used initially as "add-on" therapy. The use of lamotrigine has also been found to be effective as monotherapy following withdrawal of concomitant antiepileptic drugs.
Initial monotherapy treatment in newly diagnosed paediatric patients is not recommended.

4.2 Dose and Method of Administration

General considerations.

Restarting therapy.

Prescribers should assess the need for escalation to maintenance dose when restarting lamotrigine in patients who have discontinued lamotrigine for any reason, since the risk of serious rash is associated with high initial doses and exceeding the recommended dose escalation for lamotrigine (see Section 4.4 Special Warnings and Precautions for Use). The greater the interval of time since the previous dose, the more consideration should be given to escalation to the maintenance dose. When the interval since discontinuing lamotrigine exceeds five half-lives (see Section 5.2 Pharmacokinetic Properties), lamotrigine should generally be escalated to the maintenance dose according to the appropriate schedule.
It is recommended that lamotrigine not be restarted in patients who have discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefit clearly outweighs the risk.

Initial dose.

It is strongly recommended that therapy with Noumed Lamotrigine be initiated at the recommended doses. Careful incremental titration of the dose may decrease the severity of skin rashes.
If a calculated dose of lamotrigine (e.g. for use in children and patients with hepatic impairment) does not equate to whole Noumed Lamotrigine tablets, the dose to be administered is that equal to the lower number of whole tablets. If the calculated dose is 1-2 mg, 2 mg lamotrigine may be taken on alternate days for the first two weeks. If the calculated daily dose is less than 1 mg then lamotrigine should not be administered.
The minimum strength available for Noumed Lamotrigine is 25 mg. Therefore, if the calculated dose is less than 25 mg, other lamotrigine products available in 2 mg and 5 mg strengths should be used instead of Noumed Lamotrigine.

Add-on or withdrawal of concomitant antiepileptic drugs.

When concomitant antiepileptic drugs are withdrawn to achieve lamotrigine monotherapy or other antiepileptic drugs (AEDs) are added-on to treatment regimens containing lamotrigine, consideration should be given to the effect this may have on lamotrigine pharmacokinetics (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
The dose of lamotrigine following the withdrawal of concomitant antiepileptic drugs will be dependent upon the pharmacokinetics of the drugs being withdrawn, together with the overall clinical response of the patient. The withdrawal of enzyme inducing antiepileptic drugs (e.g. phenytoin and carbamazepine) may not require a reduction in the lamotrigine dose unless there is a need due to safety considerations. An increase in the lamotrigine dose may, however, be required following the withdrawal of enzyme inhibiting antiepileptic drugs (e.g. sodium valproate) (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Discontinuation of lamotrigine in patients with epilepsy.

As with other antiepileptic drugs, abrupt withdrawal of lamotrigine may provoke rebound seizures and should be avoided wherever possible. Unless safety concerns (for example serious skin reactions) require an abrupt withdrawal, the dose of lamotrigine should be gradually decreased over a period of two weeks.

Monotherapy in adults and children over 12 years of age.

The initial Noumed Lamotrigine dose in monotherapy is 25 mg once a day for two weeks, followed by 50 mg once a day for two weeks. Thereafter, the dose should be increased by a maximum of 50 to 100 mg every one to two weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 100 to 200 mg/day given once a day or as two divided doses (see Table 1).

Add-on therapy.

In adults and children over 12 years of age.

In those patients taking sodium valproate, the initial Noumed Lamotrigine dose is 25 mg every alternate day for two weeks, followed by 25 mg once a day for two weeks. Thereafter, the dose should be increased by a maximum of 25-50 mg every 1-2 week until the optimal response is achieved. The usual maintenance dose is 100 to 200 mg/day given once a day or as a divided dose (see Table 1).
The initial Noumed Lamotrigine dose in those patients not taking sodium valproate is 50 mg once a day for two weeks, followed by 100 mg/day given in two divided doses for two weeks. Thereafter, the dose should be increased by a maximum of 100 mg every 1-2 week until the optimal response is achieved. The usual maintenance dose is 200 to 400 mg/day given as a divided dose (see Table 1).
In open continuation studies, some patients were safely maintained on doses of lamotrigine in the range 500 to 700 mg daily for periods of up to approximately one year at the time of study completion.
In those patients taking other medications that do not significantly inhibit or induce lamotrigine glucuronidation (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions), the initial lamotrigine dose is 25 mg once a day for two weeks, followed by 50 mg once a day for two weeks. Thereafter, the dose should be increased by a maximum of 50 to 100 mg every one to two weeks until the optimal response is achieved. The usual maintenance dose to achieve an optimal response is 100 to 200 mg/day given once a day or as two divided doses.
Because of a risk of rash, the initial dose and subsequent dose escalation should not be exceeded (see Section 4.4 Special Warnings and Precautions for Use).

In children aged 2 to 12 years.

The minimum strength available for Noumed Lamotrigine is 25 mg. Therefore, if the calculated dose is less than 25 mg, other lamotrigine products available in 2 mg and 5 mg strengths should be used instead of Noumed Lamotrigine.
In patients taking sodium valproate with/without any other AED, the initial lamotrigine dose is 0.15 mg/kg bodyweight/day given once a day for two weeks, followed by 0.3 mg/kg bodyweight/day given once a day for two weeks. Thereafter, the dose should be increased by a maximum of 0.3 mg/kg bodyweight/day every 1-2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 1-5 mg/kg bodyweight/day given once a day or as a divided dose, with a maximum of 200 mg/day (see Table 2).
In those patients taking enzyme inducing AEDs with/without other AEDs (except sodium valproate) the initial lamotrigine dose is 0.6 mg/kg bodyweight/day given as a divided dose for two weeks, followed by 1.2 mg/kg for two weeks. Thereafter the dose should be increased by a maximum of 1.2 mg/kg every 1-2 weeks until optimal response is achieved. The usual maintenance dose is 5-15 mg/kg bodyweight/day given as a divided dose, with a maximum of 400 mg/day (see Table 2).
In patients taking other medications that do not significantly inhibit or induce lamotrigine glucuronidation (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions), the initial lamotrigine dose is 0.3 mg/kg bodyweight/day given once a day or in two divided doses for two weeks, followed by 0.6 mg/kg/day given once a day or in two divided doses for two weeks. Thereafter, the dose should be increased by a maximum of 0.6 mg/kg every one to two weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 1 to 10 mg/kg/day given once a day or in two divided doses, with a maximum of 200 mg/day.

General dosing considerations for add-on therapy.

For patients receiving lamotrigine in combination with other antiepileptic drugs, whether or not optimal dosing has been achieved, a re-evaluation of all antiepileptic drugs in the regimen should be considered if a change or no improvement in seizure control or an appearance or worsening of adverse experiences is observed (see Section 4.4 Special Warnings and Precautions for Use).

