Lamictal 200mg chewable/dispersible tablets

  • Name:

    Lamictal 200mg chewable/dispersible tablets

  • Company:
    info
  • Active Ingredients:

    Lamotrigine

  • Legal Category:

    Product subject to medical prescription which may be renewed (B)

Patient Information Leaflet Patient Information Leaflet last updated on medicines.ie: 05/11/18

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Summary of Product Characteristics last updated on medicines.ie: 5/11/2018

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GlaxoSmithKline (Ireland) Ltd

GlaxoSmithKline (Ireland) Ltd

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When a pharmaceutical company changes any document, a new version is published on medicines.ie. For each version, we show the dates it was published on medicines.ie and the reasons for change.

Updated on 5 November 2018 PIL

Reasons for updating

  • Change to section 2 - what you need to know - contraindications
  • Change to section 2 - pregnancy, breast feeding and fertility
  • Change to section 4 - possible side effects

Updated on 5 November 2018 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

To update SmPC Section 4.4, 4.6, 4.8, PIL Section 2 & Section 4 in line with CMDh adopted PRAC recommendation. Inclusion of Brugada syndrome and haemophagocytic lymphohistiocytosis in take special care. Also a note to woman that are breastfeeding to observe if any symptoms are observed in the baby.

Updated on 13 July 2018 SmPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

  • Update to SmPC Section 4.5 - Interaction with other medicinal products and other forms of interaction – Update wording on Lamictal and Locosomide/Perampanel interaction in the SmPC.
  • Update to SmPC Section 4.6 - Pregnancy and lactation – typographical mistake, removal of the word ‘therefore’

Updated on 26 February 2018 SmPC

Reasons for updating

  • New SmPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 26 February 2018 SmPC

Reasons for updating

  • Change to section 10 - Date of revision of the text
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 4.5 - updated with the Lamotrigine and cytochrome P450 interactions. Hepatic drug metabolising replaced with cytochrome P450.

Updated on 3 November 2016 SmPC

Reasons for updating

  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 4.5 Interaction with other medicinal products and other forms of interaction - Update wording on OCT-2 inhibition in the SMPC.

Please note that the combined SPC for Lamictal chewable/dispersible Tablets will no longer be used. The SPC for Lamictal chewable/dispersibleTablets will now be individual SPC documents for each strength - SPC for 2mg, SPC for 5mg, SPC for 25mg, SPC for 50mg, SPC for 100mg and SPC for 200mg (6 individual SPCs in total).

The history of the Combined Lamictal chewable/dispersible tablet SPC is attached to the Lamictal chewable/dispersible 200mg Tablets, so the trail of changes remains intact for future perusal. The SPC for 2mg, SPC for 5mg, SPC for 25mg, SPC for 50mg, and SPC for 100mg will be added to Medicines.IE as 'new' documents.

Updated on 18 April 2016 SmPC

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text
  • Correction of spelling/typing errors
  • Change to improve clarity and readability

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company



Section 4.6 – minor text deletion

Section 4.8 – addition of alopecia as a uncommon side effect. Addition of  drug reaction with eosinophilia and systemic symptoms (DRESS) has been reported.

Updated on 14 April 2016 PIL

Reasons for updating

  • Change to instructions about missed dose
  • Change to side-effects
  • Change to information about pregnancy or lactation
  • Change to date of revision
  • Change to improve clarity and readability

Updated on 14 April 2016 PIL

Reasons for updating

  • New PIL for new product

Updated on 3 February 2016 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 5.1 - Pharmacodynamic properties

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

A pregnancy variation was submitted after the bipolar variation but approved before the HPRA approved the bipolar disorder on 12/01/2016.  The SPC is now updated with the pregnancy variation approval text.

The changes to the SPC for the bipolar variation approved on 12/01/2016 are:

Description of change to SPC:

·         4.2          Posology and method of administration – explanation of why Lamictal is not recommended for use in children below 18 years of age because a randomised withdrawal study demonstrated no significant efficacy and showed increased reporting of suicidality (see section 4.4 and 5.1).

