Albuterol (Ventolin): Drug Whys
Generic Name: Albuterol (multiple manufacturers)
Common Brand Name: Ventolin (GlaxoSmithKline — U.S.)
Popularity: 14th most commonly prescribed drug between 2002 — 2007 (U.S.)
Class: Short acting bronchodilator (selective beta-2 agonist)
Treatment Uses — For prevention and treatment of reversible bronchospasm. Treatment of asthma and prevention of exercise-induced asthma. Also used to prevent bronchospasm from anesthesia during bronchoscopy and to decrease airway resistance during mechanical ventilation. In COPD, albuterol improves airflow, increases exercise capacity and improves quality of life. Used for treatment of chronic cough, to improve cough associated with pertussis and as an adjunct in treating hyperkalemia. Treatment of pediatric respiratory conditions including: Cystic Fibrosis, RDS (Respiratory Distress Syndrome) in preterm infants, and RSV (Respiratory Synytial Virus). Oral and intravenous (not available in United States) albuterol has been used with varying effectiveness for treatment of depression, tremors of Parkinson's Disease, premature labor and congestive heart failure. Albuterol is not useful or effective in bronchiolitis, adenovirus, Muscular Dystrophy, urinary incontinence in the elderly, or for improvement of exercise performance in nonasthmatics.
Revised treatment guidelines for asthma were published in 2007 by the National Heart Lung and Blood Institute (NHBLI). Short acting beta agonists (SABA) such as albuterol are the drug of choice for treating acute asthma symptoms and exacerbations on an as-needed basis. Best practice management of asthma aims to limit use of SABAs to less than two times weekly. In other words, regularly scheduled, daily, or chronic use of inhaled short acting beta agonists is not recommended for long term control of asthma. Based on these guidelines, SABA inhalers should last for months. Use of long-term bronchodilators with inhaled corticosteroids or other medications can achieve this goal if prescribed and used properly.
Dosing and Administration — Albuterol metered dose inhalers (MDI) typically deliver 108 micrograms of albuterol with each actuation. For acute asthma exacerbation in adults, four to eight oral inhalations are recommended every 20 minutes for up to four hours, then every one to four hours as needed. For bronchospasm, use two oral inhalations every four to six hours as needed or one oral inhalation every four hours as needed. For exercised induced asthma, two inhalations are recommended 15 to 30 minutes before exercising.
Pediatric dosing is similar. For acute asthma exacerbations, MDI dosing is four to eight oral inhalations every 20 minutes for three doses, then every one to four hours as needed. Children under 5 years of age are rarely capable of using an MDI. Those between 8 and 10 years of age tend not to be able to properly use an MDI during acute asthma episodes. In these populations, a spacer or mask should be used. Such interface devices are comparable to nebulized albuterol delivery in children as young as 1 year of age during acute asthma exacerbations. For bronchospasm in children aged 4 years and older, two oral inhalations every four to six hours or one inhalation every four hours as needed. There are no additional published recommendations for MDI use in children under 4 years old. In children aged 4 and older with exercise induced asthma, two oral inhalations 15 to 30 minutes before exercising are recommended.
While some prescribing literature cautions against more than 12 puffs daily, numerous studies have demonstrated that standard dosing recommendations are insufficient to achieve bronchodilation in many patients. Maximum effect can require doses of up to 44 puffs per day. Dosing should be targeted to patient response.
Patient technique is critical for proper delivery of albuterol to the lungs. Patients are instructed to breathe out fully through the mouth, close their lips around the mouthpiece and breathe in slowly and deeply while fully depressing the canister. Breath should be held for up to 10 seconds before exhaling. Delivery of albuterol to the lungs is considerably enhanced when MDI's are used with a spacer device, which allows deposition of the aerosolized albuterol into a chamber before the patient inhales. Despite the (often strong) personal preferences of practitioners, it is repeated studies make it virtually inarguable that albuterol delivered by an MDI with spacer is equivalent to nebulized albuterol in alert, cooperative adults and children over 4. Note that MDI's need to be "primed" by spraying the aerosol into the air (away from face and eyes), before first use and when the canister has not been used for more than 14 days. The number of sprays required for priming varies between brands of inhaler.
Regardless of the method patients use to deliver respiratory meds, prehospital providers should incorporate assessment and review of technique as a standard component of care.
