Ultomiris Dosage

Generic name: ravulizumab 300mg in 30mL
Drug class: Selective immunosuppressants

Medically reviewed by Drugs.com. Last updated on Apr 7, 2023.

Important Dosage Information

ULTOMIRIS may be administered as an intravenous infusion (ULTOMIRIS vial for intravenous administration) in adult or pediatric patients one month of age and older or as a subcutaneous injection for maintenance (ULTOMIRIS on-body delivery system for subcutaneous administration) in adult patients.

Vials are intended for intravenous use only, and on-body delivery systems (prefilled cartridge and on-body injector) are intended for subcutaneous maintenance use only.

Recommended Vaccination and Prophylaxis

Vaccinate patients for meningococcal disease according to current ACIP guidelines to reduce the risk of serious infection [see Warnings and Precautions (5.1, 5.3)].

Provide 2 weeks of antibacterial drug prophylaxis to patients if ULTOMIRIS must be initiated immediately and vaccines are administered less than 2 weeks before starting ULTOMIRIS therapy.

Healthcare professionals who prescribe ULTOMIRIS must enroll in the ULTOMIRIS REMS [see Warnings and Precautions (5.1)].

Intravenous Administration in Adult and Pediatric Patients with PNH, aHUS, or gMG

The recommended intravenous ULTOMIRIS loading and maintenance dosing in adult and pediatric patients, one month of age or older weighing 5 kg or greater, with PNH or aHUS, or in adult patients with gMG weighing 40 kg or greater, is based on the patient's body weight, as shown in Table 1, with maintenance doses administered every 4 or 8 weeks, starting 2 weeks after loading dose.

The intravenous (IV) dosing schedule is allowed to occasionally vary within 7 days of the scheduled infusion day (except for the first maintenance dose of ULTOMIRIS); but subsequent doses should be administered according to the original schedule.

Following a missed intravenous ULTOMIRIS dose, the patient should contact their health care provider immediately.

Table 1: ULTOMIRIS Vial for Intravenous (IV) Administration Weight-Based Dosing Regimen – PNH, aHUS, or gMG*
Indications	Body Weight Range (kg)	Loading Dose (mg)†	Maintenance Dose (mg) and Dosing Interval
* See Tables 5, 6, 8, and 9 for selection of the proper total volume and maximum infusion rate [see Dosage and Administration (2.6)] † See Table 2 for intravenous ULTOMIRIS treatment initiation instruction and timing of loading dose and maintenance dose
PNH and aHUS	5 to less than 10	600	300	Every 4 weeks
	10 to less than 20	600	600	Every 4 weeks
	20 to less than 30	900	2,100	Every 8 weeks
	30 to less than 40	1,200	2,700	Every 8 weeks
PNH, aHUS, and gMG	40 to less than 60	2,400	3,000	Every 8 weeks
	60 to less than 100	2,700	3,300
	100 or greater	3,000	3,600

Refer to Table 2 for treatment initiation instructions in patients who are complement inhibitor treatment-naïve, or switching treatment from subcutaneous (SUBQ) administration of ULTOMIRIS or eculizumab.

Table 2: ULTOMIRIS Vial for Intravenous (IV) Administration Treatment Initiation Instructions – PNH, aHUS, or gMG
Population	Weight-based ULTOMIRIS IV Loading Dose	Time of First ULTOMIRIS IV Weight-based Maintenance Dose
* Adult patients with PNH and aHUS only
Not currently on ULTOMIRIS or eculizumab treatment	At treatment start	2 weeks after ULTOMIRIS IV loading dose
Currently treated with eculizumab	At time of next scheduled eculizumab dose	2 weeks after ULTOMIRIS IV loading dose
Currently treated with ULTOMIRIS on-body delivery system for subcutaneous administration (SUBQ)*	Not applicable	1 week after last ULTOMIRIS SUBQ maintenance dose

Subcutaneous Administration in Adult Patients with PNH or aHUS

Subcutaneous (SUBQ) dosing of ULTOMIRIS is not approved for use in pediatric patients.

