DUAKLIR PRESSAIR aclidinium bromide and formoterol fumarate 400 ug; 12 ug Powder, Metered
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Anticholinergic class.
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🏭 Manufacturer & labeler
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🩺 Clinical
Aclidinium is used as a long term treatment to prevent wheezing, shortness of breath, coughing, and chest tightness in patients with chronic obstructive pulmonary disease (COPD, a group of diseases that affect the lungs and airways) such as chronic bronchitis (swelling of the air passages that lead to the lungs) and emphysema (damage to air sacs in the lungs). Aclidinium is in a class of medications called bronchodilators. It works by relaxing and opening the air passages to the lungs to make breathing easier.
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🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
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UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
1 inactive ingredient listed in the exact product block matched to this NDC.
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ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
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💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per g | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Duaklir Pressair 400 ug/1; 12 ugthis 70515-0001-03 | Covis | 1 pouch | — | — | FDA listed | — |
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⏳ Availability & generic status
We did not find an FDA-approved generic match for this exact strength, form and route. Patent/protection dates below may affect future generic timing.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 10085974 ↗ | Method of use | U-2513 | Mar 13, 2029 |
| US 11000517 ↗ | Method of use | U-2513 | Mar 13, 2029 |
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📊 Medicare Part D spend CMS · PART D · 2026 (Q1)
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 70515-0001-01 | 1 POUCH in 1 CARTON (70515-001-01) / 1 INHALER in 1 POUCH / 60 POWDER, METERED in 1 INHALER | 2019-03-29 | Active |
| 70515-0001-03 You're viewing this | 1 POUCH in 1 CARTON (70515-001-03) / 1 INHALER in 1 POUCH / 30 POWDER, METERED in 1 INHALER | 2019-03-29 | Active |
Pack size FAQ
What quantity is in NDC 70515-0001-03?
What NDC number is used to bill for this package of DUAKLIR PRESSAIR aclidinium bromide and formoterol fumarate 400 ug; 12 ug Powder, Metered?
🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | — Not published for this NDC Most self-administered / retail products have no J-code — that is normal. |
| Medicaid utilization (CMS SDUD) | — Not published for this NDC CMS reports utilization only for NDCs with Medicaid claims above its privacy threshold. |
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE DUAKLIR PRESSAIR is a combination of aclidinium bromide (an anticholinergic) and formoterol fumarate (a LABA) indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). Limitations of Use: DUAKLIR PRESSAIR is not indicated for the relief of acute bronchospasm or for the treatment of asthma [see Warnings and Precautions ( 5.1 , 5.4 )] . DUAKLIR PRESSAIR is a combination of aclidinium bromide an anticholinergic, and formoterol fumarate, a long-acting beta 2 -adrenergic agonist (LABA) indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD).
( 1 ) Limitations of Use: Not indicated for the relief of acute bronchospasm or for the treatment of asthma. ( 1 , 5.4 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION The recommended dose of DUAKLIR PRESSAIR is one oral inhalation of 400 mcg/12 mcg, twice daily (once in the morning and once in the evening). Do not take more than one inhalation twice daily. • For oral inhalation only. ( 2 ) • 400 mcg/12 mcg, twice daily (once in the morning and once in the evening). ( 2 )
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Inhalation Powder. DUAKLIR PRESSAIR is a breath-actuated multi-dose dry powder inhaler metering 400 mcg of aclidinium bromide and 12 mcg of formoterol fumarate per actuation. • Inhalation Powder. ( 3 ) • Breath-actuated multi-dose dry powder inhaler metering 400 mcg of aclidinium bromide and 12 mcg of formoterol fumarate per actuation. ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Use of a long-acting beta 2 -adrenergic agonist (LABA), including formoterol fumarate, one of the active ingredients in DUAKLIR PRESSAIR, without an inhaled corticosteroid is contraindicated in patients with asthma [see Warnings and Precautions (5.1) ] . DUAKLIR PRESSAIR is not indicated for the treatment of asthma. DUAKLIR PRESSAIR is contraindicated in patients with: • Severe hypersensitivity to milk proteins [see Warnings and Precautions (5.5) ] . • Hypersensitivity to aclidinium bromide, formoterol fumarate, or to any component of the product [see Warnings and Precautions (5.5) ] . • Use of a long-acting beta 2 -adrenergic agonist (LABA), including formoterol fumarate, one of the active ingredients in DUAKLIR PRESSAIR, without an inhaled corticosteroid is contraindicated in patients with asthma.
( 1 , 4 ) • Hypersensitivity to aclidinium bromide or formoterol fumarate or to any component of this product. ( 4 , 5.5 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS • Asthma-related death: Long-acting beta 2 -adrenergic agonists as monotherapy (without an inhaled corticosteroid) for asthma increase the risk of serious asthma-related events. ( 5.1 ) • Do not initiate in acutely deteriorating COPD or to treat acute symptoms. ( 5.2 ) • Do not use in combination with an additional medicine containing a LABA because of risk of overdose.
