Albuterol Sulfate Inhalation Solution

AccuNeb® (albuterol sulfate) inhalation solution is a sterile, clear, colorless solution of the sulfate salt of racemic albuterol, albuterol sulfate. Albuterol sulfate is a relatively selective beta2-adrenergic bronchodilator (see CLINICAL PHARMACOLOGY). The chemical name for albuterol sulfate is α1 [(tert-butylamino) methyl]-4-hydroxy-mxylene-α, α'-diol sulfate (2:1) (salt), and its established chemical structure is as follows:

The molecular weight of albuterol sulfate is 576.7 and the empirical formula is (C13H21NO3)2•H2SO4. Albuterol sulfate is a white crystalline powder, soluble in water and slightly soluble in ethanol. The World Health Organization recommended name for albuterol is salbutamol.

AccuNeb (albuterol sulfate) Inhalation Solution is supplied in two strengths in unit dose vials. Each unit dose vial contains either 0.75 mg of albuterol sulfate (equivalent to 0.63 mg of albuterol) or 1.50 mg of albuterol sulfate (equivalent to 1.25 mg of albuterol) with sodium chloride and sulfuric acid in a 3-mL isotonic, sterile, aqueous solution. Sodium chloride is added to adjust isotonicity of the solution and sulfuric acid is added to adjust pH of the solution to 3.5 (see HOW SUPPLIED).

AccuNeb (albuterol sulfate) Inhalation Solution does not require dilution prior to administration by nebulization. For AccuNeb (albuterol sulfate inhalation solution) , like all other nebulized treatments, the amount delivered to the lungs will depend on patient factors, the jet nebulizer utilized, and compressor performance. Using the Pari LC Plus™ nebulizer (with face mask or mouthpiece) connected to a Pari PRONEB™ compressor, under in vitro conditions, the mean delivered dose from the mouth piece (% nominal dose) was approximately 43% of albuterol (1.25 mg strength) and 39% of albuterol (0.63 mg strength) at a mean flow rate of 3.6 L/min. The mean nebulization time was 15 minutes or less. AccuNeb (albuterol sulfate inhalation solution) should be administered from a jet nebulizer at an adequate flow rate, via a mouthpiece or face mask (see DOSAGE AND ADMINISTRATION).

AccuNeb (albuterol sulfate) Inhalation Solution is supplied as a 3 mL, clear, colorless, sterile, preservative-free, aqueous solution in two different strengths, 0.63 mg and 1.25 mg, of albuterol (equivalent to 0.75 mg of albuterol sulfate or 1.5 mg of albuterol sulfate per 3 mL) in unit-dose low-density polyethylene (LDPE) vials. Each unit-dose LDPE vial is protected in a foil pouch, and each foil pouch contains 5 unit-dose LDPE vials. Each strength of AccuNeb (albuterol sulfate inhalation solution) (albuterol sulfate) Inhalation Solution is available in a shelf carton containing multiple foil pouches.

AccuNeb® (albuterol sulfate) Inhalation Solution, 0.63 mg (potency expressed as albuterol) contains 0.75 mg albuterol sulfate per 3 mL in unit-dose vials and is available in the following packaging configuration.

NDC 49502-692-03 5 foil pouches, each containing 5 vials, total 25 vials per carton

AccuNeb® (albuterol sulfate) Inhalation Solution, 1.25 mg (potency expressed as albuterol) contains 1.50 mg albuterol sulfate per 3 mL in unit-dose vials and is available in the following packaging configuration.

NDC 49502-693-03 5 foil pouches, each containing 5 vials, total 25 vials per carton

Storage

Store between 2°C and 25°C (36°F - 77°F). Protect from light and excessive heat.

Store unit-dose vials in protective foil pouch at all times. Once removed from the foil pouch, use vial(s) within one week. Discard the vial if the solution is not colorless.

Keep out of the reach of children.

