early consideration should be given to adding anti-inflammatory agents, e.g., corticosteroids, to the therapeutic regimen. cardiovascular effects: albuterol sulfate inhalation aerosol, like other beta-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients as measured by pulse rate, blood pressure, and/or symptoms. although such effects are uncommon after administration of albuterol sulfate inhalation aerosol 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, albuterol sulfate inhalation aerosol, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension. do not exceed recommended dose: 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: immediate hypersensitivity reactions may occur after administration of albuterol sulfate, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.

of the usable inhalations, the background behind the number in the dose indicator display window changes to red at 20 actuations or lower. albuterol sulfate inhalation aerosol should be discarded when the dose indicator display window shows zero. exercise induced bronchospasm prevention the usual dosage for adults and children 4 years of age and older is two inhalations 15 to 30 minutes before exercise. to maintain proper use of this product, it is important that the mouthpiece be washed and dried thoroughly at least once a week. the inhaler may cease to deliver medication if not properly cleaned and dried thoroughly (see precautions, information for patients section). keeping the plastic mouthpiece clean is very important to prevent medication buildup and blockage. the inhaler may cease to deliver medication if not properly cleaned and air dried thoroughly. if the mouthpiece becomes blocked, washing the mouthpiece will remove the blockage. if a previously effective dose regimen fails to provide the usual response, this may be a marker of destabilization of asthma and requires reevaluation of the patient and the treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids.

(n=193) cfc 11/12 propelled albuterol inhaler (n=186) hfa-134a placebo inhaler (n=186) *this table includes all adverse events (whether considered by the investigator drug related or unrelated to drug) which occurred at an incidence rate of at least 3.0% in the albuterol sulfate inhalation aerosol group and more frequently in the albuterol sulfate inhalation aerosol group than in the hfa-134a placebo inhaler group. application site disorders inhalation site sensation 6 9 2 inhalation taste sensation 4 3 3 body as a whole allergic reaction/symptoms 6 4 <1 back pain 4 2 3 fever 6 2 5 central and peripheral nervous system tremor 7 8 2 gastrointestinal system nausea 10 9 5 vomiting 7 2 3 heart rate and rhythm disorder tachycardia 7 2 <1 psychiatric disorders nervousness 7 9 3 respiratory system disorders respiratory disorder (unspecified) 6 4 5 rhinitis 16 22 14 upper resp tract infection 21 20 18 urinary system disorder urinary tract infection 3 4 2 adverse events reported by less than 3% of the patients receiving albuterol sulfate inhalation aerosol, and by a greater proportion of albuterol sulfate inhalation aerosol patients than placebo patients, which have the potential to be related to albuterol sulfate inhalation aerosol include: dysphonia, increased sweating, dry mouth, chest pain, edema, rigors, ataxia, leg cramps, hyperkinesia, eructation, flatulence, tinnitus, diabetes mellitus, anxiety, depression, somnolence, rash. palpitation and dizziness have also been observed with albuterol sulfate inhalation aerosol. adverse events reported in a 4-week pediatric clinical trial comparing albuterol sulfate inhalation aerosol and a cfc 11/12 propelled albuterol inhaler occurred at a low incidence rate and were similar to those seen in the adult trials. in small, cumulative dose studies, tremor, nervousness, and headache appeared to be dose related. rare cases of urticaria, angioedema, rash, bronchospasm, and oropharyngeal edema have been reported after the use of inhaled albuterol. in addition, albuterol, like other sympathomimetic agents, can cause adverse reactions such as hypertension, angina, vertigo, central nervous system stimulation, insomnia, headache, metabolic acidosis, and drying or irritation of the oropharynx. to report suspected adverse reactions, contact sandoz inc. at 1-800-525-8747 or fda at 1-800-fda-1088 or www.fda.gov/medwatch.

