Albuterol

MEDICATION SAFETY ISSUES
Sound-alike/look-alike issues:
Albuterol may be confused with Albutein®, atenolol
Proventil® may be confused with Bentyl®, Prilosec® Prinivil®
Salbutamol may be confused with salmeterol
Ventolin® may be confused with phentolamine, Benylin®, Vantin®
Volmax® may be confused with Flomax®

SPECIAL ALERTS
Stolen Medication: Albuterol Inhalation Solution Unit-Dose Vials - Updated September 18th, 2009

For information on affected NDC/lot numbers, please refer to:
Notice to pharmacists concerning theft in Texas (September 10th): http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm181772.htm
Dey-issued advisory concerning theft in Florida (September 11th): http://www.fda.gov/NewsEvents/PublicHealthFocus/ucm182091.htm
FDA advisory to consumers (September 17th): http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm182846.htm

U.S. BRAND NAMES — AccuNeb®; ProAir® HFA; Proventil® HFA; Ventolin® HFA; VoSpire ER®

PHARMACOLOGIC CATEGORY
Beta2 Agonist

DOSING: ADULTS
Bronchospasm:
Metered-dose inhaler: 2 puffs every 4-6 hours as needed (NIH Guidelines, 2007):
Solution for nebulization: 2.5 mg every 4-8 hours as needed; Quick relief: 1.25-5 mg every 4 to 8 hours as needed (NIH Guidelines, 2007)
Oral: 2-4 mg/dose 3-4 times/day; maximum dose not to exceed 32 mg/day (divided doses)
Extended release: 8 mg every 12 hours; maximum dose not to exceed 32 mg/day (divided doses). A 4 mg dose every 12 hours may be sufficient in some patients, such as adults of low body weight.
I.V. continuous infusion (Ventolin® I.V. solution [not available in U.S.]): Severe bronchospasm and status asthmaticus: Initial: 5 mcg/minute; may increase up to 10-20 mcg/minute at 15- to 30-minute intervals if needed

Exacerbation of asthma (acute, severe) (NIH Guidelines, 2007):
Metered-dose inhaler: 4-8 puffs every 20 minutes for up to 4 hours, then every 1-4 hours as needed
Solution for nebulization: 2.5-5 mg every 20 minutes for 3 doses, then 2.5-10 mg every 1-4 hours as needed, or 10-15 mg/hour by continuous nebulization

Exercise-induced bronchospasm (prevention):Metered-dose inhaler: 2 puffs 5-30 minutes prior to exercise

DOSING: PEDIATRIC

(For additional information see "Albuterol (salbutamol): Pediatric drug information")
Bronchospasm:
Oral, regular release:
Children 2-6 years: 0.1-0.2 mg/kg/dose 3 times/day (maximum: 12 mg/day)
Children 6-12 years: 2 mg/dose 3-4 times/day (maximum 24 mg/day)
Children >12 years: 2-4 mg/dose 3-4 times/day (maximum: 32 mg/day)
Oral, extended release:
Children 6-12 years: 4 mg every 12 hours (maximum: 24 mg/day)
Children >12 years: 8 mg every 12 hours (maximum 32 mg/day)
Metered-dose inhaler (90 mcg/puff): NIH Guidelines, 2007: Quick relief:
Children ≤ 4 years: 1-2 puffs every 4-6 hours as needed
Children 5-11 years: 2 puffs every 4-6 hours as needed
Children ≥ 12 years: 2 puffs every 4-6 hours as needed
Solution for nebulization:
Manufacturer's recommendations:
Children 2-12 years (AccuNeb®): 0.63-1.25 mg every 4-6 hours as needed
Children ≥ 12 years: 2.5 mg every 4-8 hours as needed
NIH Guidelines, 2007: Quick relief:
Children ≤ 4 years: 0.63-2.5 mg every 4-6 hours as needed
Children ≥ 5 years: 1.25-5 mg every 4-8 hours as needed
I.V. (Ventolin® I.V. solution [not available in U.S.]): Dosage not established for children

