Label: IPRATROPIUM BROMIDE AND ALBUTEROL SULFATE solution

Mechanism of Action

Pharmacokinetics

Albuterol Sulfate

Intravenous studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations amounting to approximately 5% of plasma concentrations. In structures outside of the blood-brain barrier (pineal and pituitary glands), albuterol concentrations were found to be 100 times those found in whole brain.

Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrythmias and sudden death (with histological evidence of myocardial necrosis) when beta-agonists and methylxanthines are administered concurrently. The clinical significance of these findings is unknown.

Ipratropium Bromide

Autoradiographic studies in rats have shown that ipratropium does not penetrate the blood-brain barrier.

Ipratropium Bromide and Albuterol Sulfate Inhalation Solution

In 30-day studies in Sprague-Dawley rats and Beagle dogs, subcutaneous doses of up to 205.5 mcg/kg of ipratropium administered with up to 1000 mcg/kg albuterol in rats and 3.16 mcg/kg ipratropium and 15 mcg/kg albuterol in dogs (less than the maximum recommended daily inhalation dose for adults on a mg/m 2 basis) did not cause death or potentiation of the cardiotoxicity induced by albuterol administered alone.

PARADOXICAL BRONCHOSPASM

In the clinical study of Ipratropium Bromide and Albuterol Sulfate Inhalation Solution, paradoxical bronchospasm was not observed. However, paradoxical bronchospasm has been observed with both inhaled ipratropium bromide and albuterol products and can be life-threatening. If this occurs, Ipratropium Bromide and Albuterol Sulfate Inhalation Solution should be discontinued immediately and alternative therapy instituted.

DO NOT EXCEED RECOMMENDED DOSE

Fatalities have been reported in association with excessive use of inhaled products containing sympathomimetic amines and with the home use of nebulizers.

CARDIOVASCULAR EFFECTS

Ipratropium Bromide and Albuterol Sulfate Inhalation Solution, like 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 for Ipratropium Bromide and Albuterol Sulfate Inhalation Solution 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, Ipratropium Bromide and Albuterol Sulfate Inhalation Solution, like other sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.

IMMEDIATE HYPERSENSITIVITY REACTIONS

Immediate hypersensitivity reactions to albuterol and/or ipratropium bromide may occur after the administration of Ipratropium Bromide and Albuterol Sulfate Inhalation Solution as demonstrated by rare cases of urticaria, angioedema, rash, pruritis, oropharyngeal edema, bronchospasm, and anaphylaxis.

General

Information for Patients

The action of Ipratropium Bromide and Albuterol Sulfate Inhalation Solution should last up to 5 hours. Ipratropium Bromide and Albuterol Sulfate Inhalation Solution should not be used more frequently than recommended. Patients should be instructed not to increase the dose or frequency of Ipratropium Bromide and Albuterol Sulfate Inhalation Solution without consulting their healthcare provider. If symptoms worsen, patients should be instructed to seek medical consultation.

Patients must avoid exposing their eyes to this product as temporary pupillary dilation, blurred vision, eye pain, or precipitation or worsening of narrow-angle glaucoma may occur, and therefore proper nebulizer technique should be assured, particularly if a mask is used.

If a patient becomes pregnant or begins nursing while on Ipratropium Bromide and Albuterol Sulfate Inhalation Solution, they should contact their healthcare provider about use of Ipratropium Bromide and Albuterol Sulfate Inhalation Solution.

See the illustrated Patient’s Instruction for Use in the product package insert.

Drug Interactions

Carcinogenesis, Mutagenesis, Impairment of Fertility

Pregnancy

Labor and Delivery

Oral albuterol sulfate has been shown to delay preterm labor in some reports. Because of the potential of albuterol to interfere with uterine contractility, use of Ipratropium Bromide and Albuterol Sulfate Inhalation Solution during labor should be restricted to those patients in whom the benefits clearly outweigh the risks.

