Epsylam DT

Epsylam DT

lamotrigine

Manufacturer:

Aurobindo Pharma

Distributor:

Unimed
Full Prescribing Info
Contents
Lamotrigine.
Description
Lamotrigine Dispersible Tablets 50 mg: Each uncoated tablet contains Lamotrigine 50 mg.
Lamotrigine Dispersible Tablets 100 mg: Each uncoated tablet contains Lamotrigine 100 mg.
Excipients/Inactive Ingredients: Cellulose Microcrystalline, Heavy Magnesium Carbonate, Polacrilin Potassium, Sucralose, Povidone, Purified Water, Black Currant Flavour and Magnesium Stearate.
Action
Pharmacology: Pharmacodynamics: Mechanism of Action: Lamotrigine is a use-dependent blocker of voltage gated sodium channels. It produce a use- and voltage-dependent block of sustained repetitive firing in cultured neurons and inhibits pathological release of glutamate (the amino acid which plays a key role in the generation of epileptic seizures), as well as inhibiting glutamate-evoked bursts of action potentials.
Pharmacokinetics: Absorption: Lamotrigine is rapidly and completely absorbed from the gut with no significant first pass metabolism. Peak plasma concentrations occur approximately 2.5 hours following administration. Maximum plasma concentration is slightly delayed after food but the extent of absorption is unaffected. The pharmacokinetics is linear up to 450mg, the highest single dose tested. There is considerable inter-individual variation in steady state maximum concentrations but within an individual concentrations vary very little.
Distribution: Lamotrigine 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 to 1.22 l/kg.
Metabolism: 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 drugs metabolized by cytochrome P450 enzymes are unlikely to occur.
Elimination: The apparent plasma clearance in healthy subjects is approximately 30mL/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 feces. 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).
The half-life of Lamotrigine is greatly affected by concomitant medication. Mean half-life is reduced to approximately 14 hours when given with enzyme-inducing drugs such as carbamazepine and phenytoin and is increased to a mean of approximately 70 hours when coadministered with sodium valproate alone.
Linearity: The pharmacokinetics of Lamotrigine is linear up to 450mg, the highest single dose tested.
Indications/Uses
Epilepsy: Adults: Lamotrigine is indicated for use as adjunctive or monotherapy in the treatment of epilepsy, for partial seizures and generalized seizures, including tonic-clonic seizures and the seizures associated with Lennox-Gastaut Syndrome.
Children (2 to 12 years of age): Lamotrigine is indicated as adjunctive therapy in the treatment of epilepsy, for partial seizures and generalized seizures including tonic-clonic seizures and the seizures associated with Lennox-Gastaut syndrome (above 3 years of age only).
Initial monotherapy treatment in newly diagnosed paediatric patients is not recommended.
After epileptic control has been achieved during adjunctive therapy, concomitant anti epileptic drugs (AEDs) may be withdrawn and patients continued on Lamotrigine monotherapy.
Bipolar Disorder: Adults (18 years of age and over): Lamotrigine is indicated for the prevention of mood episodes in patients with bipolar disorder, predominantly by preventing depressive episodes.
Dosage/Direction for Use
Lamotrigine dispersible tablets may be chewed, dispersed in a small volume of water (at least enough to cover the whole tablet) or swallowed whole with a little water.
If a calculated dose of Lamotrigine, e.g. for use in children (epilepsy only) or patients with hepatic impairment, cannot be divided into multiple lower strength tablets, the dose to be administered is that equal to the nearest lower strength of whole tablets.
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 Precautions). 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, 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: When concomitant antiepileptic drugs are withdrawn to achieve Lamotrigine monotherapy or other AEDs are added-on to treatment regimes containing Lamotrigine, consideration should be given to the effect this may have on Lamotrigine pharmacokinetics (see Interactions).
Dosage in Epilepsy Monotherapy: Adults (over 16 years of age) (see Table 1): The initial Lamotrigine dose in monotherapy is 25 mg once a day for two weeks, followed by 50 mg once a day for two weeks. Thereafter, the dose should be increased by a maximum of 50 to 100 mg every one to two weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 100 to 200 mg/day given once a day or as two divided doses. Some patients have required 500 mg/day of Lamotrigine to achieve the desired response.
Because of a risk of rash the initial dose and subsequent dose escalation should not be exceeded (see Precautions).
Dosage in Epilepsy Add-On Therapy: Adults (over 12 years of age) (see Table 1): In patients taking valproate with/without any other AED, the initial Lamotrigine dose is 25 mg every alternate day for two weeks, followed by 25 mg once a day for two weeks. Thereafter, the dose should be increased by a maximum of 25 to 50 mg every one two weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal optimal response is 100 to 200 mg/day given once a day or in two divided doses.
In those patients taking concomitant AEDs or other medications (see Interactions) that induce Lamotrigine glucuronidation with/without other AEDs (except valproate), the initial Lamotrigine dose is 50 mg once a day for two weeks, followed by 100 mg/day given in two divided doses for two weeks.
Thereafter, the dose should be increased by a maximum of 100 mg every one to two weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 200 to 400 mg/day given in two divided doses.
Some patients have required 700 mg/day of Lamotrigine to achieve the desired response.
In those patients taking oxcarbazepine without any other inducers or inhibitors of Lamotrigine glucuronidation, the initial Lamotrigine dose is 25 mg once a day for two weeks, followed by 50 mg once a day for two weeks. Thereafter, the dose should be increased by a maximum of 50 to 100 mg every one to two weeks until the optimal response is 100 to 200 mg/day given once a day or as two divided doses. (See Table 1.)

