Rozanolixizumab-noli (Monograph)

Drug class: Immunomodulatory Agents

Medically reviewed by Drugs.com on Mar 10, 2024. Written by ASHP.

Introduction

Humanized IgG₄P monoclonal antibody; neonatal Fc receptor blocker.

Uses for Rozanolixizumab-noli

Myasthenia Gravis

Treatment of generalized myasthenia gravis in adults who are anti-acetylcholine receptor (AChR) or anti-muscle-specific tyrosine kinase (MuSK) antibody positive (designated an orphan drug by FDA for this use).

Conventional therapy for generalized myasthenia gravis includes immunosuppressive agents, removal of antibodies by plasma exchange, and, in some cases, thymectomy. Complement inhibitors (e.g., eculizumab, ravulizumab) may be options for AChR-positive disease. Rituximab should be considered in patients with MuSK-positive disease and unsatisfactory response to initial immunotherapy. Specific place in therapy for rozanolixizumab-noli not yet established.

Rozanolixizumab-noli Dosage and Administration

General

Pretreatment Screening

• Evaluate need for age-appropriate immunizations according to immunization guidelines before initiation of a new rozanolixizumab treatment cycle.

• Delay rozanolixizumab administration in patients with active infection until infection is resolved.

Patient Monitoring

• Monitor for signs and symptoms of infection or aseptic meningitis.

• Monitor for signs and symptoms of hypersensitivity reactions during treatment with rozanolixizumab and for 15 minutes after administration is complete.

Administration

Sub-Q Infusion

Administered via sub-Q infusion by healthcare provider.

Available as a colorless to pale brownish-yellow, clear to slightly opalescent solution in single-dose vials containing rozanolixizumab-noli 280 mg/2 mL (140 mg/mL).

Administer using an appropriate sub-Q infusion pump; use a pump where the administered volume can be pre-set, as each vial of rozanolixizumab-noli contains excess volume for priming the infusion line.

Manufacturer recommends the following for administration: syringe pump occlusion alarm limits at maximum setting; administration tubing length ≤61 cm; and infusion set with needle of 26 gauge or larger. Refer to infusion pump manufacturer instructions for full preparation and administration information.

Allow vials to reach room temperature for approximately 30 minutes prior to administration; do not use heating devices.

Administer the drug within 4 hours of puncturing vial and immediately after priming infusion set.

Use transfer needles to fill syringe with rozanolixizumab-noli, then remove needle and attach infusion set to syringe. Follow manufacturer instructions to prepare infusion pump and prime tubing.

Infuse into lower right or lower left part of abdomen, below the navel; do not infuse where skin is tender, bruised, red, or hard, and avoid infusing into tattoos, scars, or stretch marks. Rotate infusion sites with each infusion.

Infuse at a constant flow rate, up to 20 mL/hour.

Do not flush infusion line when infusion is complete; the volume of infusion has been adjusted to account for losses in the line.

Missed doses may be administered up to 4 days after the scheduled time point. Then, resume regular dosing schedule until treatment cycle is completed.

Dosage

Adults

Myasthenia Gravis

Sub-Q Infusion

Recommended dosage based on patient body weight (see Table 1).

Administer via sub-Q infusion pump at rate of up to 20 mL/hour once weekly for 6 weeks.

Administer subsequent treatment cycles based on clinical evaluation; safety of initiating subsequent cycles sooner than 63 days from the start of the previous treatment cycle not established.

Special Populations

Hepatic Impairment

No specific dosage recommendations.

Renal Impairment

No specific dosage recommendations.

Geriatric Patients

No specific dosage recommendations.

Related/similar drugs

Vyvgart, Zilbrysq, pyridostigmine, Mestinon, neostigmine, Ultomiris, Soliris

Cautions for Rozanolixizumab-noli

Contraindications

• None.

Warnings/Precautions

Infections

Increased risk of infection.

Delay administration of rozanolixizumab in patients with active infection until infection resolves. Monitor for clinical signs and symptoms of infection during treatment. If serious infection occurs, administer appropriate treatment and consider withholding rozanolixizumab until infection resolves.

Immunization with vaccines during rozanolixizumab treatment not studied. Safety of immunization with live or live-attenuated vaccines and response to immunization with any vaccine unknown. Because rozanolixizumab reduces IgG levels, vaccination with live or live-attenuated vaccines not recommended during treatment. Before initiating a new treatment cycle, evaluate need for age-appropriate vaccines according to immunization guidelines.

Aseptic Meningitis

Serious cases of aseptic meningitis (also referred to as drug-induced aseptic meningitis) reported.

If symptoms of aseptic meningitis develop, initiate diagnostic workup and treatment according to standard of care.

Hypersensitivity Reactions

Hypersensitivity reactions, including angioedema and rash, reported.

Monitor for clinical signs and symptoms of hypersensitivity reactions during treatment and for 15 minutes after administration is complete.