 

·         4.4          Special warnings and precautions for use– skin rash section updated to remove ‘epileptic’ children. Also minor typographical changes have been made to the tables.

 

·         5.1 Pharmacodynamic properties – addition of study for Children (10-12 years of age) and Adolescents (13-17 years of age)

 

Updated on 19 January 2016 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 5.1 - Pharmacodynamic properties
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Description of change to SPC:

·         4.2          Posology and method of administration – explanation of why Lamictal is not recommended for use in children below 18 years of age because a randomised withdrawal study demonstrated no significant efficacy and showed increased reporting of suicidality (see section 4.4 and 5.1).

 

·         4.4          Special warnings and precautions for use– skin rash section updated to remove ‘epileptic’ children. Also minor typographical changes have been made to the tables.

 

·         5.1 Pharmacodynamic properties – addition of study for Children (10-12 years of age) and Adolescents (13-17 years of age)

Updated on 18 January 2016 PIL

Reasons for updating

  • Change to date of revision
  • Change to MA holder contact details
  • Change to improve clarity and readability

Updated on 28 July 2015 SmPC

Reasons for updating

  • Change to section 4.6 - Pregnancy and lactation
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 4.6 - amendments to the wording in the Pregnancy section for lamictal following completion of a case control study to monitor specific birth defects following in utero exposure to lamotrigine conducted through the European Network of Congenital Anomaly and Twin Registers (EUROCAT) - WWE113038/WEUKBRE3885 (voluntary PASS ) .

Updated on 15 July 2015 PIL

Reasons for updating

  • Change to date of revision
  • Change to MA holder contact details

Updated on 15 July 2015 SmPC

Reasons for updating

  • Change to section 7 - Marketing authorisation holder
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 7 - change to Ireland MAH address

Updated on 19 May 2015 SmPC

Reasons for updating

  • Change to section 6.3 - Shelf life
  • Change to section 6.5 - Nature and contents of container
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Introduction of 5 mg bottle pack

Updated on 14 May 2015 PIL

Reasons for updating

  • Change to date of revision
  • Introduction of new pack/pack size

Updated on 3 March 2015 PIL

Reasons for updating

  • Change to date of revision
  • Change to side-effects

Updated on 3 March 2015 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 4.8 - Undesirable effects – addition of nightmares with the frequency unknown

Updated on 23 October 2014 SmPC

Reasons for updating

  • Change to section 1 - Name of medicinal product
  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 3 - Pharmaceutical form
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects
  • Change to section 6.3 - Shelf life
  • Change to section 6.5 - Nature and contents of container
  • Change to section 8 - MA number
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Section 1,2, 3, 4.2, 6.3, 6.5 and 8 – dispersible chewable tablets has been replaced with chewable dispersible tablets.
Section 3 – addition of size of tablet
Section 4.4 – minor editorial changes
-addition of drug Reaction with Eosinophilia and Systemic Symptoms (DRESS); also known as hypersensitivity syndrome (HSS).
-If the patient has developed DRESS with the use of lamotrigine, treatment with lamotrigine must not be re-started in this patient at any time.
Section 4.8 – addition of drug Reaction with Eosinophilia and Systemic Symptoms (DRESS) with frequency of very rare.
- Addition of HPRA AE contact information

Updated on 22 October 2014 PIL

Reasons for updating

  • Change of trade or active ingredient name
  • Change to warnings or special precautions for use
  • Change to side-effects
  • Change to further information section
  • Change to date of revision
  • Addition of information on reporting a side effect.

Updated on 15 May 2014 PIL

Reasons for updating

  • Change of manufacturer
  • Change to date of revision

Updated on 23 January 2014 SmPC

Reasons for updating

  • Change to section 4.9 - Overdose

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

 

4.9 Overdose

Under the subheading ‘Symptoms and signs’, updated as follows:

Acute ingestion of doses in excess of 10 to 20 times the maximum therapeutic dose has been reported, including fatal cases.  Overdose has resulted in symptoms including nystagmus, ataxia, impaired consciousness, grand mal convulsion and coma. QRS broadening (intraventricular conduction delay) has also been observed in overdose patients. Broadening of QRS duration to more than 100 msec may be associated with more severe toxicity.

