Label: IPRATROPIUM BROMIDE solution

Prescribing Information

Rx Only

The active ingredient, ipratropium bromide monohydrate, USP, is an anticholinergic bronchodilator chemically described as 8-azoniabicyclo [3.2.1]- octane, 3-(3-hydroxy-1-oxo-2-phenylpropoxy)-8-methyl-8-(1-methylethyl)-, bromide, monohydrate (endo, syn)-, (±)-; a synthetic quaternary ammonium compound, chemically related to atropine.

Ipratropium Bromide Monohydrate  C 20H 30BrNO 3•H 2O  Mol.Wt. 430.4

Ipratropium bromide is a white crystalline substance, freely soluble in water and lower alcohols. It is a quaternary ammonium compound and thus exists in an ionized state in aqueous solutions. It is relatively insoluble in non-polar media.

Ipratropium Bromide Inhalation Solution is administered by oral inhalation with the aid of a nebulizer. It contains ipratropium bromide, USP 0.02% (anhydrous basis) in a sterile, preservative-free, isotonic saline solution, pH-adjusted to 3.4 (3 to 4) with hydrochloric acid.

Ipratropium bromide is an anticholinergic (parasympatholytic) agent that, based on animal studies, appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released from the vagus nerve.

Anticholinergics prevent the increases in intracellular concentration of cyclic guanosine monophosphate (cyclic GMP) that are caused by interaction of acetylcholine with the muscarinic receptor on bronchial smooth muscle.

The bronchodilation following inhalation of ipratropium bromide is primarily a local, site-specific effect, not a systemic one. Much of an administered dose is swallowed but not absorbed, as shown by fecal excretion studies. Following nebulization of a 2 mg dose, a mean 7% of the dose was absorbed into the systemic circulation either from the surface of the lung or from the gastrointestinal tract. The half-life of elimination is about 1.6 hours after intravenous administration. Ipratropium bromide is minimally (0 to 9% in vitro) bound to plasma albumin and a 1-acid glycoproteins. It is partially metabolized. Autoradiographic studies in rats have shown that ipratropium bromide does not penetrate the blood-brain barrier. Ipratropium bromide has not been studied in patients with hepatic or renal insufficiency. It should be used with caution in those patient populations.

In controlled 12-week studies in patients with bronchospasm associated with chronic obstructive pulmonary disease (chronic bronchitis and emphysema) significant improvements in pulmonary function (FEV 1 increases of 15% or more) occurred within 15 to 30 minutes, reached a peak in 1 to 2 hours, and persisted for periods of 4 to 5 hours in the majority of patients, with about 25% to 38% of the patients demonstrating increases of 15% or more for at least 7 to 8 hours. Continued effectiveness of ipratropium bromide inhalation solution was demonstrated throughout the 12-week period. In addition, significant increases in forced vital capacity (FVC) have been demonstrated. However, ipratropium bromide did not consistently produce significant improvement in subjective symptom scores nor in quality of life scores over the 12-week duration of study.

Additional controlled 12-week studies were conducted to evaluate the safety and effectiveness of ipratropium bromide inhalation solution administered concomitantly with the beta adrenergic bronchodilator solutions metaproterenol and albuterol compared with the administration of each of the beta agonists alone. Combined therapy produced significant additional improvement in FEV 1 and FVC. On combined therapy, the median duration of 15% improvement in FEV 1 was 5 to 7 hours, compared with 3 to 4 hours in patients receiving a beta agonist alone.

Ipratropium Bromide Inhalation Solution administered either alone or with other bronchodilators, especially beta adrenergics, is indicated as a bronchodilator for maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease, including chronic bronchitis and emphysema.

Ipratropium bromide is contraindicated in known or suspected cases of hypersensitivity to ipratropium bromide, or to atropine and its derivatives.

The use of ipratropium bromide inhalation solution as a single agent for the relief of bronchospasm in acute COPD exacerbation has not been adequately studied. Drugs with faster onset of action may be preferable as initial therapy in this situation. Combination of ipratropium bromide and beta agonists has not been shown to be more effective than either drug alone in reversing the bronchospasm associated with acute COPD exacerbation.

