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RESLIZUMAB

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Reslizumab is an interleukin-5 (IL-5) antagonist (IgG4, kappa), used to treat adults with severe asthma with an eosinophilic phenotype.

Specific Substances

    1) CAS 241473-69-8
    2) Reslizumabum
    3) Sch-55700

Available Forms Sources

    A) FORMS
    1) Reslizumab is available as 100 mg/100 mL (10 mg/mL) solution in single-use vials (Prod Info CINQAIR(R) intravenous injection, 2016).
    B) USES
    1) Reslizumab is indicated for the add-on maintenance treatment of adults with severe asthma with an eosinophilic phenotype. It is not indicated for the treatment of other eosinophilic conditions or for the relief of acute bronchospasm or status asthmaticus (Prod Info CINQAIR(R) intravenous injection, 2016).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Reslizumab is indicated for the add-on maintenance treatment of adults with severe asthma and an eosinophilic phenotype. It is not indicated for the treatment of other eosinophilic conditions or for the relief of acute bronchospasm or status asthmaticus.
    B) PHARMACOLOGY: Reslizumab is an interleukin-5 (IL-5) antagonist (IgG4, kappa) that blocks the binding of IL-5 to the surface of eosinophils, thus reducing the production and survival of the eosinophil. However, the specific mechanism of reslizumab in the treatment of asthma has not been established.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) MOST COMMON (greater than or equal to 2%): Oropharyngeal pain. OTHER EFFECTS: Anaphylaxis, anti-reslizumab antibody response, CPK elevations, and musculoskeletal events, including musculoskeletal chest pain, neck pain, extremity pain, muscle spasms, fatigue, and musculoskeletal pain.
    E) WITH POISONING/EXPOSURE
    1) There have been no reports of overdose. Clinical events are anticipated to be similar to adverse events reported with reslizumab therapy.
    0.2.20) REPRODUCTIVE
    A) There are no adequate and well-controlled studies of reslizumab use in pregnant women. However, monoclonal antibodies, such as reslizumab, are known to cross the placenta in a linear fashion, and therefore, may be transmitted to the developing fetus with use, especially during the second and third trimester of pregnancy. No data are available on the presence of reslizumab in human breast milk, and the effects on the nursing infant and on milk production are not known.
    0.2.21) CARCINOGENICITY
    A) In clinical trials, malignant neoplasm developed in patients receiving reslizumab.

Laboratory Monitoring

    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    C) Monitor vital signs and CK following significant overdose.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF TOXICITY
    1) Treatment is symptomatic and supportive. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.
    B) DECONTAMINATION
    1) PREHOSPITAL: Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    2) HOSPITAL: Consider activated charcoal if the overdose is recent, the patient is not vomiting, and is able to maintain airway.
    C) AIRWAY MANAGEMENT
    1) Ensure adequate ventilation and perform endotracheal intubation early in patients with severe allergic reactions.
    D) ANTIDOTE
    1) None.
    E) ENHANCED ELIMINATION
    1) It is unknown if hemodialysis would be effective in overdose.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    2) OBSERVATION CRITERIA: Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.
    3) ADMISSION CRITERIA: Patients with severe symptoms despite treatment should be admitted.
    4) CONSULT CRITERIA: Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    G) PITFALLS
    1) When managing a suspected overdose, the treating physician should be cognizant of the possibility of multi-drug involvement.
    H) PHARMACOKINETICS
    1) Vd: Approximately 5 L (limited distribution to extravascular tissue). Metabolism: Reslizumab is degraded by enzymatic proteolysis into small peptides and amino acids. Total body clearance: Approximately 7 mL/hr. Elimination half-life: 24 days.
    I) DIFFERENTIAL DIAGNOSIS
    1) Includes other agents that may cause elevated CK or musculoskeletal pain.

Range Of Toxicity

    A) TOXICITY: In clinical trials, single doses of reslizumab up to 732 mg IV did not cause dose-related toxicity.
    B) THERAPEUTIC DOSE: ADULT: 3 mg/kg IV infusion over 20 to 50 minutes every 4 weeks. PEDIATRIC: Safety and effectiveness have not been established in pediatric patients.