Updated on 22 January 2014 PIL

Reasons for updating

  • Change to instructions about overdose

Updated on 30 September 2013 SmPC

Reasons for updating

  • Change to section 2 - Qualitative and quantitative composition
  • Change to section 4.3 - Contraindications
  • Change to Section 4.8 – Undesirable effects - how to report a side effect
  • Change to section 5.2 - Pharmacokinetic properties
  • Change to section 6.1 - List of excipients
  • Change to section 6.6 - Special precautions for disposal and other handling

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

Changes to:

Section 2 - QUALITATIVE AND QUANTITATIVE COMPOSITION
Section 4.3 - Contraindications,
Section 4.8 - Undesirable effects,
Section 5.2 - Pharmacokinetic properties,
Section 6.1 - List of excipients,
Section 6.6 - Special precautions for disposal,

Updated on 24 September 2013 PIL

Reasons for updating

  • Change of manufacturer

Updated on 17 September 2012 SmPC

Reasons for updating

  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

 

4.2     Posology and method of administration

Table 2: Children and adolescents aged 2 to 12 years - recommended treatment regimen in epilepsy (total daily dose in mg/kg body weight/day)

 

Treatment regimen

Weeks 1 + 2

Weeks 3 + 4

Usual maintenance dose

 

Monotherapy of typical absence seizures:

0.3 mg/kg/day (once a day or two divided doses)

0.6 mg/kg/day (once a day or two divided doses)

1 – 150 mg/kg/day, although some patients have required higher doses (up to 15 mg/kg/day) to achieve desired response

(once a day or two divided doses)

 

To achieve maintenance, doses may be increased by maximum of 0.6 mg/kg/day every one to two weeks until optimal response is achieved, with a maximum maintenance dose of 200mg/day

 

4.4     Special warnings and precautions for use

 

All patients (adults and children) who develop a rash should be promptly evaluated and Lamictal withdrawn immediately unless the rash is clearly not related to lamotrigine treatment. It is recommended that Lamictal 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 or TEN with the use of lamotrigine, treatment with lamotrigine must not be re-started in this patient at any time.

 

 

4.8         Undesirable effects

 

The undesirable effects have been divided intofor epilepsy and bipolar disorder indications specific sectionsare based on the data currently available. However, both sectionsThe table below should be consulted when considering the overall safety profile of lamotrigine.

 

Adverse reactions identified from epilepsy monotherapy clinical trials (identified by a dagger ), from bipolar disorder clinical trials (identified by a section mark §) and during other clinical experience are listed in the table below by their incidence in clinical trials.

 

The following convention has been utilised for the classification of undesirable effects:-  Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1000 to <1/100); rare (>1/10,000 to <1/1000); very rare (<1/10,000), not known (cannot be estimated from the available data).

 

Epilepsy

 

System Organ Class

Adverse Event

Frequency

Nervous System Disorders

Headache§

 

Somnolence§, dizziness§, tremor, insomnia agitation§

Ataxia

 

Nystagmus

 

UAgitation, unsteadiness, movement disorders, worsening of Parkinson's disease 3, extrapyramidal effects, choreoathetosis, increase in seizure frequency

 

Aseptic meningitis (see section 4.4)

Very Common

Common

 

 

Uncommon

 

Rare

 

Very Rare

 

 

 

 

Not known

Gastrointestinal disorders

Nausea, vomiting, diarrhoea , dry mouth§

Common

Musculoskeletal and connective tissue disorders

Arthralgia§

 

Lupus‑like reactions

Common

 

Very rare

General disorders and administration site conditions

Tiredness, pain§, back pain§

Common

 

5In double‑blind, adjunctive clinical trials in adults, skin rashes occurred in up to 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. The rash, usually maculopapular in appearance, generally appears within eight weeks of starting treatment and resolves on withdrawal of Lamictal (see section 4.4).

