Sulthiame

Usage

Sulthiame is an old antiepileptic drug, less commonly used now. It has been used for childhood epilepsy with centrotemporal spikes particularly popular in some European countries. Low level evidence studies suggest it might be effective as additional therapy in a range of drug resistant epilepsies (generalised, focal and mixed epilepsies, Electrical Status Epilepticus in Sleep (ESES), Epileptic Encephalopathy with Continuous Spike and Wave (CSWS), other epileptic encephalopathies, myoclonic epilepsies).1 2 Consultation with neurology is recommended.

Mechanism of action: carbonic anhydrase inhibitor.

Resources

  • 1. Nina Swiderska, Daniel Hawcutt, Victoria Eaton, Faye Stockton, Ram Kumar, Rachel Kneen, and Richard Appleton Sulthiame in refractory paediatric epilepsies: An experience of an ‘old’ antiepileptic drug in a tertiary paediatric neurology unit, Seizure : 20 (10), December 2011, Pages 805-808
  • 2. Philip Patsalos & Erik St Louis. The Epilepsy Prescriber’s Guide to Antiepileptic Drugs, 3rd Ed. Cambridge University Press.

Side effects

For a complete list of side-effects, consult MIMS.

Side effects:

  • Paraesthesia of the extremities and face
  • Ataxia
  • Dizziness, Headache, Diplopia
  • Tachypnoea, hyperpnoea, dyspnoea
  • Drowsiness
  • Tachycardia
  • Loss of appetite, anorexia and weight loss
  • Gastric complaints
  • Hypersalivation
  • Cognitive slowing

Other notable side effects:

  • Rashes including Steven-Johnson syndrome and TEN
  • Carbonic anhydrase inhibitors can lead to metabolic acidosis and kidney stones

Rare Side-effects

  • Anxiety, suicidal ideation and hallucinations
  • Joint pains
  • Fatigue from a myaesthenia-like syndrome
  • Insomnia
  • Renal impairment

All anticonvulsants are potentially teratogenic and this is often dose related (see section: AED Prescribing - Pregnancy)

For a complete list of adverse effects, appropriate formularies should be consulted.

Dosing

  • Initial dose: 3-5 mg/kg/day in 2 divided doses.
  • A start dose is 50mg twice daily and common maintenance dose is 200mg to 400mg.
  • This maintenance dose is usually: 5-10 mg/kg/day (MIMS states 10-15mg).
  • Sulthiame should be given with plenty of water
  • Dosages per kilogram can only be used in children of weight approximately up to 30-40kgs. Consult appropriate formularies for higher weights and in the adult range.
  • These dosages are only a guideline and appropriate formularies should be consulted as needed.

Preparations

  • Tablets: 50mg tablets and 200mg tablets
  • There is no IV preparation.

Interactions | Precautions

Precautions

  • Dosage change required in renal and hepatic impairment.
  • Sulthiame may not be used in cases of known hypersensitivity to sulphur containing medications, other sulphonamides. 
  • Sulthiame should not be used in patients with known acute porphyria, hyperthyroidism or severe hypertension.

Drug Interactions

  • Sulthiame inhibits hepatic metabolism and so this medication does interact with other AEDs especially phenytoin.
  • Other interactions: carbamazepine, phenobarbitone, lamotrigine, primidone.
  • Should generally not be used in patients already receiving acetazolamide, topiramate, or the ketogenic diet, because these also predispose to metabolic acidosis.

Weaning

  • When ceasing Sulthiame, may need to adjust the doses of concurrent medications as Sulthiame can affect the plasma levels of other medications.
  • A gradual reduction should be undertaken.
  • Rapid discontinuation may induce withdrawal seizures and should only be undertaken if there are safety concerns (Stevens-Johnson syndrome, sulphur drug reaction).

Pregnancy

  • Usage in pregnancy needs to be discussed with a neurologist.
  • There are animal studies that show adverse effects on the foetus, but there are no controlled studies in humans. Sulthiame is classified as class D teratogen in pregnancy (MIMS).