Dosage & Administration
By using PrescriberAI, you agree to the AI Terms of Use.
Cinqair Prescribing Information
Anaphylaxis to CINQAIR was reported in 0.3% of asthma patients in placebo-controlled clinical studies
Anaphylaxis can be life-threatening. CINQAIR should be administered by a healthcare professional prepared to manage anaphylaxis. Patients should be observed for an appropriate period of time after CINQAIR administration. If severe systemic reactions, including anaphylaxis, occur, stop administration of CINQAIR immediately and provide appropriate medical treatment. Prior to CINQAIR administration, inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care if symptoms occur. Discontinue CINQAIR use permanently if the patient experiences signs or symptoms of anaphylaxis
The following adverse reactions are discussed in other sections of the labeling:
- Anaphylaxis[see Warnings and Precautions ]
- Malignancy[see Warnings and Precautions ]
The most common adverse reaction (incidence greater than or equal to 2%) includes oropharyngeal pain. .
To report SUSPECTED ADVERSE REACTIONS, contact Teva Pharmaceuticals at 1-888-483-8279 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
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. The data described below reflect exposure to CINQAIR in 1611 patients with asthma, including 1120 exposed for up to 16 weeks, 1006 exposed for 6 months, 759 exposed for 1 year, and 249 exposed for longer than 2 years. The above referenced safety exposure for CINQAIR is derived from placebo-controlled studies ranging from 15 to 52 weeks in duration (CINQAIR 0.3 mg/kg and 3 mg/kg [n=1131] and placebo [n=730]) and 480 new CINQAIR 3 mg/kg exposures (previously on placebo) from a single open-label extension study (n=1051). 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
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
Adverse reactions that occurred at greater than or equal to 2% incidence and more commonly than in the placebo group included 1 event: oropharyngeal pain (2.6% vs. 2.2%).
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.
Myalgia was reported in 1% (10/1028) of patients in the CINQAIR 3 mg/kg group compared to 0.5% (4/730) of patients in the placebo group. 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.
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). In the long-term, open-label study, treatment-emergent anti-reslizumab antibodies were detected in 49/1014 (4.8%) of CINQAIR-treated (3 mg/kg) asthma patients over 36 months. 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
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.
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:
- 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.
- CINQAIR should be administered by a healthcare professional prepared to manage anaphylaxis[see Warnings and Precautions ].
- 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.
Anaphylaxis to CINQAIR was reported in 0.3% of asthma patients in placebo-controlled clinical studies
Anaphylaxis can be life-threatening. CINQAIR should be administered by a healthcare professional prepared to manage anaphylaxis. Patients should be observed for an appropriate period of time after CINQAIR administration. If severe systemic reactions, including anaphylaxis, occur, stop administration of CINQAIR immediately and provide appropriate medical treatment. Prior to CINQAIR administration, inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care if symptoms occur. Discontinue CINQAIR use permanently if the patient experiences signs or symptoms of anaphylaxis
CINQAIR® is indicated for the add-on maintenance treatment of patients with severe asthma aged 18 years and older with an eosinophilic phenotype
The asthma development program for CINQAIR 3 mg/kg (administered once every 4 weeks) included 4 randomized, double-blind, placebo-controlled studies (Studies I-IV) 16 to 52 weeks in duration involving 981 patients 12 years of age and older. While patients aged 12 to 17 years were included in these trials, CINQAIR is not approved for use in this age group
Studies I and II were 52-week studies in 953 patients with asthma who were required to have a blood eosinophil count of at least 400/mcL (within 3 to 4 weeks of dosing), and at least 1 asthma exacerbation requiring systemic corticosteroid use over the past 12 months. The majority of patients (82%) were on medium-high dose inhaled corticosteroids plus a long-acting beta agonist (ICS/LABA) at baseline. Maintenance oral corticosteroids (OCS) (up to 10 mg of prednisone per day or equivalent) were allowed; 106 (11%) patients were on OCS at baseline. CINQAIR 3 mg/kg administered once every 4 weeks for a total of 13 doses was evaluated compared with placebo.
Study III was a 16-week study in 315 patients who were required to have a blood eosinophil count of at least 400/mcL at screening (within 3 to 4 weeks of dosing). Maintenance OCS were not allowed. CINQAIR 3 mg/kg or 0.3 mg/kg administered once every 4 weeks for a total of 4 doses was evaluated compared with placebo. While 2 doses of CINQAIR were studied, CINQAIR 3 mg/kg is the only recommended dose
Study IV was a 16-week study in 496 patients unselected for baseline blood eosinophil levels (approximately 80% of patients had a screening [within 3 to 4 weeks of dosing] blood eosinophil count of less than 400/mcL). Maintenance OCS were not allowed. CINQAIR 3 mg/kg administered once every 4 weeks for a total of 4 doses was evaluated compared with placebo.
The demographics and baseline characteristics of these 4 studies is provided in Table 1.