The recommended subcutaneous ULTOMIRIS maintenance dose is 490 mg once weekly in adult patients greater than or equal to 40 kg body weight with PNH or aHUS. The 490 mg dose of ULTOMIRIS is delivered using 2 on-body delivery systems. Each on-body delivery system consists of 1 on-body injector and 1 prefilled cartridge containing 245 mg of ravulizumab.

The subcutaneous dosing schedule is allowed to occasionally vary by ± 1 day of the scheduled dose day, but the subsequent dose should be administered according to the original schedule.

Following a missed or partial subcutaneous ULTOMIRIS dose, the patient should contact their health care provider immediately.

Refer to Table 3 for treatment initiation instructions in patients who are complement inhibitor treatment-naïve, or switching treatment from intravenous administration of ULTOMIRIS or eculizumab.

Table 3: ULTOMIRIS On-Body Delivery System for Subcutaneous (SUBQ) Administration Treatment Initiation Instructions – Adults with PNH or aHUS
Population	Weight-based ULTOMIRIS IV Loading Dose*	Time of First ULTOMIRIS 490 mg SUBQ Maintenance Dose
* See Table 1 for weight-based ULTOMIRIS IV loading dose in patients with body weight ≥ 40 kg
Not currently on ULTOMIRIS or eculizumab treatment	At treatment start	2 weeks after ULTOMIRIS IV loading dose
Currently treated with eculizumab	At time of next scheduled eculizumab dose	2 weeks after ULTOMIRIS IV loading dose
Currently treated with ULTOMIRIS intravenous (IV) administration	Not applicable	8 weeks after last ULTOMIRIS IV maintenance dose

Dosing Considerations

Supplemental Dose of ULTOMIRIS

Plasma exchange (PE), plasmapheresis (PP), and intravenous immunoglobulin (IVIg) have been shown to reduce ULTOMIRIS serum levels. A supplemental dose of ULTOMIRIS is required in the setting of PE, PP, or IVIg (Table 4).

Table 4: Supplemental Dose of ULTOMIRIS after PE, PP, or IVIg*
Body Weight Range (kg)	Most Recent ULTOMIRIS Dose (mg)	Supplemental Dose (mg) following each PE or PP Intervention	Supplemental Dose (mg) following Completion of an IVIg Cycle
Abbreviations: IVIg = intravenous immunoglobulin; PE = plasma exchange; PP = plasmapheresis
* See Table 7 and Table 10 for selection of the proper total volume and maximum infusion rate [see Dosage and Administration (2.6)]
40 to less than 60	2,400	1,200	600
40 to less than 60	3,000	1,500	600
60 to less than 100	2,700	1,500	600
60 to less than 100	3,300	1,800	600
100 or greater	3,000	1,500	600
100 or greater	3,600	1,800	600
Timing of ULTOMIRIS Supplemental Dose		Within 4 hours following each PE or PP intervention	Within 4 hours following completion of an IVIg cycle

Preparation and Administration

Preparation of ULTOMIRIS Vials for Intravenous Administration

Each vial of ULTOMIRIS is intended for single-dose only.

ULTOMIRIS vials are for intravenous administration by a healthcare provider and are intended for intravenous administration only.

Dilute before use.

Do not mix ULTOMIRIS 100 mg/mL (3 mL and 11 mL vials) and 10 mg/mL (30 mL vial) concentrations together.

Use aseptic technique to prepare ULTOMIRIS as follows:

1.

The number of vials to be diluted is determined based on the individual patient's weight and the prescribed dose [see Dosage and Administration (2.2)].

2.

Prior to dilution, visually inspect the solution in the vials; the solution should be free of any particulate matter or precipitation. Do not use if there is evidence of particulate matter or precipitation.

3.

Withdraw the calculated volume of ULTOMIRIS from the appropriate number of vials and dilute in an infusion bag using 0.9% Sodium Chloride Injection, USP to a final concentration of:

50 mg/mL for the 3 mL and 11 mL vial sizes or
5 mg/mL for the 30 mL vial size.

The product should be mixed gently. Do not shake. Protect from light. Do not freeze.