Nebulized administration for acute asthma exacerbations in adults is dosed at 2.5 to 5 milligrams every 20 minutes for three doses, then 2.5 to 10 milligrams every one to four hours as needed, or 10 to 15 milligrams per hour by continuous nebulization. Pediatric dosing for acute asthma exacerbations is 0.15 milligrams per kilogram (with a minimum dose of 2.5 milligrams) every 20 minutes for 3 doses then 0.15 to 0.3 milligrams per kilogram up to 10 milligrams per dose every one to four hours as needed, or 0.5 milligrams per kilogram per hour by continuous nebulization.
For ongoing treatment of bronchospasm in adults and children aged 2 and older who weigh at least 15 kilograms, 2.5 milligrams of 0.083 percent nebulized albuterol solution (which equates to 3 ml) can be given by inhalation over 5 to 15 minutes, three to four times daily as needed. When 0.5 percent albuterol solution is nebulized, 0.5 milliliters of the solution (which contains 2.5 milligrams of albuterol) should be diluted with 2.5 milliliters of normal saline to yield a 0.083 percent solution.
Again, while some product literature cautions against more than six nebulizer treatments per day, repeated studies show 2.5 mg nebulized doses given at 20 minute intervals provide the best efficacy (compared to higher doses, and shorter or longer dosing intervals). "Continuous albuterol" nebulizer treatments are quite effective in emergency situations to break severe bronchospasm. In the pediatric population, continuous albuterol for acute asthma has been shown to have no greater incidence of side effects, decrease costs, and shorten hospitalization time.
Higher doses of albuterol are safe and effective as an adjunctive, temporary measure to treat hyperkalemia (high blood potassium levels), as seen in patients with renal failure. Adult doses of up to 20 mg by nebulizer or up to 13 puffs by MDI, and pediatric nebulized doses of 2.5 to 5 mg will drop serum potassium concentrations within two hours, peak at four hours and return to baseline levels within 24 to 36 hours following albuterol discontinuation. As the results are quite variable, it is recommended that albuterol alone not be used to treat hyperkalemia.
Traditionally, MDI’s have used chlorofluorocarbons (CFC) as propellants. To address environmental concerns that CFC's deplete the ozone atmospheric layer, new formulations are being marketed with HFA (hydrofluoroalkan-134a) propellant. Both CFC and HFA albuterol are similarly effective. After December 31 this year, MDIs containing CFCs will no longer be manufactured, delivered, or sold in the United States. The Food and Drug Administration (FDA) claims an adequate supply of environmentally friendly HFA inhalers exists, but some pharmacies are already experiencing product shortages. Switching from CFC to HFA inhalers requires a new prescription. Increased cost will be an issue for many patients; HFA inhalers are considerably more expensive. Cheaper generic equivalents will not hit the market at least until patents expire in 2012. To put albuterol MDI use in perspective, there are roughly 52 million albuterol inhaler prescriptions written in the U.S. annually. Approximately 65 percent have already been switched from CFC to HFA inhalers.
New HFA inhalers look and feel different from CFC inhalers. Patients may wonder if they are as effective. Clinical studies show them to be equally effective at usual doses but, after 12 inhalations with an HFA MDI, higher plasma levels of albuterol are observed. These are accompanied by more systemic effects (such as tachycardia). Patients will discover other differences. HFA inhalers taste and feel differently than CFC inhalers. HFA inhalers have a warmer plume temperature, slower spray burst and their fluid is stickier than CFC inhalers. These spray characteristics might affect performance when used with spacer devices but this has yet to be studied. The increased stickiness mandates more frequent washing to prevent clogging. Each manufacturer provides specific cleaning instructions with their MDI. Because the liquid inside an HFA inhaler cannot be felt when the MDI is shaken, telling when it is empty can be challenging — in fact, HFA inhalers don't feel full even when they are. Unlike CFC inhalers, they can't be submerged in water to check for remaining medication and may be damaged if the user does so. Many HFA inhalers include a counter that displays the number of remaining doses available in the canister.
Albuterol also comes in oral, intravenous, sublingual, and dry powder inhaler forms; most of which are not available in the United States.
Dose adjustments are not necessary in geriatric patients treated with albuterol. Caution is well warranted when using albuterol in patients with known or suspected coronary artery disease owing to its obvious cardiac (beta agonist) effects.
The lethal dose of albuterol in mice and young rats is 2,000 milligrams per kilogram which would equate to 6,800 times the maximum recommended daily inhalation dose in adults or 3,200 times the maximum for children. In overdose anticipated symptoms would reflect excessive beta adrenergic stimulation. Judicious use of a cardioselective beta adrenergic blocker may be considered with consideration that it may induce bronchospasm. There is not sufficient evidence to determine whether hemodialysis is effective in albuterol overdose.
