FDA label 305f5d1e-afe6-642b-e054-00144ff88e88

WARNINGS AND PRECAUTIONS •Paradoxical bronchospasm may occur and should be treated immediately with alternative therapy. (5.1)•Need for more doses of VENTOLIN HFA than usual may be a sign of deterioration of asthma and requires reevaluation of treatment. (5.2)•Cardiovascular effects may occur with beta-adrenergic agonists use. Consider discontinuation of VENTOLIN HFA if these effects occur. Use with caution in patients with underlying cardiovascular disorders. (5.4)•Immediate hypersensitivity reactions may occur. Discontinue VENTOLIN HFA if immediate hypersensitivity reactions occur. (5.6) Inhaled albuterol sulfate can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, VENTOLIN HFA should be discontinued immediately and alternative therapy instituted. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister. Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient needs more doses of VENTOLIN HFA than usual, this may be a marker of destabilization of asthma and requires reevaluation of the patient and treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids. The use of beta-adrenergic agonist bronchodilators alone may not be adequate to control asthma in many patients. Early consideration should be given to adding anti-inflammatory agents, e.g., corticosteroids, to the therapeutic regimen. VENTOLIN HFA, like all other beta 2 -adrenergic agonists, can produce clinically significant cardiovascular effects in some patients such as changes in pulse rate or blood pressure. If such effects occur, VENTOLIN HFA may need to be discontinued. In addition, beta-agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, prolongation of the QTc interval, and ST segment depression. The clinical relevance of these findings is unknown. Therefore, VENTOLIN HFA, like all other sympathomimetic amines, should be used with caution in patients with underlying cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma. The exact cause of death is unknown, but cardiac arrest following an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected. Immediate hypersensitivity reactions may occur after administration of albuterol sulfate inhalation aerosol, as demonstrated by cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema. Discontinue VENTOLIN HFA if immediate hypersensitivity reactions occur. VENTOLIN HFA, like other sympathomimetic amines, should be used with caution in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus and in patients who are unusually responsive to sympathomimetic amines. Large doses of intravenous albuterol have been reported to aggravate preexisting diabetes mellitus and ketoacidosis. As with other beta-agonists, albuterol may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects. The decrease is usually transient, not requiring supplementation.

ADVERSE REACTIONS Use of VENTOLIN HFA may be associated with the following: •Paradoxical bronchospasm [see Warnings and Precautions (5.1)] •Cardiovascular effects [see Warnings and Precautions (5.4)] •Immediate hypersensitivity reactions [see Warnings and Precautions (5.6)] •Hypokalemia [see Warnings and Precautions (5.8)] The safety data described below reflects exposure to VENTOLIN HFA in 248 patients treated with VENTOLIN HFA in 3 placebo-controlled clinical trials of 2 to 12 weeks’ duration. The data from adults and adolescents is based upon 2 clinical trials in which 202 patients with asthma 12 years of age and older were treated with VENTOLIN HFA 2 inhalations 4 times daily for 12 weeks’ duration. The adult/adolescent population was 92 female, 110 male and 163 white, 19 black, 18 Hispanic, 2 other. The data from pediatric patients are based upon 1 clinical trial in which 46 patients with asthma 4 to 11 years of age were treated with VENTOLIN HFA 2 inhalations 4 times daily for 2 weeks’ duration. The population was 21 female, 25 male and 25 white, 17 black, 3 Hispanic, 1 other. Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adults and Adolescents 12 Years of Age and Older: The two 12-week, randomized, double-blind studies in 610 adolescent and adult patients with asthma that compared VENTOLIN HFA, a CFC 11/12-propelled albuterol inhaler, and an HFA-134a placebo inhaler. Overall, the incidence and nature of the adverse reactions reported for VENTOLIN HFA and a CFC 11/12-propelled albuterol inhaler were comparable. Table 1 lists the incidence of all adverse reactions (whether considered by the investigator to be related or unrelated to drug) from these studies that occurred at a rate of 3% or greater in the group treated with VENTOLIN HFA and more frequently in the group treated with VENTOLIN HFA than in the HFA-134a placebo inhaler group. Table 1. Overall Adverse Reactions With ≥3% Incidence in 2 Large 12-Week Clinical Trials in Adolescents and Adults a Adverse Reaction Percent of Patients VENTOLIN HFA (n = 202) % CFC 11/12-Propelled Albuterol Inhaler (n = 207) % Placebo HFA-134a (n = 201) % Ear, nose, and throat Throat irritation 10 6 7 Upper respiratory inflammation 5 5 2 Lower respiratory Viral respiratory infections 7 4 4 Cough 5 2 2 Musculoskeletal Musculoskeletal pain 5 5 4 a This table includes all adverse reactions (whether considered by the investigator to be drug-related or unrelated to drug) that occurred at an incidence rate of at least 3.0% in the group treated with VENTOLIN HFA and more frequently in the group treated with VENTOLIN HFA than in the HFA-134a placebo inhaler group. Adverse reactions reported by less than 3% of the adolescent and adult patients receiving VENTOLIN HFA and by a greater proportion of patients receiving VENTOLIN HFA than receiving HFA-134a placebo inhaler and that have the potential to be related to VENTOLIN HFA include diarrhea, laryngitis, oropharyngeal edema, cough, lung disorders, tachycardia, and extrasystoles. Palpitation and dizziness have also been observed with VENTOLIN HFA. Pediatric Patients: Results from the 2-week pediatric clinical study in patients with asthma 4 to 11 years of age showed that this pediatric population had an adverse reaction profile similar to that of the adolescent and adult populations. Three studies have been conducted to evaluate the safety and efficacy of VENTOLIN HFA in patients between birth and 4 years of age. The results of these studies did not establish the efficacy of VENTOLIN HFA in this age-group [see Pediatric Use (8.4)] . Since the efficacy of VENTOLIN HFA has not been demonstrated in children between birth and 48 months of age, the safety of VENTOLIN HFA in this age-group cannot be established. However, the safety profile observed in the pediatric population under 4 years of age was comparable to that observed in the older pediatric patients and in adolescents and adults. Where adverse reaction incidence rates were greater in patients under 4 years of age compared with older patients, the higher incidence rates were noted in all treatment arms, including placebo. These adverse reactions included upper respiratory tract infection, nasopharyngitis, pyrexia, and tachycardia. In addition to the adverse reactions listed in section 6.1, the following adverse reactions have been identified during postapproval use of VENTOLIN HFA. 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. Cases of paradoxical bronchospasm, hoarseness, arrhythmias (including atrial fibrillation, supraventricular tachycardia), and hypersensitivity reactions (including urticaria, angioedema, rash) have been reported after the use of VENTOLIN HFA. In addition, albuterol, like other sympathomimetic agents, can cause adverse reactions such as hypokalemia, hypertension, peripheral vasodilatation, angina, tremor, central nervous system stimulation, hyperactivity, sleeplessness, headache, muscle cramps, drying or irritation of the oropharynx, and metabolic acidosis.