5In clinical trials in adults, skin rashes occurred in up to 8-12% of patients taking lamotrigine and in 5-6% of patients taking placebo. The skin rashes led to the withdrawal of lamotrigine treatment in 2% of patients. The rash, usually maculopapular in appearance, generally appears within eight weeks of starting treatment and resolves on withdrawal of Lamictal (see section 4.4).

 

 

Bipolar Disorder

 

The undesirable effects below should be considered alongside those seen in epilepsy for an overall safety profile of lamotrigine.  Adverse events included in the table were identified during bipolar disorder clinical trials.

 

System Organ Class

Adverse Event

Frequency

Nervous system disorders

Headache

 

Agitation, somnolence, dizziness

 

Very common

 

Common

 

Gastrointestinal disorders

Dry mouth

Common

 

Skin and subcutaneous tissue disorders

Skin rash

 

StevensJohnson Syndrome

Very common1

 

Rare

Musculoskeletal and connective tissue disorders

Arthralgia

Common

General disorders and administration site conditions

Pain, back pain.

Common

 

 

There have been reports of decreased bone mineral density, osteopenia, osteoporosis and fractures in patients on long-term therapy with lamotrigine. The mechanism by which lamotrigine affects bone metabolism has not been identified.

 

1 When all bipolar disorder studies (controlled and uncontrolled) conducted with lamotrigine are considered, skin rashes occurred in 12% of patients on lamotrigine. Whereas, in controlled clinical trials with bipolar disorder patients, skin rashes occurred in 8% of patients taking lamotrigine and in 6% of patients taking placebo.

 

 

Updated on 12 September 2012 PIL

Reasons for updating

  • Change to side-effects

Updated on 14 December 2011 SmPC

Reasons for updating

  • Change to section 4.4 - Special warnings and precautions for use
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.8 - Undesirable effects
  • Change to section 10 - Date of revision of the text

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

 

4.4     Special warnings and precautions for use

 

Skin rash

 

 

Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, facial oedema, abnormalities of the blood and liver and aseptic meningitis (see section 4.8). The syndrome shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation and multiorgan failure. It is important to note that early manifestations of hypersensitivity (for example 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 Lamictal discontinued if an alternative aetiology cannot be established.

 

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.

 

 

4.5     Interaction with other medicinal products and other forms of interaction

 

Table 6: Effects of other medicinal products on glucuronidation of lamotrigine

 

Medicinal products that significantly inhibit glucuronidation of lamotrigine

Medicinal products that significantly induce glucuronidation of lamotrigine

Medicinal products that do not significantly inhibit or induce glucuronidation of lamotrigine

Valproate

Phenytoin

Oxcarbazepine

 

Carbamazepine

Felbamate

 

Phenobarbitone

Gabapentin

 

Primidone

Levetiracetam

 

Rifampicin

Pregabalin

 

Lopinavir/ritonavir

Topiramate

 

Ethinyloestradiol/ levonorgestrel combination**

Zonisamide

 

Atazanavir/ritonavir*

Lithium

 

 

Buproprion

 

 

Olanzapine

 

 

Aripiprazole

 

In a study of 18 adult patients with bipolar I disorder, receiving an established regimen of lamotrigine (100-400 mg/day), doses of aripiprazole were increased from 10 mg/day to a target of 30 mg/day over a 7 day period and continued once daily for a further 7 days.  An average reduction of approximately 10% in Cmax and AUC of lamotrigine was observed. An effect of this magnitude is not expected to be of clinical consequence.

 

Data from in vitro assessment demonstrate that lamotrigine, but not the N(2)-glucuronide metabolite, is an inhibitor of Organic Transporter 2 (OCT 2) at potentially clinically relevant concentrations. These data demonstrate that lamotrigine is a more potent in vitro inhibitor of OCT 2 than cimetidine, with IC50 values of 53.8 μM and 186 μM, respectively. Co-administration of lamotrigine with renally excreted medicinal products which are substrates of OCT2 (e.g. metformin, gabapentin and varenicline) may result in increased plasma levels of these medicinal products.

