BREZTRI AEROSPHERE is a combination of budesonide, an inhaled corticosteroid (ICS); glycopyrrolate, an anticholinergic; and formoterol fumarate, a long-acting beta 2 -adrenergic agonist (LABA), indicated for:
the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients. ( 1.1 )
the maintenance treatment of asthma in adult and pediatric patients 12 years of age and older. ( 1.2 ) Limitations of Use: Not indicated for the relief of acute bronchospasm. ( 1.3 , 5.1 , 5.2 )
1.1Maintenance Treatment of Chronic Obstructive Pulmonary Disease
BREZTRI AEROSPHERE is indicated for the maintenance treatment of chronic obstructive pulmonary disease (COPD) in adult patients.
1.2Maintenance Treatment of Asthma
BREZTRI AEROSPHERE is indicated for the maintenance treatment of asthma in adult and pediatric patients 12 years of age and older.
1.3Limitations of Use
BREZTRI AEROSPHERE is not indicated for the relief of acute bronchospasm [see Warnings and Precautions (5.1 , 5.2) ] .
Contraindications
BREZTRI AEROSPHERE is contraindicated in the following conditions:
Primary treatment of status asthmaticus or other acute episodes of COPD or asthma where intensive measures are required [see Warnings and Precautions (5.2) ] .
Hypersensitivity to budesonide, glycopyrrolate, formoterol, or any of the excipients [see Warnings and Precautions (5.11) and Description (11) ] .
Primary treatment of status asthmaticus or other acute episodes of asthma or COPD requiring intensive measures. ( 4 )
Hypersensitivity to budesonide, glycopyrrolate, formoterol fumarate, or to any of the excipients. ( 4 )
LABA as monotherapy (without an inhaled-corticosteroid) is associated with an increased risk of serious asthma-related events. ( 5.1 )
Do not initiate in acutely deteriorating COPD or asthma. Do not use to relieve acute symptoms. ( 5.2 )
Do not use in combination with an additional therapy containing a LABA because of the risk of overdose. ( 5.3 )
Candida albicans infection of the mouth and pharynx may occur. Monitor patients periodically. Advise the patient to rinse his/her mouth with water without swallowing after inhalation to help reduce the risk. ( 5.4 )
Increased risk of pneumonia in patients with COPD. Monitor patients for signs and symptoms of pneumonia. ( 5.5 )
Potential worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infections; ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. ( 5.6 )
Risk of impaired adrenal function when transferring from systemic corticosteroids. Taper patients slowly from systemic corticosteroids if transferring to BREZTRI AEROSPHERE. ( 5.7 )
Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, consider appropriate therapy. ( 5.8 )
If paradoxical bronchospasm occurs, discontinue BREZTRI AEROSPHERE and institute alternative therapy. ( 5.10 )
Use with caution in patients with cardiovascular disorders because of beta-adrenergic stimulation. ( 5.12 )
Assess for decrease in bone mineral density initially and periodically thereafter. ( 5.13 )
Monitor growth in pediatric patients. ( 5.14 )
Glaucoma and cataracts may occur with long-term use of ICS. Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to contact a healthcare provider immediately if symptoms occur. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use BREZTRI AEROSPHERE long term. ( 5.15 )
Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to contact a healthcare provider immediately if symptoms occur. ( 5.16 )
Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis. ( 5.17 )
Be alert to hypokalemia and hyperglycemia. ( 5.18 )
5.1Serious Asthma-Related
Events – Hospitalizations, Intubations, Death Use of long-acting beta 2 -adrenergic agonists (LABA) as monotherapy [without inhaled corticosteroid (ICS)] for asthma is associated with an increased risk of asthma-related death. Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy.
When a LABA is used in fixed‑dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone (see Serious Asthma-Related Events with ICS/LABA) . Available data do not suggest an increased risk of death with use of LABA in patients with COPD. Serious Asthma-Related Events with ICS/LABA Four large, 26-week, randomized, blinded, active-controlled clinical safety trials were conducted to evaluate the risk of serious asthma-related events when LABA were used in fixed-dose combination with ICS compared to ICS alone in patients with asthma.
