1. Name Of The Medicinal Product
Lamotrigine 5 mg Dispersible Tablets
2. Qualitative And Quantitative Composition
Each tablet contains lamotrigine 5 mg
For excipients, see 6.1.
3. Pharmaceutical Form
“Dispersible Tablet”
White or almost white, capsule shape, biconvex, uncoated tablets with “5” marked on one side.
4. Clinical Particulars
4.1 Therapeutic Indications
Epilepsy
Adults and adolescents aged 13 years and above
− Adjunctive or monotherapy treatment of partial seizures and generalised seizures, including tonic-clonic seizures.
− Seizures associated with Lennox-Gastaut syndrome. Lamotrigine Dispersible Tablets is given as adjunctive therapy but may be the initial antiepileptic drug (AED) to start with in Lennox-Gastaut syndrome.
Children and adolescents aged 2 to 12 years
− Adjunctive treatment of partial seizures and generalised seizures, including tonic-clonic seizures and the seizures associated with Lennox-Gastaut syndrome.
− Monotherapy of typical absence seizures.
Bipolar disorder
Adults aged 18 years and above
− Prevention of depressive episodes in patients with bipolar I disorder who experience predominantly depressive episodes (see section 5.1).
Lamotrigine Dispersible Tablets is not indicated for the acute treatment of manic or depressive episodes.
4.2 Posology And Method Of Administration
Administration
Lamotrigine Dispersible Tablets may be chewed, dispersed in a small volume of water (at least enough to cover the tablet) or swallowed whole with a little water.
If the calculated dose of lamotrigine (for example for treatment of children with epilepsy or patients with hepatic impairment) does not equate to whole tablets, the dose to be administered is that equal to the lower number of whole tablets.
Restarting therapy
Prescribers should assess the need for escalation to maintenance dose when restarting Lamotrigine Dispersible Tablets in patients who have discontinued Lamotrigine Dispersible Tablets 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). 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), Lamotrigine Dispersible Tablets should generally be escalated to the maintenance dose according to the appropriate schedule.
It is recommended that Lamotrigine Dispersible Tablets 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.
Epilepsy
The recommended dose escalation and maintenance doses for adults and adolescents aged 13 years and above (Table 1) and for children and adolescents aged 2 to 12 years (Table 2) are given below. Because of a risk of rash the initial dose and subsequent dose escalation should not be exceeded (see section 4.4).
When concomitant AEDs are withdrawn or other AEDs/medicinal products are added on to treatment regimes containing lamotrigine, consideration should be given to the effect this may have on lamotrigine pharmacokinetics (see section 4.5).
Table 1: Adults and adolescents aged 13 years and above - recommended treatment regimen in epilepsy
Treatment regimen
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Weeks 1 + 2
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Weeks 3 + 4
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Usual maintenance dose
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Monotherapy:
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25mg/day (once a day)
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50mg/day (once a day)
|
100 - 200mg/day (once a day or two divided doses)
To achieve maintenance, doses may be increased by maximum of 50 - 100mg everyone to two weeks until optimal response is achieved
500mg/day has been required by some patients to achieve desired response
|
Adjunctive therapy WITH valproate (inhibitor of lamotrigine glucuronidation - see section 4.5):
|
|
|
|
This dosage regimen should be used with valproate regardless of any concomitant medicinal products
|
12.5mg/day (given as 25mg on alternate days)
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25mg/day (once a day)
|
100 - 200mg/day (once a day or two divided doses)
To achieve maintenance, doses may be increased by maximum of 25 - 50mg every one to two weeks until optimal response is achieved
|
Adjunctive therapy WITHOUT valproate and WITH inducers of lamotrigine glucuronidation (see section 4.5):
|
|
|
|
This dosage regimen should be used without valproate but with:
phenytoin
carbamazepine
phenobarbital
primidone
rifampicin
lopinavir/ritonavir
|
50mg/day (once a day)
|
100mg/day (two divided doses)
|
200 - 400mg/day (two divided doses)
To achieve maintenance, doses may be increased by maximum of 100mg every one to two weeks until optimal response is achieved
700mg/day has been required by some patients to achieve desired response
|
Adjunctive therapy WITHOUT valproate and WITHOUT inducers of lamotrigine glucuronidation (see section 4.5):
|
|
|
|
This dosage regimen should be used with other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation
|
25mg/day (once a day)
|
50mg/day (once a day)
|
100 - 200mg/day (once a day or two divided doses)
To achieve maintenance, doses may be increased by maximum of 50 - 100mg every one to two weeks until optimal response is achieved
|
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 with concurrent valproate should be used.