Exacerbation of asthma (acute, severe) (NIH Guidelines, 2007):
Metered-dose inhaler (90 mcg/puff):
Children <12 years: 4-8 puffs every 20 minutes for 3 doses, then every 1-4 hours as needed
Children ≥ 12 years: 4-8 puffs every 20 minutes for up to 4 hours, then every 1-4 hours as needed
Solution for nebulization:
Children <12 years: 0.15 mg/kg (minimum: 2.5 mg) every 20 minutes for 3 doses, then 0.15-0.3 mg/kg (maximum: 10 mg) every 1-4 hours as needed, or 0.5 mg/kg/hour by continuous nebulization
Children ≥ 12 years: 2.5-5 mg every 20 minutes for 3 doses, then 2.5-10 mg every 1-4 hours as needed, or 10-15 mg/hour by continuous nebulization

Exercise-induced bronchospasm (prevention):Metered-dose inhaler (90 mcg/puff):
Children ≤ 4 years: 1-2 puffs 5 minutes prior to exercise (NIH Guidelines, 2007)
Children >4 years: 2 puffs 5-30 minutes prior to exercise

DOSING: ELDERLY
Inhalation: Refer to adult dosing.

Bronchospasm (treatment): Oral: 2 mg 3-4 times/day; maximum: 8 mg 4 times/day

DOSING: RENAL IMPAIRMENT — Not removed by hemodialysis

DOSAGE FORMS — Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product; [CAN] = Canadian brand name

Aerosol, for oral inhalation: 90 mcg/metered inhalation (17 g) [200 metered inhalations; contains chlorofluorocarbons] [DSC]

Aerosol, for oral inhalation:
ProAir® HFA: 90 mcg/metered inhalation (8.5 g) [200 metered inhalations; chlorofluorocarbon free]
Proventil® HFA: 90 mcg/metered inhalation (6.7 g) [200 metered inhalations; chlorofluorocarbon free]
Ventolin® HFA: 90 mcg/metered inhalation (8 g) [60 metered inhalation; chlorofluorocarbon free]; (18 g) [200 metered inhalations; chlorofluorocarbon free]

Injection, solution, as sulphate:
Ventolin® I.V. [CAN]: 1 mg/1mL (5 mL) [not available in U.S.]

Solution for nebulization [preservative free]: 0.021% (3 mL); 0.042% (3 mL); 0.083% (3 mL); 0.5% (0.5 mL, 20 mL)
AccuNeb®: 0.021% (3 mL); 0.042% (3 mL)

Syrup, oral: 2 mg/5 mL (480 mL)

Tablet, oral: 2 mg, 4 mg

Tablet, extended release, oral: 4 mg, 8 mg
VoSpire ER®: 4 mg, 8 mg

DOSAGE FORMS: CONCISE — [CAN] = Canadian brand name

Aerosol, for oral inhalation:
ProAir® HFA: 90 mcg/metered inhalation (8.5 g)
Proventil® HFA: 90 mcg/metered inhalation (6.7 g)
Ventolin® HFA: 90 mcg/metered inhalation (8 g, 18 g)

Injection, solution, as sulphate:
Ventolin® I.V. [CAN]: 1 mg/1mL (5 mL) [not available in U.S.]

Solution for nebulization [preservative free]: 0.021% (3 mL); 0.042% (3 mL); 0.083% (3 mL); 0.5% (0.5 mL, 20 mL)
AccuNeb®: 0.021% (3 mL); 0.042% (3 mL)

Syrup, oral: 2 mg/5 mL

Tablet, oral: 2 mg, 4 mg

Tablet, extended release, oral: 4 mg, 8 mg
VoSpire ER®: 4 mg, 8 mg

GENERIC EQUIVALENT AVAILABLE — Yes

ADMINISTRATION
Metered-dose inhaler: Shake well before use; prime prior to first use, and whenever inhaler has not been used for >2 weeks or when it has been dropped, by releasing 3-4 test sprays into the air (away from face). A spacer device or valved holding chamber is recommended for use with metered-dose inhalers.

Solution for nebulization: Concentrated solution should be diluted prior to use. Blow-by administration is not recommended, use a mask device if patient unable to hold mouthpiece in mouth for administration.

Infusion solution (Ventolin® I.V.): Do not inject undiluted. Reduce concentration by at least 50% before infusing. Administer as a continuous infusion via infusion pump. Discard unused portion of infusion within 24 hours of preparation.

Oral: Do not crush or chew extended release tablets.

