Version May 2024
Life-threatening and fatal meningococcal infections have occurred in patients treated with complement inhibitors; zilucoplan is a complement inhibitor. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Complete or update meningococcal vaccination (for serogroups A, C, W, and Y, and serogroup B) at least 2 weeks prior to administering the first dose of zilucoplan, unless the risk of delaying therapy outweighs the risk of developing a meningococcal infection. Comply with the most current Advisory Committee on Immunization Practices (ACIP) recommendations for meningococcal vaccinations in patients receiving a complement inhibitor. Persons receiving zilucoplan are at increased risk for invasive disease caused by Neisseria meningitidis, even if they develop antibodies following vaccination. Monitor patients for signs of meningococcal infections and evaluate immediately if infection is suspected.
Because of the risk of serious meningococcal infections, zilucoplan is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called ZILBRYSQ REMS.
Myasthenia gravis, generalized (alternative agent):
Note: Safety: Vaccinate with meningococcal vaccine (serogroups A, C, W, and Y and serogroup B) at least 2 weeks prior to treatment initiation; revaccinate as appropriate according to current guidelines. If urgent zilucoplan initiation is necessary and <2 weeks after vaccination, provide at least 2 weeks antibacterial prophylaxis (Ref). Use: For use in patients with anti-acetylcholine receptor (AChR) antibody–positive myasthenia gravis as monotherapy, as bridge therapy to slower-acting agents, or in combination with glucocorticoids in patients with glucocorticoid-resistant or glucocorticoid-dependent disease (Ref).
SUBQ: Dose according to actual body weight (see table below) once daily. Administer at approximately the same time each day.
|
Actual body weight |
Zilucoplan dose |
|---|---|
|
<56 kg |
16.6 mg SUBQ once daily |
|
≥56 to <77 kg |
23 mg SUBQ once daily |
|
≥77 kg |
32.4 mg SUBQ once daily |
Missed dose: Administer missed dose as soon as possible and resume dosing as scheduled; do not administer >1 dose per day.
Dosage adjustment for concomitant therapy: Significant drug interactions exist, requiring dose/frequency adjustment or avoidance. Consult drug interactions database for more information.
No dosage adjustment necessary.
Mild to moderate impairment (Child-Turcotte-Pugh class A and B) : No dosage adjustment necessary.
Severe impairment (Child-Turcotte-Pugh class C): There are no dosage adjustments provided in the manufacturer’s labeling (has not been studied).
Meningococcal infection: Withhold zilucoplan therapy in patients undergoing meningococcal infection treatment until infection is resolved.
Pancreatitis, suspected: Withhold zilucoplan therapy until pancreatitis is resolved or ruled out.
Refer to adult dosing.
The following adverse drug reactions and incidences are derived from product labeling unless otherwise specified. Reported adverse reactions are for adults.
>10%:
Gastrointestinal: Diarrhea (11%)
Local: Injection-site reaction (29%)
Respiratory: Upper respiratory tract infection (14%)
1% to 10%:
Gastrointestinal: Increased serum amylase (5%), increased serum lipase (7%), nausea (≤8%), pancreatic disease (cyst: 1%), pancreatitis (2%), vomiting (≤8%)
Genitourinary: Urinary tract infection (8%)
Immunologic: Antibody development (anti-drug antibodies: 2%; anti-polyethylene glycol antibodies: 9%)
Frequency not defined:
Hematologic & oncologic: Eosinophilia
Infection: Meningococcal infection
Unresolved Neisseria meningitidis infection.
Concerns related to adverse effects:
• Infection: Zilucoplan blocks terminal complement activation and therefore may increase the risk for susceptibility to bacterial infections, especially encapsulated bacteria, such as infections caused by Neisseria meningitidis but also Streptococcus pneumoniae, Haemophilus influenzae, and, to a lesser extent, Neisseria gonorrhoeae. Vaccinate for S. pneumoniae and H. influenzae type b (Hib) according to the Advisory Committee on Immunization Practices (ACIP) guidelines.
• Meningococcal infection: The use of zilucoplan increases susceptibility to serious meningococcal infections (septicemia and/or meningitis). Meningococcal disease due to any serogroup may occur. Complete or update meningococcal vaccination (for serogroups A, C, W, and Y, and serogroup B) at least 2 weeks prior to administering the first dose of zilucoplan, unless the risk of delaying therapy outweighs the risk of developing a meningococcal infection. If urgent zilucoplan therapy is indicated in an unvaccinated patient, administer meningococcal vaccine(s) as soon as possible and provide at least 2 weeks of antibacterial prophylaxis (Mbaeyi 2020). To reduce the risk for meningococcal disease, consider antimicrobial prophylaxis with oral antibiotics (penicillin, or macrolides if allergic to penicillin) for the duration of zilucoplan therapy (Mbaeyi 2020; McNamara 2017). Educate patients on signs/symptoms of meningitis and steps necessary to seek immediate medical care. Revaccinate for meningococcal disease according to ACIP recommendations for meningococcal vaccinations in patients receiving a complement inhibitor, taking the duration of zilucoplan therapy into consideration.
