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Reslizumab

Class: Interleukin Antagonists
Brands: Cinqair

Warning(s)

Warning: Anaphylaxis1

See full prescribing information for complete boxed warning.1

  • Anaphylaxis occurred with reslizumab infusion in 0.3% of patients in placebo-controlled studies.1

  • Patients should be observed for an appropriate period of time after reslizumab infusion; healthcare professionals should be prepared to manage anaphylaxis that can be life-threatening.1

  • Discontinue reslizumab immediately if the patient experiences anaphylaxis.1

Introduction

Reslizumab is an interleukin antagonist.

Uses for Reslizumab

Reslizumab has the following uses:

Reslizumab is an interleukin-5 antagonist monoclonal antibody (IgG4 kappa) indicated for add-on maintenance treatment of patients with severe asthma aged 18 years and older, and with an eosinophilic phenotype. 1

Reslizumab has the following limitations of use:

Reslizumab is not indicated for treatment of other eosinophilic conditions or relief of acute bronchospasm or status asthmaticus.1

Reslizumab Dosage and Administration

General

Reslizumab is available in the following dosage form(s) and strength(s):

Injection: 100 mg/10 mL (10 mg/mL) solution in single-use vials.1

Dosage

It is essential that the manufacturer's labeling be consulted for more detailed information on dosage and administration of this drug. Dosage summary:

  • Reslizumab is for intravenous infusion only. Do not administer as an intravenous push or bolus.1

  • Reslizumab should be administered in a healthcare setting by a healthcare professional prepared to manage anaphylaxis.1

  • Recommended dosage regimen is 3 mg/kg once every 4 weeks by intravenous infusion over 20-50 minutes.1

Cautions for Reslizumab

Contraindications

Known hypersensitivity to reslizumab or any of its excipients.1

Warnings/Precautions

Anaphylaxis

Anaphylaxis to reslizumab was reported in 0.3% of asthma patients in placebo-controlled clinical studies. These events were observed during or within 20 minutes after completion of the reslizumab infusion and reported as early as the second dose of reslizumab. Manifestations included dyspnea, decreased oxygen saturation, wheezing, vomiting, and skin and mucosal involvement, including urticaria. In all 3 cases, reslizumab was discontinued. 1

Anaphylaxis can be life-threatening. Reslizumab should be administered in a healthcare setting by a healthcare professional prepared to manage anaphylaxis. Patients should be observed for an appropriate period of time after reslizumab administration. If severe systemic reactions, including anaphylaxis, occur, stop administration of reslizumab immediately and provide appropriate medical treatment. Prior to discharge, inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care if symptoms occur. Discontinue reslizumab use permanently if the patient experiences signs or symptoms of anaphylaxis.1

Acute Asthma Symptoms or Deteriorating Disease

Reslizumab should not be used to treat acute asthma symptoms or acute exacerbations. Do not use reslizumab to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with reslizumab.1

Malignancy

In placebo-controlled clinical studies, 6/1028 (0.6%) patients receiving 3 mg/kg reslizumab had at least 1 malignant neoplasm reported compared to 2/730 (0.3%) patients in the placebo group. The observed malignancies in reslizumab-treated patients were diverse in nature and without clustering of any particular tissue type. The majority of malignancies were diagnosed within less than six months of exposure to reslizumab.1

Reduction of Corticosteroid Dosage

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 therapy with reslizumab. Reductions in corticosteroid dose, if appropriate, should be gradual and performed under the supervision of a physician. Reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.1

Parasitic (Helminth) Infection

Eosinophils may be involved in the immunological response to some helminth infections. Patients with known parasitic infections were excluded from participation in clinical studies. It is unknown if reslizumab will influence the immune response against parasitic infections. Treat patients with pre-existing helminth infections before initiating reslizumab. If patients become infected while receiving treatment with reslizumab and do not respond to anti-helminth treatment, discontinue treatment with reslizumab until infection resolves.1

Specific Populations

Pregnancy

The data on pregnancy exposure from the clinical trials are insufficient to inform on drug-associated risk. Monoclonal antibodies, such as reslizumab, 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 trimester of pregnancy. Reslizumab has a long half-life. This should be taken into consideration.1 In animal reproduction studies, there was no evidence of embryo-fetal adverse developmental effects with intravenous administration of reslizumab during organogenesis to pregnant mice and rabbits at doses that produced exposures up to approximately 6 times the exposure at the maximum recommended human dose (MRHD) in mice and approximately 17 times the exposure at the MRHD in rabbits.1 The estimated background risk of major birth defects and miscarriage for the indicated population(s) are unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.1

In women with poorly or moderately controlled asthma, evidence demonstrates that there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. The level of asthma control should be closely monitored in pregnant women and treatment adjusted as necessary to maintain optimal control. 1

