Lamotrigine 25mg tablets Taj Pharma

  1. Name of the medicinal product

Lamotrigine 25mg tablets Taj Pharma
Lamotrigine 50mg tablets Taj Pharma
Lamotrigine 100mg tablets Taj Pharma

  1. Qualitative and quantitative composition

a) Each uncoated tablet contains:
Lamotrigine USP                           25mg
Excipients                                       q.s

b) Each uncoated tablet contains:
Lamotrigine USP                           50mg
Excipients                                       q.s

c) Each uncoated tablet contains:
Lamotrigine USP                           100mg
Excipients                                       q.s

For the full list of excipients, see section 6.1

  1. Pharmaceutical form

Tablet.

  1. Clinical particulars

4.1 Therapeutic indications

Epilepsy:

Adults and adolescents aged 13 years and above

  • Adjunctive or monotherapy treatment of partial seizures and generalized seizures, including tonic-clonic seizures.
  • Seizures associated with Lennox-Gastaut syndrome. Lamotrigine is given as an adjunctive therapy but may be the initial antiepileptic drug (AED) to start with in Lennox-Gastaout syndrome.

Children and adolescents aged 2 to 12 years

  • Adjunctive treatment of partial seizures and generalized 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 is not indicated for the acute treatment of manic or depressive episodes.

4.2 Posology and method of administration

Lamotrigine tablets should be swallowed whole. If the tablets require halving ( to take half the dose or to facilitate ease of swallowing), the halves should also be swallowed whole and not be chewed or crushed

Use a tablet cutter to halve tablets. Alternatively, keeping the score-line side facing upwards, hold both the upper and lower sides of the tablet, on either side of the score-line, using the thumb and index finger of both hands (Fig. A) and halve the tablet by pressing down and away from the score-line so that the tablet opens at the score-line side. Do not hold on to the shoulder (end) of the tablet, on either side of the score-line (Fig. B), when halving since this may cause the tablet to crumble.

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.

For doses not realisable/practicable with this medicinal product, other strengths of this medicinal product or other pharmaceutical forms and products are available.

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). 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 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.

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 Weeks 1+2 Weeks 3+4 Usual maintenance dose
Monotherapy: 25 mg/day

(once a day)

50 mg/day

(once a day)

100-200 mg/day

(once a day or two divided doses)

To achieve maintenance, doses may increased by maximum of 50-100 mg every one to two weeks until optimal response is achieved.

500 mg/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 12.5 mg/day

(given as 25 mg on alternate days)

25 mg/day

(once a day)

100-200 mg/day

(once a day or two divided doses)

To achieve maintenance, doses may be increased by maximum of 25-50 mg 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

carbamazepin

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

50 mg/day

(once a day)

100 mg/day

(two divided doses)

200-400 mg/day

(two divided doses)

To achieve maintenance, doses may be increased by maximum of 100 mg 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 25 mg/day

(once a day)

50 mg/day

(once a day)

100-200 mg/day

(once a day or two divided doses)

To achieve maintenance, doses may be increased by maximum of 50-100 mg 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.

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)

1-15 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

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 0.15 mg/kg/day*

(once a day)

0.3 mg/kg/day

(once a day)

1-5 mg/kg/day

(once a day or two divided doses)

To achieve maintenance, doses may be increased by maximum of 0.3 mg/kg/day 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

carbamazepin

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

0.6 mg/kg/day

(two divided doses)

1.2 mg/kg/day

(two divided doses)

5-15 mg/kg/day

(once a day or two divided doses)

To achieve maintenance, doses may be increased by maximum of 1.2mg/kg/day every one to two weeks until optimal response is achieved, with a maximum maintenance dose of 400 mg/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 0.3 mg/kg/day

(once a day or two divided doses)

0.6 mg/kg/day

(once a day or two divided doses)

1-10 mg/kg/day

(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, with a maximum of maintenance dose of 200 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 with concurrent valproate should be used.
*NOTE: The recommended dosing schedule for children may not be achievable with the current strengths of the tablets.

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 monotherapy.

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 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 25 mg/day

(once a day)

50 mg/day

(once a day or two divided doses)

100 mg/day

(once a day or two divided doses)

200 mg/day – usual target dose for optimal response (once a day or two divided doses).

Doses in the range 100 – 400 mg/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 12.5 mg/day

(given as 25 mg on alternate days)

25 mg/day

(once a day)

50 mg/day

(once a day or two divided doses)

100 mg/day – usual target dose for optimal response (once day or two divided doses)

Maximum dose of 200 mg/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

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

50 mg/day

(once a day)

100 mg/day

(two divided doses)

200 mg/day

(two divided doses)

300 mg/day in week 6, If necessary increasing to usual target dose of 400 mg/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 escalations as recommended for lamotrigine with concurrent valproate should be used.

* The target stabilisation dose will alter depending on clinical response.

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 recommended for lamotrigine is to initially maintain the current dose and adjust the lamotrigine treatment based on clinical response.
* Dose may be increased to 400 mg/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 200 mg/day 100 mg/day Maintain this dose (100 mg/day)
300 mg/day 150 mg/day Maintain this dose (150 mg/day)
400 mg/day 200 mg/day Maintain this dose (200 mg/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

phenobarbitone

primidone

rifampicin

lopinavir/ritonavir

200 mg/day 200 mg/day 300 mg/day 400 mg/day
150 mg/day 150 mg/day 225 mg/day 300 mg/day
100 mg/day 100 mg/day 150 mg/day 200 mg/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 (200 mg/day; 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 with concurrent valproate should be used.

Discontinuation of Lamotrigine 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 without a step-wise reduction of dose.

Paediatric population

Lamotrigine 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).

General dosing recommendations for Lamotrigine in special patient populations

Women taking hormonal contraceptives

The use of an ethinyloestradiol/levonorgestrel (30 µg/150 µg) 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 100 mg/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 of lamotrigine 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- 100 mg 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.