( 5.3 ) • If paradoxical bronchospasm occurs, discontinue DUAKLIR PRESSAIR and institute alternative therapy. ( 5.4 ) • Use with caution in patients with cardiovascular disorders. ( 5.6 ) • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus and ketoacidosis.
( 5.7 ) • Be alert to hypokalemia and hyperglycemia. ( 5.8 ) • Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to contact a physician immediately if symptoms occur.
( 5.9 ) • Worsening urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to consult a physician immediately if symptoms occur. ( 5.10 )
5.1Serious Asthma-Related Events-Hospitalizations, Intubations, Death • The safety and efficacy of DUAKLIR PRESSAIR in patients with asthma have not been established. DUAKLIR PRESSAIR is not indicated for the treatment of asthma. [see Contraindications (4) ] . • Use of LABA as monotherapy [without inhaled corticosteroids (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 LABA are 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. • A 28-week, placebo-controlled, U.S. trial comparing the safety of another LABA (salmeterol) with placebo, each added to usual asthma therapy, showed an increase in asthma-related deaths in subjects receiving salmeterol (13/13,176 in subjects treated with salmeterol vs 3/13,179 in subjects treated with placebo; relative risk: 4.37 [95% CI: 1.25, 15.34]).
The increased risk of asthma-related death is considered a class effect of LABAs, including formoterol fumarate, one of the active ingredients in DUAKLIR PRESSAIR. • No trial adequate to determine whether the rate of asthma-related deaths is increased in subjects treated with DUAKLIR PRESSAIR has been conducted. • Available data do not suggest an increased risk of death with use of LABA in patients with COPD.
5.2Deterioration of Disease and Acute Episodes DUAKLIR PRESSAIR should not be initiated in patients with acutely deteriorating COPD, which may be a life-threatening condition. DUAKLIR PRESSAIR has not been studied in patients with acutely deteriorating COPD. The use of DUAKLIR PRESSAIR in this setting is inappropriate.
DUAKLIR PRESSAIR is intended as twice daily maintenance treatment for COPD and should not be used for the relief of acute symptoms, i.e., as rescue therapy for treatment of acute episodes of bronchospasm. DUAKLIR PRESSAIR has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled short-acting beta 2 -agonist.
When beginning treatment with DUAKLIR PRESSAIR, patients who have been taking oral or inhaled, short-acting beta 2 -agonists on a regular basis (e.g., four times a day) should be instructed to discontinue the regular use of these drugs and use them only for symptomatic relief of acute respiratory symptoms. When prescribing DUAKLIR PRESSAIR, the healthcare provider should also prescribe an inhaled, short-acting beta 2 -agonist and instruct the patient on h…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS LABAs, such as formoterol fumarate, one of the active ingredients in DUAKLIR PRESSAIR, increase the risk of asthma-related death. DUAKLIR PRESSAIR is not indicated for the treatment of asthma [see Warnings and Precautions (5.1) ] . The following adverse reactions are described in greater detail elsewhere in the labeling: • Paradoxical bronchospasm [see Warnings and Precautions (5.4) ] • Immediate hypersensitivity reactions [see Contraindications (4) , Warnings and Precautions (5.5) ] • Cardiovascular effects [see Warnings and Precautions (5.6)] • Worsening of narrow-angle glaucoma [see Warnings and Precautions (5.9) ] • Worsening of urinary retention [see Warnings and Precautions (5.10) ] Most common adverse reactions (incidence ≥ 3% and more common than with placebo) include: upper respiratory tract infection, headache and, back pain.
( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Covis Pharma at 1-877-411-2510 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1Clinical Trials Experience 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. The clinical program for DUAKLIR PRESSAIR included 6501 subjects with COPD in 2 placebo-controlled and 1 active-controlled 24-week lung function trials, one long-term safety extension study of 28 weeks and 2 other clinical trials.
A total of 1893 subjects have received at least 1 dose of DUAKLIR PRESSAIR. 24-Week Trials The frequency of common adverse reactions in Table 1 below is based upon pooled data from two, double-blind, placebo-controlled parallel group clinical trials (Trials 1 and 2, n=1729 and n=1669) in 3398 adult patients with moderate to severe COPD. Of these, 60% were male and 94% were Caucasian.
They had a mean age of 64 years and an average smoking history of 46 pack-years, with 49% identified as current smokers. At screening, the mean post-bronchodilator percent predicted forced expiratory volume in 1 second (FEV 1 ) was 54% (range: 28% to 80%) and the mean percent reversibility was 15% (range: -19% to 69%). Table 1 shows all adverse reactions that occurred with a frequency of greater than or equal to 3% in the DUAKLIR PRESSAIR group in the two 24-week placebo-controlled trials where the rates in the DUAKLIR PRESSAIR group exceeded placebo.
