Riltrava Aerosphere: Uses, Dosage & Side Effects
A fixed-dose triple-therapy pressurized inhaler containing budesonide, glycopyrronium and formoterol fumarate for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adults
Riltrava Aerosphere is a pressurized metered-dose inhaler (pMDI) that delivers three complementary respiratory medicines in a single device: budesonide (an inhaled corticosteroid, ICS), glycopyrronium (a long-acting muscarinic antagonist, LAMA) and formoterol fumarate (a long-acting beta2-agonist, LABA). It is licensed for the maintenance treatment of adult patients with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately controlled by a dual combination of an ICS with a LABA or a LABA with a LAMA. Each actuation delivers 160 micrograms of budesonide, 7.2 micrograms of glycopyrronium and 5 micrograms of formoterol fumarate. The usual dose is two inhalations twice daily. Riltrava Aerosphere is a maintenance therapy—not a rescue inhaler—and patients must always carry a separate short-acting bronchodilator for relief of sudden symptoms.
Quick Facts: Riltrava Aerosphere
Key Takeaways
- Riltrava Aerosphere combines three medicines in one inhaler (budesonide 160 mcg, glycopyrronium 7.2 mcg and formoterol fumarate 5 mcg per actuation) to reduce airway inflammation and provide sustained bronchodilation in moderate-to-severe COPD.
- The standard dose is two inhalations twice daily (morning and evening) at approximately the same times each day. Prime the new inhaler with four test sprays and shake the canister thoroughly for 5 seconds before each use because the formulation is a suspension.
- It is a preventive maintenance treatment, not a rescue inhaler. Always carry a short-acting bronchodilator (e.g., salbutamol) for the immediate relief of acute symptoms or exacerbations.
- The most clinically important recognized risks are oral candidiasis (thrush), dysphonia (hoarse voice), and a small increased risk of pneumonia associated with the inhaled corticosteroid component. Rinsing the mouth with water after each dose reduces oral side effects.
- Riltrava Aerosphere is licensed for adults with COPD only. It is not indicated for the treatment of asthma and should not be used to manage acute bronchospasm or respiratory distress of any cause.
What Is Riltrava Aerosphere and What Is It Used For?
Riltrava Aerosphere is a fixed-dose triple-combination inhaler indicated for the long-term maintenance treatment of adult patients with moderate to severe chronic obstructive pulmonary disease (COPD). Each pressurized canister contains three complementary bronchoactive drugs formulated together using a specialized co-suspension delivery technology. The purpose of combining three molecules with distinct mechanisms of action in a single device is to optimize disease control, simplify treatment regimens and improve adherence compared with patients using two or three separate inhalers. The product is marketed internationally under several brand names including Riltrava Aerosphere, Breztri Aerosphere and Trixeo Aerosphere, depending on the regulatory jurisdiction; the formulation and dose are identical across these trade names.
COPD is a progressive lung disease characterized by persistent airflow limitation and chronic inflammation of the airways and lung parenchyma, most commonly resulting from long-term exposure to tobacco smoke, biomass fuel smoke, occupational dusts and environmental pollutants. Patients typically experience breathlessness on exertion, chronic cough, sputum production and recurrent episodes of acute symptom worsening known as exacerbations. The three drugs in Riltrava Aerosphere target different physiological processes that contribute to these symptoms, producing additive and complementary therapeutic effects that exceed those achievable with any single agent alone.
How the Three Active Ingredients Work Together
Budesonide is a synthetic glucocorticosteroid with potent local anti-inflammatory activity. When delivered by inhalation, it binds to intracellular glucocorticoid receptors in airway epithelial and inflammatory cells, modulating the transcription of numerous genes involved in the inflammatory cascade. The net effect is a broad suppression of pro-inflammatory cytokines, chemokines, leukotrienes and prostaglandins, together with reduced recruitment and activation of inflammatory cells such as eosinophils, neutrophils and lymphocytes in the airway wall. In patients with COPD and a history of frequent exacerbations, this ICS component has been shown to reduce the annual rate of moderate-to-severe flare-ups.
Glycopyrronium (also written as glycopyrrolate in some regions) is a long-acting muscarinic antagonist (LAMA). It competitively and reversibly blocks the M3 muscarinic acetylcholine receptor on the surface of airway smooth-muscle cells and submucosal glands. By blocking the parasympathetic bronchoconstrictor tone that is typically elevated in COPD, glycopyrronium produces sustained relaxation of the airway smooth muscle and reduces mucus hypersecretion. Its long-acting pharmacokinetic profile supports a twice-daily dosing interval when combined in the Aerosphere formulation.
Formoterol fumarate is a long-acting beta2-agonist (LABA) with a rapid onset of action. It stimulates beta2-adrenergic receptors coupled to stimulatory G-proteins on airway smooth-muscle cells, increasing intracellular cyclic adenosine monophosphate (cAMP) and producing prompt, prolonged bronchodilation. Unlike salmeterol, formoterol begins to exert a measurable bronchodilating effect within a few minutes of inhalation, although patients should still carry a separate rescue inhaler because Riltrava Aerosphere is not licensed or intended for the relief of acute symptoms.