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 dose 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 lamotrigine 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).

4.3 Contraindications

Hypersensitivity to lamotrigine, sunset yellow aluminium lake or to any of the excipients listed in section 6.1.

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 cutaneous rashes Stevens-Johnson syndrome (SJS),toxic epidermal necrolysis (TEN) Drug Reaction with Eosinophilia and Systemic Symptoms (DRESS); also known as hypersensitivity syndrome (HSS) (See section 4.8)

Patients should be advised of the signs and symptoms and monitored closely for skin reactions. The highest risk for occurrence of SJS or TEN is within the first weeks of treatment.

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 hospitalization 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 withdrawn immediately unless the rash is clearly not related to lamotrigine treatment. 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 re-started in this patient at any time.

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 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 or symptoms are present the patient should be evaluated immediately and lamotrigine 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 reexposure 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.

Clinical worsening and suicide risk

Suicidal ideation and behaviour have been reported in patients treated with AEDs in several indications. A meta-analysis of randomized 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 of 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. Therefore patients receiving lamotrigine 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 (30 µg/150 µg) 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 (ethinyloestadiol/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 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, e.g. breakthrough bleeding.

Dihydrofolate reductase

Lamotrigine has a slight inhibitory effect on dihydrofolic acid reductase, hence there is a possibility of interference with folate metabolism during long-term therapy (see section 4.6). 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 up to 1 year or red blood cell folate concentrations for up to 5 years.

Renal failure

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.

Patients taking other preparations containing lamotrigine

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

Excipients of Lamotrigine tablets

Lamotrigine contains lactose monohydrate. Patients with rare hereditary problems of galactose intolerance, the Lapp lactase deficiency or glucose-galactose malabsorption should not take this medicine.

Lamotrigine 100 mg tablets contains sunset yellow aluminium lake, which may cause allergic reactions.

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 may provoke rebound seizures. Unless safety concerns (for example rash) require an abrupt withdrawal, the dose of lamotrigine should be gradually decreased over a period of two weeks.

There are reports in the literature that severe convulsive seizures including status epilepticus may lead to rhabdomyolysis, multiorgan 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 treament of typical absence seizures, efficacy may not be maintained in all patients.

Precautions relating to bipolar disorder

Paediatric population

Treatment with antidepressants is associated with an increased risk of suicidal thinking and behaviour in children and adolescents with major depressive disorder and other psychiatric disorders.

Brugada-type ECG

Arrhythmogenic ST-T abnormality and typical Brugada ECG pattern has been reported in patients treated with lamotrigine.The use of lamotrigine should be carefully considered in patients with Brugada syndrome.

Haemophagocytic lymphohistiocytosis (HLH)

HLH has been reported in patients taking lamotrigine (see section 4.8). HLH is characterised by signs and symptoms, like fever, rash, neurological symptoms, hepatosplenomegaly, lymphadenopathy, cytopenias, high serum ferritin, hypertriglyceridaemia and abnormalities of liver function and coagulation. Symptoms occur generally within 4 weeks of treatment initiation, HLH can be life threatening.

Patients should be informed of the symptoms associated with HLH and should be advised to seek medical attention immediately if they experience these symptoms while on lamotrigine therapy.

Immediately evaluate patients who develop these signs and symptoms and consider a diagnosis of HLH. Lamotrigine should be promptly discontinued unless an alternative aetiology can be established.

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

Carbamazepine

Phenobarbitone

Primidone

Rifampicin

Lopinavir/ritonavir

Ethinyloestradiol/ levonogestrel combination**

Atazanavir/ritonavir*

Oxcarbazepine

Felbamate

Gabapentin

Levetiracetam

Pregabalin

Topiramate

Zonisamide

Lithium

Buproprion

Olanzapine

Aripiprazole

*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).

Interactions involving antiepileptic drugs

Valproate, which inhibits the glucuronidation of lamotrigine, reduces the metabolism of lamotrigine and increases the mean half-life of lamotrigine nearly two-fold. In patients receiving concomitant therapy with valproate, the appropriate treatment regimen should be used (see section 4.2).

Certain AEDs (such as phenytoin, carbamazepine, phenobarbitone and primidone) which induce hepatic drug-metabolising enzymes induce the glucuronidation of lamotrigine and enhance the metabolism of lamotrigine. In patients receiving concomitant therapy with phenytoin, carbamazepine, pheonbarbitone or primidone, the appropriate treatment regimen should be used (see section 4.2).

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.

There are reports in the literature of decreased lamotrigine levels when lamotrigine was given in combination with oxcarbazepine. However, in a prospective study in healthy adult volunteers using 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. Therefore in patients receiving concomitant therapy with oxcarbazepine, the treatment regimen for lamotrigine adjunctive therapy without valproate and without inducers of lamotrigine glucuronidation should be used (see section 4.2).

In a study of healthy volunteers, coadministration of felbamate (1200 mg twice daily) with lamotrigine (100 mg twice daily for 10 days) appeared to have no clinically relevant effects on the pharmacokinetics of lamotrigine.

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 interactions between levetiracetam and lamotrigine were assessed by evaluating serum concentrations of both agents during placebo-controlled clinical trials. These data indicate that lamotrigine does not influence the pharmacokinetics of levetiracetam and 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. There are no pharmacokinetic interactions between lamotrigine and pregabalin.

Topiramate resulted in no change in plasma concentrations of lamotrigine. Administration of lamotrigine resulted in a 15% increase in topiramate concentrations.

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.

Although changes in the plasma concentrations of other AEDs have been reported, controlled studies have shown no evidence that lamotrigine affects the plasma concentrations of concomitant AEDs. Evidence from in vitro studies indicates that lamotrigine does not displace other AEDs 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.

Multiple oral doses of bupropion had no statistically significant effects on the single dose pharmacokinetics of lamotrigine in 12 subjects and had only a slight increase in the AUC of lamotrigine glucuronide.

