Active Ingredient: Lamotrigine
Prevention of depressive episodes in patients with bipolar I disorder who experience predominantly depressive episodes.
For this indication, competent medicine agencies globally authorize below treatments:
Oral
25 - 400 mg
From 12.5 To 200 mg 2 time(s) per day every day
The recommended dose escalation and maintenance doses for adults of 18 years of age and above are given in the tables below. The transition regimen involves escalating the dose of lamotrigine to a maintenance stabilisation dose over six weeks after which other psychotropic medicinal products and/or AEDs can be withdrawn, if clinically indicated. The dose adjustments following addition of other psychotropic medicinal products and/or AEDs are also provided below. Because of the risk of rash the initial dose and subsequent dose escalation should not be exceeded.
Adults aged 18 years and above – recommended dose escalation to the maintenance total daily stabilisation dose in treatment of bipolar disorder:
| Treatment Regimen | Weeks 1+2 | Weeks 3+4 | Week 5 | Target Stabilisation Dose (Week 6)* |
|---|---|---|---|---|
| Monotherapy with lamotrigine OR adjunctive therapy WITHOUT valproate and WITHOUT inducers of lamotrigine glucuronidation: | ||||
| This dosage regimen should be used with other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation | 25 mg/day (once a day) | 50 mg/day (once a day or two divided doses) | 100 mg/day (once a day or two divided doses) | 200 mg/day-usual target dose for optimal response (once a day or two divided doses). Doses in the range 100-400 mg/day used in clinical trials |
| Adjunctive therapy WITH valproate (inhibitor of lamotrigine glucuronidation): | ||||
| This dosage regimen should be used with valproate regardless of any concomitant medicinal products | 12.5 mg/day (given as 25 mg on alternate days) | 25 mg/day (once a day) | 50 mg/day (once a day or two divided doses) | 100 mg/day-usual target dose for optimal response (once a day or two divided doses). Maximum dose of 200 mg/day can be used depending on clinical response. |
| Adjunctive therapy WITHOUT valproate and WITH inducers of lamotrigine glucuronidation: | ||||
| This dosage regimen should be used without valproate but with: phenytoin, carbamazepine, phenobarbitone, primidone, rifampicin, lopinavir/ritonavir | 50 mg/day (once a day) | 100 mg/day (two divided doses) | 200 mg/day (two divided doses) | 300 mg/day in week 6, if necessary increasing to usual target dose of 400 mg/day in week 7, to achieve optimal response (two divided doses) |
In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known, the dose escalation as recommended for lamotrigine with concurrent valproate, should be used.
* The Target stabilisation dose will alter depending on clinical response
Adults aged 18 years and above – maintenance stabilisation total daily dose following withdrawal of concomitant medicinal products in treatment of bipolar disorder:
Once the target daily maintenance stabilisation dose has been achieved, other medicinal products may be withdrawn as shown below.
| Treatment Regimen | Current lamotrigine stabilisation dose (prior to withdrawal) | Week 1 (beginning with withdrawal) | Week 2 | Week 3 onwards* |
|---|---|---|---|---|
| Withdrawal of valproate (inhibitor of lamotrigine glucuronidation), depending on original dose of lamotrigine: | ||||
| When valproate is withdrawn, double the stabilisation dose, not exceeding an increase of more than 100 mg/week | 100 mg/day | 200 mg/day | Maintain this dose (200 mg/day) (two divided doses) | |
| 200 mg/day | 300 mg/day | 400 mg/day | Maintain this dose (400 mg/day) | |
| Withdrawal of inducers of lamotrigine glucuronidation, depending on original dose of lamotrigine: | ||||
| This dosage regimen should be used when the following are withdrawn: phenytoin, carbamazepine, phenobarbitone, primidone, rifampicin, lopinavir/ritonavir | 400 mg/day | 400 mg/day | 300 mg/day | 200 mg/day |
| 300 mg/day | 300 mg/day | 225 mg/day | 150 mg/day | |
| 200 mg/day | 200 mg/day | 150 mg/day | 100 mg/day | |
| Withdrawal of medicinal products that do NOT significantly inhibit or induce lamotrigine glucuronidation: | ||||
| This dosage regimen should be used when other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation are withdrawn | Maintain target dose achieved in dose escalation (200 mg/day; two divided doses) (dose range 100-400 mg/day) | |||
In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known, the treatment regimen recommended for lamotrigine is to initially maintain the current dose and adjust the lamotrigine treatment based on clinical response.
* Dose may be increased to 400 mg/day as needed
Adults aged 18 years and above – adjustment of lamotrigine daily dosing following the addition of other medicinal products in treatment of bipolar disorder:
There is no clinical experience in adjusting the lamotrigine daily dose following the addition of other medicinal products. However, based on interaction studies with other medicinal products, the following recommendations can be made:
| Treatment Regimen | Current lamotrigine stabilisation dose (prior to addition) | Week 1 (beginning with addition) | Week 2 | Week 3 onwards |
|---|---|---|---|---|
| Addition of valproate (inhibitor of lamotrigine glucuronidation-see section 4.5), depending on original dose of lamotrigine: | ||||
| This dosage regimen should be used when valproate is added regardless of any concomitant medicinal products | 200 mg/day | 100 mg/day | Maintain this dose (100 mg/day) | |
| 300 mg/day | 150 mg/day | Maintain this dose (150 mg/day) | ||
| 400 mg/day | 200 mg/day | Maintain this dose (200 mg/day) | ||
| Addition of inducers of lamotrigine glucuronidation in patients NOT taking valproate, depending on original dose of lamotrigine: | ||||
| This dosage regimen should be used when the following are added without valproate: phenytoin, carbamazepine, phenobarbitone, primidone, rifampicin, lopinavir/ritonavir | 200 mg/day | 200 mg/day | 300 mg/day | 400 mg/day |
| 150 mg/day | 150 mg/day | 225 mg/day | 300 mg/day | |
| 100 mg/day | 100 mg/day | 150 mg/day | 200 mg/day | |
| Addition of medicinal products that do NOT significantly inhibit or induce lamotrigine glucuronidation: | ||||
| This dosage regimen should be used when other medicinal products that do not significantly inhibit or induce lamotrigine glucuronidation are added | Maintain target dose achieved in dose escalation (200 mg/day; dose range 100-400 mg/day) | |||
In patients taking medicinal products where the pharmacokinetic interaction with lamotrigine is currently not known, the treatment regimen as recommended for lamotrigine with concurrent valproate, should be used.
In clinical trials, there was no increase in the incidence, severity or type of adverse reactions following abrupt termination of lamotrigine versus placebo. Therefore, patients may terminate lamotrigine dispersible tablets without a step wise reduction of dose.
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