Crovalimab

Crovalimab is a prescription medication indicated for the treatment of adult and pediatric patients 13 years and older with paroxysmal nocturnal hemoglobinuria (PNH) and body weight of at least 40 kg.

• Crovalimab is available under the following different brand names: Piasky, crovalimab-akkz.

Common side effects of Crovalimab include:

• infusion-related reactions 
• viral infections 
• respiratory tract infections including infections of the lungs
• Type III hypersensitivity reactions 
• cold symptoms
• pain or swelling of the nose or throat

Serious side effects of Crovalimab include:

• meningococcal infection: symptoms such as fever, headache with a stiff neck or stiff back, rash, confusion, high heart rate, muscle aches, with flu-like symptoms, headache, eyes sensitive to light, and nausea or vomiting
• Type III hypersensitivity reactions: symptoms such as joint pain, numbness and tingling or a feeling of pins and needles, muscle or bone pain especially of the hands and feet, rash or skin problems, fever, itching, weakness, tiredness, or lack of energy, headache, stomach trouble or pain, and kidney problems
• serious infections caused by encapsulated bacteria, including infections caused by Neisseria spp., Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria gonorrhoeae

Rare side effects of Crovalimab include:

• none 

Seek medical care or call 911 at once if you have the following serious side effects:

• Severe headache, confusion, slurred speech, arm or leg weakness, trouble walking, coordination loss, unsteady, very stiff muscles, high fever, profuse sweating, or tremors.
• Serious eye symptoms such as sudden vision loss, blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.
• Serious heart symptoms include fast, irregular, or pounding heartbeats; fluttering in the chest; shortness of breath; sudden dizziness, lightheadedness, or passing out.

This is not a complete list of side effects and other serious side effects or health problems that may occur because of the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may report side effects or health problems to FDA at 1-800-FDA-1088.

Adult and pediatric dosage

Injection, solution

• 340 mg/2 mL single-dose vial

Paroxysmal nocturnal hemoglobinuria

Adult and pediatric dosage

• The dosing schedule is allowed to occasionally vary within 2 days of the scheduled administration day (except at Day 1 and Day 2); if this occurs, subsequent doses should be administered according to a regular schedule

Modification of maintenance dose is required if body weight changes to become consistently greater than or lower than 100 kg during therapy

• More than or equal to 40 kg to less than 100 kg
• Loading dose
  • Day 1: 1,000 mg IV
  • Days 2, 8, 15, 22: 340 mg SC
• Maintenance dose
  • Day 29: 680 mg SC and every 4 weeks thereafter
  • More than or equal to 100 kg
• Loading dose
  • Day 1: 1,500 mg IV
  • Days 2, 8, 15, 22: 340 mg SC
• Maintenance dose
• Day 29: 1,020 mg SC and every 4 weeks thereafter
• Switching from another complement inhibitor
• Consider the benefits of timing the switch from C5 inhibitors versus the risks of Type III hypersensitivity reactions
• For patients switching from another C5 inhibitor (eg, eculizumab, ravulizumab), the first crovalimab IV loading dose should be administered no sooner than the time of the next scheduled complement inhibitor administration
• Administration of additional SC loading doses and maintenance doses should follow as described above

Dosage Considerations – Should be Given as Follows: 

• See “Dosages”

If your medical doctor is using this medicine to treat your pain, your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor, health care provider, or pharmacist first.

• Crovalimab has severe interactions with no other drugs
• Crovalimab has serious interactions with no other drugs
• Crovalimab has moderate interactions with no other drugs
• Crovalimab has minor interactions with no other drugs

This information does not contain all possible interactions or adverse effects. Visit the RxList Drug Interaction Checker for any drug interactions. Therefore, before using this product, tell your doctor or pharmacist about all the products you use. Keep a list of all your medications with you and share this information with your doctor and pharmacist. Check with your healthcare professional or doctor for additional medical advice, health questions, or concerns.

Contraindications

• Unresolved serious Neisseria meningitidis infection
• Known serious hypersensitivity reaction to crovalimab or its excipients

Effects of drug abuse

• None

Short-Term Effects

• See “What Are Side Effects Associated with Using Crovalimab?”

Long-Term Effects

• See “What Are Side Effects Associated with Using Crovalimab?”