Management of hypersensitivity reactions depends on type and severity of reaction. If hypersensitivity reaction occurs, institute appropriate measures as needed; advise patients experiencing signs and symptoms of hypersensitivity reactions to seek medical attention.

Immunogenicity

Anti-drug antibodies (including neutralizing antibodies) detected.

Patients with anti-drug antibodies had decreased rozanolixizumab trough concentrations compared to patients without anti-drug antibodies. However, such antibodies (including neutralizing antibodies) had no clinically meaningful impact on efficacy or safety of the drug.

Specific Populations

Pregnancy

Limited data in pregnant women.

In animal studies, increased embryonic death, reduced body weight, and impaired immune function observed in the absence of maternal toxicity.

Lactation

No data on the presence of rozanolixizumab-noli in human milk, effects on the breast-fed infant, or effects on milk production. Maternal IgG known to be present in human milk.

Consider developmental and health benefits of breastfeeding, along with the mother's clinical need for rozanolixizumab-noli and any potential adverse effects on the breast-fed child from the drug or underlying maternal condition.

Pediatric Use

Safety and effectiveness not established in pediatric patients.

Geriatric Use

Clinical studies did not include sufficient numbers of patients ≥65 years of age to determine whether they respond differently from younger adult patients.

Hepatic Impairment

No pharmacokinetic studies conducted. Hepatic impairment not expected to affect pharmacokinetics of rozanolixizumab-noli.

Renal Impairment

No dedicated pharmacokinetic study conducted. Renal impairment not expected to affect pharmacokinetics of rozanolixizumab-noli; no dosage adjustment required. Based on population pharmacokinetic analysis, renal function (eGFR 38–161 mL/min per 1.73 m²) had no clinically significant impact on rozanolixizumab-noli apparent clearance.

Common Adverse Effects

Most common adverse effects (≥10%): headache, infections, diarrhea, pyrexia, hypersensitivity reactions, nausea.

Drug Interactions

No formal drug-drug interaction studies performed.

Not metabolized by CYP enzymes; therefore, interactions with concomitant medications that are substrates, inducers, or inhibitors of CYP enzymes unlikely.

Drugs Binding to Human Neonatal Fc Receptor

Rozanolixizumab-noli may decrease concentrations of compounds that bind to human neonatal Fc receptor (e.g., immunoglobulin products, monoclonal antibodies, or antibody derivatives containing the human Fc domain of the immunoglobulin G [IgG] subclass), leading to decreased systemic exposures and reduced effectiveness of such medications.

Closely monitor for reduced effectiveness of medications that bind to human neonatal Fc receptor. When concomitant long-term use is essential for patient care, consider discontinuing rozanolixizumab-noli and using alternative therapies.

Rozanolixizumab-noli Pharmacokinetics

Absorption

Bioavailability

Exhibits non-linear pharmacokinetics.

Following sub-Q administration, exposure increased in a greater than dose proportional manner over dose range of 1–20 mg/kg.

Peak plasma levels achieved after approximately 2 days.

Special Populations

Pharmacokinetics not affected by age, sex, or race.

Distribution

Extent

Unknown if present in human milk.

Elimination

Metabolism

Expected to be degraded by proteolytic enzymes into small peptides and amino acids.

Stability

Storage

Parenteral

Solution for Sub-Q Infusion

Unopened vials: 2–8°C in the original carton to protect from light; do not shake or freeze.

May be stored at room temperature (up to 25°C) for a single period of up to 30 days in the original carton to protect from light; once vial has been stored at room temperature, do not return to refrigeration.

Actions

• Recombinant, humanized IgG₄P monoclonal antibody expressed in a genetically engineered Chinese hamster ovary cell line.

• Binds to neonatal Fc receptor, resulting in reduction of circulating IgG.

• When administered to patients testing positive for acetylcholine receptor (AChR) and muscle-specific tyrosine kinase (MuSK) autoantibodies, reductions in total IgG levels and AChR/MuSK autoantibody levels observed.

Advice to Patients

• Instruct patients to communicate any history of infections to the healthcare provider and to contact their healthcare provider if they develop any symptoms of infection.

• Advise patients to complete age-appropriate vaccines according to immunization guidelines prior to initiation of a new treatment cycle of rozanolixizumab-noli. Administration of live or live-attenuated vaccines is not recommended during treatment.

• Inform patients that rozanolixizumab-noli may cause aseptic meningitis, and instruct patients to contact their healthcare provider if symptoms consistent with meningitis develop.

• Inform patients about signs and symptoms of hypersensitivity reactions, and advise patients to contact their healthcare provider immediately if these signs or symptoms occur.

• Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary or herbal supplements, as well as any concomitant illnesses.

• Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.

• Inform patients of other important precautionary information.

Additional Information

The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer’s labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

Rozanolixizumab-noli is obtained through designated specialty pharmacies and distributors. Contact manufacturer or consult the manufacturer website ([Web]) for specific availability information.

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