Accuneb

In deciding to use a medicine, the risks of taking the medicine must be weighed against the good it will do. This is a decision you and your doctor will make. For this medicine, the following should be considered:

Allergies

Tell your doctor if you have ever had any unusual or allergic reaction to this medicine or any other medicines. Also tell your health care professional if you have any other types of allergies, such as to foods, dyes, preservatives, or animals. For non-prescription products, read the label or package ingredients carefully.

Pediatric

Appropriate studies performed to date have not demonstrated pediatric-specific problems that would limit the usefulness of albuterol inhalation aerosol (eg, Proair® HFA) in children 4 years of age and older, albuterol inhalation powder (eg, Proair® Respiclick®) in children 4 years of age and older, and albuterol inhalation solution (eg, Accuneb®) in children 2 years of age and older. However, safety and efficacy have not been established for the albuterol inhalation aerosol and albuterol inhalation powder in children younger than 4 years of age, and albuterol inhalation solution in children younger than 2 years of age.

Geriatric

Appropriate studies performed to date have not demonstrated geriatric-specific problems that would limit the usefulness of albuterol inhalation aerosol (eg, Proair® HFA) and albuterol inhalation powder (eg, Proair® Respiclick®) in geriatric patients. However, elderly patients are more likely to have age-related heart, kidney, or liver problems, which may require caution and an adjustment in the dose for patients receiving albuterol inhalation aerosol and albuterol inhalation powder.

No information is available on the relationship of age to the effects of albuterol inhalation solution (eg, Accuneb®) in geriatric patients.

Pregnancy

Breast Feeding

There are no adequate studies in women for determining infant risk when using this medication during breastfeeding. Weigh the potential benefits against the potential risks before taking this medication while breastfeeding.

Interactions with Medicines

Although certain medicines should not be used together at all, in other cases two different medicines may be used together even if an interaction might occur. In these cases, your doctor may want to change the dose, or other precautions may be necessary. When you are taking this medicine, it is especially important that your healthcare professional know if you are taking any of the medicines listed below. The following interactions have been selected on the basis of their potential significance and are not necessarily all-inclusive.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Amineptine
• Amitriptyline
• Amitriptylinoxide
• Amoxapine
• Atomoxetine
• Clomipramine
• Desipramine
• Dibenzepin
• Doxepin
• Imipramine
• Iobenguane I 123
• Levalbuterol
• Lofepramine
• Melitracen
• Nortriptyline
• Opipramol
• Protriptyline
• Tianeptine
• Trimipramine

Using this medicine with any of the following medicines may cause an increased risk of certain side effects, but using both drugs may be the best treatment for you. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Digoxin

Interactions with Food/Tobacco/Alcohol

Certain medicines should not be used at or around the time of eating food or eating certain types of food since interactions may occur. Using alcohol or tobacco with certain medicines may also cause interactions to occur. Discuss with your healthcare professional the use of your medicine with food, alcohol, or tobacco.

Other Medical Problems

The presence of other medical problems may affect the use of this medicine. Make sure you tell your doctor if you have any other medical problems, especially:

• Allergy to milk proteins, history or—Proair® Respiclick® should not be used in patients with this condition.

• Diabetes or
• Heart or blood vessel disease or
• Heart rhythm problems (eg, arrhythmia) or
• Hypertension (high blood pressure) or
• Hyperthyroidism (overactive thyroid) or
• Hypokalemia (low potassium in the blood) or
• Seizures, history of—Use with caution. May make these conditions worse.

• Kidney disease—Use with caution. The effects may be increased because of slower removal of the medicine from the body.

Accuneb is indicated for the relief of bronchospasm in patients 2 to 12 years of age with asthma (reversible obstructive airway disease).

General

Large doses of intravenous albuterol have been reported to aggravate pre-existing diabetes mellitus and ketoacidosis. As with other beta-agonists, inhaled and intravenous albuterol may produce a 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 potassium supplementation.

Information for Patients

The action of Accuneb may last up to six hours, and therefore it should not be used more frequently than recommended. Do not increase the dose or frequency of medication without consulting your physician. If you find that treatment with Accuneb 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. All asthma medication should only be used under the supervision and direction of a physician. Common effects with medications such as Accuneb include palpitations, chest pain, rapid heart rate, tremor, or nervousness.

If you are pregnant or nursing, contact your physician about the use of Accuneb. Effective and safe use of Accuneb includes an understanding of the way it should be administered.

If the solution in the vial changes color or becomes cloudy, you should not use it.

The drug compatibility (physical and chemical), clinical efficacy, and safety of Accuneb solution, when mixed with other drugs in a nebulizer, has not been established.

See illustrated Patient's Instructions for Use.

Drug Interactions

Other short-acting sympathomimetic aerosol bronchodilators or epinephrine should not be used concomitantly with Accuneb.

