IPRATROPIUM

Main information

  • Trade name:
  • IPRATROPIUM BROMIDE solution
  • Composition:
  • IPRATROPIUM BROMIDE ANHYDROUS 0.5 mg in 2.5 mL
  • Prescription type:
  • PRESCRIPTION DRUG
  • Medicine domain:
  • Humans
  • Medicine type:
  • Allopathic drug

Documents

Localization

  • Available in:
  • IPRATROPIUM BROMIDE solution
    United States
  • Language:
  • English

Status

  • Source:
  • DailyMed - NLM - National Library of Medicine
  • Authorization status:
  • Abbreviated New Drug Application
  • Last update:
  • 15-01-2018

Summary of Product characteristics: dosage, interactions, side effects

IPRATROPIUM BROMIDE- ipratropium bromide solution

A-S Medication Solutions

----------

IPRATROPIUM BROMIDE INHALATION SOLUTION, 0.02%

Prescribing Information

Rx Only

DESCRIPTION

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

H BrNO H O 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.

CLINICAL PHARMACOLOGY

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 -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 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 and FVC.

On combined therapy, the median duration of 15% improvement in FEV was 5 to 7 hours, compared

with 3 to 4 hours in patients receiving a beta agonist alone.

INDICATIONS AND USAGE

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.

CONTRAINDICATIONS

Ipratropium bromide is contraindicated in known or suspected cases of hypersensitivity to ipratropium

bromide, or to atropine and its derivatives.

WARNINGS

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.

PRECAUTIONS

General

Ipratropium bromide should be used with caution in patients with narrow-angle glaucoma, prostatic

hypertrophy or bladder-neck obstruction.

Information for Patients

Patients should be advised that temporary blurring of vision, precipitation or worsening of narrow-

angle glaucoma or eye pain may result if the solution comes into direct contact with the eyes. Use of a

nebulizer with mouthpiece rather than face mask may be preferable, to reduce the likelihood of the

nebulizer solution reaching the eyes. Patients should be advised that 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. Patients should be reminded that ipratropium bromide inhalation

solution should be used consistently as prescribed throughout the course of therapy.

Drug Interactions

Ipratropium bromide has been shown to be a safe and effective bronchodilator when used in conjunction

with beta adrenergic bronchodilators. Ipratropium bromide has also been used with other pulmonary

medications, including methylxanthines and corticosteroids, without adverse drug interactions.

Carcinogenesis, Mutagenesis, Impairment of Fertility

Two-year oral carcinogenicity studies in rats and mice have revealed no carcinogenic potential at

dietary doses up to 6 mg/kg/day of ipratropium bromide.

Results of various mutagenicity studies (Ames test, mouse dominant lethal test, mouse micronucleus test

and chromosome aberration of bone marrow in Chinese hamsters) were negative.

Fertility of male or female rats at oral doses up to 50 mg/kg/day was unaffected by ipratropium bromide

administration. At doses above 90 mg/kg increased resorption and decreased conception rates were

observed.

Pregnancy

TERATOGENIC EFFECTS

Pregnancy Category B

Oral reproduction studies performed in mice, rats and rabbits at doses of 10, 100, and 125 mg/kg

respectively, and inhalation reproduction studies in rats and rabbits at doses of 1.5 and 1.8 mg/kg (or

approximately 38 and 45 times the recommended human daily dose) respectively, have demonstrated no

evidence of teratogenic effects as a result of ipratropium bromide. However, no adequate or well-

controlled studies have been conducted in pregnant women. Because animal reproduction studies are not

always predictive of human response, ipratropium bromide should be used during pregnancy only if

clearly needed.

Nursing Mothers

It is not known whether ipratropium bromide is excreted in human milk. Although lipid-insoluble

quaternary bases pass into breast milk, it is unlikely that ipratropium bromide would reach the infant to a

significant extent, especially when taken by inhalation since ipratropium bromide is not well absorbed

systemically after inhalation or oral administration. However, because many drugs are excreted in

human milk, caution should be exercised when ipratropium bromide is administered to a nursing woman.