Table 1: Adverse Reactions with DUAKLIR PRESSAIR ≥3% Incidence and More Common than with Placebo in Subjects with COPD Treatment Adverse Reactions Preferred Term DUAKLIR PRESSAIR (N=720) % Aclidinium (N=722) % Formoterol (N=716) % Placebo (N=526) % Upper respiratory tract infection Includes Viral Upper Respiratory Tract Infection and Upper Respiratory Tract Infection 8.9 7.6 8.9
6.3Headache 6.3 6.6 7.7
5.1Back pain 3.8 3.3 3.5
3.4Other adverse reactions reported in clinical studies with an incidence of >1% but less than 3% with DUAKLIR PRESSAIR but more common than with placebo were cough, sinusitis, influenza, tooth abscess, insomnia, dizziness, dry mouth, oropharyngeal pain, muscle spasms, musculoskeletal pain, arthralgia, pain in extremity, urinary tract infection, and blood creatine phosphokinase increased. The adverse events reported in the 24-week active-controlled trial were consistent with those observed in 24-week placebo-controlled trials.
Long-Term Safety Extension Trial In a 28-week safety extension trial, 918 subjects who successfully completed Trial 2 were treated for up to an additional 28 weeks for a total treatment period of up to 52 weeks with DUAKLIR PRESSAIR, aclidinium 400 mcg, formoterol fumarate 12 mcg administered twice daily or placebo. Because the subjects continued from Trial 2 into the safety extension trial, the demographic and baseline characteristics of the long-term safety extension trial were similar to those of the placebo-controlled efficacy trials described ab…
🔄 Drug Interactions ▾
7 DRUG INTERACTIONS No formal drug interaction studies have been performed with DUAKLIR PRESSAIR. • Use of other adrenergic by any route may potentiate the effect of DUAKLIR PRESSAIR. Use with caution. ( 5.3 , 7.1 ) • Xanthine derivatives, steroids, diuretics or non-potassium sparing diuretics may potentiate hypokalemia or ECG changes.
Use with caution. ( 7.2 , 7.3 ) • Diuretics: Use with caution. Electrocardiographic changes and/or hypokalemia associated with non-potassium sparing diuretics may worsen with concomitant beta 2 -agonists.
( 7.3 ) • Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate effect of formoterol fumarate on cardiovascular system. ( 7.4 ) • Beta-blockers: Use with caution and only when medically necessary.
( 7.5 ) • Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administrations of DUAKLIR PRESSAIR with other anticholinergic-containing drugs. ( 7.6 )
7.1Adrenergic 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 DUAKLIR PRESSAIR, may be potentiated [see Warnings and Precautions (5.7) ] .
7.2Xanthine Derivatives, Steroids Concomitant treatment with xanthine derivatives, or steroids may potentiate any hypokalemic effect of beta-adrenergic agonists such as formoterol, a component of DUAKLIR PRESSAIR.
7.3Non-Potassium Sparing Diuretics The electrocardiographic changes and/or hypokalemia that may result from the administration of non-potassium-sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is not known, caution is advised in the coadministration of beta-agonists with non–potassium-sparing diuretics.
7.4Monoamine Oxidase Inhibitors and Tricyclic Antidepressants, QTc Prolonging Drugs DUAKLIR PRESSAIR, as with other drugs containing beta 2 -agonists, should be administered with caution to patients being treated with monoamine oxidase inhibitors, 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 have an increased risk of ventricular arrhythmias.
7.5Beta-Blockers Beta-adrenergic receptor antagonists (beta-blockers) and DUAKLIR PRESSAIR may inhibit the effect of each other when administered concurrently. Beta-blockers not only block the therapeutic effects of beta 2 -agonists, such as formoterol, a component of DUAKLIR PRESSAIR, but may produce severe bronchospasm in COPD patients. Therefore, patients with COPD 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. In this setting, cardioselective beta-blockers could be considered, although they should be administered with caution.
7.6Anticholinergics There is a potential for an additive interaction with concomitantly used anticholinergic medications. Therefore, avoid coadministration of DUAKLIR PRESSAIR with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic effects [see Warnings and Precautions ( 5.3 , 5.4 ) and Adverse Reactions (6) ] .
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS
8.1Pregnancy Risk Summary There are no adequate and well-controlled studies of DUAKLIR PRESSAIR or its individual components, formoterol fumarate or aclidinium bromide, in pregnant women to inform drug-associated risks. No adverse developmental effects were seen with inhalation administration of aclidinium bromide to pregnant rats and rabbits during organogenesis at 15 or 20 times, respectively, the maximum recommended human daily inhaled dose (MRHDID). However, reduced pup weights were seen when pregnant rats continued inhalation administration through lactation at 5 times the MRHDID of aclidinium bromide.
