Dosages
Side effects in children
Warnings & precautions in children
Contra-indications in children

Interactions
PK
Renal impairment
References

Topiramate

Generic name
Topiramate
Brand name
ATC Code
N03AX11

Pharmacokinetics in children

The pharmacokinetics of topiramate in children are linear, as in adults who received adjuvant therapy. The clearance is independent of the dose and the steady-state plasma concentrations, which rise depending on the dose. In children, however, the clearance is stronger and the elimination half-life shorter. The plasma concentration of topiramate for the same mg/kg dose can therefore be lower in children than in adults. Just as with adults, enzyme-reducing antiepileptic drugs lower the steady-state plasma concentrations.

Rosenfeld et al. 1999 observed a tmax of 1-3 hours and the following halflife parameters with a dose of 3-9 mg/kg/day:

Age n= t1/2
4-7 years 11 7,7-8 hours
8-11 years 12 11,3-11,7 hours
12-17 years 12 12,3-12,8 hours

Ferrari et al. 2003 observed the following clearance:

Age n= Mean dose Cl/F
< 10 years 14 6,5±2,2 mg/kg/day 112±82 ml/kg/hour
10-15 years 11 7,2±2,0 mg/kg/day 66±22 ml/kg/hour
16-30 years 17 4,7±1,9 mg/kg/day 42±16 ml/kg/hour

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

No information is present at this moment.

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Available formulations

No information is present at this moment.

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Dosages

Epilepsy, adjuvant therapy
  • Oral
    • 2 years up to 18 years
      • Initial dose: 1 - 3 mg/kg/day in 1 dose for 1 week..
      • Maintenance dose: increase every 1-2 weeks in steps of 1-3 mg/kg/day to 5 - 9 mg/kg/day in 2 doses. Doses up to 30 mg/kg/day have been studied and were generally well tolerated..

      • Titrate to the lowest possible effective dose.
Epilepsy, monotherapy
  • Oral
    • 6 years up to 18 years
      • Initial dose: 0.5 - 1 mg/kg/day in 1 dose
      • Maintenance dose: increase every 1-2 weeks in steps of 0.5-1 mg/kg/day in 2 doses to approximately 2 mg/kg/day in 2 doses. (Approximately 100 mg / day).
Migraine prophylaxis
  • Oral
    • 12 years up to 18 years
      • Initial dose: 25 mg/day in 1 dose
      • Maintenance dose: increase every 1-2 weeks in steps of 25 mg/day to 50 - 200 mg/day in 2 doses. Max: 200 mg/day.

      • Usual maintenance dose: 100-200 mg/day

        Medicinal prophylaxis can only be commenced in severe seizures or when seizures occur more than twice a month for more than 3 months. This should be given for a maximum of 6 months, after which an attempt can be made to phase the medication out.

        The study by Powers (2017) shows that the efficacy of topiramate in migraine prophylaxis is not more effective compared to placebo. Nevertheless, experts believe that treatment with topiramate can be considered in individual cases.
CAVE: PREGNANCY PREVENTION PROGRAMM FOR THIS DRUG
  • Route of administration not applicable

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Renal impaiment in children > 3 months

Adjustment in renal impairment as specified:

GFR 50-80 ml/min/1.73 m2
Dose adjustment not needed
GFR 30-50 ml/min/1.73 m2
50% of usual single dose for both initial dose and maintenance dose.
GFR 10-30 ml/min/1.73 m2
50% of usual single dose for both initial dose and maintenance dose.
GFR < 10 ml/min/1.73 m2
A general recommendation is not provided.
Clinical consequences

With impaired renal function, topiramate half-life and AUC increase. This increases the risk of side effects.

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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

Side effects that have been reported more often (≥ 2×) in children than in adults: changed appetite, hyperchloraemic acidosis, hypokalaemia, changed behaviour, aggression, apathy, sleep disorders, suicidal behaviour, attention disorders, lethargy, increased tear production, sinus bradycardia, problems with the gait.

Side effects reported only in children: eosinophilia, psychomotor hyperactivity, vertigo, vomiting, hyperthermia, fever, difficulty in learning


 

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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

When symptoms of metabolic acidosis occur (Kussmaul breathing, dyspnea, anorexia, nausea, vomiting, extreme fatigue, tachycardia or arrhythmia) and possibly in conditions or treatments that make patients susceptible to metabolic acidosis (such as kidney diseases, epileptic status, diarrhoea, surgery, ketogenic diet), determination of serum bicarbonate levels is recommended during treatment. Chronic metabolic acidosis in children can cause osteomalacia and slow down the growth rate. However, effects on growth and bone-related consequences have not been systematically investigated.

Sufficient fluid intake is recommended in order to reduce the risk of kidney stones and reduce the risk of heat-related side effects. Reduced sweating and hyperthermia have been reported, particularly in young children at high temperatures.

