Pharmacokinetic variability and clinical use of lacosamide in children and adolescents in Denmark and Norway

Margrete Larsen Burns, Marina Nikanorova, Arton Baftiu, Jan Borg Rasmussen, Svein I Johannessen, Cecilie Johannessen Landmark

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

BACKGROUND: The indication for the antiepileptic drug (AED) lacosamide (LCM) was recently extended to include children from the age of four. Real-life data on the use and serum concentrations of LCM in children and adolescents are limited. The purpose of this study was to investigate the use of LCM in this patient group in relation to age, co-medication, dose, serum concentrations and duration of treatment, and to examine pharmacokinetic variability.

METHODS: Children and adolescents (<18 years) who had serum concentrations of LCM measured from January 2012 to June 2018 were retrospectively identified from the therapeutic drug monitoring (TDM) databases at two national epilepsy centers in Norway and Denmark. Clinical data were collected from request forms and medical records.

RESULTS: Data from 124 patients were included, 61 girls/63 boys. Weight was available for 76 patients. Median age was 15 years (range 2-17 years), dose of LCM 300 mg/day (76-600 mg/day) and serum concentration 18 µmol/L (5-138 µmol/L) [4.5 mg/L (1.3-34.5 mg/L)]. Pharmacokinetic variability was demonstrated as the concentration/(dose/kg) ratio ranged from 1.3 to 9.4 (µmol/L)/(mg/kg) and was affected by age. Polytherapy with 1-3 other AEDs was noted in 107 patients (86%). Treatment was continued beyond 1 year in 71% (n=45) of the 63 patients where such information was available, and all of these 45 patients had serum concentrations within the defined reference range. The 1-year retention rate was higher in patients not concomitantly using other sodium channel blocking drugs (82% vs 56%).

CONCLUSION: The study demonstrates pharmacokinetic variability in and between age groups, which indicates usefulness of TDM. More than two thirds of patients continued treatment beyond one year, suggesting reasonable effectiveness.

OriginalsprogEngelsk
TidsskriftTherapeutic Drug Monitoring
Vol/bind41
Udgave nummer3
Sider (fra-til)340-347
ISSN0163-4356
DOI
StatusUdgivet - jun. 2019

Fingeraftryk

Denmark
Norway
Pharmacokinetics
Serum
Drug Monitoring
Pharmaceutical Databases
lacosamide
Medical Records
Reference Values
Age Groups
Weights and Measures
Pharmaceutical Preparations

Citer dette

Burns, M. L., Nikanorova, M., Baftiu, A., Rasmussen, J. B., Johannessen, S. I., & Landmark, C. J. (2019). Pharmacokinetic variability and clinical use of lacosamide in children and adolescents in Denmark and Norway. Therapeutic Drug Monitoring, 41(3), 340-347. https://doi.org/10.1097/FTD.0000000000000599
Burns, Margrete Larsen ; Nikanorova, Marina ; Baftiu, Arton ; Rasmussen, Jan Borg ; Johannessen, Svein I ; Landmark, Cecilie Johannessen. / Pharmacokinetic variability and clinical use of lacosamide in children and adolescents in Denmark and Norway. I: Therapeutic Drug Monitoring. 2019 ; Bind 41, Nr. 3. s. 340-347.
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abstract = "BACKGROUND: The indication for the antiepileptic drug (AED) lacosamide (LCM) was recently extended to include children from the age of four. Real-life data on the use and serum concentrations of LCM in children and adolescents are limited. The purpose of this study was to investigate the use of LCM in this patient group in relation to age, co-medication, dose, serum concentrations and duration of treatment, and to examine pharmacokinetic variability.METHODS: Children and adolescents (<18 years) who had serum concentrations of LCM measured from January 2012 to June 2018 were retrospectively identified from the therapeutic drug monitoring (TDM) databases at two national epilepsy centers in Norway and Denmark. Clinical data were collected from request forms and medical records.RESULTS: Data from 124 patients were included, 61 girls/63 boys. Weight was available for 76 patients. Median age was 15 years (range 2-17 years), dose of LCM 300 mg/day (76-600 mg/day) and serum concentration 18 µmol/L (5-138 µmol/L) [4.5 mg/L (1.3-34.5 mg/L)]. Pharmacokinetic variability was demonstrated as the concentration/(dose/kg) ratio ranged from 1.3 to 9.4 (µmol/L)/(mg/kg) and was affected by age. Polytherapy with 1-3 other AEDs was noted in 107 patients (86{\%}). Treatment was continued beyond 1 year in 71{\%} (n=45) of the 63 patients where such information was available, and all of these 45 patients had serum concentrations within the defined reference range. The 1-year retention rate was higher in patients not concomitantly using other sodium channel blocking drugs (82{\%} vs 56{\%}).CONCLUSION: The study demonstrates pharmacokinetic variability in and between age groups, which indicates usefulness of TDM. More than two thirds of patients continued treatment beyond one year, suggesting reasonable effectiveness.",
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Burns, ML, Nikanorova, M, Baftiu, A, Rasmussen, JB, Johannessen, SI & Landmark, CJ 2019, 'Pharmacokinetic variability and clinical use of lacosamide in children and adolescents in Denmark and Norway', Therapeutic Drug Monitoring, bind 41, nr. 3, s. 340-347. https://doi.org/10.1097/FTD.0000000000000599

Pharmacokinetic variability and clinical use of lacosamide in children and adolescents in Denmark and Norway. / Burns, Margrete Larsen; Nikanorova, Marina; Baftiu, Arton; Rasmussen, Jan Borg; Johannessen, Svein I; Landmark, Cecilie Johannessen.