Adverse developmental effects occurred when rabbits were orally dosed with aclidinium bromide at approximately 1,400 times the MRHDID [see Data] . Formoterol fumarate alone, administered by the oral route, was teratogenic in rats and rabbits at 1,200 and 49,000 times the MRHDID, respectively. Formoterol fumarate was also embryocidal, increased pup loss at birth and during lactation, and decreased pup weight in rats at 85 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 teratogenic, embryocidal, or developmental effects were seen in rats that received inhalation doses up to 280 times the MRHDID [ see Data ]. The estimated background risk of major birth defects and miscarriage of the indicated populations is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Labor or Delivery There are no well-controlled human studies that have investigated the effects of DUAKLIR PRESSAIR during labor and delivery. Because of the potential for beta-agonist interference with uterine contractility, use of DUAKLIR PRESSAIR during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.
Data Animal Data Aclidinium bromide In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 6-17, no evidence of structural alterations was observed at approximately 15 times the maximum recommended human daily inhaled dose (MRHDID) [based on summed AUCs of aclidinium bromide and its metabolites at inhaled doses less than or equal to 5.0 mg/kg/day]. However, in a pre- and post-natal development study, decreased pup weights were observed when pregnant rats were exposed from gestation day 6 and continuing during the lactation period at approximately 5 times the MRHDID [based on summed AUCs of aclidinium bromide and its metabolites at inhaled doses greater than or equal to 0.2 mg/kg/day].
Maternal toxicity was also observed at inhaled doses greater than or equal to 0.2 mg/kg/day. In an embryo-fetal development study in pregnant Himalayan rabbits administered inhaled doses of aclidinium bromide during the period of organogenesis from gestation days 6-19, no evidence of structural alterations was observed at approximately 20 times the MRHDID [based on summed AUCs of aclidinium bromide and its metabolites at inhaled doses less than or equal to 3.6 mg/kg/day]. However, in another embryo-fetal development study in pregnant Himalayan rabbits dosed orally from gestation days 6-19, increased incidences of additional liver lobes (3-5%), as compared to 0% in the control group, were observed at approximately 1,400 times the MRHDID [based on summed AUCs of aclidinium bromide and its metabolites at oral doses greater than or equal to 150 mg/kg/day], and decreased fetal body weights were observed at approximately 2,300 times the MRHDID [based on summed AUCs of aclidinium bromide and its metabolites at oral doses greater than or equal to 300 mg/kg/day].
These fetal findings were observed in the presence of maternal toxicity. Formoterol fumarate In a fertility…
🤰 Pregnancy ▾
8.1Pregnancy Risk Summary There are no adequate and well-controlled studies of DUAKLIR PRESSAIR or its individual components, formoterol fumarate or aclidinium bromide, in pregnant women to inform drug-associated risks. No adverse developmental effects were seen with inhalation administration of aclidinium bromide to pregnant rats and rabbits during organogenesis at 15 or 20 times, respectively, the maximum recommended human daily inhaled dose (MRHDID). However, reduced pup weights were seen when pregnant rats continued inhalation administration through lactation at 5 times the MRHDID of aclidinium bromide.
Adverse developmental effects occurred when rabbits were orally dosed with aclidinium bromide at approximately 1,400 times the MRHDID [see Data] . Formoterol fumarate alone, administered by the oral route, was teratogenic in rats and rabbits at 1,200 and 49,000 times the MRHDID, respectively. Formoterol fumarate was also embryocidal, increased pup loss at birth and during lactation, and decreased pup weight in rats at 85 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 teratogenic, embryocidal, or developmental effects were seen in rats that received inhalation doses up to 280 times the MRHDID [ see Data ]. The estimated background risk of major birth defects and miscarriage of the indicated populations is unknown.
In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. Clinical Considerations Labor or Delivery There are no well-controlled human studies that have investigated the effects of DUAKLIR PRESSAIR during labor and delivery. Because of the potential for beta-agonist interference with uterine contractility, use of DUAKLIR PRESSAIR during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.
Data Animal Data Aclidinium bromide In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 6-17, no evidence of structural alterations was observed at approximately 15 times the maximum recommended human daily inhaled dose (MRHDID) [based on summed AUCs of aclidinium bromide and its metabolites at inhaled doses less than or equal to 5.0 mg/kg/day]. However, in a pre- and post-natal development study, decreased pup weights were observed when pregnant rats were exposed from gestation day 6 and continuing during the lactation period at approximately 5 times the MRHDID [based on summed AUCs of aclidinium bromide and its metabolites at inhaled doses greater than or equal to 0.2 mg/kg/day].
