Apo-Lamotrigine

Apo-Lamotrigine

lamotrigine

Manufacturer:

Apotex

Distributor:

Pharmaforte
Full Prescribing Info
Contents
Lamotrigine.
Description
Each tablet contains Lamotrigine 25 mg or 100 mg, respectively.
Action
ATC Code: N 03 AX 09.
Pharmacology:
Pharmacodynamics: Mechanism of Action: The results of pharmacological studies suggest that lamotrigine is a use-dependent blocker of voltage-gated sodium channels. It produces a use- and voltage-dependent block of sustained repetitive firing in cultured neurones 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.
Pharmacodynamic Effects: In tests designed to evaluate the central nervous system effects of drugs, the results obtained using doses of lamotrigine 240 mg administered to healthy volunteers did not differ from placebo, whereas both phenytoin 1000 mg and diazepam 10 mg, each significantly impaired fine visual motor coordination and eye movements, increased body sway and produced subjective sedative effects. In another study, single oral doses of carbamazepine 600 mg significantly impaired fine visual motor coordination and eye movements, while increasing both body sway and heart rate, whereas results with lamotrigine at doses of 150 and 300 mg did not differ from placebo.
Melanin Binding: Lamotrigine binds to melanin-containing tissues eg, in the eye and pigmented skin. It has been found in the uveal tract up to 52 weeks after a single dose in rodents.
Clinical Studies: Clinical Efficacy in the Prevention of Depressive Episodes in Patients with Bipolar Disorder: Two pivotal studies have demonstrated efficacy in the prevention of depressive episodes in patients with bipolar I disorder.
Clinical study SCAB20003 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 Apo-Lamotrigine monotherapy or Apo-Lamotrigine plus psychotropic medication, patients were randomly assigned into 1 of 5 treatment groups: Apo-Lamotrigine (50, 200, 400 mg/day), lithium (serum levels of 0.8-1.1 mmol/L) or placebo for a maximum of 76 weeks (18 months). Treatment regimens were maintained until an emerging mood episode (depressive or manic) deemed it necessary to intervene with additional pharmacotherapy or electroconvulsive therapy (ECT).
The primary endpoint was "time to intervention for a mood episode (TIME)", where the interventions were either additional pharmacotherapy or ECT. This endpoint was analyzed using 3 methods of handling data from patients who were withdrawn prior to having an intervention. The p-values for these analyses ranged from 0.003-0.029. In supportive analyses of time to 1st depressive episode and time to 1st manic/hypomanic or mixed episode, the Apo-Lamotrigine patients had longer times to 1st depressive episode than placebo patients (p=0.047), and the treatment difference with respect to time to manic/hypomanic or mixed episodes was not statistically significant.
Clinical study SCAB2006 was a multicentre, double-blind, double dummy, placebo and lithium-controlled, randomised, flexible dose evaluation of Apo-Lamotrigine in the long-term prevention of relapse and recurrence of mania and/or depression in patients with bipolar I disorder who had recently or were currently experiencing a manic or hypomanic episode. Once stabilised using Apo-Lamotrigine monotherapy or Apo-Lamotrigine plus psychotropic medication, patients were randomly assigned into 1 of 3 treatment groups: Apo-Lamotrigine (100-400 mg/day), lithium (serum levels of 0.8-1.1 mmol/L) or placebo for a maximum of 76 weeks (18 months). Treatment regimens were maintained until an emerging mood episode (depressive or manic) deemed it necessary to intervene with additional pharmacotherapy or ECT.
The primary endpoint was "TIME", where the interventions were either additional pharmacotherapy or ECT. This endpoint was analyzed using 3 methods of handling data from patients who were withdrawn prior to having an intervention. The p-values for these analyses ranged from 0.003-0.023. In supportive analyses of time to 1st depressive episode and time to 1st manic/hypomanic or mixed episode, the Apo-Lamotrigine patients had longer times to 1st depressive episode than placebo patients (p=0.015), and the treatment difference with respect to time to manic/hypomanic or mixed episodes was not statistically significant.
In clinical trials, propensity to induce destabilisation, mania or hypomania whilst on Apo-Lamotrigine therapy was not significantly different to placebo.
Pharmacokinetics: Absorption: Lamotrigine is rapidly and completely absorbed from the gut with no significant first-pass metabolism. Peak plasma concentrations occur approximately 2.5 hrs after oral drug administration. Time to maximum concentration is slightly delayed after food but the extent of absorption is unaffected. The pharmacokinetics is linear up to 450 mg, the highest single dose tested. There is considerable interindividual 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 0.92-1.22 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 antiepileptic drugs (AEDs) and data suggest that interactions between lamotrigine and drugs metabolised by cytochrome P-450 enzymes are unlikely to occur.
Elimination: The mean steady-state clearance in healthy adults is 39±>14 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 drug-related material is excreted in faeces. Clearance and half-life are independent of dose. The mean elimination half-life in healthy adults is 24-35 hrs. 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 medication. Mean half-life is reduced to approximately 14 hrs when given with glucuronidation-inducing drugs eg, carbamazepine and phenytoin and is increased to a mean of approximately 70 hrs when co-administered with valproate alone (see Dosage & Administration and Interactions).