sulting in relaxation. albuterol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles. albuterol acts as a functional antagonist to relax the airway irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor challenges. increased cyclic amp concentrations are also associated with the inhibition of release of mediators from mast cells in the airway. albuterol has been shown in most clinical trials to have more effect on the respiratory tract, in the form of bronchial smooth muscle relaxation, than isoproterenol at comparable doses while producing fewer cardiovascular effects. controlled clinical studies and other clinical experience have shown that inhaled albuterol, like other beta-adrenergic agonist drugs, can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes. preclinical intravenous studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations amounting to approximately 5% of the plasma concentrations. in structures outside the blood-brain barrier (pineal and pituitary glands), albuterol concentrations were found to be 100 times those in the whole brain. studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta 2 -agonist and methylxanthines were administered concurrently. the clinical significance of these findings is unknown. propellant hfa-134a is devoid of pharmacological activity except at very high doses in animals (380 to 1300 times the maximum human exposure based on comparisons of auc values), primarily producing ataxia, tremors, dyspnea, or salivation. these are similar to effects produced by the structurally related chlorofluorocarbons (cfcs), which have been used extensively in metered dose inhalers. in animals and humans, propellant hfa-134a was found to be rapidly absorbed and rapidly eliminated, with an elimination half-life of 3 to 27 minutes in animals and 5 to 7 minutes in humans. time to maximum plasma concentration (t max ) and mean residence time are both extremely short, leading to a transient appearance of hfa-134a in the blood with no evidence of accumulation. pharmacokinetics in a single-dose bioavailability study which enrolled six healthy, male volunteers, transient low albuterol levels (close to the lower limit of quantitation) were observed after administration of two puffs from both albuterol sulfate inhalation aerosol and a cfc 11/12 propelled albuterol inhaler. no formal pharmacokinetic analyses were possible for either treatment, but systemic albuterol levels appeared similar. clinical trials in a 12-week, randomized, double-blind, double-dummy, active- and placebo-controlled trial, 565 patients with asthma were evaluated for the bronchodilator efficacy of albuterol sulfate inhalation aerosol (193 patients) in comparison to a cfc 11/12 propelled albuterol inhaler (186 patients) and an hfa-134a placebo inhaler (186 patients). serial fev1 measurements (shown below as percent change from test-day baseline) demonstrated that two inhalations of albuterol sulfate inhalation aerosol produced significantly greater improvement in pulmonary function than placebo and produced outcomes which were clinically comparable to a cfc 11/12 propelled albuterol inhaler. the mean time to onset of a 15% increase in fev1 was 6 minutes and the mean time to peak effect was 50 to 55 minutes. the mean duration of effect as measured by a 15% increase in fev1 was 3 hours. in some patients, duration of effect was as long as 6 hours. in another clinical study in adults, two inhalations of albuterol sulfate inhalation aerosol taken 30 minutes before exercise prevented exercise-induced bronchospasm as demonstrated by the maintenance of fev1 within 80% of baseline values in the majority of patients. in a 4-week, randomized, open-label trial, 63 children, 4 to 11 years of age, with asthma were evaluated for the bronchodilator efficacy of albuterol sulfate inhalation aerosol (33 pediatric patients) in comparison to a cfc 11/12 propelled albuterol inhaler (30 pediatric patients). serial fev1 measurements as percent change from test-day baseline demonstrated that two inhalations of albuterol sulfate inhalation aerosol produced outcomes which were clinically comparable to a cfc 11/12 propelled albuterol inhaler. the mean time to onset of a 12% increase in fev1 for albuterol sulfate inhalation aerosol was 7 minutes and the mean time to peak effect was approximately 50 minutes. the mean duration of effect as measured by a 12% increase in fev1 was 2.3 hours. in some pediatric patients, duration of effect was as long as 6 hours. in another clinical study in pediatric patients, two inhalations of albuterol sulfate inhalation aerosol taken 30 minutes before exercise provided comparable protection against exercise-induced bronchospasm as a cfc 11/12 propelled albuterol inhaler. fev1 graph

r cannot be assured after 200 actuations, and when the dose indicator display window shows zero, even though the canister is not completely empty. the canister should be discarded when the labeled number of actuations have been used. warning: avoid spraying in eyes. contents under pressure. do not puncture or incinerate. exposure to temperatures above 120°f may cause bursting. keep out of reach of children. albuterol sulfate inhalation aerosol does not contain chlorofluorocarbons (cfcs) as the propellant. relabeled by: enovachem pharmaceuticals torrance, ca 90501 the brands listed are the registered trademarks of their respective owners and are not trademarks of sandoz inc. rev. july 2021 46293491