Maternal toxicity was also observed at inhaled doses greater than or equal to 0.2 mg/kg/day. In an embryo-fetal development study in pregnant Himalayan rabbits administered inhaled doses of aclidinium bromide during the period of organogenesis from gestation days 6-19, no evidence of structural alterations was observed at approximately 20 times the MRHDID [based on summed AUCs of aclidinium bromide and its metabolites at inhaled doses less than or equal to 3.6 mg/kg/day]. However, in another embryo-fetal development study in pregnant Himalayan rabbits dosed orally from gestation days 6-19, increased incidences of additional liver lobes (3-5%), as compared to 0% in the control group, were observed at approximately 1,400 times the MRHDID [based on summed AUCs of aclidinium bromide and its metabolites at oral doses greater than or equal to 150 mg/kg/day], and decreased fetal body weights were observed at approximately 2,300 times the MRHDID [based on summed AUCs of aclidinium bromide and its metabolites at oral doses greater than or equal to 300 mg/kg/day].
These fetal findings were observed in the presence of maternal toxicity. Formoterol fumarate In a fertility and reproduction study, male r…
🧒 Pediatric Use ▾
8.4Pediatric Use DUAKLIR PRESSAIR is not indicated for use in children. The safety and effectiveness of DUAKLIR PRESSAIR in the pediatric population have not been established.
🧓 Geriatric Use ▾
8.5Geriatric Use Based on available data for DUAKLIR PRESSAIR or its active components, no adjustment of dosage in geriatric patients is warranted [see Clinical Pharmacology (12.3) ] . Of the 720 COPD patients exposed to DUAKLIR PRESSAIR for 24 weeks in two placebo-controlled clinical trials, 238 were less than 60 years, 301 were greater than or equal to 60 to less than 70 years, and 181 were greater than or equal to 70 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects.
Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
🆘 Overdosage ▾
10 OVERDOSAGE DUAKLIR PRESSAIR contains both aclidinium and formoterol fumarate; therefore, the risks associated with overdosage for the individual components described below apply to DUAKLIR PRESSAIR. The most common symptoms are blurred vision, dry mouth, nausea, muscle spasms, tremor, headache, palpitations, and systolic hypertension. Treatment of overdosage consists of discontinuation of DUAKLIR PRESSAIR together with institution of appropriate symptomatic and/or supportive therapy.
🧬 Clinical Pharmacology ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action DUAKLIR PRESSAIR DUAKLIR PRESSAIR contains two bronchodilators: aclidinium a long-acting muscarinic antagonist (also known as an anticholinergic) and formoterol a long-acting beta 2 -adrenergic agonist. Further information regarding these two substances is provided below. The mechanism of action described below for the individual components apply to DUAKLIR PRESSAIR.
These drugs represent two different classes of medications (a long-acting antimuscarinic agent and a selective long-acting beta 2 -adrenergic receptor agonist) that have different effects on clinical and physiological indices of COPD. Aclidinium bromide Aclidinium bromide is a long-acting antimuscarinic agent, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5.
In the airways, it exhibits pharmacological effects through inhibition of M3 receptors at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies, prevention of acetylcholine-induced bronchoconstriction effects was dose-dependent and lasted longer than 24 hours.
The clinical relevance of these findings is unknown. The bronchodilation following inhalation of aclidinium bromide is predominantly a site-specific effect. Formoterol fumarate Formoterol fumarate is a long-acting selective beta 2 -adrenergic receptor agonist (LABA) (beta 2 -agonist).
Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In-vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta 2 -receptors than at beta 1 -receptors. The in-vitro binding selectivity to beta 2 -over beta 1 -adrenoceptors is higher for formoterol than for albuterol (5 times), whereas salmeterol has a higher (3 times) beta‑selectivity ratio than formoterol.
Although beta 2 -receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta 1 -receptors are the predominant receptors in the heart, there are also beta 2 -receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta 2 -agonists may have cardiac effects. The pharmacologic effects of beta 2 -adrenoceptor agonist drugs, including formoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP).
Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. In vitro tests show that formoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Formoterol also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper responsiveness.
The relevance of these in vitro and animal findings to humans is unknown.
12.2Pharmacodynamics Cardiovascular effects DUAKLIR PRESSAIR The effect of DUAKLIR PRESSAIR on cardiac rhythm was assessed in a subset of subjects using 24-hour Holter monitoring in the 24-week placebo-controlled trials. The Holter monitoring population included 114 subjects on DUAKLIR PRESSAIR, 118 subjects on aclidinium bromide 400 mcg, 121 subjects on formoterol fumarate 12 mcg, and 81 subjects on placebo. No clinically meaningful effects on cardiac rhythm were observed.