General dosing recommendations in special patient populations.

Women taking hormonal contraceptives.

(a) Starting lamotrigine in patients already taking hormonal contraceptives.

Although an oral contraceptive has been shown to increase the clearance of lamotrigine (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions), no adjustment to the recommended dose escalation guidelines for lamotrigine should be necessary solely based on the use of hormonal contraceptives.
Dose escalation should follow the recommended guidelines based on whether lamotrigine is added:
to an enzyme inhibitor of lamotrigine for e.g. sodium valproate;
to an enzyme inducer of lamotrigine for e.g. carbamazepine, phenytoin, phenobarbital, primidone or rifampicin, or lopinavir/ritonavir;
in absence of sodium valproate, carbamazepine, phenytoin, phenobarbital, primidone, rifampicin or lopinavir/ritonavir.

(b) Starting hormonal contraceptive in patients already taking maintenance doses of lamotrigine and not taking an enzyme inducer of lamotrigine.

The maintenance doses of lamotrigine may need to be increased by as much as two fold according to the individual clinical response (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

(c) Stopping hormonal contraceptives in patients already taking maintenance doses of lamotrigine and not taking an enzyme inducers of lamotrigine.

The maintenance doses of lamotrigine may need to be decreased by as much as 50% according to the individual clinical response (see Section 4.4 Special Warnings and Precautions for Use; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).
The elderly. To date, there is no evidence to suggest that the response of this age group differs from that in young patients with epilepsy. The dosage schedule recommended in adults and children more than 12 years of age can be applied to the elderly population (aged 65 years or more). As older patients are more likely to suffer from intercurrent illness and require medications to treat other medical conditions, lamotrigine should be used cautiously in these patients and they should be monitored regularly.
Hepatic impairment. Initial, escalation and maintenance doses should generally be reduced by approximately 50% in patients with moderate (Child-Pugh grade B) and 75% in severe (Child-Pugh grade C) hepatic impairment. Escalation and maintenance doses should be adjusted accordingly to clinical response.
Renal impairment. Caution should be exercised when administering lamotrigine to patients with renal failure. For patients with end-stage renal failure, initial doses of lamotrigine should be based on patient's AED regimen; reduced maintenance doses may be effective for patients with significant renal functional impairment.

Method of administration.

All Noumed Lamotrigine tablets which have been formulated as dispersible/chewable tablets, may be swallowed whole, chewed or dispersed in a small volume of water (at least enough to cover the whole tablet).

4.3 Contraindications

Noumed Lamotrigine tablets are contraindicated in individuals with known hypersensitivity to lamotrigine, or to any other ingredients listed (see Section 6.1 List of Excipients).

4.4 Special Warnings and Precautions for Use

Skin rash.

See Boxed Warnings regarding the risk of severe, potentially life-threatening rash associated with the use of lamotrigine.
There have been reports of adverse skin reactions, which have generally occurred within the first 8 weeks after initiation of lamotrigine treatment. The majority of rashes are mild and self-limiting, however serious rashes requiring hospitalisation and discontinuation of lamotrigine have been reported. These have included potentially life-threatening rashes such as Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) (see Section 4.8 Adverse Effects (Undesirable Effects)). Although benign rashes also occur with lamotrigine, it is not possible to predict reliably which rashes will prove to be life threatening.
In adults enrolled in studies utilising the current lamotrigine dosing recommendations the incidence of serious skin rashes is approximately 1 in 500 in epilepsy patients. Approximately half of these cases have been reported as SJS (1 in 1000).
The risk of serious skin rashes is higher in children than in adults. Available data from a number of studies suggest the incidence of rashes associated with hospitalisation in epileptic children is from 1 in 300 to 1 in 100.
In children, the initial presentation of a rash can be mistaken for an infection. Physicians should consider the possibility of a drug reaction in children that develop symptoms of rash and fever during the first eight weeks of therapy.
Additionally, the overall risk of rash appears to be strongly associated with:
high initial doses of lamotrigine and exceeding the recommended dose escalation of lamotrigine therapy; and
concomitant use of sodium valproate, which increases the mean half-life of lamotrigine nearly two-fold (see Section 4.2 Dose and Method of Administration).
Caution is also required when treating patients with a history of allergy or rash to other antiepileptic drugs as the frequency of non-serious rash after treatment with lamotrigine was approximately three times higher in these patients than in those without such history.
All patients (adults and children) who develop a rash should be promptly evaluated and lamotrigine withdrawn immediately unless the rash is clearly not drug related. It is recommended that lamotrigine not be restarted in patients who have discontinued due to rash associated with prior treatment with lamotrigine unless the potential benefit clearly outweighs the risk. If the patient has developed SJS, TEN or DRESS with the use of lamotrigine, treatment with lamotrigine must not be restarted in this patient at any time.

Hypersensitivity syndrome.

Rash has also been reported as part of a hypersensitivity syndrome, known as DRESS, associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, facial oedema, abnormalities of the blood and liver and aseptic meningitis. Eosinophilia is often present. Some reports have been fatal or life-threatening. The syndrome shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation (DIC), rhabdomyolysis and multiorgan failure. Very rarely, rhabdomyolysis has been observed in patients experiencing severe hypersensitivity reactions, however, it is not possible to determine whether rhabdomyolysis occurred as part of the initial hypersensitivity reaction or if it was a consequence of the clinical complexity of the cases. It is important to note that early manifestations of hypersensitivity (e.g. fever, lymphadenopathy) may be present even though rash is not evident. If such signs and symptoms are present the patient should be evaluated immediately and lamotrigine discontinued if an alternative aetiology cannot be established.

Haemophagocytic lymphohistiocytosis.

There have been reports of haemophagocytic lymphohistiocytosis (HLH) with use of lamotrigine in paediatric and adult patients. HLH is an aggressive and life-threatening syndrome of pathologic immune activation characterised by clinical signs and symptoms of extreme systemic inflammation. It is associated with high mortality rates if not recognised early and treated. Most patients with HLH are acutely ill with multi-organ involvement. Common findings include fever, hepatosplenomegaly, rash, lymphadenopathy, neurologic symptoms, cytopenias, high serum ferritin and liver function and coagulation abnormalities. Symptoms have been reported to occur within 8 to 24 days following the initiation of treatment. Diagnosis is often complicated because early signs and symptoms such as fever and rash are not specific and thus it may also be confused with other serious immune-related adverse reactions such as DRESS/hypersensitivity syndrome. All patients who develop fever or rash and/or early manifestations of pathologic immune activation should be evaluated immediately, and a diagnosis of HLH should be considered. Lamotrigine should be discontinued if HLH is suspected and an alternative aetiology for the signs and symptoms cannot be established.
Prior to initiation of treatment with lamotrigine, patients should be informed that excessive immune activation may occur with lamotrigine and they should be advised to seek immediate medical attention if they experience symptoms of HLH (such as fever, rash of lymphadenopathy) during lamotrigine treatment.

