Zilbrysq (zilucoplan sodium)
Complement Inhibitors Subcutaneous Syringe (Ml)
Last reviewed · Source: First Databank (FDB) drug data
Overview
Zilucoplan sodium is a complement protein C5 inhibitor.
Zilucoplan, a 15 amino-acid, synthetic macrocyclic peptide, is a complement inhibitor that binds to the complement protein C5. By binding to the complement protein C5, zilucoplan inhibits its cleavage to C5a and C5b, preventing the generation of the terminal complement complex, C5b-9. The exact mechanism by which zilucoplan exerts its therapeutic effect in generalized myasthenia gravis (gMG) is unknown but is presumed to involve reduction of C5b-9 deposition at the neuromuscular junction.
A dose-dependent inhibition of complement was observed in clinical studies. In the primary efficacy study, 97.5% complement inhibition was observed by the end of the first week and sustained throughout the 12-week treatment period for patients with gMG treated with the recommended dosage regimen of zilucoplan.
The pharmacokinetics of zilucoplan are not time dependent. Following subcutaneous administration, the increase in peak plasma concentration is approximately dose proportional and increase in AUC is less than dose proportional. Zilucoplan reaches peak plasma concentration between 3-6 hours post-dose.
Following daily subcutaneous dosing, the peak plasma concentration and systemic exposure increase by approximately 3-fold. In the primary efficacy study, steady state trough concentrations were reached by 4 weeks of treatment with zilucoplan through 12 weeks.
Zilucoplan and its 2 major metabolites (RA103488 and RA102758) are highly bound to plasma proteins (>99%). As a peptide, zilucoplan is expected to be degraded via catabolic pathways into small peptides and amino acids. The metabolite RA103488, formed mainly because of cytochrome P-450 4F2, has pharmacological activity similar to zilucoplan; however, this metabolite 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 are approximately 10% of the parent AUC. The contribution of RA103488 to pharmacological activity is expected to be low.
Excretion of zilucoplan and its metabolite in urine and feces is negligible (<1% of the dose). The mean plasma terminal half-life of zilucoplan is approximately 172 hours (7-8 days). The pharmacokinetics of zilucoplan are not significantly affected by age, sex, or race based on a population pharmacokinetics analysis.
USES: Zilucoplan is used to treat a certain muscle condition (generalized myasthenia gravis). It may help to improve symptoms of muscle weakness.
Generic name: zilucoplan sodium
Pronunciation: (ZIL-ue-KOE-plan)
Drug class: Complement Inhibitors
Therapeutic class: Locomotor System
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Zilbrysq
Indications
The following indications are listed for Zilbrysq:
- Anti-Acetylcholine Receptor (Achr) Antibody Positive Generalized Myasthenia Gravis
Also known as: Achr-Ab(+) Generalized Myasthenia Gravis.
Dosing
Dosage of zilucoplan sodium is expressed in terms of zilucoplan.
Zilucoplan is administered by subcutaneous injection. The drug is available as a clear to slightly opalescent, colorless solution in single-dose prefilled syringes containing zilucoplan 16.6 mg/0.416 mL, 23 mg/0.574 mL, or 32.4 mg/0.81 mL. Zilucoplan does not contain preservatives.
Zilucoplan is intended for use under the guidance and supervision of a healthcare professional. Patients may self-inject zilucoplan after proper training. Provide training to patients and/or caregivers on subcutaneous injection technique according to the instructions for use provided by the manufacturer.
Store zilucoplan prefilled syringes at 2-8degreesC in the original carton to protect from light until dispensing. After dispensing, patients or caregivers may store zilucoplan under refrigeration (2-8degreesC) until the expiration date on the carton, or at room temperature (<=30degreesC) for up to 3 months after removing from the refrigerator or until the expiration date, whichever occurs first. Do not freeze.
If stored in the refrigerator and when ready to use, take 1 zilucoplan prefilled syringe out of the refrigerator and place it on a clean, flat surface. Allow the drug to reach room temperature away from direct sunlight (30-45 minutes) before injection. Do not heat or place in the microwave. Immediately return the carton with the other prefilled syringes to the refrigerator.
If stored at room temperature and when ready to use, take 1 zilucoplan prefilled syringe from the carton. Do not return zilucoplan to the refrigerator after it has been stored at room temperature.
