Zilucoplan

Q: Is Zilucoplan available over the counter?

Zilucoplan is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

Prescription

상품명: ZILBRYSQ

제형

Injection

투여 경로

SUBCUTANEOUS

제조사

UCB, Inc.

About This Medication

11 DESCRIPTION Zilucoplan, a complement inhibitor, is a 15 amino-acid, synthetic macrocyclic peptide. The molecular formula of zilucoplan is C 172 H 278 N 24 O 55 in free acid form and its molecular weight is 3562.23 Daltons (free acid form). The chemical name for zilucoplan sodium is: acetyl‐[L-lysyl 1 -L-valyl 2 -L-glutamyl 3 -L-arginyl 4 -L phenylalanyl 5 -L aspartyl 6 ]- N -methyl L-aspartyl 7 -L tert-leucyl 8 -L tyrosyl 9 -L-7-azatryptophyl 10 -L glutamyl 11 -L-tyrosyl 12 -L prolyl 13 -L cyclohexylglycyl 14 -[L-lysyl 15 , N ε -palmitoyl-γ-L-glutamyl-(1-amino-3,6,9,12,15,18,21,24,27,30,33,36,39,42,45,48,51,54,57,60,63,66,69,72-tetracosaoxapentaheptacontan-75-oyl)], cyclic (Lactam 1-6), tetra sodium. The primary structure for zilucoplan sodium is shown below: ZILBRYSQ injection is a sterile, clear to slightly opalescent, colorless, preservative-free, buffered solution of zilucoplan (as zilucoplan sodium) for subcutaneous injection, in single-dose prefilled syringes. The solution pH is between 6.5 and 7.5. ZILBRYSQ is supplied in three dose strengths containing 16.6 mg /0.416 mL, 23 mg /0.574 mL, and 32.4 mg/0.81 mL of zilucoplan free acid equivalent to 17 mg, 23.6 mg, and 33.2 mg of zilucoplan sodium, respectively. Additionally, each mL of the solution contains dibasic sodium phosphate, anhydrous (4.11 mg); monobasic sodium phosphate, monohydrate (2.9 mg); sodium chloride (4.42 mg); and water for injection. Chemical Structure

유효 성분

성분	함량
Zilucoplan	-

적응증 및 용법

1 INDICATIONS AND USAGE ZILBRYSQ is indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. ZILBRYSQ is a complement inhibitor indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. ( 1 )

작용 원리

12.1 Mechanism of Action Zilucoplan binds to the complement protein C5 and inhibits its cleavage to C5a and C5b, preventing the generation of the terminal complement complex, C5b-9. The precise mechanism by which zilucoplan exerts its therapeutic effect in generalized myasthenia gravis is unknown but is presumed to involve reduction of C5b-9 deposition at the neuromuscular junction.