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|
|
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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
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Weeks 1 + 2
|
Weeks 3 + 4
|
Usual maintenance dose
|
Monotherapy of typical absence seizures:
|
0.3mg/kg/day (once a day or two divided doses)
|
0.6mg/kg/day (once a day or two divided doses)
|
1 - 10mg/kg/day, although some patients have required higher doses (up to 15mg/kg/day) to achieve desired response (once a day or two divided doses)
To achieve maintenance, doses may be increased by maximum of 0.6mg/kg/day every one to two weeks until optimal response is achieved
|
Adjunctive therapy WITH valproate (inhibitor of lamotrigine glucuronidation - see section 4.5):
|
|
|
|
This dosage regimen should be used with valproate regardless of any other concomitant medicinal products
|
0.15mg/kg/day * (once a day)
|
0.3mg/kg/day (once a day)
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1 - 5mg/kg/day (once a day or two divided doses)
To achieve maintenance, doses may be increased by maximum of 0.3mg/kg every one to two weeks until optimal response is achieved, with a maximum maintenance dose of 200mg/day
|
Adjunctive therapy WITHOUT valproate and WITH inducers of lamotrigine glucuronidation (see section 4.5):
|
|
|
|
This dosage regimen should be used without valproate but with:
phenytoin
carbamazepine
phenobarbital
primidone
rifampicin
lopinavir/ritonavir
|
0.6mg/kg/day (two divided doses)
|
1.2mg/kg/day (two divided doses)
|
5 - 15mg/kg/ day (once a day or two divided doses)
To achieve maintenance, doses may be increased by maximum of 1.2mg/kg every one to two weeks until optimal response is achieved, with a maximum maintenance dose of 400mg/day
|
Adjunctive therapy WITHOUT valproate and WITHOUT inducers of lamotrigine glucuronidation (see section 4.5):
|
|
|
|
This dosage regimen should be used with other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation
|
0.3mg/kg/day (once a day or two divided doses)
|
0.6mg/kg/day (once a day or two divided doses)
|
1 - 10mg/kg/day (once a day or two divided doses)
To achieve maintenance, doses may be increased by maximum of 0.6mg/kg every one to two weeks until optimal response is achieved, with a maximum of maintenance dose of 200mg/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 with concurrent valproate should be used.
|
|
|
|
* If the calculated daily dose in patients taking valproate is 2.5mg or more but less than 5mg, then Lamotrigine 5mg dispersible/chewable tablets may be taken on alternate days for the first two weeks. If the calculated daily dose in patients taking valproate is less than 2.5mg, then Lamotrigine should not be administered.
|
|
|
|
To ensure a therapeutic dose is maintained the weight of a child must be monitored and the dose reviewed as weight changes occur. It is likely that patients aged two to six years will require a maintenance dose at the higher end of the recommended range.
If epileptic control is achieved with adjunctive treatment, concomitant AEDs may be withdrawn and patients continued on Lamotrigine Dispersible Tablets monotherapy.
It should be noted that with the currently available Lamotrigine 5mg dispersible/chewable tablet strength, it is not possible to accurately initiate lamotrigine therapy using the recommended dosing guidelines in paediatric patients weighing less than 17kg
Children below 2 years
There are limited data on the efficacy and safety of lamotrigine for adjunctive therapy of partial seizures in children aged 1 month to 2 years (see section 4.4). There are no data in children below 1 month of age. Thus Lamotrigine Dispersible Tablets is not recommended for use in children below 2 years of age. If, based on clinical need, a decision to treat is nevertheless taken, see sections 4.4, 5.1 and 5.2.
Bipolar disorder
The recommended dose escalation and maintenance doses for adults of 18 years of age and above are given in the tables below. The transition regimen involves escalating the dose of lamotrigine to a maintenance stabilisation dose over six weeks (Table 3) after which other psychotropic medicinal products and/or AEDs can be withdrawn, if clinically indicated (Table 4). The dose adjustments following addition of other psychotropic medicinal products and/or AEDs are also provided below (Table 5). Because of the risk of rash the initial dose and subsequent dose escalation should not be exceeded (see section 4.4).
