Piasky (crovalimab-akkz)

No dosing information is available for this tab.

Crovalimab-akkz is administered as an IV infusion for the first dose and as a subcutaneous injection for subsequent doses. Crovalimab-akkz should only be administered by a healthcare provider.

Each carton of crovalimab-akkz contains a 340 mg/2 mL (170 mg/mL) single-dose vial. Each vial of crovalimab-akkz is for 1-time use in a single patient.

Store crovalimab-akkz vials at 2-8degreesC in the original carton to protect from light. Do not freeze or shake. Once removed from refrigeration, unopened vials may be kept in their original carton at room temperature (<=30degreesC) for <=7 days. Prior to administration, unopened vials may be stored at room temperature if needed and then returned to refrigeration; the total combined time out of refrigeration should not exceed 7 days and the temperature should not exceed 30degreesC. If stored at room temperature for >7 days, discard the vials.

No dosing information is available for this tab.

No dosing information is available for this tab.

Crovalimab-akkz is expected to undergo metabolism via lysosomal proteolysis into small peptides and amino acids.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Crovalimab/C5 Complement Inhibitors

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Crovalimab is a complement C5 inhibitor which binds to epitopes on C5. Other complement C5 inhibitors such as eculizumab and ravulizumab bind to different epitopes on C5. Use of multiple complement inhibitors may lead to formation of drug-target-drug complexes (DTDCs) which may increase the risk of serious type III hypersensitivity reactions.(1)

CLINICAL EFFECTS: Use of multiple complement inhibitors may lead to formation of drug-target-drug complexes (DTDCs) which may increase the risk of serious type III hypersensitivity reactions. Type III hypersensitivity reactions can present as vasculitis, serum sickness, lymphadenopathy with arthralgias, rheumatoid arthritis, or glomerulonephritis.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of crovalimab states caution is advised when switching patients between other complement C5 inhibitors such as eculizumab or ravulizumab. The formation of drug-target-drug complexes (DTDCs) can occur when switching therapies. DTDCs are expected to be cleared within approximately 8 weeks (with eculizumab) or longer (with ravulizumab). Consider the risks and benefits of the timing of switching therapies with the risk of type III hypersensitivity reactions.(1) Monitor patients closely for signs of type III hypersensitivity reactions.(1) If patients develop a hypersensitivity reaction, for mild or moderate Type III hypersensitivity reactions, administer symptomatic treatment, such as topical corticosteroids, antihistamines, antipyretics, and/or analgesics. For severe reactions, initiate and taper oral or systemic corticosteroids therapy as clinically indicated.(1)

DISCUSSION: Clinical drug interaction studies with crovalimab have not been performed. Use of multiple complement inhibitors may lead to formation of drug-target-drug complexes (DTDCs) which may increase the risk of serious type III hypersensitivity reactions.(1) In clinical trials, type III hypersensitivity reactions were reported in 19% of patients who switched from eculizumab or ravulizumab to crovalimab. Also, type III hypersensitivity reactions were documented in 25% of patients who switched from crovalimab to either eculizumab or ravulizumab.(1)

Igg Antibodies And Derivatives/Efgartigimod-Alfa

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Efgartigimod-alfa binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of efgartigimod-alfa states that efgartigimod-alfa should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, efgartigimod-alfa should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with efgartigimod-alfa have not been performed. Efgartigimod-alfa may decrease concentrations of compounds that bind to the human FcRn.(3)

Igg Antibodies And Derivatives/Nipocalimab-Aahu

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Nipocalimab-aahu binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medicines that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of nipocalimab-aahu states that nipocalimab-aahu should not be combined with long-term use of FcRn-binding medications. If the medication is essential for the patient, nipocalimab-aahu should be discontinued.(3)

DISCUSSION: Clinical drug interaction studies with nipocalimab-aahu have not been performed. Nipocalimab-aahu may decrease concentrations of compounds that bind to the human FcRn.(3)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Igg Antibodies And Derivatives/Rozanolixizumab-Noli

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: The neonatal Fc receptor (FcRn) prevents catabolism and mediates recycling of IgG and albumin, which leads to their long persistence in the body.(1,2) Rozanolixizumab-noli binds to FcRn and may decrease systemic exposure of other ligands of FcRn, like immunoglobulins and IgG-based antibodies.(3)

CLINICAL EFFECTS: The effectiveness of medications that bind to FcRn may be decreased.(3)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of rozanolixizumab-noli states that concurrent use with medications that bind to the human neonatal Fc receptor (FcRn) should be closely monitored for reduced effectiveness of these medications. If long-term use of such medications is essential for the patient, consider discontinuing rozanolixizumab-noli and use alternative therapies.(3)

DISCUSSION: Clinical drug interaction studies with rozanolixizumab-noli have not been performed. Rozanolixizumab-noli may decrease concentrations of compounds that bind to the human FcRn.(3)

*Initiation in patients with unresolved serious Neisseria meningitidis infection.