In a study in healthy adult volunteers, 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 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. Following the co-administration of risperidone 2 mg with lamotrigine, 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 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.

In vitro experiments indicated that the formation of lamotrigine’s primary metabolite, the 2-N-glucuronide, was minimally inhibited by co-incubation with amitriptyline, bupropion, clonazepam, haloperidol or lorazepam. These experiments also suggested that metabolism of lamotrigine was unlikely to be inhibited by clozapine, fluoxetine, phenelzine, risperidone, sertraline or trazodone. In addition, a study of bufuralol metabolism using human liver microsome preparations suggested that lamotrigine would not reduce the clearance of medicinal products metabolised predominantly by CYP2D6.

Interactions involving hormonal contraceptives

Effect of hormonal contraceptives on lamotrigine pharmacokinetics

In a study of 16 female volunteers, dosing with 30 µg ethinyloestradiol/150 µg levonorgestrel in a combined oral contraceptive pill caused an approximately two-fold increase in lamotrigine oral clearance, resulting in an average 52% and 39% reduction in lamotrigine AUC and Cmax, respectively. Serum lamotrigine concentrations increased during the course of the week of inactive treatment (including the “pill-free” week), with pre-dose concentrations at the end of the week of inactive treatment being, on average, approximately two-fold higher than during co-therapy (see section 4.4). No adjustments to the recommended dose escalation guidelines for lamotrigine should be necessary solely based on the use of hormonal contraceptives, but the maintenance dose of lamotrigine will need to be increased or decreased in most cases when starting or stopping hormonal contraceptives (see section 4.2).

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 ethinyloestradiol component of a combined oral contraceptive pill. A modest increase in oral clearance of the levonorgestrel component was observed, resulting in an average 19% and 12% reduction in levonorgestrel AUC and Cmax, respectively. Measurement of serum FSH, LH and oestradiol 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 the 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). 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 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).

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 an inhibitor of OCT 2, with an IC50 value of 53.8 μM. 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.

4.6 Fertility, pregnancy and lactation

Risk related to antiepileptic drugs in general

Specialist advice should be given to women who are of childbearing potential. The antiepileptic treatment 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. Monotherapy should be preferred whenever possible because therapy with multiple AEDs could be associated with a higher risk of congenital malformations than monotherapy, depending on the associated antiepileptics.

Risk related to lamotrigine

Pregnancy

A large amount of data on pregnant women exposed to lamotrigine monotherapy during the first trimester of pregnancy (more than 8700) do not suggest a substantial increase in the risk for major congenital malformations including oral clefts. Animal studies have shown developmental toxicity (see section 5.3).

If therapy with lamotrigine 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. 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.

Breast-feeding

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.

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 ,such as sedation, rash and poor weight gain.

Fertility

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

4.7 Effects on ability to drive and use machines

As there is individual variation in response to all AED therapy, patients taking lamotrigine to treat epilepsy should consult their physician on the specific issues of driving and epilepsy.

No studies on the effects on the ability to drive and use machines have been performed. Two volunteer studies have demonstrated that the effect of lamotrigine on fine visual motor co-ordination, eye movements, body sway and subjective sedative effects did not differ from placebo. In clinical trials with lamotrigine adverse reactions of a neurological character such as dizziness and diplopia have been reported. Therefore, patients should see how lamotrigine therapy affects them before driving or operating machinery.

4.8 Undesirable effects

The undesirable effects for epilepsy and bipolar disorder indications are based on available data from controlled clinical studies and other clinical experience and are listed in the table below. Frequency categories are derived from controlled clinical studies (epilepsy monotherapy (identified by†) and bipolar disorder (identified by §)). Where frequency categories differ between clinical trial data from epilepsy and bipolar disorder the most conservative frequency is shown. However, where no controlled clinical trial data are available, frequency categories have been obtained from other clinical experience.

The following convention has been utilized for the classification of undesirable effects:

Very common: (≥1/10)

Common: (≥1/100 to <1/10)

Uncommon: (≥1/1,000 to <1/100)

Rare: (≥1/10,000 to <1/1,000)

Very rare: (<1/10,000), not known (frequency cannot be estimated from the available data).

System Organ Class Adverse Event Frequency
Blood and lymphatic system disorders Haematological abnormalities1 including neutropenia, leucopenia, anaemia, thrombocytopenia, pancytopenia, aplastic anaemia, agranulocytosis

Haemophagocytic lymphohistiocytosis (HLH)

Very rare
Lymphadenopathy1 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
Hypogammaglobulinaemia Not known
Psychiatric Disorders Aggression, irritability Common
Confusion, hallucinations, tics Very rare
Nightmares Not known
Nervous System Disorders Headache†§ Very Common
Somnolence†§, dizziness†§, tremor, insomnia agitation§ Common
Ataxia Uncommon
Nystagmus Rare
Unsteadiness, movement disorders, worsening of Parkinson’s disease 3, extrapyramidal effects, choreoathetosis, increase in seizure frequency Very Rare
Aseptic meningitis (see section 4.4) Rare
Eye disorders Diplopia, blurred vision Uncommon
Conjunctivitis Rare
Gastrointestinal disorders Nausea, vomiting, diarrhoea, dry mouth§ Common
Hepatobiliary disorders Hepatic failure, hepatic dysfunction4, increased liver function tests Very rare
Skin and subcutaneous tissue disorders Skin rash5†§ Very common
Alopecia Uncommon
Stevens–Johnson Syndrome § Rare
Toxic epidermal necrolysis Very rare
Drug Reaction with Eosinophilia and Systemic Symptoms Very rare
Musculoskeletal and connective tissue disorders Arthralgia§ Common
Lupus-like reactions Very rare
General disorders and administration site conditions Tiredness, pain§, back pain§ Common

Description of selected adverse reactions

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

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 Lamotrigine 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 In 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 Lamotrigine (see section 4.4).