Three trials included adult and adolescent patients aged ≥12 years: one trial compared budesonide/formoterol to budesonide; one trial compared fluticasone propionate/salmeterol inhalation powder to fluticasone propionate inhalation powder; and one trial compared mometasone furoate/formoterol to mometasone furoate. The fourth trial included pediatric patients 4 to 11 years of age and compared fluticasone propionate/salmeterol inhalation powder to fluticasone propionate inhalation powder.
BREZTRI AEROSPHERE is not indicated for patients 4 to 11 years of age. The primary safety endpoint for all four trials was serious asthma‑related events (hospitalizations, intubations and death). A blinded adjudication committee determined whether events were asthma-related. The three adult and adolescent trials were designed to rule out a risk margin of 2.0, and the pediatric trial was designed to rule out a risk of 2.7.
Each individual trial met its pre-specified objective and demonstrated non-inferiority of ICS/LABA to ICS alone. A meta-analysis of the three adult and adolescent trials did not show a significant increase in risk of a serious asthma-related event with ICS/LABA fixed-dose combination compared with ICS alone (Table 1). These trials were not designed to rule out all risk for serious asthma-related events with ICS/LABA compared with ICS.
Table 1: Meta-analysis of Serious Asthma-Related Events in Patients with Asthma Aged 12 Years and Older ICS/LABA (N=17,537) Randomized patients who had taken at least 1 dose of study drug. Planned treatment used for analysis. ICS (N=17,552) ICS/LABA vs ICS Hazard ratio (95% CI) Estimated using a Cox proportional hazards model of time to first event with baseline hazards stratified by each of the 3 trials. Serious asthma-related event Number of patients with event that occurred within 6 months after the first use of study drug or 7 days after the last date of study drug, whichever date was later.
Patients can have one or more events, but only the first event was counted for analysis. A single, blinded, independent adjudication committee determined whether events were asthma-related. 116 105 1.10 (0.85, 1.44) Asthma-related death 2 0 Asthma-related intubation (endotracheal) 1 2 Asthma-related hospitalization (≥24-hour stay) 115 105 ICS=Inhaled Corticosteroid, LABA=Long-acting Beta2-adrenergic Agonist The pediatric safety trial included 6208 pediatric patients 4 to 11 years of age who received ICS/LABA (fluticasone propionate/salmeterol inhalation powder) or ICS (fluticasone propionate inhalation powder).
In this trial, 27/3107 (0.9%) patients randomized to ICS/LABA and 21/3101 (0.7%) patients randomized to ICS experienced a serious asthma-related event. There were no asthma-related deaths or intubations. ICS/LABA did not show a significantly increased risk of a serious asthma-related event compared to ICS based on the pre-specified risk margin (2.7), with an estimated hazard ratio of time to first event of 1.29 (95% CI: 0.73, 2.27).
BREZTRI AEROSPHERE is not indicated for use in pediatric patients aged 11 years and younger. Salmeterol Multicenter Asthma Research Trial (SMART) A 28-week, placebo-controlled U.S. trial that compared the safety of salmeterol with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in patients receiving salmeterol (13/13,176 in patients treated with salmeterol vs. 3/13,179 in patients treated with placebo; relative risk: 4.37 [95% CI 1.25, 15.34]).
Use of background ICS was not required in SMART. The increased risk of asthma-related death is considered a class effect of LABA monotherapy.
5.2Deterioration of Disease and Acute Episodes
BREZTRI AEROSPHERE should not be initiated in patients with acutely deteriorating COPD or asthma, which may be a life-threatening condition. BREZTRI AEROSPHERE has not been studied in patients with acutely deteriorating COPD or asthma. The use of BREZTRI AEROSPHERE in this setting is not appropriate. Increasing use of inhaled, short-acting beta 2 -agonists is a marker of deteriorating asthma. In this situation, the patient requires immediate re-evaluation with reassessment of the treatment regimen, giving special consideration to the possible need for additional therapeutic options.
Patients sh
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Interactions
No formal drug interaction studies have been performed with BREZTRI AEROSPHERE.
