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Aclidinium Bromide And Formoterol Fumarate
FDA Drug Information • Also known as: Duaklir Pressair
- Brand Names
- Duaklir Pressair
- Route
- RESPIRATORY (INHALATION)
- Dosage Form
- POWDER, METERED
- Product Type
- HUMAN PRESCRIPTION DRUG
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)...What Is Aclidinium Bromide And Formoterol Fumarate Used For?
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 )Side Effects (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. 6.1 Clinical 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 6.3 Headache 6.3 6.6 7.7 5.1 Back pain 3.8 3.3 3.5 3.4 Other 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...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 ) 7.1 Adrenergic 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) ] . 7.2 Xanthine 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. 7.3 Non-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. 7.4 Monoamine 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. 7.5 Beta-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...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 )Pregnancy and Breastfeeding
8.1 Pregnancy 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...
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.
How Supplied
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.
About This Information
This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.
What are side effects?
Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.
What are drug interactions?
Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.