Apo-Lamotrigine

Apo-Lamotrigine Dosage/Direction for Use

lamotrigine

Manufacturer:

Apotex

Distributor:

Pharmaforte
Full Prescribing Info
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Epilepsy: When concomitant AEDs are withdrawn to achieve Apo-Lamotrigine monotherapy or other AEDs are added-on to treatment regimes containing lamotrigine, consideration should be given to the effect this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].
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