Aseptic meningitis.

Therapy with lamotrigine increases the risk of developing aseptic meningitis. Because of the potential for serious outcomes of untreated meningitis due to other causes, patients should also be evaluated for other causes of meningitis and treated as appropriate.
Postmarketing cases of aseptic meningitis have been reported in paediatric and adult patients taking lamotrigine for various indications. Symptoms upon presentation have included headache, fever, nausea, vomiting, nuchal rigidity, rash, photophobia, myalgia, chills, altered consciousness and somnolence. Symptoms have been reported to occur within 1 day to one and a half months following the initiation of treatment.
Aseptic meningitis was reversible on withdrawal of the drug in most cases, but recurred in a number of cases on re‐exposure to lamotrigine. Re‐exposure resulted in a rapid return of symptoms that were frequently more severe. Lamotrigine should not be restarted in patients who have discontinued due to aseptic meningitis associated with prior treatment of lamotrigine. Some of the patients treated with lamotrigine who developed aseptic meningitis had underlying diagnoses of systemic lupus erythematosus or other autoimmune diseases.

Abrupt withdrawal.

As with other antiepileptic drugs for the treatment of epilepsy, abrupt withdrawal of lamotrigine may provoke rebound seizures. Unless safety concerns (for example serious skin reactions) require an abrupt withdrawal, the dose of lamotrigine should be gradually decreased over a period of two weeks.
When concomitant antiepileptic drugs are withdrawn to achieve lamotrigine monotherapy or other antiepileptic drugs are added-on to lamotrigine monotherapy, considerations should be given to the effect this may have on lamotrigine pharmacokinetics (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Suicidal behaviour and ideation.

Symptoms of depression and/or bipolar disorder may occur in patients with epilepsy, and there is evidence that patients with epilepsy and bipolar disorder has an elevated risk for suicidality.
Twenty-five to 50% of patients with bipolar disorder attempt suicide at least once, and may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviours (suicidality) whether or not they are taking medications for bipolar disorder, including lamotrigine.

Risk associated with lamotrigine.

The incidence of suicidal ideation and behaviour was evaluated in a pooled analysis of placebo-controlled clinical trials with lamotrigine involving a total of 6467 patients from a number of indications, including studies in epilepsy and bipolar disorder.
In the subset of bipolar disorder trials, the rate of events was numerically, but not statistically significantly, greater for lamotrigine (29/1212 [2.4%]) compared with placebo (19/1054 [1.8%]). In a pooled analysis of psychiatric indications, events were more common in the first month of treatment, in patients taking lamotrigine. Behavioural events were more common in males.
In the subset of epilepsy trials, there were no statistically significant differences in the rate of events between lamotrigine and placebo. Although the number of suicidal ideation and behaviour events was too low (6/1073 [0.6%] on lamotrigine and 2/805 [0.3%] on placebo) to allow a definitive comparison between treatment groups, the relative rate reported from this lamotrigine analysis is consistent with a possible class effect reported by the US Food and Drug Administration, based on their meta-analysis of 11 anticonvulsant drugs including lamotrigine.

Risk associated with antiepileptic drugs in general.

Antiepileptic drugs, including lamotrigine, 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 3 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 lamotrigine or any other AED must balance this risk with the risk of untreated illness. Epilepsy and many other illnesses for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behaviour. Should suicidal thoughts and behaviour emerge during treatment, the prescriber needs to consider whether the emergence of these symptoms in any given patient may be related to the illness being treated.
Patients, their caregivers and families should be informed that AEDs increase the risk of suicidal thoughts and behaviour and should be advised of the need to be alert for the emergence of worsening of the signs and symptoms of depression, any unusual changes in mood or behaviour, or the emergence of suicidal thoughts, behaviour, or thoughts about self-harm. Behaviours of concern should be reported immediately to the treating doctor.

Hormonal contraceptives.

Effect of hormonal contraceptives on lamotrigine efficacy.

An ethinylestradiol/levonorgestrel (30 microgram/150 microgram) combination has been demonstrated to increase the clearance of lamotrigine by approximately two-fold resulting in decreased lamotrigine levels (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). Following titration, higher maintenance doses of lamotrigine (by as much as two-fold) may be needed to attain a maximal therapeutic response. In women already not taking an inducer of lamotrigine glucuronidation and taking a hormonal contraceptive that include one week of inactive medication (e.g. "pill free week"), gradual transient increase in lamotrigine levels will occur during the week of inactive medication. These increases will be greater when lamotrigine dose increases are made in the days before or during the week of inactive medication (see Section 4.2 Dose and Method of Administration).
Clinicians should exercise appropriate clinical management of women starting or stopping hormonal contraceptives during lamotrigine therapy and lamotrigine dosing adjustment may be needed.
Other oral contraceptive and HRT treatment have not been studied, though they may similarly affect lamotrigine pharmacokinetic parameters.

Effects of lamotrigine on hormonal contraceptive efficacy.

An interaction study in 16 healthy volunteers has shown that when lamotrigine and a hormonal contraceptive (ethinylestradiol/ levonorgestrel combination) are administered in combination, there is a modest increase in levonorgestrel clearance and changes in serum FSH and LH (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions). The impact of these changes on ovarian ovulatory activity is unknown. However, the possibility of these changes resulting in decreased contraceptive efficacy in some patients taking hormonal preparations with lamotrigine cannot be excluded. Therefore patients should be instructed to promptly report changes in their menstrual pattern, i.e. breakthrough bleeding.

Effect of lamotrigine on organic cationic transporter 2 (OCT 2) substrates.

Lamotrigine is an inhibitor of renal tubular secretion via OCT 2 proteins. This may result in increased plasma levels of certain drugs that are substantially excreted via this route. Co-administration of lamotrigine with OCT 2 substrates with a narrow therapeutic index e.g. dofetilide is not recommended.

Dihydrofolate reductase.

Lamotrigine is a weak inhibitor of dihydrofolate reductase, hence there is a possibility of interference with folate metabolism during long-term therapy. During prolonged human dosing, however, lamotrigine did not induce significant changes in the haemoglobin concentration, mean corpuscular volume, or serum or red blood cell folate concentrations up to 1 year, or red blood cell folate concentrations up to 5 years.

Patients taking other lamotrigine containing preparations.

Lamotrigine should not be administered to patients currently being treated with any other preparation containing lamotrigine without consulting a doctor.

Others.

There are reports in the literature that severe convulsive seizures including status epilepticus may lead to rhabdomyolysis, multiorgan failure and disseminated intravascular coagulation, sometimes with a fatal outcome. Similar cases have occurred in association with the use of lamotrigine.
A very rare association with Brugada-type ECG has been observed following lamotrigine use. Therefore, careful consideration should be given before using lamotrigine in patients with Brugada syndrome.