Serious potentially life-threatening skin rashes, including Stevens–Johnson syndrome and toxic epidermal necrolysis (Lyell’s Syndrome) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported. Although the majority recover on withdrawal of lamotrigine treatment, some patients experience irreversible scarring and there have been rare cases of associated death (see section 4.4).

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).

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

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

Reporting of suspected adverse reactions

Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product.

4.9 Overdose

Symptoms and signs

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.

Treatment

In the event of overdose, 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 for 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).

  1. Pharmacological properties

5.1 Pharmacodynamic properties

Pharmacotherapeutic group: Other Antiepileptics

Mechanism of action:

The results of pharmacological studies suggest that lamotrigine is a use- and voltage-dependent blocker of voltage gated sodium channels. It inhibits sustained, repetitive firing of neurons and inhibits release of glutamate (the neurotransmitter which plays a key role in the generation of epileptic seizures). These effects are likely to contribute to the anticonvulsant properties of lamotrigine.

In contrast, the mechanisms by which lamotrigine exerts its therapeutic action in bipolar disorder have not been established, although interaction with voltage gated sodium channels is likely to be important.

Pharmacodynamic effects

In tests designed to evaluate the central nervous system effects of medicinal products, the results obtained using doses of 240 mg lamotrigine administered to healthy volunteers did not differ from placebo, whereas both 1000 mg phenytoin and 10 mg diazepam each significantly impaired fine visual motor co-ordination 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 co-ordination 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 efficacy and safety in children aged 1 to 24 months

The efficacy and safety of adjunctive therapy in partial seizures in patients aged 1 to 24 months has been evaluated in a small double-blind placebo-controlled withdrawal study. Treatment was initiated in 177 subjects, with a dose titration schedule similar to that of children aged 2 to 12 years. Lamotrigine 2 mg tablets are the lowest strength available, therefore the standard dosing schedule was adapted in some cases during the titration phase (for example, by administering a 2 mg tablet on alternate days when the calculated dose was less than 2 mg). Serum levels were measured at the end of week 2 of titration and the subsequent dose either reduced or not increased if the concentration exceeded 0.41 µg/mL, the expected concentration in adults at this time point. Dose reductions of up to 90% were required in some patients at the end of week 2. Thirty-eight responders (> 40% decrease in seizure frequency) were randomized to placebo or continuation of lamotrigine. The proportion of subjects with treatment failure was 84% (16/19 subjects) in the placebo arm and 58% (11/19 subjects) in the lamotrigine arm. The difference was not statistically significant: 26.3%, CI95% -2.6% <> 50.2%, p=0.07.

A total of 256 subjects between 1 to 24 months of age have been exposed to lamotrigine in the dose range 1 to 15 mg/kg/day for up to 72 weeks. The safety profile of lamotrigine in children aged 1 month to 2 years was similar to that in older children except that clinically significant worsening of seizures (>=50%) was reported more often in children under 2 years of age (26%) as compared to older children (14%).

Clinical efficacy and safety in Lennox-Gastaut syndrome

There are no data for monotherapy in seizures associated with Lennox-Gastaut syndrome.

Clinical efficacy in the prevention of mood episodes in patients with bipolar disorder

The efficacy of lamotrigine in the prevention of mood episodes in patients with bipolar I disorder has been evaluated in two studies.

Study SCAB2003 was a multicentre, double-blind, double dummy, placebo and lithium-controlled, randomised fixed dose evaluation of the long-term prevention of relapse and recurrence of depression and/or mania in patients with bipolar I disorder who had recently or were currently experiencing a major depressive episode. Once stabilised using lamotrigine monotherapy or adjunctive therapy, patients were randomly assigned into one of five treatment groups: lamotrigine (50, 200, 400 mg/day), lithium (serum levels of 0.8 to 1.1 mMol/L) or placebo for a maximum of 76 weeks (18 months). The primary endpoint was “Time to Intervention for a Mood Episode (TIME)”, where the interventions were additional pharmacotherapy or electroconvulsive therapy (ECT). Study SCAB2006 had a similar design as study SCAB2003, but differed from study SCAB2003 in evaluating a flexible dose of lamotrigine (100 to 400 mg/day) and including patients with bipolar I disorder who had recently or were currently experiencing a manic episode. The results are shown in Table 7.

Table 7: Summary of results from studies investigating the efficacy of lamotrigine in the prevention of mood episodes in patients with bipolar I disorder

‘Proportion’ of patients being event free at week 76
Study SCAB2003

Bipolar I

Study SCAB2006

Bipolar I

Inclusion criterion Major depressive episode Major manic episode
Lamotrigine Lithium Placebo Lamotrigine Lithium Placebo
Intervention free 0.22 0.21 0.12 0.17 0.24 0.04
p-value Log rank test 0.004 0.006 0.023 0.006
Depression free 0.51 0.46 0.41 0.82 0.71 0.40
p-value Log rank test 0.047 0.209 0.015 0.167
Free of mania 0.70 0.86 0.67 0.53 0.64 0.37
p-value Log rank test 0.339 0.026 0.280 0.006

In supportive analyses of time to first depressive episode and time to first manic/hypomanic or mixed episode, the lamotrigine-treated patients had significantly longer times to first depressive episode than placebo patients, and the treatment difference with respect to time to manic/hypomanic or mixed episodes was not statistically significant.

The efficacy of lamotrigine in combination with mood stabilisers has not been adequately studied.

Children (10-12 years of age) and Adolescents (13-17 years of age)

A multicentre, parallel group, placebo-controlled, double-blind, randomised withdrawal study, evaluated the efficacy and safety of lamotrigine IR as add-on maintenance therapy to delay mood episodes in male and female children and adolescents (age 10-17 years) who had been diagnosed with bipolar I disorder and who had remitted or improved from a bipolar episode while treated with lamotrigine in combinations with concomitant antipsychotic or other moodstabilising drugs. The result of the primary efficacy analysis (time to occurrence of a bipolar event – TOBE) did not reach statistical significance (p=0.0717), thus efficacy was not shown. In addition, safety results showed increased reporting of suicidal behaviours in lamotrigine treated patients: 5% (4 patients) in the lamotrigine arm compared to 0 in placebo (see section 4.2).