*Known serious hypersensitivity to crovalimab-akkz or any ingredient in the formulation.

• Lactation
• Meningococcal meningitis
• Meningococcemia

• Infection

There are no moderate contraindications for this drug.

Adverse effects reported in >=10% of patients receiving crovalimab-akkz include infusion-related reactions, respiratory tract infections, viral infections, and type III hypersensitivity reactions.

More Frequent

• Hypersensitivity drug reaction
• Upper respiratory infection
• Viral infection

Rare or Very Rare

• Meningitis
• Peripheral demyelinating neuropathy

Less Frequent

• Acute abdominal pain
• Arthralgia
• Diarrhea
• Fatigue
• Fever
• Headache disorder
• Hyperuricemia
• Infection
• Myalgia
• Nausea
• Peripheral edema
• Petechiae
• Skin rash

No enhanced messaging available.

Safety and efficacy of crovalimab-akkz for the treatment of PNH have been established in pediatric patients >=13 years of age with a body weight >=40 kg. Use of crovalimab for this indication is supported by evidence from adequate and well-controlled clinical trials conducted in adults with additional pharmacokinetic, pharmacodynamic, efficacy, and safety data in pediatric patients 13-17 years of age.

Safety and efficacy of crovalimab-akkz have not been established in pediatric patients <13 years of age and in those weighing <40 kg.

Exposure to crovalimab-akkz in pediatric patients with PNH weighing >=40 kg was similar to that of adult patients.

Available data on crovalimab-akkz use during pregnancy are insufficient to evaluate for a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. Human immunoglobulin G (IgG) antibody crosses the placenta and its transport increases as pregnancy progresses, peaking during the third trimester. Because of this, it is possible that crovalimab-akkz may be transmitted from the mother to the developing fetus.

Untreated PNH in pregnancy is associated with risks to the mother and fetus; adverse maternal outcomes included worsening cytopenias, thrombosis, infections, bleeding, miscarriages, and increased maternal mortality, and adverse fetal outcomes included fetal death and preterm delivery.

In an enhanced pre- and postnatal development study, no adverse developmental outcomes were detected at 6 months of follow-up in monkeys who received crovalimab-akkz during the period of organogenesis through delivery at maternal exposures 14 times the human exposure at the maximum recommended human dose.

No data are available on the presence of crovalimab-akkz in human or animal milk; however, endogenous IgG and monoclonal antibodies are transferred into human milk. The effects of crovalimab-akkz on the breast-fed child or on milk production are unknown. The effects of local GI exposure to crovalimab-akkz and limited systemic exposure in the breast-fed child are unknown.

Because of the potential for serious adverse reactions in a breast-fed child, advise patients to avoid breast-feeding during treatment and for 9 months following the final dose of crovalimab-akkz.

The manufacturer makes no specific dosage recommendations for geriatric patients. However, dosage of crovalimab-akkz should be selected with caution in geriatric patients because of age-related decreases in hepatic, renal, and/or cardiac function and greater frequency of concomitant disease or other drug therapy.

Clinical studies of crovalimab-akkz did not include sufficient numbers of patients >=65 years of age to assess differences in response compared to younger adults. In general, dosage of crovalimab-akkz should be selected with caution in geriatric patients because of age-related decreases in hepatic, renal and/or cardiac function and greater frequency of concomitant disease or other drug therapy.

In the COMMODORE 1, 2, and 3 studies, 10.9% of patients who received crovalimab-akkz were >=65 years of age. In complement inhibitor-naive patients, serious adverse reactions were reported in 8% of patients >=65 years of age compared to 4% of patients 18-64 years of age. In patients being switched to crovalimab-akkz from another C5 inhibitor, serious adverse reactions were reported in 7% of patients >=65 years of age compared to 4% of patients 18-64 years of age.