COMPATIBILITY
Intravenous solution: Stable in water for injection, NS, D5W, and D5NS when mixed in PC bags or glass bottles. Avoid addition of other medications to infusion solution.

Solution for nebulization: Compatible with cromolyn sodium, budesonide inhalation suspension, ipratropium solution for nebulization

USE — Bronchodilator in reversible airway obstruction due to asthma or COPD; prevention of exercise-induced bronchospasm

USE - UNLABELED / INVESTIGATIONAL — As tocolytic agent (injectable form; not available in U.S.)

ADVERSE REACTIONS SIGNIFICANT — Incidence of adverse effects is dependent upon age of patient, dose, and route of administration.

Cardiovascular: Angina, atrial fibrillation, arrhythmias, chest discomfort, chest pain, extrasystoles, flushing, hyper-/hypotension, palpitation, supraventricular tachycardia, tachycardia

Central nervous system: CNS stimulation, dizziness, drowsiness, headache, insomnia, irritability, lightheadedness, migraine, nervousness, nightmares, restlessness, seizure

Dermatologic: Angioedema, rash, urticaria

Endocrine & metabolic: Hyperglycemia, hypokalemia, lactic acidosis

Gastrointestinal: Diarrhea, dry mouth, dyspepsia, gastroenteritis, nausea, unusual taste, vomiting

Genitourinary: Micturition difficulty

Local: Injection: Pain, stinging

Neuromuscular & skeletal: Muscle cramps, musculoskeletal pain, tremor, weakness

Otic: Otitis media, vertigo

Respiratory: Asthma exacerbation, bronchospasm, cough, epistaxis, laryngitis, oropharyngeal drying/irritation, oropharyngeal edema, pharyngitis, rhinitis, upper respiratory inflammation, viral respiratory infection

Miscellaneous: Allergic reaction, anaphylaxis, diaphoresis, lymphadenopathy

Postmarketing and/or case reports: Anxiety, glossitis, hoarseness, myocardial ischemia, pulmonary edema, throat irritation, tongue ulceration

CONTRAINDICATIONS — Hypersensitivity to albuterol, adrenergic amines, or any component of the formulation

Injection formulation (not available in U.S.): Patients with tachyarrhythmias; risk of abortion during first or second trimester

WARNINGS / PRECAUTIONS
Concerns related to adverse effects: Bronchospasm: Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response. Hypersensitivity reactions: Immediate hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm) have been reported.

Disease-related concerns: Asthma: Appropriate use: Optimize anti-inflammatory treatment before initiating maintenance treatment with albuterol. Do not use as a component of chronic therapy without an anti-inflammatory agent. Only the mildest forms of asthma (Step 1 and/or exercise-induced) would not require concurrent use based upon asthma guidelines. Cardiovascular disease: Use with caution in patients with cardiovascular disease (arrhythmia or hypertension or HF); beta-agonists may cause elevation in blood pressure, heart rate and result in CNS stimulation/excitation. Beta2-agonists may also increase risk of arrhythmias. Diabetes: Use with caution in patients with diabetes mellitus; beta2-agonists may increase serum glucose. Glaucoma: Use with caution in patients with glaucoma; may elevate intraocular pressure. Hyperthyroidism: Use with caution in hyperthyroidism; may stimulate thyroid activity. Hypokalemia: Use with caution in patients with hypokalemia; beta2-agonists may decrease serum potassium. Seizures: Use with caution in patients with seizure disorders; beta-agonists may result in CNS stimulation/excitation.

Special populations: Pediatrics: Face masks should be used in children <4 years of age.

Dosage form specific issues: Chlorofluorocarbons: Patient response may vary between inhalers that contain chlorofluorocarbons and those which are chlorofluorocarbon-free.

Other warnings/precautions: Appropriate use: Do not exceed recommended dose; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics. Patient information: Patients must be instructed to seek medical attention in cases where acute symptoms are not relieved or a previous level of response is diminished. The need to increase frequency of use may indicate deterioration of asthma, and treatment must not be delayed. A spacer device or valved holding chamber is recommended when using a metered-dose inhaler.