not use the albuterol sulfate inhalation aerosol actuator with a canister of medicine from any other inhaler. do not use the albuterol sulfate inhalation aerosol canister with an actuator from any other inhaler. figure a before you use albuterol sulfate inhalation aerosol for the first time make sure that the pointer on the dose indicator is pointing to the right of the “200” inhalation mark in the dose indicator display window ( see figure a ). each canister of albuterol sulfate inhalation aerosol contains 200 puffs of medicine. this does not include the sprays of medicine used for priming your inhaler. the dose indicator display window will continue to move after every 10 puffs. the number in the dose indicator display window will continue to change after every 20 puffs. the color in the dose indicator display window will change to red, as shown in the shaded area, when there are only 20 puffs of medicine left in your inhaler ( see figure b ). this is when you need to refill your prescription or ask your doctor if you need another prescription for albuterol sulfate inhalation aerosol. figure b priming your albuterol sulfate inhalation aerosol inhaler: before you use albuterol sulfate inhalation aerosol for the first time, you should prime your inhaler. if you do not use your albuterol sulfate inhalation aerosol for more than 2 weeks, you should re-prime it before use. remove the cap from the mouthpiece ( see figure c ). check inside the mouthpiece for objects before use. make sure the canister is fully inserted into the actuator. hold the inhaler in an upright position away from your face and shake the inhaler well . press down fully on the center of the dose indicator to release a spray of medicine. you may hear a soft click from the dose indicator as it counts down during use. repeat the priming step 3 more times to release a total of 4 sprays of medicine. shake the inhaler well before each priming spray. after the 4 priming sprays, the dose indicator should be pointing to 200. there are now 200 puffs of medicine left in the canister. your inhaler is now ready to use. using your albuterol sulfate inhalation aerosol inhaler: step 1: shake the inhaler well before each use. remove the cap from the mouthpiece ( see figure c ). check inside the mouthpiece for objects before use. make sure the canister is fully inserted into the actuator. figure c step 2: breathe out as fully as you comfortably can through your mouth. hold the inhaler in the upright position with the mouthpiece pointing towards you and place the mouthpiece fully into the mouth ( see figure d ). close your lips around the mouthpiece. figure d step 3: while breathing in deeply and slowly, press down on the center of the dose indicator with your index finger until the canister stops moving in the actuator and a puff of medicine has been released ( see figure d ). then stop pressing the dose indicator. step 4: hold your breath as long as you comfortably can, up to 10 seconds. remove the inhaler from your mouth, and then breathe out. step 5: if your doctor has prescribed additional puffs of albuterol sulfate inhalation aerosol , wait 1 minute, then shake the inhaler well. repeat steps 3 through 5 in the section “using your albuterol sulfate inhalation aerosol inhaler”. step 6: replace the cap right away after use. cleaning your albuterol sulfate inhalation aerosol inhaler: it is very important that you keep the mouthpiece clean so that medicine will not build up and block the spray through the mouthpiece. clean the mouthpiece 1 time each week or if your mouthpiece becomes blocked ( see figure f ). step 1: remove the canister from the actuator and take the cap off the mouthpiece. do not clean the metal canister or let it get wet. step 2: wash the mouthpiece through the top and bottom with warm running water for 30 seconds ( see figure e ). figure e step 3: shake off as much water from the mouthpiece as you can. step 4: look in the mouthpiece to make sure any medicine buildup has been completely washed away. if the mouthpiece is blocked with buildup, little to no medicine will come out of the mouthpiece ( see figure f ). if there is any buildup, repeat steps 2 through 4 in the section “cleaning your albuterol sulfate inhalation aerosol inhaler” . figure f step 5: let the mouthpiece air-dry such as overnight ( see figure g ). do not put the canister back into the actuator if it is still wet. figure g step 6: when the mouthpiece is dry, put the canister back in the actuator and put the cap on the mouthpiece. note: if you need to use your albuterol sulfate inhalation aerosol inhaler before it is completely dry, put the canister back in the actuator and shake the inhaler well. press down on the center of the dose indicator 2 times to release a total of 2 sprays into the air, away from your face. take your dose as prescribed then clean and air-dry your inhaler as described in the section “cleaning your albuterol sulfate inhalation aerosol inhaler” . how should i store albuterol sulfate inhalation aerosol? store albuterol sulfate inhalation aerosol at room temperature between 20° to 25°c (68° to 77°f). store with the mouthpiece down. avoid exposing albuterol sulfate inhalation aerosol to extreme heat and cold. do not puncture or burn the canister. keep your albuterol sulfate inhalation aerosol inhaler and all medicines out of the reach of children. relabeled by: enovachem pharmaceuticals torrance, ca 90501 this instructions for use has been approved by the u.s. food and drug administration. rev. july 2021 46293491 fig-a fig-b fig-c fig-d fig-e fig-f fig-g