 

The clinical significance of this has not been clearly defined, however care should be taken in patients co‑administered with these medicinal products.

 

 

4.8         Undesirable effects

 

The undesirable effects have been divided into epilepsy and bipolar specific sections based on the data currently available. However, both sections should be consulted when considering the overall safety profile of lamotrigine.

 

Adverse reactions identified from monotherapy clinical trials (identified by a dagger ) and during other clinical experience are listed in the table below by their incidence in clinical trials.

 

The following convention has been utilised for the classification of undesirable effects:-  Very common (>1/10); common (>1/100 to <1/10); uncommon (>1/1000 to <1/100); rare (>1/10,000 to <1/1000); very rare (<1/10,000), not known (cannot be estimated from the available data).

 

Epilepsy

 

System Organ Class

Adverse Event

Frequency

Blood and lymphatic system disorders

Haematological abnormalities1 including neutropenia, leucopenia, anaemia, thrombocytopenia, pancytopenia, aplastic anaemia, agranulocytosis


Lymphadenopathy1

 

 

Very rare

 

Not known

Immune System Disorders

Hypersensitivity syndrome2 (including such symptoms as, fever, lymphadenopathy, facial oedema, abnormalities of the blood and liver, disseminated intravascular coagulation, multi organ failure).




Very Rare

Psychiatric Disorders

Aggression, irritability

 

Confusion, hallucinations, tics

Common

 

Very rare

Nervous System Disorders

Headache

 

Somnolence, dizziness, tremor, insomnia

Ataxia

 

Nystagmus

 

Agitation, unsteadiness, movement disorders, worsening of Parkinson's disease 3, extrapyramidal effects, choreoathetosis, increase in seizure frequency

 

Aseptic meningitis (see section 4.4)

Very Common

Common

 

Uncommon

 

Rare

 

Very Rare

 

 

 

 

Not known

Eye disorders

Diplopia, blurred vision

 

Conjunctivitis

Uncommon

 

Rare

Gastrointestinal disorders

Nausea, vomiting, diarrhoea

Common

Hepatobiliary disorders

Hepatic failure, hepatic dysfunction4, increased liver function tests

Very rare

Skin and subcutaneous tissue disorders

Skin rash5

 

Stevens–Johnson Syndrome

 

Toxic epidermal necrolysis

Very common

 

Rare

 

Very rare

Musculoskeletal and connective tissue disorders

Lupus‑like reactions

Very rare

General disorders and administration site conditions

Tiredness

Common

 

Description of selected adverse reactions

 

1 Haematological abnormalities and lymphadenopathy may or may not be associated with the hypersensitivity syndrome (see Immune system disorders2).

 

2 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 and multiorgan failure. It is important to note that early manifestations of hypersensitivity (for example 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 Lamictal discontinued if an alternative aetiology cannot be established.

 

3 These effects have been reported during other clinical experience. 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.

 

4 Hepatic dysfunction usually occurs in association with hypersensitivity reactions but isolated cases have been reported without overt signs of hypersensitivity.

 

5

Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms (see Immune system disorders2).

 

Bipolar Disorder

 

The undesirable effects below should be considered alongside those seen in epilepsy for an overall safety profile of lamotrigine.  Adverse events included in the table were identified during bipolar disorder clinical trials.

 

System Organ Class

Adverse Event

Frequency

Nervous system disorders

Headache

 

Agitation, somnolence, dizziness

 

Very common

 

Common

 

Gastrointestinal disorders

Dry mouth

Common

 

Skin and subcutaneous tissue disorders

Skin rash

 

Stevens–Johnson Syndrome

Very common1

 

Rare

Musculoskeletal and connective tissue disorders

Arthralgia

Common

General disorders and administration site conditions

Pain, back pain.

Common

 

1 When all bipolar disorder studies (controlled and uncontrolled) conducted with lamotrigine are considered, skin rashes occurred in 12% of patients on lamotrigine. Whereas, in controlled clinical trials with bipolar disorder patients, skin rashes occurred in 8% of patients taking lamotrigine and in 6% of patients taking placebo.