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Because of a risk of rash the initial dose and subsequent dose escalation should not be exceeded (see Precautions).
Children (2 to 12 years of age) (see Table 2): In patients taking valproate with/without any other AED, the initial Lamotrigine dose is 0.15 mg/kg bodyweight/day given once a day for two weeks, followed by 0.3 mg/kg/day once a day for two weeks. Thereafter, the dose should be increased by a maximum of 0.3 mg/kg every one to two weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 1 to 5 mg/kg/day given once a day or in two divided doses, with a maximum of 200 mg/day.
In those patients taking concomitant AEDs or other medications (see Interactions) that induce Lamotrigine glucuronidation with/without other AEDs (except valproate), the initial Lamotrigine dose is 0.6 mg/kg bodyweight/day given in two divided doses for two weeks, followed by 1.2 mg/kg/day given in two divided doses for two weeks. Thereafter, the dose should be increased by a maximum of 1.2 mg/kg every one to two weeks until the optimal response is 5 to 15 mg/kg/day given in two divided doses, with a maximum of 400 mg/day.
In patients taking oxcarbazepine without any inducers or inhibitors of Lamotrigine glucuronidation, the initial Lamotrigine dose is 0.3 mg/kg bodyweight/day given once a day or in two divided doses for two weeks, followed by 0.6 mg/kg/day given once a day or in two divided doses for two weeks. Thereafter, the dose should be increased by a maximum of 0.6 mg/kg every one to two weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 1 to 10 mg/kg/day given once a day or in two divided doses, with a maximum of 200 mg/day.
To ensure a therapeutic dose is maintained the weight of a child must be monitored and the dose reviewed as weight changes occur. (See Table 2.)

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Because of a risk of rash the initial dose and subsequent dose escalation should not be exceeded (see Precautions).
It is likely that patients aged two to six years will require a maintenance dose at the higher end of the recommended range.
Children aged less than 2 years: There is insufficient information on the use of Lamotrigine in children aged less than two years.
Bipolar Disorder: Adults (18 years of age and over): Because of the risk of rash the initial dose and subsequent dose escalation should not be exceeded (see Precautions).
Lamotrigine is recommended for use in bipolar patients at risk for a future depressive episode.
The following transition regimen should be followed to prevent recurrence of depressive episodes. The transition regimen involves escalating the dose of Lamotrigine to a maintenance stabilization dose over six weeks (see Table 3) after which other psychotropic and/or antiepileptic drugs can be withdrawn, if clinically indicated (see Table 4).
Adjunctive therapy should be considered for the prevention of manic episodes, as efficacy with Lamotrigine in mania has not been conclusively established. (See Table 3.)