Use in hepatic impairment.

Lamotrigine is cleared primarily by metabolism in the liver. Lamotrigine should be administered with caution in patients with hepatic impairment as clearance is reduced (see Section 4.2 Dose and Method of Administration, Hepatic impairment).

Use in renal impairment.

In single dose studies in subjects with end stage renal failure, plasma concentrations of lamotrigine were not significantly altered. However, accumulation of the glucuronide metabolite is to be expected; caution should, therefore, be exercised in treating patients with renal failure.

Use in the elderly.

No data available.

Paediatric use (under 2 years of age).

Lamotrigine has not been studied as monotherapy in children less than 2 years of age or as add-on therapy in children less than 1 month of age.
The safety and efficacy of lamotrigine as add-on therapy of partial seizures in children aged 1 month to 2 years has not been established (trial data shows plasma concentrations may be unexpectedly high in some patients in this age group). Therefore lamotrigine is not recommended in children less than 2 years of age.

Effects on laboratory tests.

Lamotrigine has been reported to interfere with the assay used in some rapid urine drug screens, which can result in false positive readings, particularly for phencyclidine (PCP). A more specific alternative chemical method should be used to confirm a positive result.

4.5 Interactions with Other Medicines and Other Forms of Interactions

Uridine 5'-diphospho (UDP)-glucuronyl transferases (UGTs) have been identified as the enzymes responsible for metabolism of lamotrigine. There is no evidence that lamotrigine causes clinically significant induction or inhibition of hepatic oxidative drug-metabolising enzymes, and interactions between lamotrigine and drugs metabolised by cytochrome P450 enzymes are unlikely to occur. Lamotrigine may induce its own metabolism but the effect is modest and unlikely to have significant clinical consequences. See Table 4.
Approximately 96% of a given dose of lamotrigine is eliminated by conjugation metabolism mediated by glucuronyl-transferases. Cytochrome P450 is not involved in the elimination of lamotrigine to any significant extent. Therefore the likelihood that lamotrigine inhibits the elimination of drugs metabolised by cytochrome P450 is low.

Interactions involving AEDs.

Certain antiepileptic drugs (such as phenytoin, carbamazepine, phenobarbitone and primidone) which induce hepatic drug-metabolising enzymes induce the metabolism glucuronidation of lamotrigine and enhance the metabolism of lamotrigine (see Section 4.2 Dose and Method of Administration). Other drug-classes which induce hepatic drug-metabolising enzymes may also enhance the metabolism of lamotrigine.
Sodium valproate, which inhibits the glucuronidation of lamotrigine, reduces the metabolism of lamotrigine and increases the mean half-life of lamotrigine nearly two fold (see Section 4.4 Special Warnings and Precautions for Use; Section 4.2 Dose and Method of Administration).
There have been reports of central nervous system events including dizziness, ataxia, diplopia, blurred vision and nausea in patients taking carbamazepine following the introduction of lamotrigine. These events usually resolve when the dose of carbamazepine is reduced. A similar effect was seen during a study of lamotrigine and oxcarbazepine in healthy adult volunteers, but dose reduction was not investigated.
In a steady-state pharmacokinetic interaction study in healthy adult volunteers using daily doses of 200 mg lamotrigine and 1200 mg oxcarbazepine, oxcarbazepine did not alter the metabolism of lamotrigine and lamotrigine did not alter the metabolism of oxcarbazepine.
In a study of healthy volunteers, coadministration of felbamate (1,200 mg twice daily) with lamotrigine (100 mg twice daily for 10 days) appeared to have no clinically relevant effects on the pharmacokinetics of lamotrigine. However, the incidence of adverse effects was higher during combination therapy (90%) than during lamotrigine and placebo (48%). Adverse effects were predominantly related to the central nervous system or gastrointestinal tract, including dizziness, headache and nausea.
Based on a retrospective analysis of plasma levels in patients who received lamotrigine both with and without gabapentin, gabapentin does not appear to change the apparent clearance of lamotrigine.
Potential drug interactions between levetiracetam and lamotrigine were assessed by evaluating serum concentrations of both agents during placebo-controlled clinical trials. These data indicate that levetiracetam does not influence the pharmacokinetics of lamotrigine.
Steady-state trough plasma concentrations of lamotrigine were not affected by concomitant pregabalin (200 mg 3 times daily) administration.
In a study of patients with epilepsy, coadministration of zonisamide (200 to 400 mg/day) with lamotrigine (150 to 500 mg/day) for 35 days had no significant effect on the pharmacokinetics of lamotrigine. Increases in serum concentrations of zonisamide, leading to symptoms and signs of zonisamide toxicity, have been reported when lamotrigine was added to previously stable zonisamide therapy.
Increases in the plasma concentrations of other antiepileptic drugs have been reported in a few patients, however controlled studies have shown no evidence that lamotrigine affects the plasma concentrations of concomitant antiepileptic drugs. Evidence from in vitro studies indicates that lamotrigine does not displace other antiepileptic drugs from protein binding sites.

Interactions involving other psychoactive agents.

The pharmacokinetics of lithium after 2 g of anhydrous lithium gluconate given twice daily for six days to 20 healthy subjects were not altered by co-administration of 100 mg/day lamotrigine.
In a steady-state pharmacokinetic interaction study in healthy adult volunteers, daily doses of 15 mg olanzapine reduced the AUC and Cmax of lamotrigine by an average of 24% and 20% respectively. An effect of this magnitude is not generally expected to be clinically relevant. Lamotrigine at 200 mg daily dose did not affect the pharmacokinetics of olanzapine.
Multiple oral doses of lamotrigine 400 mg daily had no clinically significant effect on the single dose pharmacokinetics of 2 mg risperidone in 14 healthy adult volunteers. However, 12 out of the 14 volunteers reported somnolence compared to 1 out of 20 when risperidone was given alone, and none when lamotrigine was administered alone. In clinical trials of patients who took risperidone with lamotrigine or placebo, 4 out of 53 patients (7.5%) who received lamotrigine and risperidone reported the occurrence of somnolence or sedation, compared to 2 out of 62 patients (3.2%) who had taken placebo and risperidone.
In vitro experiments indicated that the formation of lamotrigine's primary metabolite, the 2-N-glucuronide, was inhibited by co-incubation with sodium valproate, bupropion, clonazepam, amitriptyline, haloperidol, and lorazepam. Sodium valproate is known to reduce the clearance of lamotrigine in vivo (see above). In these experiments, the largest effect (after that of sodium valproate) was observed with bupropion; however, multiple oral doses of bupropion had no statistically significant effects on the single dose pharmacokinetics of a low dose (100 mg) of lamotrigine in 12 subjects and caused only a slight increase in the AUC of lamotrigine glucuronide. This observation suggests that the risk of a clinically relevant interaction with amitriptyline, clonazepam, haloperidol or lorazepam is therefore unlikely. The in vitro experiments also suggested that clearance of lamotrigine is unlikely to be affected by clozapine, phenelzine, risperidone, sertraline, trazodone or fluoxetine. Bufuralol metabolism data from human liver microsomes suggest that lamotrigine does not reduce the clearance of drugs eliminated predominantly by CYP2D6.