용량 및 투여 방법

2 DOSAGE AND ADMINISTRATION Obtain baseline amylase and lipase. ( 2.2 ) For subcutaneous injection only. ( 2.3 ) Recommended dosage ( 2.3 ): Body Weight Once Daily Dosage Plunger Rod Color of Prefilled Syringe Less than 56 kg 16.6 mg RUBINE RED 56 kg to less than 77 kg 23 mg ORANGE 77 kg and above 32.4 mg DARK BLUE See Full Prescribing Information for instructions on dosage, preparation, and administration. ( 2.4 , 2.5 ) 2.1 Recommended Vaccination and Prophylaxis for Meningococcal Infection Vaccinate patients against meningococcal infection (serogroups A, C, W, Y, and B) according to current ACIP recommendations at least 2 weeks prior to initiation of ZILBRYSQ [see Warnings and Precautions (5.1) ] . If urgent ZILBRYSQ therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer these vaccines as soon as possible [see Warnings and Precautions (5.1) ] . Healthcare providers who prescribe ZILBRYSQ must enroll in the ZILBRYSQ REMS [see Warnings and Precautions (5.2) ] . 2.2 Recommended Testing Before Initiating ZILBRYSQ Before initiating ZILBRYSQ, obtain baseline lipase and amylase levels [see Warnings and Precautions (5.4) ] . 2.3 Recommended Dosage The recommended dosage of ZILBRYSQ is given once daily as a subcutaneous injection and is dependent on actual body weight (see Table 1 ). Table 1: Total Daily Dosage by Body Weight Range Body Weight Once Daily Dosage Plunger Rod Color of Prefilled Syringe Less than 56 kg 16.6 mg RUBINE RED 56 kg to less than 77 kg 23 mg ORANGE 77 kg and above 32.4 mg DARK BLUE 2.4 Preparation Instructions ZILBRYSQ prefilled syringes can be stored in a refrigerator in the original carton. ZILBRYSQ can also be stored at room temperature in the original carton for up to 3 months or until the expiration date, whichever occurs first. If stored in the refrigerator: Before injecting, take 1 ZILBRYSQ prefilled syringe out of the refrigerator and place it on a clean, flat surface. Allow ZILBRYSQ to reach room temperature out of direct sunlight (30 to 45 minutes). Do not heat or place in microwave. Immediately return the carton with the other prefilled syringes to the refrigerator. If stored at room temperature: Remove 1 ZILBRYSQ prefilled syringe from the carton. Do not return ZILBRYSQ to the refrigerator after it has been stored at room temperature. Visually inspect ZILBRYSQ for particulate matter and discoloration prior to administration. ZILBRYSQ is a clear to slightly opalescent, colorless solution. Do not use if the solution contains visible particles, is cloudy, or if foreign particulate matter is present. ZILBRYSQ does not contain preservatives; unused portions of drug remaining in the syringe should be discarded. Each prefilled syringe is single-dose only. 2.5 Administration Instructions ZILBRYSQ is intended for use under the guidance and supervision of a healthcare professional. Patients may self-inject ZILBRYSQ after training in subcutaneous injection technique. Provide proper training to patients and/or caregivers on the subcutaneous injection technique of ZILBRYSQ according to the "Instructions for Use" [see Instructions for Use ] . Administer ZILBRYSQ subcutaneously into areas of the abdomen, thighs, or back of the upper arms that are not tender, bruised, red, or hard. Avoid injecting into areas with scars or stretch marks. Rotate injection sites for each administration. Administration of ZILBRYSQ in the upper, outer arm should be performed by a caregiver. When using ZILBRYSQ prefilled syringes, inject the full contents of the single-dose prefilled syringe. Discard ZILBRYSQ prefilled syringe after use. Do not reuse. Instruct the patient that the daily dose should be administered at approximately the same time each day. If a dose is missed, administer the dose as soon as possible. Thereafter, resume dosing at the regular scheduled time. Do not administer more than 1 dose per day.

Side Effects Overview

6 ADVERSE REACTIONS The following clinically significant adverse reactions are discussed in greater detail in other sections of the labeling: Serious Meningococcal Infections [see Warnings and Precautions (5.1) ] Other Infections [see Warnings and Precautions (5.3) ] Pancreatitis and Other Pancreatic Conditions [see Warnings and Precautions (5.4) ] The most common adverse reactions (≥10%) in patients with gMG were injection site reactions, upper respiratory tract infection, and diarrhea. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact UCB, Inc. at 844-599-2273 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. A total of 212 patients were treated with ZILBRYSQ 0.3 mg/kg in clinical studies in gMG. Of these, 137 patients were exposed for at least 6 months, and 87 were exposed for at least 1 year. In a placebo-controlled study (Study 1) in patients with gMG, 86 patients received ZILBRYSQ 0.3 mg/kg [see Clinical Studies (14) ] . Of these 86 patients, approximately 61% were female, 77% were White, 8% were Asian, and 8% were of Hispanic or Latino ethnicity. The mean age at study entry was 52.6 years (range 21 to 75 years). Table 2 summarizes the adverse reactions reported in at least 5% of patients treated with ZILBRYSQ and more frequently than placebo. The most common adverse reactions (reported in at least 10% of patients treated with ZILBRYSQ) were injection site reactions, upper respiratory tract infections, and diarrhea. Table 2: Adverse Reactions in at least 5% of Patients Treated with ZILBRYSQ and More Frequently than in Patients who Received Placebo in Study 1 Adverse Reaction ZILBRYSQ 0.3 mg/kg (n=86) % Placebo (n=88) % Injection site reactions 29 16 Upper respiratory tract infections 14 7 Diarrhea 11 2 Urinary tract infection 8 5 Nausea or vomiting 8 7 Lipase increased 7 0 Amylase increased 5 1 Pancreatic Events In addition to increases in amylase and lipase observed in Study 1, pancreatic events, including pancreatitis and pancreatic cysts have been observed in patients taking ZILBRYSQ [see Warnings and Precautions (5.4) ] . Adverse Laboratory Changes in Clinical Trials Additional laboratory abnormalities included transient elevations of blood eosinophils, which were of uncertain clinical significance. 6.2 Postmarketing Experience Adverse Reactions from Observational Studies Morphea In the open-label extension studies, which included 213 patients, morphea was observed in 10 (5%) patients; most cases had a time to onset longer than one year after start of treatment and were mild to moderate in severity. One patient discontinued ZILBRYSQ because of morphea.

