Active Ingredient: Ravulizumab
Ravulizumab is indicated in the treatment of patients with a body weight of 10 kg or above with atypical haemolytic uremic syndrome (aHUS) who are complement inhibitor treatment-naïve or have received eculizumab for at least 3 months and have evidence of response to eculizumab.
For this indication, competent medicine agencies globally authorize below treatments:
For:
Regimen A: In case that patient weight is ≥ 40 kg and patient weight is ≤ 60 kg, intravenous, 2,400 milligrams ravulizumab, one dose, over the duration of 2 weeks. Afterwards, in case that patient weight is ≥ 40 kg and patient weight is ≤ 60 kg, intravenous, 3,000 milligrams ravulizumab, once every 8 weeks, over the duration of 6 months.
Regimen B: In case that patient weight is ≥ 60 kg and patient weight is ≤ 100 kg, intravenous, 2,700 milligrams ravulizumab, one dose, over the duration of 2 weeks. Afterwards, in case that patient weight is ≥ 60 kg and patient weight is ≤ 100 kg, intravenous, 3,300 milligrams ravulizumab, once every 8 weeks, over the duration of 6 months.
Regimen C: In case that patient weight is ≥ 100 kg, intravenous, 3,000 milligrams ravulizumab, one dose, over the duration of 2 weeks. Afterwards, in case that patient weight is ≥ 100 kg, intravenous, 3,600 milligrams ravulizumab, once every 8 weeks, over the duration of 6 months.
The recommended dosing regimen consists of a loading dose followed by maintenance dosing, administered by intravenous infusion. The doses to be administered are based on the patient’s body weight, as shown in Table 1. For adult patients (≥18 years of age), maintenance doses should be administered at a once every 8-week interval, starting 2 weeks after loading dose administration.
Dosing schedule is allowed to occasionally vary by ± 7 days of the scheduled infusion day (except for the first maintenance dose of ravulizumab), but the subsequent dose should be administered according to the original schedule.
Table 1. Ravulizumab weight-based dosing regimen for adult patients with body weight greater than or equal to 40 kg:
| Body weight range (kg) | Loading dose (mg) | Maintenance dose (mg)* | Dosing interval |
|---|---|---|---|
| ≥40 to <60 | 2,400 | 3,000 | Every 8 weeks |
| ≥60 to <100 | 2,700 | 3,300 | Every 8 weeks |
| ≥100 | 3,000 | 3,600 | Every 8 weeks |
* First maintenance dose is administered 2 weeks after loading dose.
Treatment initiation instructions in patients who are complement-inhibitor treatment-naïve or switching treatment from eculizumab are shown in Table 2.
Table 2. Ravulizumab treatment initiation instructions:
| Population | Weight-based ravulizumab loading dose | Time of first ravulizumab weight- based maintenance dose |
|---|---|---|
| Not currently on ravulizumab or eculizumab treatment | At treatment start | 2 weeks after ravulizumab loading dose |
| Currently treated with eculizumab | At time of next scheduled eculizumab dose | 2 weeks after ravulizumab loading dose |
In aHUS, ravulizumab treatment to resolve thrombotic microangiopathy (TMA) manifestations should be for a minimum duration of 6 months, beyond which length of treatment needs to be considered for each patient individually. Patients who are at higher risk for TMA recurrence, as determined by the treating healthcare provider (or clinically indicated), may require chronic therapy.
Plasma exchange (PE), plasmapheresis (PP) and intravenous immunoglobulin (IVIg) have been shown to reduce ravulizumab serum levels. A supplemental dose of ravulizumab is required in the setting of PE, PP or IVIg (Table 3).
Table 3. Supplemental dose of ravulizumab after PP, PE, or IVIg:
| Body weight range (kg) | Most recent ravulizumab dose (mg) | Supplemental dose (mg) following each PE or PP intervention | Supplemental dose (mg) following completion of an IVIg cycle |
|---|---|---|---|
| ≥40 to <60 | 2,400 | 1,200 | 600 |
| 3,000 | 1,500 | ||
| ≥60 to <100 | 2,700 | 1,500 | 600 |
| 3,300 | 1,800 | ||
| ≥100 | 3,000 | 1,500 | 600 |
| 3,600 | 1,800 | ||
| Timing of ravulizumab supplemental dose | Within 4 hours following each PE or PP intervention | Within 4 hours following completion of an IVIg cycle | |
Abbreviations: IVIg = intravenous immunoglobulin, kg = kilogram, PE = plasma exchange, PP = plasmapheresis
No dose adjustment is required for patients with aHUS aged 65 years and over. There is no evidence indicating any special precautions are required for treating a geriatric population – although experience with ravulizumab in elderly patients with aHUS in clinical studies is limited.
Ravulizumab should not be administered as an intravenous push or bolus injection.
For:
Regimen A: In case that patient weight is ≥ 10 kg and patient weight is ≤ 20 kg, intravenous, 600 milligrams ravulizumab, one dose, over the duration of 2 weeks. Afterwards, in case that patient weight is ≥ 10 kg and patient weight is ≤ 20 kg, intravenous, 600 milligrams ravulizumab, once every 4 weeks.