I: Therapeutic Drug Monitoring, Bind 41, Nr. 3, 06.2019, s. 340-347.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Pharmacokinetic variability and clinical use of lacosamide in children and adolescents in Denmark and Norway

AU - Burns, Margrete Larsen

AU - Nikanorova, Marina

AU - Baftiu, Arton

AU - Rasmussen, Jan Borg

AU - Johannessen, Svein I

AU - Landmark, Cecilie Johannessen

PY - 2019/6

Y1 - 2019/6

N2 - BACKGROUND: The indication for the antiepileptic drug (AED) lacosamide (LCM) was recently extended to include children from the age of four. Real-life data on the use and serum concentrations of LCM in children and adolescents are limited. The purpose of this study was to investigate the use of LCM in this patient group in relation to age, co-medication, dose, serum concentrations and duration of treatment, and to examine pharmacokinetic variability.METHODS: Children and adolescents (<18 years) who had serum concentrations of LCM measured from January 2012 to June 2018 were retrospectively identified from the therapeutic drug monitoring (TDM) databases at two national epilepsy centers in Norway and Denmark. Clinical data were collected from request forms and medical records.RESULTS: Data from 124 patients were included, 61 girls/63 boys. Weight was available for 76 patients. Median age was 15 years (range 2-17 years), dose of LCM 300 mg/day (76-600 mg/day) and serum concentration 18 µmol/L (5-138 µmol/L) [4.5 mg/L (1.3-34.5 mg/L)]. Pharmacokinetic variability was demonstrated as the concentration/(dose/kg) ratio ranged from 1.3 to 9.4 (µmol/L)/(mg/kg) and was affected by age. Polytherapy with 1-3 other AEDs was noted in 107 patients (86%). Treatment was continued beyond 1 year in 71% (n=45) of the 63 patients where such information was available, and all of these 45 patients had serum concentrations within the defined reference range. The 1-year retention rate was higher in patients not concomitantly using other sodium channel blocking drugs (82% vs 56%).CONCLUSION: The study demonstrates pharmacokinetic variability in and between age groups, which indicates usefulness of TDM. More than two thirds of patients continued treatment beyond one year, suggesting reasonable effectiveness.

AB - BACKGROUND: The indication for the antiepileptic drug (AED) lacosamide (LCM) was recently extended to include children from the age of four. Real-life data on the use and serum concentrations of LCM in children and adolescents are limited. The purpose of this study was to investigate the use of LCM in this patient group in relation to age, co-medication, dose, serum concentrations and duration of treatment, and to examine pharmacokinetic variability.METHODS: Children and adolescents (<18 years) who had serum concentrations of LCM measured from January 2012 to June 2018 were retrospectively identified from the therapeutic drug monitoring (TDM) databases at two national epilepsy centers in Norway and Denmark. Clinical data were collected from request forms and medical records.RESULTS: Data from 124 patients were included, 61 girls/63 boys. Weight was available for 76 patients. Median age was 15 years (range 2-17 years), dose of LCM 300 mg/day (76-600 mg/day) and serum concentration 18 µmol/L (5-138 µmol/L) [4.5 mg/L (1.3-34.5 mg/L)]. Pharmacokinetic variability was demonstrated as the concentration/(dose/kg) ratio ranged from 1.3 to 9.4 (µmol/L)/(mg/kg) and was affected by age. Polytherapy with 1-3 other AEDs was noted in 107 patients (86%). Treatment was continued beyond 1 year in 71% (n=45) of the 63 patients where such information was available, and all of these 45 patients had serum concentrations within the defined reference range. The 1-year retention rate was higher in patients not concomitantly using other sodium channel blocking drugs (82% vs 56%).CONCLUSION: The study demonstrates pharmacokinetic variability in and between age groups, which indicates usefulness of TDM. More than two thirds of patients continued treatment beyond one year, suggesting reasonable effectiveness.

U2 - 10.1097/FTD.0000000000000599

DO - 10.1097/FTD.0000000000000599

M3 - Journal article

C2 - 30688870

VL - 41

SP - 340

EP - 347

JO - Therapeutic Drug Monitoring

JF - Therapeutic Drug Monitoring

SN - 0163-4356

IS - 3

ER -