The pharmacological rationale for combining an ICS, a LAMA and a LABA is supported by the pivotal phase III ETHOS (Efficacy and Safety of Triple Therapy in Obstructive Lung Disease) trial, which enrolled more than 8,500 patients with moderate-to-very-severe COPD and a history of at least one moderate or severe exacerbation in the preceding year. Over 52 weeks, budesonide/glycopyrronium/formoterol significantly reduced the annual rate of moderate-to-severe exacerbations compared with both dual LAMA/LABA therapy (glycopyrronium/formoterol) and dual ICS/LABA therapy (budesonide/formoterol). The triple-therapy arm also demonstrated improvements in trough FEV1, the St George’s Respiratory Questionnaire score and, in a pre-specified analysis, all-cause mortality.
The Aerosphere Co-Suspension Technology
A defining technical feature of Riltrava Aerosphere is its Aerosphere delivery system, a proprietary co-suspension formulation that distinguishes the product from conventional solution- and suspension-based pressurized metered-dose inhalers. In a standard pMDI suspension, the active drug crystals are dispersed directly in the liquefied propellant, which can result in uneven distribution, sedimentation, and flocculation of particles. These physical instabilities can lead to dose variability, particularly for products that contain multiple drugs at different concentrations.
The Aerosphere system addresses this challenge by incorporating micron-sized, porous phospholipid carrier particles (made primarily of distearoylphosphatidylcholine and calcium chloride) into which the three drug particles associate. These low-density carrier particles suspend uniformly in the propellant and co-deliver all three active ingredients to the lungs in a consistent ratio with every actuation. Scintigraphic studies have demonstrated that the Aerosphere technology achieves substantial central and peripheral lung deposition, including in patients with reduced inspiratory flow rates, an important consideration for a COPD population that frequently has compromised respiratory mechanics.
Therapeutic Indications
Riltrava Aerosphere is indicated as a maintenance treatment in adult patients with moderate to severe chronic obstructive pulmonary disease who are not adequately controlled by the combination of an inhaled corticosteroid and a long-acting beta2-agonist, or by the combination of a long-acting beta2-agonist and a long-acting muscarinic antagonist. It is intended for daily, regular use to reduce the frequency of acute exacerbations, improve lung function, relieve symptoms and enhance exercise tolerance and health-related quality of life.
The product is not licensed for the treatment of asthma, for patients under 18 years of age, or for the relief of acute bronchospasm. It is also not appropriate as initial therapy for newly diagnosed COPD; national and international guidelines such as the Global Initiative for Chronic Obstructive Lung Disease (GOLD) strategy recommend a stepwise approach, typically starting with a single long-acting bronchodilator and escalating to dual and then triple therapy in patients with persistent symptoms or continued exacerbations. Your prescribing physician will determine whether triple therapy is appropriate for your individual clinical profile.
What Should You Know Before Using Riltrava Aerosphere?
Contraindications
Riltrava Aerosphere must not be used in anyone with a known hypersensitivity (allergy) to any of the three active ingredients—budesonide, glycopyrronium bromide or formoterol fumarate dihydrate—or to any of the excipients in the formulation, which include the propellant norflurane (HFA-134a), distearoylphosphatidylcholine and calcium chloride. Allergic reactions to inhaled medicines are uncommon but can manifest as facial swelling, tongue or throat swelling, difficulty swallowing, urticaria (hives), bronchospasm, breathing difficulties or sudden faintness. If any of these symptoms occur after using the inhaler, stop use immediately and seek emergency medical attention.
Riltrava Aerosphere is strictly a maintenance medication and should never be used to treat an acute episode of breathlessness, bronchospasm or a COPD exacerbation. Although formoterol has a rapid onset of bronchodilation, the dose delivered by Riltrava Aerosphere is not sufficient for reliable rescue use, and repeated additional actuations increase the risk of cardiovascular side effects without providing adequate symptom relief. Patients must always have a separate short-acting bronchodilator available, such as salbutamol (albuterol), terbutaline or ipratropium bromide.
Warnings and Precautions
Riltrava Aerosphere is for preventive (maintenance) use only. It will not provide rapid relief of an acute COPD exacerbation or severe breathlessness. Always carry a separate fast-acting reliever inhaler. If your rescue inhaler is needed more frequently than usual, or if your usual dose of Riltrava Aerosphere becomes less effective at controlling your symptoms, contact your doctor promptly—your treatment plan may need to be reviewed.
Consult your doctor or pharmacist before starting Riltrava Aerosphere if you have any of the following conditions or circumstances:
- Heart disease, heart rhythm disorders, or uncontrolled hypertension: Long-acting beta2-agonists such as formoterol can cause increases in heart rate, palpitations, and small changes in blood pressure and QT interval. Patients with ischaemic heart disease, recent myocardial infarction, tachyarrhythmias (including atrial fibrillation, supraventricular tachycardia or extrasystoles), severe heart failure, or prolonged QT interval should use Riltrava Aerosphere with caution under specialist supervision.
- Hyperthyroidism, phaeochromocytoma or severe hypokalaemia: These conditions may be aggravated by beta2-agonists. Particular care is needed for patients on concomitant diuretics (especially non-potassium-sparing), methylxanthines or systemic corticosteroids because of additive hypokalaemia risk.
- Diabetes mellitus: High doses of beta2-agonists and systemic corticosteroid exposure can raise blood glucose. Diabetic patients may require closer glucose monitoring, especially when treatment is initiated.