Table 3: Adults aged 18 years and above - recommended dose escalation to the maintenance total daily stabilisation dose in treatment of bipolar disorder
Treatment Regimen
|
Weeks 1 + 2
|
Weeks 3 + 4
|
Week 5
|
Target Stabilisation Dose (Week 6)*
|
Monotherapy with lamotrigine OR adjunctive therapy WITHOUT valproate and WITHOUT inducers of lamotrigine glucuronidation (see section 4.5):
|
|
|
|
|
This dosage regimen should be used with other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation
|
25mg/day (once a day)
|
50mg/day (once a day or two divided doses
|
100mg/day (once a day or two divided doses)
|
200mg/day – usual target dose for optimal response (once a day or two divided doses)
Doses In the range 100 - 400mg/day used in clinical trials
|
Adjunctive therapy WITH valproate (inhibitor of lamotrigine glucuronidation - see section 4.5):
|
|
|
|
|
This dosage regimen should be used with valproate regardless of any concomitant medicinal products
|
12.5mg/day (given as 25mg on alternate days)
|
25mg/day (once a day)
|
50mg/day (once a day or two divided doses)
|
100mg/day – usual target dose for optimal response (once a day or two divided doses)
Maximum dose of 200mg/day can be used depending on clinical response
|
Adjunctive therapy WITHOUT valproate and WITH inducers of lamotrigine glucuronidation (see section 4.5):
|
|
|
|
|
This dosage regimen should be used without valproate but with:
phenytoin
carbamazepine
phenobarbital
primidone
rifampicin
lopinavir/ritonavir
|
50mg/day (once a day)
|
100mg/day (two divided doses)
|
200mg/day (two divided doses)
|
300mg/day in week 6, if necessary increasing to usual target dose of 400mg/day in week 7, to achieve optimal response (two divided doses)
|
In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known (see section 4.5), the dose escalation as recommended for lamotrigine with concurrent valproate, should be used.
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|
|
|
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* The Target stabilisation dose will alter depending on clinical response
Table 4: Adults aged 18 years and above - maintenance stabilsation total daily dosefollowing 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
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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
|
100mg/day
|
200mg/day
|
Maintain this dose (200mg/day)
(two divided doses)
|
|
200mg/day
|
300mg/day
|
400mg/day
|
Maintain this dose (400mg/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
phenobarbital
primidone
rifampicin
lopinavir/ritonavir
|
400mg/day
|
400mg/day
|
300mg/day
|
200mg/day
|
300mg/day
|
300mg/day
|
225mg/day
|
150mg/day
|
|
200mg/day
|
200mg/day
|
150mg/day
|
100mg/day
|
|
Withdrawal of medicinal products that do NOT signifcantly 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 (200mg/day; two divided doses)
(dose range 100 - 400mg/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 with concurrent valproate should be used.
|
|
|
|
|
* Dose may be increased to 400mg/day as needed
Table 5: Adults aged 18 years and above - adjustment of lamotrigine daily dosing following the addition of other medicinal products in treatment of bipolar disorder
There is no clinical experience in adjusting the lamotrigine daily dose following the addition of other medicinal products. However, based on interaction studies with other medicinal products, the following recommendations can be made:
Treatment Regimen
|
Current lamotrigine stabilisation dose (prior to addition)
|
Week 1 (beginning with addition)
|
Week 2
|
Week 3 onwards
|
Addition of valproate (inhibitor of lamotrigine glucuronidation - see section 4.5), depending on original dose of lamotrigine:
|
|
|
|
|
This dosage regimen should be used when valproate is added regardless of any concomitant medicinal products
|
200mg/day
|
100mg/day
|
Maintain this dose
(100mg/day)
|
|
300mg/day
|
150mg/day
|
Maintain this dose
(150mg/day)
|
|
|
400mg/day
|
200mg/day
|
Maintain this dose
(200mg/day)
|
|
|
Addition of inducers of lamotrigine glucuronidation in patients NOT taking valproate (see section 4.5), depending on original dose of lamotrigine:
|
|
|
|
|
This dosage regimen should be used when the following are added without valproate:
phenytoin
carbamazepine
phenobarbital
primidone
rifampicin
lopinavir/ritonavir
|
200mg/day
|
200mg/day
|
300mg/day
|
400mg/day
|
150mg/day
|
150mg/day
|
225mg/day
|
300mg/day
|
|
100mg/day
|
100mg/day
|
150mg/day
|
200mg/day
|
|
Addition 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 added
|
Maintain target dose achieved in dose escalation (200mg/day; dose range 100-400mg/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 with concurrent valproate, should be used.
|
|
|
|
|
Discontinuation of Lamotrigine Dispersible Tablets in patients with bipolar disorder
In clinical trials, there was no increase in the incidence, severity or type of adverse reactions following abrupt termination of lamotrigine versus placebo. Therefore, patients may terminate Lamotrigine Dispersible Tablets without a step-wise reduction of dose.
