The active components in DuoNeb® Inhalation Solution are albuterol sulfate and ipratropium bromide.
Albuterol sulfate, is a salt of racemic albuterol and a relatively selective β2-adrenergic bronchodilator chemically described as α1-[(tert-butylamino)methyl]-4-hydroxy-m-xylene-α, α'-diol sulfate (2:1) (salt). It has a molecular weight of 576.7 and the empirical formula is (C13H21NO3)2•H2SO4. It is a white crystalline powder, soluble in water and slightly soluble in ethanol. The World Health Organization recommended name for albuterol base is salbutamol.
Ipratropium bromide is an anticholinergic bronchodilator chemically described as 8-azoniabicyclo [3.2.1]-octane, 3-(3-hydroxy-1-oxo-2-phenylpropoxy)-8methyl-8-(1-methylethyl)-, bromide, monohydrate (endo, syn)-, (±)-; a synthetic quaternary ammonium compound, chemically related to atropine. It has a molecular weight of 430.4 and the empirical formula is C20H30BrNO3•H2O. It is a white crystalline substance, freely soluble in water and lower alcohols, and insoluble in lipophilic solvents such as ether, chloroform, and fluorocarbons.
Each 3 mL vial of DuoNeb contains 3.0 mg (0.1%) of albuterol sulfate (equivalent to 2.5 mg (0.083%) of albuterol base) and 0.5 mg (0.017%) of ipratropium bromide in an isotonic, sterile, aqueous solution containing sodium chloride, hydrochloric acid to adjust to pH 4, and edetate disodium, USP (a chelating agent).
DuoNeb is a clear, colorless solution. It does not require dilution prior to administration by nebulization. For DuoNeb Inhalation Solution, like all other nebulized treatments, the amount delivered to the lungs will depend on patient factors, the jet nebulizer utilized, and compressor performance. Using the Pari-LC-Plus™ nebulizer (with face mask or mouthpiece) connected to a PRONEB™ compressor system, under in vitro conditions, the mean delivered dose from the mouth piece (% nominal dose) was approximately 46% of albuterol and 42% of ipratropium bromide at a mean flow rate of 3.6 L/min. The mean nebulization time was 15 minutes or less. DuoNeb should be administered from jet nebulizers at adequate flow rates, via face masks or mouthpieces (see DOSAGE AND ADMINISTRATION).
DuoNeb Inhalation Solution is a combination of the β2-adrenergic bronchodilator, albuterol sulfate, and the anticholinergic bronchodilator, ipratropium bromide.
DuoNeb is indicated for the treatment of bronchospasm associated with COPD in patients requiring more than one bronchodilator.
DuoNeb is contraindicated in patients with a history of hypersensitivity to any of its components, or to atropine and its derivatives.
In the clinical study of DuoNeb, paradoxical bronchospasm was not observed. However, paradoxical bronchospasm has been observed with both inhaled ipratropium bromide and albuterol products and can be life-threatening. If this occurs, DuoNeb should be discontinued immediately and alternative therapy instituted.
Fatalities have been reported in association with excessive use of inhaled products containing sympathomimetic amines and with the home use of nebulizers.
DuoNeb, like other beta adrenergic agonists, can produce a clinically significant cardiovascular effect in some patients as measured by pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon for DuoNeb at recommended doses, if they occur, the drug may need to be discontinued. In addition, beta agonists have been reported to produce ECG changes, such as flattening of the T-wave, prolongation of the QTc interval, and ST segment depression. The clinical significance of these findings is unknown. Therefore, DuoNeb, like other sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
Immediate hypersensitivity reactions to albuterol and/or ipratropium bromide may occur after the administration of DuoNeb as demonstrated by rare cases of urticaria, angioedema, rash, pruritus, oropharyngeal edema, bronchospasm, and anaphylaxis.
The action of DuoNeb should last up to 5 hours. DuoNeb should not be used more frequently than recommended. Patients should be instructed not to increase the dose or frequency of DuoNeb without consulting their healthcare provider. If symptoms worsen, patients should be instructed to seek medical consultation.
Patients must avoid exposing their eyes to this product as temporary papillary dilation, blurred vision, eye pain, or precipitation or worsening of narrow-angle glaucoma may occur, and therefore proper nebulizer technique should be assured, particularly if a mask is used.
If a patient becomes pregnant or begins nursing while on DuoNeb, they should contact their healthcare provider about use of DuoNeb.
See the illustrated Patient's Instruction for Use in the product package insert.
Oral albuterol sulfate has been shown to delay preterm labor in some reports. Because of the potential of albuterol to interfere with uterine contractility, use of DuoNeb during labor should be restricted to those patients in whom the benefits clearly outweigh the risks.
It is not known whether the components of DuoNeb are excreted in human milk. Although lipid-insoluble quaternary bases pass into breast milk, it is unlikely that ipratropium bromide would reach the infant to an important extent, especially when taken as a nebulized solution. Because of the potential for tumorigenicity shown for albuterol sulfate in some animals, a decision should be made whether to discontinue nursing or discontinue DuoNeb, taking into account the importance of the drug to the mother.
The safety and effectiveness of DuoNeb in patients below 18 years of age have not been established.
Of the total number of subjects in clinical studies of DuoNeb, 62 percent were 65 and over, while 19 percent were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and 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.