Special Patient Populations: Children: Clearance adjusted for body weight is higher in children than in adults with the highest values in children <5 years. The half-life of lamotrigine is generally shorter in children than in adults with a mean value of approximately 7 hrs when given with enzyme-inducing drugs eg, carbamazepine and phenytoin and increasing to mean values of 45-50 hrs when co-administered with valproate alone. (See Dosage & Administration.)
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 (0.31-0.65 mL/min/kg) obtained in 9 studies with non-elderly adults after single doses of 30-450 mg.
Patients with Renal Impairment: Twelve volunteers with chronic renal failure and another 6 individuals undergoing hemodialysis were each given a single 100-mg dose of lamotrigine. Mean CL/F were 0.42 mL/min/kg (chronic renal failure), 0.33 mL/min/kg (between hemodialysis) and 1.57 mL/min/kg (during hemodialysis) compared to 0.58 mL/min/kg in healthy volunteers. Mean plasma half-lives were 42.9 hrs (chronic renal failure), 57.4 hrs (between hemodialysis) and 13 hrs (during hemodialysis), compared to 26.2 hrs in healthy volunteers. On average, approximately 20% (range = 5.6-35.1) of the amount of lamotrigine present in the body was eliminated during a 4-hr hemodialysis session. For this patient population, initial doses of Apo-Lamotrigine should be based on patients' AED regimen; reduced maintenance doses may be effective for patients with significant renal functional impairment.
Patients with 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 0.1 mL/min/kg in patients with grade A, B or C (Child-Pugh classification) hepatic impairment, respectively, compared to 0.34 mL/min/kg in the healthy controls. Initial, escalation and maintenance doses should generally be reduced by approximately 50% in patients with moderate (Child-Pugh grade B) and 75% in patients with severe (Child-Pugh grade C) hepatic impairment. Escalation and maintenance doses should be adjusted according to clinical response.
Toxicology: Preclinical Safety Data: Reproductive toxicology studies with lamotrigine in animals at doses in excess of the human therapeutic dosage showed no teratogenic effects. However, as lamotrigine is a weak inhibitor of dihydrofolate reductase, there is a theoretical risk of human foetal malformations when the mother is treated with a folate inhibitor during pregnancy.
The results of a wide range of mutagenicity tests indicate that lamotrigine does not present a genetic risk to man.
Lamotrigine was not carcinogenic in long-term studies in the rat and mouse.
Indications/Uses
Epilepsy: Adults (>12 years): As adjunctive or monotherapy in the treatment of epilepsy, for partial seizures and generalised seizures, including tonic-clonic seizures and the seizures associated with Lennox-Gastaut syndrome.
Children (2-12 years): As adjunctive therapy in the treatment of epilepsy, for partial seizures and generalised seizures including tonic-clonic seizures and the seizures associated with Lennox-Gastaut syndrome.
Initial monotherapy treatment in newly diagnosed paediatric patients is not recommended.
After epileptic control has been achieved during adjunctive therapy, concomitant AEDs may be withdrawn and patients continued on Apo-Lamotrigine monotherapy.
Bipolar Disorder: Adults (≥18 years): Prevention of depressive episodes in patients with bipolar disorder. Safety and efficacy of Apo-Lamotrigine in the acute treatment of mood episodes has not been established.
The physician who elects to use Apo-Lamotrigine for periods extending beyond 18 months should periodically re-evaluate the long-term usefulness of the drug for the individual patient.
Dosage/Direction for Use
Apo-Lamotrigine dispertab 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 Apo-Lamotrigine eg, 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.
It is strongly recommended that therapy with lamotrigine is initiated at the recommended doses. Careful incremental titration of the dose may decrease the severity of skin rashes. There are suggestions, yet to be proven, that the risk of severe, potentially life-threatening rash may be increased by co-administration of Apo-Lamotrigine with valproate. However, cases have been reported in the absences of these factors. Therefore, it is important that the dosing recommendations are to be followed closely.
Restarting Therapy: Prescribers should assess the need for escalation to maintenance dose when restarting Apo-Lamotrigine in patients who have discontinued Apo-Lamotrigine for any reason, since the risk of serious rash is associated with high initial doses and exceeding the recommended dose escalation for Apo-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 Apo-Lamotrigine exceeds 5 half-lives (see Pharmacology: Pharmacokinetics under Actions), Apo-Lamotrigine should generally be escalated to the maintenance dose according to the appropriate schedule. It is recommended that Apo-Lamotrigine not be restarted in patients who have discontinued due to rash associated with prior treatment with Apo-Lamotrigine unless the potential benefit clearly outweighs the risk.
Epilepsy: When concomitant AEDs are withdrawn to achieve Apo-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).
Adults (>12 years): (See Table 1.)

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Monotherapy: Initial Dose: 25 mg once a day for 2 weeks, followed by 50 mg once a day for 2 weeks. Thereafter, the dose should be increased by a maximum of 50-100 mg every 1-2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 100-200 mg/day given once a day or as 2 divided doses. Some patients have required 500 mg/day of Apo-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).
