ADVERSE REACTIONS

Adverse reaction information concerning Ipratropium Bromide and Albuterol Sulfate Inhalation Solution was derived from the 12-week controlled clinical trial.

ADVERSE EVENTS OCCURRING IN ≥ 1% OF ≥ 1 TREATMENT GROUP(S) AND WHERE THE COMBINATION TREATMENT SHOWED THE HIGHEST PERCENTAGE

Body System COSTART Term	Albuterol n (%)	Ipratropium n (%)	Ipratropium and Albuterol n (%)
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)
DIGESTIVE
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)
MUSCULO-SKELETAL
Cramps leg	8 (1.1)	6 (0.8)	11 (1.4)
RESPIRATORY
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)
UROGENITAL
Infection urinary tract	3 (0.4)	9 (1.2)	12 (1.6)

Additional adverse reactions reported in more than 1% of patients treated with Ipratropium Bromide and Albuterol Sulfate Inhalation Solution 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, mydriasis, paradoxical bronchospasm, wheezing, exacerbation of COPD symptoms, drowsiness, aching, flushing, upper respiratory tract infection, palpitations, taste perversion, elevated heart rate, sinusitis, back pain, sore throat and metabolic acidosis. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

WARNINGS

Paradoxical Bronchospasm

In the clinical study of Ipratropium Bromide and Albuterol Sulfate Inhalation Solution, 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, Ipratropium Bromide and Albuterol Sulfate Inhalation Solution should be discontinued immediately and alternative therapy instituted.

Do Not Exceed Recommended Dose

Fatalities have been reported in association with excessive use of inhaled products containing sympathomimetic amines and with the home use of nebulizers.

Cardiovascular Effect

Ipratropium Bromide and Albuterol Sulfate Inhalation Solution, 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 Ipratropium Bromide and Albuterol Sulfate Inhalation Solution 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, Ipratropium Bromide and Albuterol Sulfate Inhalation Solution, like other sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Immediate Hypersensitivity Reactions

Immediate hypersensitivity reactions to albuterol and/or ipratropium bromide may occur after the administration of Ipratropium Bromide and Albuterol Sulfate Inhalation Solution as demonstrated by rare cases of urticaria, angioedema, rash, pruritus, oropharyngeal edema, bronchospasm, and anaphylaxis.