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**The target stabilization dose will alter depending on clinical response.
Adjunct therapy with inhibitors of Lamotrigine glucuronidation e.g. valproate: In patients taking glucuronidation inhibiting concomitant drugs such as valproate the initial Lamotrigine dose is 25 mg every alternate day for two weeks, followed by 25 mg once a day for two weeks. The dose should be increased to 50 mg once a day (or in two divided doses) in week 5. The usual target dose to achieve optimal response is 100 mg/day given once a day or in two divided doses. However, the dose can be increased to a maximum daily dose of 200 mg, depending on clinical response.
Adjunct therapy with inducers of Lamotrigine glucuronidation in patients NOT taking inhibitors such as valproate. This dosage regimen should be used with phenytoin, carbamazepine, phenobarbitone, primidone and other drugs known to induce Lamotrigine glucuronidation (see Interactions): In those patients currently taking drugs that induce Lamotrigine glucuronidation and not taking valproate, the initial Lamotrigine dose is 50 mg once a day for two weeks, followed by 100 mg/day given in two divided doses for two weeks. The dose should be increased to 200 mg/day given as two divided doses in week 5. The dose may increased in week 6 to 300 mg/day however, the usual target dose to achieve optimal response is 400 mg/day given in two divided doses which may be given from week 7.
Monotherapy with Lamotrigine or Adjunctive therapy in patients taking lithium, bupropion, olanzapine, oxcarbazepine, or other agents known not to significantly induce or inhibit Lamotrigine glucuronidation: The initial Lamotrigine dose in patients who are taking lithium, bupropion, olanzapine, oxcarbazepine and are not taking inducers or inhibitors of Lamotrigine glucuronidation or are taking Lamotrigine in monotherapy, is 25 mg once a day for two weeks, followed by 50 mg once a day (or in two divided doses) for two weeks. The dose should be increased to 100 mg/day in week 5. The usual target dose to achieve optimal response is 200 mg/day given once a day or as two divided doses. However, a range of 100 to 400 mg was used in clinical trials.
Once the target daily maintenance stabilization dose has been achieved, other psychotropic medications may be withdrawn as laid out in the dosage schedule as follows (see Table 4).

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Following withdrawal of adjunct therapy with inhibitors of Lamotrigine glucuronidation e.g. valproate: The dose of Lamotrigine should be increased to double the original target stabilization dose and maintained at this, once valproate has been terminated.
Following withdrawal of inducers of Lamotrigine glucuronidation depending on original dose. This dosage regimen should be used with phenytoin, carbamazepine, phenobarbitone, primidone, Or with other inducers of Lamotrigine glucuronidation (see Interactions): The dose of Lamotrigine should be gradually reduced over three weeks as the glucuronidation inducer is withdrawn.
Following withdrawal of other psychotropic or AED drugs with no significant pharmacokinetic interaction with Lamotrigine e.g. lithium, bupropion, olanzapine, excarbazepine: The target dose achieved in the dose escalation programme should be maintained throughout withdrawal of the other medication.
Adjustment of Lamotrigine daily dosing in patients with Bipolar Disorder following addition of other medications There is no clinical experience in adjusting the Lamotrigine daily dose following the addition of other medications. However, based on drug interaction studies, the following recommendations can be made (see Table 5, as follows).