Add-On Therapy: In patients taking valproate with/without any other AED, the initial Apo-Lamotrigine dose is 25 mg every alternate day for 2 weeks, followed by 25 mg once a day for 2 weeks. Thereafter, the dose should be increased by a maximum of 25-50 mg every 1-2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 100-200 mg/day given once a day or in 2 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 Apo-Lamotrigine dose is 50 mg once a day for 2 weeks, followed by 100 mg/day given in 2 divided doses for 2 weeks.
Thereafter, the dose should be increased by a maximum of 100 mg every 1-2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 200-400 mg/day given in 2 divided doses.
Some patients have required 700 mg/day of Apo-Lamotrigine to achieve the desired response.
In those patients taking oxcarbazepine without any other inducers or inhibitors of lamotrigine glucuronidation, the initial Apo-Lamotrigine dose is 25 mg once a day for 2 weeks, followed by 50 mg once a day for 2 weeks. Thereafter, the dose should be increased by a maximum of 50-100 mg every 1-2 weeks until the optimal response is achieved. The usual maintenance dose to achieve an optimal response is 100-200 mg/day given once a day or as 2 divided doses.
Because of a risk of rash, the initial dose and subsequent dose escalation should not be exceeded (see Precautions).
Children (2-12 years): (See Table 2.)

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In patients taking valproate with/without any other AED, the initial Apo-Lamotrigine dose is 0.15 mg/kg body weight/day given once a day for 2 weeks, followed by 0.3 mg/kg/day once a day for 2 weeks. Thereafter, the dose should be increased by a maximum of 0.3 mg/kg every 1-2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 1-5 mg/kg/day given once a day or in 2 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 Apo-Lamotrigine dose is 0.6 mg/kg body weight/day given in 2 divided doses for 2 weeks, followed by 1.2 mg/kg/day given in 2 divided doses for 2 weeks. Thereafter, the dose should be increased by a maximum of 1.2 mg/kg every 1-2 weeks until the optimal response is achieved. The usual maintenance dose to achieve optimal response is 5-15 mg/kg/day given in 2 divided doses, with a maximum of 400 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.
Because of a risk of rash, the initial dose and subsequent dose escalation should not be exceeded (see Precautions).
It is likely that patients 2-6 years will require a maintenance dose at the higher end of the recommended range.
Children (<2 years): There is insufficient information on the use of Apo-Lamotrigine in children <2 years.
Bipolar Disorder: Adults (≥18 years): Because of the risk of rash, the initial dose and subsequent dose escalation should not be exceeded (see Precautions).
Apo-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 Apo-Lamotrigine to a maintenance stabilisation dose over 6 weeks (see Table 3) after which other psychotropic and/or AEDs can be withdrawn, if clinically indicated (see Table 4).
Adjunctive therapy should be considered for the prevention of manic episodes, as efficacy with Apo-Lamotrigine in mania has not been conclusively established. There is no evidence of an increased risk of mania, hypomania or mixed type episodes with lamotrigine treatment compared to placebo. (See Table 3.)

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Adjunct Therapy with Inhibitors of Lamotrigine Glucuronidation eg, Valproate: In patients taking glucuronidation-inhibiting concomitant drugs eg, valproate, the initial Apo-Lamotrigine dose is 25 mg every alternate day for 2 weeks, followed by 25 mg once a day for 2 weeks. The dose should be increased to 50 mg once a day (or in 2 divided doses) in week 5. The usual target dose to achieve optimal response is 100 mg/day given once a day or in 2 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 eg, 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 Apo-Lamotrigine dose is 50 mg once a day for 2 weeks, followed by 100 mg/day given in 2 divided doses for 2 weeks. The dose should be increased to 200 mg/day given as 2 divided doses in week 5. The dose may be increased in week 6 to 300 mg/day however, the usual target dose to achieve optimal response is 400 mg/day given in 2 divided doses which may be given from week 7.
Monotherapy with Apo-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 Apo-Lamotrigine dose in patients who are taking lithium, bupropion, olanzapine, oxcarbazepine and are not taking inducers or inhibitors of lamotrigine glucuronidation or are taking Apo-Lamotrigine in monotherapy, is 25 mg once a day for 2 weeks, followed by 50 mg once a day (or in 2 divided doses) for 2 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 2 divided doses. However, a range of 100-400 mg was used in clinical trials.
Once the target daily maintenance stabilisation 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 eg, Valproate: The dose of Apo-Lamotrigine should be increased to double the original target stabilisation dose and maintained at this, once valproate has been terminated.
Following Withdrawal of Adjunct Therapy with Inducers of Lamotrigine Glucuronidation Depending on Original Maintenance Dose: This regimen should be used with phenytoin, carbamazepine, phenobarbitone, primidone or other drugs known to induce Apo-Lamotrigine glucuronidation (see Interactions).
The dose of Apo-Lamotrigine should be gradually reduced over 3 weeks as the glucuronidation inducer is withdrawn.