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

Adverse reaction information concerning ipratropium bromide inhalation solution is derived from 12-week active-controlled clinical trials. Additional information is derived from foreign post-marketing experience and the published literature.

All adverse events, regardless of drug relationship, reported by three percent or more patients in the 12-week controlled clinical trials appear in the table below.

Additional adverse reactions reported in less than three percent of the patients treated with ipratropium bromide include tachycardia, palpitations, eye pain, urinary retention, urinary tract infection and urticaria. Cases of precipitation or worsening of narrow-angle glaucoma, mydriasis, and acute eye pain have been reported.

Lower respiratory adverse reactions (bronchitis, dyspnea and bronchospasm) were the most common events leading to discontinuation of ipratropium bromide therapy in the 12-week trials. Headache, mouth dryness and aggravation of COPD symptoms are more common when the total daily dose of ipratropium bromide equals or exceeds 2,000 mcg.

Allergic-type reactions such as skin-rash, angioedema of tongue, lips and face, urticaria, laryngospasm and anaphylactic reaction have been reported. Many of the patients had a history of allergies to other drugs and/or foods.

Acute systemic overdosage by inhalation solution is unlikely since ipratropium bromide is not well absorbed after inhalation at up to four-fold the recommended dose, or after oral administration at up to forty-fold the recommended dose. The oral LD 50 of ipratropium bromide ranged between 1001 and 2010 mg/kg in mice; between 1667 and 4000 mg/kg in rats; and between 400 and 1300 mg/kg in dogs.

The usual dosage of ipratropium bromide inhalation solution is 500 mcg (1 Unit-Dose Vial) administered three to four times a day by oral nebulization, with doses 6 to 8 hours apart. Ipratropium bromide inhalation solution unit-dose vials contain 500 mcg ipratropium bromide, USP anhydrous in 2.5 mL normal saline. Ipratropium bromide inhalation solution can be mixed in the nebulizer with albuterol or metaproterenol if used within one hour. Drug stability and safety of Ipratropium Bromide Inhalation Solution when mixed with other drugs in a nebulizer have not been established.

Ipratropium Bromide Inhalation Solution Unit Dose Vial is supplied as a 0.02% clear, colorless solution containing 2.5 mL.

NDC 76204-100-25, 25 vials per carton / 25 vials per foil pouch

NDC 76204-100-30, 30 vials per carton / 30 vials per foil pouch

NDC 76204-100-01, 30 vials per carton / 1 vial per foil pouch

NDC 76204-100-60, 60 vials per carton / 30 vials per foil pouch

Each vial is made from a low density polyethylene (LDPE) resin.

Vials are supplied in a foil pouch.

ATTENTION PHARMACIST: Detach "Patient's Instructions for Use" from Package Insert and dispense with solution.

Rx Only

Manufactured by:
The Ritedose Corporation
Columbia, SC 29203 for
Ritedose Pharmaceuticals, LLC
Columbia, SC 29203

To report SUSPECTED ADVERSE
REACTIONS, contact Ritedose
Pharmaceuticals, LLC
at 1-855-806-3300 or FDA
at 1-800-FDA-1088 or www.fda.gov/medwatch

RPIN0044
JAN 2013

Ipratropium Bromide

Inhalation Solution 0.02%

Read complete instructions carefully before using.

1. Twist open the top of one unit dose vial and squeeze the contents into the nebulizer reservoir. (Figure 1).
   

   

2. Connect the nebulizer reservoir to the mouthpiece or face mask (Figure 2).
   

   

3. Connect the nebulizer to the compressor.
4. Sit in a comfortable, upright position; place the mouthpiece in your mouth (Figure 3) or put on the face mask and turn on the compressor. If a face mask is used, care should be taken to avoid leakage around the mask as temporary blurring of vision, pupil enlargement, precipitation or worsening of narrow angle glaucoma, or eye pain may occur if the solution comes into direct contact with the eyes.
   

   

5. Breathe as calmly, deeply, and evenly as possible until no more mist is formed in the nebulizer chamber (about 5 to 15 minutes). At this point, the treatment is finished.
6. Clean the nebulizer (see manufacturer's instructions).

