Label: IPRATROPIUM BROMIDE solution

The active ingredient in ipratropium bromide inhalation solution is ipratropium bromide monohydrate. It 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 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. Each mL contains ipratropium bromide 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 inhalation solution 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 inhalation solution has not been studied in patients with hepatic or renal insufficiency. It should be used with caution in those patient populations.

In controlled twelve-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 1-2 hours, and persisted for periods of 4-5 hours in the majority of patients, with about 25-38% of the patients demonstrating increases of 15% or more for at least 7-8 hours. Continued effectiveness of ipratropium bromide 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 5-7 hours, compared with 3-4 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 inhalation solution 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 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 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 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 is a clear, colorless solution containing 2.5 mL, packaged in cartons as listed below:

NDC 0487-9801-25, 25 vials per carton / 5 vials per foil pouch

NDC 0487-9801-30, 30 vials per carton / 5 vials per foil pouch

NDC 0487-9801-60, 60 vials per carton / 5 vials per foil pouch

NDC 0487-9801-01, 30 vials per carton / 1 vial per foil pouch

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

Principal Display Panel – Pouch Label (5 Vial Card)

NDC 0487-9801-25, NDC 0487-9801-30 and NDC 0487-9801-60

Ipratropium Bromide Inhalation Solution, 0.02%

0.5 mg / 2.5 mL

FOR ORAL INHALATION ONLY

NOT FOR INJECTION

Each low density polyethylene vial contains:

2.5 mL ipratropium bromide inhalation solution, 0.02% preservative-free isotonic, sterile, aqueous solution containing sodium chloride. Adjusted to pH 3.4 (3 to 4) with hydrochloric acid.

Usage Dosage: See accompanying prescribing information.

Store between 15°C and 30°C (59°F 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.

Manufactured By:

Nephron Pharmaceuticals Corporation

West Columbia, SC 29172

Rx Only

STERILE

5 x 2.5 mL Sterile Unit-Dose Vials

Principal Display Panel – Carton (25 Count)

NDC 0487-9801-25

Ipratropium Bromide Inhalation Solution, 0.02%

0.5 mg / 2.5 mL vial

FOR ORAL INHALATION ONLY

NOT FOR INJECTION

Usage Dosage: See accompanying prescribing information.

Store between 15°C and 30°C (59°F 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

Principal Display Panel – Carton (30 Count)

NDC 0487-9801-30

Ipratropium Bromide Inhalation Solution, 0.02%

0.5 mg / 2.5 mL vial

FOR ORAL INHALATION ONLY

NOT FOR INJECTION

Usage Dosage: See accompanying prescribing information.

Store between 15°C and 30°C (59°F 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

Principal Display Panel – Carton (60 Count)

NDC 0487-9801-60

Ipratropium Bromide Inhalation Solution, 0.02%

0.5 mg / 2.5 mL vial

FOR ORAL INHALATION ONLY

NOT FOR INJECTION

Each 2.5 mL unit-dose vial contains Ipratropium Bromide, 0.02% equal to 0.5 mg of Ipratropium Bromide (anhydrous basis) in a sterile, preservative-free, isotonic saline solution; pH is adjusted to 3.4 (3 to 4) with hydrochloric acid.

Store between 15°C and 30°C (59°F and 86°F).

Protect from light.

Store unused vials in the foil pouch.

Rx Only

Carton contains 60 x 2.5 mL Sterile Unit-Dose Vials

(Twelve foil pouches, each pouch contains five 2.5 mL vials)

Principal Display Panel – Pouch Label (individually wrapped vials)

NDC 0487-9801-01

Ipratropium Bromide Inhalation Solution, 0.02%

0.5 mg / 2.5 mL

FOR ORAL INHALATION ONLY

NOT FOR INJECTION

Each mL contains ipratropium bromide inhalation solution, 0.02% in a sterile, preservative-free, isotonic saline solution, pH adjusted to 3.4 (3 to 4) with hydrochloric acid. Each vial is made from a low-density polyethylene (LDPE) resin.

Usual Dosage: See accompanying prescribing information.

Store between 15° and 30°C (59° and 86°F).

Protect from light.

Rx Only

STERILE

One 2.5 mL Unit-Dose Vial

Manufactured By:

Nephron Pharmaceuticals Corporation

West Columbia, SC 29172

Principal Display Panel – Carton (30 individually wrapped vials)

NDC 0487-9801-01

Ipratropium Bromide Inhalation Solution, 0.02%

0.5 mg / 2.5 mL

For Oral Inhalation Only

Not for Injection

Each low density polyethylene vial contains:

2.5 mL ipratropium bromide inhalation solution, 0.02% preservative-free isotonic sterile aqueous solution containing sodium chloride. Adjusted to pH 3.4 (3 to 4) with hydrochloric acid.

Rx Only

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