Following Withdrawal of Adjunct Therapy with Other Psychotropic or AEDs with No Significant Pharmacokinetic Interaction with Apo-Lamotrigine eg, Lithium, Bupropion, Olanzapine, Oxcarbazepine: The target dose achieved in the dose escalation programme should be maintained throughout withdrawal of the other medication.
Adjustment of Apo-Lamotrigine Daily Dosing in Patients with Bipolar Disorder Following Addition of Other Medications: There is no clinical experience in adjusting the Apo-Lamotrigine daily dose following the addition of other medications. However, based on drug interaction studies, the following recommendations can be made: (See Table 5.)

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Discontinuation of Apo-Lamotrigine in Patients with Bipolar Disorder: In clinical trials, there was no increase in the incidence, severity or type of adverse experiences following abrupt termination of Apo-Lamotrigine versus placebo. Therefore, patients may terminate Apo-Lamotrigine without a stepwise reduction of dose.
Children and Adolescents (<18 years): Apo-Lamotrigine is not indicated for use in bipolar disorder in children and adolescents <18 years (see Use in Children under Precautions). Safety and efficacy of Apo-Lamotrigine in bipolar disorder has not been evaluated in this age group. Therefore, a dosage recommendation cannot be made.
General Dosing Recommendations for Apo-Lamotrigine in Special Patient Populations: Women Taking Hormonal Contraceptives: Starting Apo-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 adjustments to the recommended dose escalation guidelines for Apo-Lamotrigine should be necessary solely based on the use of hormonal contraceptives. Dose escalation should follow the recommended guidelines based on whether lamotrigine is added to an inhibitor of lamotrigine glucuronidation eg, valproate; whether Apo-Lamotrigine is added to an inducer of lamotrigine glucuronidation eg, carbamazepine, phenytoin, phenobarbital, primidone or rifampin; or whether Apo-Lamotrigine is added in the absence of valproate, carbamazepine, phenytoin, phenobarbital, primidone or rifampicin (see Table 1 for epilepsy and Table 3 for bipolar patients).
Starting Hormonal Contraceptives in Patients Already Taking Maintenance Doses of Apo-Lamotrigine and Not Taking Inducers of Lamotrigine Glucuronidation: The maintenance dose of Apo-Lamotrigine may need to be increased by as much as 2-fold according to the individual clinical response (see Precautions and Interactions).
Stopping Hormonal Contraceptives in Patients Already Taking Maintenance Doses of Apo-Lamotrigine and Not Taking Inducers of Lamotrigine Glucuronidation: The maintenance dose of Apo-Lamotrigine may need to be decreased by as much as 50% according to the individual clinical response (see Precautions and Interactions).
Elderly (>65 years): No dosage adjustment from recommended schedule is required. The pharmacokinetics of Apo-Lamotrigine in this age group does not differ significantly from a non-elderly adult population. As older patients are more likely to suffer from intercurrent illness and require medications to treat other medical conditions, lamotrigine should be used cautiously in these patients and they should be monitored regularly.
Hepatic Impairment: Initial, escalation and maintenance doses should generally be reduced by approximately 50% in patients with moderate (Child-Pugh grade B) and 75% in severe (Child-Pugh grade C) hepatic impairment. Escalation and maintenance doses should be adjusted according to clinical response (see Pharmacology: Pharmacokinetics under Actions).
Renal Impairment: Caution should be exercised when administering Apo-Lamotrigine to patients with renal failure. For patients with end-stage renal failure, initial doses of Apo-Lamotrigine should be based on patients' AED regimen; reduced maintenance doses may be effective for patients with significant renal functional impairment (see Precautions). For more detailed pharmacokinetic information, see Pharmacology: Pharmacokinetics under Actions.
Apo-Lamotrigine may be taken with or without food [Dispersible tab may be chewed, swallowed whole or dispersed in water/ diluted fruit juice. To disperse, add the tab to a small amount of liquid in a glass (1 tsp or enough to cover). When the tab is completely dispersed (approx 1 min), swirl the solution & consume the entire quantity immediately].
Overdosage
Symptoms: Acute ingestion of doses in excess of 10-20 times the maximum therapeutic dose has been reported. Overdose has resulted in symptoms including nystagmus, ataxia, impaired consciousness and coma.
Treatment: In the event of overdosage, the patient should be admitted to a hospital and given appropriate supportive therapy. Gastric lavage should be performed if indicated.
Contraindications
Individuals with known hypersensitivity to lamotrigine or any other ingredient of Apo-Lamotrigine.
Special Precautions
Skin Rash: There have been reports of adverse skin reactions, which have generally occurred within the first 8 weeks after initiation of Apo-Lamotrigine treatment. The majority of rashes are mild and self-limiting, however, serious rashes requiring hospitalisation and discontinuation of Apo-Lamotrigine have also been reported. These have included potentially life-threatening rashes eg, Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) (see Adverse Reactions). It is not possible to predict reliably which rashes will prove to be life-threatening. Accordingly, Apo-Lamotrigine should ordinarily be discontinued at the first sign of rash, unless the rash is clearly not drug related. Discontinuation of treatment may not prevent a rash from becoming life-threatening or permanently disabling or disfiguring.
