Sulthiame

Usage

  • Sulthiame is an old anti-seizure medication, less commonly used now.
  • It should not be used first line, and may be a useful adjunct in refractory epilepsy.
  • It has been used for Self-Limited Epilepsy with CentroTemporal Spikes (SeLECTS), 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, Epileptic Encephalopathy with Spike Wave Activation in Sleep (EE-SWAS, previously ESES), other epileptic encephalopathies, myoclonic epilepsies).1 2  
  • Consultation with neurology is recommended.
  • Mechanism of action: carbonic anhydrase inhibitor.

Resources

Side effects

For a complete list of side effects, consult MIMS.

Possible 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:

  • Rash including Steven-Johnson syndrome and Toxic Epidermal Necrolysis (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

  • The below initiation and escalation doses are only a guide and need to be individualised based on patient (age, weight, co-morbidities), disease (seizure type, frequency, duration) and medication (metabolism, interactions, side-effect profile) characteristics.

 

  • Situations that require more careful consideration include children with higher weights, polytherapy, or multiple co-morbidities. Consultation with appropriate formularies or a paediatric neurologist may be required in specific circumstances.

Commonly used regime

  • 2-12 years (<30kg): Initially 3-5 mg/kg/day in 2 divided doses, then increase gradually every 1-2 weeks, up to a usual maintenance dose of 5-15mg/kg/day.
  • 30-40kg: Initially 50mg twice daily, gradually increase every 1-2 weeks by 50-100mg/day in divided doses, until optimum response reached. Common maintenance dose is 200-400mg/day.
  • Please consult appropriate formularies for dosing above 30-40kgs.
  • Sulthiame should be given with plenty of water.
  • Tablets should be administered whole.

Preparations

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

Monitoring

  • Bicarbonate may drop during sulthiame therapy and monitoring may be required.
  • 25-hydroxyvitamin D levels should be monitored in all patients, as sulthiame can alter vitamin D metabolism and bone mineral density. Consider DEXA bone scan in patients at risk for osteopenia.

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.
  • Known interaction between sulthiame and primidone, leading to dizziness, unsteady gait, and drowsiness.
  • Other interactions: carbamazepine, phenobarbitone, lamotrigine, primidone.
  • Should generally not be used in patients already receiving acetazolamide, topiramate, zonisamide, or the ketogenic diet, because these also predispose to metabolic acidosis and to kidney stones.
  • Known interaction with alcohol, which can cause headache, nausea, vomiting, respiratory depression, hypotension, arrhythmia, decreased level of consciousness.

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).

 

Information last reviewed: 3/05/2023.