CONTRAINDICATIONS
Albuterol formulations are contraindicated in patients with a history of hypersensitivity to
albuterol or any of the formulation components.
WARNINGS
Paradoxical Bronchospasm: Albuterol can produce paradoxical bronchospasm, which
may be life threatening. If paradoxical bronchospasm occurs, albuterol 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 or vial. Solutions: Fatalities have been reported in
association with excessive use of inhaled sympathomimetic drugs and with the home use
of nebulizers. It is therefore essential that the physician instruct the patient in the need for
further evaluation if his/her asthma becomes worse.
Cardiovascular Effects: Albuterol, like all other beta-adrenergic agonists, can produce a
clinically significant cardiovascular effect in some patients as measured by pulse rate,
blood pressure, and/or symptoms. Although such effects are uncommon after
administration of albuterol at recommended doses, if they occur, the drug 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 significance of these findings is
unknown. Therefore, albuterol, like all sympathomimetic amines, should be used with
caution in patients with cardiovascular disorders, especially coronary insufficiency,
cardiac arrhythmias, and hypertension.
Deterioration of Asthma: Asthma may deteriorate acutely over a period of hours or
chronically over several days or longer. If the patient needs more doses of albuterol 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).
Immediate Hypersensitivity Reactions: Immediate hypersensitivity reactions may occur
after administration of albuterol, as demonstrated by rare cases or urticaria, angioedema,
rash, bronchospasm, and oropharyngeal edema and, for inhalation aerosol and capsules
for inhalation, anaphylaxis.
Use of Anti-Inflammatory Agents: 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).
Additional Information for Inhalation Aerosol: The contents of albuterol inhalation
aerosol are under pressure. Do not puncture. Do not use or store near heat or open
flame. Exposure to temperatures above 120°F may cause bursting. Never throw
container into fire or incinerator. Keep out of reach of children.
Additional Information for Inhalation Solution 0.05%: Microbial Contamination: To
avoid microbial contamination, proper aseptic technique should be used each time the
bottle is opened. Precautions should be taken to prevent contact of the dropper tip of the
bottle with any surface, including the nebulizer reservoir and associated ventilatory
equipment. In addition, if the solution changes color or becomes cloudy, it should not be
used.
Additional Information for Inhalation Capsules: Inhalation of capsule particles may
result if damage to the capsule has occurred from handling by the patient.
PRECAUTIONS
General
Albuterol, as with all sympathomimetic amines, should be used with caution in patients
with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and
hypertension; 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. Inhalation Aerosol and Inhalation Solutions: Clinically significant
changes in systolic and diastolic blood pressure have been seen in individual patients and
could be expected to occur in some patients after use of any beta-adrenergic
bronchodilator.
Additional Information for Inhalation Aerosol: Although there have been no reports
concerning the use of albuterol inhalation aerosol during labor and delivery, it has been
reported that high doses of albuterol administered intravenously inhibit uterine
contractions. Although this effect is extremely unlikely as a consequence of aerosol use, it
should be kept in mind.
Additional Information for Inhalation Solution: Repeated dosing with 0.15 mg/kg of
albuterol inhalation solution in children aged 5 to 17 years who were initially
normokalemic has been associated with an asymptomatic decline of 20% to 25% in
serum potassium levels.
Information for the Patient
The action of albuterol may last up to 6 hours or longer. Albuterol should not be used
more frequently than recommended. Do not increase the dose or frequency of albuterol
without consulting your physician. If you find that treatment with albuterol becomes less
effective for symptomatic relief, your symptoms become worse, and/or you need to use
the product more frequently than usual, you should seek medical attention immediately.
While you are using albuterol, other inhaled drugs and asthma medications should be
taken only as directed by your physician. Common adverse effects include palpitations,
chest pain, rapid heart rate, and tremor or nervousness. If you are pregnant or nursing,
contact your physician about use of albuterol. Effective and safe use of albuterol includes
an understanding of the way that it should be administered.