In adults enrolled in studies utilizing the current Apo-Lamotrigine dosing recommendations, the incidence of serious skin rashes is approximately 1 in 500 in epilepsy patients. Approximately ½ of these cases have been reported as SJS (1 in 1000).
In clinical trials in patients with bipolar disorder, the incidence of serious rash is approximately 1 in 1000.
The risk of serious skin rashes in children is higher than in adults. Available data from a number of studies suggest the incidence of rashes associated with hospitalisation in epileptic children is from 1 in 300 to 1 in 100.
In children, the initial presentation of a rash can be mistaken for an infection, physicians should consider the possibility of a drug reaction in children that develop symptoms of rash and fever during the first 8 weeks of therapy.
Additionally, the overall risk of rash appears to be strongly associated with: High initial doses of Apo-Lamotrigine and exceeding the recommended dose escalation of Apo-Lamotrigine therapy (see Dosage & Administration); concomitant use of valproate (see Dosage & Administration).
All patients (adults and children) who develop a rash should be promptly evaluated and Apo-Lamotrigine withdrawn immediately unless the rash is clearly not drug related. It is recommended that Apo-Lamotrigine not be restarted in patients who have discontinued due to rash associated with prior treatment with Apo-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 Adverse Reactions). The syndrome shows a wide spectrum of clinical severity and may, rarely, lead to disseminated intravascular coagulation (DIC) and multi-organ failure. It is important to note that early manifestations of hypersensitivity (eg, 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 Apo-Lamotrigine discontinued if an alternative aetiology cannot be established.
Hormonal Contraceptives: Effects of Hormonal Contraceptives on Apo-Lamotrigine Efficacy: An ethinyloestradiol/levonorgestrel (30 mcg/150 mcg) combination has been demonstrated to increase the clearance of lamotrigine by approximately 2-fold resulting in decreased lamotrigine levels (see Interactions).
Following titration, higher maintenance doses of lamotrigine (by as much as 2-fold) may be needed to attain a maximal therapeutic response. In women not already taking an inducer of lamotrigine glucuronidation and taking a hormonal contraceptive that includes 1 week of inactive medication (eg, "pill-free week"), gradual transient increases in lamotrigine levels will occur during the week of inactive medication. These increases will be greater when lamotrigine dose increases are made in the days before or during the week of inactive medication. For dosing instructions, see General Dosing Recommendations for Apo-Lamotrigine in Special Patient Populations under Dosage & Administration.
Clinicians should exercise appropriate clinical management of women starting or stopping hormonal contraceptives during Apo-Lamotrigine therapy and lamotrigine dosing adjustments may be needed.
Effects of Other Hormonal Contraceptive Preparations or HRT on Apo-Lamotrigine: Other oral contraceptive and HRT treatments have not been studied, though they may similarly affect lamotrigine pharmacokinetic parameters.
Effects of Apo-Lamotrigine on Hormonal Contraceptive Efficacy: An interaction study in 16 healthy volunteers has shown that when lamotrigine and a hormonal contraceptive (ethinyloestradiol/levonorgestrel combination) are administered in combination, there is a modest increase in levonorgestrel clearance and changes in serum FSH and LH (see Interactions). The impact of these changes on ovarian ovulatory activity is unknown. However, the possibility of these changes resulting in decreased contraceptive efficacy in some patients taking hormonal preparations with Apo-Lamotrigine cannot be excluded. A limited number of reports have been received of unexpected pregnancies and of menstrual bleeding disorders (eg, breakthrough bleeding) occurring with the concomitant use of Apo-Lamotrigine and hormonal contraceptives. Therefore, patients should be instructed to promptly report changes in their menstrual pattern ie, breakthrough bleeding while receiving Apo-Lamotrigine in combination with these medications.
Acute Multi-Organ Failure: Multi-organ failure, which in some cases has been fatal or irreversible, has been observed in patients receiving Apo-Lamotrigine. Fatalities associated with multi-organ failure and various degrees of hepatic failure have been reported in 2 of 3796 adult patients and 4 of 2435 paediatric patients who received Apo-Lamotrigine in clinical trials. No such fatalities have been reported in bipolar patients in clinical trials. Rare fatalities from multi-organ failure have also been reported in compassionate plea and post-marketing use. The majority of these deaths occurred in association with other serious medical events, including status epilepticus, overwhelming sepsis and hantavirus, making it difficult to identify the initial cause.
Additionally, 3 patients (a 45-year old woman, a 3.5-year old boy and an 11-year old girl) developed multi-organ dysfunction and disseminated intravascular coagulation 9-14 days after Apo-Lamotrigine was added to their AED regimens. Rash and elevated transaminases were also present in all patients and rhabdomyolysis was noted in 2 patients. Both paediatric patients were receiving concomitant therapy with valproate, while the adult patient was being treated with carbamazepine and clonazepam. All patients subsequently recovered with supportive care after treatment with Apo-Lamotrigine was discontinued.