Study I (N=489) | Study II (N=464) | Study III (N=315) | Study IV (N=496) | |
|---|---|---|---|---|
Mean age (yr) | 47 | 47 | 44 | 45 |
Female (%) | 63 | 63 | 58 | 64 |
White (%) | 73 | 73 | 81 | 67 |
Duration of asthma, mean (yr) | 19 | 18 | 20 | 26 |
Baseline Pre-bronchodilator FEV1, mean % predictedBaseline for lung function and eosinophil count is the day of randomization. | 64 | 69 | 70 | 67 |
Baseline Reversibility, mean % ΔFEV1post-SABA | 26 | 28 | 25 | 26 |
Baseline mean blood eosinophil count/mcL | 660 | 649 | 614 | 280 |
Mean number of exacerbations in previous year | 1.99 | 1.94 | 2.03 | 1.86 |
FEV1=forced expiratory volume in 1 second; SABA=short-acting beta agonist.
All patients had to be on inhaled corticosteroid (ICS) background therapy and could have been receiving any combination of background therapies (ICS with or without another controller [non-ICS and/or OCS]).
The primary endpoint for Studies I and II was the frequency of asthma exacerbations for each patient during the 52-week treatment period. An asthma exacerbation was defined as a worsening of asthma that required at least 1 of the following medical interventions:
1) Either the use of a systemic corticosteroid, or ≥ 2-fold an increase in the use of ICS for 3 or more days, and/or
2) Asthma-related emergency treatment including at least 1 of the following: an unscheduled visit to their healthcare professional for nebulizer treatment or other urgent treatment to prevent worsening of asthma symptoms; a visit to the emergency room for asthma-related treatment; or an asthma-related hospitalization.
The medical intervention had to be corroborated with at least 1 of the following: 1) a decrease in forced expiratory volume in 1 second (FEV1) by 20% or more from baseline, 2) a decrease in peak expiratory flow rate (PEFR) by 30% or more from baseline on 2 consecutive days, or 3) worsening of symptoms or other clinical signs per physician evaluation of the event.
In Studies I and II, patients receiving CINQAIR 3 mg/kg administered once every 4 weeks had significant reductions in the rate of all asthma exacerbations compared to placebo (Table 2). Exacerbations requiring the use of a systemic corticosteroid (e.g., OCS) as well as exacerbations resulting in hospitalization or an emergency room visit were each reduced with CINQAIR 3 mg/kg.
Table 2: Frequency of Asthma Exacerbations during the 52-Week Treatment Period in Patients with Severe Asthma with an Eosinophilic Phenotype (Studies I and II) Randomized patients | |||
|---|---|---|---|
Treatment Arm | Asthma Exacerbation Rate | Rate Ratio (95% CI) | |
All exacerbations | |||
Study I | CINQAIR 3 mg/kg (n=245) | 0.90 | 0.5 (0.37, 0.67) |
Placebo (n=244) | 1.80 | ||
Study II | CINQAIR 3 mg/kg (n=232) | 0.86 | 0.41 (0.28, 0.59) |
Placebo (n=232) | 2.11 | ||
Exacerbations requiring systemic corticosteroid use | |||
Study I | CINQAIR 3 mg/kg (n=245) | 0.72 | 0.45 (0.33, 0.62) |
Placebo (n=244) | 1.60 | ||
Study II | CINQAIR 3 mg/kg (n=232) | 0.65 | 0.39 (0.27, 0.58) |
Placebo(n=232) | 1.66 | ||
Exacerbations resulting in a hospitalization and/or emergency room visit | |||
Study I | CINQAIR 3 mg/kg (n=245) | 0.14 | 0.66 (0.32, 1.36) |
Placebo(n=244) | 0.21 | ||
Study II | CINQAIR 3 mg/kg (n=232) | 0.03 | 0.69 (0.29, 1.65) |
Placebo (n=232) | 0.05 | ||
The proportion of patients who did not experience an asthma exacerbation during the 52-week treatment period was higher in the CINQAIR 3 mg/kg group (62% and 75%) compared with the placebo group (46% and 55%), in Studies I and II, respectively. The time to first asthma exacerbation was significantly longer for the groups receiving CINQAIR 3 mg/kg compared with placebo in both Studies I and II. A representative figure from Study I is shown below (Figure 1). Study II showed similar results.
The effect of CINQAIR 3 mg/kg administered once every 4 weeks on FEV1over time relative to placebo was assessed in all 4 studies (Table 3). FEV1was the primary endpoint in the 16-week lung function studies: Study III (Figure 2) and Study IV.
Study III also studied a lower dose, CINQAIR 0.3 mg/kg, that produced significant but numerically smaller changes in FEV1and blood eosinophil reduction compared with the 3 mg/kg dose. While 2 doses of CINQAIR were studied, CINQAIR 3 mg/kg is the only recommended dose
Study IV was the only study to test CINQAIR 3 mg/kg in asthma patients unselected for blood eosinophils (measured 3 to 4 weeks prior to dosing); association of treatment effect (i.e., difference between CINQAIR and placebo in the change in FEV1at Week 16) and baseline blood eosinophils was not observed.
