Pharmacokinetics in children

Half-life

Age	T1/2 Without  enzyme inducing or inhibiting agents	T1/2 combined with  enzyme inducing agents like carbamazepin or phenytoin	T1/2 when combined with valproate
2-26 months (n=143)	38 hours	23 hours	136 hours
26 months -12 years	-	7 hours	45-50 hours

dose recommendation of formulary compared to licensed use (on-label versus off-label)

No information is present at this moment.

Available formulations

No information is present at this moment.

Dosages

Epilepsy, monotherapy or as adjuvant for drugs that are not enzyme inhibitors or enzyme inducers

Oral 2 years up to 13 years [2] PHASING-IN SCHEDULE: Weeks 1-2: 0.3 mg/kg/day in 1-2 doses Weeks 3-4: 0.6 mg/kg/day in 1-2 doses, then increase step by step every 1-2 weeks by a maximum of 0.6 mg/kg to 1-15 mg/kg/day in 1 to 2 doses, maximum 200 mg/day 13 years up to 18 years [1] [2] PHASING-IN SCHEDULE: Weeks 1-2: 25 mg/day in a single dose, Weeks 3-4: 50 mg/day in a single dose, then increase with dose increments of 50-100 mg every 1-2 weeks to 100-200 mg/day in 1 to 2 doses, max 500 mg/day

Epilepsy, in combination with valproic acid or other enzyme inhibitors

Oral 2 years up to 13 years [1] [2] PHASING-IN SCHEDULE: Weeks 1-2: 0.15 mg/kg/day in a single dose, Weeks 3-4: 0.3 mg/kg/day in a single dose, then increase step by step every 1-2 weeks by a maximum of 0.3 mg/kg to 1-5 mg/kg/day in 1 to 2 doses, maximum 200 mg/day 13 years up to 18 years [1] [2] PHASING-IN SCHEDULE: Weeks 1-2: 25 mg per 2 days Weeks 3-4: 25 mg/day in a single dose, then increase with dose increments of 25-50 mg every 1-2 weeks to 100-200 mg/day in 1 to 2 doses

Epilepsy, in combination with enzyme inducers

Oral 2 years up to 13 years [1] [2] PHASING-IN SCHEDULE: Weeks 1-2: 0.6 mg/kg/day in 2 doses Weeks 3-4: 1.2 mg/kg/day in 2 doses, then increase step by step every 1-2 weeks by a maximum of 1.2 mg/kg to 5-15 mg/kg/day in 2 doses, maximum 400 mg/day 13 years up to 18 years [1] [2] PHASING-IN SCHEDULE: Weeks 1-2: 50 mg/day in a single dose, Weeks 3-4: 100 mg/day in 2 doses, then increase with dose increments of max 100 mg every 1-2 weeks to 200-400 mg/day in 2 doses, max 700 mg/day.

Renal impaiment in children > 3 months

GFR ≥10 ml/min/1.73m2: Dose adjustment not required.

GFR <10 ml/min/1.73m2: A general recommendation on dose adjustment cannot be provided.

In single-dose studies, increases in the AUC and half-life of lamotrigine have been observed. The increases were not however deemed to be significant.

The complete list of all undesirable drug reactions can be found in the national Summary of Product Characteristics (SmPC) – click here

Side effects in children

Skin rash (maculo-papular), headaches, nausea, fatigue, agitation, small risk of toxic epidermal necrolysis (TEN). [Rademaker 2008] The risk of severe rashes in children is greater than in adults [SmPC] The risk of severe skin rashes is higher in children than in adults. Data available to date from a number of studies suggest that the incidence of rashes which require in-patient treatment in children is 1 in 300 to 1 in 100 (SmPC Lamictal).

The complete list of all contra-indications can be found in the national Summary of Product Characteristics (SmPC) – click here

Contra-indications

No information available on specific contra indications in children.

The complete list of all warnings and precautions can be found in the national Summary of Product Characteristics (SmPC) – click here

Warnings & precautions in children

Because of the rashes, the dosage should be increased gradually. In children, the first signs of a rash can be interpreted incorrectly as an infection. If children get symptoms of fever or rash during the first eight weeks of treatment, the person treating them must consider the possibility of a reaction to the drug

For bipolar disorders, use in children under 18 years of age is not recommended because lamotrigine was ineffective in an RCT and there was an increased number of patients with suicidal tendencies.

No data are available for children on lamotrigine on growth, sexual maturation as well as cognitive, emotional and behavioral development.

In children taking lamotrigine for the treatment of typical absences efficacy may not be maintained in all patients.

Lamotrigine can aggravate ravet syndrome [Wallace et al. (2016) and Guerrini et al (1998)]

 

Interactions

The complete list of all interactions can be found in the national Summary of Product Characteristics (SmPC) – click here

• NERVOUS SYSTEM
• ANTIEPILEPTICS

ANTIEPILEPTICS

This pages provides a list of drugs from the same ATC class for comparison. This does not necessarily mean that these drugs are interchangeable.

Barbiturates and derivatives
	Phenobarbital Related Medicines Menu">	N03AA02

Hydantoin derivatives
	Phenytoin Related Medicines Menu">	N03AB02

Succinimide derivatives
	Ethosuximide Related Medicines Menu">	N03AD01

Carboxamide derivatives
	Carbamazepine Related Medicines Menu">	N03AF01

Fatty acid derivatives
	Valproic acid (sodiumvalproate) Related Medicines Menu">	N03AG01

Other antiepileptics
	Levetiracetam Related Medicines Menu">	N03AX14

References

1. Werkgroep Richtlijnen Epilepsie, Epilepsie. Richtlijnen voor diagnostiek en behandeling, epilepsie.neurologie.nl, vastgesteld 11-06-2018
2. GlaxoSmithKline BV, SmPC Lamictal (RVG 19115, 19116, 19117) 22-04-2024, www.geneesmiddeleninformatiebank.nl
3. Gerlach M, Mehler-Wex C, Walitza S, Warnke A, Wewetzer C., Neuro-/Psychopharmaka im Kindes- und Jugendalter: Grundlagen und Therapie. , Springer-Verlag Berlin Heidelberg , 2016, 3.Auflage, 368
4. Wallace A,, Pharmacotherapy for Dravet Syndrome, Paediatr Drugs, 2016, Jun;18(3), 197-208
5. Guerrini R. et al, Antiepileptic Drug-Induced Worsening of Seizures in Children, Epilepsia, 1998, 39(Suppl. 3), SZ-SIO

Changes

Therapeutic Drug Monitoring

Overdose