Strong cytochrome P450 3A4 inhibitors (e.g. ritonavir): Use with caution. May cause systemic corticosteroid effects. ( 7.1 )
Other adrenergic drugs may potentiate effect: Use with caution. ( 7.2 )
Diuretics, xanthine derivatives or steroids may potentiate hypokalemia or ECG changes. Use with caution. ( 7.3 , 7.4 )
Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate effect of formoterol fumarate on cardiovascular system. ( 7.5 )
Beta-blockers: Use with caution. May block bronchodilatory effects of beta-agonists and produce severe bronchospasm. ( 7.6 )
Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administration of BREZTRI AEROSPHERE with other anticholinergic-containing drugs. ( 7.7 )
7.1Inhibitors of Cytochrome P450 3A4
The main route of metabolism of corticosteroids, including budesonide, a component of BREZTRI AEROSPHERE, is via cytochrome P450 isoenzyme 3A4 (CYP3A4). After oral administration of ketoconazole, a strong inhibitor of CYP3A4, the mean plasma concentration of orally administered budesonide increased. Concomitant administration of a CYP3A4 inhibitor may inhibit the metabolism of, and increase the systemic exposure to, budesonide.
Caution should be exercised when considering the coadministration of BREZTRI AEROSPHERE with long-term ketoconazole and other known strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, telithromycin) [see Warnings and Precautions (5.9) ] .
7.2Adrenergic Drugs
If additional adrenergic drugs are to be administered by any route, they should be used with caution because the sympathetic effects of formoterol, a component of BREZTRI AEROSPHERE, may be potentiated [see Warnings and Precautions (5.3) ] .
7.3Xanthine Derivatives, Steroids, or Diuretics
Concomitant treatment with xanthine derivatives, steroids, or diuretics may potentiate the hypokalemic effect of beta 2 -adrenergic agonists such as formoterol, a component of BREZTRI AEROSPHERE.
7.4Non-Potassium Sparing Diuretics
The hypokalemia and/or ECG changes that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta 2 -agonists, especially when the recommended dose of the beta 2 -agonist is exceeded.
BREZTRI AEROSPHERE, as with other beta 2 -agonists, should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants or other drugs known to prolong the QTc interval because the action of adrenergic agonists on the cardiovascular system may be potentiated by these agents. Drugs that are known to prolong the QTc interval may be associated with an increased risk of ventricular arrhythmias.
7.6Beta-adrenergic Receptor Blocking Agents
Beta-adrenergic receptor antagonists (beta-blockers) and BREZTRI AEROSPHERE may interfere with the effect of each other when administered concurrently. Beta-blockers not only block the therapeutic effects of beta 2 -agonists, but may produce severe bronchospasm in COPD and asthma patients. Therefore, patients with COPD or asthma should not normally be treated with beta-blockers. However, under certain circumstances, e.g., as prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-blockers in patients with COPD or asthma.
In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.
7.7Anticholinergics
There is a potential for an additive interaction with concomitantly used anticholinergic medications. Therefore, avoid coadministration of BREZTRI AEROSPHERE with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic adverse effects [see Warnings and Precautions (5.9 , 5.10 ) and Adverse Reactions (6.1) ].
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
There are no adequate and well-controlled studies with BREZTRI AEROSPHERE or with two of its individual components, glycopyrrolate or formoterol fumarate, in pregnant women to inform a drug-associated risk; however, studies are available for the other component, budesonide. In animal reproduction studies, budesonide alone, administered by the subcutaneous route, caused structural abnormalities, was embryocidal, and reduced fetal weights in rats and rabbits at 0.3 and 0.75 times maximum recommended human daily inhaled dose (MRHDID), respectively, but these effects were not seen in rats that received inhaled doses up to 4 times the MRHDID.
Studies of pregnant women who received inhaled budesonide alone during pregnancy have not shown increased risk of abnormalities. Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroid exposure than humans. Formoterol fumarate alone, administered by the oral route in rats and rabbits, caused structural abnormalities at 1500 and 61,000 times the MRHDID, respectively.
Formoterol fumarate was also embryocidal, increased pup loss at birth and during lactation, and decreased pup weight in rats at 110 times the MRHDID. These adverse effects generally occurred at large multiples of the MRHDID when formoterol fumarate was administered by the oral route to achieve high systemic exposures. No structural abnormalities, embryocidal, or developmental effects were seen in rats that received inhalation doses up to 350 times the MRHDID.