Clinical Effects

Summary Of Exposure

    A) USES: Reslizumab is indicated for the add-on maintenance treatment of adults with severe asthma and an eosinophilic phenotype. It is not indicated for the treatment of other eosinophilic conditions or for the relief of acute bronchospasm or status asthmaticus.
    B) PHARMACOLOGY: Reslizumab is an interleukin-5 (IL-5) antagonist (IgG4, kappa) that blocks the binding of IL-5 to the surface of eosinophils, thus reducing the production and survival of the eosinophil. However, the specific mechanism of reslizumab in the treatment of asthma has not been established.
    C) EPIDEMIOLOGY: Overdose is rare.
    D) WITH THERAPEUTIC USE
    1) MOST COMMON (greater than or equal to 2%): Oropharyngeal pain. OTHER EFFECTS: Anaphylaxis, anti-reslizumab antibody response, CPK elevations, and musculoskeletal events, including musculoskeletal chest pain, neck pain, extremity pain, muscle spasms, fatigue, and musculoskeletal pain.
    E) WITH POISONING/EXPOSURE
    1) There have been no reports of overdose. Clinical events are anticipated to be similar to adverse events reported with reslizumab therapy.

Respiratory

    3.6.2) CLINICAL EFFECTS
    A) PAIN IN THROAT
    1) WITH THERAPEUTIC USE
    a) In clinical trials, oropharyngeal pain developed in 2.6% of patients receiving reslizumab and 2.2% of placebo patients (Prod Info CINQAIR(R) intravenous injection, 2016).

Musculoskeletal

    3.15.2) CLINICAL EFFECTS
    A) INCREASED CREATINE KINASE LEVEL
    1) WITH THERAPEUTIC USE
    a) In clinical trials, transient creatine phosphokinase (CPK) elevations over normal baseline developed in 20% of patients receiving reslizumab and 18% of placebo patients. CPK elevations greater than 10 X Upper Limit of Normal (ULN) occurred in 0.8% patients receiving reslizumab and 0.4% of placebo patients (Prod Info CINQAIR(R) intravenous injection, 2016).
    B) MUSCLE PAIN
    1) WITH THERAPEUTIC USE
    a) Musculoskeletal events on the day of infusion, including musculoskeletal chest pain, neck pain, extremity pain, muscle spasms, fatigue, and musculoskeletal pain were reported in 2.2% of patients receiving reslizumab and 1.5% of placebo patients (Prod Info CINQAIR(R) intravenous injection, 2016)

Immunologic

    3.19.2) CLINICAL EFFECTS
    A) HYPERSENSITIVITY REACTION
    1) WITH THERAPEUTIC USE
    a) In clinical trials, anaphylaxis developed in 3 patients, during or within 20 minutes after completing infusion and reported as early as second dose. Symptoms included dyspnea, decreased oxygen saturation, wheezing, vomiting, and skin and mucosal reactions, including urticaria (Prod Info CINQAIR(R) intravenous injection, 2016).
    B) ANTIBODY DEVELOPMENT
    1) WITH THERAPEUTIC USE
    a) In clinical trials, anti-reslizumab antibody response developed in 5.4% (53/983) of patients receiving reslizumab from up to 16 weeks to more than 2 years. Anti-reslizumab antibody response developed in 4.8% (49/1014) of patients receiving reslizumab over 36 months. Antibody responses detected were of low titer and generally transient (Prod Info CINQAIR(R) intravenous injection, 2016).