Effect of hormonal contraceptives on lamotrigine pharmacokinetics.

In a study of 16 female volunteers, 30 microgram ethinylestradiol/150 microgram levonorgestrel in a combined oral contraceptive pill caused an approximately two-fold increase in a lamotrigine oral clearance, resulting in an average 52% and 39% reduction in lamotrigine AUC and Cmax, respectively. Serum lamotrigine concentration gradually increased during the course of the week of inactive medication, with pre-dose concentrations at the end of the week of inactive medication being on average approximately two-fold higher than during co-therapy (see Section 4.2 Dose and Method of Administration; Section 4.4 Special Warnings and Precautions for Use).

Effect of lamotrigine on hormonal contraceptive pharmacokinetics.

In a study of 16 female volunteers, a steady state dose of 300 mg lamotrigine had no effect on the pharmacokinetics of the ethinylestradiol component of a combined oral contraceptive pill. A modest increase in the oral clearance of levonorgestrel component was observed, resulting in an average 19% and 12% reduction in levonorgestrel AUC and Cmax respectively. Measurement of serum FSH, LH and estradiol during the study indicated some loss of suppression of ovarian hormonal activity in some women, although measurement of serum progesterone indicated that there was no hormonal evidence of ovulation in any of 16 subjects. The impact of the modest increase in levonorgestrel clearance and the changes in serum FSH and LH on ovarian ovulatory activity is unknown (see Section 4.4 Special Warnings and Precautions for Use). The effects of doses of lamotrigine other than 300 mg/day have not been studied and studies with other female hormonal preparations have not been conducted.

Interactions involving other medications.

Rifampicin.

In a study in 10 male volunteers, rifampicin increased lamotrigine clearance and decreased lamotrigine half-life due to induction of the hepatic enzymes responsible for glucuronidation. In patients receiving concomitant therapy with rifampicin, the treatment regimen recommended for lamotrigine and concurrent hepatic enzyme inducers should be used (see Section 4.2 Dose and Method of Administration).

Lopinavir/ritonavir.

In a study in healthy volunteers, lopinavir/ritonavir approximately halved the plasma concentrations of lamotrigine, probably by induction of glucuronidation. In patients receiving concomitant therapy with lopinavir/ritonavir, the treatment regimen recommended for lamotrigine and concurrent glucuronidation inducers should be used (see Section 4.2 Dose and Method of Administration).

Paracetamol.

A study in healthy male volunteers found that there was a slightly enhanced elimination of lamotrigine in the presence of paracetamol but this was not considered to be clinically significant.

4.6 Fertility, Pregnancy and Lactation

Effects on fertility.

Fertility was reduced following oral administration of lamotrigine to male and female rats at a dose eliciting signs of toxicity (20 mg/kg/day). There is no experience of the effect of lamotrigine on human fertility.
(Category D)
Lamotrigine should not be used in pregnancy unless, in the opinion of the physician, the potential benefits of treatment to the mother outweigh any possible risks to the developing foetus.
Postmarketing data from several prospective pregnancy registries have documented outcomes in over 2000 women exposed to lamotrigine monotherapy during the first trimester of pregnancy. Overall, these data do not suggest a substantial increase in the risk for major congenital malformations, although data from a limited number of registries have reported an increase in the risk of isolated oral cleft malformations. A case control study did not demonstrate an increased risk of oral clefts compared to other defects following exposure to lamotrigine.
The North American Antiepileptic Drug Pregnancy (NAAED) registry has reported a marked and statistically significant increase in the rate of isolated oral cleft malformations. The observed prevalence of oral clefts was 24 fold higher than in the Brigham and Women's Hospital (BWH) birth malformation surveillance programme, the reference population for the registry. Overall, the NAAED registry identified five cases of oral clefts in 564 exposed women giving a prevalence rate of 8.9/1000.
In a pooled analysis of other pregnancy registries, the rate of isolated oral clefts with lamotrigine monotherapy was 4 in 2226 giving a prevalence rate of 1.79/1000. This prevalence is at the upper end of, but does not exceed, the rates of general population prevalence reported in the literature.
Physiological changes during pregnancy may affect lamotrigine levels and/or therapeutic effect. There have been reports of decreased lamotrigine levels during pregnancy. Appropriate clinical management of pregnant women during lamotrigine therapy should be ensured.
Lamotrigine is a weak inhibitor of dihydrofolate reductase and studies in rats have shown a decrease in folic acid during pregnancy. There is a theoretical risk of human foetal malformations when the mother is treated with a folate inhibitor during pregnancy.
It is recommended that women on antiepileptic drugs receive pregnancy counseling with regard to the risk of foetal abnormalities. Women who are planning to become pregnant, or who are pregnant, while being treated with lamotrigine should take a folate supplement before conception and for the first 12 weeks of pregnancy, for example 5 mg of folate daily. Specialist prenatal diagnosis including detailed midtrimester ultrasound should be offered to pregnant women.
Notwithstanding the potential risks, no sudden discontinuation of antiepileptic therapy should be undertaken, as this may lead to breakthrough seizures which could have serious consequences for both the mother and the foetus. Antiepileptic drugs 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. The risk to the mother and foetus of uncontrolled epilepsy should be considered when deciding on treatment options.
Reproductive toxicology studies with lamotrigine in mice, rats and rabbits at dosage up to 100 mg/kg/day, 25 mg/kg/day and 30 mg/kg/day, respectively, did not reveal a clear teratogenic effect. An increased incidence of poorly ossified skeletal elements and rib anomalies, foetal weight decreases, prolonged gestation, fewer pups, increased incidence of still births, and reduced pup viability during lactation were observed in rats following administration of up to 25 mg/kg/day. These fetotoxic effects may have been due to maternal toxicity.
 Lamotrigine has been reported to pass into breast milk in highly variable concentrations, resulting in total lamotrigine levels in infants of up to approximately 50% of the mothers. Therefore, in some breast-fed infants, serum concentrations of lamotrigine may reach levels at which pharmacological effects occur. The potential benefits of breast-feeding should be weighed against the potential risk of adverse effects occurring in the infant.
Lamotrigine and/or its metabolites pass into the milk of lactating rats (approximately 5% of the dose was transferred to the litter). Oral administration of lamotrigine 20 mg/kg/day to rats during late gestation and lactation was associated with reduced pup viability, concomitant with signs of maternal toxicity.

