Reslizumab

Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution, Intravenous [preservative free]:

Cinqair: 100 mg/10 mL (10 mL)

Pharmacology

Mechanism of Action

Reslizumab is an interleukin-5 antagonist (IgG4 kappa). IL-5 is the major cytokine responsible for the growth and differentiation, recruitment, activation, and survival of eosinophils (a cell type associated with inflammation and an important component in the pathogenesis of asthma). Reslizumab, by inhibiting IL-5 signaling, reduces the production and survival of eosinophils; however, the mechanism of reslizumab action in asthma has not been definitively established.

Pharmacokinetics/Pharmacodynamics

Distribution

V_d: ~5 L

Metabolism

Undergoes proteolytic degradation via enzymes into small peptides and amino acids.

Half-Life Elimination

~24 days

Use: Labeled Indications

Asthma: Add-on maintenance treatment of severe asthma in adults with an eosinophilic phenotype

Limitations of use: Not indicated for treatment of other eosinophilic conditions or for the relief of acute bronchospasm or status asthmaticus.

Contraindications

Hypersensitivity to reslizumab or any component of the formulation

Dosage and Administration

Dosing: Adult

Asthma: IV: 3 mg/kg once every 4 weeks.

Dosing: Geriatric

Refer to adult dosing.

Reconstitution

Remove vial from refrigerator; to minimize foaming, do not shake. Solution is clear to slightly hazy/opalescent, colorless to slight yellow liquid; proteinaceous particles may be present in the solution that appear translucent to white; do not administer if discolored. Withdraw calculated volume from vial and, to minimize foaming, add slowly to 50 mL NS infusion bag. Gently invert the bag; do not shake. Compatible bags are polyvinylchloride (PVC) or polyolefin. The time between preparation and administration should not exceed 16 hours. Do not mix with other drugs. Vials are single-use only; discard unused portion.

Administration

IV: For IV infusion only. Allow diluted solution to reach room temperature. Use an infusion set with an in-line, low protein-binding filter (pore size: 0.2 micron); compatible filters are polyethersulfone (PES), polyvinylidene fluoride (PVDF), nylon, and cellulose acetate. Infuse over 20 to 50 minute period (may vary depending on total volume being infused) and then flush the IV administration set with NS after the infusion is finished. Do not administer as an IV push or bolus and do not infuse concomitantly in the same IV line with other agents. Observe patient during and for an appropriate time following infusion.

Dietary Considerations

Formulation may contain sucrose.

Storage

Store intact vials in refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze or shake. Protect from light; store in original package. After dilution in NS in infusion bag, administer immediately or store in a refrigerator at 2°C to 8°C (36°F to 46°F) or at room temperature up to 25°C (77°F), protected from light, for up to 16 hours.

Drug Interactions

There are no known significant interactions.

Adverse Reactions

Immunologic: Antibody development (5%)

Neuromuscular & skeletal: Increased creatine phosphokinase (20%; transient), myalgia (1%)

Respiratory: Oropharyngeal pain (3%)

<1%, postmarketing, and/or case reports: Anaphylaxis

Warnings/Precautions

Concerns related to adverse effects:

• Anaphylaxis [US Boxed Warning]: Anaphylaxis was reported in 0.3% of asthma patients in placebo-controlled studies; these events were observed during or within 20 minutes after completion of infusion, and may occur as early as the second dose. Observe patients for an appropriate period of time after administration. Manifestations included dyspnea, decreased oxygen saturation, wheezing, vomiting, skin and mucosal involvement, including urticaria. If severe systemic reactions, including anaphylaxis occur, discontinue administration immediately and provide appropriate medical treatment.
• Malignancies: Malignancies were observed during clinical trials with the majority being diagnosed within less than 6 months of drug exposure; neoplasms observed were diverse with no predominant histologic type.

Disease-related concerns:

• Asthma: Not indicated for the treatment of acute asthma symptoms (eg, acute bronchospasm) or acute exacerbations, including status asthmaticus. Appropriate rescue medication should be available. Patients who experience continued uncontrolled asthma or worsening of symptoms following treatment initiation with reslizumab should seek medical attention.
• Helminth infections: It is unknown if administration of reslizumab will influence a patient's immune response against parasitic infections. Therefore, patients with preexisting helminth infections should undergo treatment of the infection prior to initiation of reslizumab therapy. Patients who become infected during reslizumab treatment and do not respond to anti-helminth therapy should discontinue reslizumab until the infection resolves.

Concurrent drug therapy issues:

• Corticosteroids: Do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of reslizumab. Reductions in corticosteroid dose should be gradual, if appropriate. Clinicians should note that a reduction in corticosteroid dose may be associated with withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.

Other warnings/precautions:

• Limitation of use: Eosinophilic conditions: Reslizumab is not indicated for the treatment of other eosinophilic conditions.

Monitoring Parameters

Anaphylaxis/hypersensitivity reactions (during and after infusion); peak flow, and/or other pulmonary function tests; monitor for signs of infection

Pregnancy

Pregnancy Considerations

Reslizumab is a humanized monoclonal antibody (IgG₄). Potential placental transfer of human IgG is dependent upon the IgG subclass and gestational age, generally increasing as pregnancy progresses. The lowest exposure would be expected during the period of organogenesis (Palmeira 2012; Pentsuk 2009). The long half-life of reslizumab should be considered if required for a pregnant woman.

Patient Education

What is this drug used for?

• It is used to treat asthma.
• Do not use this drug to treat an asthma attack. Use a rescue inhaler. Talk with your doctor.

Frequently reported side effects of this drug

• Throat pain

Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:

• Infusion reaction
• Shortness of breath
• Nausea
• Vomiting
• Dizziness
• Passing out
• Flushing
• Pale skin
• Confusion
• Fast heartbeat
• Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.

Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.

Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.