Reproductive

    3.20.1) SUMMARY
    A) There are no adequate and well-controlled studies of reslizumab use in pregnant women. However, monoclonal antibodies, such as reslizumab, are known to cross the placenta in a linear fashion, and therefore, may be transmitted to the developing fetus with use, especially during the second and third trimester of pregnancy. No data are available on the presence of reslizumab in human breast milk, and the effects on the nursing infant and on milk production are not known.
    3.20.2) TERATOGENICITY
    A) ANIMAL STUDIES
    1) In animal studies, IV reslizumab during organogenesis did not result in adverse developmental effects at doses of up to 17 times the maximum recommended human dose (Prod Info CINQAIR(R) intravenous injection, 2016).
    3.20.3) EFFECTS IN PREGNANCY
    A) RISK SUMMARY
    1) There are no adequate and well-controlled studies of reslizumab use in pregnant women. However, monoclonal antibodies, such as reslizumab, are known to cross the placenta in a linear fashion, and therefore, may be transmitted to the developing fetus with use, especially during the second and third trimester of pregnancy. Reslizumab also has a long half-life (Prod Info CINQAIR(R) intravenous injection, 2016).
    3.20.4) EFFECTS DURING BREAST-FEEDING
    A) BREAST MILK
    1) No data are available on the presence of reslizumab in human breast milk, and the effects on the nursing infant and on milk production are not known. However, reslizumab was excreted into the milk of lactating animals at exposures up to 6 times the maximum recommended human dose (based on AUC). Reslizumab levels were approximately 5% to 7% of maternal serum concentrations (Prod Info CINQAIR(R) intravenous injection, 2016).
    2) Before administering reslizumab to a lactating woman, consider the developmental and health benefits of breastfeeding and the mother's clinical need for reslizumab versus the potential adverse effects on the nursing infant from exposure (Prod Info CINQAIR(R) intravenous injection, 2016).
    3.20.5) FERTILITY
    A) ANIMAL STUDIES
    1) In animal studies, no effects on male or female mating or fertility were observed when parenteral mice were administered reslizumab doses up to about 6 times the MRHD on an AUC basis (Prod Info CINQAIR(R) intravenous injection, 2016).

Carcinogenicity

    3.21.2) SUMMARY/HUMAN
    A) In clinical trials, malignant neoplasm developed in patients receiving reslizumab.
    3.21.3) HUMAN STUDIES
    A) MALIGNANCY
    1) In clinical trials, malignant neoplasm developed in 0.6% (6/1028) of patients receiving 3 mg/kg of reslizumab and 0.3% (2/730) of patients in the placebo group. Malignancies in clinical trials were diverse in nature and not of any particular tissue type. Most were diagnosed within less than 6 months of treatment (Prod Info CINQAIR(R) intravenous injection, 2016).
    3.21.4) ANIMAL STUDIES
    A) LACK OF EFFECT
    1) In a 6-month bioassay, no evidence of carcinogenicity was observed when Tg.rasH2 mice were administered reslizumab IV once every 2 weeks for 26 consecutive weeks (13 total doses) (Prod Info CINQAIR(R) intravenous injection, 2016).

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    C) Monitor vital signs and CK following significant overdose.