12.3Pharmacokinetics Absorption Following twice-daily oral inhalation administration of DUAKLIR PRESSAIR in COPD patients, mean maximum aclidinium and formoterol concentrations of 128 p…
🧬 Mechanism of Action ▾
12.1Mechanism of Action DUAKLIR PRESSAIR DUAKLIR PRESSAIR contains two bronchodilators: aclidinium a long-acting muscarinic antagonist (also known as an anticholinergic) and formoterol a long-acting beta 2 -adrenergic agonist. Further information regarding these two substances is provided below. The mechanism of action described below for the individual components apply to DUAKLIR PRESSAIR.
These drugs represent two different classes of medications (a long-acting antimuscarinic agent and a selective long-acting beta 2 -adrenergic receptor agonist) that have different effects on clinical and physiological indices of COPD. Aclidinium bromide Aclidinium bromide is a long-acting antimuscarinic agent, which is often referred to as an anticholinergic. It has similar affinity to the subtypes of muscarinic receptors M1 to M5.
In the airways, it exhibits pharmacological effects through inhibition of M3 receptors at the smooth muscle leading to bronchodilation. The competitive and reversible nature of antagonism was shown with human and animal origin receptors and isolated organ preparations. In preclinical in vitro as well as in vivo studies, prevention of acetylcholine-induced bronchoconstriction effects was dose-dependent and lasted longer than 24 hours.
The clinical relevance of these findings is unknown. The bronchodilation following inhalation of aclidinium bromide is predominantly a site-specific effect. Formoterol fumarate Formoterol fumarate is a long-acting selective beta 2 -adrenergic receptor agonist (LABA) (beta 2 -agonist).
Inhaled formoterol fumarate acts locally in the lung as a bronchodilator. In-vitro studies have shown that formoterol has more than 200-fold greater agonist activity at beta 2 -receptors than at beta 1 -receptors. The in-vitro binding selectivity to beta 2 -over beta 1 -adrenoceptors is higher for formoterol than for albuterol (5 times), whereas salmeterol has a higher (3 times) beta‑selectivity ratio than formoterol.
Although beta 2 -receptors are the predominant adrenergic receptors in bronchial smooth muscle and beta 1 -receptors are the predominant receptors in the heart, there are also beta 2 -receptors in the human heart comprising 10% to 50% of the total beta-adrenergic receptors. The precise function of these receptors has not been established, but they raise the possibility that even highly selective beta 2 -agonists may have cardiac effects. The pharmacologic effects of beta 2 -adrenoceptor agonist drugs, including formoterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3', 5'-adenosine monophosphate (cyclic AMP).
Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. In vitro tests show that formoterol is an inhibitor of the release of mast cell mediators, such as histamine and leukotrienes, from the human lung. Formoterol also inhibits histamine-induced plasma albumin extravasation in anesthetized guinea pigs and inhibits allergen-induced eosinophil influx in dogs with airway hyper responsiveness.
The relevance of these in vitro and animal findings to humans is unknown.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING DUAKLIR PRESSAIR 400 mcg/12 mcg (aclidinium bromide and formoterol fumarate inhalation powder) is supplied in a sealed bag with a desiccant sachet and is available in 60 metered doses (NDC 0310-0900-60) and 30 metered doses (NDC 0310-0900-30). The active ingredients are administered using a multi-dose dry powder inhaler, PRESSAIR®, which delivers 60 doses or 30 doses of aclidinium bromide and formoterol fumarate powder for oral inhalation. The PRESSAIR inhaler is a white and orange colored device and is comprised of an assembled plastic dosing mechanism with a dose indicator, a drug-product storage unit containing the drug-product formulation, and a mouthpiece covered by an orange protective cap.
Store DUAKLIR PRESSAIR in a dry place at 20°C-25°C (68°F-77°F); excursions permitted to 15-30°C (59-86°F) [see USP Controlled Room Temperature]. Do not store the inhaler on a vibrating surface. The PRESSAIR inhaler should be stored inside the sealed bag and only be opened immediately before use.
Throw away the bag and the desiccant sachet. Throw away (dispose of) the PRESSAIR inhaler after the marking “0” with a red background shows in the middle of the dose indicator, when the device is empty and locks out, or 2 months after the date you opened the sealed bag that the inhaler comes in, whichever comes first. Keep out of reach of children.
📋 Description ▾
11 DESCRIPTION DUAKLIR PRESSAIR consists of a dry powder formulation of aclidinium bromide and formoterol fumarate for oral inhalation only. Aclidinium bromide, is an anticholinergic with specificity for muscarinic receptors. Aclidinium bromide is a synthetic, quaternary ammonium compound, chemically described as 1-azoniabicyclo[2.2.2]octane, 3-[(hydroxydi-2-thienylacetyl)oxy]-1-(3-phenoxypropyl)-, bromide, (3 R )-.
The structural formula is: Aclidinium bromide is a white powder with a molecular formula of C 26 H 30 NO 4 S 2 Br and a molecular mass of 564.56. It is very slightly soluble in water and ethanol and sparingly soluble in methanol. Formoterol fumarate, a racemate, is a selective beta 2 -adrenergic agonist.
