Boxed WARNING: Serious Meningococcal Infections
PIASKY increases the risk of serious and life-threatening infections caused by Neisseria meningitidis.
- Complete or update meningococcal vaccination at least 2 weeks prior to the first dose of PIASKY, unless the risks of delaying PIASKY outweigh the risks of developing a serious infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccination in patients receiving a complement inhibitor.
- Patients are at increased risk for invasive disease caused by Neisseria meningitidis even if they develop antibodies following vaccination. Monitor patients for early signs of serious meningococcal infections and evaluate immediately if infection is suspected.
PIASKY is available only through a restricted program under a Risk Evaluation and Mitigation Strategy called the PIASKY REMS.
Contraindications
- For initiation in patients with an unresolved serious Neisseria meningitidis infection.
- Patients with a known serious hypersensitivity to crovalimab or any of the excipients.
Warnings and Precautions
Serious Meningococcal Infection
PIASKY increases a patient’s susceptibility to serious, life threatening, or fatal meningococcal infections (meningococcemia/or meningitis) in any serogroup, including non-groupable strains. Life threatening or 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 least 2 weeks prior to administration of the first dose of PIASKY according to the current Advisory Committee on Immunization Practices (ACIP) recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of PIASKY therapy.
If urgent therapy with PIASKY is indicated in a patient who is not up to date with meningococcal vaccine, provide the patient with prophylactic antibiotics and administer meningococcal vaccines as soon as possible.
Vaccination may not be sufficient to prevent meningococcal infection. Closely monitor patients for early signs of meningococcal infection and evaluate patients immediately if infection is suspected. Promptly treat known infections. Inform patients to seek immediate medical care if signs and symptoms occur. Consider interruption of PIASKY in patients for serious meningococcal infection.
PIASKY REMS
Due to the increased risk of serious meningococcal infections, PIASKY is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the PIASKY REMS. Under PIASKY REMS, healthcare providers must enroll in the program.
Healthcare providers must counsel patients about the risk of serious meningococcal infections, provide the patients with the REMS educational materials, ensure that patients are vaccinated with meningococcal vaccines and provide the patient with antibiotic prophylaxis if PIASKY must be started urgently, and the patient is not up to date with both meningococcal vaccines at least 2 weeks prior to the first dose of PIASKY. Patients must be instructed to carry the Patient Safety Card with them at all times during and for 11 months following treatment with PIASKY. Enrollment in the PIASKY REMS and additional information are available by telephone: 1-866-4My-Skyy (469-7599) or at www.PIASKYREMS.com.
Type III Hypersensitivity Reactions Related to Drug-Target-Drug Complexes
Patients who are switching from another C5 inhibitor ( e.g. eculizumab or ravulizumab) to PIASKY or from PIASKY to another C5 inhibitor are at risk of serious Type III hypersensitivity reactions related to the formation of drug-target-drug-complexes (DTDCs), because PIASKY and the other C5 inhibitors bind different epitopes of C5. In clinical trials, Type III Hypersensitivity reactions were reported in 39 out of 201 patients (19%) who switched from eculizumab or ravulizumab to PIASKY. Four of these patients (10%) had not fully recovered from symptoms of Type III hypersensitivity reactions at the time of their last follow up visit. In addition, Type III hypersensitivity reactions were reported in 2 of 8 patients (25%) who switched from PIASKY to eculizumab or ravulizumab, including one patient who developed Grade 3 axonal neuropathy.
Symptoms of Type III hypersensitivity reactions that occurred in more than 2 patients were arthralgia, rash, pyrexia, myalgia, headache, fatigue, petechiae and abdominal pain. Among patients who experienced Type III hypersensitivity reactions, 8 (21%) had events that were considered serious due to hospitalization. Symptoms of serious Type III hypersensitivity reactions included pyrexia and arthralgia. Type III hypersensitivity reactions can also cause renal abnormalities.
Healthcare providers should consider the benefits of the timing of switching C5 inhibitors vs. the risks of Type III hypersensitivity reactions. Patients are expected to no longer be at risk of Type III hypersensitivity reactions if the prior C5 inhibitor has been cleared from the body prior to starting PIASKY or if PIASKY has been cleared from the body prior to starting another C5 inhibitor. Therefore, initiating PIASKY sooner than 5.5 half-lives from the last dose of a C5 inhibitor (e.g., eculizumab or ravulizumab) or initiating a C5 inhibitor (e.g., eculizumab or ravulizumab) sooner than 5.5 half-lives from the last dose of PIASKY increases the risk of Type III hypersensitivity reactions.
Based on time-to-onset of Type III hypersensitivity reactions observed in clinical trials, patients should be monitored for the first 30 days of the new therapy for the occurrence of symptoms of Type III hypersensitivity reactions. 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 corticosteroid therapy as clinically indicated.
Other infections
PIASKY may increase susceptibility to infections, especially with encapsulated bacteria, such as infections with Neisseria spp. but also Streptococcus pneumoniae, Haemophilus influenzae, and to a lesser extent, Neisseria gonorrhoeae. Children treated with PIASKY may be at increased risk of developing serious infections due to Streptococcus pneumoniae and Haemophilus influenzae type b (Hib). Vaccinate patients against Streptococcus pneumoniae and Haemophilus influenzae type b (Hib) infections according to ACIP recommendations. If PIASKY is administered to patients with active systemic infections, monitor closely for signs and symptoms of worsening infection. If the patient’s infection worsens, consider whether to discontinue PIASKY.
Infusion- and Injection-Related Reactions
Administration of PIASKY may cause infusion-related reactions or systemic injection-related reactions, depending on the route of administration. These may include hypersensitivity reactions (including anaphylaxis) but also a range of other symptoms such as injection site pain, erythema, headache or myalgia.
If a serious hypersensitivity reaction occurs, discontinue PIASKY treatment immediately and institute appropriate treatment, per standard of care.
Monitoring PNH Manifestations after Discontinuation of PIASKY
In case of PIASKY discontinuation, patients who do not switch to another treatment for PNH, must be closely monitored for at least 20 weeks for signs and symptoms of serious hemolysis, identified by elevated lactate dehydrogenase (LDH) levels, along with a sudden decrease in hemoglobin, or re-appearance of symptoms such as fatigue, hemoglobinuria, abdominal pain, dyspnea, major adverse vascular events (including thrombosis), dysphagia, erectile dysfunction or renal impairment.
If signs and symptoms of hemolysis occur after discontinuation of PIASKY, consider restarting treatment with PIASKY, if appropriate, or initiating another treatment for PNH.
Most Common Adverse Reactions
The most common adverse drug reactions (incidence ≥10%) were infusion-related reactions, respiratory tract infection, viral infection, and Type III hypersensitivity reactions.
You may report side effects to the FDA at (800) FDA-1088 or www.fda.gov/medwatch. You may also report side effects to Genentech at (888) 835-2555.
Please see the full Prescribing Information for additional Important Safety Information, including Boxed WARNING.