경고 및 주의 사항

5 WARNINGS AND PRECAUTIONS Other Infections: Use caution when administering ZILBRYSQ to patients with any other systemic infection. ( 5.3 ) Pancreatitis and pancreatic cysts have been reported in patients treated with ZILBRYSQ. Discontinue ZILBRYSQ in patients with suspected pancreatitis and initiate appropriate management until pancreatitis is ruled out or has resolved. ( 5.4 ) 5.1 Serious Meningococcal Infections ZILBRYSQ, a complement inhibitor, increases a patient's susceptibility to serious, life-threatening, or fatal infections caused by meningococcal bacteria (septicemia 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. The initiation of ZILBRYSQ treatment is contraindicated in patients with unresolved serious Neisseria meningitidis infection. 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 ZILBRYSQ, according to current ACIP recommendations for patients receiving a complement inhibitor. Revaccinate patients in accordance with ACIP recommendations considering the duration of ZILBRYSQ therapy. Note that ACIP recommends an administration schedule in patients receiving complement inhibitors that differs from the administration schedule in the vaccine prescribing information. If urgent ZILBRYSQ therapy is indicated in a patient who is not up to date with meningococcal vaccines according to ACIP recommendations, provide the patient with antibacterial drug prophylaxis and administer meningococcal vaccines as soon as possible. Various durations and regimens of antibacterial drug prophylaxis have been considered, but the optimal durations and drug regimens for prophylaxis and their efficacy have not been studied in unvaccinated or vaccinated patients receiving complement inhibitors, including ZILBRYSQ. The benefits and risks of treatment with ZILBRYSQ, as well as the benefits and risks of antibacterial drug prophylaxis in unvaccinated or vaccinated patients, must be considered against the known risks for serious infections caused by Neisseria meningitidis . Vaccination does not eliminate the risk of meningococcal infections, despite development of antibodies following vaccination. Closely monitor patients for early signs and symptoms of meningococcal infection and evaluate patients immediately if infection is suspected. Inform patients of these signs and symptoms and instruct patients to seek immediate medical care if these signs and symptoms occur. Promptly treat known infections. Meningococcal infection may become rapidly life-threatening or fatal if not recognized and treated early. Consider interruption of ZILBRYSQ in patients who are undergoing treatment for serious meningococcal infection, depending on the risks of interrupting treatment in the disease being treated [ see Contraindications (4) ] . ZILBRYSQ is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) [see Warnings and Precautions (5.2) ] . 5.2 ZILBRYSQ REMS ZILBRYSQ is available only through a restricted program under a REMS called ZILBRYSQ REMS, because of the risk of serious meningococcal infections [see Warnings and Precautions (5.1) ] . Notable requirements of the ZILBRYSQ REMS include the following: Prescribers must enroll in the REMS. Prescribers must counsel patients about the risk of serious meningococcal infection. Prescribers must provide the patients with the REMS educational materials. Prescribers must assess patient vaccination status for meningococcal vaccines (against serogroups A, C, W, Y, and B) and vaccinate if needed according to current ACIP recommendations two weeks prior to the first dose of ZILBRYSQ. Prescribers must provide a prescription for antibacterial drug prophylaxis if treatment must be started urgently and the patient is not up to date with meningococcal vaccines according to current ACIP recommendations at least two weeks prior to the first dose of ZILBRYSQ. Pharmacies that dispense ZILBRYSQ must be certified in the REMS and must verify prescribers are certified. Patients must receive counseling from the prescriber about the need to receive meningococcal vaccines per ACIP recommendations, the need to take antibiotics as directed by the prescriber, and the signs and symptoms of meningococcal infection. Patients must be instructed to carry the Patient Safety Card with them at all times during and for 2 months following treatment discontinuation with ZILBRYSQ. Further information is available at www.ZILBRYSQREMS.com or 1-877-414-8353. 5.3 Other Infections Serious infections with Neisseria species (other than Neisseria meningitidis ), including disseminated gonococcal infections, have been reported in patients treated with complement inhibitors. ZILBRYSQ blocks terminal complement activation; therefore, patients may have increased susceptibility to infections, especially with encapsulated bacteria, such as infections caused by Neisseria meningitidis but also Streptococcus pneumoniae , Haemophilus influenzae , and to a lesser extent, Neisseria gonorrhoeae . Administer vaccinations for the prevention of Streptococcus pneumoniae infection according to ACIP recommendations. Patients receiving ZILBRYSQ are at increased risk for infections due to these organisms, even if they develop antibodies following vaccination. 5.4 Pancreatitis and Other Pancreatic Conditions Pancreatitis and pancreatic cysts have been reported in patients treated with ZILBRYSQ. During the open-label extension studies, seven (3.3%) patients experienced pancreatic events, including 4 (1.9%) patients with pancreatitis and 3 (1.4%) with pancreatic cysts. In the 3-month, double-blind Study 1, adverse reactions of increased lipase were reported in six (6.9%) patients treated with ZILBRYSQ compared to no patients on placebo, and adverse reactions of increased amylase were reported in four (4.7%) patients treated with ZILBRYSQ compared to one (1.1%) patient on placebo. Lipase levels exceeded three times the upper limit of normal in six (7%) patients after being started on ZILBRYSQ compared to no patients on placebo. Patients should be informed of this risk before starting ZILBRYSQ. Obtain lipase and amylase levels at baseline before starting treatment with ZILBRYSQ. Discontinue ZILBRYSQ in patients with suspected pancreatitis and initiate appropriate management until pancreatitis is ruled out or has resolved.