Accuneb should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants or within 2 weeks of discontinuation of such agents, since the action of albuterol on the vascular system may be potentiated.

Beta-receptor blocking agents not only block the pulmonary effect of beta-agonists, such as Accuneb, but may produce severe bronchospasm in asthmatic patients. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances (e.g., prophylaxis after myocardial infarction), there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma. In this setting, cardioselective beta-blockers should be considered, although they should be administered with caution.

The ECG changes and/or hypokalemia that may result from the administration of non-potassium sparing diuretics (such as loop or thiazide diuretics) can be acutely worsened by beta-agonists, especially when the dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, caution is advised in the co-administration of beta-agonists with non-potassium sparing diuretics.

Mean decreases of 16% to 22% in serum digoxin levels were demonstrated after single dose intravenous and oral administration of albuterol, respectively, to normal volunteers who had received digoxin for 10 days. The clinical significance of these findings for patients with obstructive airway disease who are receiving albuterol and digoxin on a chronic basis is unclear. Nevertheless, it would be prudent to carefully evaluate the serum digoxin levels in patients who are currently receiving digoxin and albuterol.

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 and above dietary doses of 2 mg/kg (approximately equivalent to the maximum recommended daily inhalation dose for Accuneb on a mg/m2 basis). In another study, this effect was blocked by the co-administration of propranolol, a non-selective beta-adrenergic antagonist.

In an 18-month study in CD-1 mice, albuterol sulfate showed no evidence of tumorigenicity at dietary doses up to 500 mg/kg (approximately 140 times the maximum recommended daily inhalation dose of Accuneb on a mg/m2 basis). In a 22-month study in Golden hamsters, albuterol sulfate showed no evidence of tumorigenicity at dietary doses up to 50 mg/kg (approximately 20 times the maximum recommended daily inhalation dose of Accuneb on a mg/m2 basis).

Albuterol sulfate was not mutagenic in the Ames test or a mutation test in yeast. Albuterol sulfate was not clastogenic in a human peripheral lymphocyte assay or in an AH1 strain mouse micronucleus assay.

Reproduction studies in rats demonstrated no evidence of impaired fertility at oral doses of albuterol sulfate up to 50 mg/kg (approximately 30 times the maximum recommended daily inhalation dose of Accuneb on a mg/m2 basis).

Pregnancy

Pregnancy Category C

Albuterol has been shown to be teratogenic in mice. A study in CD-1 mice given albuterol subcutaneously showed cleft palate formation in 5 of 111 (4.5%) fetuses at 0.25 mg/kg (less than the maximum recommended daily inhalation dose of Accuneb on a mg/m2 basis) and cleft palate formation in 10 of 108 (9.3%) fetuses at 2.5 mg/kg (approximately equal to the maximum recommended daily inhalation dose of Accuneb on a mg/m2 basis). The drug did not induce cleft palate formation when administered subcutaneously at a dose of 0.025 mg/kg (less than the maximum recommended daily inhalation dose of Accuneb on a mg/m2 basis). Cleft palate formation also occurred in 23 of 72 (30.5%) fetuses from females treated subcutaneously with 2.5 mg/kg isoproterenol (positive control). A reproduction study in Stride rabbits revealed cranioschisis in 7 of 19 (37%) fetuses when albuterol sulfate was administered orally at 50 mg/kg (approximately 60 times the maximum recommended daily inhalation dose of Accuneb on a mg/m2 basis).

A study in which pregnant rats were dosed with radiolabelled albuterol sulfate demonstrated that drug-related material was transferred from the maternal circulation to the fetus.

There are no adequate and well-controlled studies of the use of albuterol sulfate 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 reported in the offspring of patients being treated with albuterol. Some of the mothers were taking multiple medications during their pregnancies. Because no consistent pattern of defects can be discerned, a relationship between albuterol use and congenital anomalies has not been established.

Labor and Delivery

Oral albuterol has been shown to delay pre-term labor in some reports. There are presently no well-controlled studies that demonstrate that it will stop pre-term labor or prevent labor at term. Because of the potential for beta agonist interference with uterine contractility, use of Accuneb for relief of bronchospasm during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.

Albuterol has not been approved for the management of pre-term labor. The benefit:risk ratio when albuterol is administered for tocolysis has not been established. Serious adverse reactions, including pulmonary edema, have been reported following administration of albuterol to women in labor.

Nursing Mothers

It is not known whether this drug is excreted in human milk. 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

Safety and effectiveness of Accuneb 1.25 mg and 0.63 mg have been established in pediatric patients between the ages of 2 and 12 years. The use of Accuneb in these age groups is supported by evidence from adequate and well-controlled studies of Accuneb in children age 6 to 12 years and published reports of albuterol sulfate trials in pediatric patients 3 years of age and older. The safety and effectiveness of Accuneb in children below 2 years of age have not been established.

