Stiripentol

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.