Phenytoin, carbamazepine, sodium valproate and lamotrigine (Formulary)

TAM (Treatments and Medicines) NHS Highland
NHS Highland
  • MHRA advice: Valproate use in men: as a precaution, men and their partners should use effective contraception (September 2024) (www.gov.uk).
  • MHRA advice: Valproate (Belvo, Convulex, Depakote, Dyzantil, Epilim, Epilim Chrono or Chronosphere, Episenta, Epival, and Syonell): new safety and educational materials to support regulatory measures in men and women under 55 years of age (January 2024) (www.gov.uk).
  • MHRA advice: Antiepileptic drugs in pregnancy: updated advice following comprehensive safety review (January 2021) (www.gov.uk).
  • MHRA advice: Antiepileptic drugs: updated advice on switching between different manufacturers’ products (November 2017) (www.gov.uk).
  • MHRA advice: Antiepileptics: risk of suicidal thoughts and behaviour (December 2014) (www.gov.uk).
  • MHRA advice: Antiepileptics: adverse effects on bone (December 2014) (www.gov.uk).

FSRH CEU Guidance: Drug Interactions with Hormonal Contraception (May 2022).
SPS article: Using contraception with enzyme-inducing medicines (Feb 2023).
Also see BNF: Epilepsy.

  • Phenytoin is the only antiepileptic where regular monitoring is helpful.
  • Sampling for carbamazepine and sodium valproate is usually only used to confirm toxicity or poor compliance (see also Therapeutic drug monitoring guidance).
  • The drugs below should control approximately 70% of patients singly or in combination. In situations where epilepsy remains poorly controlled, other drugs may have to be used, usually on specialist advice. Refer to the BNF for doses of the preparations below.

PHENYTOIN

Therapy notes

NHS Improvement Patient Safety Alert: Risk of death and severe harm from error with injectable phenytoin (November 2016): Use of injectable phenytoin is error-prone throughout the prescribing, preparation, administration and monitoring processes; all relevant staff should be made aware of appropriate guidance on the safe use of injectable phenytoin to reduce the risk of error.

  • Has a narrow therapeutic index and the relationship between dose and plasma concentration is non-linear; small changes in dose may result in significant changes in plasma concentration.
  • Measure plasma phenytoin concentration 3 days after initiating treatment to confirm the patient’s metabolism is not remarkably different from the norm, and then 7 days after initiation with subsequent doses of phenytoin adjusted accordingly.
  • Within or around the therapeutic level, dose changes should be no larger than 25mg.
  • If plasma concentrations are unchanged over a 3 to 5 day period, the monitoring interval may be increased to once weekly in the acute clinical setting.
  • In stable patients requiring long-term therapy, generally monitor levels every 6 months.
  • Take care when converting from the oral phenytoin (sodium) capsules to the phenytoin (base) suspension (90mg in 15mL is considered to be approximately equivalent to 100mg phenytoin sodium).
  • Note: For older or immobile patients on long-term phenytoin therapy, consider their increased risk of osteoporosis.

 

Formulation and dosage details

Formulation:

Capsules 25mg, 50mg, 100mg, 300mg

Dosage:

By mouth: initially 3mg/kg to 4mg/kg daily or 150mg to 300mg daily (as a single dose or in 2 divided doses) increased gradually as necessary, usual dose 200mg to 500mg daily.

Formulation and dosage details

Formulation:

Suspension 30mg(base)/5mL

Dosage:

By mouth: initially 3mg/kg to 4mg/kg daily or 150mg to 300mg daily (as a single dose or in 2 divided doses) increased gradually as necessary, usual dose 200mg to 500mg daily.

Formulation and dosage details

Formulation:

Solution for injection 250mg/5mL

CARBAMAZEPINE

Therapy notes

MHRA advice: Carbamazepine, oxcarbazepine and eslicarbazepine: potential risk of serious skin reactions (December 2014) (www.gov.uk).

  • Has a wider therapeutic range than phenytoin. Start doses low and increase every 1 to 2 weeks.

Formulation and dosage details

Formulation:

Tablets (Tegretol®) 100mg, 200mg, 400mg

Dosage:

Epilepsy: by mouth: initially 100mg to 200mg once or twice daily, increased slowly in increments of 100mg to 200mg every 2 weeks to usual dose of 400mg to 1·2 grams daily in divided doses. In some cases 1·6 grams to 2 grams daily may be needed.

Formulation and dosage details

Formulation:

Modified release tablets (Tegretol® Prolonged Release) 200mg, 400mg

Dosage:

Epilepsy: by mouth: initially 100mg to 200mg once or twice daily, increased slowly in increments of 100mg to 200mg every 2 weeks to usual dose of 400mg to 1·2 grams daily in divided doses. In some cases 1·6 grams to 2 grams daily may be needed.