Additional Information for Inhalation Aerosol: In general, the technique for
administering albuterol inhalation aerosol to children is similar to that for adults, since
children's smaller ventilatory exchange capacity automatically provides proportionally
smaller aerosol intake. Children should use albuterol aerosol under adult supervision, as
instructed by the patient's physician. (See PATIENT PACKAGE INSERT.)
Additional Information for Inhalation Solutions: Drug compatibility (physical and
chemical), efficacy, and safety of albuterol inhalation solution when mixed with other
drugs in a nebulizer have not been established. 0.05% Solution Only: To avoid microbial
contamination, proper aseptic techniques should be used each time the bottle is opened.
Precautions should be taken to prevent contact of the dropper tip of the bottle with any
surface, including the nebulizer reservoir and associated ventilatory equipment. In
addition, if the solution changes color or becomes cloudy, it should not be used.
See PATIENT PACKAGE INSERT.
Additional Information for Capsules for Inhalation: Children should use albuterol
capsules for inhalation under adult supervision, as instructed by the patient's physician.
See PATIENT PACKAGE INSERT.
Carcinogenesis, Mutagenesis, and Impairment of Fertility
In a 2–year study in Sprague-Dawley rats, albuterol sulfate caused a significant
dose-related increase in the incidence of benign leiomyomas of the mesovarium at dietary
doses of 2.0, 10, and 50 mg/kg. [Inhalation Solutions: Approximately 2, 8, and 40
times, respectively, the maximum recommended daily inhalation dose for adults on a
mg/m2 basis or approximately 3/5, 3, and 15 times, respectively, the maximum
recommended daily inhalation dose in children on a mg/m2 basis.] [Capsules for
Inhalation: Approximately 7, 35 and 170 times, respectively, the maximum
recommended daily inhalation dose for adults on a mg/m2 basis or approximately 3, 15
and 80 times, respectively, the maximum recommended daily dose in children on a mg/m2
basis.] [Inhalation Aerosol: Approximately 15, 70 and 340 times, respectively, the
maximum recommended daily inhalation dose for adults on a mg/m2 basis or
approximately 6, 30 and 160 times, respectively, the maximum recommended daily
inhalation dose for children on a mg/m2 basis.] In another study this effect was blocked
by the coadministration of propranolol, a non-selective beta-adrenergic antagonist. In an
18–month study in CD-1 mice, albuterol sulfate showed no evidence of tumorgenicity at
dietary doses of up to 500 mg/kg. [Inhalation Solutions: Approximately 200 times the
maximum recommended daily inhalation dose for adults on a mg/m2 basis or
approximately 75 times the maximum recommended daily inhalation dose for children on
a mg/m2 basis.] [Capsules for Inhalation: Approximately 850 times the maximum
recommended daily inhalation dose for adults on a mg/m2 basis or approximately 400
times the maximum recommended daily inhalation dose for children on a mg/m2 basis.]
[Inhalation Aerosol: Approximately 1700 times the maximum recommended daily
inhalation dose for adults on a mg/m2 basis or approximately 800 times the maximum
recommended daily inhalation dose for children on a mg/m2 basis.] In a 22–month study
in the Golden hamster, albuterol sulfate showed no evidence of tumorgenicity at dietary
doses of up to 50 mg/kg [approximately 25 times for adults, 10 times for children
[inhalation solution], 120 times for adults, and 55 times for children [capsules for
inhalation] and 225 times for adults and 110 times for children [inhalation aerosol] the
maximum recommended daily inhalation dose a mg/m2 basis).
Albuterol sulfate was not mutagenic in the Ames test with or without metabolic activation
using tester strains S. typhimurium TA1537, TA1538, and TA98 or E. coli WP2,
WP2uvrA, and WP67. No forward mutation was seen in yeast strain S. cerevisiae S9
nor any mitotic gene conversion in yeast strain S. cerevisiae JD1 with or without
metabolic activation. Fluctuation assays in S. typhimurium TA98 and E. coli WP2, both
with metabolic activation, were negative. Albuterol sulfate was not clastogenic in a human
peripheral lymphocyte assay or in an AH1 strain mouse micronucleus assay at
intraperitoneal doses of up to 200 mg/kg.