Regimen B: In case that patient weight is ≥ 20 kg and patient weight is ≤ 30 kg, intravenous, 900 milligrams ravulizumab, one dose, over the duration of 2 weeks. Afterwards, in case that patient weight is ≥ 20 kg and patient weight is ≤ 30 kg, intravenous, 2,100 milligrams ravulizumab, once every 8 weeks.
Regimen C: In case that patient weight is ≥ 30 kg and patient weight is ≤ 40 kg, intravenous, 1,200 milligrams ravulizumab, one dose, over the duration of 2 weeks. Afterwards, in case that patient weight is ≥ 30 kg and patient weight is ≤ 40 kg, intravenous, 2,700 milligrams ravulizumab, once every 8 weeks.
Regimen D: In case that patient weight is ≥ 40 kg and patient weight is ≤ 60 kg, intravenous, 2,400 milligrams ravulizumab, one dose, over the duration of 2 weeks. Afterwards, in case that patient weight is ≥ 40 kg and patient weight is ≤ 60 kg, intravenous, 3,000 milligrams ravulizumab, once every 8 weeks.
Regimen E: In case that patient weight is ≥ 60 kg and patient weight is ≤ 100 kg, intravenous, 2,700 milligrams ravulizumab, one dose, over the duration of 2 weeks. Afterwards, in case that patient weight is ≥ 60 kg and patient weight is ≤ 100 kg, intravenous, 3,300 milligrams ravulizumab, once every 8 weeks.
Regimen F: In case that patient weight is ≥ 100 kg, intravenous, 3,000 milligrams ravulizumab, one dose, over the duration of 2 weeks. Afterwards, in case that patient weight is ≥ 100 kg, intravenous, 3,600 milligrams ravulizumab, once every 8 weeks.
These patients should be treated in accordance with the adult dosing recommendations (See Table 1).
Table 1. Ravulizumab weight-based dosing regimen for adult patients with body weight greater than or equal to 40 kg:
| Body weight range (kg) | Loading dose (mg) | Maintenance dose (mg)* | Dosing interval |
|---|---|---|---|
| ≥40 to <60 | 2,400 | 3,000 | Every 8 weeks |
| ≥60 to <100 | 2,700 | 3,300 | Every 8 weeks |
| ≥100 | 3,000 | 3,600 | Every 8 weeks |
* First maintenance dose is administered 2 weeks after loading dose.
Treatment initiation instructions in patients who are complement-inhibitor treatment-naïve or switching treatment from eculizumab are shown in Table 2.
Table 2. Ravulizumab treatment initiation instructions:
| Population | Weight-based ravulizumab loading dose | Time of first ravulizumab weight- based maintenance dose |
|---|---|---|
| Not currently on ravulizumab or eculizumab treatment | At treatment start | 2 weeks after ravulizumab loading dose |
| Currently treated with eculizumab | At time of next scheduled eculizumab dose | 2 weeks after ravulizumab loading dose |
The weight-based doses and dosing intervals for paediatric patients ≥10 kg to <40 kg are shown in Table 3.
For patients switching from eculizumab to ravulizumab, the loading dose of ravulizumab should be administered 2 weeks after the last eculizumab infusion, and then maintenance doses should be administered per weight-based dosing regimen shown in Table 3, starting 2 weeks after loading dose administration.
Table 3. Ravulizumab weight-based dosing regimen for paediatric patients with aHUS below 40 kg:
| Body weight range (kg) | Loading dose (mg) | Maintenance dose (mg)* | Dosing interval |
|---|---|---|---|
| ≥10 to <20 | 600 | 600 | Every 4 weeks |
| ≥20 to <30 | 900 | 2,100 | Every 8 weeks |
| ≥30 to <40 | 1,200 | 2,700 | Every 8 weeks |
* First maintenance dose is administered 2 weeks after loading dose
In aHUS, ravulizumab treatment to resolve thrombotic microangiopathy (TMA) manifestations should be for a minimum duration of 6 months, beyond which length of treatment needs to be considered for each patient individually. Patients who are at higher risk for TMA recurrence, as determined by the treating healthcare provider (or clinically indicated), may require chronic therapy.
Plasma exchange (PE), plasmapheresis (PP) and intravenous immunoglobulin (IVIg) have been shown to reduce ravulizumab serum levels. A supplemental dose of ravulizumab is required in the setting of PE, PP or IVIg (Table 4).
Table 4. Supplemental dose of ravulizumab after PP, PE, or IVIg:
| Body weight range (kg) | Most recent ravulizumab dose (mg) | Supplemental dose (mg) following each PE or PP intervention | Supplemental dose (mg) following completion of an IVIg cycle |
|---|---|---|---|
| ≥40 to <60 | 2,400 | 1,200 | 600 |
| 3,000 | 1,500 | ||
| ≥60 to <100 | 2,700 | 1,500 | 600 |
| 3,300 | 1,800 | ||
| ≥100 | 3,000 | 1,500 | 600 |
| 3,600 | 1,800 | ||
| Timing of ravulizumab supplemental dose | Within 4 hours following each PE or PP intervention | Within 4 hours following completion of an IVIg cycle | |
Abbreviations: IVIg = intravenous immunoglobulin, kg = kilogram, PE = plasma exchange, PP = plasmapheresis
Ravulizumab should not be administered as an intravenous push or bolus injection.
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