CINQAIR

Immunotherapies for Reactive and Obstructive Airway Diseases
Interleukin-5 (IL-5) Inhibitors

For intravenous (IV) infusion administration only. Do not administer via IV push or bolus or by any other route.
Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Infusion Preparation:
Remove the appropriate number of vials from refrigeration. To minimize foaming, do not shake reslizumab.
The solution is a clear to slightly hazy/opalescent, colorless to slightly yellow liquid. Proteinaceous particles may be present that appear as translucent to white, amorphous particulates. Do not use if the solution is discolored or if other foreign particulate matter is present.
Withdraw the necessary volume of reslizumab based on the weight-based dosage needed. Discard any remaining unused portion in open vials. The vials are for single-use only.
Must be further diluted prior to administration.
Inject contents slowly into an infusion bag of 50 mL of 0.9% Sodium Chloride Injection to minimize foaming. Reslizumab is compatible with polyvinylchloride (PVC) or polyolefin infusion bags.
Gently invert the bag to mix the solution. Do NOT shake. Do not mix or dilute with other drugs.
Administer the infusion immediately after preparation.
Storage following dilution: If not used immediately, the prepared infusion may be stored in the refrigerator at 2 to 8 degrees C (36 to 46 degrees F) or at room temperature up to 25 degrees C (77 degrees F), protected from light, for up to 16 hours. The time between preparation of reslizumab and administration should not exceed 16 hours.
 
Intravenous Infusion Administration:
Give only in a healthcare setting by professionals prepared to manage anaphylaxis.
If the infusion was refrigerated prior to use, allow the refrigerated infusion solution to reach room temperature before administration. Do not use a warming device to bring the infusion to room temperature.
Use an infusion set with an in-line, low protein-binding filter (pore size of 0.2 micron). Reslizumab is compatible with polyethersulfone (PES), polyvinylidene fluoride (PVDF), nylon, and cellulose acetate in-line infusion filters.
Infuse intravenously over 20 to 50 minutes. Infusion time may vary depending on the total volume to be infused.
Do not infuse reslizumab in the same intravenous line with other agents. No compatibility studies have been conducted to evaluate co-administration with other agents.
Observe the patient during the infusion and for an appropriate amount of time following the infusion for adverse reactions. Discontinue the infusion immediately if the patient experiences a severe systemic reaction, including anaphylaxis, and treat appropriately.
Flush the intravenous administration set with 0.9% Sodium Chloride Injection to ensure complete administration.

serious hypersensitivity reactions or anaphylaxis / Rapid / 0-1.0
new primary malignancy / Delayed / 0.6-0.6

antibody formation / Delayed / 4.8-5.4
hypotension / Rapid / Incidence not known
dyspnea / Early / Incidence not known
wheezing / Rapid / Incidence not known

pharyngitis / Delayed / 2.6-2.6
musculoskeletal pain / Early / 2.2-2.2
myalgia / Early / 1.0-1.0
urticaria / Rapid / Incidence not known
rash / Early / Incidence not known
dizziness / Early / Incidence not known
vomiting / Early / Incidence not known
sinusitis / Delayed / Incidence not known
headache / Early / Incidence not known
nasal congestion / Early / Incidence not known
cough / Delayed / Incidence not known
fatigue / Early / Incidence not known
muscle cramps / Delayed / Incidence not known

CINQAIR

Rx

An intravenously administered humanized monoclonal antibody that targets interleukin 5 and reduces eosinophil-meditated inflammation of the airways
Indicated in adults for add-on maintenance treatment of severe asthma with an eosinophilic phenotype
Anaphylaxis has been reported as early as the second dose; monitor patients closely during and after infusion

3 mg/kg IV infusion once every 4 weeks. Discontinue the infusion immediately if the patient experiences a severe systemic reaction, including anaphylaxis.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.

CINQAIR Intravenous Inj Sol: 1mL, 10mg

3 mg/kg IV infusion once every 4 weeks.

3 mg/kg IV infusion once every 4 weeks.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Not indicated.

Not indicated.

Reslizumab is an interleukin-5 antagonist (IgG4, kappa). IL-5 is the major cytokine involved in the growth, differentiation, recruitment, activation, and survival of eosinophils. Eosinophils are one of multiple cell types involved in the inflammatory pathogenesis of asthma. Reslizumab binds to and inhibits the bioactivity of IL-5 by blocking its binding to the alpha chain of the IL-5 receptor complex expressed on the eosinophil surface. Reductions in eosinophil production and survival are produced by the inhibition of IL-5 signaling.

Reslizumab is administered intravenously by infusion. Minimal distribution into extravascular tissues is expected due to a volume of distribution of approximately 5 liters. Reslizumab is degraded by enzymatic proteolysis into small peptides and amino acids. It is not expected to go through a target-mediated clearance due to soluble target binding. Reslizumab clearance is approximately 7 mL/hour. The half-life of reslizumab is approximately 24 days.
 
During clinical studies with reslizumab dose of 3 mg/kg, a 92% reduction in eosinophil counts was observed following the first dose and maintained through 52 weeks of treatment with no signs of tachyphylaxis. Early eosinophil reduction (days 2 to 3 post-treatment) was observed in 35 of 245 patients. Eosinophils returned to baseline approximately 120 days after the last dose. Systemic exposure appears to be unaffected by the presence of treatment-emergent anti-reslizumab antibodies.
 
Affected cytochrome P450 (CYP450) isoenzymes and drug transporters: None
In vitro data indicate that IL-5 and reslizumab are unlikely to affect CYP1A2, CYP2B6, or CYPA4 activity.

Peak and overall exposure to reslizumab after intravenous infusion are similar across patient populations of healthy adults and those with asthma using weight-based dosing. Peak serum concentrations of reslizumab are typically observed at the end of the infusion. Concentrations decline in a biphasic manner. During pharmacokinetic analyses, serum concentrations accumulated 1.5 to 1.9-fold following multiple doses. Greater reductions in eosinophil serum concentrations are produced with higher drug concentrations.

Pregnancy exposure data is insufficient to inform on drug-associated risk with reslizumab. Monoclonal antibodies, such as reslizumab, are transported across the placenta in a linear fashion as pregnancy progresses; therefore, potential fetal effects are likely to be greater during the second and third trimesters. Reslizumab has a long half-life of 24 days; this time should be taken into account when considering exposure during pregnancy. In two development studies conducted in mice and rabbits, there was no evidence of fetal harm with IV reslizumab administration during organogenesis at drug exposures approximately 6 times the maximum recommended human dose (MRHD, 3 mg/kg IV) in rabbits and approximately 17 times the MHRD in mice. In women with poorly or moderately controlled asthma, there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Asthma control should be closely monitored during pregnancy and treatment adjusted to maintain optimal control.

There is no information regarding the presence of reslizumab in human milk, the effects on the breast-fed infant, or the effects on milk production. Reslizumab is a humanized monoclonal antibody (IgG1 kappa), and human immunoglobulin G (IgG) is present in human milk in small amounts. The FDA-approved product label recommends considering the developmental and health benefits of breast-feeding, the mother's need for reslizumab therapy, and potential adverse effects of the drug or inadequately treated asthma on the breast-fed infant. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, health care providers are encouraged to report the adverse effect to the FDA.