Children and adolescents below 18 years
Lamotrigine Dispersible Tablets is not recommended for use in children below 18 years of age due to a lack of data on safety and efficacy (see section 4.4).
General dosing recommendations for Lamotrigine Dispersible Tablets in special patient populations
Women taking hormonal contraceptives
The use of an ethinyloestradiol/levonorgestrel (30µg/150µg) combination increases the clearance of lamotrigine by approximately two-fold, resulting in decreased lamotrigine levels. Following titration, higher maintenance doses of lamotrigine (by as much as two-fold) may be needed to attain a maximal therapeutic response. During the pill-free week, a two-fold increase in lamotrigine levels has been observed. Dose-related adverse events cannot be excluded. Therefore, consideration should be given to using contraception without a pill-free week, as first-line therapy (for example, continuous hormonal contraceptives or non-hormonal methods; see sections 4.4 and 4.5).
Starting hormonal contraceptives in patients already taking maintenance doses of lamotrigine and NOT taking inducers of lamotrigine glucuronidation
The maintenance dose of lamotrigine will in most cases need to be increased by as much as two-fold (see sections 4.4 and 4.5). It is recommended that from the time that the hormonal contraceptive is started, the lamotrigine dose is increased by 50 to 100mg/day every week, according to the individual clinical response. Dose increases should not exceed this rate, unless the clinical response supports larger increases. Measurement of serum lamotrigine concentrations before and after starting hormonal contraceptives may be considered, as confirmation that the baseline concentration of lamotrigine is being maintained. If necessary, the dose should be adapted. In women taking a hormonal contraceptive that includes one week of inactive treatment ("pill-free week"), serum lamotrigine level monitoring should be conducted during week 3 of active treatment, i.e. on days 15 to 21 of the pill cycle. Therefore, consideration should be given to using contraception without a pill-free week, as first-line therapy (for example, continuous hormonal contraceptives or non-hormonal methods; see sections 4.4 and 4.5).
Stopping hormonal contraceptives in patients already taking maintenance doses of lamotrigine and NOT taking inducers oflamotrigine glucuronidation
The maintenance dose of lamotrigine will in most cases need to be decreased by as much as 50% (see sections 4.4 and 4.5). It is recommended to gradually decrease the daily dose of lamotrigine by 50-100mg each week (at a rate not exceeding 25% of the total daily dose per week) over a period of 3 weeks, unless the clinical response indicates otherwise. Measurement of serum lamotrigine concentrations before and after stopping hormonal contraceptives may be considered, as confirmation that the baseline concentration of lamotrigine is being maintained. In women who wish to stop taking a hormonal contraceptive that includes one week of inactive treatment ("pill-free week"), serum lamotrigine level monitoring should be conducted during week 3 of active treatment, i.e. on days 15 to 21 of the pill cycle. Samples for assessment of lamotrigine levels after permanently stopping the contraceptive pill should not be collected during the first week after stopping the pill.
Starting lamotrigine in patients already taking hormonal contraceptives
Dose escalation should follow the normal dose recommendation described in the tables.
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.
Elderly(above 65 years)
The pharmacokinetics of lamotrigine in this age group do not differ significantly from a non-elderly population and therefore no dosage adjustment is required.
Renal impairment
Caution should be exercised when administering Lamotrigine Dispersible Tablets 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
Doses should generally be reduced by approximately 50% in patients with moderate hepatic impairment (Child-Pugh grade B) and 75% in patients with severe hepatic impairment (Child-Pugh grade C). Escalation and maintenance doses should be adjusted according to clinical response.
4.3 Contraindications
Hypersensitivity to Lamotrigine Dispersible Tablets or any of the excipients of this product
4.4 Special Warnings And Precautions For Use
Skin rash
There have been reports of adverse skin reactions, which have generally occurred within the first eight 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 also been reported. These have included potentially life-threatening rashes such as Stevens-Johnson syndrome and toxic epidermal necrolysis (see section 4.8).
In adults enrolled in studies utilizing 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 Stevens-Johnson syndrome (1 in 1000). In clinical trials in patients with bipolar disorder, the incidence of serious rash is approximately 1 in 1000.
The risk of serious skin rashes in children is higher 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 reaction to lamotrigine treatment 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 (see section 4.2)
− concomitant use of valproate (see section 4.2).
Caution is also required when treating patients with a history of allergy or rash to other AEDs 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 Dispersible Tablets withdrawn immediately unless the rash is clearly not related to lamotrigine treatment. It is recommended that Lamotrigine Dispersible Tablets 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.