4.7 Effects on Ability to Drive and Use Machines

Two volunteer studies have demonstrated that the effect of lamotrigine on fine visual motor coordination, eye movements, body sway and subjective sedative effects did not differ from placebo. In clinical trials with lamotrigine adverse effects of a neurological nature, such as dizziness and blurred vision, have been reported.
Therefore, patients should see how lamotrigine therapy affects them before driving or operating machinery. As there is individual variation in response to all antiepileptic drug therapy patients should consult their physician on the specific issues of driving and epilepsy.

4.8 Adverse Effects (Undesirable Effects)

In double-blind, add-on, placebo-controlled clinical trials in adults, skin rashes occurred in 10% of patients taking lamotrigine and in 5% of patients taking placebo. The skin rashes led to the withdrawal of lamotrigine treatment in 2% of patients in all clinical trials. The rash, usually maculopapular in appearance, generally appears within eight weeks of starting treatment and resolves on withdrawal of lamotrigine.
Serious, potentially life threatening skin rashes, including Stevens-Johnson syndrome and toxic epidermal necrolysis (Lyell Syndrome) have been reported. Although the majority recover on drug withdrawal, some patients experience irreversible scarring and there have been rare cases of associated death (see Section 4.4 Special Warnings and Precautions for Use).
The overall risk of rash appears to be strongly associated with:
High initial doses of lamotrigine and exceeding the recommended dose escalation of lamotrigine therapy (see Section 4.2 Dose and Method of Administration).
Concomitant use of sodium valproate, which increases the mean half-life of lamotrigine nearly two fold (see Section 4.2 Dose and Method of Administration).
Caution is also required when treating patients with a history of allergy or rash to other antiepileptic drugs as the frequency of non-serious rash after treatment with lamotrigine was approximately three times higher in these patients than in those without such history.
Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, facial oedema and abnormalities of the blood and liver. The syndrome shows a wide spectrum of clinical severity and may rarely lead to disseminated intravascular coagulation (DIC) and multiorgan failure. It is important to note that early manifestations of hypersensitivity (e.g. fever, lymphadenopathy) may be present even though rash is not evident. If such signs and symptoms are present the patient should be evaluated immediately and lamotrigine discontinued if an alternative aetiology cannot be established.
Table 5 presents a comparison of adverse experiences reported during clinical trials with lamotrigine. Data are presented, in decreasing order of the incidence seen in lamotrigine patients, from the pooled placebo-controlled add-on studies that have been conducted with lamotrigine. For comparison, data are also presented from pooled monotherapy studies that have been conducted with lamotrigine. These adverse experiences have been reported most commonly during the initial weeks of treatment with lamotrigine.
Irritability/aggression, tiredness, drowsiness, agitation, confusion and hallucinations have also been reported. In children hyperkinesia has been reported (5%). Very rarely, lupus-like reactions have been reported.
Arthralgia was reported commonly during the clinical development program for lamotrigine in bipolar disorder.
There have been reports of haematological abnormalities and lymphadenopathy, which may or may not be associated with the hypersensitivity syndrome. These have included neutropoenia, leucopoenia, anaemia, thrombocytopenia, pancytopenia, and very rarely aplastic anaemia and agranulocytosis.
Movement disorders such as tics, unsteadiness, ataxia, nystagmus and tremor have also been reported. There have been reports that lamotrigine may worsen parkinsonian symptoms in patients with pre-existing Parkinson's disease, and isolated reports of extrapyramidal effects and choreoathetosis in patients without this underlying condition.
Elevations of liver functions tests and rare reports of hepatic dysfunction, including hepatic failure, have been reported. Hepatic dysfunction usually occurs in association with hypersensitivity reactions but isolated cases have been reported without overt signs of hypersensitivity.
The incidence of adverse reactions to marketed drugs, such as lamotrigine, is difficult to reliably assess due to the nature of spontaneous, voluntary, reporting systems and the problems associated with estimating the total exposure to the drug. With these limitations in mind the data below has been generated from post-marketing data collected for lamotrigine. The adverse experiences included are those believed to be probably causally related to lamotrigine (at least in some instances) and are grouped by body system with an estimate of the frequency with which the reaction may be seen in the lamotrigine treated patient population (whether or not due to the drug in individual cases).

Postmarketing experience.

Frequency estimates of adverse effects seen with lamotrigine from post-marketing are defined as very common (≥ 1/10), common (≥ 1/100, < 1/10), uncommon (≥ 1/1,000, < 1/100), rare (≥ 1/10,000, < 1/1,000) and very rare (< 1/10,000).

Gastrointestinal system disorders.

Very common: nausea, vomiting.
Common: diarrhoea.
Uncommon: anorexia.

Blood and lymphatic system disorders.

Uncommon: transient leucopenia or thrombocytopenia.
Very rare: lymphadenopathy.
There have been reports of haematological abnormalities and lymphadenopathy which may or may not be associated with the hypersensitivity syndrome (see Section 4.4 Special Warnings and Precautions for Use). The haematological abnormalities have included neutropenia, leucopenia, anaemia, thrombocytopenia, pancytopenia, and very rarely aplastic anaemia and agranulocytosis.

Immune system disorders.

Very rare: hypersensitivity syndrome (DRESS) (see Section 4.4 Special Warnings and Precautions for Use).
Unknown: haemophagocytic lymphohistiocytosis (HLH) (see Section 4.4 Special Warnings and Precautions for Use).
There have been reports of HLH with use of lamotrigine. Most patients with HLH are acutely ill with multiorgan involvement. Common findings include fever, hepatosplenomegaly, rash, lymphadenopathy, neurologic symptoms, cytopenias, high serum ferritin and liver function and coagulation abnormalities.

Eye disorders.

Very common: diplopia, blurred vision.
Uncommon: conjunctivitis, photophobia.

Psychiatric disorders.

Common: aggression, irritability.
Uncommon: confusion.
Very rare: tics, hallucinations, nightmares.

Nervous system disorders.

Very common: headache, somnolence, ataxia, dizziness.
Common: nystagmus, insomnia, tremor, hyperkinesia (reported in children).
Uncommon: agitation.
Rare: aseptic meningitis (see Section 4.4 Special Warnings and Precautions for Use).
Very rare: increase in seizure frequency, unsteadiness, movement disorders, worsening of Parkinson's disease, extrapyramidal effects, choreoathetosis.
There have been reports that lamotrigine may worsen parkinsonian symptoms in patients with pre-existing Parkinson's disease, and isolated reports of extrapyramidal effects and choreoathetosis in patients without this underlying condition.

Skin and subcutaneous tissue disorders.