Refer to the following reference tables for IV preparation and minimum infusion duration:

ULTOMIRIS 100 mg/mL (3 mL and 11 mL vials): see Table 5 (loading doses), Table 6 (maintenance doses), and Table 7 (supplemental doses)
ULTOMIRIS 10 mg/mL (30 mL vial): see Table 8 (loading doses), Table 9 (maintenance doses), and Table 10 (supplemental doses)

4.: Administer the prepared solution immediately following preparation.
5.: If the diluted ULTOMIRIS infusion solution is not used immediately, storage under refrigeration at 2°C - 8°C (36°F - 46°F) must not exceed 24 hours taking into account the expected infusion time. Once removed from refrigeration, administer the diluted ULTOMIRIS infusion solution within 6 hours if prepared with ULTOMIRIS 30 mL vials or within 4 hours if prepared with ULTOMIRIS 3 mL or 11 mL vials.

Intravenous Administration of ULTOMIRIS (Healthcare Providers)

Only administer as an intravenous infusion through a 0.2 or 0.22 micron filter.

Dilute ULTOMIRIS to a final concentration of:

50 mg/mL for the 3 mL and 11 mL vial sizes or
5 mg/mL for the 30 mL vial size.

Prior to administration, allow the admixture to adjust to room temperature (18°C - 25°C, 64°F - 77°F). Do not heat the admixture in a microwave or with any heat source other than ambient air temperature.

Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration, whenever solution and container permit.

Table 5: IV Loading Dose Reference Table for ULTOMIRIS 100 mg/mL (3 mL and 11 mL Vials)
Body Weight Range (kg)*	Loading Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl Diluent† (mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
* Body weight at time of treatment. † Dilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP. ‡ For PNH and aHUS indications only.
5 to less than 10‡	600	6	6	12	1.4	9
10 to less than 20‡	600	6	6	12	0.8	15
20 to less than 30‡	900	9	9	18	0.6	30
30 to less than 40‡	1,200	12	12	24	0.5	48
40 to less than 60	2,400	24	24	48	0.8	60
60 to less than 100	2,700	27	27	54	0.6	90
100 or greater	3,000	30	30	60	0.4	150

Table 6: IV Maintenance Dose Reference Table for ULTOMIRIS 100 mg/mL (3 mL and 11 mL Vials)
Body Weight Range (kg)*	Maintenance Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl Diluent† (mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
* Body weight at time of treatment. † Dilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP. ‡ For PNH and aHUS indications only.
5 to less than 10‡	300	3	3	6	0.8	8
10 to less than 20‡	600	6	6	12	0.8	15
20 to less than 30‡	2,100	21	21	42	1.3	33
30 to less than 40‡	2,700	27	27	54	1.1	50
40 to less than 60	3,000	30	30	60	0.9	67
60 to less than 100	3,300	33	33	66	0.7	95
100 or greater	3,600	36	36	72	0.5	144

Table 7: IV Supplemental Dose Reference Table for ULTOMIRIS 100 mg/mL (3 mL and 11 mL vials)
Body Weight Range (kg)*	Supplemental Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl Diluent† (mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
Note: Refer to Table 4 for selection of ravulizumab supplemental dose
* Body weight at time of treatment. † Dilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.
40 to less than 60	600	6	6	12	0.25	48
	1,200	12	12	24	0.42	57
	1,500	15	15	30	0.5	60
60 to less than 100	600	6	6	12	0.20	60
	1,500	15	15	30	0.36	83
	1,800	18	18	36	0.42	86
100 or greater	600	6	6	12	0.17	71
	1,500	15	15	30	0.25	120
	1,800	18	18	36	0.28	129

Table 8: IV Loading Dose Reference Table for ULTOMIRIS 10 mg/mL (30 mL Vial)
Body Weight Range (kg)*	Loading Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl Diluent† (mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
* Body weight at time of treatment. † Dilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP. ‡ For PNH and aHUS indications only.
5 to less than 10‡	600	60	60	120	3.8	32
10 to less than 20‡	600	60	60	120	1.9	64
20 to less than 30‡	900	90	90	180	1.5	120
30 to less than 40‡	1,200	120	120	240	1.3	185
40 to less than 60	2,400	240	240	480	1.9	253
60 to less than 100	2,700	270	270	540	1.7	318
100 or greater	3,000	300	300	600	1.8	334

