CINQAERO: Uses, Dosage & Side Effects

What Is CINQAERO and What Is It Used For?

CINQAERO contains the active substance reslizumab, a humanized immunoglobulin G4 kappa (IgG4κ) monoclonal antibody produced using recombinant DNA technology. Monoclonal antibodies are highly specialized proteins engineered to recognize and bind to one specific molecular target in the body with exceptional precision. In the case of reslizumab, that target is interleukin-5 (IL-5), a cytokine – a type of signaling protein – that plays a central and indispensable role in the biology of eosinophils, a type of white blood cell intimately involved in allergic and asthmatic inflammation.

Eosinophils are granulocytes that normally constitute only 1–3% of circulating white blood cells. However, in patients with eosinophilic asthma, these cells accumulate in abnormally high numbers in both the blood and the airways. Eosinophilic asthma is a distinct phenotype of asthma, estimated to affect approximately 50–60% of patients with severe asthma. It is characterized by persistent airway eosinophilia (elevated eosinophil counts in sputum, bronchoalveolar lavage fluid, or bronchial tissue) and typically blood eosinophilia as well. Patients with this phenotype tend to experience more frequent and severe asthma exacerbations, faster decline in lung function over time, greater mucus plugging of the airways, and a disproportionately heavy burden of symptoms despite receiving high doses of inhaled corticosteroids combined with other controller medications such as long-acting beta-agonists (LABAs), leukotriene modifiers, or long-acting muscarinic antagonists (LAMAs).

IL-5 is the primary cytokine responsible for regulating almost every aspect of eosinophil biology. It promotes eosinophil differentiation from precursor cells in the bone marrow, stimulates their maturation, prolongs their survival by inhibiting apoptosis (programmed cell death), enhances their activation, and drives their recruitment from the bloodstream into tissues – particularly the lung airways in the context of asthma. IL-5 signals through the IL-5 receptor alpha subunit (IL-5Rα), which is expressed on the surface of eosinophils and their precursors, in combination with the common beta chain (βc) shared with the receptors for IL-3 and GM-CSF. By binding to circulating IL-5 with high affinity and specificity, reslizumab blocks IL-5 from engaging with its receptor, effectively shutting down the primary signaling pathway that sustains the eosinophilic inflammatory cascade.

The clinical development of reslizumab was supported by two duplicate pivotal phase III randomized, double-blind, placebo-controlled trials (Study 3082 and Study 3083), each enrolling approximately 490 patients with inadequately controlled asthma despite medium-to-high-dose inhaled corticosteroid therapy and who had blood eosinophil counts of at least 400 cells per microliter at screening. In both studies, patients receiving intravenous reslizumab at 3 mg/kg every 4 weeks for 52 weeks demonstrated statistically significant and clinically meaningful reductions in the rate of clinical asthma exacerbations compared with placebo. The pooled analysis showed a 54% reduction in exacerbation rates (rate ratio 0.46, 95% CI 0.37–0.58, p < 0.0001). Additionally, reslizumab-treated patients showed significant improvements in forced expiratory volume in 1 second (FEV1), with improvements evident as early as 4 weeks after the first infusion and sustained throughout the 52-week treatment period. Patient-reported outcomes, including the Asthma Quality of Life Questionnaire (AQLQ) and the Asthma Control Questionnaire (ACQ), also improved significantly in the reslizumab groups.

CINQAERO was first approved by the U.S. Food and Drug Administration (FDA) in March 2016 under the brand name Cinqair, and subsequently by the European Medicines Agency (EMA) in August 2016 as CINQAERO. It is now approved in numerous countries across Europe, North America, and other regions worldwide. Reslizumab is one of three anti-IL-5 biologic therapies currently available for severe eosinophilic asthma, alongside mepolizumab (Nucala), which also targets IL-5 directly, and benralizumab (Fasenra), which targets the IL-5 receptor alpha subunit. Each agent differs in its route of administration (intravenous versus subcutaneous), dosing schedule, and specific mechanism of eosinophil reduction.