- Narrow-angle glaucoma or a predisposition to it: The muscarinic antagonist glycopyrronium can theoretically precipitate acute angle-closure glaucoma in susceptible individuals if inadvertently sprayed into the eyes. Avoid contact with the eyes when actuating the inhaler. Seek medical attention if you develop eye pain, blurred vision, visual halos, coloured images or red eyes.
- Urinary retention or bladder-neck obstruction (including benign prostatic hyperplasia): Antimuscarinic drugs can worsen these conditions. Patients should report new or worsening difficulty passing urine promptly.
- Severe renal impairment: Glycopyrronium is predominantly excreted by the kidneys. Patients with severe renal impairment or end-stage renal disease requiring dialysis should be treated with caution and only if the expected benefit outweighs the risk.
- Active or latent tuberculosis, and other respiratory infections: Inhaled corticosteroids can suppress local immunity and may allow reactivation of latent TB or worsening of active infection. Untreated fungal, bacterial or viral respiratory infections should be adequately addressed before initiating or escalating ICS therapy.
- Hepatic impairment: Budesonide and formoterol undergo hepatic metabolism via CYP3A4. In patients with severe liver disease, systemic exposure to both drugs may be increased; clinical surveillance for systemic corticosteroid effects is appropriate.
- Switching from oral corticosteroids: Patients transitioning from systemic corticosteroid therapy to inhaled corticosteroid-containing inhalers must be carefully tapered under medical supervision, as adrenal insufficiency symptoms (fatigue, weakness, joint pain, nausea, weight loss) can develop. Supplementary oral corticosteroids may be needed during periods of physiological stress such as trauma, surgery or severe infection.
Inhaled corticosteroids used in COPD—including the budesonide component of Riltrava Aerosphere—are associated with a small but consistent increase in the risk of pneumonia compared with non-ICS inhaler regimens. Contact your doctor promptly if you develop new or worsening productive cough, fever, chills, chest pain, or increased breathlessness, as these may signal an evolving lower respiratory tract infection that requires prompt evaluation and possibly antibiotic treatment.
Inhaled medicines can occasionally cause immediate wheezing, coughing or breathing difficulty shortly after inhalation (paradoxical bronchospasm). If this happens, stop using Riltrava Aerosphere immediately, use your rescue bronchodilator, and contact your doctor, who may recommend an alternative formulation or device.
Pregnancy and Breastfeeding
There is limited clinical experience with Riltrava Aerosphere specifically in human pregnancy, as COPD predominantly affects older adults and pregnancy is uncommon in this population. Data on the individual components—budesonide, glycopyrronium and formoterol—from observational registries and large population-based cohort studies have not demonstrated a consistent teratogenic signal at inhaled therapeutic doses. Nevertheless, Riltrava Aerosphere should be used during pregnancy only if the expected benefit to the mother justifies any potential risk to the fetus, and the decision should be made in consultation with a specialist.
Budesonide passes into breast milk in very small amounts after inhalation, and systemic exposure in the breastfed infant is expected to be negligible. Data on glycopyrronium and formoterol in breast milk are more limited. A decision on whether to continue Riltrava Aerosphere while breastfeeding should weigh the benefit of maintenance COPD therapy to the mother against any theoretical risk to the infant. If Riltrava Aerosphere is felt to be essential, monitor the infant for any unusual symptoms and consult a healthcare professional.
Driving and Operating Machinery
Riltrava Aerosphere has no or negligible influence on the ability to drive and operate machinery under normal conditions. However, dizziness and blurred vision are uncommon reported adverse effects. Patients who experience these symptoms should avoid driving or operating machinery until they resolve.
How Does Riltrava Aerosphere Interact with Other Drugs?
Riltrava Aerosphere contains three active drugs, each with its own pharmacological profile and interaction potential. Although systemic exposure following inhalation is generally low, certain combinations can increase the risk of systemic side effects, reduce the efficacy of the medicine, or produce additive cardiac effects. Inform your healthcare provider about every medicine you are currently taking, including prescription drugs, over-the-counter preparations, herbal remedies and recreational substances.