금기

4 CONTRAINDICATIONS ZILBRYSQ is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection [see Warnings and Precautions (5.1) ] . ZILBRYSQ is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection. ( 4 )

약동학

12.3 Pharmacokinetics The population pharmacokinetics (PK) analysis showed that zilucoplan PK was not time dependent. Following single daily subcutaneous administration of ZILBRYSQ (0.05 mg/kg, 0.1 mg/kg, 0.2 mg/kg, and 0.4 mg/kg) in healthy subjects, increase in peak plasma concentration was approximately dose proportional and increase in area under the curve was less than dose proportional. Absorption Following single and multiple daily subcutaneous administration of ZILBRYSQ 0.3 mg/kg in healthy subjects, zilucoplan reached peak plasma concentration generally between 3 to 6 hours post-dose. Following daily subcutaneous dosing of ZILBRYSQ 0.3 mg/kg for 14 days in healthy subjects, both the peak plasma concentration and exposure (AUC tau ) increased by approximately 3-fold. In Study 1 [see Clinical Studies (14) ] , after daily repeated subcutaneous administration of ZILBRYSQ 0.3 mg/kg, plasma concentrations of zilucoplan were consistent, with steady state trough concentrations being reached by four weeks of treatment with ZILBRYSQ through twelve weeks. Distribution The mean volume of distribution at steady state was 3.51 L in the population pharmacokinetics analysis for adult patients with gMG. Zilucoplan and its 2 major metabolites are highly bound to plasma proteins (>99%). Elimination The mean plasma terminal half-life of zilucoplan was approximately 172 hours (7 to 8 days). Metabolism As a peptide, ZILBRYSQ is expected to be degraded into small peptides and amino acids via catabolic pathways. In plasma, two major metabolites, RA103488 and RA102758, were detected. The metabolite RA103488, formed mainly because of cytochrome CYP450 4F2, has pharmacological activity similar to zilucoplan but is present at a much lower concentration compared to zilucoplan. The metabolite RA102758, formed by protease mediated degradation, is pharmacologically inactive. The AUCs of both metabolites were approximately 10% of the parent AUC. The contribution of RA103488 to pharmacological activity is therefore expected to be low. Excretion Excretion of zilucoplan and its metabolite in urine and feces was negligible (<1% of the dose). Specific Populations Age, Sex, and Race A population pharmacokinetics analysis assessing the effects of age, sex, and race did not suggest any clinically significant impact of these covariates on zilucoplan exposures. Patients with Renal Impairment A dedicated clinical study compared the pharmacokinetics of a single subcutaneous dose of ZILBRYSQ 0.3 mg/kg in subjects with severe renal impairment (as defined by a creatinine clearance <30 mL/min estimated by Cockcroft-Gault formula) to that of matched healthy subjects with normal renal function. A decrease in zilucoplan exposure (AUC 0-inf ) of 13% was observed. This change in zilucoplan exposures is not expected to be clinically significant. No dose adjustment is required in patients with renal impairment. Patients with Hepatic Impairment A dedicated clinical study compared the pharmacokinetics of a single subcutaneous dose of ZILBRYSQ 0.3 mg/kg in subjects with moderate hepatic impairment (as indicated by a Child-Pugh category of moderate [score of 7 to 9]) to that of matched healthy subjects with normal hepatic function. A decrease in zilucoplan exposure (AUC 0-inf ) of 24% was observed. This change in zilucoplan exposures is not expected to be clinically significant. No dose adjustment is required in patients with mild or moderate hepatic impairment. The pharmacokinetics of zilucoplan in patients with severe hepatic impairment have not been studied. Drug Interactions Clinical drug interaction studies have not been performed with zilucoplan. In vitro studies have shown that zilucoplan is not a substrate of major cytochrome P450 (CYP) enzymes (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A) or transporters (P-gp, BCRP, OATP1B1, and OATP1B3). Based on the results from in vitro drug interaction testing, clinically relevant interactions between zilucoplan and substrates of CYP enzymes (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A, and 4F), uridine diphosphoglucuronosyl transferases (UGTs; 1A1, 1A3, 1A4, 1A6, 1A9, 2B7, and 2B15), and transporters (P-gp, BCRP, OATP1B1, OATP1B3, OAT1, OAT3, MATE1, MATE2-K, OCT1, and OCT2) is unlikely.