Binding in the Eye and Other Melanin-Containing Tissues: Because lamotrigine binds to melanin, it could accumulate in melanin-rich tissues over time. This raises the possibility that lamotrigine may cause toxicity in these tissues after extended use. Although ophthalmological testing was performed in 1 controlled clinical trial, the testing was inadequate to exclude subtle effects or injury occurring after long-term exposure. Moreover, the capacity of available tests to detect potentially adverse consequences, if any, of lamotrigine's binding to melanin is unknown.
Accordingly, although there are no specific recommendations for periodic ophthalmological monitoring, prescribers should be aware of the possibility of long-term ophthalmologic effects.
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, Apo-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.
Aseptic Meningitis: Therapy with lamotrigine increases the risk of developing aseptic meningitis. Because of the potential for serious outcomes of untreated meningitis due to other causes, patients should also be evaluated for other causes of meningitis and treated as appropriate. Post-marketing cases of aseptic meningitis have been reported in paediatric and adult patients taking lamotrigine for various indications. Symptoms upon presentation have included headache, fever, nausea, vomiting, and nuchal rigidity. Rash, photophobia, myalgia, chills, altered consciousness, and somnolence were also noted in some cases. Symptoms have been reported to occur within 1 day to one and a half months following the initiation of treatment. In most cases, symptoms were reported to resolve after discontinuation of lamotrigine. Re-exposure resulted in a rapid return of symptoms (from within 30 minutes to 1 day following re-initiation of treatment) that were frequently more severe. Some of the patients treated with lamotrigine who developed aseptic meningitis had underlying diagnoses of systemic lupus erythematosus or other autoimmune diseases. Cerebrospinal fluid (CSF) analyzed at the time of clinical presentation in reported cases was characterized by a mild to moderate pleocytosis, normal glucose levels, and mild to moderate increase in protein. CSF white blood cell count differentials showed a predominance of neutrophils in a majority of the cases, although a predominance of lymphocytes was reported in approximately one third of the cases. Some patients also had new onset of signs and symptoms of involvement of other organs (predominantly hepatic and renal involvement), which may suggest that in these cases the aseptic meningitis observed was part of a hypersensitivity reaction.
Patients Taking Other Preparations Containing Lamotrigine: Apo-Lamotrigine 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 Apo-Lamotrigine may provoke rebound seizures. Unless safety concerns (eg, rash) require an abrupt withdrawal, the dose of Apo-Lamotrigine should be gradually decreased over a period of 2 weeks.
There are reports in the literature that severe convulsive seizures including status epilepticus may lead to rhabdomyolysis, multi-organ dysfunction and disseminated intravascular coagulation, sometimes with fatal outcome. Similar cases have occurred in association with the use of Apo-Lamotrigine.
Bipolar Disorder: Clinical Worsening and Suicide Risk Associated with Bipolar Disorder: Patients with bipolar disorder may experience worsening of their depressive symptoms and/or the emergence of suicidal ideation and behaviours (suicidality) whether or not they are taking medications for bipolar disorder. Patients 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.
High risk patients eg, 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, appear to be at a greater risk of suicidal thoughts or suicide attempts, and should receive careful monitoring during treatment.
Patients (and 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 emergence of suicidal ideation/behaviour 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 emergence of suicidal ideation/behaviour, especially if these symptoms are severe, abrupt in onset or were not part of the patient's presenting symptoms.
Effects on the Ability to Drive or Operate Machinery: Two volunteer studies have demonstrated that the effect of Apo-Lamotrigine on fine visual motor coordination, eye movements, body sway and subjective sedative effects did not differ from placebo. In clinical trials with Apo-Lamotrigine, adverse events of a neurological character eg, dizziness and diplopia have been reported. Therefore, patients should see how Apo-Lamotrigine therapy affects them before driving or operating machinery.
Epilepsy: As there is individual variation in response to all antiepileptic drug therapy, patients should consult their physician on the specific issues of driving and epilepsy.
Haemophagocytic lymphohistiocytosis (HLH): HLH has occurred in patients taking lamotrigine. HLH is a syndrome of pathological immune activation, which can be life threatening, characterised by clinical signs and symptoms such as 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.
Immediately evaluate patients who develop these signs and symptoms and consider a diagnose of HLH. Lamotrigine should be discontinued unless an alternative aetiology can be established.
Use in Pregnancy & Lactation: Administration of lamotrigine did not impair fertility in animal reproductive studies.
There is no experience of the effect of Apo-Lamotrigine on human fertility.
Post-marketing data from several prospective pregnancy registries have documented outcomes in over 2000 women exposed to Apo-Lamotrigine monotherapy during the 1st trimester of pregnancy. Whilst the data provide no evidence for a substantial increase in the overall risk of major birth malformations associated with Apo-Lamotrigine, one registry has reported an increase in the risk of isolated oral cleft malformations. This increased has not been confirmed in a pooled analysis of the data from six other registries.
The data on use of Apo-Lamotrigine in polytherapy combinations are insufficient to assess whether the risk of malformation associated with other agents is affected by concomitant Apo-Lamotrigine use.
As with other medicines, Apo-Lamotrigine should only be used during pregnancy if the expected benefits outweigh the potential risks.