Glycopyrrolate alone, administered by the subcutaneous route in rats and rabbits, did not cause structural abnormalities or affect fetal survival at exposures approximately 1350 and 2700 times from MRHDID, respectively. Glycopyrrolate had no effects on the physical, functional, and behavioral development of rat pups with exposures up to 1350 times the MRHDID. The estimated background risk of major birth defects and miscarriage for the indicated population is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2-4% and 15-20%, respectively. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate.
Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control. Labor or Delivery: There are no well-controlled human trials that have investigated the effects of BREZTRI AEROSPHERE on preterm labor or labor at term. Because of the potential for beta-agonist interference with uterine contractility, use of BREZTRI AEROSPHERE during labor should be restricted to those patients in whom the benefits clearly outweigh the risks.
Data Human Data Studies of pregnant women have not shown that inhaled budesonide increases the risk of abnormalities when administered during pregnancy. The results from a large population-based prospective cohort epidemiological study reviewing data from three Swedish registries covering approximately 99% of the pregnancies from 1995-1997 (i.e., Swedish Medical Birth Registry; Registry of Congenital Malformations; Child Cardiology Registry) indicate no increased risk for congenital malformations from the use of inhaled budesonide during early pregnancy.
Congenital malformations were studied in 2014 infants born to mothers reporting the use of inhaled budesonide for asthma in early pregnancy (usually 10-12 weeks after the last menstrual period), the period when most major organ malformations occur. The rate of recorded congenital malformations was similar compared to the general population rate (3.8% vs. 3.5%, respectively). In addition, after exposure to inhaled budesonide, the number of infants born with orofacial clefts was similar to the expected number in the normal population (4 children vs. 3.3, respectively).
These same data were utilized in a second study bringing the total to 2,534 infants whose mothers were exposed to inhaled budesonide. In this study, the rate of congenital malformations among infants whose mothers were exposed to inhaled budesonide during early pregnancy was not different from the rate for all newborn babies during the same period (3.6%). Animal Data Budesonide In a fertility and reproduction study male rats were subcutaneously dosed for 9 weeks and females for 2 weeks prior to pairing and throughout the mating period.
Females were dosed up until weaning of their offspring. Budesonide caused a decrease in prenatal viability and viability of the offspring at birth and during lactation, along with a decrease in maternal body weight gain, at a dose 0.3 times the MRHDID (on a mcg/m 2 basis at maternal subcutaneous doses of 20 mcg/kg/day and above). No such effects were noted at a dose 0.08 times the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 5 mcg/kg/day).
In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation days 6 to 18, budesonide produced fetal loss, decreased fetal weight, and skeletal abnormalities at a dose 0.75 times the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 25 mcg/kg/day). In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 6-15, budesonide produced similar adverse fetal effects at doses approximately 8 times the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 500 mcg/kg/day).
In another embryo-fetal development study in pregnant rats, no structural abnormalities or embryocidal effects were seen at doses up to 4 times the MRHDID (on a mcg/m 2 basis at maternal inhalation doses up to 250 mcg/kg/day). In a peri-and post-natal development study, rats dosed from gestation day 15 to postpartum day 21, budesonide had no effects on delivery, but did affect growth and development of offspring. Offspring survival was reduced, and surviving offspring had decreased mean body weights at birth and during lactation at doses 0.3 times the MRHDID and higher (on a mcg/m 2 basis at maternal subcutaneous doses of 20 mcg/kg/day and higher).
These findings occurred in the presence of maternal toxicity. Formoterol Fumarate In a fertility and reproduction study, male rats were orally dosed for at least 9 weeks and females for 2 weeks prior to pairing and throughout the mating period. Females were either dosed up to gestation day 19 or up until weaning of their offspring. Males were dosed up to 25 weeks. Umbilical hernia was observed in rat fetuses at oral doses 1500 times the MRHDID (on a mcg/m 2 basis at maternal oral doses of 3000 mcg/kg/day and higher).
