Results The combination produced a significantly greater peak and mean improvement in forced expiratory volume in 1 second over albuterol base alone on both test days. Similar changes were seen with forced vital capacity.
Evaluations of clinical status were better for patients receiving combination therapy, and some improvements were statistically significant. The overall incidence of adverse effects was similar in the 2 treatment groups.
Conclusion We conclude that a combination of ipratropium bromide and albuterol sulfate is more effective at improving pulmonary function than albuterol base alone, with no potentiation of adverse effects.
The 2 medications appear to have different modes and sites of action in the lung. Ipratropium is an anticholinergic compound that blocks bronchoconstriction by competing with acetylcholine for airway binding sites.
The difference in mechanism and possibly in site of action suggests a clinical rationale for combining the 2 agents in the treatment of COPD. Thus, this study was undertaken to compare the effects of combination therapy directly with a marketed albuterol base aerosol. The objective of the study was to compare the safety and efficacy of a combination aerosol containing ipratropium bromide and albuterol sulfate with albuterol base in patients with COPD. Three hundred fifty-seven patients were enrolled at 17 centers in a day randomized, double-blind, parallel-group trial.
Patients were required to be aged 40 years or older and to have a diagnosis of COPD. Since smoking is a primary risk factor for COPD, patients were required to have a smoking history of more than 10 pack-years. They were also required to have been using at least 2 prescribed bronchodilators for control of their COPD symptoms during the 3-month period before the trial.
Patients with a history of asthma, allergic rhinitis, or atopy or a total blood eosinophil count of more than 0. The overall mean age of patients was There were men and women. The mean duration of disease was 9. Overall, the mean FEV 1 compared with Patients were randomized into 2 treatment groups, received the combination aerosol and received albuterol.
They were instructed to take 2 puffs of their medication 4 times daily for 29 days. They were allowed to take up to 2 extra puff doses per day for the control of symptoms.
Patients were requested to record the number of doses taken each day on medication dosing cards. The study protocol therefore resulted in a comparison of equivalent doses of the combination therapy with albuterol.
Concomitant medications were carefully monitored. Inhaled bronchodilators other than the study drugs were not allowed during the treatment period. The use of long-term oral corticosteroids were allowed if the patient was stabilized with a minimal dose for at least 1 month before the study period.
Temporary increases in the steroid dose or additions of steroids required for the treatment of exacerbations were allowed for a maximum of 7 days during the day treatment period. Pulmonary function testing was postponed until at least 48 hours, but not more than 7 days, after the last increase or addition of steroids.
Theophylline was allowed for maintenance therapy if the dosage was stable for 1 month before the study period. Two 5-day increases in the theophylline dose or additions of theophylline were allowed for the treatment of exacerbations.
Pulmonary function testing was postponed until at least 48 hours, but not more than 7 days, after the last increase or addition of theophylline. Before admission to the trial, informed consent was obtained and a complete medical history, a lead electrocardiogram, and a physical examination were performed. Baseline laboratory evaluation included complete blood cell count; serum analyses of total protein, albumin, total bilirubin, aspartate aminotransferase, alkaline phosphatase, lactate dehydrogenase, urea nitrogen, creatinine, uric acid, calcium, inorganic phosphorus, and glucose levels; urinalysis, and total blood eosinophil count.
Patients were then stabilized for 1 week with their concomitant COPD medications; test medications were excluded during this time to establish a baseline. This trial conformed to the informed consent provisions and institutional review board provisions of the Code of Federal Regulations.
Pulmonary function testing was carried out on days 1 and 29 of the treatment period. The patients were instructed not to use their inhaled medication for at least 12 hours before testing. Baseline spirometry was performed. Patients then took 2 puffs of their trial medication. Spirometry measurements were taken 15, 30, and 60 minutes after drug administration and hourly after that for a total of 6 hours.
All pulmonary function tests were conducted in triplicate, and the results from the spirometric maneuver with the greatest sum of FEV 1 and FVC was used for analysis. The primary efficacy variable was FEV 1 , and the primary efficacy end points were peak change from test-day baseline duration of action and area under the curve AUC above test-day baseline.
Biweekly physicians' global evaluations and patients' assessment of symptoms wheezing, coughing, chest tightness, and shortness of breath were used to evaluate effects of the drugs on the patients' underlying COPD. The patients' symptoms were graded from 0 not present to 3 severe. Safety end points were frequency of adverse events, changes from baseline physical examination findings over the 29 days, and changes from baseline in vital signs during the pulmonary function test days.
Adverse events were recorded at each visit by the physician, including date of onset, number of minutes between the time of the last dose of study medication and the onset of the event, end date, intensity of the event, treatment required, outcome of the event, and the investigator's assessment of each event's relationship to the study drug. When patients could not complete 6 hours of testing, the data were handled as follows: if testing was stopped early for reasons unrelated to COPD, the last recorded value on that test day was used for all subsequent missing values, provided at least 4 hours of testing had been completed.
If testing was halted because of lack of response, the lowest value observed for that patient on that test day was used for data following testing interruption. Analysis of covariance with terms for treatment, study site, and treatment-by-site interaction was used to compare the 2 treatment groups. The baseline data were used as the covariate.
Fisher exact test was used to compare adverse events and other frequency information. Baselines for the 2 treatment groups were comparable on each of the test days and were stable over the course of the study.
A total of patients completed the trial and were available for efficacy analysis: in the combined therapy group and in the albuterol group. The overall response to combined therapy was superior to albuterol alone, especially during the first 4 hours of testing Figure 1. The mean peak response for the combined therapy group was significantly greater than for the albuterol group. The median onset time for each group on each test day was by 15 minutes, which was the first test point after drug administration.
