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.
Important: Dosing information
Initiation and escalation doses on this webpage are a guide only.
All medications must be individualised based on:
- patient age, weight, co-morbidities
- disease, seizure type, frequency, duration
- medication metabolism, interactions, side-effect profile characteristics.
Further consultation with appropriate formularies or a paediatric neurologist may be required.
Dosing
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.
Formulary
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 myasthenia-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.
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.
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).
Resources
This information is reviewed annually by the Sydney Children’s Hospitals Network Paediatric Epilepsy NSW working group which includes medical, nursing, and pharmacy representation.