In 2 separate embryo-fetal development studies, pregnant mice and rabbits received a single reslizumab dose during the period of organogenesis at 2, 10, and 50 mg/kg (0.4, 1.5, and 6 times the exposures achieved at the 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). Reslizumab was not teratogenic in mice or rabbits. Embryo-fetal development of interleukin-5 (IL-5) deficient mice has been reported to be generally unaffected relative to wild-type mice.1 In a prenatal and postnatal development study, pregnant CD-1 mice received reslizumab during organogenesis on gestation days 6 and 18 and on postnatal day 14 at 10 or 50 mg/kg (1.5 and 6 times the exposures achieved at the MRHD on an AUC basis). Reslizumab did not have any effects on fetal development up to approximately 4 months after birth. Reslizumab crossed the placenta of pregnant mice. Serum concentrations in pups were approximately 6-8% of those in the dams (parental female mice) on postnatal day 14.1

Lactation

It is not known whether reslizumab is present in human milk, and the effects of reslizumab on the breast fed infant and on milk production are not known. However, human IgG is known to be present in human milk. Reslizumab was present in the milk of lactating mice following dosing during pregnancy. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for reslizumab and any potential adverse effects on the breast-fed child from reslizumab or the underlying maternal condition. 1

Reslizumab was excreted in milk of lactating CD-1 mice that received reslizumab at 10 or 50 mg/kg (1.5 and 6 times the exposures achieved at the MRHD on an AUC basis) during pregnancy on gestation days 6 and 18 and on postnatal day 14. Levels of reslizumab in milk were approximately 5-7% of maternal serum concentrations.1

Pediatric Use

Reslizumab is not indicated for use in pediatric patients less than 18 years of age. The safety and effectiveness in pediatric patients (aged 17 years and younger) have not been established.1

Reslizumab was evaluated in 39 patients aged 12 to less than 18 years with asthma in two 52-week exacerbation studies and one 16-week lung function study. In the exacerbation studies, patients were required to have at least 1 asthma exacerbation requiring systemic corticosteroid use in the year prior to study entry. In these studies, the asthma exacerbation rate was higher in adolescent patients treated with reslizumab than placebo (reslizumab n=14, rate 2.86, 95% CI [1.02 to 8.09] and placebo n=11, rate 1.37, 95% CI [0.57 to 3.28]: rate ratio 2.09, 95% CI [0.82 to 5.36]).1

Geriatric Use

Reslizumab was evaluated in 122 patients aged 65 years and older with asthma in two 52-week exacerbation studies and two 16-week lung function studies. No overall differences in safety or effectiveness were observed between these patients and younger patients. Based on available data, no adjustment of the dosage of reslizumab in geriatric patients is necessary.1

Common Adverse Effects

The most common adverse reaction (incidence greater than or equal to 2%) includes oropharyngeal pain.1

Drug Interactions

Specific Drugs

It is essential that the manufacturer's labeling be consulted for more detailed information on interactions with this drug, including possible dosage adjustments. Interaction highlights:

No formal clinical drug interaction studies have been performed with reslizumab.1

Actions

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. Reslizumab binds to IL-5 with a dissociation constant of 81 pM, inhibiting the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil surface. Inflammation is an important component in the pathogenesis of asthma. Multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) are involved in inflammation. 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.1

Advice to Patients

Patient Counseling Information

See FDA approved patient labeling (Patient Information).1

Inform patients that hypersensitivity reactions, including anaphylaxis, have occurred with administration of reslizumab. Educate patients on the signs and symptoms of hypersensitivity reactions and anaphylaxis (e.g., skin or mucosal involvement, airway compromise, reduced blood pressure). Instruct patients to contact their healthcare professional immediately if they experience symptoms of an allergic reaction after they have received their infusion of reslizumab.1

Inform patients that reslizumab does not treat acute asthma symptoms or acute exacerbations. Inform patients to seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with reslizumab.1

Counsel reslizumab-treated patients about the risk of malignancies.1

Inform patients not to discontinue systemic or inhaled corticosteroids except under the direct supervision of a physician. Inform patients that reduction in corticosteroid dose may be associated with systemic withdrawal symptoms and/or unmask conditions previously suppressed by systemic corticosteroid therapy.1

Additional Information

AHFS First Release. For additional information until a more detailed monograph is developed and published, the manufacturer's labeling should be consulted. It is essential that the manufacturer's labeling be consulted for more detailed information on usual uses, dosage and administration, cautions, precautions, contraindications, potential drug interactions, laboratory test interferences, and acute toxicity.

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.

Reslizumab

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Parenteral

Injection, Solution, Concentrate

10 mg /1 mL

Cinqair

Teva Respiratory LLC

AHFS DI Essentials. © Copyright, 2016, American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

Date published: September 13, 2016
Last reviewed: September 13, 2016
Date modified: October 12, 2016

References

1. Teva Respiratory, LLC. CINQAIR (Reslizumab) INTRAVENOUS prescribing information. 2016 June.

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