Study of the effect of lamotrigine on cardiac conduction

A study in healthy adult volunteers evaluated the effect of repeat doses of lamotrigine (up to 400 mg/day) on cardiac conduction, as assessed by 12-lead ECG. There was no clinically significant effect of lamotrigine on QT interval compared to placebo.

5.2 Pharmacokinetic properties

Absorption

Lamotrigine is rapidly and completely absorbed from the gut with no significant first-pass metabolism. Peak plasma concentrations occur approximately 2.5 hours after oral administration of lamotrigine. Time to maximum concentration is slightly delayed after food but the extent of absorption is unaffected. There is considerable inter-individual variation in steady state maximum concentrations but within an individual, concentrations rarely vary.

Distribution

Binding to plasma proteins is about 55%; it is very unlikely that displacement from plasma proteins would result in toxicity.

The volume of distribution is 0.92 to1.22 L/kg.

Biotransformation

UDP-glucuronyl transferases have been identified as the enzymes responsible for metabolism of lamotrigine.

Lamotrigine induces its own metabolism to a modest extent depending on dose. However, there is no evidence that lamotrigine affects the pharmacokinetics of other AEDs and data suggest that interactions between lamotrigine and medicinal products metabolised by cytochrome P450 enzymes are unlikely to occur.

Elimination

The apparent plasma clearance in healthy subjects is approximately 30 mL/min. Clearance of lamotrigine is primarily metabolic with subsequent elimination of glucuronide-conjugated material in urine. Less than 10% is excreted unchanged in the urine. Only about 2% of lamotrigine-related material is excreted in faeces. Clearance and half-life are independent of dose. The apparent plasma half-life in healthy subjects is estimated to be approximately 33 hours (range 14 to 103 hours). In a study of subjects with Gilbert’s syndrome, mean apparent clearance was reduced by 32% compared with normal controls but the values are within the range for the general population.

The half-life of lamotrigine is greatly affected by concomitant medicinal products. Mean half-life is reduced to approximately 14 hours when given with glucuronidation-inducing medicinal products such as carbamazepine and phenytoin and is increased to a mean of approximately 70 hours when co-administered with valproate alone (see section 4.2).

Linearity

The pharmacokinetics of lamotrigine are linear up to 450mg, the highest single dose tested.

Special patient populations

Children

Clearance adjusted for body weight is higher in children than in adults with the highest values in children under five years. The half-life of lamotrigine is generally shorter in children than in adults with a mean value of approximately 7 hours when given with enzyme-inducing medicinal products such as carbamazepine and phenytoin and increasing to mean values of 45 to 50 hours when co-administered with sodium valproate alone (see section 4.2).

Infants aged 2 to 26 months

In 143 paediatric patients aged 2 to 26 months, weighing 3 to 16 kg, clearance was reduced compared to older children with the same body weight, receiving similar oral doses per kg body weight as children older than 2 years. The mean half-life was estimated at 23 hours in infants younger than 26 months on enzyme-inducing therapy, 136 hours when co-administered with valproate and 38 hours in subjects treated without enzyme inducers/inhibitors. The inter-individual variability for oral clearance was high in the group of paediatric patients of 2 to 26 months (47%). The predicted serum concentration levels in children of 2 to 26 months were in general in the same range as those in older children, though higher Cmax levels are likely to be observed in some children with a body weight below 10 kg.

Elderly

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 nine studies with non-elderly adults after single doses of 30 to 450 mg.

Renal impairment

Twelve volunteers with chronic renal failure, and another six individuals undergoing haemodialysis were each given a single 100 mg dose of lamotrigine. Mean clearances were 0.42 mL/min/kg (chronic renal failure), 0.33 mL/min/kg (between hemodialysis) and 1.57 mL/min/kg (during hemodialysis), compared with 0.58 mL/min/kg in healthy volunteers. Mean plasma half-lives were 42.9 hours (chronic renal failure), 57.4 hours (between hemodialysis) and 13.0 hours (during hemodialysis), compared with 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 hemodialysis session.

For this patient population, initial doses of lamotrigine should be based on the patient’s concomitant medicinal products; reduced maintenance doses may be effective for patients with significant renal functional impairment (see sections 4.2 and 4.4).

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 with 0.34 mL/min/kg in the healthy controls. Initial, escalation and maintenance doses should generally be reduced in patients with moderate or severe hepatic impairment (see section 4.2).

5.3 Preclinical safety data

Non-clinical data reveal no special hazard for humans based on studies of safety pharmacology, repeated dose toxicity, genotoxicity and carcinogenic potential.

In reproductive and developmental toxicity studies in rodents and rabbits, no teratogenic effects but reduced foetal weight and retarded skeletal ossification were observed, at exposure levels below or similar to the expected clinical exposure. Since higher exposure levels could not be tested in animals due to the severity of maternal toxicity, the teratogenic potential of lamotrigine has not been characterised above clinical exposure.

In rats, enhanced foetal as well as post-natal mortality was observed when lamotrigine was administered during late gestation and through the early post-natal period. These effects were observed at the expected clinical exposure.

In juvenile rats, an effect on learning in the Biel maze test, a slight delay in balanopreputial separation and vaginal patency and a decreased postnatal body weight gain in F1 animals were observed at exposures approximately two-times higher than the therapeutic exposures in human adults.

Animal experiments did not reveal impairment of fertility by lamotrigine. Lamotrigine reduced foetal folic acid levels in rats. Folic acid deficiency is assumed to be associated with an enhanced risk of congenital malformations in animal as well as in humans.