Formulation and dosage details

Formulation:

Suppositories 125mg, 250mg

SODIUM VALPROATE

Therapy notes

Valproate medicines are contraindicated in women and girls of childbearing potential unless conditions of Pregnancy Prevention Programme are met (MHRA advice April 2018)

  • National Patient Safety Alert: Valproate: organisations to prepare for new regulatory measures for oversight of prescribing to new patients and existing female patients (November 2023) (www.gov.uk).
  • MHRA advice: Valproate: dispense full packs of valproate-containing medicines (October 2023) (www.gov.uk).
  • MHRA advice: Valproate: reminder of current Pregnancy Prevention Programme requirements; information on new safety measures to be introduced in the coming months (December 2022) (www.gov.uk).
  • MHRA advice: Antiepileptic drugs in pregnancy: updated advice following comprehensive safety review (January 2021) (www.gov.uk).
  • MHRA advice: Valproate Pregnancy Prevention Programme: temporary advice for management during coronavirus (COVID-19) (May 2020) (www.gov.uk).
  • MHRA advice: Valproate (Epilim▼, Depakote▼) pregnancy prevention programme: updated educational materials (February 2020) (www.gov.uk).
  • MHRA advice: Antiepileptic drugs: updated advice on switching between different manufacturers’ products (November 2018) (www.gov.uk).
  • Risk Minimisation Materials
  • MHRA Drug Safety Update articles
  • Plasma concentrations do not always correlate with efficacy, hence routine monitoring is usually unhelpful.

Formulation and dosage details

Formulation:

Enteric Coated tablets (Epilim®) 200mg, 500mg

Dosage:

By mouth: initially 600mg daily given in 2 divided doses, preferably after food, increasing by 200mg daily at 3 day intervals to a maximum of 2.5 grams daily in divided doses; usual maintenance 1 to 2 grams daily.

Formulation and dosage details

Formulation:

Crushable tablets (Epilim®) 100mg

Dosage:

By mouth: initially 600mg daily given in 2 divided doses, preferably after food, increasing by 200mg daily at 3 day intervals to a maximum of 2.5 grams daily in divided doses; usual maintenance 1 to 2 grams daily.

Formulation and dosage details

Formulation:

Modified release tablets (Epilim Chrono®) 200mg, 300mg, 500mg

Dosage:

By mouth: initially 600mg daily given in 2 divided doses, preferably after food, increasing by 200mg daily at 3 day intervals to a maximum of 2.5 grams daily in divided doses; usual maintenance 1 to 2 grams daily.

Formulation and dosage details

Formulation:

Modified release granules (Epilim Chronosphere® MR) 50mg, 100mg, 250mg, 500mg, 750mg, 1 gram

Dosage:

By mouth: initially 600mg daily given in 2 divided doses, preferably after food, increasing by 200mg daily at 3 day intervals to a maximum of 2.5 grams daily in divided doses; usual maintenance 1 to 2 grams daily.

Formulation and dosage details

Formulation:

Modified release granules (Episenta®) 500mg, 1 gram

Dosage:

By mouth: initially 600mg daily given in 2 divided doses, preferably after food, increasing by 200mg daily at 3 day intervals to a maximum of 2.5 grams daily in divided doses; usual maintenance 1 to 2 grams daily.

Formulation and dosage details

Formulation:

Solution for injection 300mg/3mL

LAMOTRIGINE

Therapy notes

  • Note: serious skin reactions including Stevens-Johnson syndrome and toxic epidermal necrolysis have developed, especially in children. Most rashes occur in the first 8 weeks. Factors associated include concomitant use of valproate, initial lamotrigine dosing higher than recommended and more rapid dose escalation than recommended. Aplastic anaemia, bone marrow depression and pancytopenia have been associated rarely with lamotrigine. If suspected stop drug immediately.
  • Advise women on lamotrigine monotherapy that due to the risk of reduced seizure control whilst on combined hormonal contraception (CHC), and the potential for toxicity in the CHC-free week, the risks of using CHC may outweigh the benefits.

Formulation and dosage details

Formulation:

Tablets 25mg, 50mg, 100mg, 200mg

Dosage:

Monotherapy: initially 25mg daily for 14 days, increased to 50mg daily for further 14 days, then increased by a maximum of 50mg to 100mg every 7 to 14 days, usual maintenance 100mg to 200mg daily in 1 to 2 divided doses.
Adjunctive therapy with valproate: initially 25mg every other day for 14 days, then 25mg daily for further 14 days, thereafter increased by a maximum of 25mg to 50mg every 7 to 14 days, usual maintenance as above for monotherapy.
Adjunctive therapy (with enzyme inducing drugs) without valproate: initially 50mg daily for 14 days then 50mg twice daily for a further 14 days, thereafter increased by maximum of 100mg every 7 to 14 days, usual maintenance 200mg to 400mg daily in 2 divided doses.

Formulation and dosage details

Formulation:

Dispersible tablets 5mg, 25mg, 100mg

Dosage:

Monotherapy: initially 25mg daily for 14 days, increased to 50mg daily for further 14 days, then increased by a maximum of 50mg to 100mg every 7 to 14 days, usual maintenance 100mg to 200mg daily in 1 to 2 divided doses.
Adjunctive therapy with valproate: initially 25mg every other day for 14 days, then 25mg daily for further 14 days, thereafter increased by a maximum of 25mg to 50mg every 7 to 14 days, usual maintenance as above for monotherapy.
Adjunctive therapy (with enzyme inducing drugs) without valproate: initially 50mg daily for 14 days then 50mg twice daily for a further 14 days, thereafter increased by maximum of 100mg every 7 to 14 days, usual maintenance 200mg to 400mg daily in 2 divided doses.

Editorial Information

Document Id: F078