Major Interactions
| Interacting Drug or Class | Mechanism and Effect | Clinical Advice |
|---|---|---|
| Potent CYP3A4 inhibitors (ritonavir, cobicistat, ketoconazole, itraconazole, clarithromycin, telithromycin, voriconazole) |
Budesonide and formoterol are metabolized by CYP3A4. Potent inhibitors can significantly increase systemic exposure to budesonide, raising the risk of adrenal suppression, Cushing-like features and glucocorticoid side effects. Formoterol levels may also rise, enhancing beta2-agonist effects. | Concurrent use should generally be avoided. Where combination therapy is unavoidable, monitor closely for systemic corticosteroid effects and cardiac or metabolic adverse events, and consider alternative treatments for HIV, fungal infections or other indications. |
| Non-selective beta-blockers (propranolol, sotalol, carvedilol, timolol eye drops) |
Oppose the bronchodilator effect of formoterol by blocking beta2-adrenoceptors, potentially worsening airway obstruction and reducing the efficacy of Riltrava Aerosphere. May also mask tachycardic signs of acute bronchospasm. | Non-selective beta-blockers are generally contraindicated in patients with COPD who rely on beta2-agonist therapy. If beta-blockade is essential (e.g., for heart failure or post-myocardial infarction), cardioselective agents such as bisoprolol or metoprolol are preferred and should be initiated at low doses with close monitoring. |
| Other LABA or LAMA medicines (salmeterol, vilanterol, tiotropium, umeclidinium, aclidinium) |
Duplicate therapy increases the total dose of beta2-agonist or antimuscarinic drug without improving efficacy, magnifying cardiovascular and antimuscarinic side effects including tachycardia, tremor, dry mouth and urinary retention. | Do not use Riltrava Aerosphere in combination with any other LABA- or LAMA-containing inhaler. If another long-acting bronchodilator is being switched from, stop it before initiating Riltrava Aerosphere. |
| QT-prolonging drugs (quinidine, disopyramide, class III antiarrhythmics, some antipsychotics, macrolide and fluoroquinolone antibiotics) |
Formoterol can produce small additive prolongations of the QT interval; when combined with other QT-prolonging drugs the risk of ventricular arrhythmia (including torsades de pointes) is increased, particularly in patients with underlying electrolyte disturbance or cardiac disease. | Use with caution. Consider baseline and follow-up ECG monitoring and correction of hypokalaemia or hypomagnesaemia. Avoid the combination if possible in patients with long QT syndrome or a history of torsades de pointes. |
| Monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants, linezolid | May potentiate the cardiovascular effects of beta2-agonists, increasing the risk of hypertension, tachycardia and arrhythmia. | Use with caution and avoid combination where possible. If concurrent therapy is unavoidable, monitor blood pressure and heart rate carefully, particularly during dose initiation or changes. |
Minor Interactions
| Interacting Drug or Class | Mechanism and Effect | Clinical Advice |
|---|---|---|
| Thiazide and loop diuretics | Beta2-agonists shift potassium intracellularly; when combined with diuretics that promote potassium excretion, the risk of clinically significant hypokalaemia is increased, particularly in severe COPD or heart failure. | Monitor serum potassium in at-risk patients. Consider potassium-sparing agents or potassium supplementation if hypokalaemia develops. |
| Xanthines (theophylline, aminophylline) | Additive bronchodilation but also additive cardiovascular stimulation and potential for tachycardia, tremor and hypokalaemia. | Combination therapy is sometimes prescribed but requires careful monitoring of symptoms, heart rate and serum potassium. Avoid unnecessary concurrent use. |
| Other systemic or inhaled corticosteroids | Additive corticosteroid burden increases the risk of systemic side effects such as adrenal suppression, osteoporosis, skin thinning, cataracts and glaucoma, particularly with long-term use. | Avoid unnecessary duplication of corticosteroid therapy. Where combination is temporarily required (e.g., during a severe exacerbation), ensure careful tapering and monitoring under medical supervision. |
| Drugs with antimuscarinic activity (tricyclic antidepressants, some antihistamines, some anti-Parkinson drugs) |
Additive antimuscarinic effects can worsen dry mouth, constipation, urinary retention and blurred vision. | Advise patients about the possible additive antimuscarinic burden. Review the overall anticholinergic load in elderly patients because of the increased risk of cognitive impairment. |
| Halogenated general anaesthetics | Can potentiate the cardiac effects of beta2-agonists, increasing the risk of arrhythmias during anaesthesia. | Inform the anaesthetist about the use of Riltrava Aerosphere ahead of any planned surgery. If possible, avoid the last dose on the morning of surgery if general anaesthesia with halogenated agents is planned. |
No clinically significant interactions have been reported between Riltrava Aerosphere and commonly used cardiovascular medicines such as ACE inhibitors, angiotensin receptor blockers, statins, calcium-channel blockers or direct oral anticoagulants at standard doses. Short-acting beta2-agonist rescue inhalers (for example, salbutamol) can be used in addition to Riltrava Aerosphere for acute symptom relief, but excessive use of rescue bronchodilators is a warning sign that your COPD may be poorly controlled and should prompt a medical review.
What Is the Correct Dosage of Riltrava Aerosphere?
Always use Riltrava Aerosphere exactly as your doctor has instructed. Do not change the dose, frequency or device without first consulting your healthcare provider. The following dosage information reflects the marketing authorization in the European Union and in regions where the product is licensed under the Riltrava, Breztri or Trixeo Aerosphere brand names. Individual prescribing may vary depending on local regulatory approvals.
Adults
Adult Dosing (18 years and older)
Recommended maintenance dose: Two inhalations in the morning and two inhalations in the evening (total: four inhalations per day)
Drug delivered per inhalation: 160 micrograms budesonide, 7.2 micrograms glycopyrronium and 5 micrograms formoterol fumarate dihydrate
Total daily dose: 640 mcg budesonide + 28.8 mcg glycopyrronium + 20 mcg formoterol fumarate
Maximum recommended daily dose: Four inhalations per day. Do not exceed this dose under any circumstances.
Riltrava Aerosphere is designed for long-term, regular, twice-daily use. Consistent dosing at intervals of approximately 12 hours provides steady delivery of all three medicines and maximizes both bronchodilation and anti-inflammatory effects. Patients who forget a single dose should not double the next dose (see Missed Dose). Attempting to compensate for missed doses with extra inhalations increases the risk of cardiovascular and antimuscarinic side effects without providing additional therapeutic benefit.
The clinical effect of Riltrava Aerosphere begins within minutes of the first inhalation because of the rapid onset of the formoterol component. However, the full therapeutic benefit—particularly the anti-inflammatory effects of budesonide and the exacerbation-reducing effect of triple therapy—develops over several weeks of regular use. Do not stop taking the medicine because you feel better; discontinuation can lead to the return of inflammation, worsening lung function and a higher risk of exacerbation.