DEY®, Napa, CA 94558.  JAN 07

The expected symptoms with overdosage are those of excessive beta-adrenergic stimulation and/or occurrence or exaggeration of symptoms such as seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats per minute, arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, and exaggeration of the pharmacological effects listed in ADVERSE REACTIONS. Hypokalemia may also occur. As with all sympathomimetic aerosol medications, cardiac arrest and even death may be associated with abuse of AccuNeb (albuterol sulfate inhalation solution) . Treatment consists of discontinuation of AccuNeb (albuterol sulfate inhalation solution) together with appropriate symptomatic therapy. The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. There is insufficient evidence to determine if dialysis is beneficial for overdosage of AccuNeb (albuterol sulfate inhalation solution) .

The oral median lethal dose of albuterol sulfate in mice is greater than 2000 mg/kg (approximately 580 times the maximum recommended daily inhalation dose of AccuNeb (albuterol sulfate inhalation solution) on a mg/m² basis). The subcutaneous median lethal dose of albuterol sulfate in mature rats and small young rats is approximately 450 mg/kg and 2000 mg/kg, respectively (approximately 260 and 1200 times the maximum recommended daily inhalation dose of AccuNeb (albuterol sulfate inhalation solution) on a mg/m² basis). The inhalation median lethal dose has not been determined in animals.

Paradoxical Bronchospasm

Inhaled albuterol sulfate can produce paradoxical bronchospasm that may be life threatening. If paradoxical bronchospasm occurs, PROVENTIL® HFA Inhalation Aerosol 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.

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 PROVENTIL HFA Inhalation Aerosol than usual, this may be a marker of destabilization of asthma and requires re-evaluation of the patient and treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids.

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, to the therapeutic regimen.

Cardiovascular Effects

PROVENTIL HFA Inhalation Aerosol, like other betaadrenergic agonists, can produce clinically significant cardiovascular effects in some patients as measured by pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration of PROVENTIL HFA Inhalation Aerosol at recommended doses, if they occur, the drug may need to be discontinued. In addition, beta-agonists have been reported to produce 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, PROVENTIL HFA Inhalation Aerosol, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

Do Not Exceed Recommended Dose

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

Immediate hypersensitivity reactions may occur after administration of albuterol sulfate, as demonstrated by rare cases of urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.

It is important to keep this medication on hand at all times. Get your prescription refilled before you run out of medicine completely. Keep using all of your other medications as prescribed by your doctor.

Talk with your doctor if any of your asthma medications do not seem to work as well in treating or preventing attacks. If it seems like you need to use more of any of your medications in a 24-hour period, talk with your doctor. An increased need for medication could be an early sign of a serious asthma attack.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222. An overdose of albuterol can be fatal.

Extreme heat can cause the medicine canister to burst. Do not store your inhaler in your car on hot days. Do not throw an empty canister into open flame.

You should not use this medication if you are allergic to albuterol.

To make sure you can safely use albuterol, tell your doctor if you have any of these other conditions:

• heart disease, high blood pressure, or congestive heart failure;
• a heart rhythm disorder;
• a seizure disorder such as epilepsy;
• diabetes; or
• overactive thyroid.

FDA pregnancy category C. It is not known whether albuterol will harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant while using this medication.

It is not known whether albuterol passes into breast milk or if it could harm a nursing baby. You should not breast-feed while you are using albuterol.

An albuterol inhaler should not be given to a child younger than 4 years old. Albuterol solution in a nebulizer should not be given to a child younger than 2 years of age.

Clinical Trial Experience: Adverse events reported in > 1% of patients receiving AccuNeb (albuterol sulfate inhalation solution) and more frequently than in patients receiving placebo in a four-week double-blind study are listed in the following table.

Table 1: Adverse Events with an Incidence of > 1% of Patients Receiving AccuNeb (albuterol sulfate inhalation solution) and Greater than Placebo (expressed as % of treatment group)

There was one case of ST segment depression in the 1.25 mg AccuNeb (albuterol sulfate inhalation solution) treatment group.

No clinically relevant laboratory abnormalities related to AccuNeb (albuterol sulfate inhalation solution) administration were seen in this study.

Postmarketing Experience

Metabolic acidosis has been reported after the use of albuterol sulfate inhalation solution. Because this reaction is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate its frequency or establish a causal relationship to drug exposure..

Read the entire FDA prescribing information for AccuNeb (Albuterol Sulfate Inhalation Solution)