Table 9: IV Maintenance Dose Reference Table for ULTOMIRIS 10 mg/mL (30 mL Vial)
Body Weight Range (kg)*	Maintenance Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl Diluent† (mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
* Body weight at time of treatment. † Dilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP. ‡ For PNH and aHUS indications only.
5 to less than 10‡	300	30	30	60	1.9	32
10 to less than 20‡	600	60	60	120	1.9	64
20 to less than 30‡	2,100	210	210	420	3.3	128
30 to less than 40‡	2,700	270	270	540	2.8	193
40 to less than 60	3,000	300	300	600	2.3	261
60 to less than 100	3,300	330	330	660	2	330
100 or greater	3,600	360	360	720	2.2	328

Table 10: IV Supplemental Dose Reference Table for ULTOMIRIS 10 mg/mL (30 mL vial)
Body Weight Range (kg)*	Supplemental Dose (mg)	ULTOMIRIS Volume (mL)	Volume of NaCl Diluent† (mL)	Total Volume (mL)	Minimum Infusion Time (hr)	Maximum Infusion Rate (mL/hr)
Note: Refer to Table 4 for selection of ravulizumab supplemental dose
* Body weight at time of treatment. † Dilute ULTOMIRIS only using 0.9% Sodium Chloride Injection, USP.
40 to less than 60	600	60	60	120	0.5	240
	1,200	120	120	240	1.0	240
	1,500	150	150	300	1.2	250
60 to less than 100	600	60	60	120	0.4	300
	1,500	150	150	300	1.0	300
	1,800	180	180	360	1.1	327
100 or greater	600	60	60	120	0.4	300
	1,500	150	150	300	1.0	300
	1,800	180	180	360	1.1	327

If an adverse reaction occurs during the intravenous administration of ULTOMIRIS, the infusion may be slowed or stopped at the discretion of the physician. Monitor the patient for at least 1 hour following completion of the infusion for signs or symptoms of an infusion-related reaction.

Preparation of ULTOMIRIS On-Body Delivery System for Subcutaneous Administration

ULTOMIRIS on-body delivery system is intended for administration by patients/caregivers. Patients/caregivers may administer after training from a healthcare provider. Refer to the Instructions for Use for detailed instructions on how to use and administer subcutaneous ULTOMIRIS.

Remove 2 cartons of ULTOMIRIS on-body delivery system for subcutaneous administration from the refrigerator. Two on-body injectors and 2 prefilled cartridges are required for a full dose (490 mg).
Inspect the packaging. The on-body injectors or cartridges should not be used if they have been dropped or appear to be broken or damaged.
Wait at least 45 minutes for the on-body injectors and prefilled cartridges in the cartons to naturally reach room temperature prior to administration. Do not return to the refrigerator. Discard after 3 days if unused.
Before administration, visually inspect the solution. The solution should not be injected if it contains flakes or particles, or is cloudy or discolored.

Subcutaneous Administration of ULTOMIRIS On-Body Delivery System

ULTOMIRIS on-body delivery system is for subcutaneous administration into the abdomen, thigh, or upper arm region. A patient may self-administer, or the patient caregiver may administer ULTOMIRIS on-body delivery system after the healthcare provider determines it is appropriate. Injection sites should be rotated, and injections should not be given into areas where the skin is tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks. The 2 on-body delivery systems can be administered concurrently or sequentially. Each injection is delivered over approximately 10 minutes.

Load the first clean cartridge into the first on-body injector and secure in place before closing the cartridge door on the injector. Do not insert the cartridge more than 5 minutes before the injection to avoid drying out the solution.
Peel away the adhesive backing of the first on-body injector and apply onto the clean, dry, chosen injection site (thigh, abdomen, or upper arm).
Start the injection by firmly pressing and releasing the blue start button.
Do not remove until the injection is complete (signaled by the solid green status light, 3 beeping sounds, and the white plunger filling the medicine window).
Repeat steps 1-4 for the second on-body injector.

If an allergic reaction occurs during the subcutaneous administration of ULTOMIRIS, treatment should be stopped, the on-body injector(s) should be removed, and the patient should seek medical attention prior to further administration.

The patient should monitor for signs or symptoms of infusion-related reaction for at least 1 hour following completion of the injection.

Any unused medicinal product and waste material should be disposed of in accordance with local requirements.