Usage
- 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.
Resources:
Side effects
Possible side effects:
- Anorexia
- Weight loss, especially when administered with sodium valproate
- Drowsiness
- Ataxia
- 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
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.
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.
Interactions | 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 fivefold 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.
Information last reviewed: 5/05/2023.