Very common: Skin rash.
Uncommon: erythema multiforme, Stevens-Johnson Syndrome, alopecia.
Rare: exfoliative dermatitis, toxic epidermal necrolysis.
Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms (see Section 4.4 Special Warnings and Precautions for Use).

Musculoskeletal system disorders.

Very rare: rhabdomyolysis (see Section 4.4 Special Warnings and Precautions for Use), lupus-like reactions.

General disorders.

Common: tiredness.

Hepatobiliary system disorders.

Rare: Liver function test elevated, hepatic dysfunction/failure.
Hepatic dysfunction usually occurs in association with hypersensitivity reactions but isolated cases have been reported without overt signs of hypersensitivity.

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

Symptoms and signs.

Overdose has resulted in the following clinical features: nystagmus, ataxia, dizziness, somnolence, blurred vision, headache, vomiting, impaired consciousness, increased seizures and coma. Acute ingestion of doses in excess of 10 to 30 times the maximum therapeutic dose has been reported. Overdoses involving quantities up to 15 g have been reported for lamotrigine, some of which have been fatal.
A patient who ingested a dose calculated to be between 4 and 5 g lamotrigine was admitted to hospital with coma lasting 8 - 12 hours, followed by recovery over the next 2 - 3 days. A further patient who ingested 5.6 g lamotrigine was found unconscious. Following treatment with activated charcoal for suspected intoxication the patient recovered after sleeping for 16 hours.

Treatment.

No specific antidotes are available to treat overdosage. In the event of overdosage, the patient should be admitted to hospital and given appropriate supportive therapy as clinically indicated. Measures should be taken to protect the airway, as consciousness may be impaired.
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.

The precise mechanism of the anticonvulsant action of lamotrigine is not certain. The results of neurochemical and electrophysiological studies with various in vitro and in vivo preparations indicate that lamotrigine can inhibit voltage gated sodium channels and reduce the release of glutamate, an excitatory amino acid implicated in the pathophysiology of epilepsy. It is possible that these effects underlie inhibition of the sustained repetitive firing of action potentials characteristic of neurons in epileptic foci, thereby limiting the spread of seizures.
In tests designed to evaluate the central nervous system effects of drugs, the results obtained using doses of 240 mg lamotrigine administered to healthy adult volunteers did not differ from placebo, whereas both 1000 mg phenytoin and 10 mg diazepam each significantly impaired fine visual motor coordination and eye movements, increased body sway and produced subjective sedative effects.
In another study, single oral doses of 600 mg carbamazepine significantly impaired fine visual motor coordination and eye movements, while increasing both body sway and heart rate, whereas results with lamotrigine at doses of 150 mg and 300 mg did not differ from placebo.

Clinical trials.

Adult add-on treatment of partial and generalised seizures.

The efficacy and safety of lamotrigine has been demonstrated in 6 double blind, placebo controlled, crossover studies (n=221) with duration of lamotrigine treatment ranging from 8 - 12 weeks, using doses up to 400 mg. Additionally, a double blind, placebo controlled, parallel study was performed with fixed doses of lamotrigine (300 mg, 500 mg) vs placebo. The median percentage reduction in total seizure count on lamotrigine compared with placebo significantly favoured lamotrigine in 5 of the 6 crossover trials. Overall 23% (range 7 - 67%) of patients in the trials showed a > 50% reduction in total seizures in lamotrigine compared with placebo. The median reduction (%) from baseline in total seizures during weeks 13 - 24 was 14% on placebo compared with 23% on lamotrigine 300 mg and 32% on lamotrigine 500 mg. The difference from placebo was statistically significant for lamotrigine 500 mg but not for lamotrigine 300 mg. The commonest adverse experiences affected the central nervous system (ataxia, dizziness, diplopia) and occurred more frequently on 500 mg lamotrigine than 300 mg lamotrigine in the controlled parallel study. Across the controlled trials, approximately 10% of patients on lamotrigine developed a rash compared with 5% on placebo, with approximately 3% of patients on lamotrigine withdrawing with this adverse experience.

Paediatric add on therapy.

The safety and efficacy of lamotrigine has been demonstrated in 285 children with refractory epilepsy aged 2 to 12 years in 5 open add-on trials of 48 weeks duration. Lamotrigine appeared effective in both partial and generalised seizure types. Across all seizure types, 34% of patients experienced > 50% reduction in seizures. The modal maintenance dose was 5 - 15 mg/kg for those not taking sodium valproate and 1 - 5 mg/kg for those taking sodium valproate. 7% of patients discontinued lamotrigine with a rash. In patients on concomitant sodium valproate, 2% withdrew with a rash when their daily dose of lamotrigine in the first week of treatment was < 0.5 mg/kg compared with 13% withdrawn with rash at an initial dose of lamotrigine > 0.5 mg/kg. 155 Patients aged 2 to 18 years (123 patients aged 12 years or under) continued to receive lamotrigine for up to 4 years. Four percent of these patients withdrew because of adverse experiences. Lamotrigine had no effect on expected normal weight and height increase when taken for periods of up to 4 years.

Adult monotherapy.

In two 48 week, double blind, randomised, active controlled (carbamazepine and phenytoin respectively) clinical trials of lamotrigine monotherapy, in the treatment of newly diagnosed epilepsy, have been conducted. An additional randomised, active controlled (carbamazepine), open trial in this patient population has also been conducted. A total of 784 patients from these three studies were analyzed. These studies indicate that the efficacy of lamotrigine monotherapy, in both generalised and partial seizures, may be comparable to that seen with carbamazepine and phenytoin. The escalation dose of lamotrigine in these studies that was associated with the lowest incidence of rash leading to withdrawal (2.2%) was 25 mg daily for the first two weeks, followed by 50 mg daily for the next two weeks, to achieve a maintenance dose of 100 to 200 mg/day by weeks 5-6 (see Section 4.5 Interactions with Other Medicines and Other Forms of Interactions; Section 4.8 Adverse Effects (Undesirable Effects)).

Lennox-Gastaut syndrome.

