Cinqair Drug Information

CINQAIR ® is indicated for the add-on maintenance treatment of patients with severe asthma aged 18 years and older with an eosinophilic phenotype. Limitation of Use: CINQAIR is not indicated for treatment of other eosinophilic conditions. CINQAIR is not indicated for the relief of acute bronchospasm or status asthmaticus.

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. Discontinue the infusion immediately if the patient experiences a severe systemic reaction, including anaphylaxis.

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 Remove CINQAIR from the refrigerator. To minimize foaming, do not shake CINQAIR. 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.

Withdraw the proper volume of CINQAIR from the vial(s), based on the recommended weight-based dosage. Discard any unused portion. 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.

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 CINQAIR should be administered by a healthcare professional prepared to manage anaphylaxis. If refrigerated prior to administration, allow the diluted CINQAIR solution to reach room temperature. 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. 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.

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. Observe the patient over the infusion and for an appropriate period of time following infusion.

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.

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. Overall, 2195 subjects received at least 1 dose of CINQAIR. While a lower dose of CINQAIR 0.3 mg/kg (n=103) was included in a clinical trial, 3 mg/kg is the only recommended dose.

While subjects aged 12 to 17 years were included in these trials, CINQAIR is not approved for use in this age group. Serious adverse reactions that occurred in placebo-controlled studies in more than 1 subject and in a greater percentage of subjects treated with CINQAIR (n=1131) than placebo (n=730) included anaphylaxis (3 subjects vs. 0 subjects, respectively). The 3 subjects who experienced anaphylaxis were discontinued from the clinical studies.

Malignancy also occurred more commonly in patients treated with CINQAIR than placebo (0.6% and 0.3%, respectively). CPK elevations and muscle-related adverse reactions Elevated baseline creatine phosphokinase (CPK) was more frequent in patients randomized to CINQAIR (14%) versus placebo (9%). Transient CPK elevations in patients with normal baseline CPK values were observed more frequently with CINQAIR (20%) versus placebo (18%) during routine laboratory assessments.

CPK elevations >10 x ULN, regardless of baseline CPK value, were 0.8% in the CINQAIR group compared to 0.4% in the placebo group. CPK elevations >10 x ULN were asymptomatic and did not lead to treatment discontinuation. On the day of infusion, musculoskeletal adverse reactions were reported in 2.2% and 1.5% of patients treated with CINQAIR 3 mg/kg and placebo, respectively.

These reactions included (but were not limited to) musculoskeletal chest pain, neck pain, muscle spasms, extremity pain, muscle fatigue, and musculoskeletal pain.

Immunogenicity As with all therapeutic proteins, there is a potential for immunogenicity. In placebo-controlled studies, a treatment-emergent anti-reslizumab antibody response developed in 53/983 (5.4%) of CINQAIR-treated patients (3 mg/kg). The antibody responses were of low titer and often transient.

Neutralizing antibodies were not evaluated. There was no detectable impact of the antibodies on the clinical pharmacokinetics, pharmacodynamics, clinical efficacy, and safety of CINQAIR. Product-specific IgE antibodies were not detected in patients who reported anaphylactic reactions.

The data reflect the percentage of patients whose test results were positive for antibodies to reslizumab in specific assays. The observed incidence of antibody response is highly dependent on several factors, including assay sensitivity and specificity, assay methodology, sample handling, timing of sample collection, concomitant medication, and underlying disease. For these reasons, comparison of the incidence of antibodies to reslizumab with the incidence of antibodies to other products may be misleading.

No formal clinical drug interaction studies have been performed with CINQAIR.

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.

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. 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 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.

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. 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.

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.

CINQAIR is contraindicated in patients who have known hypersensitivity to reslizumab or any of its excipients.

Single doses of up to 732 mg have been administered intravenously to subjects in clinical trials without evidence of dose-related toxicities. There is no specific treatment for an overdose with CINQAIR. If overdose occurs, the patient should be treated supportively with appropriate monitoring as necessary.