Treatment

Monitoring

    A) No specific laboratory tests are necessary unless otherwise clinically indicated.
    B) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    C) Monitor vital signs and CK following significant overdose.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) ACTIVATED CHARCOAL
    1) PREHOSPITAL ACTIVATED CHARCOAL ADMINISTRATION
    a) Consider prehospital administration of activated charcoal as an aqueous slurry in patients with a potentially toxic ingestion who are awake and able to protect their airway. Activated charcoal is most effective when administered within one hour of ingestion. Administration in the prehospital setting has the potential to significantly decrease the time from toxin ingestion to activated charcoal administration, although it has not been shown to affect outcome (Alaspaa et al, 2005; Thakore & Murphy, 2002; Spiller & Rogers, 2002).
    1) In patients who are at risk for the abrupt onset of seizures or mental status depression, activated charcoal should not be administered in the prehospital setting, due to the risk of aspiration in the event of spontaneous emesis.
    2) The addition of flavoring agents (cola drinks, chocolate milk, cherry syrup) to activated charcoal improves the palatability for children and may facilitate successful administration (Guenther Skokan et al, 2001; Dagnone et al, 2002).
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.2) PREVENTION OF ABSORPTION
    A) ACTIVATED CHARCOAL
    1) CHARCOAL ADMINISTRATION
    a) Consider administration of activated charcoal after a potentially toxic ingestion (Chyka et al, 2005). Administer charcoal as an aqueous slurry; most effective when administered within one hour of ingestion.
    2) CHARCOAL DOSE
    a) Use a minimum of 240 milliliters of water per 30 grams charcoal (FDA, 1985). Optimum dose not established; usual dose is 25 to 100 grams in adults and adolescents; 25 to 50 grams in children aged 1 to 12 years (or 0.5 to 1 gram/kilogram body weight) ; and 0.5 to 1 gram/kilogram in infants up to 1 year old (Chyka et al, 2005).
    1) Routine use of a cathartic with activated charcoal is NOT recommended as there is no evidence that cathartics reduce drug absorption and cathartics are known to cause adverse effects such as nausea, vomiting, abdominal cramps, electrolyte imbalances and occasionally hypotension (None Listed, 2004).
    b) ADVERSE EFFECTS/CONTRAINDICATIONS
    1) Complications: emesis, aspiration (Chyka et al, 2005). Aspiration may be complicated by acute respiratory failure, ARDS, bronchiolitis obliterans or chronic lung disease (Golej et al, 2001; Graff et al, 2002; Pollack et al, 1981; Harris & Filandrinos, 1993; Elliot et al, 1989; Rau et al, 1988; Golej et al, 2001; Graff et al, 2002). Refer to the ACTIVATED CHARCOAL/TREATMENT management for further information.
    2) Contraindications: unprotected airway (increases risk/severity of aspiration) , nonfunctioning gastrointestinal tract, uncontrolled vomiting, and ingestion of most hydrocarbons (Chyka et al, 2005).
    6.5.3) TREATMENT
    A) SUPPORT
    1) MANAGEMENT OF TOXICITY
    a) Treatment is symptomatic and supportive. In patients with acute allergic reaction, oxygen therapy, bronchodilators, diphenhydramine, corticosteroids, vasopressors and epinephrine may be required.
    B) MONITORING OF PATIENT
    1) No specific laboratory tests are necessary unless otherwise clinically indicated.
    2) Plasma concentrations are not readily available or clinically useful in the management of overdose.
    3) Monitor vital signs and CK following significant overdose.
    C) HYPERSENSITIVITY REACTION
    1) SUMMARY
    a) Mild to moderate allergic reactions may be treated with antihistamines with or without inhaled beta adrenergic agonists, corticosteroids or epinephrine. Treatment of severe anaphylaxis also includes oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.
    2) BRONCHOSPASM
    a) ALBUTEROL
    1) ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007). CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 mg/kg (up to 10 mg) every 1 to 4 hours as needed, or 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    3) CORTICOSTEROIDS
    a) Consider systemic corticosteroids in patients with significant bronchospasm.
    b) PREDNISONE: ADULT: 40 to 80 milligrams/day. CHILD: 1 to 2 milligrams/kilogram/day (maximum 60 mg) in 1 to 2 divided doses divided twice daily (National Heart,Lung,and Blood Institute, 2007).
    4) MILD CASES
    a) DIPHENHYDRAMINE
    1) SUMMARY: Oral diphenhydramine, as well as other H1 antihistamines can be used as indicated (Lieberman et al, 2010).
    2) ADULT: 50 milligrams orally, or 10 to 50 mg intravenously at a rate not to exceed 25 mg/min or may be given by deep intramuscular injection. A total of 100 mg may be administered if needed. Maximum daily dosage is 400 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    3) CHILD: 5 mg/kg/24 hours or 150 mg/m(2)/24 hours. Divided into 4 doses, administered intravenously at a rate not exceeding 25 mg/min or by deep intramuscular injection. Maximum daily dosage is 300 mg (Prod Info diphenhydramine HCl intravenous injection solution, intramuscular injection solution, 2013).
    5) MODERATE CASES