Adverse reaction information concerning DuoNeb was derived from the 12-week controlled clinical trial.
|NUMBER OF PATIENTS||761||754||765|
|N (%) Patients with AE||327 (43.0)||329 (43.6)||367 (48.0)|
|BODY AS A WHOLE|
|Pain||8 (1.1)||4 (0.5)||10 (1.3)|
|Pain chest||11 (1.4)||14 (1.9)||20 (2.6)|
|Diarrhea||5 (0.7)||9 (1.2)||14 (1.8)|
|Dyspepsia||7 (0.9)||8 (1.1)||10 (1.3)|
|Nausea||7 (0.9)||6 (0.8)||11 (1.4)|
|Cramps leg||8 (1.1)||6 (0.8)||11 (1.4)|
|Bronchitis||11 (1.4)||13 (1.7)||13 (1.7)|
|Lung Disease||36 (4.7)||34 (4.5)||49 (6.4)|
|Pharyngitis||27 (3.5)||27 (3.6)||34 (4.4)|
|Pneumonia||7 (0.9)||8 (1.1)||10 (1.3)|
|Infection urinary tract||3 (0.4)||9 (1.2)||12 (1.6)|
Additional adverse reactions reported in more than 1% of patients treated with DuoNeb included constipation and voice alterations.
In the clinical trial, there was a 0.3% incidence of possible allergic-type reactions, including skin rash, pruritus, and urticaria.
Additional information derived from the published literature on the use of albuterol sulfate and ipratropium bromide singly or in combination includes precipitation or worsening of narrow-angle glaucoma, acute eye pain, blurred vision, paradoxical bronchospasm, wheezing, exacerbation of COPD symptoms, drowsiness, aching, flushing, upper respiratory tract infection, palpitations, taste perversion, elevated heart rate, sinusitis, back pain and sore throat.
The effects of overdosage with DuoNeb are expected to be related primarily to albuterol sulfate, since ipratropium bromide is not well-absorbed systemically after oral or aerosol administration. The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of symptoms such as seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats per minute, arrhythmia, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, and exaggeration of pharmacological effects uled in ADVERSE REACTIONS. Hypokalemia may also occur. As with all sympathomimetic aerosol medications, cardiac arrest and even death may be associated with abuse of DuoNeb. Treatment consists of discontinuation of DuoNeb together with appropriate symptomatic therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of DuoNeb.
The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/kg (approximately 540 times the maximum recommended daily inhalation dose of DuoNeb on a mg/m2 basis). The subcutaneous median lethal dose of albuterol sulfate in mature rats and small young rats is approximately 450 and 2000 mg/kg respectively (approximately 240 and 1100 times the maximum recommended daily inhalation dose of DuoNeb on a mg/m2 basis, respectively). The inhalation median lethal dose has not been determined in animals. The oral median lethal dose of ipratropium bromide in mice, rats and dogs is greater than 1000 mg/kg, approximately 1700 mg/kg and approximately 400 mg/kg, respectively (approximately 1400, 4600, and 3600 times the maximum recommended daily inhalation dose in adults on a mg/m2 basis, respectively).
The recommended dose of DuoNeb is one 3 mL vial administered 4 times per day via nebulization with up to 2 additional 3 mL doses allowed per day, if needed. Safety and efficacy of additional doses or increased frequency of administration of DuoNeb beyond these guidelines has not been studied and the safety and efficacy of extra doses of albuterol sulfate or ipratropium bromide in addition to the recommended doses of DuoNeb have not been studied.
The use of DuoNeb can be continued as medically indicated to control recurring bouts of bronchospasm. If a previously effective regimen fails to provide the usual relief, medical advice should be sought immediately, as this is often a sign of worsening COPD, which would require reassessment of therapy.
A Pari-LC-Plus™ nebulizer (with face mask or mouthpiece) connected to a PRONEB™ compressor was used to deliver DuoNeb to each patient in one U.S. clinical study. The safety and efficacy of DuoNeb delivered by other nebulizers and compressors have not been established.
DuoNeb should be administered via jet nebulizer connected to an air compressor with an adequate air flow, equipped with a mouthpiece or suitable face mask.
DuoNeb is supplied as a 3-mL sterile solution for nebulization in sterile low-density polyethylene unit-dose vials. Store in pouch until time of use. Supplied in cartons as uled below.
NDC 49502-672-30 30 vials per carton/5 vials per foil pouch
NDC 49502-672-60 60 vials per carton/5 vials per foil pouch
NDC 49502-672-31 30 vials per carton/1 vial per foil pouch
Store between 2°C and 30°C (36°F and 86°F). Protect from light.
DuoNeb is a registered trademark of Dey, L.P.
Patient's Instructions for Use
Read this patient information completely every time your prescription is filled as information may have changed. Keep these instructions with your medication as you may want to read them again.
DuoNeb should only be used under the direction of a physician.Your physician and pharmacist have more information about DuoNeb and the condition for which it has been prescribed. Contact them if you have additional questions.
Storing your Medicine
Store DuoNeb between 2°C and 30°C (36°F and 86°F). Vials should be protected from light before use, therefore, keep unused vials in the foil pouch or carton. Do not use after the expiration (EXP) date printed on the carton.
DuoNeb is supplied as a single-dose, ready-to-use vial containing 3 mL of solution. No mixing or dilution is needed. Use one new vial for each nebulizer treatment.
FOLLOW THESE DIRECTIONS FOR USE OF YOUR NEBULIZER/COMPRESSOR OR THE DIRECTIONS GIVEN BY YOUR HEALTHCARE PROVIDER. A TYPICAL EXAMPLE IS SHOWN BELOW.
Instructions for Use