Note: Use only as directed by your physician. More frequent administration or higher doses are not recommended. Ipratropium Bromide Inhalation Solution can be mixed in the nebulizer with albuterol or metaproterenol if used within one hour but not with other drugs. Drug stability and safety of Ipratropium Bromide Inhalation Solution when mixed with other drugs in the nebulizer have not been established.

Store between 59°F (15°C) and 86°F (30°). Protect from light. Store unused vials in the foil pouch.

ADDITIONAL INSTRUCTIONS:
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Manufactured by:
The Ritedose Corporation
Columbia, SC 29203 for
Ritedose Pharmaceuticals, LLC
Columbia, SC 29203

To report SUSPECTED ADVERSE
REACTIONS, contact Ritedose
Pharmaceuticals, LLC
at 1-855-806-3300 or FDA
at 1-800-FDA-1088 or www.fda.gov/medwatch

JAN 2013

NDC 76204-100-25

Ipratropium Bromide Inhalation Solution, 0.02%
0.5 mg / 2.5 mL

FOR ORAL INHALATION ONLY

INGREDIENTS: Each low density polyethylene vial contains: 2.5 mL Ipratropium Bromide 0.02%, preservative free, isotonic sterile aqueous solution containing sodium chloride. Adjusted to pH 3.4 (3 to 4) with hydrochloric acid.
Usual Dosage: See accompanying prescribing information.
Store between 15° and 30°C (59° and 86°F). Protect from light. Store unused vials in the foil pouch.
ATTENTION PHARMACIST: Detach "Patient's Instructions For Use" from package insert and dispense with solution.

Rx Only

25 x 2.5 mL Sterile Unit-Dose Vials

NDC 76204-100-30

Ipratropium Bromide Inhalation Solution, 0.02%
0.5 mg / 2.5 mL

FOR ORAL INHALATION ONLY

INGREDIENTS: Each low density polyethylene vial contains: 2.5 mL Ipratropium Bromide 0.02%, preservative free, isotonic sterile aqueous solution containing sodium chloride. Adjusted to pH 3.4 (3 to 4) with hydrochloric acid.
Usual Dosage: See accompanying prescribing information.
Store between 15° and 30°C (59° and 86°F). Protect from light. Store unused vials in the foil pouch.
ATTENTION PHARMACIST: Detach "Patient's Instructions For Use" from package insert and dispense with solution.

Rx Only

30 x 2.5 mL Sterile Unit-Dose Vials

NDC 76204-100-60

Ipratropium Bromide Inhalation Solution, 0.02%
0.5 mg / 2.5 mL

FOR ORAL INHALATION ONLY

INGREDIENTS: Each low density polyethylene vial contains: 2.5 mL Ipratropium Bromide 0.02%, preservative free, isotonic sterile aqueous solution containing sodium chloride. Adjusted to pH 3.4 (3 to 4) with hydrochloric acid.
Usual Dosage: See accompanying prescribing information.
Store between 15° and 30°C (59° and 86°F). Protect from light. Store unused vials in the foil pouch.
ATTENTION PHARMACIST: Detach "Patient's Instructions For Use" from package insert and dispense with solution.

Rx Only

60 x 2.5 mL Sterile Unit-Dose Vials

NDC 76204-100-01

Ipratropium Bromide Inhalation Solution, 0.02%
0.5 mg / 2.5 mL

FOR ORAL INHALATION ONLY

INGREDIENTS: Each low density polyethylene vial contains: 2.5 mL Ipratropium Bromide 0.02%, preservative free, isotonic sterile aqueous solution containing sodium chloride. Adjusted to pH 3.4 (3 to 4) with hydrochloric acid.
Usual Dosage: See accompanying prescribing information.
Store between 15° and 30°C (59° and 86°F). Protect from light.
ATTENTION PHARMACIST: Detach "Patient's Instructions For Use" from package insert and dispense with solution.

Rx Only

30 x 2.5 mL Sterile Unit-Dose Vials, each in a foil pouch