    a) EPINEPHRINE: INJECTABLE SOLUTION: It should be administered early in patients by IM injection. Using a 1:1000 (1 mg/mL) solution of epinephrine. Initial Dose: 0.01 mg/kg intramuscularly with a maximum dose of 0.5 mg in adults and 0.3 mg in children. The dose may be repeated every 5 to 15 minutes, if no clinical improvement. Most patients respond to 1 or 2 doses (Nowak & Macias, 2014).
    6) SEVERE CASES
    a) EPINEPHRINE
    1) INTRAVENOUS BOLUS: ADULT: 1 mg intravenously as a 1:10,000 (0.1 mg/mL) solution; CHILD: 0.01 mL/kg intravenously to a maximum single dose of 1 mg given as a 1:10,000 (0.1 mg/mL) solution. It can be repeated every 3 to 5 minutes as needed. The dose can also be given by the intraosseous route if IV access cannot be established (Lieberman et al, 2015). ALTERNATIVE ROUTE: ENDOTRACHEAL ADMINISTRATION: If IV/IO access is unavailable. DOSE: ADULT: Administer 2 to 2.5 mg of 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube. CHILD: DOSE: 0.1 mg/kg to a maximum of 2.5 mg administered as a 1:1000 (1 mg/mL) solution diluted in 5 to 10 mL of sterile water via endotracheal tube (Lieberman et al, 2015).
    2) INTRAVENOUS INFUSION: Intravenous administration may be considered in patients poorly responsive to IM or SubQ epinephrine. An epinephrine infusion may be prepared by adding 1 mg (1 mL of 1:1000 (1 mg/mL) solution) to 250 mL D5W, yielding a concentration of 4 mcg/mL, and infuse this solution IV at a rate of 1 mcg/min to 10 mcg/min (maximum rate). CHILD: A dosage of 0.01 mg/kg (0.1 mL/kg of a 1:10,000 (0.1 mg/mL) solution up to 10 mcg/min (maximum dose 0.3 mg) is recommended for children (Lieberman et al, 2010). Careful titration of a continuous infusion of IV epinephrine, based on the severity of the reaction, along with a crystalloid infusion can be considered in the treatment of anaphylactic shock. It appears to be a reasonable alternative to IV boluses, if the patient is not in cardiac arrest (Vanden Hoek,TL,et al).
    7) AIRWAY MANAGEMENT
    a) OXYGEN: 5 to 10 liters/minute via high flow mask.
    b) INTUBATION: Perform early if any stridor or signs of airway obstruction.
    c) CRICOTHYROTOMY: Use if unable to intubate with complete airway obstruction (Vanden Hoek,TL,et al).
    d) BRONCHODILATORS are recommended for mild to severe bronchospasm.
    e) ALBUTEROL: ADULT: 2.5 to 5 milligrams in 2 to 4.5 milliliters of normal saline delivered per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 2.5 to 10 mg every 1 to 4 hours as needed, or 10 to 15 mg/hr by continuous nebulization as needed (National Heart,Lung,and Blood Institute, 2007).
    f) ALBUTEROL: CHILD: 0.15 milligram/kilogram (minimum 2.5 milligrams) per nebulizer every 20 minutes up to 3 doses. If incomplete response administer 0.15 to 0.3 milligram/kilogram (maximum 10 milligrams) every 1 to 4 hours as needed OR administer 0.5 mg/kg/hr by continuous nebulization (National Heart,Lung,and Blood Institute, 2007).
    8) MONITORING
    a) CARDIAC MONITOR: All complicated cases.
    b) IV ACCESS: Routine in all complicated cases.
    9) HYPOTENSION
    a) If hypotensive give 500 to 2000 milliliters crystalloid initially (20 milliliters/kilogram in children) and titrate to desired effect (stabilization of vital signs, mentation, urine output); adults may require up to 6 to 10 L/24 hours. Central venous or pulmonary artery pressure monitoring is recommended in patients with persistent hypotension.
    1) VASOPRESSORS: Should be used in refractory cases unresponsive to repeated doses of epinephrine and after vigorous intravenous crystalloid rehydration (Lieberman et al, 2010).
    2) DOPAMINE: Initial Dose: 2 to 20 micrograms/kilogram/minute intravenously; titrate to maintain systolic blood pressure greater than 90 mm Hg (Lieberman et al, 2010).
    10) H1 and H2 ANTIHISTAMINES
    a) SUMMARY: Antihistamines are second-line therapy and are used as supportive therapy and should not be used in place of epinephrine (Lieberman et al, 2010).
    1) DIPHENHYDRAMINE: ADULT: 25 to 50 milligrams via a slow intravenous infusion or IM. PEDIATRIC: 1 milligram/kilogram via slow intravenous infusion or IM up to 50 mg in children (Lieberman et al, 2010).
    b) RANITIDINE: ADULT: 1 mg/kg parenterally; CHILD: 12.5 to 50 mg parenterally. If the intravenous route is used, ranitidine should be infused over 10 to 15 minutes or diluted in 5% dextrose to a volume of 20 mL and injected over 5 minutes (Lieberman et al, 2010).
    c) Oral diphenhydramine, as well as other H1 antihistamines, can also be used as indicated (Lieberman et al, 2010).
    11) DYSRHYTHMIAS
    a) Dysrhythmias and cardiac dysfunction may occur primarily or iatrogenically as a result of pharmacologic treatment (epinephrine) (Vanden Hoek,TL,et al). Monitor and correct serum electrolytes, oxygenation and tissue perfusion. Treat with antiarrhythmic agents as indicated.
    12) OTHER THERAPIES
    a) There have been a few reports of patients with anaphylaxis, with or without cardiac arrest, that have responded to vasopressin therapy that did not respond to standard therapy. Although there are no randomized controlled trials, other alternative vasoactive therapies (ie, vasopressin, norepinephrine, methoxamine, and metaraminol) may be considered in patients in cardiac arrest secondary to anaphylaxis that do not respond to epinephrine (Vanden Hoek,TL,et al).