What Should You Know Before Taking CINQAERO?

Contraindications

The only absolute contraindication to CINQAERO is hypersensitivity (allergy) to reslizumab or to any of the other ingredients in the formulation. The excipients in CINQAERO include sodium acetate trihydrate, glacial acetic acid, sucrose, and water for injections. If you have a known allergy to any of these substances, you must not receive CINQAERO.

Anaphylactic reactions have been observed in clinical trials with reslizumab. In the controlled clinical trials, anaphylaxis was reported in 0.3% of patients receiving reslizumab (3 out of 1,028 patients). These reactions occurred during or within 20 minutes of completing the infusion and included symptoms such as dyspnea (difficulty breathing), decreased oxygen saturation, wheezing, urticaria (hives), and skin flushing. All cases were managed with standard emergency treatment including epinephrine and were resolved. Due to this risk, CINQAERO must always be administered in a healthcare setting where personnel and equipment for managing anaphylaxis are immediately available.

Warnings and Precautions

Before starting CINQAERO, discuss the following with your healthcare provider:

• Parasitic (helminth) infections: Eosinophils play a critical role in the immune response against helminth (parasitic worm) infections. Since reslizumab reduces circulating eosinophil levels, it may impair your body’s ability to fight existing or new parasitic infections. If you have a current parasitic infection, it should be treated and resolved before starting CINQAERO. If you develop a parasitic infection during treatment and do not respond to antiparasitic therapy, temporary discontinuation of CINQAERO should be considered. If you live in or travel to regions where helminth infections are endemic (common), discuss this with your doctor.
• Acute asthma symptoms: CINQAERO should not be used to treat acute asthma symptoms, acute bronchospasm, or status asthmaticus. It is a maintenance treatment designed to prevent exacerbations over time and has no role in the emergency management of acute asthma attacks. Patients should continue to carry and use their rescue inhaler (e.g., short-acting beta-agonist) as needed.
• Corticosteroid reduction: Do not abruptly discontinue systemic or inhaled corticosteroids upon starting CINQAERO. Corticosteroid dose reductions, if appropriate, should be gradual and performed under the supervision of a physician. Abrupt withdrawal of corticosteroids can lead to systemic withdrawal symptoms or unmasking of conditions such as eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome) that were previously suppressed by corticosteroid therapy.
• Allergic reactions during infusion: Tell your healthcare provider immediately if you experience symptoms such as itching, difficulty breathing, wheezing, fever, chills, dizziness, headache, nausea, vomiting, abdominal discomfort, skin rash, flushing, or swelling during or after the infusion.

Children and Adolescents

CINQAERO is not approved for use in children and adolescents under 18 years of age. The safety and efficacy of reslizumab have not been established in pediatric patients. The clinical trials that supported approval enrolled only adult patients (aged 18 years and older). For children and adolescents with severe eosinophilic asthma, healthcare providers should consider age-appropriate biologic alternatives that have been studied and approved for younger age groups, such as mepolizumab (approved for children aged 6 years and older) or benralizumab (approved for adolescents aged 12 years and older in some regions).

Pregnancy and Breastfeeding

If you are pregnant, think you may be pregnant, or are planning to become pregnant, consult your doctor before receiving CINQAERO. There are limited data from the use of reslizumab in pregnant women. As a monoclonal antibody (IgG4), reslizumab is expected to cross the placenta, particularly during the second and third trimesters, when active transport of IgG across the placenta increases substantially. Animal reproductive studies have not been conducted with reslizumab. As a precaution, CINQAERO should preferably be avoided during pregnancy unless the potential benefit to the mother clearly justifies the potential risk to the fetus. Women of childbearing potential should discuss the need for contraception with their doctor.