Pharmacology/Pharmacokinetics/Stability — Following either MDI or nebulized administration, initial response occurs within five minutes and lasts for four to six hours. Peak response to MDI albuterol occurs from 30 to 120 minutes following administration whereas nebulized albuterol peaks between 60 and 120 minutes.
The kidneys excrete 64 — 98 percent of inhaled albuterol. Between 10.2 to 12 percent is eliminated in feces. Albuterol may be excreted in human breast milk. Inhaled beta-2 agonists delivered by MDI deliver the least amount of drug to maternal systemic circulation and would minimize exposure of the nursing infant. The World Health Organization rates albuterol compatible with breastfeeding. The general consensus on bronchodilator use during pregnancy is that hypoxia secondary to poorly controlled asthma presents far greater risk to the fetus than any potential harm from the bronchodilator drugs. There have been no case reports of fetal harm associated with albuterol use during pregnancy.
Albuterol is a direct-acting agent that relaxes smooth muscle walls of the bronchi, uterus, and skeletal muscle vascular bed. The mechanism of action is a relatively selective effect on beta-2 receptors. Albuterol may reduce chemical mediator release from pulmonary mast cells and improve ability of cilia to clear mucus.
Nebulized albuterol should be stored between 36 and 77 F and MDI's between 59 and 77 F. Inhalers stored at excessive (more than 120 F) temperatures for more than one to two days may explode from the expansion of the propellant in the canister. HFA propelled inhalers should be shaken well before each inhalation. Most MDI albuterol inhalers contain 200 doses.
Cautions and Warnings — Albuterol should not be given to patients hypersensitive to the drug or any of its components (i.e. CFC or HFA propellants). It should be used cautiously in patients with known coronary artery disease, history of arrhythmias, hypertension, hyperthyroidism, seizure disorders, diabetes, glaucoma, or hypokalemia. While tachycardia is frequently a protocol contraindication to albuterol, it may be a relative contraindication. Experienced practitioners often anticipate reduced heart rates owing to improved oxygenation and decreased work of breathing following an albuterol treatment.
Important Side Effects and Interactions — Tachycardia is the most common side effect of albuterol, occurring in up to 10 percent of patients treated with heart rate increases from 10 to 15 beats per minutes following therapeutic doses. Nausea and throat irritation also are reported to occur in up to 10 percent of patients. Dizziness, tremors, headache, and vomiting each have reported incidences of 7 percent. Albuterol lowers peripheral vascular resistance (i.e. vasodilates) which is speculated to cause the occasionally reported tachycardia. This vasodilation leads to rare reports of hypotension. Increased blood pressure probably occurs more often. Albuterol also tends to increase blood glucose levels.
When using a beta agonist in the patients with known or suspected cardiovascular disease, be alert for angina, tachyarrythmias including ventricular ectopy, and ischemia.
There are 42 drugs reported to interact with albuterol, all minor and most rather poorly documented. Two might be of interest to pre-hospital providers: MAO Inhibitors (Monamine Oxidase Inhibitors) and NMBA's (Neuromuscular Blocking Agents). Albuterol has been associated with an increased risk of tachycardia and agitation when given to patients also taking MAO Inhibitors. Effects of NMBA's, particularly vecuronium and pancuronium, have been reported prolonged in the presence of albuterol.
Average Costs — U.S.
• Metered dose inhaler — 17 gram (generic)*
Patient cost: $13.99 each
ALS Service cost: $11.00 each
Large Hospital cost: $2.94 each
*(Wal Mart® and Target don’t include MDIs in their $4/month programs)
• Premixed 2.5 mg/3cc saline for nebulization — 0.083% (generic)
Patient cost: $0.030 each*
ALS Service cost: $0.27 each
Large Hospital cost: $0.15 each
*(Wal Mart® will supply 25 doses as a 1 month supply at $4.00 or 75 doses at $10.00 for 90 day supply. Curiously, Target and Walgreens 1 month supply is 75 doses 90 day supply is 225 doses, at $4.00 and $10.00 for Target and $1.00 per week at Walgreens)
- MICROMEDEX® Healthcare Series: Thomson Micromedex, Greenwood Village, Colorado (accessed November, 2008).
- Albany Medical Center Pharmacy, Albany, New York.