Pediatric Use

Safety and effectiveness in the pediatric population below the age of 12 have not been established.

ADVERSE REACTIONS

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.

All Adverse Events, from a Double-blind, Parallel, 12-week Study of patients with COPD

PERCENT OF PATIENTS

Ipratropium Metaproterenol

Ipratropium/

Metaproterenol

Albuterol

Ipratropium/

Albuterol

(500 mcg

t.i.d.)

(15 mg t.i.d.)

(500 mcg t.i.d./

15 mg t.i.d.)

(2.5 mg

t.i.d.)

(500 mcg

t.i.d./

2.5 mg t.i.d.)

n = 219

n = 212

n = 108

n = 205

n = 100

Body as a Whole-General

Disorders

Headache

Pain

Influenza-like symptoms

Back Pain

Chest Pain

Cardiovascular Disorders

Hypertension/Hypertension

Aggravated

Central & Peripheral

Nervous System

Dizziness

Insomnia

Tremor

Nervousness

Gastrointestinal System

Disorders

Mouth Dryness

Nausea

Constipation

Musculo-skeletal System

Disorders

Arthritis

Respiratory System

Disorders (Lower)

Coughing

Dyspnea

13.2

16.7

12.7

Bronchitis

14.6

24.5

15.7

16.6

20.0

Bronchospasm

Sputum Increased

Respiratory Disorder

Respiratory System

*

Disorders (Upper)

Upper Respiratory Tract

Infection

13.2

11.3

12.2

16.0

Pharyngitis

Rhinitis

Sinusitus

OVERDOSAGE

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 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.

DOSAGE AND ADMINISTRATION

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.

HOW SUPPLIED

Product: 50090-0668

NDC: 50090-0668-0 25 mL in a 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

Patient's Instructions for Use

Ipratropium Bromide

Inhalation Solution 0.02%

All adverse events, regardless of drug relationship, reported by three percent or more patients in the 12-week

controlled clinical trials.

Read complete instructions carefully before using.

5.

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.

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

(Figure 1).

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

Connect the nebulizer to the compressor.

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.

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.

Clean the nebulizer (see manufacturer's instructions).

ADDITIONAL INSTRUCTIONS:

____________________________________

____________________________________

____________________________________

____________________________________

____________________________________

____________________________________

____________________________________

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

Ipratropium Bromide

IPRATROPIUM BROMIDE

ipratropium bromide solution

Product Information

Product T ype

HUMAN PRESCRIPTION

DRUG

Ite m Code

(S ource )

NDC:50 0 9 0 -0 6 6 8 (NDC:76 20 4-10 0 )

Route of Administration

RESPIRATORY

(INHALATION)

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

A-S Medication Solutions

IPRATRO PIUM BRO MIDE (UNII: J6 9 7UZ2A9 J) (IPRATROPIUM -

UNII:GR8 8 G0 I6 UL)

IPRATROPIUM BROMIDE

ANHYDROUS

0 .5 mg

in 2.5 mL

Inactive Ingredients

Ingredient Name

Stre ng th

So dium Chlo ride (UNII: 451W47IQ8 X)

Hydro chlo ric Acid (UNII: QTT1758 2CB)

Wa ter (UNII: 0 59 QF0 KO0 R)

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:50 0 9 0 -0 6 6 8 -0

1 in 1 CARTON

11/28 /20 14

1

25 mL in 1 POUCH ; Type 0 : No t a Co mbinatio n Pro duct

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 756 9 3

0 2/0 1/20 11

Labeler -

A-S Medication Solutions (830016429)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

A-S Medicatio n So lutio ns

8 30 0 16 429

RELABEL(50 0 9 0 -0 6 6 8 )

Revised: 10/2017