Sulthiame | Epilepsy clinician handbook

  • 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).
  • Consultation with neurology is recommended.
  • Mechanism of action: carbonic anhydrase inhibitor.

Possible side effects

For a complete list of side effects, consult MIMS.

  • 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 anti-seizure medications are potentially teratogenic and this is often dose related. For a complete list of adverse effects, appropriate formularies should be consulted.

Interactions and 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).

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