Nursing Mothers

It is not known whether the components of Ipratropium Bromide and Albuterol Sulfate Inhalation Solution are excreted in human milk. Although lipid-insoluble quaternary bases pass into breast milk, it is unlikely that ipratropium bromide would reach the infant to an important extent, especially when taken as a nebulized solution. Because of the potential for tumorigenicity shown for albuterol sulfate in some animals, a decision should be made whether to discontinue nursing or discontinue Ipratropium Bromide and Albuterol Sulfate Inhalation Solution, taking into account the importance of the drug to the mother.

Pediatric Use

The safety and effectiveness of Ipratropium Bromide and Albuterol Sulfate Inhalation Solution in patients below 18 years of age have not been established.

Geriatric Use

Of the total number of subjects in clinical studies of Ipratropium Bromide and Albuterol Sulfate Inhalation Solution, 62 percent were 65 and over, while 19 percent were 75 and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.

Storage and Handling

PROTECT FROM LIGHT. The unit-dose vial should remain stored in the protective foil pouch until time of use.

Store at 20°C to 25°C (68°F and 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature].

Manufactured by:

Nephron Pharmaceuticals Corporation

West Columbia, SC 29172

For Customer Service, Call 1-800-443-4313

STORING YOUR MEDICINE

Store Ipratropium Bromide and Albuterol Sulfate Inhalation Solution at 20°C to 25°C (68°F and 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Vials should be protected from light before use, therefore, keep unused vials in the foil pouch or carton. Do not use after the expiration (EXP) date printed on the carton.

DOSE

Ipratropium Bromide and Albuterol Sulfate Inhalation Solution is supplied as a single-dose, ready-to-use vial containing 3 mL of solution. No mixing or dilution is needed. Use one new vial for each nebulizer treatment.

INSTRUCTIONS FOR USE

FOLLOW THESE DIRECTIONS FOR USE OF YOUR NEBULIZER / COMPRESSOR OR THE DIRECTIONS GIVEN BY YOUR HEALTHCARE PROVIDER. A TYPICAL EXAMPLE IS SHOWN NEARBY.

1. Remove one vial from the foil pouch. Place remaining vials back into the pouch for storage.
2. Twist the cap completely off the vial and squeeze the contents into the nebulizer reservoir (Figure 1).
   
3. Connect the nebulizer to the mouthpiece or face mask (Figure 2).
   
4. Connect the nebulizer to the compressor
5. Sit in a comfortable, upright position; place the mouthpiece in your mouth (Figure 3) or put on the face mask (Figure 4); and turn on the compressor.
   
6. Breathe as calmly, deeply and evenly as possible through your mouth until no more mist is formed in the nebulizer chamber (about 5 - 15 minutes). At this point, the treatment is finished.
7. Clean the nebulizer (see manufacturer's instructions).

PATIENT INFORMATION

Ipratropium Bromide 0.5 mg
and Albuterol Sulfate 3 mg*
Inhalation Solution, USP

*Equivalent to 2.5 mg albuterol base

Prescription Only.

Read the patient information that comes with Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg before you start using it and each time you get a refill. There may be new information. This leaflet does not take the place of talking with your doctor about your medical condition or your treatment.

What is Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg?

Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg is a combination of two medicines called bronchodilators. Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg contains albuterol sulfate, which is a beta-adrenergic agonist, and ipratropium bromide, which is an anticholinergic. These two medicines work together to help open the airways in your lungs. Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg is used to help treat airway narrowing (bronchospasm) that happens with chronic obstructive pulmonary disease (COPD) in adult patients who need to use more than one bronchodilator medicine.

Who should not use Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3mg?

Do not use Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg if you: Are allergic to any of the ingredients in Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg or to atropine. The active ingredients are albuterol sulfate and ipratropium bromide. See the end of this leaflet for a complete list of ingredients in Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg.

Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg has not been studied in patients younger than 18 years of age.

What should I tell my doctor before I start using Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg?