Its chemical name is (±)-2-hydroxy-5-[(1RS)-1-hydroxy-2-[[(1RS)-2-(4-methoxyphenyl)-1methylethyl]-amino]ethyl]formanilide fumarate dihydrate. The structural formula is: Formoterol fumarate (as a dihydrate) has a molecular weight of 840.91, and its molecular formula is (C 19 H 24 N 2 O 4 ) 2 • C 4 H 4 O 4 •2H 2 O. Formoterol fumarate is a white to yellowish crystalline powder, which is freely soluble in glacial acetic acid, soluble in methanol, sparingly soluble in ethanol and isopropanol, slightly soluble in water, and practically insoluble in acetone, ethyl acetate, and diethyl ether.
DUAKLIR PRESSAIR is a breath-actuated multi-dose dry powder inhaler. Each actuation of DUAKLIR PRESSAIR provides a metered dose of 12 mg of the formulation which contains lactose monohydrate (which may contain milk proteins) as the carrier, 400 mcg of aclidinium bromide (equivalent to 343 mcg of aclidinium), and 12.0 mcg of formoterol fumarate (as a dihydrate, equivalent to 11.5 mcg of formoterol fumarate anhydrous and 9.8 mcg of formoterol). This results in delivery of 396 mcg of aclidinium bromide (equivalent to 340 mcg of aclidinium) and 11.8 mcg of formoterol fumarate (as a dihydrate, equivalent to 11.3 mcg of formoterol fumarate anhydrous and 9.7 mcg of formoterol) from the mouthpiece, based on in vitro testing at an average flow rate of approximately 63 L/min with constant volume of 2 L.
The amount of drug delivered to the lungs will vary depending on patient factors such as inspiratory flow rate and inspiratory time. aclidinium_bromide_structural_formula formoterol_fumarate_structural_formula
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION See FDA-approved Patient Labeling (Patient Information and Instructions for Use) • Serious Asthma-Related Events Inform patients that LABAs, such as formoterol fumarate, one of the active ingredients in DUAKLIR PRESSAIR, when used alone (without an inhaled corticosteroid), increase the risk of serious asthma-related events, including asthma-related death. DUAKLIR PRESSAIR is not indicated for the treatment of asthma. • Not for Acute Symptoms DUAKLIR PRESSAIR is not meant to relieve acute symptoms of COPD and extra doses should not be used for that purpose.
Instruct patients to seek medical attention immediately if they experience a worsening of symptoms or a need for more inhalations of their rescue inhaler than usual. Instruct patients not to stop therapy with DUAKLIR PRESSAIR without physician/provider guidance since symptoms may recur after discontinuation. • Do Not Use Additional Long-Acting Beta 2 -Agonists Instruct patients to not use other medicines containing a LABA. Patients should not use more than the recommended dose of DUAKLIR PRESSAIR.
Instruct patients who have been taking inhaled, short-acting beta-agonists on a regular basis to discontinue the regular use of these products and use them only for the symptomatic relief of acute symptoms. • Paradoxical Bronchospasm Inform patients that DUAKLIR PRESSAIR can cause paradoxical bronchospasm. Advise patients that if paradoxical bronchospasm occurs, patients should discontinue DUAKLIR PRESSAIR. • Visual Effects Eye pain or discomfort, blurred vision, visual halos, or colored images in association with red eyes from conjunctival congestion and corneal edema may be signs of acute narrow-angle glaucoma.
Inform patients to consult a physician immediately should any of these signs and symptoms develop. Inform patients that care must be taken not to allow the powder to enter into the eyes as this may cause blurring of vision and pupil dilation. • Urinary Retention Difficulty passing urine and dysuria may be symptoms of new or worsening prostatic hyperplasia or bladder outlet obstruction. Patients should be instructed to consult a physician immediately should any of these signs or symptoms develop. • Immediate Hypersensitivity Reactions Inform patients that anaphylaxis, angioedema (including swelling of the lips, tongue, or throat), urticaria, rash, bronchospasm, or itching, may occur after administration of DUAKLIR PRESSAIR.
Advise patient to immediately discontinue treatment and consult a physician should any of these signs or symptoms develop. • Risks Associated with Beta 2 -Agonist Therapy Inform patients of adverse effects associated with beta 2 -agonists, such as palpitations, chest pain, rapid heart rate, tremor, or nervousness. • Instructions for Administering DUAKLIR PRESSAIR It is important for patients to understand how to correctly use DUAKLIR PRESSAIR. Instruct patients not to use more than the recommended dose of DUAKLIR PRESSAIR or with other medicines containing LABAs as excessive use may lead to significant cardiovascular effects including fatalities.
