reslizumab (Rx)

>10%

Elevated CPK, transient (20%)

1-10%

Treatment-emergent antibody response (5.4%)

Oropharyngeal pain (2.6%)

Musculoskeletal (2.2%)

Myalgias (1%)

<1%

Elevated CPK >10x ULN (0.8%)

Malignancy (0.6%)

Anaphylaxis (0.3%)

Contraindications

Known hypersensitivity to reslizumab or its excipients

Cautions

Anaphylaxis reported observed during or within 20 minutes after completion of the IV infusion and reported as early as the second dose (see Black Box Warnings)

Not for use to treat acute asthma symptoms or acute exacerbations

No clinical studies have been conducted to assess reduction of maintenance corticosteroid dosages following administration of reslizumab; do not discontinue systemic or inhaled corticosteroids abruptly upon initiation of reslizumab therapy

Diverse malignancies observed with reslizumab vs placebo in clinical trials (0.6% vs 0.3%)

Treat patients with pre-existing helminth infections before initiating reslizumab; if patients become infected during reslizumab treatment and do not respond to antihelminth treatment, discontinue reslizumab until infection resolves

Pregnancy

Data are insufficient regarding drug-associated risk during pregnancy

Monoclonal antibodies are transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential effects on a fetus are likely to be greater during the second and third trimesters of pregnancy

Reslizumab has a long half-life; this should be taken into consideration

Clinical considerations

• Increased risk of preeclampsia in women with poorly or moderately controlled asthma
• Prematurity, low birth weight, and small for gestational age observed in neonates whose mothers have poor or moderate asthma control
• Asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control

Animal studies

• Not teratogenic in mice or rabbits; data based on 2 single-dose studies in pregnant mice and rabbits during organogenesis 0.4, 1.5, and 6 times the exposures achieved at the maximum recommended human dose (MRHD) in mice on an AUC basis and 0.67, 3.3, and 17 times the exposures achieved at the MRHD in rabbits on a mg/kg basis

Lactation

Unknown if distributed in human breast milk; however, human IgG is known to be present in human milk

Consider the developmental and health benefits of breastfeeding along with the mother’s clinical need for the drug, and any potential adverse effects on the breastfed infant from the drug or from the underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Interleukin-5 (IL-5) antagonist monoclonal antibody (IgG kappa); binds to IL-5, thereby inhibiting IL-5 bioactivity by blocking its binding to IL-5 alpha receptor complex expressed on the eosinophil surface

IL-5 is the major cytokine responsible for eosinophil growth and differentiation, recruitment, activation, and survival

Inflammation is an important component of asthma pathogenesis

Multiple cell types (eg, mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (eg, histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation

In patients with asthma, the eosinophilic phenotype is associated with compromised lung function, more frequent symptoms, and increased risk of exacerbations

Absorption

Peak plasma concentration: Observed at end of IV infusion

Distribution

Vd: 5 L

Metabolism

Similar to other monoclonal antibodies, reslizumab is degraded by enzymatic proteolysis into small peptides and amino acids

Elimination

Half-life: 24 days

Clearance: 7 mL/hr

IV Preparation

Remove from refrigerator

To minimize foaming, do not shake

Inspect visually for particulate matter and discoloration prior to administration; solution should appear clear to slightly hazy/opalescent, colorless to slightly yellow liquid

Since reslizumab is a protein, proteinaceous particles may be present in the solution that appear as translucent to white, amorphous particulates

Do not administer if discolored or if other foreign particulate matter is present

Withdraw proper volume from the vial(s) based on recommended weight-based dosage; discard any unused portion

Dispense syringe contents slowly to minimize foaming into a 50-mL 0.9% NaCl infusion bag

Compatible with polyvinylchloride (PVC) or polyolefin infusion bags

Gently invert bag to mix solution; do not shake

Do not mix or dilute with other drugs

Administer immediately after preparation; if not used immediately, refrigerate diluted solution at 2-8°C (36-46°F) or at room temperature up to 25ºC (77ºF), protected from light, for up to 16 hr

The time between preparation and administration should not exceed 16 hr

IV Administration

For IV infusion only following further dilution; do not administer as IV push or bolus

Administer in a healthcare setting by a healthcare professional prepared to manage anaphylaxis

If refrigerated before administration, allow diluted solution to reach room temperature

Use an infusion set with in-line, low protein-binding filter (pore size of 0.2-micron)

Compatible with polyethersulfone (PES), polyvinylidene fluoride (PVDF), nylon, and cellulose acetate in-line infusion filters

Infuse diluted solution IV over 20-50 minutes; infusion time may vary depending on the total volume to be infused as based on patient weight

Do not infuse concomitantly in the same IV line with other agents; no physical or biochemical compatibility studies conducted

Monitor for hypersensitivity during the infusion and for an appropriate period afterwards

Upon infusion completion, flush IV line with 0.9% NaCl to ensure that entire reslizumab dose has been administered

Storage

Unopened vials

• Refrigerate at 2-8ºC (36-46°F)
• Do not freeze
• Do not shake
• Protect the vials from light by storing in the original package until time of use

Diluted solution

• If not used immediately, refrigerate at 2-8°C (36-46°F) or at room temperature up to 25ºC (77ºF), protected from light, for up to 16 hr
• Time between preparation and administration should not exceed 16 hr
• Do not shake