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Discontinuation of Lamotrigine in patients with Bipolar Disorder: Children and adolescents (less than 18 years of age): Lamotrigine is not indicated for use in bipolar disorder in children and adolescents aged less than 18 years (see Precautions). Safety and efficacy of Lamotrigine bipolar disorder has not been evaluated in this age group. Therefore, a dosage recommendation cannot be made.
General Dosing Recommendations for Lamotrigine in Special Patient Population: Women taking hormonal contraceptives: Starting Lamotrigine in patients already taking hormonal contraceptives: Although an oral contraceptive has been shown to increase the clearance of Lamotrigine (see Precautions and Interactions), no adjustment to the recommended dose escalation guidelines for Lamotrigine should be necessary solely based on the use of hormonal contraceptives. Dose escalation should follow the recommended guidelines based on whether Lamotrigine is added to valproate (an inhibitor of Lamotrigine glucuronidation), or to an inducer of Lamotrigine glucuronidation, or whether Lamotrigine is added in the absence of valproate or an inducer of Lamotrigine glucuronidation (see Table 1 for epilepsy and Table 3 for bipolar disorder patients).
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 Precautions and Interactions). 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.
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 Precautions and Interactions). It is recommended to gradually decrease the daily dose of Lamotrigine by 50 to 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.
Use with atazanavir/ritonavir: Although atazanavir/ritonavir has been shown to reduce Lamotrigine plasma concentrations (see Interactions), no adjustments to the recommended dose escalation guidelines for Lamotrigine should be necessary solely based on the use of atazanavir/ritonavir. Dose escalation should follow the recommended guidelines based on whether Lamotrigine is added to valproate (an inhibitor of Lamotrigine glucuronidation), or to an inducer of Lamotrigine glucuronidation, or whether Lamotrigine is added, or decreased if atazanavir/ritonavir is discontinued.
Elderly (over 65 years of age): No dosage adjustment from recommended schedule is required. The pharmacokinetics of Lamotrigine in this age group do not differ significantly from a non-elderly adult population.
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.
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' AED regimen; reduced maintenance doses may be effective for patients with significant renal functional impairment (see Precautions).
Overdosage
Symptoms and signs: Acute ingestion of doses in excess of 10-20 times the maximum therapeutic dose has been reported. Symptoms of overdose include nystagmus, ataxia, impaired consciousness and coma.
Treatment: In the event of overdosage, 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. There is no experience with haemodialysis as treatment of overdose.
Contraindications
Lamotrigine is contraindicated in individuals with known hypersensitivity to Lamotrigine.
Special Precautions
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 hospitalization and discontinuation of Lamotrigine have also been reported. These have included potentially life threatening rashes such as Stevens Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) (see Side Effects).
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 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 Dosage & Administration); Concomitant use of valproate (see Dosage & Administration).
Caution is also required when treating patients with a history of allergy or rash to other antiepileptic drugs as the frequency of non-serious rash after treatment with Lamotrigine was approximately three times higher in these patients than in those without such history.
All patients (adults and children) who develop a rash should be promptly evaluated and Lamotrigine withdrawn immediately unless the rash is clearly not drug related. It is recommended that Lamotrigine not be restarted in patients who have discontinued due to rash associated with prior treatment with Lamotrigine unless the potential benefit clearly outweighs the risk.
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 (see Side Effects). The syndrome shows a wide spectrum of clinical severity and may, rarely lead to disseminated intravascular coagulation (DIC) and multiorgan failure. It is important to note that early manifestations of hypersensitivity (e.g. fever, lymphadenopathy) may be present even though rash is not evident. If such signs and symptoms are present the patient should be evaluated immediately and Lamotrigine discontinued if an alternative aetiology cannot be established.
Suicide risk: Symptoms of depression and/or bipolar disorder may occur in patients with epilepsy, and there is evidence that patients with epilepsy and bipolar disorder have an elevated risk for suicidality.
Twenty-five to 50% of patients with bipolar disorder attempt suicide at least once, and may experience worsening of their depressive symptoms and/or the emergency of suicidal ideation and behaviours (suicidality) whether or not they are talking medications for bipolar disorder, including Lamotrigine.
Suicidal ideation and behavior have been reported in patients treated with AEDs in several indications, including epilepsy and bipolar disorder. A meta-analysis of randomized placebo-controlled trials and behavior. 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. Patients (and caregivers of patients) should be advised to seek medical advice should signs of suicidal ideation of behavior emerge.
Clinical worsening in bipolar disorder: 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 behavior 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.
Patients (ad caregivers of patients) should be alerted about the need to monitor for any worsening of their condition (including development of new symptoms) and/or the emergency of suicidal ideation/behavior or thoughts of harming themselves and to seek medical advice immediately if these symptoms present.
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 emergency of suicidal ideation/behavior, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
Hormal contraceptives: Effects of hormonal contraceptives on Lamotrigine efficacy: An ethinyloestradiol/levonorgestrel (30 mcg/150 mcg) combination has been demonstrated to increase the clearance of Lamotrigine by approximately two-fold resulting in decreased Lamotrigine levels (see Interactions). Following titration, higher maintenance doses of Lamotrigine (by as much two fold) will be needed in most cases to attain a maximal therapeutic response. In women not already taking an inducer of Lamotrigine glucuronidation and taking a hormonal contraceptive that includes one week of inactive medication (e.g. "pill-free week"), gradual transient increases in Lamotrigine levels will occur during the week of inactive medication.
Clinicians should exercise appropriate clinical management of women starting or stopping hormonal contraceptives during Lamotrigine therapy and Lamotrigine dosing adjustments will be needed in most cases.