 

 

10.     DATE OF REVISION OF THE TEXT

 

20 July 2011

Updated on 6 December 2011 PIL

Reasons for updating

  • Change of contraindications

Updated on 13 December 2010 PIL

Reasons for updating

  • Change to drug interactions
  • Change to dosage and administration

Updated on 22 September 2010 SmPC

Reasons for updating

  • Change to section 4.9 - Overdose
  • Change to section 10 - Date of revision of the text
  • Change to section 1 - Name of medicinal product
  • Change to section 4.2 - Posology and method of administration
  • Change to section 4.5 - Interaction with other medicinal products and other forms of interaction
  • Change to section 4.6 - Pregnancy and lactation

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

SUMMARY OF PRODUCT CHARACTERISTICS

 

1.       NAME OF THE MEDICINAL PRODUCT

 

Lamictal 2 mg dispersible/chewable tablets.

 

 

4.2     Posology and method of administration

 

 

Table 4:  Adults aged 18 years and above - maintenance stabilisation total daily dose following withdrawal of concomitant medicinal products in treatment of bipolar disorder

Once the target daily maintenance stabilisation dose has been achieved, other medicinal products may be withdrawn as shown below.

 

Treatment Regimen

Current lamotrigine stabilisation dose (prior to withdrawal)

 

Week 1 (beginning with withdrawal)

Week 2

Week 3 onwards *

 

Withdrawal of valproate (inhibitor of lamotrigine glucuronidation – see section 4.5), depending on original dose of lamotrigine:

When valproate is withdrawn, double the stabilisation dose, not exceeding an increase of more than 100 mg/week

100 mg/day

 

200 mg/day

 

Maintain this dose (200 mg/day)

(two divided doses)

 

200 mg/day

 

300 mg/day

 

400 mg/day

 

Maintain this dose (400 mg/day)

 

Withdrawal of inducers of lamotrigine glucuronidation (see section 4.5), depending on original dose of lamotrigine:

This dosage regimen should be used when the following are  withdrawn:

 

phenytoin

carbamazepine

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

 

400 mg/day

 

400 mg/day

300 mg/day

200 mg/day

300 mg/day

 

300 mg/day

225 mg/day

150 mg/day

200 mg/day

 

200 mg/day

150 mg/day

100 mg/day

Withdrawal of medicinal products that do NOT significantly inhibit or induce lamotrigine glucuronidation (see section 4.5):

This dosage regimen should be used when other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation are withdrawn

 

Maintain target dose achieved in dose escalation (200 mg/day; two divided doses)

(dose range 100 ‑ 400 mg/day)

 

 

In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the treatment regimen as recommended for lamotrigine is to initially maintain the current dose and adjust the lamotrigine treatment based on clinical response.with concurrent valproate, should be used.

 

* Dose may be increased to 400 mg/day as needed

 

 

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4.2     Posology and method of administration

 

Starting and stopping hormonal contraceptives in patients already taking maintenance doses of lamotrigine and TAKING inducers of lamotrigine glucuronidation

Adjustment to the recommended maintenance dose of lamotrigine may not be required.

 

Use with atazanavir/ritonavir

 

No adjustments to the recommended dose escalation of lamotrigine should be necessary when lamotrigine is added to the existing atazanavir/ritonavir therapy.

In patients already taking maintenance doses of lamotrigine and not taking glucuronidation inducers, the lamotrigine dose may need to be increased if atazanavir/ritonavir is added, or decreased if atazanavir/ritonavir is discontinued. Plasma lamotrigine monitoring should be conducted before and during 2 weeks after starting or stopping atazanavir/ritonavir, in order to see if lamotrigine dose adjustment is needed (see section 4.5).

 

Use with lopinavir/ritonavir

No adjustments to the recommended dose escalation of lamotrigine should be necessary when lamotrigine is added to the existing lopinavir/ritonavir therapy.