Lamotrigine caused a dose-related inhibition of the hERG channel tail current in human embryonic kidney cells. The IC50 was approximately nine-times above the maximum therapeutic free concentration. Lamotrigine did not cause QT prolongation in animals at exposures up to approximately two-times the maximum therapeutic free concentration. In a clinical study, there was no clinically significant effect of lamotrigine on QT interval in healthy adult volunteers (see section 5.1).

  1. Pharmaceutical particulars

6.1 List of excipients

Cellulose, microcrystalline, Lactose monohydrate, Sodium starch glycolate, Magnesium stearate, Povidone

6.2 Incompatibilities

Not applicable.

6.3 Shelf life

4 years

6.4 Special precautions for storage

This medicinal product does not require any special storage conditions.

6.5 Nature and contents of container

Clear PVC/Aluminium blister packs:

Pack sizes: 1, 7, 10, 14, 20, 21, 28, 30, 40, 42, 46, 50, 56, 60, 90, 98, 100, 200, 250, 500 tablets.

Not all pack sizes may be marketed.

6.6 Special precautions for disposal and other handling

No special requirements.

7. Manufactured By:
Taj Pharmaceuticals Ltd. (Mumbai, India)
Unit No. 214, Old Bake House,
Maharashtra Chambers of commerce Lane,Fort,
Mumbai-400001 at: Ahmedabad- Gujarat, INDIA.

Lamotrigine 25mg tablets Taj Pharma
Lamotrigine 50mg tablets Taj Pharma
Lamotrigine 100mg tablets Taj Pharma

Patient Information leaflet

Read all of this leaflet carefully before you start taking this medicine.

  • Keep this leaflet. You may need to read it again.
  • If you have any further questions, ask your doctor or pharmacist.
  • This medicine has been prescribed for you. Do not pass it on to others. It may harm them, even if their symptoms are the same as yours.
  • If any of the side effects get serious, or if you notice any side effects not listed in this leaflet, please tell your doctor or pharmacist.

In this leaflet

1 What Lamotrigine tablets are and what they are used for
2 Before you take Lamotrigine tablets
3 How to take Lamotrigine tablets
4 Possible side effects
5 How to store Lamotrigine tablets
6 Further information

1 What Lamotrigine tablets are and what they are used for

Lamotrigine tablets belong to a group of medicines called anti-epileptics. They are used to treat two conditions – epilepsy and bipolar disorder.

Lamotrigine tablets treat epilepsy by blocking the signals in the brain that trigger epileptic seizures (fits).

  • For adults and children aged 13 years and over
    Lamotrigine tablets can be used on their own or with other medicines, to treat epilepsy. Lamotrigine tablets can also be used with other medicines to treat the seizures that occur with a condition called Lennox-Gastaut syndrome.
  • For children aged between 2 and 12 years
    Lamotrigine tablets can be used with other medicines, to treat the same conditions. They can be used on their own to treat a type of epilepsy called typical absence seizures.

Lamotrigine tablets also treat bipolar disorder.

People with bipolar disorder (sometimes called manic depression) have extreme mood swings, with periods of mania (excitement or euphoria) alternating with periods of depression (deep sadness or despair). For adults aged 18 years and over Lamotrigine tablets can be used on their own or with other medicines, to prevent the periods of depression that occur in bipolar disorder. It is not yet known how Lamotrigine tablets work in the brain to have this effect.

2 Before you take Lamotrigine tablets

Do not take Lamotrigine tablets if you

  • are allergic (hypersensitive) to lamotrigine or any of the other ingredients of Lamotrigine tablets (listed in Section 6)
  • have liver problems.

If these apply to you, tell your doctor, and don’t take Lamotrigine tablets.

Take special care with Lamotrigine tablets

Your doctor needs to know before you take Lamotrigine tablets if you

  • have problems with your kidneys
  • have ever developed a rash when you’ve taken lamotrigine or other medicines for epilepsy
  • are already taking medicine that contains lamotrigine
  • have Parkinsons disease.

If any of these apply to you, tell your doctor, who may decide to lower your dose or that Lamotrigine tablets are not suitable for you.

Watch out for important symptoms

If you develop any of these symptoms after you start taking Lamotrigine tablets, get a doctor’s help straight away:

  • an unusual skin reaction, such as redness or rashes
  • sore mouth or eyes
  • high temperature (fever), flu-like symptoms or drowsiness
  • swelling around your face, or swollen glands in your neck, armpit or groin
  • unexpected bleeding or bruising, or your fingers turning blue
  • sore throat or more infections (such as colds) than usual.

These symptoms are more likely to happen during the first few months of treatment with Lamotrigine tablets, especially if you start on too high a dose, if your dose is increased too quickly or if you’re taking Lamotrigine tablets with another medicine called valproate. Children are more likely to be affected than adults.

The symptoms listed above can develop into more serious problems, such as organ failure or a very severe skin condition, if they are not treated.

If you notice any of these symptoms, see a doctor as soon as possible. Your doctor may decide to carry out tests on your liver, kidneys or blood, and may tell you to stop taking Lamotrigine tablets.

Severe skin reactions

Potentially life-threatening skin rashes (Steven-Johnson syndrome, toxic epidermal necrolysis, DRESS) have been reported with the use of Lamotrigine, appearing initially as reddish target-like spots or circular patches often with central blisters on the trunk. Additional signs to look for include ulcers in the mouth, throat, nose, genitals and conjunctivitis (red and swollen eyes).

These potentially life-threatening skin rashes are often accompanied by flu-like symptoms. The rash may progress to widespread blistering or peeling of the skin. The highest risk for occurrence of serious skin reactions is within the first weeks of treatment. If you have developed Stevens-Johnson syndrome or toxic epidermal necrolysis with the use of lamotrigine, you must not be re-started on lamotrigine at any time.