Other oral contraceptives and HRT treatments have not been studied, though they may similarly effect Lamotrigine pharmacokinetic parameters.
Effects of Lamotrigine on hormonal contraceptive efficacy: Combination of Lamotrigine with hormonal contraceptive (ethinyloestradiol/levonorgestrel combination) has shown there is a modest increase in levonorgestrel clearance and changes in serum FSH and LH. 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 preparation with Lamotrigine cannot be excluded. Therefore, patients should be instructed to promptly report changes in their menstrual pattern, i.e. breakthrough bleeding.
Effect of Lamotrigine on organic cationic transporter 2 (OCT 2) substrates: Lamotrigine is an inhibitor of renal tubular secretion via OCT 2 proteins. This may result in increased plasma levels of certain drugs that are substantially excreted via this route. Coadministration of Lamotrigine with OCT 2 substrates with a narrow therapeutic index e.g. dofetilide is not recommended.
Dihydrofolate reductase: Lamotrigine is a weak inhibitor of dihydrofolate reductase, hence there is a possibility of interference with folate metabolism during long-term therapy. 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.
Patients taking other preparations containing Lamotrigine: Lamotrigine tablets and dispersible/chewable tablets should not be administered to patients currently being treated with any other preparation containing Lamotrigine without consulting a doctor.
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 convusive 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.
Bipolar Disorder: Children and adolescents (less than 18 years of age): Treatment with antidepressants is associated with an increased risk of suicidal thinking and behavior in children and adolescents with major depressive disorder and other psychiatric disorders.
Renal failure: In patient with end stage failure, plasma concentrations of Lamotrigine were not significantly altered. However, an accumulation of the glucuronide metabolite is to be expected; caution should therefore be exercised in treating patients with renal failure.
Use In Pregnancy & Lactation
Pregnancy: Women exposed to lamotrigine monotherapy during pregnancy cannot exclude an increased risk of congenital malformations.
In therapy with lamotrigine is considered necessary during pregnancy, the lowest possible therapeutic dose is recommended.
Lactation: Lamotrigine has been reported to pass into breast milk in highly variable concentrations, resulting in total Lamotrigine levels in infants of up to approximately 50% of the mother's. Therefore, in some breast-fed infants, serum concentrations of Lamotrigine may reach levels at which pharmacological effects occur. Among a limited group of exposed infants, no adverse effects were observed.
The potential benefits of breast-feeding should be weighed against the potential risk of adverse effects occurring in the infant. Should a woman decide to breastfeed while on therapy with Lamotrigine, the infants should be monitored for adverse effects.
Side Effects
The undesirable effects have been divided into epilepsy and bipolar specific sections based on the data currently available. However, both sections should be consulted when considering the overall safety profile of Lamotrigine. Adverse reactions identified through post-marketing surveillance are included in the Epilepsy as follows.
Epilepsy: Skin and subcutaneous tissue disorders: Very common: Skin rash.
Rare: Stevens Johnson syndrome.
Very Rare: Toxic epidermal necrolysis.
The rash, usually maculopapular in appearance, generally within eight weeks of starting treatment and resolves on withdrawal of Lamotrigine (see Precautions).
Rarely, serious potentially life-threatening skin rashes, including Stevens Johnson syndrome and toxic epidermal necrolysis (Lyell's syndrome) have been reported. Although the majority recover on drug withdrawal, some patients experience irreversible scaring and there have been rare cases of associated death (see Precautions).
The overall risk of rash, appearance to be strongly associated with: High initial doses of Lamotrigine and exceeding the recommended dose escalation of Lamotrigine therapy (see Dosage & Administration); Concomitant use of valproate (see Dosage & Administration).
Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms (see Immune system disorders** as follows).
Blood and lymphatic system disorders: Very rare: Haematological abnormalities (including neutropenia, leucopenia, anaemia, thrombocytopenia, pancytopenia, aplastic anaemia, agranulocytosis, lymphadenopathy.
Haematological abnormalities and lymphadenopathy may or may not be associated with the hypersensitivity syndrome (see Immune system disorders** as follows).
Immune system disorders: Very rare: Hypersensitivity syndrome** (including such symptoms as fever, lymphadenopathy, facial oedema, abnormalities of the blood and liver, disseminated intravascular coagulation (DIC) multi-organ failure).
**Rash has also been reported as part of a hypersensitivity syndrome associated with a variable pattern of systemic symptoms including fever, lymphadenopathy, facial oedema and abnormalities of the blood and liver. The syndrome shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation (DIC) and multiorgan failure. It is important to note that early manifestations of hypersensitivity (e.g. fever, lymphadenopathy) may be present even though rash is not evident. If such signs and symptoms are present the patient should be evaluated immediately and Lamotrigine discontinued if an alternative aetiology cannot be established.
Psychiatric disorders: Common: Aggression, irritability.
Very rare: Tics, hallucinations, confusion.
Nervous system disorders: Very common: Somnolence, ataxia, headache, dizziness.
Common: Nystagmus, tremor, insomnia.
Very rare: Aseptic meningitis, agitation, unsteadiness, movement disorders, worsening of Parkinson's disease, extrapyramidal effects, choreoathetosis, increase in seizure frequency.
Eye disorders: Very common: Diplopia, blurred vision.
Rare: Conjunctivitis.
Gastrointestinal disorders: Very common: Nausea, vomiting.
Common: Diarrhoea.
Hepatobiliary disorders: Very rare: Increased liver function tests, hepatic dysfunction, hepatic failure.
Hepatic dysfunction usually occurs in association with hypersensitivity reactions but isolated cases have been reported without overt signs of hypersensitivity.
Musculoskeletal and connective tissue disorders: Very rare: Lupus-like reactions.
General disorders and administration site conditions: Common: Tiredness.
Bipolar Disorder: The undesirable effects as follows should be considered alongside those seen in epilepsy for an overall safety profile of Lamotrigine.
Skin and subcutaneous tissue disorders: Very common: Skin rash.
Rare: Stevens Johnson syndrome.
Nervous system disorders: Very common: Headache.
Common: Agitation, somnolence, dizziness.
Musculoskeletal and connective tissue disorders: Common: Arthralgia.
General disorders and administration site conditions: Common: pain, back pain.
Drug Interactions
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 drugs metabolized by cytochrome P450 enzymes are unlikely to occur. Lamotrigine may induce its own metabolism, but the effect is modest and unlikely to have significant clinical consequences. (See Table 6.)