Lamotrigine may be of benefit as add-on therapy for seizures associated with Lennox-Gastaut Syndrome.
A double blind, placebo controlled, add-on, parallel study was conducted in patients aged 3 to 25 years with Lennox-Gastaut syndrome. These patients were being treated with a combination of up to 3 antiepileptic drugs including carbamazepine, clobazam, clonazepam, diazepam, ethosuximide, lorazepam, nitrazepam, oxcarbazepine, phenobarbitone, primidone, phenytoin, sodium valproate or vigabatrin. There are no data available on the use of lamotrigine as the sole drug treatment of Lennox-Gastaut Syndrome. No single drug is likely to be of benefit.
After a 4 week run in period, patients (age range 2 - 28 years) were randomised to receive either lamotrigine (age range 3 - 25) or placebo for 16 weeks (including dose escalation period in the first 6 weeks of treatment) in addition to their existing therapy. Addition of lamotrigine to existing therapy resulted in a median reduction in counts of major motor seizures (drop attacks and tonic-clonic seizures) of 32% compared with a reduction of 9% in patients on existing therapy with add-on placebo. The results were also significantly in favour of lamotrigine when drop attacks and generalised tonic-clonic seizures were analysed separately, but not for atypical absence seizures. Rash was recorded in 7/79 lamotrigine add-on patients vs 4/90 placebo add-on patients. Four percent of add-on lamotrigine patients and 8% of add-on placebo patients were withdrawn with adverse experiences. 3% discontinued lamotrigine because of rash compared with 1% on placebo. In the lamotrigine group, one patient was hospitalised because of rash and a second was reported to have developed Stevens-Johnson syndrome but did not require hospitalization. 4% of patients on placebo and no patients on lamotrigine were withdrawn because of worsening seizures.

5.2 Pharmacokinetic Properties

Absorption.

In healthy volunteers, lamotrigine is rapidly and completely absorbed from the gut. The peak plasma concentration occurs 2.5 hours after oral drug administration.

Distribution.

Lamotrigine is 55% bound to plasma proteins; it is unlikely that displacement from plasma proteins would result in toxicity. The volume of distribution is 0.92 to 1.22 L/kg.

Metabolism.

Following multiple administrations of lamotrigine (150 mg twice daily) to normal volunteers there is a modest induction of its own metabolism. Based on the available data, however, there is no clinical evidence that lamotrigine induces mono-oxygenase enzymes to an extent that would cause important interactions with drugs metabolised by these enzymes.
Ninety-four percent of a radiolabelled dose of lamotrigine given to human volunteers was recovered in the urine over a period of 168 hours. Only 2% was recovered in the faeces. Lamotrigine is extensively metabolised in man and the major metabolite is an N-glucuronide, which accounts for 65% of the dose recovered in the urine. A further 8% of the dose is recovered in the urine as unchanged lamotrigine. Another N-glucuronide metabolite is present at about one-tenth of the concentration of the major metabolite.

Excretion.

The mean elimination half-life is 29 hours and the pharmacokinetic profile is linear up to 450 mg, the highest single dose tested. The half-life of lamotrigine is greatly affected by concomitant medication with a mean value of approximately 14 hours when given with enzyme inducing drugs such as carbamazepine and phenytoin, and increasing to a mean of approximately 70 hours when co-administered with sodium valproate alone (see Section 4.2 Dose and Method of Administration; Section 4.5 Interactions with Other Medicines and Other Forms of Interactions).

Special populations.

Children (under 12 years).

Clearance adjusted for bodyweight is higher in children aged 12 years and under than in adults, with the highest values in children under 5 years. The half-life of lamotrigine is generally shorter in children than in adults with a mean of approximately 7 hours when given with enzyme inducing drugs such as carbamazepine and phenytoin, and increasing to mean values of approximately 45 to 55 hours when co-administered with sodium valproate alone (see Section 4.2 Dose and Method of Administration).

Elderly (65 to 76 years).

Results of a population pharmacokinetic analysis including both young and elderly patients with epilepsy, enrolled in the same trials, indicated that the clearance of lamotrigine did not change to a clinically relevant extent. After single doses apparent clearance decreased by 12% from 35 mL/min at age 20 to 31 mL/min at 70 years. The decrease after 48 weeks of treatment was 10% from 41 to 37 mL/min between the young and elderly groups. In addition, pharmacokinetics of lamotrigine was studied in 12 healthy elderly subjects following a 150 mg single dose. The mean clearance in the elderly (0.39 mL/min/kg) lies within the range of the mean clearance values (0.31 to 0.65 mL/min/kg) obtained in 9 studies with non-elderly adults after single doses of 30 to 450 mg.

Renal impairment.

Twelve volunteers with chronic renal failure, and another 6 individuals undergoing haemodialysis were each given a single 100 mg dose of lamotrigine. Mean CL/F were 0.42 mL/min/kg (chronic renal failure), 0.33 mL/min/kg (between haemodialysis), and 1.57 mL/min/kg (during haemodialysis) compared to 0.58 mL/min/kg in healthy volunteers. Mean plasma half-lives were 42.9 hours (chronic renal failure), 57.4 hours (between haemodialysis) and 13.0 hours (during haemodialysis), compared to 26.2 hours in healthy volunteers. On average, approximately 20% (range = 5.6 to 35.1) of the amount of lamotrigine present in the body was eliminated during a 4-hour haemodialysis session. For this patient population, initial doses of lamotrigine should be based on patients' antiepileptic drugs (AEDs) regimen; reduced maintenance doses may be effective for patients with significant renal functional impairment (see Section 4.4 Special Warnings and Precautions for Use).

Hepatic impairment.

A single-dose pharmacokinetic study was performed in 24 subjects with various degrees of hepatic impairment and 12 healthy subjects as controls. The median apparent clearance of lamotrigine was 0.31, 0.24 or 0.10 mL/min/kg in patients with Grade A, B or C (Child-Pugh Classification) hepatic impairment, respectively, compared to 0.34 mL/min/kg in the healthy controls. Reduced doses should generally be used in patients with Grade B or C hepatic impairment (see Section 4.2 Dose and Method of Administration).

5.3 Preclinical Safety Data

Genotoxicity.

Lamotrigine was not genotoxic in assays for gene mutation or chromosomal damage.

Carcinogenicity.

There was no evidence of carcinogenicity following daily oral administration of lamotrigine to mice and rats for up to two years at doses of up to 30 and 10 mg/kg respectively.

6 Pharmaceutical Particulars

6.1 List of Excipients

Noumed Lamotrigine tablets contain the following inactive ingredients: microcrystalline cellulose, calcium carbonate, crospovidone, povidone, mixed berries flavour, aspartame, hyprolose, maltodextrin, purified talc, colloidal anhydrous silica, magnesium stearate.

6.2 Incompatibilities

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

6.3 Shelf Life

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

6.4 Special Precautions for Storage

Store below 25°C. Keep dry. Protect from light.

6.5 Nature and Contents of Container

The tablets are packaged in either Al/PA-Al/PVC (cold form) blisters or PVC/PVDC-Al blisters in a printed box. Each box contains 56 tablets.

6.6 Special Precautions for Disposal

In Australia, any unused medicine or waste material should be disposed of in accordance with local requirements.

6.7 Physicochemical Properties

Chemical structure.


Chemical Name: 3,5-diamino-6-(2,3-dichlorophenyl)-1,2,4-triazine.

CAS number.

84057-84-1.
Molecular Weight: 256.10.

7 Medicine Schedule (Poisons Standard)

S4 - Prescription Only Medicine.

Summary Table of Changes