If you develop a rash or these skin symptoms, seek immediate advice from a doctor and tell them that you are taking this medicine.

Risk of increased or severe seizures

The seizures in some types of epilepsy may occasionally become worse or happen more often while you’re taking Lamotrigine tablets. Some patients may experience severe seizures, which may cause serious health problems. If your seizures happen more often, or if you experience a severe seizure while you’re taking Lamotrigine tablets, see a doctor as soon as possible.

Thoughts of harming yourself or suicide

Anti-epileptic medicines are used to treat several conditions, including epilepsy and bipolar disorder. People with bipolar disorder can sometimes have thoughts of harming themselves or committing suicide. If you have bipolar disorder, you may be more likely to think like this:

  • when you first start treatment
  • if you have previously had thoughts about harming yourself or about suicide
  • if you are under 25 years old.

If you have distressing thoughts or experiences, or if you notice that you feel worse or develop new symptoms while you’re taking Lamotrigine tablets, see a doctor as soon as possible or go to the nearest hospital for help.

A small number of people with epilepsy being treated with Lamotrigine tablets have also had thoughts of harming or killing themselves. If at any time you have these thoughts, immediately contact your doctor.

Lamotrigine tablets should not be given to people aged under 18 years to treat bipolar disorder.

Medicines to treat depression and other mental health problems increase the risk of suicidal thoughts and behaviour in children and adolescents aged under 18 years.

Taking other medicines

Tell your doctor or pharmacist if you’re taking any other medicines, if you’ve taken any recently or if you start taking new ones – these include herbal medicines or other medicines you bought without a prescription.

If you are taking certain medicines, your doctor may need to check the dose of Lamotrigine tablets.

These include:

  • oxcarbazepine, felbamate, gabapentin, levetiracetam, pregabalin, topiramate or zonisamide for epilepsy
  • lithium for mental health problems
  • bupropion for mental health problems or to stop smoking

Tell your doctor if you are taking any of these.

Some medicines interact with Lamotrigine tablets or make it more likely that you’ll have side effects.

These include:

  • valproate or carbamazepine for epilepsy and mental health problems
  • phenytoin, primidone or phenobarbitone for epilepsy
  • olanzapine or risperidone for mental health problems
  • rifampicin, an antibiotic
  • a combination of lopinavir, atazanavir and ritonavir used to treat Human Immunodeficiency Virus (HIV) infection
  • hormonal contraceptives, such as the Pill (see below)
  • orlistat used in obesity.

Tell your doctor if you are taking, or if you start or stop taking any of these.

Hormonal contraceptives (such as the Pill) can affect the way Lamotrigine tablets work

Your doctor may recommend that you use a particular type of hormonal contraceptive, or another method of contraception, such as condoms, a cap or a coil. If you are using a hormonal contraceptive like the Pill, your doctor may take samples of your blood to check the level of Lamotrigine tablets. If you plan to start using a hormonal contraceptive talk to your doctor, who will discuss suitable methods of contraception with you.

Lamotrigine tablets can also affect the way hormonal contraceptives work, although it’s unlikely to make them less effective. If you are using a hormonal contraceptive and you notice any changes in your menstrual pattern, such as breakthrough bleeding or spotting between periods, tell your doctor. These may be signs that Lamotrigine tablets are affecting the way your contraceptive is working.

Pregnancy and breast feeding

Talk to your doctor if you’re pregnant, if you might be pregnant, or if you’re planning to become pregnant.

You should not stop treatment for your epilepsy while you’re pregnant. However, there is an increased risk of birth defects in babies whose mothers took Lamotrigine tablets during pregnancy. These defects include cleft lip or cleft palate. Your doctor may advise you to take extra folic acid if you’re planning to become pregnant and while you’re pregnant.

Pregnancy may also alter the effectiveness of Lamotrigine tablets, so your doctor may take samples of your blood to check the level of Lamotrigine tablets, and may adjust your dose.

Talk to your doctor if you’re breast feeding or planning to breast feed. Lamotrigine passes into breast milk and may affect your baby. Your doctor will discuss the risks and benefits of breast feeding while you’re taking Lamotrigine tablets, and will check your baby from time to time if you decide to breast feed.

Driving and using machines

If you have epilepsy, talk to your doctor about driving and using machines.

Lamotrigine tablets can cause dizziness and double vision, do not drive or operate machines if you are affected.

Important information about some of the ingredients of Lamotrigine tablets

Lamotrigine tablets contain small amounts of a sugar called lactose. If you have intolerance to lactose or any other sugars, tell your doctor, and don’t take Lamotrigine tablets

3 How to take Lamotrigine tablets

Always use Lamotrigine tablets exactly as your doctor has told you to. Check with your doctor or pharmacist if you’re not sure.

How much Lamotrigine to take

It may take a while to find the best dose of Lamotrigine tablets for you. The dose you take will depend on:

  • your age
  • whether you are taking Lamotrigine tablets with other medicines
  • whether you have problems with your kidneys or liver.

Your doctor will start you on a low dose, and gradually increase the dose over a few weeks until you reach a dose that works for you (called the effective dose). Never take more Lamotrigine tablets than your doctor tells you to.

The usual effective dose of Lamotrigine tablets for adults and children aged over 12 years is between 100mg and 400mg each day.

For children aged 2 to 12 years, the effective dose depends on their body weight – usually, it’s between 1mg and 15mg for each kilogram of the child’s weight, up to a maximum of 400mg daily.

How to take your dose of Lamotrigine tablets

Take your dose of Lamotrigine tablets once or twice a day, as your doctor advises. You can take it with or without food.

Your doctor may also advise you to start or stop taking other medicines, depending on what condition you’re being treated for and the way you respond to treatment.

  • Swallow your tablets whole. Don’t break, chew or crush them.
  • Always take the full dose that your doctor has prescribed. Never take only part of a tablet.

If you take more Lamotrigine tablets than you should

If anyone takes too many Lamotrigine tablets, contact a doctor or pharmacist immediately.