Study | FEV1Change in mL |
Study I | 137 (76, 198) |
Study II | 93 (30, 155) |
Study III | 160 (60, 259) |
Study IVStudy IV studied asthma patients unselected for blood eosinophils | 76 (-6,158) |
Improvements in FEV1were observed at 4 weeks following the first dose of CINQAIR for Studies I and II and maintained through Week 52.
The Asthma Control Questionnaire-7 (ACQ-7) and Asthma Quality of Life Questionnaire (AQLQ) were both assessed in Studies I, II, and III. The responder rate for both measures was defined as an improvement in score of 0.5 or more as threshold over 16 weeks.
- For ACQ-7, the responder rate for those randomized to CINQAIR vs. placebo was 69% vs. 65% for Study I, 70% vs. 58% for Study II, and 64% vs. 58% for Study III.
- For AQLQ, the responder rate for those randomized to CINQAIR vs. placebo was 66% vs. 58% for Study I, 67% vs. 55% for Study II, and 64% vs. 48% for Study III.
- CINQAIR is not indicated for treatment of other eosinophilic conditions.
- CINQAIR is not indicated for the relief of acute bronchospasm or status asthmaticus [see Warnings and Precautions (.)]
5.2 Acute Asthma Symptoms or Deteriorating DiseaseCINQAIR should not be used to treat acute asthma symptoms or acute exacerbations. Do not use CINQAIR to treat acute bronchospasm or status asthmaticus. Patients should seek medical advice if their asthma remains uncontrolled or worsens after initiation of treatment with CINQAIR.
- CINQAIR is for intravenous infusion only. Do not administer as an intravenous push or bolus ()
2.1 DosingCINQAIR 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 ]. - CINQAIR should be administered by a healthcare professional prepared to manage anaphylaxis ()
2.2 Preparation and Administration InstructionsCINQAIR 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[see Warnings and Precautions ].
- 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.
- Recommended dosage regimen is 3 mg/kg once every 4 weeks by intravenous infusion over 20-50 minutes ()
2.1 DosingCINQAIR 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 ].
Injection: 100 mg/10 mL (10 mg/mL), clear to slightly hazy/opalescent, colorless to slightly yellow solution in single-use vials.
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
The pharmacokinetics (PK) of reslizumab were characterized in healthy adults (n=130), in patients with asthma (n=438), and in other patient populations (n=236). The PK characteristics of reslizumab were similar across these populations. Inter-individual variability in peak and overall exposure was approximately 20-30%.
Peak serum concentrations were typically observed at the end of the infusion. Serum reslizumab concentrations generally declined from peak in a biphasic manner. Following multiple doses, serum concentrations of reslizumab accumulated approximately 1.5 to 1.9-fold.
Systemic exposure to reslizumab appeared to be unaffected by the presence of treatment-emergent anti-reslizumab antibodies.
Reslizumab has a volume of distribution of approximately 5 liters, suggesting minimal distribution to the extravascular tissues.
Similar to other monoclonal antibodies, reslizumab is degraded by enzymatic proteolysis into small peptides and amino acids. As reslizumab binds to a soluble target, it is not expected to go through a target-mediated clearance.
Reslizumab clearance was approximately 7 mL/hour. Reslizumab has a half-life of about 24 days.
Population PK analyses demonstrated that there was no significant effect of age, race, or gender on the PK of reslizumab.
No clinical studies were conducted to assess the effect of hepatic impairment on the PK of reslizumab. The results of population PK analyses indicated that there was no significant difference in the PK of reslizumab between patients with normal liver function tests (total bilirubin less than or equal to the ULN and aspartate aminotransferase [AST] less than or equal to the ULN) and mildly increased liver function tests (total bilirubin above the ULN and less than or equal to 1.5-times the ULN or AST greater than ULN and total bilirubin less than or equal to the ULN).
No clinical studies have been conducted to assess the effect of renal impairment on the PK of reslizumab. The results of population PK analyses indicated that there was no significant difference in the PK of reslizumab between patients with normal renal function (estimated glomerular filtration rate [eGFR] greater than or equal to 90 mL/min/1.73 m2), mild renal impairment (eGFR 60-89 mL/min/1.73 m2), and moderate renal impairment (eGFR 30-59 mL/min/1.73 m2).
No formal clinical drug interaction studies have been conducted with reslizumab. Population PK analyses indicate that concomitant use of either leukotriene antagonists or corticosteroids does not affect the PK of reslizumab.
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 2 to 4% and 15 to 20%, respectively.
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.
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.
CINQAIR is contraindicated in patients who have known hypersensitivity to reslizumab or any of its excipients
Anaphylaxis to CINQAIR was reported in 0.3% of asthma patients in placebo-controlled clinical studies
Anaphylaxis can be life-threatening. CINQAIR should be administered by a healthcare professional prepared to manage anaphylaxis. Patients should be observed for an appropriate period of time after CINQAIR administration. If severe systemic reactions, including anaphylaxis, occur, stop administration of CINQAIR immediately and provide appropriate medical treatment. Prior to CINQAIR administration, inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care if symptoms occur. Discontinue CINQAIR use permanently if the patient experiences signs or symptoms of anaphylaxis