Children and Adolescents
Paediatric Population
Riltrava Aerosphere is not indicated for use in children or adolescents under 18 years of age. Safety and efficacy in the paediatric population have not been established, and COPD—the only licensed indication—is not a disease of childhood. There is no therapeutic rationale for prescribing this product to patients under 18.
Elderly
Elderly Patients (65 years and older)
No dose adjustment is required for elderly patients. Standard adult dosing applies. However, older adults may be more susceptible to the cardiovascular effects of formoterol and the antimuscarinic side effects of glycopyrronium, including dry mouth, urinary retention, constipation and confusion. Regular review of the indication, adherence and adverse effects is recommended, particularly in patients aged 75 years or older or with multimorbidity.
Patients with Kidney or Liver Disease
Renal and Hepatic Impairment
Renal impairment: Mild to moderate renal impairment does not require dose adjustment. In severe renal impairment (creatinine clearance below 30 mL/min) or end-stage renal disease requiring dialysis, Riltrava Aerosphere should be used only when the anticipated benefit outweighs the potential risk, as systemic exposure to glycopyrronium may be increased.
Hepatic impairment: No dose adjustment is required in mild to moderate hepatic impairment. In severe hepatic impairment, budesonide and formoterol systemic exposure may be increased because of reduced first-pass metabolism via CYP3A4; patients should be monitored for systemic corticosteroid and beta2-agonist effects.
Missed Dose
If you forget to take a dose of Riltrava Aerosphere, take it as soon as you remember, unless it is almost time for the next scheduled dose. In that case, skip the missed dose and continue with your regular dosing schedule. Do not take a double dose to make up for a forgotten one. Setting a daily reminder, coupling dosing with established daily routines (such as brushing teeth morning and evening) and using a dose-counter inhaler or medication diary can help establish consistent adherence.
Overdose
An overdose of Riltrava Aerosphere may produce exaggerated pharmacological effects of each of the three active components. The most likely features relate to the formoterol (LABA) component: tremor, headache, palpitations, tachycardia, raised blood pressure, arrhythmia, hyperglycaemia, metabolic acidosis, hypokalaemia, nausea and dizziness. Overdose with the glycopyrronium (LAMA) component may cause dry mouth, blurred vision, flushing, urinary retention, constipation and tachycardia. Overdose with the budesonide (ICS) component from a single acute event is unlikely to cause significant harm, but chronic overdose can lead to adrenal suppression, reduced bone mineral density, cataracts and Cushingoid features.
In the event of a suspected overdose, contact your doctor, local poisons information service or emergency services immediately. Treatment is supportive and symptomatic; cardiac monitoring may be required, and serum potassium should be measured and corrected if low. Beta-blockers should generally be avoided because of the risk of precipitating severe bronchospasm; if urgent treatment of tachyarrhythmia is needed, cardioselective beta-blockers should be used with caution and under specialist supervision.
How to Use the Riltrava Aerosphere Inhaler Correctly
Correct inhaler technique is essential to ensure that the medicine reaches the small airways where it needs to act. Review the following steps with your doctor, nurse or pharmacist when the inhaler is first prescribed, and at regular reviews thereafter:
- Prime the inhaler if it is new or unused for more than 7 days. Shake the canister vigorously for 5 seconds and release four test sprays into the air, away from your face, shaking for 5 seconds before each spray. This ensures a uniform suspension and reliable dose delivery.
- Remove the mouthpiece cap and inspect the mouthpiece for dust, debris or foreign objects. Clean if necessary by wiping with a dry cloth; do not submerge the canister in water.
- Shake the canister vigorously for at least 5 seconds. Riltrava Aerosphere is a suspension formulation, and thorough shaking is critical to deliver a consistent dose of all three medicines.
- Breathe out gently and fully away from the inhaler mouthpiece. Do not breathe out into the mouthpiece, as this can moisten the device and impair function.
- Hold the inhaler upright with your thumb on the base and your index finger on the top of the canister. Place the mouthpiece between your teeth and close your lips firmly around it.
- Begin to inhale slowly and deeply through your mouth. At the same time, press down firmly on the top of the canister to release one puff. Continue to breathe in slowly and steadily until your lungs feel full.
- Remove the inhaler from your mouth and hold your breath for approximately 10 seconds, or as long as is comfortable. This allows the medicine to settle deep in the airways.
- Wait at least 30 seconds and then repeat the procedure from step 3 to deliver the second inhalation. Each prescribed dose consists of two inhalations.
- Rinse your mouth with water and spit it out. Do not swallow. This simple step substantially reduces the risk of oral candidiasis (thrush) and hoarseness caused by deposition of the budesonide component in the mouth and throat.
- Replace the mouthpiece cap to protect the mouthpiece and keep it clean between doses.
If you find it difficult to coordinate pressing the canister with breathing in, ask your doctor or pharmacist whether a spacer (valved holding chamber) compatible with Riltrava Aerosphere is available in your country. A spacer eliminates the need for exact hand-breath coordination and can also reduce oropharyngeal drug deposition, lowering the risk of oral thrush and hoarseness. Use of a spacer is particularly helpful for elderly patients, those with reduced dexterity, and anyone who cannot demonstrate correct pMDI technique at a review.
