Stiripentol | Epilepsy clinician handbook
Stiripentol is for use in Dravet syndrome (DS) as adjunctive therapy to at least two other anti-seizure medications (particularly clobazam with valproate).
Available on PBS for use in patients with DS with generalised tonic-clonic seizures or generalised clonic seizures that are not adequately controlled by at least two other anti-seizure medications.
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
Dosage
- On PBS criteria, a neurologist must initiate or be consulted in ongoing treatment
- Start slow and go slow.
Commonly used regime
Adapted from AMH and MIMS, seek advice as needed:
- Give daily dosage in 2 or 3 divided doses.
- Oral: Initially 20mg/kg/day for one week. Dosage escalation is age dependent - consult appropriate formularies
- <30kg: increase by 10mg/kg per week to a dosage of 50mg/kg/day.
- As a precaution, for vulnerable patients or patients on clobazam and valproate, start at 10mg/kg daily, to allow for dose adjustments should side effects occur.
- Dosages per kilogram can only be used up to weights of 30-40kgs. It is important to consult formularies in children of weights > 30kgs as needed.
- Slower titrations are recommended if side effects such as sedation are noted, or while adjusting other medications.
- There is no clinical data to support clinical safety of stiripentol at doses > 50mg/kg/day.
- There is no clinical data to support the use of stiripentol as monotherapy in DS.
- Efficacy should be apparent within 2-4 weeks. If no benefit is seen at 6-8 weeks and at maximum dosage, may not be effective.
- If stopping, may need to adjust the dosage of concurrent medicines.
- Do not stop abruptly. Taper dosage gradually.
Preparations
- Should be taken with food, as stiripentol degrades rapidly in the acid environment of an empty stomach.
- Stiripentol 250 and 500mg capsule. Do not chew.
- Stiripentol 250mg and 500mg powder for oral suspension.
Monitoring and levels
- Before commencing stiripentol, do FBC, LFT and renal function tests, then repeat at intervals.
- Blood levels for stiripentol are not available.
- Monitoring of concomitant antiepileptic drugs is essential as stiripentol inhibits the metabolism of many drugs.
- Monitor weight and growth during treatment.
Formulary
Possible side effects
- Anorexia
- Weight loss, especially when administered with sodium valproate
- Drowsiness
- Ataxi
- Hypotonicity
- Dystonia, tremor
- Insomnia
- Fatigue
- Nausea and vomiting
Other notable side effects
- Neutropenia
- Altered behaviour: aggressiveness and irritability
- Hyperkinesia
- Raised Gamma GT notably when combined with valproate
Dangerous side effects
- Cutaneous photosensitivity, rash, urticaria
- All anti-seizure medications are potentially teratogenic and this is often dose related
Interactions and precautions
Because of inhibitory interactions with clobazam and valproate, the daily dosage of these anticonvulsants may need to be reduced by 25-30%. The impetus for reduction in valproate dosage usually relates to gastrointestinal adverse effects, such as loss of appetite and weight loss with combined therapy.
Carbamazepine, phenytoin and phenobarbitone should generally not be used in conjunction with stiripentol for DS, due to drug interaction and the potential to worsen seizures. Approximately two-to three-fold increases in clobazam and five-fold increases in norclobazam plasma levels respectively have been reported with co-administration of stiripentol in children with DS.
Because stiripentol is a potent inhibitor of hepatic enzymes, the following drug combinations require particular caution:
- Ergot alkaloids
- Immunosuppressants (tacrolimus, cyclosporine, sirolimus): nephrotoxicity.
- Statins: rhabdomyolysis
- Theophylline, caffeine toxicity.
Potential teratogen. History of delirium: contraindicated. The manufacturer recommends avoiding use in renal and hepatic impairment.
Monitoring and levels
- Before commencing stiripentol, do FBC, LFT and renal function tests, then repeat at intervals.
- Blood levels for stiripentol are not available.
- Monitoring of concomitant antiepileptic drugs is essential as stiripentol inhibits the metabolism of many drugs.
- Monitor weight and growth during treatment.
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.