Tell your doctor about all of your conditions, including if you:

• Have heart problems. This includes coronary artery disease and heart rhythm problems.
• Have high blood pressure
• Have diabetes
• Have or had seizures
• Have a thyroid problem called hyperthyroidism
• Have an eye problem called narrow-angle glaucoma
• Have liver or kidney problems
• Have problems urinating due to bladder-neck blockage or an enlarged prostate (men)
• Are pregnant or planning to become pregnant. It is not known if Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg can harm your unborn baby. You and your doctor will have to decide if Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg is right for you during a pregnancy.
• Are breastfeeding. It is not known if Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg passes into your milk or if it can harm your baby. You and your doctor should decide whether you should take Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg or breastfeed, but not both.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins and herbal supplements. Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg and other medicines can interact. This may cause serious side effects. Especially tell your doctor if you take:

• Other medicines that contain anticholinergics such as ipratropium bromide. This also includes medicines used for Parkinson’s disease.
• Other medicines that contain beta-agonists such as albuterol sulfate. These are usually used to treat airway narrowing (bronchospasm).
• Medicines called beta-blockers. These are usually used for high blood pressure or heart problems.
• Medicines called “water pills” (diuretics).
• Medicines for depression called monoamine oxidase inhibitors (MAOIs) or tricyclic antidepressants.

Ask your doctor or pharmacist if you are not sure if you take any of these types of medicines. Know the medicines you take. Keep a list of them and show it to your doctor and pharmacists when you get a new medicine.

How should I use Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg?

• Read the Patient’s Instructions for Use that you get with your prescription. Talk to your doctor or pharmacist if you have any questions.
• Take Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg exactly as prescribed by your doctor. Do not change your dose or how often you use Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg without talking to your doctor. Inhale Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg through your mouth and into your lungs using a machine called a nebulizer.
• Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg may help to open your airways for up to 5 hours after taking this medicine. If Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg does not help your airway narrowing (bronchospasm) or your bronchospasm gets worse, call your doctor right away or get emergency help if needed.

What should I avoid while using Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg?

Do not get Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg in your eyes. Be careful not to spray Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg in your eyes while you are using your nebulizer. Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg can cause the following short-term eye problems:

• Enlarged pupils
• Blurry vision
• Eye pain

Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg can cause a serious eye problem called narrow-angle glaucoma or worsen the narrow-angle glaucoma you already have.

What are the possible side effects with Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg?

Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg may cause the following serious side effects:

• Worsening of the narrowing in your airways (bronchospasm). This side effect can be life-threatening and has happened with both of the medicines that are in Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg. Stop Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg and call your doctor right away or get emergency help if your breathing problems get worse while or after using Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg.
• Serious and life-threatening allergic reactions. Symptoms of a serious allergic reaction include:
  • Hives, rash
  • Swelling of your face, eyelids, lips, tongue, or throat, and trouble swallowing
  • Worsening of your breathing problems such as wheezing, chest tightness or shortness of breath
  • Shock (loss of blood pressure and consciousness)

The most common side effects with Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg include lung disease, sore throat, chest pain, constipation, diarrhea, bronchitis, urinary tract infection, leg cramps, nausea, upset stomach, voice changes, and pain.

These are not all the side effects with Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg. For a complete list, ask your doctor or pharmacist.

How should I store Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg?

• Store Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg at 20°C to 25°C (68°F and 77°F); excursions permitted between 15°C and 30°C (59°F and 86°F) [see USP Controlled Room Temperature]. Protect from light. Keep the unused vials in the foil pouch or carton.
• Safely discard Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg that is out-of-date or no longer needed.
• Keep Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg and all medicines out of the reach of children.

General advice about Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg

Medicines are sometimes prescribed for conditions that are not mentioned in the patient information leaflets. Do not use Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg for a condition for which it was not prescribed. Do not give Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg to other people, even if they have the same symptoms you have. It may harm them.

This leaflet summarizes the most important information about Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg. If you would like more information, talk with your doctor. You can ask your doctor or pharmacist for information about Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg that is written for health professionals.

What are the ingredients in Ipratropium Bromide 0.5 mg and Albuterol Sulfate 3 mg?

Active Ingredients: ipratropium bromide and albuterol sulfate.

Inactive Ingredients: sodium chloride, water for injection, and hydrochloric acid to adjust pH.