Crovalimab Dosage

Medically reviewed by Drugs.com. Last updated on Aug 19, 2024.

Applies to the following strengths: akkz 340 mg/2 mL

Usual Adult Dose for Paroxysmal Nocturnal Hemoglobinuria

40 kg to less than 100 kg:

Initial loading dose: 1000 mg IV once on Day 1
Subsequent loading doses: 340 mg subcutaneously once a week on Days 2, 8, 15 and 22
Maintenance dose: 680 mg subcutaneously every 4 weeks starting on Day 29

100 kg or greater:

Initial loading dose: 1500 mg IV once on Day 1
Subsequent loading doses: 340 mg subcutaneously once a week on Days 2, 8, 15 and 22
Maintenance dose: 1020 mg subcutaneously every 4 weeks starting on Day 29

Comments:

Administer Day 1 loading dose as an IV infusion over 60 minutes (1000 mg dose) or 90 minutes (1500 mg dose); infusion time is allowed to vary by 10 minutes more or less.
Dosing is based on actual patient body weight.
Modify the maintenance dose if body weight changes and is consistently greater than or less than 100 kg.
When switching from another C5 inhibitor, the first dose of this drug should be given at the time of the next scheduled complement inhibitor administration.
Ensure protection against meningococcal infection through vaccination prior to therapy or with use of antibacterial prophylaxis.

Use: For the treatment of paroxysmal nocturnal hemoglobinuria (PNH) in patients with a body weight of at least 40 kg

Usual Pediatric Dose for Paroxysmal Nocturnal Hemoglobinuria

AGE 13 YEARS OR OLDER:
40 kg to less than 100 kg:

Initial loading dose: 1000 mg IV once on Day 1
Subsequent loading doses: 340 mg subcutaneously once a week on Days 2, 8, 15 and 22
Maintenance dose: 680 mg subcutaneously every 4 weeks starting on Day 29

100 kg or greater:

Initial loading dose: 1500 mg IV once on Day 1
Subsequent loading doses: 340 mg subcutaneously once a week on Days 2, 8, 15 and 22
Maintenance dose: 1020 mg subcutaneously every 4 weeks starting on Day 29

Comments:

Administer Day 1 loading dose as an IV infusion over 60 minutes (1000 mg dose) or 90 minutes (1500 mg dose); infusion time is allowed to vary by 10 minutes more or less.
Dosing is based on actual patient body weight.
Modify the maintenance dose if body weight changes and is consistently greater than or less than 100 kg.
When switching from another C5 inhibitor, the first dose of this drug should be given at the time of the next scheduled complement inhibitor administration.
Ensure protection against meningococcal infection through vaccination prior to therapy or with use of antibacterial prophylaxis.

Use: For the treatment of pediatric patients 13 years and older with PNH and a body weight of at least 40 kg

Renal Dose Adjustments

Data not available

Comments:

Renal dysfunction had no clinically significant effect on exposure to this drug.

Liver Dose Adjustments

Data not available

Comments:

Mild liver dysfunction had no clinically significant effect on exposure to this drug.
This drug has not been studied in patients with moderate or severe liver dysfunction.

Precautions

The US FDA requires a Risk Evaluation and Mitigation Strategy (REMS) for this drug. It includes elements to assure safe use and an implementation system. For additional information: www.accessdata.fda.gov/scripts/cder/rems/index.cfm

US BOXED WARNINGS:

RISK OF MENINGITIS: This drug, a complement inhibitor, increases the risk of serious infections caused by Neisseria meningitis. Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors. Infections may become rapidly life-threatening or fatal if not recognized or treated early.
VACCINATION RECOMMENDATIONS: Complete or update vaccination for meningococcal bacteria (for serogroups A, C, W, Y, and B) at least 2 weeks prior to the first dose of this drug, unless the risks of delaying therapy outweigh the risk of developing a serious infection. Consult the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients receiving a complement inhibitor.
INVASIVE DISEASE: Treated patients are at increased risk of invasive disease caused by N meningitidis, even if they develop antibodies following vaccination. Monitor patients for early signs of serious meningococcal infections and evaluate immediately if infection is suspected.
REMS PROGRAM: Because of the risk of serious meningococcal infections, this drug is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS).

CONTRAINDICATIONS:

Treatment initiation in patients with unresolved serious Neisseria meningitidis infection
Known serious hypersensitivity reaction to the active component or to any of the ingredients

Safety and efficacy have not been established in patients younger than 13 years and in those with a body weight less than 40 kg.