<table ID="_Refid_339752d9-8dbb-4e42-85c6-79d8db3ba"> <caption>Table 1. Overall Adverse Reactions With &#x2265;3% Incidence in 2 Large 12-Week Clinical Trials in Adolescents and Adults ^a </caption> <col span="1" width="39%"/> <col span="1" width="26%"/> <col span="1" width="28%"/> <col span="1" width="23%"/> <tbody> <tr> <td> <paragraph>Adverse Reaction</paragraph> </td> <td> <paragraph>Percent of Patients</paragraph> </td> </tr> <tr> <td> <paragraph>VENTOLIN HFA</paragraph> <paragraph>(n = 202)</paragraph> <paragraph>%</paragraph> </td> <td> <paragraph>CFC 11/12-Propelled</paragraph> <paragraph>Albuterol Inhaler</paragraph> <paragraph>(n = 207)</paragraph> <paragraph>%</paragraph> </td> <td> <paragraph>Placebo HFA-134a</paragraph> <paragraph>(n = 201)</paragraph> <paragraph>%</paragraph> </td> </tr> <tr> <td> <paragraph>Ear, nose, and throat</paragraph> </td> <td/> <td/> <td/> </tr> <tr> <td> <paragraph>Throat irritation</paragraph> </td> <td> <paragraph>10</paragraph> </td> <td> <paragraph>6</paragraph> </td> <td> <paragraph>7</paragraph> </td> </tr> <tr> <td> <paragraph>Upper respiratory inflammation</paragraph> </td> <td> <paragraph>5</paragraph> </td> <td> <paragraph>5</paragraph> </td> <td> <paragraph>2</paragraph> </td> </tr> <tr> <td> <paragraph>Lower respiratory</paragraph> </td> <td/> <td/> <td/> </tr> <tr> <td> <paragraph>Viral respiratory infections</paragraph> </td> <td> <paragraph>7</paragraph> </td> <td> <paragraph>4</paragraph> </td> <td> <paragraph>4</paragraph> </td> </tr> <tr> <td> <paragraph>Cough</paragraph> </td> <td> <paragraph>5</paragraph> </td> <td> <paragraph>2</paragraph> </td> <td> <paragraph>2</paragraph> </td> </tr> <tr> <td> <paragraph>Musculoskeletal</paragraph> </td> <td/> <td/> <td/> </tr> <tr> <td> <paragraph>Musculoskeletal pain</paragraph> </td> <td> <paragraph>5</paragraph> </td> <td> <paragraph>5</paragraph> </td> <td> <paragraph>4</paragraph> </td> </tr> <tr> <td> <paragraph> ^aThis table includes all adverse reactions (whether considered by the investigator to be drug-related or unrelated to drug) that occurred at an incidence rate of at least 3.0% in the group treated with VENTOLIN HFA and more frequently in the group treated with VENTOLIN HFA than in the HFA-134a placebo inhaler group. </paragraph> </td> </tr> </tbody> </table>