Enhanced Elimination

    A) HEMODIALYSIS
    1) It is unknown if hemodialysis would be effective in overdose.

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with severe symptoms despite treatment should be admitted.
    6.3.1.2) HOME CRITERIA/ORAL
    A) A patient with an inadvertent exposure, that remains asymptomatic can be managed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) Consult a regional poison center or medical toxicologist for assistance in managing patients with severe toxicity or in whom the diagnosis is not clear.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with a deliberate overdose, and those who are symptomatic, need to be monitored until they are clearly improving and clinically stable.

Range Of Toxicity

Summary

    A) TOXICITY: In clinical trials, single doses of reslizumab up to 732 mg IV did not cause dose-related toxicity.
    B) THERAPEUTIC DOSE: ADULT: 3 mg/kg IV infusion over 20 to 50 minutes every 4 weeks. PEDIATRIC: Safety and effectiveness have not been established in pediatric patients.

Therapeutic Dose

    7.2.1) ADULT
    A) 3 mg/kg via IV infusion over 20 to 50 minutes every 4 weeks (Prod Info CINQAIR(R) intravenous injection, 2016).
    7.2.2) PEDIATRIC
    A) Safety and effectiveness have not been established in pediatric patients (Prod Info CINQAIR(R) intravenous injection, 2016).

Maximum Tolerated Exposure

    A) In clinical trials, single doses of reslizumab up to 732 mg IV did not cause dose-related toxicity (Prod Info CINQAIR(R) intravenous injection, 2016).

Pharmacology Toxicology

Pharmacologic Mechanism

    A) Reslizumab is an interleukin-5 (IL-5) antagonist (IgG4, kappa) that blocks the binding of IL-5 to the surface of eosinophils, thus reducing the production and survival of the eosinophil. However, the specific mechanism of reslizumab in the treatment of asthma has not been established (Prod Info CINQAIR(R) intravenous injection, 2016).

Physicochemical

Physical Characteristics

    A) A sterile, preservative-free, clear to slightly hazy/opalescent, colorless to slightly yellow solution for intravenous infusion (Prod Info CINQAIR(R) intravenous injection, 2016).