Consult WARNINGS section for additional precautions.

Dialysis

Data not available

Other Comments

Administration advice:

Health care providers who prescribe this drug must be enrolled in the REMS program.
At least 2 weeks prior to starting treatment, vaccinate patients for meningococcal infection (serogroups A, C, W, Y and B) according to current ACIP guidelines.
If urgent treatment is indicated in a patient not up to date with vaccination, provide antibacterial drug prophylaxis and vaccinate as soon as possible.
For patients switching from another C5 inhibitor (e.g., eculizumab, ravulizumab), consider the benefits of a timed switch between complement inhibitors versus the risk of Type III hypersensitivity reactions. It is recommended to give the first IV loading dose of this drug no sooner than the time of the next scheduled complement inhibitor administration.
For the first loading dose only (Day 1), administer IV using a dedicated infusion line with a 0.2 micron in-line filter and infuse over approximately 60 or 90 minutes based on the prescribed loading dose.
Slow or interrupt the infusion if an infusion-related reaction occurs; discontinue immediately for a serious hypersensitivity reaction.
For doses given on Day 2 and beyond, administer subcutaneously in the abdomen; rotate injection sites.
Doses requiring consecutive injections should be given at least 2 inches apart.
Avoid injecting into moles, scars, or areas where the skin is tender, bruised, red, hard, or not intact.
The dosing schedule is allowed to occasionally vary within 2 days of the administration day (except on Days 1 and 2). If this occurs, administer the subsequent dose according to the regular schedule.
If an entire or partial dose is missed, administer as soon as possible before the day of the next scheduled dose; then, administer the next dose on the regularly scheduled day. Do not make up for a missed dose by administering 2 or more doses on the same day.

Storage requirements: Consult the manufacturer product information for detailed instructions.
VIALS: Store refrigerated (2C to 8C [36F to 46F]) in the outer carton to protect from light.

Unopened vials may remain at room temperature (up to 30C [86°F]) in the outer carton for up to 7 days.
Do not freeze. Do not shake.

DILUTED SOLUTION FOR INFUSION:

Polyolefins, polyethylene, or polypropylene infusion bags: Store refrigerated for up to 64 hours protected from light, or at room temperature for up to 6 hours including infusion time under ambient light conditions.
Polyvinyl chloride infusion bags: Store refrigerated for up to 12 hours protected from light, or at room temperature for up to 6 hours including infusion time under ambient light conditions.

SYRINGES WITH UNDILUTED SOLUTION: Store capped syringe refrigerated for up to 64 hours protected from light, or at room temperature for up to 5 hours under ambient light conditions.

Reconstitution/preparation techniques:

Consult the manufacturer product information prior to preparation; volumetric dosing tables are available.
Each vial of this drug is for one-time use in only one patient.
IV infusion: This drug must be diluted in 0.9% sodium chloride injection before infusing.
Subcutaneous injection: Prepare using undiluted product; use a new vial for each injection.
This product is preservative-free; therefore, immediate use is recommended once prepared.
Protect vials and/or drug from direct sunlight during preparation.

IV compatibility:

No compatibility issues were observed between this drug and a number of drug-contacting infusion materials.
Review the manufacturer product information for a detailed description of assessed materials.

General:

Information regarding REMS is available at www.PIASKYREMS.com or 1-866-4My-Skyy (469-7599).

Monitoring:

Infections/infestations: For early signs of serious meningococcal infection (during therapy)
Hypersensitivity: For type 3 hypersensitivity reactions (during the first 30 days of therapy if switching from or to another C5 inhibitor); for infusion and injection-related reactions (during therapy)
Other: For signs and symptoms of serious hemolysis (for at least 20 weeks after therapy discontinuation if patient is not switched to another treatment)

Patient advice:

Read the US FDA-approved patient labeling (Medication Guide).
Complete or update meningococcal vaccinations at least 2 weeks prior to first dose; other vaccinations may also be recommended.
Seek immediate medical attention if signs/symptoms of meningococcal infection are suspected.
Carry the Patient Safety Card at all times during therapy and for 11 months after stopping treatment.
Know the signs and symptoms of Type 3 hypersensitivity reactions; seek immediate medical attention if symptoms occur.
Seek immediate medical attention if symptoms of serious allergic reaction occur; infusion-related or systemic injection-related reactions may occur with administration.
Report any new signs and/or symptoms of infection to your health care provider.
Understand that breastfeeding is not recommended during treatment and for 9 months after the final dose.