Brachygnathia was observed in rat fetuses at a dose 8000 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 15,000 mcg/kg/day). Pregnancy was prolonged at a dose 8000 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 15,000 mcg/kg/day). Fetal and pup deaths occurred at doses approximately 1500 times the MRHDID and higher (on a mcg/m 2 basis at oral doses of 3000 mcg/kg/day and higher) during gestation.
In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 6 to 15, no structural abnormalities, embryocidal effects, or developmental effects were seen at doses up to 350 times the MRHDID (on a mcg/m 2 basis with maternal inhalation doses up to 690 mcg/kg/day). In an embryo-fetal development study in pregnant rabbits dosed during the period of organogenesis from gestation days 6 to 18, subcapsular cysts on the liver were observed in the fetuses at a dose 61,000 times the MRHDID (on a mcg/m 2 basis with a maternal oral dose of 60,000 mcg/kg/day).
No teratogenic effects were
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Adverse reactions
The following adverse reactions are discussed in greater detail in other sections of the labeling.
Serious asthma-related events – hospitalizations, intubations, death [see Warnings and Precautions (5.1) ]
Oropharyngeal candidiasis infection [see Warnings and Precautions (5.4) ]
Increased risk of pneumonia in COPD [see Warnings and Precautions (5.5) ]
Immunosuppression and risk of infections [see Warnings and Precautions (5.6) ]
Hypercorticism and adrenal suppression [see Warnings and Precautions (5.8) ]
Paradoxical bronchospasm [see Warnings and Precautions (5.10) ]
Hypersensitivity reactions including anaphylaxis [see Contraindications (4) and Warnings and Precautions (5.11) ]
Cardiovascular effects [see Warnings and Precautions (5.12) ]
Reduction in bone mineral density [see Warnings and Precautions (5.13) ]
Growth effects in pediatric patients [see Warnings and Precautions (5.14) ]
Worsening of narrow-angle glaucoma and cataracts [see Warnings and Precautions (5.15) ]
Worsening of urinary retention [see Warnings and Precautions (5.16) ] Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice.
COPD: Most common adverse reactions (incidence ≥ 2%) are upper respiratory tract infection, pneumonia, back pain, oral candidiasis, influenza, muscle spasm, urinary tract infection, cough, sinusitis and diarrhea. ( 6.1 )
Asthma: Most common adverse reactions (incidence ≥ 2%) are nasopharyngitis, pneumonia, and headache. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact AstraZeneca at 1-800-236-9933 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
The safety of BREZTRI AEROSPHERE in COPD is based on the safety data from one 52-week exacerbation trial (ETHOS) and one 24-week lung function trial with a 28-week safety extension study, resulting in up to 52 weeks of treatment (KRONOS). In ETHOS and KRONOS, a total of 2783 subjects have received at least 1 dose of BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg [see Clinical Studies (14.1) ]. In ETHOS and KRONOS, subjects received one of the following treatments: BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg, glycopyrrolate and formoterol fumarate (GFF MDI 18 mcg/9.6 mcg), or budesonide and formoterol fumarate (BFF MDI 320 mcg/9.6 mcg).
Each treatment was administered twice daily. In ETHOS, a 52-week, randomized, double-blind clinical trial, a total of 2144 subjects with COPD received at least 1 dose of BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg (mean age: 64.7 years, 84.9% Caucasian, 59.7% male across all treatments) [see Clinical Studies (14.1) ] . In KRONOS, a 24-week, randomized, double-blind clinical trial, with a 28-week long-term safety extension resulting in up to 52 weeks of treatment, a total of 639 subjects received at least 1 dose of BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg (mean age: 65.2 years, 50.1% Caucasian, 71.2% male across all treatments) [see Clinical Studies (14.1) ] .