Cautions

• Meningococcal infection
  • Increases susceptibility to serious, life-threatening, or fatal infections caused by meningococcal bacteria (meningococcemia and/or meningitis) in any serogroup, including non-groupable strains
  • Life-threatening and fatal meningococcal infections have occurred in both vaccinated and unvaccinated patients treated with complement inhibitors
  • Complete or update meningococcal vaccination (for serogroups A, C, W, Y, and B) at 2 weeks before initiating; revaccinate according to ACIP recommendations
  • If urgent therapy is indicated, prescribe antibacterial prophylaxis and administer vaccine(s) as soon as possible
  • Consider benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, against known risks for serious infections caused by N meningitidis
  • Vaccination does not eliminate the risk of meningococcal infection, despite the development of antibodies
• REMS
  • Owing to the risk of serious meningococcal infections available only through a restricted program under a REMS 
• Prescribers must
  • Assess patient vaccination status for meningococcal vaccines and vaccinate if needed 2 weeks before initiating Crovalimab
  • Provide a prescription for antibacterial drug prophylaxis if treatment must be started urgently, and the patient is not current with both meningococcal vaccines
• Healthcare settings and pharmacies
  • Must be certified in the REMS and must verify prescribers are certified
• Patients must
  • Receive counseling from the prescriber regarding the need to receive meningococcal vaccines, to take antibiotics as directed by the prescriber, and to look for signs and symptoms of meningococcal infection
  • Carry the Patient Safety Card with them at all times during and for 11 months following treatment
• Type III hypersensitivity reactions
  • Patients who are switching from another C5 inhibitor (eg, eculizumab or ravulizumab) to crovalimab or vice versa are at risk of serious Type III hypersensitivity reactions
  • This reaction is related to formation of drug-target-drug-complexes (DTDCs), because crovalimab and these other C5 inhibitors bind different epitopes of C5
  • Symptoms may include arthralgia, rash, pyrexia, myalgia, headache, fatigue, petechiae, and abdominal pain
  • Carefully consider timing of switching from other C5 inhibitors; allow at least 5.5 half-lives from the last dose of a C5 inhibitor before initiating another C5 inhibitor
• Other infections
  • Owing to its mechanism of action, may increase susceptibility to infection, especially with encapsulated bacteria, eg, Neisseria spp. but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae
  • Children may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib); vaccinate patients against these infections according to ACIP recommendations
• Infusion- and injection-related reactions
  • Reactions following IV or SC administration may include hypersensitivity reactions (including anaphylaxis), injection site pain, erythema, headache, or myalgia
  • Discontinue if serious hypersensitivity reactions occur and institute appropriate treatment
• Monitoring following discontinuation
  • Monitor closely for at least 20 weeks for signs and symptoms of serious hemolysis if discontinued and the patient is not switched to another treatment for PNH
  • Signs and symptoms include elevated lactate dehydrogenase (LDH) levels and sudden decrease in hemoglobin, or reappearance of symptoms (eg, fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events [including thrombosis], dysphagia, erectile dysfunction, or renal impairment)
  • If sign and symptoms occur, consider restarting treatment, if appropriate, or initiating another treatment for PNH
• Drug interaction overview
  • Formation of DTDCs and Type IIII hypersensitivity
• Caution/monitor
  • Crovalimab binds different epitopes on C5 compared to eculizumab and ravulizumab, which can lead to the formation of DTDCs when patients switch between crovalimab and either eculizumab or ravulizumab
  • DTDCs comprise more than 1 unit of C5 bound to both crovalimab and to eculizumab or ravulizumab
  • DTDCs are expected to be cleared within approximately 8 weeks (in the case of eculizumab) or longer (in the case of ravulizumab) and can result in Type III hypersensitivity reactions

Pregnancy and Lactation

• Available data regarding use in pregnant women are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes
• Human IgG antibody is known to cross the placenta and its transport increases as pregnancy progresses and peaks during the third trimester; therefore, crovalimab may be transmitted from mother to developing fetus
• Clinical considerations
• PNH in pregnancy is associated with adverse maternal outcomes, including worsening cytopenias, thrombosis, infections, bleeding, miscarriages, and increased maternal mortality, and adverse fetal outcomes, including fetal death and premature delivery
• Lactation
  • Data are not available regarding the presence of crovalimab in either human or animal milk, its effects on breastfed children, or on milk production
  • Endogenous IgG and monoclonal antibodies are transferred in human milk
  • Effects of local gastrointestinal exposure and limited systemic exposure in breastfed children to crovalimab are unknown
  • Because of the potential for serious adverse reactions in a breastfed child, advise patients that breastfeeding is not recommended during treatment and for 9 months after the final dose