The active substance in CINQAERO may pass into breast milk, but only during the first few days after birth. Human IgG antibodies are known to be present in breast milk, primarily during the early neonatal period. Oral bioavailability of monoclonal antibodies is expected to be very low, as these large protein molecules would be degraded in the infant’s gastrointestinal tract. The decision to breastfeed during CINQAERO treatment should be made in consultation with your doctor, weighing the benefits of breastfeeding for the infant against the benefits of treatment for the mother.

Driving and Operating Machinery

CINQAERO is not expected to affect your ability to drive or operate machinery. Based on its pharmacological properties and the known side effect profile from clinical trials, reslizumab is unlikely to impair cognitive function, reaction times, or motor coordination. However, if you experience any unexpected adverse effects after an infusion that could affect your alertness or coordination, refrain from driving or operating machinery until you feel well again.

Important Information About Ingredients

CINQAERO contains sodium. Each 10 mL vial contains 4.6 mg sodium and each 2.5 mL vial contains 1.15 mg sodium (the main component of table salt). This corresponds to 0.23% and 0.06%, respectively, of the WHO-recommended maximum daily intake of 2 grams of sodium for an adult. This is considered essentially “sodium-free” and should not be a concern for patients on sodium-restricted diets. The total sodium content in the diluted infusion solution will include additional sodium from the 0.9% sodium chloride diluent.

How Does CINQAERO Interact with Other Drugs?

Monoclonal antibodies such as reslizumab are large protein molecules that are eliminated through intracellular catabolism (breakdown into amino acids) rather than through hepatic enzyme metabolism. Because reslizumab does not interact with cytochrome P450 (CYP) enzymes, drug transporters, or other conventional pharmacokinetic pathways, the risk of traditional drug-drug interactions is considered very low. In clinical trials, CINQAERO was administered alongside standard asthma therapies – including high-dose inhaled corticosteroids, long-acting beta-agonists (LABAs), leukotriene receptor antagonists, theophylline, and oral corticosteroids – without evidence of clinically significant interactions affecting the efficacy or safety of either reslizumab or the concomitant medications.

Nevertheless, there are important theoretical and practical considerations when using CINQAERO alongside other treatments:

Concurrent Biologic Therapies

The concomitant use of CINQAERO with other biologic therapies for asthma (such as omalizumab, mepolizumab, benralizumab, dupilumab, or tezepelumab) has not been studied in clinical trials. There are no data on the safety or efficacy of combining two or more biologic agents for asthma management. Current international guidelines, including the Global Initiative for Asthma (GINA) 2024 report and the ERS/ATS guidelines on severe asthma, do not recommend concurrent use of multiple biologics and instead advise switching between biologics if the first choice proves inadequate. If a switch is necessary, there is no mandatory washout period between biologics, though some clinicians prefer to allow a period equivalent to one dosing interval of the discontinued biologic before initiating the new one.

Vaccines

There are limited data on the immunological response to vaccination in patients receiving reslizumab. As an anti-IL-5 agent, CINQAERO specifically reduces eosinophils but is not expected to broadly impair the adaptive immune response (T-cell and B-cell function). Inactivated vaccines may be administered as clinically indicated during CINQAERO treatment. However, as a general precaution with any biologic therapy, your doctor may wish to assess vaccination timing and may recommend completing necessary vaccinations before initiating treatment when possible. If you need any vaccinations during treatment, discuss the timing with your healthcare provider.

What Is the Correct Dosage of CINQAERO?

Adults (18 years and older)

The recommended dose of CINQAERO is 3 mg/kg body weight administered once every 4 weeks as an intravenous infusion. The infusion is prepared by diluting the appropriate volume of CINQAERO concentrate into a 50 mL infusion bag of 0.9% sodium chloride (normal saline). The infusion is then delivered over approximately 20 to 50 minutes through an intravenous line equipped with a sterile, non-pyrogenic, low-protein-binding in-line filter (pore size 0.2 µm). The exact infusion time depends on the total volume being administered, which is determined by the patient’s body weight.

