Aclidinium Bromide; Formoterol
Aclidinium bromide/formoterol fumarate is an inhaled fixed-dose combination bronchodilator indicated as maintenance treatment to relieve symptoms in adult patients with chronic obstructive pulmonary disease (COPD).
Source:
EMA
Active Ingredients:
Indications
Representation
No sex-specific representation data
Efficacy
No sex-specific efficacy data
Posology
No sex-specific posology data
Potential Side Effects
No sex-specific potential side effect data
Sex- and gender-specific information
Men
Women
Disease prevalence by sex
60%
40%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
In Phase III COPD trials (ACLIFORM-COPD, AUGMENT, extension, and a 12‑month study; ~4,000 patients, 1,222 on aclidinium bromide-formoterol 340/12 micrograms), the medication produced clinically meaningful improvements in lung function (FEV1, FVC, inspiratory capacity) versus placebo and monocomponents, improved breathlessness (TDI focal score), daily COPD symptoms (E‑RS), health-related quality of life (SGRQ), reduced rescue medication use, reduced the rate of moderate/severe exacerbations by 29% versus placebo, delayed time to first exacerbation, and improved lung volumes, exercise endurance and physical activity in an 8‑week study of hyperinflated COPD patients.
The clinical development programme in COPD (including ~4,000 patients, 1,222 on aclidinium bromide-formoterol 340/12 micrograms) demonstrated that the medication improved lung function, breathlessness, daily symptoms, health-related quality of life, reduced exacerbation rates and delayed time to first exacerbation, and improved lung volumes, exercise endurance and physical activity compared with placebo and monocomponents. No sex-specific differences in efficacy were reported.
Sex-specific posology
No sex-specific data
For adult COPD patients, the recommended dose is one inhalation of aclidinium bromide-formoterol (396 micrograms aclidinium bromide / 11.8 micrograms formoterol fumarate dihydrate delivered dose) twice daily by inhalation. If a dose is missed, it should be taken as soon as possible and the next dose at the usual time; a double dose should not be taken. No dose adjustments are required in elderly patients or in patients with renal or hepatic impairment. There is no relevant use in children and adolescents under 18 years of age for COPD.
The same recommended dose applies to women as to men: one inhalation of aclidinium bromide-formoterol twice daily, with no sex-specific dose adjustments. Dose adjustments are not required in elderly patients or in patients with renal or hepatic impairment.
Sex-specific differences in possible side effects
No sex-specific data
No sex-specific data were reported in the evaluated sources.
Pregnancy / lactation
N / A
There are no data on use of aclidinium bromide-formoterol in pregnant women and it should only be used during pregnancy if the expected benefits outweigh the potential risks. It is unknown whether aclidinium or formoterol are excreted in human milk; animal studies showed small amounts in rat milk, so use in breast-feeding women should only be considered if the expected benefit to the woman outweighs any possible risk to the infant.
Sex-specific non-clinical findings
Nonclinical reproductive studies showed slight reductions in fertility and foetotoxic effects at exposures far exceeding human levels, including decreased conception rate, reduced numbers of corpora lutea and implantation losses with aclidinium, and reduced fertility (implantation losses), decreased early postnatal survival and lower birth weight with high systemic exposure to formoterol; these are considered of little relevance at therapeutic doses.
Nonclinical reproductive toxicity studies showed slight reductions in fertility and foetotoxic effects at exposures far above human levels for both aclidinium and formoterol. These included decreased conception rate, fewer corpora lutea and increased pre‑ and post‑implantation losses with aclidinium, and reduced fertility, decreased early postnatal survival and reduced birth weight with high systemic exposure to formoterol. These findings are considered of little relevance at therapeutic doses.
Disease prevalence by sex
Men
60%
Women
40%
Clinical study participation by sex
Sex distribution not reported in the evaluated sources.