Keep track of the number of doses remaining by using the integrated dose counter on the inhaler. Replace the inhaler when the counter approaches zero, even if the canister still appears to contain liquid; consistent dosing cannot be guaranteed beyond the labeled number of actuations. Clean the plastic actuator weekly by wiping the mouthpiece with a dry cloth. Do not immerse the metal canister or the actuator in water.
What Are the Side Effects of Riltrava Aerosphere?
Like all medicines, Riltrava Aerosphere can cause side effects, although not everybody experiences them. The side-effect profile reflects contributions from each of the three active components. The adverse reactions listed below are based on the pooled data from the phase III ETHOS and KRONOS clinical trials, post-marketing surveillance and the approved Summary of Product Characteristics. Frequencies are classified as very common (more than 1 in 10 patients), common (up to 1 in 10), uncommon (up to 1 in 100), rare (up to 1 in 1,000), very rare (up to 1 in 10,000) or not known (cannot be estimated from available data).
Common
May affect up to 1 in 10 patients
- Oral candidiasis (oral thrush) – white patches in the mouth or throat
- Pneumonia
- Urinary tract infection
- Dysphonia (hoarseness or voice changes)
- Cough
- Headache
- Dry mouth (xerostomia)
- Muscle spasms
- Anxiety
- Insomnia
- Palpitations
- Nausea
Uncommon
May affect up to 1 in 100 patients
- Hypersensitivity reactions (including rash, pruritus and urticaria)
- Hyperglycaemia (raised blood sugar)
- Angioedema
- Restlessness, agitation
- Tremor
- Dizziness
- Tachycardia, atrial fibrillation, supraventricular tachycardia or extrasystoles
- Throat irritation
- Paradoxical bronchospasm
- Dry skin, skin bruising
- Urinary retention
- Muscle pain, weakness or fatigue
- Chest pain
Rare
May affect up to 1 in 1,000 patients
- Immediate or delayed hypersensitivity reactions (including severe skin rashes)
- Signs and symptoms of systemic corticosteroid effects (adrenal suppression, growth retardation in the young, reduced bone mineral density, cataract, glaucoma)
- Behavioural and mood changes (depression, psychomotor hyperactivity, sleep disorders)
- Angina pectoris
- Ventricular extrasystoles
- Hypokalaemia
- Abnormal liver function tests
Very Rare
May affect up to 1 in 10,000 patients
- Severe allergic reactions (anaphylaxis)
- Blurred vision and acute angle-closure glaucoma
- Cushing’s syndrome or Cushingoid features with prolonged high-dose use
- Ventricular tachyarrhythmias including torsades de pointes
- QT-interval prolongation
- Variations in blood pressure
Not Known
Frequency cannot be estimated from available data
- Psychiatric effects including aggression and abnormal behaviour, particularly in susceptible individuals
- Hepatitis
Oral candidiasis, dysphonia and throat irritation are caused by drug deposition in the mouth and throat rather than the lungs. These can be substantially reduced by (1) rinsing the mouth thoroughly with water and spitting out after every dose, (2) using a spacer device where available to decrease oropharyngeal deposition, and (3) ensuring correct inhaler technique to maximize lung deposition. If oral thrush develops, it is usually treatable with topical antifungal preparations and rarely requires Riltrava Aerosphere to be discontinued.
Stop taking Riltrava Aerosphere and seek urgent medical attention if you experience: signs of a severe allergic reaction (swelling of the face, tongue or throat, widespread rash, difficulty breathing, sudden faintness); immediate worsening of breathing or wheezing after using the inhaler (paradoxical bronchospasm); sudden painful red eye with blurred vision or halos (possible acute angle-closure glaucoma); or features of a serious infection such as high fever, productive cough and pleuritic chest pain. Contact your doctor promptly if you develop any persistent new symptom, especially if your COPD symptoms are not controlled at the prescribed dose.
Reporting suspected side effects is important for the ongoing safety monitoring of any medicine. If you experience any adverse effects, inform your doctor or pharmacist. In many countries you can also report side effects directly to the national pharmacovigilance authority (for example, the Yellow Card scheme in the United Kingdom, the FDA MedWatch programme in the United States, or the national competent authority in your country).
How Should You Store Riltrava Aerosphere?
Correct storage of the Riltrava Aerosphere inhaler is essential to ensure that the medicine remains safe and effective throughout its shelf life. The pressurized canister contains a propellant under pressure; extreme temperatures or physical damage can compromise the device or alter the aerosol properties of the formulation.
- Temperature: Store at room temperature, not exceeding 30°C (86°F). Do not store the inhaler in locations where temperatures may fluctuate significantly, such as on a sunny windowsill, on top of a radiator, in a bathroom with high humidity, or in a parked car during hot weather.
- Protection from freezing: Do not freeze the inhaler. Freezing may damage the metering valve and alter the spray pattern. If the canister feels very cold, allow it to warm to room temperature (approximately 30 minutes) and shake vigorously for at least 5 seconds before the next use.
- Protection from direct sunlight and heat sources: Prolonged exposure to UV radiation or heat can degrade the active ingredients and the plastic actuator.
- Do not puncture, break, burn or incinerate: The canister is pressurized and should never be pierced, crushed or exposed to open flame, even when empty. Dispose of used inhalers through your pharmacy take-back scheme or in accordance with local pharmaceutical waste regulations.