Frequently Asked Questions

1 INDICATIONS AND USAGE ZILBRYSQ is indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. ZILBRYSQ is a complement inhibitor indicated for the treatment of generalized myasthenia gravis (gMG) in adult patients who are anti-acetylcholine receptor (AChR) antibody positive. ( 1 )

2 DOSAGE AND ADMINISTRATION Obtain baseline amylase and lipase. ( 2.2 ) For subcutaneous injection only. ( 2.3 ) Recommended dosage ( 2.3 ): Body Weight Once Daily Dosage Plunger Rod Color of Prefilled Syringe Less than 56 kg 16.6 mg RUBINE RED 56 kg to less than 77 kg 23 mg ORANGE 77 kg and above 32.4 mg DARK BLUE See Full Prescribing Information for instructions on dosage, preparation, and administration. ( 2.4 , 2.5 ) 2.1 Recommended Vaccination …

5 WARNINGS AND PRECAUTIONS Other Infections: Use caution when administering ZILBRYSQ to patients with any other systemic infection. ( 5.3 ) Pancreatitis and pancreatic cysts have been reported in patients treated with ZILBRYSQ. Discontinue ZILBRYSQ in patients with suspected pancreatitis and initiate appropriate management until pancreatitis is ruled out or has resolved. ( 5.4 ) 5.1 Serious Meningococcal Infections ZILBRYSQ, a complement inhibitor, increases a patient's susceptibility to serious, life-threatening, or fatal infections caused by meningococcal bacteria (septicemia and/or meningitis) …

4 CONTRAINDICATIONS ZILBRYSQ is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection [see Warnings and Precautions (5.1) ] . ZILBRYSQ is contraindicated for initiation in patients with unresolved serious Neisseria meningitidis infection. ( 4 )

Zilucoplan is a prescription medication. You will need a valid prescription from a licensed healthcare provider.

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References & Data Sources

• DailyMed — Zilucoplan drug label (National Library of Medicine)
• openFDA — Zilucoplan label data (U.S. Food & Drug Administration)
• RxNorm — RXCUI 2672496 (NLM Normalized Drug Names)
• NDC Directory — Zilucoplan (FDA National Drug Code)

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데이터 출처: DailyMed (NLM), openFDA, MFDS