The incidence of adverse reactions from the 52-week trial (ETHOS) is presented in Table 2 for subjects treated with BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg, GFF MDI 18 mcg/9.6 mcg, or BFF MDI 320 mcg/9.6 mcg. Table 2: Adverse Reactions Occurring at an Incidence of ≥ 2% of Subjects with COPD and More Common in BREZTRI AEROSPHERE Compared to GFF MDI and/or BFF MDI (ETHOS) Adverse Reaction BREZTRI AEROSPHERE BREZTRI AEROSPHERE = budesonide/glycopyrrolate/formoterol fumarate 320 mcg/18 mcg/9.6 mcg; GFF MDI = glycopyrrolate/formoterol fumarate 18 mcg/9.6 mcg; BFF MDI = budesonide/formoterol fumarate 320 mcg/9.6 mcg; all treatments were administered twice daily. 320 mcg/18 mcg/9.6 mcg N=2144 (%) GFF MDI 18 mcg/9.6 mcg N=2125 (%) BFF MDI 320 mcg/9.6 mcg N=2136 (%) Upper Respiratory Tract Infection 123 (5.7) 102 (4.8) 115 (5.4) Pneumonia 98 (4.6) 61 (2.9) 107 (5.0) Back pain 67 (3.1) 55 (2.6) 64 (3.0) Oral candidiasis 65 (3.0) 24 (1.1) 57 (2.7) Influenza 63 (2.9) 42 (2.0) 61 (2.9) Muscle spasms 60 (2.8) 19 (0.9) 53 (2.5) Urinary tract infection 58 (2.7) 60 (2.8) 41 (1.9) Cough 58 (2.7) 50 (2.4) 51 (2.4) Sinusitis 56 (2.6) 47 (2.2) 55 (2.6) Diarrhea 44 (2.1) 37 (1.7) 38 (1.8) In 24-week data from KRONOS, adverse reactions that occurred in subjects treated with BREZTRI AEROSPHERE 320 mcg/18 mcg/9.6 mcg (n=639) at an incidence of ≥ 2% included dysphonia (3.1%) and muscle spasms (3.3%).
Asthma The safety of BREZTRI AEROSPHERE for the maintenance treatment of asthma is based on the pooled safety data from two, 24 to 52-week, clinical trials (KALOS and LOGOS) [see Clinical Studies (14.2) ] . In the KALOS and LOGOS pooled safety population, a total of 1179 subjects with asthma received at least one dose of BREZTRI AEROSPHERE 320 mcg/36 mcg/9.6 mcg. The mean duration of exposure to BREZTRI AEROSPHERE 320 mcg/36 mcg/9.6 mcg twice daily was 45 weeks, with 678 (57%) subjects treated for at least 52 weeks.
The incidence of adverse reactions (≥ 2%) from the 24 to 52-week trials (KALOS and LOGOS) is presented in Table 3 for subjects treated with BREZTRI AEROSPHERE 320 mcg/36 mcg/9.6 mcg or BFF MDI 320 mcg/9.6 mcg. Table 3: Adverse Reactions with BREZTRI AEROSPHERE with an Incidence of ≥ 2% of Subjects with Asthma and More Common than with BFF MDI (KALOS and LOGOS) Adverse Reaction BREZTRI AEROSPHERE BREZTRI AEROSPHERE=budesonide/glycopyrrolate/formoterol fumarate 320 mcg/36 mcg/9.6 mcg; BFF MDI=budesonide/formoterol fumarate 320 mcg/9.6 mcg; all treatments were administered twice daily. 320 mcg/36 mcg/9.6 mcg N=1179 (%) BFF MDI 320 mcg/9.6 mcg N=1208 (%) Nasopharyngitis 111 (9.4) 101 (8.4) Pneumonia Consists of pneumonia, pneumonia bacterial, pneumonia fungal, pneumonia mycoplasma, pneumonia pneumococcal, pneumonia viral. 33 (2.8) 27 (2.2) Headache 26 (2.2) 15 (1.2) Additional Adverse Reactions Other adverse reactions that have been associated with one or more of the individual components of BREZTRI AEROSPHERE include: gastroesophageal reflux disease, dysphonia, oropharyngeal pain, renal and urinary tract infection, hyperglycemia, anxiety, insomnia, palpitations, nausea, hypersensitivity, depression, agitation, restlessness, nervousness, tremor, dizziness, angina pectoris, tachycardia, cardiac arrhythmias (e.g., atrial fibrillation, supraventricular tachycardia, and extrasystoles), throat irritation, bronchospasm, dry mouth, bruising, urinary retention, chest pain, sign or symptoms of systemic glucocorticoid steroid effects (e.g., hypofunctional adrenal gland), and abnormal behavior.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