- Keep out of sight and reach of children: Store the inhaler in a secure location where children cannot access it.
- Expiry date: Do not use Riltrava Aerosphere after the expiry date printed on the carton and canister. The expiry date refers to the last day of the stated month. Return expired inhalers to your pharmacist for safe disposal.
- Dose counter: Monitor the integrated dose counter and replace the inhaler when it nears zero, even if the canister appears to contain residual liquid. Dose delivery cannot be guaranteed beyond the labeled number of actuations.
If the inhaler is accidentally dropped, inspect it for visible damage. The canister is designed to withstand normal handling, but cracks or significant denting may compromise function. If you have any concern about the integrity of the device, return it to your pharmacy and request a replacement.
What Does Riltrava Aerosphere Contain?
Knowing the full composition of a medicine can be important, particularly for patients with known allergies, sensitivities, lactose intolerance or dietary restrictions. The composition of Riltrava Aerosphere is summarized in the table below.
| Component | Role | Details |
|---|---|---|
| Budesonide | Active ingredient — inhaled corticosteroid (ICS) | 160 micrograms per actuation. A potent synthetic glucocorticosteroid with high local anti-inflammatory activity and low systemic bioavailability due to extensive first-pass metabolism via CYP3A4. |
| Glycopyrronium bromide | Active ingredient — long-acting muscarinic antagonist (LAMA) | 9 micrograms glycopyrronium bromide, equivalent to 7.2 micrograms of glycopyrronium base, per actuation. Competitively and reversibly blocks M3 muscarinic receptors on airway smooth muscle. |
| Formoterol fumarate dihydrate | Active ingredient — long-acting beta2-agonist (LABA) | 5 micrograms per actuation. A potent, long-acting beta2-agonist with a rapid onset of bronchodilation, active for approximately 12 hours after a single inhalation. |
| Norflurane (HFA-134a) | Propellant | 1,1,1,2-tetrafluoroethane. A non-ozone-depleting hydrofluoroalkane propellant that replaced CFC propellants under the Montreal Protocol. Provides the pressure needed to generate the aerosol spray. |
| Distearoylphosphatidylcholine (DSPC) | Excipient — porous carrier particle component | A phospholipid used to form the porous microcarrier particles of the Aerosphere co-suspension technology, which ensures uniform co-delivery of all three active ingredients. |
| Calcium chloride | Excipient — carrier particle component | Assists in forming the structural matrix of the Aerosphere carrier particles together with DSPC. Present in trace amounts and not pharmacologically active at delivered doses. |
The Aerosphere co-suspension formulation distinguishes Riltrava from conventional triple-therapy inhalers by using low-density, micron-sized phospholipid carrier particles rather than dispersing drug crystals directly in the propellant. The technology was developed to address the physical challenges of suspending three different drugs at widely differing concentrations within a single pMDI, and it supports consistent dose-to-dose delivery throughout the lifespan of the inhaler.
The outer device consists of a pressurized aluminum canister fitted with a metering valve, housed within a polypropylene plastic actuator that includes an integrated dose counter and a removable mouthpiece cap. The dose counter displays the number of actuations remaining in the canister and counts down in increments of ten, helping patients to monitor when a new inhaler is needed.
Frequently Asked Questions About Riltrava Aerosphere
Riltrava Aerosphere is a fixed-dose triple-combination inhaler containing budesonide (an inhaled corticosteroid), glycopyrronium (a long-acting muscarinic antagonist) and formoterol fumarate (a long-acting beta2-agonist). It is prescribed as a daily maintenance treatment for adults with moderate to severe chronic obstructive pulmonary disease (COPD) who are not adequately controlled on a dual combination of an inhaled corticosteroid and a long-acting beta2-agonist, or a long-acting beta2-agonist and a long-acting muscarinic antagonist. It is not a rescue inhaler and is not approved for the treatment of asthma.
The recommended dose is two inhalations twice daily (morning and evening). Shake the canister well for 5 seconds before each use, breathe out gently, place the mouthpiece between your lips to form a tight seal, and as you start to breathe in slowly and deeply, press down firmly on the canister. Hold your breath for about 10 seconds, then breathe out. Wait at least 30 seconds and repeat for the second puff. Always rinse your mouth with water and spit it out after use to reduce the risk of oral thrush. If the inhaler is new or has not been used for more than 7 days, prime it with four test sprays before use.
The most common side effects are oral candidiasis (thrush), pneumonia, dysphonia (hoarse voice), urinary tract infection, cough, headache, dry mouth and muscle spasms. Most local side effects are caused by drug deposition in the mouth and throat and can be minimized by rinsing the mouth with water after every dose. Pneumonia is a recognized class effect of inhaled corticosteroids used in COPD: report any new fever, productive cough or increased breathlessness to your doctor promptly so it can be evaluated and treated if necessary.
No. Riltrava Aerosphere is licensed only for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adults and is not approved for asthma. Patients with asthma should use inhalers specifically indicated for asthma control, guided by international recommendations such as those of the Global Initiative for Asthma (GINA). Using a LABA-containing inhaler without an inhaled corticosteroid dose titrated to asthma can increase the risk of severe asthma exacerbations. If you have both asthma and COPD, your doctor will select the most appropriate inhaler for your overall clinical picture.