CINQAERO is available in two vial sizes: 2.5 mL vials containing 25 mg reslizumab and 10 mL vials containing 100 mg reslizumab. The healthcare provider will calculate the exact volume needed based on the patient’s current body weight and select the appropriate combination of vials. Any unused concentrate remaining in the vials must be discarded, as the product is preservative-free and intended for single use only.

Treatment with CINQAERO is intended for long-term use. The need for continued therapy should be assessed at least annually by the treating physician. Clinical response is typically evaluated after at least 16 weeks (4 infusions) of treatment. If no meaningful improvement in asthma control is observed after this initial period, the clinician should reassess the diagnosis and consider whether continued treatment is warranted.

Children and Adolescents

CINQAERO is not approved for use in patients under 18 years of age. No dosing recommendations can be provided for pediatric patients, as the safety and efficacy of reslizumab have not been established in this age group.

Elderly Patients

No dose adjustment is required for elderly patients. In clinical trials, a limited number of patients aged 65 years and older were treated with reslizumab, and no overall differences in safety or efficacy were observed between these patients and younger adults. However, as with any biologic therapy in elderly patients, greater sensitivity to adverse effects cannot be ruled out, and careful monitoring remains advisable.

Missed Dose

If you miss a scheduled CINQAERO infusion, contact your healthcare provider as soon as possible to arrange the next appointment. The missed dose should be administered at the earliest opportunity, and subsequent doses should be scheduled every 4 weeks from the date of the rescheduled infusion. Do not attempt to make up for a missed dose by receiving a double infusion or shortening the interval between infusions.

Overdose

In clinical trials, single intravenous doses of reslizumab up to 8.4 mg/kg (approximately 2.8 times the recommended dose) were administered to subjects in phase I studies without dose-limiting toxicity. There is no specific antidote for reslizumab overdose. In the event of an overdose, the patient should be monitored for signs or symptoms of adverse effects, and appropriate supportive treatment should be initiated as necessary. Because CINQAERO is always administered in a healthcare setting by trained professionals, the risk of accidental overdose is low.

What Are the Side Effects of CINQAERO?

Like all medicines, CINQAERO can cause side effects, although not everybody experiences them. The safety of reslizumab was evaluated in clinical trials involving over 2,600 patients with moderate-to-severe eosinophilic asthma. The overall incidence of adverse events was similar between reslizumab-treated patients and those receiving placebo, indicating a generally well-tolerated safety profile. Below is a summary of the known side effects, organized by frequency according to the standard medical convention:

Serious Side Effects

Anaphylaxis and severe allergic reactions: In controlled clinical trials, anaphylaxis was reported in approximately 0.3% of patients receiving reslizumab. These reactions typically occurred during or within 20 minutes of completing the intravenous infusion. Signs and symptoms of anaphylaxis may include sudden onset of wheezing, difficulty breathing, chest tightness, a rapid or weak pulse, dizziness or lightheadedness, swelling of the lips, tongue, or throat (angioedema), widespread hives or skin rash, flushing, nausea, vomiting, and abdominal cramping. If any of these symptoms occur during or after your CINQAERO infusion, tell your healthcare provider immediately. Due to this risk, patients are monitored during the infusion and for an appropriate period afterward, and the infusion must be administered in a healthcare setting where emergency treatment for anaphylaxis is readily available.

Elevated Creatine Phosphokinase (CPK)

Elevated CPK levels were the most commonly reported adverse event in clinical trials with reslizumab. CPK is an enzyme found mainly in the heart, brain, and skeletal muscles. Elevated CPK levels can indicate muscle stress or damage, but in most cases observed with CINQAERO, the elevations were transient (temporary), mild to moderate in severity, and not associated with clinical symptoms such as muscle pain or weakness. The mechanism underlying CPK elevation with reslizumab is not fully understood. If you experience unexplained muscle pain, tenderness, or weakness during CINQAERO treatment, inform your healthcare provider, who may order a blood test to check your CPK levels.

