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Ventolin HFA (Albuterol Sulfate HFA Inhalation) - Warnings and Precautions

 
 



WARNINGS AND PRECAUTIONS

•Paradoxical bronchospasm may occur and should be treated immediately with alternative therapy. (5.1)•Need for more doses of VENTOLIN HFA than usual may be a sign of deterioration of asthma and requires reevaluation of treatment. (5.2)•Cardiovascular effects may occur with beta-adrenergic agonists use. Consider discontinuation of VENTOLIN HFA if these effects occur. Use with caution in patients with underlying cardiovascular disorders. (5.4)•Immediate hypersensitivity reactions may occur. Discontinue VENTOLIN HFA if immediate hypersensitivity reactions occur. (5.6)

 

Inhaled albuterol sulfate can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs, VENTOLIN HFA 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.

 

Asthma may deteriorate acutely over a period of hours or chronically over several days or longer. If the patient needs more doses of VENTOLIN HFA 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.

 

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, to the therapeutic regimen.

 

VENTOLIN HFA, like all other beta2-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients such as changes in pulse rate or blood pressure. If such effects occur, VENTOLIN HFA 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 relevance of these findings is unknown. Therefore, VENTOLIN HFA, like all other sympathomimetic amines, should be used with caution in patients with underlying cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

 

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 may occur after administration of albuterol sulfate inhalation aerosol, as demonstrated by cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema. Discontinue VENTOLIN HFA if immediate hypersensitivity reactions occur.

 

VENTOLIN HFA, like other sympathomimetic amines, should be used with caution 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.

 

USE IN SPECIFIC POPULATIONS

Teratogenic Effects: Pregnancy Category C.

There are no adequate and well-controlled studies of VENTOLIN HFA or albuterol sulfate in pregnant women. During worldwide marketing experience, various congenital anomalies, including cleft palate and limb defects, have been 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. Animal reproduction studies in mice and rabbits revealed evidence of teratogenicity. VENTOLIN HFA should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

In a mouse reproduction study, subcutaneously administered albuterol sulfate produced cleft palate formation in 5 of 111 (4.5%) fetuses at exposures approximately equal to the maximum recommended human dose (MRHD) for adults on a mg/m2 basis and in 10 of 108 (9.3%) fetuses at approximately 8 times the MRHD. Similar effects were not observed at approximately one eleventh of the MRHD. Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated subcutaneously with isoproterenol (positive control).

In a rabbit reproduction study, orally administered albuterol sulfate produced cranioschisis in 7 of 19 fetuses (37%) at approximately 680 times the MRHD.

In another rabbit study, an albuterol sulfate/HFA-134a formulation administered by inhalation produced enlargement of the frontal portion of the fetal fontanelles at approximately one third of the MRHD [see Animal Toxicology and/or Pharmacology ].

 

Because of the potential for beta-agonist interference with uterine contractility, use of VENTOLIN HFA for relief of bronchospasm during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.

 

Plasma levels of albuterol sulfate and HFA-134a after inhaled therapeutic doses are very low in humans, but it is not known whether the components of VENTOLIN HFA are excreted in human milk. Because of the potential for tumorigenicity shown for albuterol in animal studies and lack of experience with the use of VENTOLIN HFA by nursing mothers, 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. Caution should be exercised when VENTOLIN HFA is administered to a nursing woman.

 

The safety and effectiveness of VENTOLIN HFA in children 4 years of age and older has been established based upon two 12-week clinical trials in patients 12 years of age and older with asthma and one 2-week clinical trial in patients 4 to 11 years of age with asthma [see Clinical Studies (14.1), Adverse Reactions]. The safety and effectiveness of VENTOLIN HFA in children under 4 years of age has not been established. Three studies have been conducted to evaluate the safety and efficacy of VENTOLIN HFA in patients under 4 years of age and the findings are described below.

Two 4-week randomized, double-blind, placebo-controlled studies were conducted in 163 pediatric patients from birth to 48 months of age with symptoms of bronchospasm associated with obstructive airway disease (presenting symptoms included: wheeze, cough, dyspnea, or chest tightness). VENTOLIN HFA or placebo HFA was delivered with either an AeroChamber Plus® Valved Holding Chamber or an Optichamber® Valved Holding Chamber with mask 3 times daily. In one study, VENTOLIN HFA 90 mcg (N = 26), VENTOLIN HFA 180 mcg (N = 25), and placebo HFA (N = 26) were administered to children between 24 and 48 months of age. In the second study, VENTOLIN HFA 90 mcg (N = 29), VENTOLIN HFA 180 mcg (N = 29), and placebo HFA (N = 28) were administered to children between birth and 24 months of age. Over the 4-week treatment period, there were no treatment differences in asthma symptom scores between the groups receiving VENTOLIN HFA 90 mcg, VENTOLIN HFA 180 mcg, and placebo in either study.

In a third study, VENTOLIN HFA was evaluated in 87 pediatric patients younger than 24 months of age for the treatment of acute wheezing. VENTOLIN HFA was delivered with an AeroChamber Plus Valved Holding Chamber in this study. There were no significant differences in asthma symptom scores and mean change from baseline in an asthma symptom score between VENTOLIN HFA 180 mcg and VENTOLIN HFA 360 mcg.

In vitro dose characterization studies were performed to evaluate the delivery of VENTOLIN HFA via holding chambers with facemasks. The studies were conducted with 2 different holding chambers with facemasks (small and medium size). The in vitro study data when simulated to patients suggest that the dose of VENTOLIN HFA presented for inhalation via a valved holding chamber with facemask will be comparable to the dose delivered in adults without a spacer and facemask per kilogram of body weight (Table 2). However, clinical studies in children under 4 years of age described above suggest that either the optimal dose of VENTOLIN HFA has not been defined in this age-group or VENTOLIN HFA is not effective in this age-group. The safety and effectiveness of VENTOLIN HFA administered with or without a spacer device in children under 4 years of age has not been demonstrated.

Table 2. In Vitro Medication Delivery Through AeroChamber Plus® Valved Holding Chamber With a Facemask

Age

Facemask

Flow Rate (L/min)

Holding Time (seconds)

Mean Medication Delivery Through AeroChamber Plus (mcg/actuation)

Body Weight 50th Percentile (kg)a

Medication Delivered per Actuation (mcg/kg)b

6 to 12 Months

Small

4.9

0

2

5

10

18.2

19.8

13.8

15.4

7.5-9.9

1.8-2.4

2.0-2.6

1.4-1.8

1.6-2.1

2 to 5 Years

Small

8.0

0

2

5

10

17.8

16.0

16.3

18.3

12.3-18.0

1.0-1.4

0.9-1.3

0.9-1.3

1.0-1.5

2 to 5 Years

Medium

8.0

0

2

5

10

21.1

15.3

18.3

18.2

12.3-18.0

1.2-1.7

0.8-1.2

1.0-1.5

1.0-1.5

>5 Years

Medium

12.0

0

2

5

10

26.8

20.9

19.6

20.3

18.0

1.5

1.2

1.1

1.1

aCenters for Disease Control growth charts, developed by the National Center for Health Statistics in collaboration with the National Center for Chronic Disease Prevention and Health Promotion (2000). Ranges correspond to the average of the 50th percentile weight for boys and girls at the ages indicated.

bA single inhalation of VENTOLIN HFA in a 70-kg adult without use of a valved holding chamber and facemask delivers approximately 90 mcg, or 1.3 mcg/kg.

Clinical studies of VENTOLIN HFA did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

 

Page last updated: 2014-10-08

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