Visually inspect zilucoplan for particulate matter and discoloration prior to administration; do not use if visible particles, cloudiness, or foreign particulate matter is observed.
Inject the full contents of the prefilled syringe. Administer the daily dose of zilucoplan at approximately the same time each day. Administer zilucoplan subcutaneously into areas of the abdomen, thighs, or back of the upper arms that are not tender, bruised, red, or hard. Do not inject into areas with scars or stretch marks. Rotate injection sites for each administration. Administration in the upper, outer arm should be performed by a caregiver.
Discard zilucoplan prefilled syringe after use; do not reuse.
If a scheduled dose of zilucoplan 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.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Zilbrysq 16.6 Mg/0.416 Ml Syrn | Maintenance | Inject 16.6 mg by subcutaneous route once daily. |
| Zilbrysq 23 Mg/0.574 Ml Syring | Maintenance | Inject 23 mg by subcutaneous route once daily. |
| Zilbrysq 32.4 Mg/0.81 Ml Syrng | Maintenance | Inject 32.4 mg by subcutaneous route once daily. |
No dosing information is available for this tab.
Drug interactions
In vitro studies have shown that zilucoplan is not a substrate of major cytochrome P-450 (CYP) isoenzymes (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, and 3A), or a substrate of transporters including P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), organic anion transporting polypeptide (OATP) 1B1, and OATP1B3.
Based on the results from in vitro drug interaction testing, clinically important interactions between zilucoplan and substrates of CYP enzymes (1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 3A, and 4F), uridine diphosphate-glucuronosyltransferase (UGTs; 1A1, 1A3, 1A4, 1A6, 1A9, 2B7, and 2B15), and transporters (P-gp, BCRP, OATP1B1, OATP1B3, organic anion transporter (OAT) 1, OAT3, multidrug and toxin extrusion (MATE) 1, MATE2-K, organic cation transporter (OCT) 1, and OCT2) are unlikely.
No clinical drug interaction studies have been conducted with zilucoplan to date.
There are no contraindication interactions for this drug.
There are no severe interactions for this drug.
There are no moderate interactions for this drug.
Contraindications
*Unresolved, seriousNeisseria meningitidis infection.
- Meningococcal meningitis
- Meningococcemia
- Infection
- Elevated serum amylase
- Elevated serum lipase
Adverse reactions
The most common adverse effects reported in >=10% of patients receiving zilucoplan were injection site reactions, upper respiratory tract infection, and diarrhea.
Less Frequent
- Acute pancreatitis
- Elevated serum lipase
Rare or Very Rare
- Meningitis
- Meningococcemia
- Pneumonia
More Frequent
- Diarrhea
- Injection site sequelae
- Upper respiratory infection
Less Frequent
- Elevated serum amylase
- Eosinophilia
- Morphea
- Nausea
- Urinary tract infection
- Vomiting
Rare or Very Rare
- Infection
Precautions
No enhanced messaging available.
Safety and efficacy of zilucoplan have not been established in pediatric patients.
There are no available data on zilucoplan use in pregnant women to inform a drug-associated risk of major birth defects, miscarriage, or other adverse maternal or fetal outcomes. When subcutaneous zilucoplan was administered to pregnant monkeys, increases in embryofetal death were observed at maternal exposures similar to those in humans at therapeutic doses; maternal toxicity was not observed.
There are no data on the presence of zilucoplan in human milk, the effects of the drug on breast-fed infants, or the effects on milk production.
Consider the developmental and health benefits of breast-feeding, along with the mother's clinical need for zilucoplan and any potential adverse effects on the breast-fed child from the drug or the underlying maternal condition.
The manufacturer makes no specific dosage recommendations for geriatric patients.
Experience in patients >=65 years of age is insufficient to determine whether they respond differently to zilucoplan than younger adults.
ICD codes
| Code | Type | Description |
|---|---|---|
| Anti-acetylcholine receptor (Achr) antibody positive generalized myasthenia gravis | ||
| G70.0 | ICD10CM | Myasthenia gravis |
| G70.00 | ICD10CM | Myasthenia gravis without (acute) exacerbation |
| G70.01 | ICD10CM | Myasthenia gravis with (acute) exacerbation |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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