Ipratropium Bromide and Albuterol Sulfate

INDICATIONS AND USAGE Ipratropium bromide and albuterol sulfate inhalation solution is indicated for the treatment of bronchospasm associated with COPD in patients requiring more than one bronchodilator.

DOSAGE AND ADMINISTRATION The recommended dose of ipratropium bromide and albuterol sulfate inhalation solution 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 ipratropium bromide and albuterol sulfate inhalation solution 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 ipratropium bromide and albuterol sulfate inhalation solution have not been studied. The use of ipratropium bromide and albuterol sulfate inhalation solution 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 TM nebulizer (with face mask or mouthpiece) connected to a PRONEB TM compressor was used to deliver ipratropium bromide and albuterol sulfate inhalation solution to each patient in one U.S. clinical study. The safety and efficacy of ipratropium bromide and albuterol sulfate inhalation solution delivered by other nebulizers and compressors have not been established. Ipratropium bromide and albuterol sulfate inhalation solution should be administered via jet nebulizer connected to an air compressor with an adequate air flow, equipped with a mouthpiece or suitable face mask.

CONTRAINDICATIONS Ipratropium bromide and albuterol sulfate inhalation solution is contraindicated in patients with a history of hypersensitivity to any of its components, or to atropine and its derivatives.

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.

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 Albuterol Ipratropium Ipratropium Bromide and Albuterol Sulfate Inhalation Solution COSTART Term NUMBER OF PATIENTS N (%) Patients with AE BODY AS A WHOLE Pain Pain chest DIGESTIVE Diarrhea Dyspepsia Nausea MUSCULO-SKELETAL Cramps leg RESPIRATORY Bronchitis Lung Disease Pharyngitis Pneumonia UROGENITAL Infection urinary tract n (%) 761 327 (43) 8 (1.1) 11 (1.4) 5 (0.7) 7 (0.9) 7 (0.9) 8 (1.1) 11 (1.4) 36 (4.7) 27 (3.5) 7 (0.9) 3 (0.4) n (%) 754 329 (43.6) 4 (0.5) 14 (1.9) 9 (1.2) 8 (1.1) 6 (0.8) 6 (0.8) 13 (1.7) 34 (4.5) 27 (3.6) 8 (1.1) 9 (1.2) n (%) 765 367 (48) 10 (1.3) 20 (2.6) 14 (1.8) 10 (1.3) 11 (1.4) 11 (1.4) 13 (1.7) 49 (6.4) 34 (4.4) 10 (1.3) 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.