Inform patients that if they miss a dose, they should take their next dose at the usual time; they should not take 2 doses at one time. Instruct patients to thoroughly read complete Instructions for Use before using DUAKLIR PRESSAIR. Manufactured for: Covis Pharma Zug, 6300 Switzerland Under license of ALMIRALL, S.A.
DUAKLIR ® and the logo are registered trademarks of Almirall, S.A., used under license by Covis Pharma. PRESSAIR ® is a registered trademark of the AstraZeneca group of companies, used under license by Covis Pharma. Patient Information DUAKLIR ™ PRESSAIR® (DU-aakl-ir PRESS-air) (aclidinium bromide and formoterol fumarate) inhalation powder, for oral Inhalation use Important: Do not get DUAKLIR PRESSAIR in your eyes.
What is DUAKLIR PRESSAIR? DUAKLIR PRESSAIR combines an anticholinergic, aclidinium bromide, and a long-acting beta 2 -adrenergic agonist (LABA medicine)…
💬 Patient Medication Information ▾
Patient Information DUAKLIR ™ PRESSAIR® (DU-aakl-ir PRESS-air) (aclidinium bromide and formoterol fumarate) inhalation powder, for oral Inhalation use Important: Do not get DUAKLIR PRESSAIR in your eyes. What is DUAKLIR PRESSAIR? DUAKLIR PRESSAIR combines an anticholinergic, aclidinium bromide, and a long-acting beta 2 -adrenergic agonist (LABA medicine) formoterol fumarate. • Anticholinergic and LABA medicines help the muscles around the airways in your lungs stay relaxed to prevent symptoms such as wheezing, cough, chest tightness, and shortness of breath.
These symptoms can happen when the muscles around the airways tighten. This makes it hard to breathe. • DUAKLIR PRESSAIR is a prescription medicine that is used to treat COPD. COPD is a chronic lung disease that includes chronic bronchitis, emphysema, or both. • DUAKLIR PRESSAIR is used long term as 1 inhalation 2 times each day to improve symptoms of COPD for better breathing and to reduce the number of flare-ups (the worsening of your COPD symptoms for several days). • DUAKLIR PRESSAIR is not for use to treat sudden symptoms of COPD.
Always have a rescue inhaler (short-acting beta 2 agonist medicine) with you to treat sudden symptoms of COPD. If you do not have a rescue inhaler, contact your healthcare provider to have one prescribed for you. • DUAKLIR PRESSAIR is not for the treatment of asthma. It is not known if DUAKLIR PRESSAIR is safe and effective in people with asthma. • DUAKLIR PRESSAIR should not be used in children.
It is not known if DUAKLIR PRESSAIR is safe and effective in children. Do not use DUAKLIR PRESSAIR if you: • have asthma and you use DUAKLIR PRESSAIR without also using a medicine called an inhaled corticosteroid. • have a severe allergy to milk proteins. Ask your healthcare provider if you are not sure. • are allergic to aclidinium bromide, formoterol fumarate, or any of the ingredients in DUAKLIR PRESSAIR.
See “What are the ingredients in DUAKLIR PRESSAIR?” below for a complete list of ingredients. Before you use DUAKLIR PRESSAIR tell your healthcare provider about all of your medical conditions, including if you: • have heart problems • have high blood pressure • have seizures • have thyroid problems • have diabetes • have eye problems especially glaucoma. DUAKLIR PRESSAIR may make your glaucoma worse. • have prostate or bladder problems, or problems passing urine.
DUAKLIR PRESSAIR may make these problems worse. • are pregnant or plan to become pregnant. It is not known if DUAKLIR PRESSAIR can harm your unborn baby. • are breastfeeding or plan to breastfeed. It is not known if the medicines, aclidinium bromide and formoterol fumarate in DUAKLIR PRESSAIR pass into your breast milk and if they can harm your baby.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. DUAKLIR PRESSAIR and certain other medicines may interact with each other. This may cause serious side effects.
Especially tell your healthcare provider if you take: • anticholinergics (including umeclidinium, tiotropium, ipratropium, aclidinium, glycopyrrolate). • other LABA medicines (including formoterol, arformoterol, salmeterol, vilanterol, indacaterol, olodaterol). • atropine Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use DUAKLIR PRESSAIR?
Read the step-by-step instructions for using DUAKLIR PRESSAIR at the end of this Patient Information. • Do not use DUAKLIR PRESSAIR unless your healthcare provider has taught you how to use the inhaler and you understand how to use it correctly. • Use DUAKLIR PRESSAIR exactly as prescribed. Do not use DUAKLIR PRESSAIR more often than prescribed. • Use 1 inhalation 2 times each day. Use DUAKLIR PRESSAIR 1 time in the morning and 1 time in the evening. • If you miss a dose of DUAKLIR PRESSAIR skip the missed dose.
Take your next dose at your usual time. Do…