Rashes have 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 (see section 4.8). 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. Patients should be warned to seek immediate medical advice if any of these signs and symptoms develop. Patients should be evaluated immediately should such signs and symptoms and Lamotrigine discontinued if an alternative aetiology cannot be established
Clinical worsening and suicide risk
Suicidal ideation and behaviour have been reported in patients treated with AEDs in several indications. A meta-analysis of randomised placebo-controlled trials of AEDs has also shown a small increased risk of suicidal ideation and behaviour. The mechanism of this risk is not known and the available data do not exclude the possibility of an increased risk for lamotrigine.
Therefore patients should be monitored for signs of suicidal ideation and behaviours and appropriate treatment should be considered. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation or behaviour emerge.
In patients with bipolar disorder, worsening of depressive symptoms and/or the emergence of suicidality may occur whether or not they are taking medications for bipolar disorder, including Lamotrigine Dispersible Tablets. Therefore patients receiving Lamotrigine Dispersible Tablets for bipolar disorder should be closely monitored for clinical worsening (including development of new symptoms) and suicidality, especially at the beginning of a course of treatment, or at the time of dose changes. Certain patients, such as those with a history of suicidal behaviour or thoughts, young adults, and those patients exhibiting a significant degree of suicidal ideation prior to commencement of treatment, may be at a greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients who experience clinical worsening (including development of new symptoms) and/or the emergence of suicidal ideation/behaviour, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
Hormonal contraceptives
Effects of hormonal contraceptives on lamotrigine efficacy
The use of an ethinyloestradiol/levonorgestrel (30µg/150µg) combination increases the clearance of lamotrigine by approximately two-fold resulting in decreased lamotrigine levels (see section 4.5). A decrease in lamotrigine levels has been associated with loss of seizure control. Following titration, higher maintenance doses of lamotrigine (by as much as two-fold) will be needed in most cases to attain a maximal therapeutic response. When stopping hormonal contraceptives, the clearance of lamotrigine may be halved. Increases in lamotrigine concentrations may be associated with dose-related adverse events.
Patients should be monitored with respect to this.
In women not already taking an inducer of lamotrigine glucuronidation and taking a hormonal contraceptive that includes one week of inactive treatment (for example "pill-free week"), gradual transient increases in lamotrigine levels will occur during the week of inactive treatment (see section 4.2). Variations in lamotrigine levels of this order may be associated with adverse effects. Therefore, consideration should be given to using contraception without a pill-free week, as first-line therapy (for example, continuous hormonal contraceptives or non-hormonal methods).
The interaction between other oral contraceptive or HRT treatments and lamotrigine 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 (ethinyloestradiol/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). The impact of these changes on ovarian ovulatory activity is unkown. 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.
Dihydrofolate reductase
Lamotrigine is a weak inhibitor of dihydrofolate reductase hence there is a possibility of interference with folate metabolism during long-term therapy. However, during prolonged human dosing, lamotrigine did not induce significant changes in the haemoglobin concentration, mean corpuscular volume, or serum or red blood cell folate concentrations for up to 1 year or red blood cell folate concentrations for up to 5 years.
Renal failure
In patients with end stage renal failure, single dose studies showed that 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.
Patients taking other preparations containing lamotrigine
Lamotrigine Dispersible Tablets should not be administered to patients currently being treated with any other preparation containing lamotrigine without consulting a doctor.
Development in children
There are no data on the effect of lamotrigine on growth, sexual maturation and cognitive, emotional and behavioural developments in children.
Precautions relating to epilepsy
As with other AEDs, abrupt withdrawal of Lamotrigine Dispersible Tablets may provoke rebound seizures. Unless safety concerns (for example rash) require an abrupt withdrawal, the dose of Lamotrigine Dispersible Tablets should be gradually decreased over a period of two weeks.
There are reports in the literature that severe convulsive seizues including status epilepticus may lead to rhabdomyolysis, multi organ dysfunction and disseminated intravascular coagulation, sometimes with fatal outcome. Similar cases have occurred in association with the use of lamotrigine.
A clinically significant worsening of seizure frequency instead of an improvement may be observed. In patients with more than one seizure type, the observed benefit of control for one seizure type should be weighed against any observed worsening in another seizure type.
Myoclonic seizures may be worsened by lamotrigine.
There is a suggestion in the data that responses in combination with enzyme inducers is less than in combination with non-enzyme inducing antiepileptic agents. The reason is unclear.
In children taking lamotrigine for the treatment of typical absence seizures, efficacy may not be maintained in all patients.
Precautions relating to bipolar disorder
Children and adolescents below 18 years
Treatment with antidepressants is associated with an increased risk of suicidal thinking and behaviou