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Interactions involving AEDs (see Dosage & Administration): Valproate, which inhibits the glucuronidation of Lamotrigine, reduces the metabolism of Lamotrigine and increases the mean half life of Lamotrigine nearly two-fold.
Certain antiepileptic agents (such as phenytoin, carbamazepine, phenobarbitone and primidone) which induce hepatic drug-metabolising enzymes induce the metabolism glucuronidation of Lamotrigine and enhance the metabolism of Lamotrigine.
There have been reports of central nervous system event 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.
Interactions of involving hormonal contraceptives: Effect of hormonal contraceptives on Lamotrigine pharmacokinetics: Serum Lamotrigine concentrations gradually increased during the course of the week of inactive medication (e.g. "pill-free week"), with pre-dose concentrations at the end of the week of inactive medication being, on average, approximately two-fold higher than during co-therapy.
Effect of Lamotrigine on hormonal contraceptive pharmacokinetics: The impact of the modest increase in levonorgestrel clearance and the changes in serum FSH and LH, on ovarian ovulatory activity in unknown (see Precautions). The effects of doses of Lamotrigine other than 300 mg/day have not been studied and studies with other female hormonal preparation have not been conducted.
Interactions involving other medications: Rifampicin increased Lamotrigine clearance and decreased Lamotrigine half-life due to induction of the hepatic enzymes responsible for glucuronidation. In patients receiving concomitant therapy with rifampicin, the treatment regimen recommended for Lamotrigine and concurrent glucuronidation inducers should be used (see Dosage & Administration).
Lopinavir/ritonavir approximately halved the plasma concentrations of Lamotrigine probably by induction of glucuronidation. In patients receiving concomitant therapy with lopinavir/ritonavir, the treatment regimen recommended for Lamotrigine and concurrent glucuronidation inducers should be used (see Dosage & Administration).
Atazanavir/ritonavir will reduce the plasma AUC and Cmax of Lamotrigine (see General Dosing Recommendations for Lamotrigine in Special Patient Population under Dosage & Administration).
Caution For Usage
Incompatibilities: Not applicable.
Storage
Store in a dry place below 30°C.
Shelf-Life: 36 months.
MIMS Class
ATC Classification
N03AX09 - lamotrigine ; Belongs to the class of other antiepileptics.
Presentation/Packing
Dispersible tab 50 mg (white to off-white, rounded square shaped uncoated tablets debossed with 'H' on multifaceted side and '79' on flat side) x 3 x 10's, 10 x 10's. 100 mg (white to off-white, rounded square shaped uncoated tablets debossed with 'H' on multifaceted side and '78' on flat side) x 3 x 10's, 10 x 10's.
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