Molecular Weight

    A) About 147 kDa (Prod Info CINQAIR(R) intravenous injection, 2016).

References

General Bibliography

    1) Alaspaa AO, Kuisma MJ, Hoppu K, et al: Out-of-hospital administration of activated charcoal by emergency medical services. Ann Emerg Med 2005; 45:207-12.
    2) Chyka PA, Seger D, Krenzelok EP, et al: Position paper: Single-dose activated charcoal. Clin Toxicol (Phila) 2005; 43(2):61-87.
    3) Dagnone D, Matsui D, & Rieder MJ: Assessment of the palatability of vehicles for activated charcoal in pediatric volunteers. Pediatr Emerg Care 2002; 18:19-21.
    4) Elliot CG, Colby TV, & Kelly TM: Charcoal lung. Bronchiolitis obliterans after aspiration of activated charcoal. Chest 1989; 96:672-674.
    5) FDA: Poison treatment drug product for over-the-counter human use; tentative final monograph. FDA: Fed Register 1985; 50:2244-2262.
    6) Golej J, Boigner H, Burda G, et al: Severe respiratory failure following charcoal application in a toddler. Resuscitation 2001; 49:315-318.
    7) Graff GR, Stark J, & Berkenbosch JW: Chronic lung disease after activated charcoal aspiration. Pediatrics 2002; 109:959-961.
    8) Guenther Skokan E, Junkins EP, & Corneli HM: Taste test: children rate flavoring agents used with activated charcoal. Arch Pediatr Adolesc Med 2001; 155:683-686.
    9) Harris CR & Filandrinos D: Accidental administration of activated charcoal into the lung: aspiration by proxy. Ann Emerg Med 1993; 22:1470-1473.
    10) Lieberman P, Nicklas R, Randolph C, et al: Anaphylaxis-a practice parameter update 2015. Ann Allergy Asthma Immunol 2015; 115(5):341-384.
    11) Lieberman P, Nicklas RA, Oppenheimer J, et al: The diagnosis and management of anaphylaxis practice parameter: 2010 update. J Allergy Clin Immunol 2010; 126(3):477-480.
    12) National Heart,Lung,and Blood Institute: Expert panel report 3: guidelines for the diagnosis and management of asthma. National Heart,Lung,and Blood Institute. Bethesda, MD. 2007. Available from URL: http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.pdf.
    13) None Listed: Position paper: cathartics. J Toxicol Clin Toxicol 2004; 42(3):243-253.
    14) Nowak RM & Macias CG : Anaphylaxis on the other front line: perspectives from the emergency department. Am J Med 2014; 127(1 Suppl):S34-S44.
    15) Pollack MM, Dunbar BS, & Holbrook PR: Aspiration of activated charcoal and gastric contents. Ann Emerg Med 1981; 10:528-529.
    16) Product Information: CINQAIR(R) intravenous injection, reslizumab intravenous injection. Teva Pharmaceuticals (per manufacturer), Frazer, PA, 2016.
    17) Product Information: diphenhydramine HCl intravenous injection solution, intramuscular injection solution, diphenhydramine HCl intravenous injection solution, intramuscular injection solution. Hospira, Inc. (per DailyMed), Lake Forest, IL, 2013.
    18) Rau NR, Nagaraj MV, Prakash PS, et al: Fatal pulmonary aspiration of oral activated charcoal. Br Med J 1988; 297:918-919.
    19) Spiller HA & Rogers GC: Evaluation of administration of activated charcoal in the home. Pediatrics 2002; 108:E100.
    20) Thakore S & Murphy N: The potential role of prehospital administration of activated charcoal. Emerg Med J 2002; 19:63-65.
    21) Vanden Hoek,TL; Morrison LJ; Shuster M; et al: Part 12: Cardiac Arrest in Special Situations 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. American Heart Association. Dallas, TX. 2010. Available from URL: http://circ.ahajournals.org/cgi/reprint/122/18_suppl_3/S829. As accessed 2010-10-21.