Oral steroids protocol for Infantile Epileptic Spasms Syndrome (IESS)

 

Prednisolone dosing: e.g. Danalone 15mg/5ml syrup

If patient weighs ≥7.5 kg, prescribe the following prednisolone dosing:

Days 1-14: 15 mg po 4 times daily – (5ml Danalone*4)

Days 15-17: 15 mg po 3 times daily – (5ml Danalone*3)

Days 18-20: 15 mg po twice daily  – (5ml Danalone*2)

Days 21-23: 15 mg po once daily – (5ml Danalone*1)

Days 24-26: 7.5 mg po once daily – (2.5ml Danalone*1)

Days 27-29: 3.5 mg po once daily – (1.2ml Danalone*1)

Day 30: Stop

 

If patient weighs <7.5 kg then then calculate prednisolone dosing using the following schedule:

Days 1-14: 8 mg/kg/day (÷ 4 doses)

Days 15-17: 6 mg/kg/day (÷ 3 doses)

Days 18-20: 4 mg/kg/day (÷ 2 doses)

Days 21-23: 2 mg/kg/day (1 dose)

Days 24-26: 1 mg/kg/day (one dose)

Days 27-29: 0.5 mg/kg/day (one dose)

Day 30: Stop

 

Instructions for Initiating Prednisolone

• Baseline BP, and CBC, glucose, Mg, Ca, electrolytes
• BP twice weekly and urine glucose monitored weekly and blood work (CBC, glucose, Mg, Ca, electrolytes) every 2 weeks while on treatment.
• Prescribe PPI e.g. omeprazole 1mg/kg/day
• Repeat EEG (wake and sleep) 10-14 days following initiation of treatment

The treating team should consider whether to initiate treatment during hospital admission and whether to perform a baseline heart echocardiogram. Local hospital nephrologists should be consulted for control of hypertension and in the event of febrile illnesses, teams should consider endocrinology and ID consultation for advice on stress dose and antibiotics.

Vaccines:

All vaccines are held during the treatment period.

o Live vaccines are held for 6 months after treatment has stopped

o Inactivated vaccines are held for 3 months after treatment has stopped

Treatment resistant cases – consider Synacthen Short Acting (doses given in mg, NOT IU)

Days 1-14: 0.75mg/m² twice daily

Days 15-17: 0.3mg/m² once daily

Days 18-20: 0.15mg/m² once daily

Days 21-23: 0.1mg/m² once daily

Days 24-29: 0.1mg/m² every other day – 3 doses total

Rationale and references

Prednisolone protocol based on Sick Kids, Toronto protocol November 2020 following comparisons between multiple international protocols:

• Protocols are split between fixed dose protocols (largely based on the ICISS trial as reported in O’Callaghan et al. 2017)[1] and weight-based protocols
• The most widely published fixed dose protocol as used in the ICISS study gives a starting dose of 10 mg*4/day  i.e. 40mg daily with increased dose to 20mg*3/day (60mg daily) if spasms continue on Day 7 or reappear. This protocol is used for example in UK[2] and Australian[3] hospitals and also in many centers in the USA[4].
• Weight-based dosing is recommended consistently as starting with 8 mg/kg/day divided 3 or 4 times a day (maximum 60mg/day) 4.
• We propose that it is not appropriate to give the same dose to young infants with early onset IESS (aged 3 months for example) as older infants due to large weight differences and therefore favour weight-based dosing for smaller infants.  The split between <7.5kg and>7.5kg reflects the upper limit of 60mg/day given also in weight-based protocols.
• We favour the more aggressive approach in the Sick Kids protocol starting with 60mg/day over the approach starting with 40mg/day with later dose increases depending on response.

Synacthen Short Acting protocol based on Nationwide Children’s Hospital, Ohio protocol[5] using Natural ACTH, with conversions made from Natural ACTH (measured in IU) to Synacthen Short Acting(measured in mg) as per advice from Dr Maya Lodzki, Clinical Pharmacist, Sheba using conversion of 0.1mg cosynotropin = 10IU ACTH (as per Alammar et al.,[6]).