• Pancreatitis and other pancreatic disease: Pancreatitis and pancreatic cysts may occur in addition to increased lipase and amylase. Monitor lipase and amylase serum concentrations.
Other warnings/precautions:
• REMS program: Counsel patients about the risk of meningococcal infection, provide REMS educational materials to patients, and ensure patients are vaccinated with meningococcal vaccines. Additional information is available at www.ZILBRYSQREMS.com or 1-877-414-8353.
Zilbrysq: FDA approved October 2023; anticipated availability is currently unknown.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution Prefilled Syringe, Subcutaneous, as sodium:
Zilbrysq: 16.6 mg/0.416 mL (0.416 mL); 23 mg/0.574 mL (0.574 mL); 32.4 mg/0.81 mL (0.81 mL)
No
Solution Prefilled Syringe (Zilbrysq Subcutaneous)
16.6MG/0.416ML (per 0.416 mL): $907.20
23MG/0.574ML (per 0.574 mL): $1,256.40
32.4MG/0.81ML (per 0.81 mL): $1,770.00
Disclaimer: A representative AWP (Average Wholesale Price) price or price range is provided as reference price only. A range is provided when more than one manufacturer's AWP price is available and uses the low and high price reported by the manufacturers to determine the range. The pricing data should be used for benchmarking purposes only, and as such should not be used alone to set or adjudicate any prices for reimbursement or purchasing functions or considered to be an exact price for a single product and/or manufacturer. Medi-Span expressly disclaims all warranties of any kind or nature, whether express or implied, and assumes no liability with respect to accuracy of price or price range data published in its solutions. In no event shall Medi-Span be liable for special, indirect, incidental, or consequential damages arising from use of price or price range data. Pricing data is updated monthly.
SUBQ: Administer at approximately the same time each day. Allow refrigerated prefilled syringe to reach room temperature prior to administration. Choose an injection site on abdomen (≥2 inches from the naval), thighs, or back of upper arm, avoiding areas with stretch marks or scars, or where skin is tender, red, bruised, or hard; rotate injection sites for subsequent injections. Do not attempt to remove air bubbles from prefilled syringe. Inject full contents of the prefilled syringe; discard after use. Prefilled syringes may be self-injected by the patient or caregiver following proper training in SUBQ injection technique.
This medication is not on the NIOSH (2016) list; however, it may meet the criteria for a hazardous drug. Zilucoplan may cause developmental toxicity and reproductive toxicity.
Use appropriate precautions for receiving, handling, storage, preparation, dispensing, transporting, administration, and disposal. Follow NIOSH and USP 800 recommendations and institution-specific policies/procedures for appropriate containment strategy (NIOSH 2016; USP-NF 2020).
Note: Facilities may perform risk assessment of some hazardous drugs to determine if appropriate for alternative handling and containment strategies (USP-NF 2020). Refer to institution-specific handling policies/procedures.
An FDA-approved patient medication guide, which is available with the product information and as follows, must be dispensed with this medication:
Zilbrysq: https://www.accessdata.fda.gov/drugsatfda_docs/label/2023/216834s000lbl.pdf#page=20
Myasthenia gravis, generalized: Treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) antibody positive.
None known.
Note: Interacting drugs may not be individually listed below if they are part of a group interaction (eg, individual drugs within “CYP3A4 Inducers [Strong]” are NOT listed). For a complete list of drug interactions by individual drug name and detailed management recommendations, use the Lexicomp drug interactions program by clicking on the “Launch drug interactions program” link above.
Abrocitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Antithymocyte Globulin (Equine): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Antithymocyte Globulin (Equine). Specifically, these effects may be unmasked if the dose of immunosuppressive therapy is reduced. Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Antithymocyte Globulin (Equine). Specifically, infections may occur with greater severity and/or atypical presentations. Risk C: Monitor therapy
Baricitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Baricitinib. Risk X: Avoid combination
Brincidofovir: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Brincidofovir. Risk C: Monitor therapy
Brivudine: May enhance the adverse/toxic effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Cladribine: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Cladribine. Risk X: Avoid combination
Coccidioides immitis Skin Test: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the diagnostic effect of Coccidioides immitis Skin Test. Management: Consider discontinuing therapeutic immunosuppressants several weeks prior to coccidioides immitis skin antigen testing to increase the likelihood of accurate diagnostic results. Risk D: Consider therapy modification
Denosumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Denosumab. Management: Consider the risk of serious infections versus the potential benefits of coadministration of denosumab and immunosuppressants. If combined, monitor for signs/symptoms of serious infections. Risk D: Consider therapy modification
Deucravacitinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Etrasimod: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Filgotinib: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk X: Avoid combination
Inebilizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Inebilizumab. Risk C: Monitor therapy
Leflunomide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Leflunomide. Management: Increase the frequency of chronic monitoring of platelet, white blood cell count, and hemoglobin or hematocrit to monthly, instead of every 6 to 8 weeks, if leflunomide is coadministered with immunosuppressive agents. Risk D: Consider therapy modification
Nadofaragene Firadenovec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Nadofaragene Firadenovec. Specifically, the risk of disseminated adenovirus infection may be increased. Risk X: Avoid combination
Natalizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Natalizumab. Risk X: Avoid combination
Ocrelizumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ocrelizumab. Risk C: Monitor therapy
Ofatumumab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ofatumumab. Risk C: Monitor therapy
Pidotimod: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Pidotimod. Risk C: Monitor therapy
Pimecrolimus: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Pimecrolimus. Risk X: Avoid combination
Polymethylmethacrylate: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the potential for allergic or hypersensitivity reactions to Polymethylmethacrylate. Management: Use caution when considering use of bovine collagen-containing implants such as the polymethylmethacrylate-based Bellafill brand implant in patients who are receiving immunosuppressants. Consider use of additional skin tests prior to administration. Risk D: Consider therapy modification
Ritlecitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ritlecitinib. Risk X: Avoid combination
Ruxolitinib (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ruxolitinib (Topical). Risk X: Avoid combination
Sipuleucel-T: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Sipuleucel-T. Management: Consider reducing the dose or discontinuing the use of immunosuppressants prior to initiating sipuleucel-T therapy. Risk D: Consider therapy modification
Sphingosine 1-Phosphate (S1P) Receptor Modulator: May enhance the immunosuppressive effect of Immunosuppressants (Therapeutic Immunosuppressant Agents). Risk C: Monitor therapy
Tacrolimus (Topical): Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tacrolimus (Topical). Risk X: Avoid combination
Talimogene Laherparepvec: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the adverse/toxic effect of Talimogene Laherparepvec. Specifically, the risk of infection from the live, attenuated herpes simplex virus contained in talimogene laherparepvec may be increased. Risk X: Avoid combination
Tertomotide: Immunosuppressants (Therapeutic Immunosuppressant Agents) may diminish the therapeutic effect of Tertomotide. Risk X: Avoid combination
Tofacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Tofacitinib. Management: Coadministration of tofacitinib with potent immunosuppressants is not recommended. Use with non-biologic disease-modifying antirheumatic drugs (DMARDs) was permitted in psoriatic arthritis clinical trials. Risk X: Avoid combination
Ublituximab: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Ublituximab. Risk C: Monitor therapy
Upadacitinib: Immunosuppressants (Therapeutic Immunosuppressant Agents) may enhance the immunosuppressive effect of Upadacitinib. Risk X: Avoid combination
Based on a placental perfusion study, zilucoplan crosses the placenta.
Based on data from animal reproduction studies, in utero exposure to zilucoplan may cause fetal harm. Fetal death was observed following SUBQ doses to pregnant monkeys with doses equivalent to the 32.4 mg/day human dose.
Agents other than zilucoplan are currently recommended for the treatment of myasthenia gravis in pregnant patients (Sanders 2016).
It is not known if zilucoplan is present in breast milk.
According to the manufacturer, the decision to breastfeed during therapy should consider the risk of infant exposure, the benefits of breastfeeding to the infant, and the benefits of treatment to the mother.
Lipase and amylase (baseline).
Zilucoplan inhibits generation of terminal complement complex C5b-9 by binding to complement protein C5 with high affinity, inhibiting its cleavage to C5a and C5b, and binding preformed C5b, sterically preventing interaction with C6. The precise mechanism by which zilucoplan exerts its therapeutic effect in generalized myasthenia gravis is unknown but is presumed to involve reduction of terminal complement complex C5b-9 deposition at the neuromuscular junction.
Onset: As early as 1 week (Howard 2023).
Distribution: Vd: 3.51 L.
Protein binding: >99% (zilucoplan and metabolites).
Metabolism: Expected to be degraded into small peptides and amino acids via catabolic pathways. Active metabolite RA103488, formed via VYP450 4F2, is not expected to contribute significant pharmacological activity. Metabolite RA102758, formed via protease-mediated degradation, is inactive.
Half-life elimination: ~172 hours.
Time to peak: 3 to 6 hours.
Excretion: Urine and feces: <1% (zilucoplan and metabolite).
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