Physiological changes during pregnancy may affect lamotrigine levels and/or therapeutic effect. There have been reports of decreased lamotrigine levels during pregnancy. Appropriate clinical management of pregnant women during Apo-Lamotrigine therapy should be ensured.
There is limited information on the use of Apo-Lamotrigine in lactation. Preliminary data indicate that lamotrigine passes into breast milk in concentrations usually of the order of 40-60% of the serum concentration. In a small number of infants known to have been breastfed, the serum concentrations of lamotrigine reached levels at which pharmacological effects may occur.
The potential benefits of breastfeeding should be weighed against the potential risk of adverse effects occurring in the infant.
Use in Children: Children and Adolescents (<18 years): Bipolar Disorder: 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.
Use In Pregnancy & Lactation
Administration of lamotrigine did not impair fertility in animal reproductive studies.
There is no experience of the effect of Apo-Lamotrigine on human fertility.
Post-marketing data from several prospective pregnancy registries have documented outcomes in over 2000 women exposed to Apo-Lamotrigine monotherapy during the 1st trimester of pregnancy. Whilst the data provide no evidence for a substantial increase in the overall risk of major birth malformations associated with Apo-Lamotrigine, one registry has reported an increase in the risk of isolated oral cleft malformations. This increased has not been confirmed in a pooled analysis of the data from six other registries.
The data on use of Apo-Lamotrigine in polytherapy combinations are insufficient to assess whether the risk of malformation associated with other agents is affected by concomitant Apo-Lamotrigine use.
As with other medicines, Apo-Lamotrigine should only be used during pregnancy if the expected benefits outweigh the potential risks.
Physiological changes during pregnancy may affect lamotrigine levels and/or therapeutic effect. There have been reports of decreased lamotrigine levels during pregnancy. Appropriate clinical management of pregnant women during Apo-Lamotrigine therapy should be ensured.
There is limited information on the use of Apo-Lamotrigine in lactation. Preliminary data indicate that lamotrigine passes into breast milk in concentrations usually of the order of 40-60% of the serum concentration. In a small number of infants known to have been breastfed, the serum concentrations of lamotrigine reached levels at which pharmacological effects may occur.
The potential benefits of breastfeeding should be weighed against the potential risk of adverse effects occurring in the infant.
Adverse Reactions
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 Apo-Lamotrigine.
The following convention has been utilised for the classification of undesirable effects: Very common (>1/10), common (>1/100, <1/10), uncommon (>1/1000, <1/100), rare (>1/10,000, <1/1000), very rare (<1/10,000).
Epilepsy: Skin and Subcutaneous Tissue Disorders: During Monotherapy Clinical Trials: Very Common: Skin rash.
During Other Clinical Experience: Very Common: Skin rash. Rare: Stevens-Johnson syndrome. Very Rare: Toxic epidermal necrolysis.
In double-blind, add-on clinical trials, skin rashes occurred in up to 10% of patients taking Apo-Lamotrigine and in 5% of patients taking placebo. The skin rashes led to the withdrawal of Apo-Lamotrigine treatment in 2% of patients. The rash, usually maculopapular in appearance, generally appears within 8 weeks of starting treatment and resolves on withdrawal of Apo-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 scarring and there have been rare cases of associated death. (See Precautions.)
The overall risk of rash appears to be strongly associated with: High initial doses of Apo-Lamotrigine and exceeding the recommended dose escalation of Apo-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, haemophagocytic lymphohistiocytosis.
Haematological abnormalities 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 DIC and multi-organ failure. It is important to note that early manifestations of hypersensitivity (eg, 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 Apo-Lamotrigine discontinued if an alternative aetiology cannot be established.
Psychiatric Disorders: Common: Irritability. Uncommon: Aggression. Very Rare: Tics, hallucinations, confusion.
Nervous System Disorders: During Monotherapy Clinical Trials: Very Common: Headache. Common: Drowsiness, insomnia, dizziness, tremor. Uncommon: Ataxia.
During Other Clinical Experience: Very Common: Headache, dizziness. Common: Nystagmus, tremor, ataxia, drowsiness, insomnia. Very Rare: Agitation, unsteadiness, movement disorders, worsening of Parkinson's disease, extrapyramidal effects, choreoathetosis, increase in seizure frequency.
There have been reports that Apo-Lamotrigine may worsen parkinsonian symptoms in patients with preexisting Parkinson's disease, and isolated reports of extrapyramidal effects and choreoathetosis in patients without this underlying condition.
Eye Disorders: Very Common: Diplopia, blurred vision. Rare: Conjunctivitis.
Gastrointestinal Disorders: During Monotherapy Clinical Trials: Common: Nausea.
During Other Clinical Experience: Common: Gastrointestinal disturbance (including vomiting and 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 following undesirable effects should be considered alongside those seen in epilepsy for an overall safety profile of Apo-Lamotrigine.
Skin and Subcutaneous Tissue Disorders: During Bipolar Disorder Clinical Trials: Very Common: Skin rash. Rare: Stevens-Johnson syndrome.
When all bipolar disorder studies (controlled and uncontrolled) conducted with Apo-Lamotrigine are considered, skin rashes occurred in 14% of patients on Apo-Lamotrigine. Whereas, in controlled clinical trials with bipolar disorder patients, skin rashes occurred in 9% of patients taking Apo-Lamotrigine and in 8% of patients taking placebo.