DRUG INTERACTIONS
Alpha-/Beta-Blockers: May diminish the therapeutic effect of Beta2-Agonists. Risk D: Consider therapy modification

Atomoxetine: May enhance the tachycardic effect of Beta2-Agonists. Risk C: Monitor therapy

Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Risk C: Monitor therapy

Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Risk D: Consider therapy modification

Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Risk C: Monitor therapy

Cannabinoids: May enhance the tachycardic effect of Sympathomimetics. Risk C: Monitor therapy

Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Risk X: Avoid combination

MAO Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy

Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Risk C: Monitor therapy

Tricyclic Antidepressants: May enhance the adverse/toxic effect of Beta2-Agonists. Risk C: Monitor therapy

ETHANOL / NUTRITION / HERB INTERACTIONS
Food: Avoid or limit caffeine (may cause CNS stimulation).

Herb/Nutraceutical: Avoid ephedra, yohimbe (may cause CNS stimulation). Avoid St John's wort (may decrease the levels/effects of albuterol).

PREGNANCY RISK FACTOR — C (show table)

PREGNANCY IMPLICATIONS — Albuterol crosses the placenta; tocolytic effects, fetal tachycardia, fetal hypoglycemia secondary to maternal hyperglycemia with oral or intravenous routes reported. Available evidence suggests safe use as an inhalation during pregnancy, and albuterol is the preferred short-acting beta agonist for use in asthma according to the NHLBI 2007 Guidelines for the Diagnosis and Management of Asthma.

Use of the parenteral formulation (not available in the U.S.) as a tocolytic agent has been associated with myocardial ischemia. Patients with a history of cardiac disease should be referred to a cardiologist for evaluation prior to initiating therapy in premature labor. If therapy is initiated, patients should be carefully monitored for ECG changes as well as for changes in fluid balance and cardiopulmonary function. Maternal pulse rate should not exceed 140 beats per minute during I.V. infusion of salbutamol. Consider discontinuing therapy with the development of signs of pulmonary edema or myocardial ischemia. Cautious use of parenteral salbutamol, as with other beta2-agonists, is also warranted when used during labor and delivery for the relief of bronchospasm.

LACTATION — Excretion in breast milk unknown/use caution

DIETARY CONSIDERATIONS — Oral forms should be administered with water 1 hour before or 2 hours after meals.

PRICING — (data from drugstore.com)
Aerosol solution (ProAir HFA)
108 (90 Base) mcg/ACT (8.5): $41.84

Aerosol solution (Proventil HFA)
108 (90 Base) mcg/ACT (6.7): $52.02

Aerosol solution (Ventolin HFA)
108 (90 Base) mcg/ACT (18): $37.99

Nebulization (AccuNeb)
0.63 mg/3 mL (75): $49.13
1.25 mg/3 mL (75): $50.99

Nebulization (Albuterol Sulfate)
0.63 mg/3 mL (3): $11.99
(2.5 MG/3ML) 0.083% (75): $18.99
(5 MG/ML) 0.5% (20): $15.99

Syrup (Albuterol Sulfate)
2 mg/5 mL (120): $12.99

Tablet, 12-hour (VoSpire ER)
4 mg (30): $56.59
8 mg (60): $204.08

Tablets (Albuterol Sulfate)
2 mg (90): $15.99
4 mg (100): $24.98

MONITORING PARAMETERS — FEV1, peak flow, and/or other pulmonary function tests; blood pressure, heart rate; CNS stimulation; serum glucose, serum potassium; asthma symptoms; arterial or capillary blood gases (if patients condition warrants)

CANADIAN BRAND NAMES — Airomir; Alti-Salbutamol; Apo-Salvent®; Apo-Salvent® CFC Free; Apo-Salvent® Respirator Solution; Apo-Salvent® Sterules; Gen-Salbutamol; PMS-Salbutamol; ratio-Inspra-Sal; ratio-Salbutamol; Rhoxal-salbutamol; Salbu-2; Salbu-4; Ventolin®; Ventolin® Diskus; Ventolin® HFA; Ventolin® I.V. Infusion; Ventrodisk