Reproduction studies in rats demonstrated no evidence of impaired fertility at oral doses
up to 50 mg/kg approximately 40 times [inhalation solution], 170 times [capsules for
inhalation] and 340 times [inhalation aerosol] the maximum recommended daily inhalation
dose for adults on a mg/m2 basis.
Pregnancy, Teratogenic Effects, Pregnancy Category C
Albuterol has been shown to be teratogenic in mice. A study in CD-1 mice at
subcutaneous doses of 0.025, 0.25, and 2.5 mg/kg (approximately 2/25, 1.0, and 8.0
[inhalation aerosol]; 1/100, 1/10, and 1.0 [inhalation solution]; 1/25, 2/5, and 4 [capsules
for inhalation] times, respectively, the maximum recommended daily inhalation dose for
adults on a mg/m2 basis), showed cleft palate formation in 5 of 111 (4.5%) fetuses at
0.25 mg/kg and in 10 of 108 (9.3%) fetuses at 2.5 mg/kg. The drug did not induce cleft
palate formation at the lowest dose, 0.025 mg/kg. Cleft palate also occurred in 22 of 72
(30.5%) fetuses from females treated with 2.5 mg/kg of isoproterenol (positive control)
subcutaneously (approximately 1.0 time [solution], 4 times [capsules] and 8 times
[inhalation aerosol] the maximum recommended daily inhalation dose for adults on a
mg/m2 basis).
A reproduction study in Stride Dutch rabbits revealed cranioschisis in 7 of 19 (37%)
fetuses when albuterol was administered orally at a 50–mg/kg dose (approximately to 80
[inhalation solution] 340 [capsules for inhalation] 680 [inhalation aerosol] times the
maximum recommended daily inhalation dose for adults on a mg/m2 basis.
There are no adequate and well-controlled studies in pregnant women. Albuterol should
be used during pregnancy only if the potential benefit justifies the potential risk to the
fetus.
During worldwide marketing experience, various congenital anomalies, including cleft
palate and limb defects, have been rarely reported in the offspring of patients being
treated with albuterol. Some of the mothers were taking multiple medications during their
pregnancies. No consistent pattern of defects can be discerned, and a relationship
between albuterol use and congenital anomalies has not been established.
Labor and Delivery
Because of the potential for beta-agonist interference with uterine contractility, use of
albuterol for relief of bronchospasm during labor should be restricted to those patients in
whom the benefits clearly outweigh the risk.
Tocolysis: Albuterol has not been approved for the management of preterm labor. The
benefit:risk ratio when albuterol is administered for tocolysis has not been established.
Serious adverse reactions, including maternal pulmonary edema, have been reported
during or following treatment of premature labor with beta2–agonists, including albuterol.
Nursing Mothers
It is not known whether this drug is excreted in human milk after inhalation of
recommended doses. Because of the potential for tumorigenicity shown for albuterol in
some animal studies, a decision should be made whether to discontinue nursing or to
discontinue the drug, taking into account the importance of the drug to the mother.
Pediatric Use
Inhalation Aerosol and Capsules for Inhalation: Safety and effectiveness in children
below 4 years of age have not been established.
Inhalation Solution: The safety and effectiveness of albuterol inhalation solution have
been established in children 2 years of age and older. Use of albuterol inhalation solution
in these age-groups is supported by evidence from adequate and well-controlled studies
of inhalation solution in adults; the likelihood that the disease course, pathophysiology,
and the drug's effect in pediatric and adult patients are substantially similar; and published
reports of trials in pediatric patients 3 years of age or older. The recommended dose for
the pediatric population is based upon three published dose comparison studies of
efficacy and safety in children 5 to 17 years, and on the safety profile in both adults and
pediatric patients at doses equal to or higher than the recommended doses. The safety
and effectiveness of albuterol inhalation solution in children below 2 years of age have not
been established.