Nervous System Disorders: During Bipolar Disorder Clinical Trials: Very Common: Headache. Common: Agitation, somnolence, dizziness. Frequency not known: Aseptic meningitis.
Musculoskeletal and Connective Tissue Disorders: During Bipolar Disorder Clinical Trials: Common: Arthralgia.
General Disorders and Administration Site Conditions: During Bipolar Disorder Clinical Trials: 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 metabolised by cytochrome P-450 enzymes are unlikely to occur. Lamotrigine may induce its own metabolism but the effect is modest and unlikely to have significant clinical consequences.
Effects of Other Drugs on Glucuronidation of Lamotrigine: Drugs That Significantly Inhibit Glucuronidation of Lamotrigine: Valproate.
Drugs That Significantly Induce Glucuronidation of Lamotrigine: Carbamazepine, phenytoin, primidone, phenobarbitone, rifampicin, ethinyloestradiol/levonorgestrel combination**.
Drugs That Do Not Significantly Inhibit or Induce Glucuronidation of Lamotrigine: Lithium, bupropion, olanzapine, oxcarbazepine.
**Other oral contraceptive and HRT treatments have not been studied, though they may similarly affect lamotrigine pharmacokinetic parameters.
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 2-fold (see Precautions and Dosage & Administration).
Certain antiepileptic agents (eg, phenytoin, carbamazepine, phenobarbitone and primidone) which induce hepatic drug-metabolising enzymes induce the metabolism glucuronidation of lamotrigine and enhance the metabolism of lamotrigine. Other drug classes which induce hepatic drug-metabolising enzymes may also enhance the metabolism of lamotrigine.
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 Apo-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.
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.
In a study in healthy adult volunteers using doses of lamotrigine 200 mg and oxcarbazepine 1200 mg, oxcarbazepine did not alter the metabolism of lamotrigine and lamotrigine did not alter the metabolism of oxcarbazepine. The pharmacokinetic interaction between lamotrigine and oxcarbazepine in children has not been studied.
Interactions Involving Other Psychoactive Agents (see Dosage & Administration): The pharmacokinetics of lithium after 2 g of anhydrous lithium gluconate given twice daily for 6 days to 20 healthy subjects were not altered by co-administration of Apo-Lamotrigine 100 mg/day.
Multiple oral doses of bupropion had no statistically significant effects on the single dose pharmacokinetics of Apo-Lamotrigine in 12 subjects and had only a slight increase in the AUC of lamotrigine glucuronide.
In a study in healthy adult volunteers, olanzapine 15 mg 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.
In vitro inhibition experiments indicated that the formation of lamotrigine's primary metabolite, the 2-N-glucuronide, was minimally affected by co-incubation with amitriptyline, bupropion, clonazepam, fluoxetine, haloperidol or lorazepam. Bufuralol metabolism data from human liver microsome suggested that lamotrigine does not reduce the clearance of drugs eliminated predominantly by CYP2D6. Results of in vitro experiments also suggest that clearance of lamotrigine is unlikely to be affected by clozapine, phenelzine, risperidone, sertraline or trazodone.
Interactions Involving Hormonal Contraceptives: Effect of Hormonal Contraceptives on Lamotrigine Pharmacokinetics: In a study of 16 female volunteers, 30 mcg ethinyl oestradiol/150 mcg levonorgestrel in a combined oral contraceptive pill caused an approximately 2-fold increase in lamotrigine oral clearance, resulting in an average 52% and 39% reduction in lamotrigine AUC and Cmax, respectively. Serum lamotrigine concentrations gradually increased during the course of the week of inactive medication (eg, "pill-free" week), with pre-dose concentrations at the end of the week of inactive medication being, on average, approximately 2-fold higher than during co-therapy.
Effect of Lamotrigine on Hormonal Contraceptive Pharmacokinetics: In a study of 16 female volunteers, a steady-state dose of lamotrigine 300 mg 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 Precautions). The effects of doses of lamotrigine other than 300 mg/day have not been studied and studies with other female hormonal preparations have not been conducted.
Interactions Involving Other Medications: In a study in 10 male volunteers, rifampicin increased lamotrigine clearance and decreased lamotrigine half-life due to induction of the hepatic enzymes responsible for glucuronidation. In patients receiving concomitant therapy with rifampicin, the treatment regimen recommended for lamotrigine and concurrent glucuronidation inducers should be used (see Dosage & Administration).
Caution For Usage
Incompatibilities: None reported.
Storage
APO-LAMOTRIGINE should be stored below 25ºC.
MIMS Class
ATC Classification
N03AX09 - lamotrigine ; Belongs to the class of other antiepileptics.
Presentation/Packing
Tab 25 mg (white, shield-shaped, flat faced, beveled edge, scored and engraved "25" on one side and "APO" on the other side) x 100's. 100 mg (peach, shield-shaped, flat faced, beveled edge, scored and engraved "LAM" over "100" on one side and engraved "APO" on the other side) x 100's.
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