Long-Term Safety

Long-term safety data from open-label extension studies extending beyond 2 years have not revealed new safety concerns with continued reslizumab treatment. The overall safety profile remained consistent with that observed in the pivotal 52-week clinical trials. No evidence of increased malignancy risk, progressive immune suppression, or development of anti-drug antibodies with clinical impact has been observed with long-term use. However, as with all biologic therapies, ongoing pharmacovigilance monitoring continues worldwide.

How Should You Store CINQAERO?

Since CINQAERO is administered exclusively in healthcare settings, storage is typically the responsibility of the hospital pharmacy or infusion center rather than the patient. However, understanding proper storage conditions is important for ensuring the integrity and efficacy of the medication:

• Temperature: Store the unopened vials in a refrigerator at 2°C to 8°C (36°F to 46°F). Do not freeze CINQAERO, and do not use any vial that has been frozen.
• Light protection: Keep the vials in the original outer carton to protect from light. The concentrate is light-sensitive and should not be exposed to prolonged light.
• After dilution: Once diluted in 0.9% sodium chloride infusion solution, CINQAERO should be administered immediately. If immediate administration is not possible, the diluted solution can be stored refrigerated at 2°C to 8°C (or at room temperature up to 25°C if dilution occurred under controlled and validated aseptic conditions), protected from light, for up to 16 hours. This 16-hour period includes the infusion time.
• Do not shake: The vials should not be shaken at any time, as this may cause foaming or aggregation of the protein.
• Visual inspection: Before use, the concentrate should be visually inspected. It should be clear to slightly opalescent, colorless to pale yellow. Small translucent-to-white, amorphous, fibrous protein particles may be present, which is normal for protein solutions. Do not use if the solution is discolored (other than pale yellow) or contains foreign particulate matter.
• Expiry date: Do not use CINQAERO after the expiry date stated on the outer carton and vial label (after “EXP”). The expiry date refers to the last day of the stated month.

Keep this medicine out of the sight and reach of children. Do not dispose of medicines via wastewater or household waste. Ask your pharmacist how to dispose of medicines no longer required. These measures help to protect the environment.

What Does CINQAERO Contain?

Active Ingredient

The active substance is reslizumab. Each milliliter of concentrate contains 10 mg of reslizumab (10 mg/mL). CINQAERO is available in two vial sizes:

• 2.5 mL vial: Contains 25 mg reslizumab
• 10 mL vial: Contains 100 mg reslizumab

Excipients (Inactive Ingredients)

The other ingredients in CINQAERO are:

• Sodium acetate trihydrate – a buffer to maintain the appropriate pH of the solution
• Glacial acetic acid – a pH-adjusting agent
• Sucrose – a stabilizer that protects the monoclonal antibody during storage
• Water for injections – the solvent

Physical Appearance and Packaging

CINQAERO concentrate for solution for infusion is a clear to slightly opalescent, colorless to pale yellow liquid supplied in glass vials. Some translucent-to-white, amorphous, or fibrous protein particles may be visible; this is normal for protein-based solutions and does not indicate degradation. CINQAERO is supplied in packs containing 1 or 2 vials of 2.5 mL, and in packs containing 1 or 2 vials of 10 mL. Not all pack sizes may be marketed in all countries.

The marketing authorization holder is Teva B.V., based in Haarlem, Netherlands. The product is manufactured at multiple sites, including UAB Teva Baltics in Vilnius, Lithuania, and Merckle GmbH in Ulm, Germany. CINQAERO is compatible with polyvinyl chloride (PVC) or polyolefin (PO) infusion bags and with integrated in-line infusion filters made from polyethersulfone (PES), polyvinylidene fluoride (PVDF), nylon, or cellulose acetate (CA) with a pore size of 0.2 µm.