In patients already taking maintenance doses of lamotrigine and not taking glucuronidation inducers, the lamotrigine dose may need to be increased if lopinavir/ritonavir is added, or decreased if lopinavir/ritonavir is discontinued. Plasma lamotrigine monitoring should be conducted before and during 2 weeks after starting or stopping lopinavir/ritonavir, in order to see if lamotrigine dose adjustment is needed (see section 4.5).

 

Elderly (above 65 years)

No dosage adjustment from the recommended schedule is required. The pharmacokinetics of lamotrigine in this age group do not differ significantly from a non‑elderly adult population (see section 5.2).

 

Renal impairment

Caution should be exercised when administering Lamictal to patients with renal failure. For patients with end‑stage renal failure, initial doses of lamotrigine should be based on patients' concomitant medicinal products; reduced maintenance doses may be effective for patients with significant renal functional impairment (see sections 4.4 and 5.2).

 

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 according to clinical response (see section 5.2).

 

 

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4.5     Interaction with other medicinal products and other forms of interaction

 

Interaction studies have only been performed in adults.

 

UDP‑glucuronyl transferases 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 medicinal products 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.

 

Table 6: Effects of other medicinal products on glucuronidation of lamotrigine

 

Medicinal products that significantly inhibit glucuronidation of lamotrigine

Medicinal products that significantly induce glucuronidation of lamotrigine

Medicinal products that do not significantly inhibit or induce glucuronidation of lamotrigine

Valproate

Phenytoin

Oxcarbazepine

 

Carbamazepine

Felbamate

 

Phenobarbitone

Gabapentin

 

Primidone

Levetiracetam

 

Rifampicin

Pregabalin

 

Lopinavir/ritonavir

Topiramate

 

Ethinyloestradiol/ levonorgestrel combination**

Zonisamide

 

Atazanavir/ritonavir*

Lithium

 

 

Buproprion

 

 

Olanzapine

* For dosing guidance (see section 4.2)

** Other oral contraceptive and HRT treatments have not been studied, though they may similarly affect lamotrigine pharmacokinetic parameters (see sections 4.2 and 4.4).

 

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4.5     Interaction with other medicinal products and other forms of interaction

 

Interactions involving other medicinal products

 

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 appropriate treatment regimen should be used (see section 4.2).

 

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 appropriate treatment regimen should be used (see section 4.2).

 

In a study in healthy adult volunteers, atazanavir/ritonavir (300 mg/100 mg) administered for 9 days reduced the plasma AUC and Cmax of lamotrigine (single 100 mg dose) by an average of 32% and 6%, respectively. In patients receiving concomitant therapy with atazanavir/ritonavir, the appropriate treatment regimen should be used (see section 4.2).

 

 

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4.6     Pregnancy and lactation

 

Risk related to antiepileptic drugs in general

 

Specialist advice should be given to women who are of childbearing potential. The need for treatment with AEDs should be reviewed when a woman is planning to become pregnant. In women being treated for epilepsy, sudden discontinuation of AED therapy should be avoided as this may lead to breakthrough seizures that could have serious consequences for the woman and the unborn child.

 

The risk of congenital malformations is increased by a factor of 2 to 3 in the offspring of mothers treated with AEDs compared with the expected incidence in the general population of approximately 3%. The most frequently reported defects are cleft lip, cardiovascular malformations and neural tube defects.  Therapy with multiple AEDs is associated with a higher risk of congenital malformations than monotherapy and therefore monotherapy should be used whenever possible.

 

Risk related to lamotrigine

 

Pregnancy

Epidemiological studies involving in total approximately 2000 women exposed to lamotrigine monotherapy during pregnancy cannot exclude an increased risk for congenital malformations. One registry has reported an increased incidence of facial clefts. Other data sets have not confirmed this finding. 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 are still too limited to exclude a moderate increase in the risk of oral clefts. Animal studies have shown developmental toxicity (see section 5.3).

 

If therapy with Lamictal is considered necessary during pregnancy, the lowest possible therapeutic dose is recommended.