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. Treatment consists of discontinuation of Accuneb 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.

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 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 on a mg/m2 basis). The inhalation median lethal dose has not been determined in animals.

The usual starting dosage for patients 2 to 12 years of age is 1.25 mg or 0.63 mg of Accuneb administered 3 or 4 times daily, as needed, by nebulization. More frequent administration is not recommended.

To administer 1.25 mg or 0.63 mg of albuterol, use the entire contents of one unit-dose vial (3 mL of 1.25 mg or 0.63 mg inhalation solution) by nebulization. Adjust nebulizer flow rate to deliver Accuneb over 5 to 15 minutes.

The use of Accuneb can be continued as medically indicated to control recurring bouts of bronchospasm. During this time most patients gain optimum benefit from regular use of the inhalation solution.

Patients 6 to 12 years of age with more severe asthma (baseline FEV1 less than 60% predicted), weight >40 kg, or patients 11 to 12 years of age may achieve a better initial response with the 1.25 mg dose.

Accuneb has not been studied in the setting of acute attacks of bronchospasm. A 2.5 mg dose of albuterol provided by a higher concentration product (2.5 mg albuterol per 3 mL) may be more appropriate for treating acute exacerbations, particularly in children 6 years old and above.

If a previously effective dosage regimen fails to provide the usual relief, medical advice should be sought immediately, as this is often a sign of seriously worsening asthma which would require reassessment of therapy.

The drug compatibility (physical and chemical), clinical efficacy and safety of Accuneb solution, when mixed with other drugs in a nebulizer have not been established.

The safety and efficacy of Accuneb have been established in clinical trials when administered using the Pari LC Plus™ nebulizer and Pari PRONEB™ compressor. The safety and efficacy of Accuneb when administered with other nebulizer systems have not been established.

Accuneb should be administered via jet nebulizer connected to an air compressor with adequate air flow, equipped with a mouthpiece or suitable face mask.

Tell your doctor about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements.

Albuterol and other medicines may affect each other and cause side effects. Albuterol may affect the way other medicines work, and other medicines may affect the way albuterol works.

Especially tell your doctor if you take:

• other inhaled medicines or asthma medicines
• beta blocker medicines
• diuretics
• digoxin
• monoamine oxidase inhibitors
• tricyclic antidepressants

This is not a complete list of albuterol drug interactions. Ask your doctor or pharmacist for more information.

Medicines can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of albuterol there are no specific foods that you must exclude from your diet when receiving albuterol.

Tell your doctor if you are breastfeeding or plan to breastfeed. 

It is not known if albuterol crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using albuterol.

Use albuterol exactly as your doctor tells you to use it.

Inhalational:

• Aerosol Spray
  • If your child needs to use albuterol, watch your child closely to make sure your child uses the inhaler correctly. Your doctor will show you how your child should use albuterol.
  • Each dose of albuterol should last up to 4 hours to 6 hours.
  • Do not increase your dose or take extra doses of albuterol without first talking to your doctor.
  • Get medical help right away if albuterol no longer helps your symptoms.
  • Get medical help right away if your symptoms get worse or if you need to use your inhaler more often.
  • While you are using albuterol, do not use other inhaled rescue medicines and asthma medicines unless your doctor tells you to do so.
  • Call your doctor if your asthma symptoms like wheezing and trouble breathing become worse over a few hours or days. Your doctor may need to give you another medicine (for example, corticosteroids) to treat your symptoms.
• Solution for Nebulization
  • The albuterol for nebulization is usually taken 3 or 4 times daily, as needed. More frequent use is not recommended.
  • Use the entire contents of one unit-dose vial. Adjust the flow rate to deliver albuterol over 5 to 15 minutes.
  • To control recurring bouts of bronchospasm, using albuterol for nebulization on a regular basis works best.
  • If the medication does not seem to be working, seek medical advice immediately. This is often a sign of seriously worsening asthma.
  • Efficacy and safety of this medication, when mixed with other drugs in a nebulizer, have not been determined.
  • The safety and efficacy of this medication have been established with the Pari LC Plus nebulizer and Pari PRONEB compressor. The safety and efficacy of albuterol for nebulization with other nebulizer systems have not been determined.
  • Albuterol for nebulization should be used with a jet nebulizer connected to an air compressor with adequate air flow. It should also be used with a mouthpiece or suitable face mask.

Oral

• The regular release tablets and syrup are usually taken three or four times a day.
• Albuterol extended release tablets must be swallowed whole with the aid of liquids.
• Do not crush or chew extended release tablets.

A decision should be made to discontinue breastfeeding or discontinue the drug, taking into account the importance of the drug to the mother. Excreted into human milk: Unknown Excreted into animal milk: Data not available Comments: The effects in the nursing infant are unknown.