Spotlight on Ravulizumab 1- Dosing

Article No. 311

21 January 2020

Information about Ravulizumab cwvz has featured regularly on the alliance website during its development to become the next generation eculizumab. In this short series a spotlight will be shone on a number of basic facts  about the use of Ravulizumab.

Ravulizumab ( trade name Ultomiris) is indicated for :

– adults with PNH

– adults and children(1 month or older)  with aHUS

to inhibit complement mediated thrombotic microagiopathy TMA.

It is not indicated for Shiga toxin e. Coli HUS.

It is supplied in a single dose vial with a strength of 300mg/30mL ( 10mg/mL).

There is a weight based dosing regimen for the number of vials needed for loading ( starting treatment for first time or transitioning from eculizumab) and maintenance ( longer term treatment) levels of Ravulizumab .

The following table shows the dose volumes for both loading and maintenance regimens  according to weight.

Body weight Steps (kg) Loading dose (mg) Maintenance dose (mg) Infusion interval

( weeks)

= 5-10 600 300 4
>10-20 600 600 4
>20-30 900 2100 8
>30-40 1200 2700 8
>40-60 2400 3000 8
> 60-100 2700 3300 8
> 100 3000 3600 8

Maintenance dosing  begins 2 weeks after the loading dose has been  administered. For the transition from eculizumab ,  the loading dose commences 2 weeks after last the eculizumab dose followed by maintenance dosing beginning two weeks later.

For children on the two lowest weight steps the infusion interval is four weeks.

Dosing is prepared by extracting the drug from the prescribed number of vials and diluting it in a solution bag contain  0.9% sodium cloride. Solution bags should not be used if sign of “particulate matter” , discolouration or “precipitation.

There is a prescribed infusion rate according to dose volume. A minimum time to complete maintenance  infusion is shown in the following table:

Body Weight step (kg) Maintenance dose volume (mg) Volume (mL) inc. diluent) Flow rate maximum

(mLper hour)

Infusion time

( minImum)

Hours

Infusion time for eculizumab per 4/8 week period

 

=5- 10 300* 60 31 1.9 2-8*
>10-20 600* 120 63 1.9 2-8*
>20-30 2100 420 127 3.3 4-16*
>30-40 2700 540 192 2.8 4-16*
>40-60 3000 600 257 2.3 2.3**
>60-100 3300 660 330 2 2.3**
>100 3600 720 327 2.2 2.3**

* child infusion time 1-4 hours   ** adult infusion time 35 minutes

Generally the minimum time for an infusion excluding preparation and monitoring is about two hours but for older children it will take around 3 hours. Infusion flow rate can be slowed down if there is a reaction in patient . The monitoring time for any reaction is 1 hour post infusion, so in a 4/8 period further time is saved. There will also be less infusion preparation time and visting/traveling time to clinic due to fewer infusions.

As well as comparably less treatment time than for eculizumab over 8 week periods , the volume of Ravulizumab administered in an 8 week period is significantly less. The following table shows the comparable volume of drug used in an  8 weekly maintenance phase:

Body Weight

Steps

(kg)

 

Dose Eculizumab

(mg)

Volume Eculizumab in 8 weeks (mg) Dose Ravulizumab (mg) Eculizumab tapering volumes
=5-10 300 900 600 n/a
>10-20 300 1200 1200 n/a
>20-30 600 2400 2100 n/a
>30-40 900 3600 2700 1800
>40-60 1200 4800 3000 1800
>60-100 1200 4800 3300 1800
>100 1200 4800 3600 1800

Where clinics have adjusted and tapered  dose levels of eculizumab to suit patients’ needs and a protocol of 900mg every 4 weeks is acheived then volumes of drug  used will be less than those for Ravulizumab. The alliance anticipates that such clinics will recalibrate their fundings and apply tapering protocols to Ravulizumab too.

Doctors should determine how long a patient needs Ravulizumab, but the alliance hopes that such decisions about withdrawal from Ravulizumab treatment should not only be based on the current evidence about safe withdrawal, but also should be made with the patient’s participation  and with adequate monitoring put in place.

 

 

 

Note :Highlights of Ravulizumab use can be seen in this document https://alexion.com/Documents/Ultomiris_USPI.pdf