If possible, show them the Lamotrigine tablets packet.

Someone who has taken too many Lamotrigine tablets may have any of these symptoms:

  • rapid, uncontrollable eye movements
  • clumsiness and lack of co-ordination, affecting their balance
  • loss of consciousness or coma.

If you forget to take Lamotrigine tablets

Don’t take extra tablets or a double dose to make up for a forgotten dose.

If you have missed taking a dose of Lamotrigine tablets ask your doctor for advice on how to start taking it again. It’s important that you do this.

Don’t stop taking Lamotrigine tablets without advice

Take Lamotrigine tablets for as long as your doctor recommends. Don’t stop unless your doctor advises you to.

If you are taking Lamotrigine tablets for epilepsy, to stop taking Lamotrigine tablets, it is important that your dose is reduced gradually, over about 2 weeks. If you suddenly stop taking Lamotrigine tablets your epilepsy may come back or get worse.

If you are taking Lamotrigine tablets for bipolar disorder, Lamotrigine tablets may take some time to work, so you are unlikely to feel better straight away. If you stop taking Lamotrigine tablets your dose will not need to be reduced gradually.

However you should still talk to your doctor first if you want to stop taking Lamotrigine tablets.

4 Possible side effects

Like all medicines, Lamotrigine tablets can cause side effects, but not everyone gets them.

Allergic reaction or potentially serious skin reaction, get a doctor’s help straight away

A small number of people taking Lamotrigine tablets have an allergic reaction or potentially serious skin reaction, which may develop into more serious, and even life-threatening, problems if they are not treated. Symptoms of these reactions include:

  • skin rashes or redness
  • sore mouth or eyes
  • high temperature (fever), flu-like symptoms or drowsiness
  • swelling around your face, or swollen glands in your neck, armpit or groin
  • unexpected bleeding or bruising, or your fingers turning blue
  • sore throat, or more infections (such as colds) than usual
  • very rarely potentially life-threatening skin rashes, Stevens-Johnson syndrome (skin condition, with severe blisters, and bleeding from the lips, eyes, mouth, nose and genital area) or Toxic epidermal necrolysis (severe skin reaction, starting with a painful red area, developing into large blisters then peeling of layers of skin) or DRESS

In many cases these symptoms will be signs of less serious side effects. However, you must be aware that they are potentially serious – so, if you notice any of these symptoms see a doctor as soon as possible. Your doctor may decide to carry out tests on your liver, kidneys or blood, and may tell you to stop taking Lamotrigine tablets.

Other side effects

Very common side effects: (affects more than 1 in 10 people):

  • headache
  • feeling dizzy or sleepy
  • clumsiness and lack of co-ordination
  • double or blurred vision
  • feeling or being sick
  • skin rash.

Common side effects: (affects less than 1 in 10 people):

  • aggression or irritability
  • rapid, uncontrollable eye movements
  • shaking or tremors
  • difficulty in sleeping
  • diarrhoea
  • dry mouth
  • feeling tired
  • pain in your back or joints, or elsewhere.

Rare side effects: (affects less than 1 in 1,000 people):

  • itchy eyes, with discharge and crusty eyelids (conjunctivitis)

Very rare side effects: (affects less than 1 in 10,000 people):

  • hallucinations (‘seeing’ or ‘hearing’ things that aren’t really there)
  • confusion or agitation
  • feeling ‘wobbly’ or unsteady when you move about
  • uncontrollable body movements (tics), uncontrollable muscle spasms affecting the eyes, head and torso, or other unusual body movements such as jerking, shaking or stiffness
  • in people who already have epilepsy, seizures happening more often
  • changes in liver function, which will show up in blood tests, or liver failure
  • changes which may show up in blood tests – including reduced numbers of red blood cells (anaemia), reduced numbers of white blood cells, reduced numbers of platelets (thrombocytopenia), reduced numbers of all these types of cell, and a disorder of the bone marrow called aplastic anaemia
  • a disorder of blood clotting, which can cause unexpected bleeding or bruising
  • in people who already have Parkinson’s disease, worsening of the symptoms.

Other (frequency not known)

  • aseptic meningitis (symptom include sensitivity to light, rash, muscle pain, fever and stiff neck), hair loss, DRESS.

There have been reports of bone disorders including osteopenia and osteoporosis (thinning of the bone) and fractures. Check with your doctor or pharmacist if you are on long-term antiepileptic medication, have a history of osteoporosis, or take steroids.

Reporting of side effects

If you get any side effects, talk to your doctor, pharmacist or nurse. This includes any possible side effects not listed in this leaflet.

5 How to store Lamotrigine tablets

Keep out of the sight and reach of children.

Do not use after the expiry date shown on the blisters, carton or bottle. The expiry date refers to the last day of that month.

Lamotrigine tablets do not require any special storage conditions.

If you have any unwanted tablets, don’t dispose of them in your waste water or your household rubbish. Take them back to your pharmacist, who will dispose of them in a way that won’t harm the environment.

6 Further information

What Lamotrigine tablets contain

  • The active substance is lamotrigine. Each tablet contains either 100mg of the active substance.
  • The other ingredients are colloidal anhydrous silica, iron oxide hydrate yellow, lactose monohydrate, magnesium stearate, microcrystalline cellulose, povidone, sodium starch glycollate and talc.

Contents of the pack

Aluminium blister packs:

Pack sizes: 1, 7, 10, 14, 20, 21, 28, 30, 40, 42, 46, 50, 56, 60, 90, 98, 100, 200, 250, 500 tablets.

Not All Packs May Be Marketed.

7. Manufactured By:
Taj Pharmaceuticals Ltd. (Mumbai, India)
Unit No. 214, Old Bake House,
Maharashtra Chambers of commerce Lane,Fort,
Mumbai-400001 at: Ahmedabad- Gujarat, INDIA.

 

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