Representation Gap
No sex-specific data
N / A
Sex-specific efficacy/accuracy
No sex-specific data
Men
In Phase III COPD trials (ACLIFORM-COPD, AUGMENT, extension, and a 12‑month study; ~4,000 patients, 1,222 on aclidinium bromide-formoterol 340/12 micrograms), the medication produced clinically meaningful improvements in lung function (FEV1, FVC, inspiratory capacity) versus placebo and monocomponents, improved breathlessness (TDI focal score), daily COPD symptoms (E‑RS), health-related quality of life (SGRQ), reduced rescue medication use, reduced the rate of moderate/severe exacerbations by 29% versus placebo, delayed time to first exacerbation, and improved lung volumes, exercise endurance and physical activity in an 8‑week study of hyperinflated COPD patients.
Women
The clinical development programme in COPD (including ~4,000 patients, 1,222 on aclidinium bromide-formoterol 340/12 micrograms) demonstrated that the medication improved lung function, breathlessness, daily symptoms, health-related quality of life, reduced exacerbation rates and delayed time to first exacerbation, and improved lung volumes, exercise endurance and physical activity compared with placebo and monocomponents. No sex-specific differences in efficacy were reported.
Sex-specific posology
No sex-specific data
Men
For adult COPD patients, the recommended dose is one inhalation of aclidinium bromide-formoterol (396 micrograms aclidinium bromide / 11.8 micrograms formoterol fumarate dihydrate delivered dose) twice daily by inhalation. If a dose is missed, it should be taken as soon as possible and the next dose at the usual time; a double dose should not be taken. No dose adjustments are required in elderly patients or in patients with renal or hepatic impairment. There is no relevant use in children and adolescents under 18 years of age for COPD.
Women
The same recommended dose applies to women as to men: one inhalation of aclidinium bromide-formoterol twice daily, with no sex-specific dose adjustments. Dose adjustments are not required in elderly patients or in patients with renal or hepatic impairment.
Sex-specific differences in possible side effects
No sex-specific data
No sex-specific data were reported in the evaluated sources.
Pregnancy / lactation
Men
N / A
Women
There are no data on use of aclidinium bromide-formoterol in pregnant women and it should only be used during pregnancy if the expected benefits outweigh the potential risks. It is unknown whether aclidinium or formoterol are excreted in human milk; animal studies showed small amounts in rat milk, so use in breast-feeding women should only be considered if the expected benefit to the woman outweighs any possible risk to the infant.
Sex-specific non-clinical findings
Men
Nonclinical reproductive studies showed slight reductions in fertility and foetotoxic effects at exposures far exceeding human levels, including decreased conception rate, reduced numbers of corpora lutea and implantation losses with aclidinium, and reduced fertility (implantation losses), decreased early postnatal survival and lower birth weight with high systemic exposure to formoterol; these are considered of little relevance at therapeutic doses.
Women
Nonclinical reproductive toxicity studies showed slight reductions in fertility and foetotoxic effects at exposures far above human levels for both aclidinium and formoterol. These included decreased conception rate, fewer corpora lutea and increased pre‑ and post‑implantation losses with aclidinium, and reduced fertility, decreased early postnatal survival and reduced birth weight with high systemic exposure to formoterol. These findings are considered of little relevance at therapeutic doses.
General information
General Efficacy
Not reported
General Posology
Not reported
Further Dose Adjustments
Not reported
Possible Side Effects
In clinical trials and post‑marketing experience, adverse reactions with Duaklir Genuair were similar to those of its individual components. The most frequently reported adverse reactions were nasopharyngitis (7.9%) and headache (6.8%), both classified as common. Other common adverse reactions included urinary tract infection, sinusitis, tooth abscess, insomnia, anxiety, dizziness, tremor, cough, diarrhoea, nausea, dry mouth, stomatitis, muscle spasms, myalgia, increased blood creatine phosphokinase and increased blood pressure. Clinically important but less frequent reactions included hypokalaemia and hyperglycaemia (uncommon), cardiac arrhythmias including atrial fibrillation and paroxysmal tachycardia, tachycardia, QTc prolongation, palpitations and angina pectoris (uncommon), bronchospasm including paradoxical bronchospasm (rare), hypersensitivity reactions including angioedema and anaphylactic reaction (rare/not known), blurred vision, dysphonia, urinary retention, rash and pruritus. The document does not specify particular reasons for treatment discontinuation.
Contraindications
Not reported
Clinical Trial Type and Population
Not reported
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EQUAL CARE® Evaluation
Medication