Cinqair

Dosing

CINQAIR is for intravenous infusion only. Do not administer as an intravenous push or bolus.

The recommended dosage regimen is 3 mg/kg once every 4 weeks administered by intravenous infusion over 20-50 minutes [see Dosage and Administration ].

Discontinue the infusion immediately if the patient experiences a severe systemic reaction, including anaphylaxis [see Contraindications , Warnings and Precautions ].

Preparation and Administration Instructions

CINQAIR is provided as a solution in a single-use vial for intravenous infusion only and should be prepared by a healthcare professional using aseptic technique as follows:

Preparation of intravenous infusion

1. Remove CINQAIR from the refrigerator. To minimize foaming, do not shake CINQAIR.
2. Inspect visually for particulate matter and discoloration prior to administration. CINQAIR solution is clear to slightly hazy/opalescent, colorless to slightly yellow liquid. Since CINQAIR 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.
3. Withdraw the proper volume of CINQAIR from the vial(s), based on the recommended weight-based dosage. Discard any unused portion.
4. Dispense syringe contents slowly into an infusion bag containing 50 mL of 0.9% Sodium Chloride Injection, USP to minimize foaming of CINQAIR (CINQAIR 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.
5. Administer immediately after preparation. If not used immediately, store diluted solutions of CINQAIR in the refrigerator at 2°C to 8°C (36°F to 46°F) or at room temperature up to 25ºC (77ºF), protected from light, for up to 16 hours. The time between preparation of CINQAIR and administration should not exceed 16 hours.

Administration instructions

1. CINQAIR should be administered by a healthcare professional prepared to manage anaphylaxis [see Warnings and Precautions ].
2. If refrigerated prior to administration, allow the diluted CINQAIR solution to reach room temperature.
3. Use an infusion set with an in-line, low protein-binding filter (pore size of 0.2 micron). CINQAIR is compatible with polyethersulfone (PES), polyvinylidene fluoride (PVDF), nylon, and cellulose acetate in-line infusion filters.
4. Infuse the diluted solution of CINQAIR intravenously, over a 20 to 50 minute period. Infusion time may vary depending on the total volume to be infused as based upon patient weight.
5. Do not infuse CINQAIR concomitantly in the same intravenous line with other agents. No physical or biochemical compatibility studies have been conducted to evaluate the co-administration of CINQAIR with other agents.
6. Observe the patient over the infusion and for an appropriate period of time following infusion.
7. Upon completion of the infusion, flush the intravenous administration set with 0.9% Sodium Chloride Injection, USP to ensure that all CINQAIR has been administered.

Pregnancy

Risk Summary

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 [see Clinical Pharmacology ]. This should be taken into consideration.

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 [see Data].

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.

Clinical Considerations

Disease-Associated Maternal and/or Embryo-Fetal Risk

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.

Data

Animal Data

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.

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 to 8% of those in the dams (parental female mice) on postnatal day 14.

Lactation

Risk Summary

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 [see Data]. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for CINQAIR and any potential adverse effects on the breast-fed child from CINQAIR or the underlying maternal condition.

Data

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.

Pediatric Use

CINQAIR 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.

CINQAIR 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 CINQAIR than placebo (CINQAIR 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]).

Geriatric Use

CINQAIR 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 CINQAIR in geriatric patients is necessary.