In adults, there have been reports of deterioration in cognitive functioning, which made it necessary to lower or stop the dose; for children there is still insufficient data in this area.

Do not discontinue treatment suddenly, but gradually reduce the dose in 2-8 weeks (SmPC).

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Interactions

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

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Barbiturates and derivatives
N03AA02
N03AA03
Hydantoin derivatives
N03AB02
Succinimide derivatives
N03AD01
Benzodiazepine derivatives
N03AE01
Carboxamide derivatives
N03AF01
N03AF02
N03AF03
Fatty acid derivatives
N03AG01
N03AG04
Other antiepileptics
N03AX23
N03AX24
N03AX10
N03AX26
N03AX18
N03AX09
N03AX14
N03AX22
N03AX16
N03AX17
N03AX03
N03AX15

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References

  1. Rademaker C.M.A. et al, Geneesmiddelen-Formularium voor Kinderen, 2007
  2. Janssen-Cilag BV, SmPC Topamax (RVG 24165, 24167, 24168) 18-03-2024, www.geneesmiddeleninformatiebank.nl
  3. Le K, et al., Is topiramate effective for migraine prevention in patients less than 18 years of age? A meta-analysis of randomized controlled trials., J Headache Pain, 2017, 18(1), 69
  4. Powers SW, et. al, Trial of Amitriptyline, Topiramate, and Placebo for Pediatric Migraine, NEJM, 2017, 376(2), 115-24
  5. Winner, P. et al, Topiramate for migraine prevention in children: a randomized, double-blind, placebo-controlled trial., Headache, 2005, 45(10), 1304-12
  6. Nederlande Vereniging voor Neurologie, Guideline: 'Medicamenteuze behandeling van migraine, medicatie-overgebruikshoofdpijn en spanningshoofdpijn', 2017
  7. Ferrari, A.R. et al, Influence of dosage, age, and co-medication on plasma topiramate concentrations in children and adults with severe epilepsy and preliminary observations on correlations with clinical response., Ther Drug Monit, 2003, 26(6), 700-8
  8. Szperka, C. L. et al, Pharmacologic Acute and Preventive Treatment for Migraine in Children and Adolescents (international guideline), JAMA Neurol, 2019
  9. Lewis, D. et al, Randomized, double-blind, placebo-controlled study to evaluate the efficacy and safety of topiramate for migraine prevention in pediatric subjects 12 to 17 years of age., Pediatrics, 2009, 123(3), 924-34
  10. Rosenfeld, W.E. et al, A study of topiramate pharmacokinetics and tolerability in children with epilepsy, Pediatr Neurol, 1999, 20(5), 339-44
  11. Lewis, D. et al, A double-blind, dose comparison study of topiramate for prophylaxis of basilar-type migraine in children: a pilot study., Headache, 2007, 10, 1409-17
  12. Winner, P. et al, Topiramate for migraine prevention in adolescents: a pooled analysis of efficacy and safety., Headache, 2006, 46(10), 1503-10
  13. Rascher, W., Summary: Negative assessment by the off-label expert group of the BfArM (Federal Institute for drugs and medical deviceds), Topiramate in migraine prophylaxis in children and adolescents, 19-09-2019
  14. Janssen-Cilag, SmPC Topamax 25mg/50mg Hartkapseln, 35033.00.00/35033.01.00, 04/2017
  15. HEXAL, SmPC Topiramat 25mg/50mg/100mg/200mg Filmtabletten, 67662.00.00/67663.00.00/67664.00.00/67665.00.00, 12/2017
  16. Janssen-Cilag, SmPC Topamax 25mg/50mg/100mg/200mg Filmtabletten, 35027.00.00/35027.01.00/35027.02.00/35027.03.00, 04/2017
  17. Heumann Pharma, SmPC Topiramat 25mg/50mg/100mg/200mg, 77516.00.00/77517.00.00/77518.00.00/77519.00.00, 12/2017
  18. Stadapharm, SmPC Topiramat 25mg/50mg/100mg/200mg, 67241.00.00/67242.00.00/67243.00.00/67244.00.00, 11/2017
  19. MMI, Gelbe Liste Online, Accessed March 21, 2018
  20. Gemeinsamer Bundesausschuss, Anlage VII zum Abschnitt M der Arzneimittel-Richtlinie - Regelungen zur Austauschbarkeit von Arzneimitteln (aut idem), 01/2018
  21. EMA, New measures to avoid topiramate exposure in pregnancy, 13 Oct 2023, EMA/455917/2023, https://www.ema.europa.eu/en/documents/referral/topiramate-article-31-referral-new-measures-avoid-topiramate-exposure-pregnancy_en.pdf
  22. Lewis, D. et al, A double-blind, dose comparison study of topiramate for prophylaxis of basilar-type migraine in children: a pilot study., Headache, 2007, 10, 1409-17

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Changes

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