Median time to peak was 1 hour for combined therapy and 30 minutes for albuterol on both test days. Median duration of action for the combined therapy group ranged from 3 to 4 hours; for albuterol it was 2 hours. The duration of action for combined therapy was significantly greater than for albuterol on day 1 only.
The overall response to combined therapy was statistically significantly better than the response to albuterol alone on each test day. Symptom scores were mild in severity, indicating the stability of the patients' disease despite the severity of the obstruction seen by spirometry. Although there were only minor changes in either treatment group over time Table 2 , statistically significant differences in favor of combination therapy were noted for wheezing and shortness of breath throughout the study and for tightness of the chest during the first 2 weeks of treatment.
Adverse events were similar between the 2 treatment groups. During active treatment, 45 Lower respiratory tract system disorders were the most commonly reported adverse events. These were reported by 16 patients receiving combined therapy 9. Investigators were asked to rate the probability that adverse events were drug related using the criteria by Karch and Lasagna, 6 ie, "possible," "probable," or "definite.
Fewer patients receiving combined therapy 7 [4. There was no evidence of potentiation of adverse events in the combined therapy group compared with albuterol base alone. The current American Thoracic Society guidelines for the care of individuals with COPD contain recommendations for step-by-step pharmacological therapy.
After you use all doses, the inhaler will lock and will not release any more medication, There is a dose indicator on the side of the inhaler that keeps track of how much medication is left in the cartridge. Check the dose indicator from time to time to see how much medication is left. When the pointer on the dose indicator enters the red area, the cartridge contains enough medication for 7 days and it is time to refill your prescription so that you will not run out of medication.
Be careful not to get albuterol and ipratropium inhalation into your eyes. If you get albuterol and ipratropium in your eyes, you may develop narrow angle glaucoma a serious eye condition that may cause loss of vision.
If you already have narrow angle glaucoma, your condition may worsen. You may experience widened pupils black circles in the center of the eyes , eye pain or redness, blurred vision, and vision changes such as seeing halos around lights, or seeing unusual colors Call your doctor if you get albuterol and ipratropium into your eyes or if you develop these symptoms.
The inhaler that comes with albuterol and ipratropium spray is designed for use only with a cartridge of albuterol and ipratropium. Never use it to inhale any other medication, and do not use any other inhaler to inhale the medication in a cartridge of albuterol and ipratropium. Before you use albuterol and ipratropium inhalation for the first time, read the written instructions that come with the inhaler or nebulizer. Ask your doctor, pharmacist, or respiratory therapist to show you how to use it.
Practice using the inhaler or nebulizer while he or she watches. Clean your inhaler or nebulizer regularly. Follow the manufacturer's directions carefully and ask your doctor or pharmacist if you have any questions about cleaning your inhaler or nebulizer. This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.
Use the missed dose as soon as you remember it. However, if it is almost time for the next dose, skip the missed dose and continue your regular dosing schedule. Do not use a double dose to make up for a missed one. Albuterol and ipratropium may cause other side effects.
Call your doctor if you have any unusual problems while you are using this medication. Keep this medication in the container it came in, tightly closed, and out of reach of children.
Keep unused vials of nebulizer solution in the foil pouch until you are ready to use them. Store the medication at room temperature and away from excess heat and moisture not in the bathroom. Do not allow the inhalation spray to freeze. Unneeded medications should be disposed of in special ways to ensure that pets, children, and other people cannot consume them. However, you should not flush this medication down the toilet. Instead, the best way to dispose of your medication is through a medicine take-back program.
It is important to keep all medication out of sight and reach of children as many containers such as weekly pill minders and those for eye drops, creams, patches, and inhalers are not child-resistant and young children can open them easily.
To protect young children from poisoning, always lock safety caps and immediately place the medication in a safe location — one that is up and away and out of their sight and reach.
In case of overdose, call the poison control helpline at If the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services at Do not let anyone else use your medication. Ask your pharmacist any questions you have about refilling your prescription. It is important for you to keep a written list of all of the prescription and nonprescription over-the-counter medicines you are taking, as well as any products such as vitamins, minerals, or other dietary supplements.
You should bring this list with you each time you visit a doctor or if you are admitted to a hospital. It is also important information to carry with you in case of emergencies.
Generic alternatives may be available. Albuterol and Ipratropium Oral Inhalation pronounced as al byoo' ter ole i pra troe' pee um. Why is this medication prescribed? How should this medicine be used? Other uses for this medicine What special precautions should I follow? What special dietary instructions should I follow?
What should I do if I forget a dose? What side effects can this medication cause? What should I know about storage and disposal of this medication? Brand names. To prepare the inhaler for use, follow these steps: Put the inhaler together before you use it for the first time. To start, take the inhaler out of the box, and keep the orange cap closed.
Press the safety catch and pull off the clear base of the inhaler. Be careful not to touch the piercing element inside of the base The inhaler must be discarded three months after you put it together. Write this date on the label of the inhaler so you will not forget when you need to discard your inhaler.
Take the cartridge out of the box and insert the narrow end into the inhaler. You can press the inhaler against a hard surface to be sure it is inserted correctly.
Replace the clear plastic base on the inhaler. Hold the inhaler upright with the orange cap closed. Turn the clear base in the direction of the white arrows until it clicks. Flip the orange cap so that it is fully open. Point the inhaler toward the ground. Press the dose release button.
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