No. Riltrava Aerosphere is a maintenance inhaler intended for daily preventive use to reduce the frequency of COPD exacerbations, improve lung function and relieve persistent symptoms. It is not designed or approved to relieve sudden breathlessness, wheezing or an acute COPD flare-up. You should always carry a separate short-acting bronchodilator (such as salbutamol or ipratropium) for immediate symptom relief. If you find yourself needing your rescue inhaler more often than usual, contact your healthcare provider because your treatment may need to be adjusted.
Yes, there is a small but real increase in the risk of pneumonia with all inhaled corticosteroid-containing inhalers used in COPD, including Riltrava Aerosphere. In the pivotal ETHOS clinical trial, pneumonia rates were around 4% with the triple combination over 52 weeks compared with approximately 2% for non-ICS comparator inhalers. The reduction in moderate-to-severe exacerbations and all-cause mortality with triple therapy is considered to outweigh this pneumonia risk in appropriately selected patients. Tell your doctor promptly if you develop new or worsening productive cough, fever, chills, chest pain or increased breathlessness.
If you forget to take a dose, use it as soon as you remember, unless it is nearly time for the next dose. In that case, skip the missed dose and continue with your normal dosing schedule. Never take a double dose to make up for a forgotten one, as this increases the risk of cardiovascular and antimuscarinic side effects without improving disease control. Setting a daily reminder or linking your inhaler routine to another daily habit (for example, brushing teeth) can help improve adherence.
There is no specific interaction between Riltrava Aerosphere and alcohol at moderate social levels. However, heavy alcohol consumption can worsen underlying heart disease and may interact with other medicines you take, so moderation is sensible. Riltrava Aerosphere generally has no or negligible influence on driving or operating machinery, but some patients may experience dizziness or blurred vision, particularly at the start of treatment. If you experience these symptoms, do not drive or operate machinery until they have resolved.
References
This article is based on the following peer-reviewed sources, regulatory documents and international clinical guidelines:
- 1 Global Initiative for Chronic Obstructive Lung Disease (GOLD). Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease. 2024 Report. Available at: goldcopd.org
- 2 European Medicines Agency (EMA). Trixeo Aerosphere (budesonide / glycopyrronium bromide / formoterol fumarate dihydrate): EPAR – Product information. Updated 2024. Available via the EMA EPAR database.
- 3 U.S. Food and Drug Administration (FDA). Breztri Aerosphere (budesonide, glycopyrrolate, and formoterol fumarate) inhalation aerosol – Prescribing Information. Reviewed 2024.
- 4 Rabe KF, Martinez FJ, Ferguson GT, et al. Triple inhaled therapy at two glucocorticoid doses in moderate-to-very-severe COPD (ETHOS). New England Journal of Medicine. 2020;383(1):35–48. doi:10.1056/NEJMoa1916046
- 5 Ferguson GT, Rabe KF, Martinez FJ, et al. Triple therapy with budesonide/glycopyrrolate/formoterol fumarate with co-suspension delivery technology versus dual therapies in chronic obstructive pulmonary disease (KRONOS). Lancet Respiratory Medicine. 2018;6(10):747–758. doi:10.1016/S2213-2600(18)30327-8
- 6 Martinez FJ, Rabe KF, Ferguson GT, et al. Reduced all-cause mortality in the ETHOS trial of budesonide/glycopyrrolate/formoterol for chronic obstructive pulmonary disease. American Journal of Respiratory and Critical Care Medicine. 2021;203(5):553–564. doi:10.1164/rccm.202006-2618OC
- 7 National Institute for Health and Care Excellence (NICE). Chronic obstructive pulmonary disease in over 16s: diagnosis and management. NICE guideline [NG115]. Updated 2019.
- 8 British National Formulary (BNF). Budesonide with formoterol and glycopyrronium. National Institute for Health and Care Excellence. Reviewed 2024.
- 9 Suissa S, Dell’Aniello S, Ernst P. Triple inhaler versus dual bronchodilator therapy in COPD: real-world effectiveness on mortality. COPD: Journal of Chronic Obstructive Pulmonary Disease. 2022;19(1):1–9.
- 10 Vestbo J, Fabbri L, Papi A, et al. Inhaled corticosteroid containing combinations and mortality in COPD. European Respiratory Journal. 2018;52(6):1801230.
- 11 Dransfield MT, Bourbeau J, Jones PW, et al. Once-daily inhaled fluticasone furoate and vilanterol versus vilanterol only for prevention of exacerbations of COPD. Lancet Respiratory Medicine. 2013;1(3):210–223. (Cited for ICS-containing combination exacerbation reduction methodology.)
- 12 Cazzola M, Rogliani P, Matera MG. The pharmacological treatment of COPD: a review of options and recent advances. Expert Review of Respiratory Medicine. 2022;16(5):463–478.
About Our Medical Review Process
All medication information on iMedic is written and reviewed by qualified healthcare professionals with expertise in clinical pharmacology and respiratory medicine. Our editorial process follows the principles of evidence-based medicine, and all content is verified against current international treatment guidelines including GOLD, NICE, the EMA Summary of Product Characteristics, the FDA prescribing information and the British National Formulary.
Content is authored by iMedic’s medical editorial team, comprising qualified healthcare professionals with expertise in pharmacology and respiratory medicine, including specialist physicians with direct experience of managing COPD and prescribing inhaler therapies.
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