 

Lamotrigine has a slight inhibitory effect on dihydrofolic acid reductase and could therefore theoretically lead to an increased risk of embryofoetal damage by reducing folic acid levels (see section 4.4). Intake of folic acid when planning pregnancy and during early pregnancy may be considered.

 

Physiological changes during pregnancy may affect lamotrigine levels and/or therapeutic effect. There have been reports of decreased lamotrigine plasma levels during pregnancy with a potential risk of loss of seizure control. After birth lamotrigine levels may increase rapidly with a risk of dose‑related adverse events. Therefore lamotrigine serum concentrations should be monitored before, during and after pregnancy, as well as shortly after birth. If necessary, the dose should be adapted to maintain the lamotrigine serum concentration at the same level as before pregnancy, or adapted according to clinical response. In addition, dose‑related undesirable effects should be monitored after birth.

 

Lactation

Data indicate that lamotrigine passes into breast milk.  In some breast‑fed infants, the serum concentrations of lamotrigine reached levels at which pharmacological effects may occur. 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 mother’s. Therefore, in some breast-fed infants, serum concentrations of lamotrigine may reach levels at which pharmacological effects occur. Among a limited group of exposed infants, no adverse effects were observed.

 

The potential benefits of breast‑feeding should be weighed against the potential risk of adverse effects occurring in the infant.  Should a woman decide to breast‑feed while on therapy with lamotrigine, the infant should be monitored for adverse effects.

 

Fertility

Animal experiments did not reveal impairment of fertility by lamotrigine (see section 5.3).

 

 

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4.9     Overdose

 

Symptoms and signs

 

Acute ingestion of doses in excess of 10 to 20 times the maximum therapeutic dose has been reported.  Overdose has resulted in symptoms including nystagmus, ataxia, impaired consciousness and coma.

 

Treatment

 

In the event of overdosageoverdose, the patient should be admitted to hospital and given appropriate supportive therapy.  Therapy aimed at decreasing absorption (activated charcoal), laxative or gastric lavage) should be performed if indicated. Further management should be as clinically indicated. There is no experience with haemodialysis as treatment of overdose. In six volunteers with kidney failure, 20% of the lamotrigine was removed from the body during a 4‑hour haemodialysis session (see section 5.2).

 

 

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10.     DATE OF REVISION OF THE TEXT

 

December 2009August 2010

Updated on 2 February 2010 SmPC

Reasons for updating

  • Change to section 4.8 - Undesirable effects

Legal category: Product subject to medical prescription which may be renewed (B)

Free text change information supplied by the pharmaceutical company

 

Section 4.8 Undesirable effects

Added the new frequency classification term ‘not known’, i.e.: not known (cannot be estimated from the available

Under the Heading  ‘Epilepsy’

-          Under the subheading Blood and Lymphatic system disorder added the side effect lymphadenopathy for which the frequency classification is not known.

-          Included lymphadenopathy as a side effect that ‘may or may not be associated with the hypersensitivity syndrome’

-          Under the subheading ‘During other Clinical experience’,added the side effect aseptic meningitis, for which the frequency classification is not known.

Updated on 26 January 2010 PIL

Reasons for updating

  • Change to warnings or special precautions for use
  • Change to drug interactions
  • Change to dosage and administration
  • Change to side-effects

Updated on 27 November 2008 PIL

Reasons for updating

  • Change due to harmonisation of patient information leaflet

Updated on 29 October 2008 SmPC

Reasons for updating

  • New SPC for new product

Legal category: Product subject to medical prescription which may be renewed (B)

Updated on 8 July 2008 PIL

Reasons for updating

  • Change to name of manufacturer

Updated on 11 April 2007 PIL

Reasons for updating

  • Change of manufacturer

Updated on 15 November 2006 PIL

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 8 June 2006 PIL

Reasons for updating

  • Change to warnings or special precautions for use

Updated on 17 January 2006 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 9 January 2006 PIL

Reasons for updating

  • Improved electronic presentation

Updated on 26 August 2005 PIL

Reasons for updating

  • New PIL for medicines.ie