INTERNATIONAL BRAND NAMES — Aero-Vent (PH); Aerolin (BR, CN, GR); Aeromol (TH); Airmax (CO); Airomir (AU, FR, HK, LU, PL, SE, TH, UY); Antomol (TH); Asmacaire (PH); Asmadil (BF, BJ, CI, ET, GH, GM, GN, KE, LR, MA, ML, MR, MU, MW, NE, NG, SC, SD, SL, SN, TN, TZ, UG, ZA, ZM, ZW); Asmalin Pulmoneb (PH); Asmatol (AR); Asmidon (JP); Asmol CFC-Free (AU); Asmovent (MY); Assal (MX); Asthalin (IN); Asthalin HFA (HK); Asthavent (ZA); Asvimol (PH); Avedox-FC (MX); Azmacon (ID); Azmasol (SG); Bajapres (CO); Bronchosal (ID); Bronchosol (TH); Broncovaleas (IT); Bronter (CO); Brusal (MX); Brytolin (PH); Butamol (AU); Buto-Asma (ES, SG, TH); Butotal (CN); Buventol (NO, SG, TW); Buventol Easyhaler (FR, TH); Cybutol (ID); Easyhaler Salbutamol (GB, IE); Epaq Inhaler (AU); Farcolin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Hivent DS (PH); Huma-Salmol (HU); Inbumed (MX); Libretin (PH); Medolin (SG); Mozal (TW); Provexel NS (PH); Pulmol-S (PE); Respax (NZ); Salamol (PL); Salbetol (IN); Salbron (ID); Salbulin (LU); Salbumed (PH); Salbutalan (MX); Salbutamol (HU, PL); Salbutamol-GW (HU); Salbutan (VE); Salbutin (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Salbutol (KP, PE); Salbutron SR (KP); Salbuven (ID); Salbuvent (PL); Salda (TH); Salden (EC); Salmaplon (IN); Salmundin Retard (DE); Salomol (TW); Sedalin (PH); Solia (TH); Steri-Neb Salamol (PL); Sultanol (AT, DE, JP); Suprasma (ID); Teoden (BR); Unibron (MX); Venalax (PH); Venetlin (JP); Venteze (ZA); Ventilan (PT); Ventilastin Novolizer (DE, FR); Ventodisk (LU, PL); Ventol (AE, BH, CY, EG, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Ventolin (AE, AR, AU, BB, BE, BF, BG, BH, BJ, BM, BS, BZ, CH, CI, CL, CR, CY, CZ, EC, EE, EG, ET, GH, GM, GN, GT, GY, HK, HN, HR, HU, ID, IE, IL, IQ, IR, IT, JM, JO, KE, KW, LB, LR, LU, LY, MA, ML, MR, MU, MW, MX, MY, NE, NG, NI, NL, OM, PA, PE, PH, PK, PL, PY, QA, SA, SC, SD, SL, SN, SR, SV, SY, TH, TN, TT, TW, TZ, UG, UY, VE, YE, ZA, ZM, ZW); Ventolin CFC-Free (AU); Ventolin [tabs./sol./sir.] (PL); Ventoline (DK, FI, FR, NO, SE); Volmax (AE, BH, CY, EC, EG, HK, HU, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Zenmolin (AE, BH, CY, EG, HK, IL, IQ, IR, JO, KW, LB, LY, OM, QA, SA, SY, YE); Zibil (MX)

MECHANISM OF ACTION — Relaxes bronchial smooth muscle by action on beta2-receptors with little effect on heart rate

PHARMACODYNAMICS / KINETICS
Onset of action: Peak effect:
Nebulization/oral inhalation: 0.5-2 hours
CFC-propelled albuterol: 10 minutes
Ventolin® HFA: 25 minutes
Oral: 2-3 hours

Duration: Nebulization/oral inhalation: 3-4 hours; Oral: 4-6 hours

Metabolism: Hepatic to an inactive sulfate

Half-life elimination: Inhalation: 3.8 hours; Oral: 3.7-5 hours

Excretion: Urine (30% as unchanged drug)

PATIENT INFORMATION — Do not exceed recommended dosage. Rinse mouth with water following each inhalation to help with dry throat and mouth. Follow specific instructions accompanying inhaler; if more than one inhalation is necessary, wait at least 1 full minute between inhalations. May cause nervousness, restlessness, insomnia; if these effects continue after dosage reduction, notify prescriber. Also report palpitations, tachycardia, chest pain, muscle tremors, dizziness, headache, flushing, or if breathing difficulty persists.