Ipratropium bromide/salbutamol

What is Ipratropium bromide/salbutamol?

• Ipratropium bromide/salbutamol (Combivent Metered Dose Inhaler; Combivent Respimat Inhalation Spray; DuoNeb Inhalant Solution) is a combination of ipratropium bromide (an anticholinergic agent) and albuterol sulfate (a beta2‑adrenergic agonist) used to treat chronic obstructive pulmonary disease (COPD).
• Ipratropium bromide/salbutamol is used by people whose symptoms have not been controlled by a single inhaled medication.

Ipratropium

Ipratropium bromide

Salbutamol

Salbutamol-3D-vdW

Salbutamol-racemic-2D-skeletal

What are the uses of this medicine?

• Ipratropium bromide/salbutamol (Combivent Metered Dose Inhaler; Combivent Respimat Inhalation Spray; DuoNeb Inhalant Solution) is indicated for use in patients with chronic obstructive pulmonary disease (COPD) on a regular aerosol bronchodilator who continue to have evidence of bronchospasm and who require a second bronchodilator.

How does this medicine work?

• Ipratropium bromide/salbutamol is a combination of the anticholinergic ipratropium bromide and the beta2-adrenergic agonist albuterol sulfate.

Ipratropium bromide:

• Ipratropium bromide is an anticholinergic (parasympatholytic) agent which, based on animal studies, appears to inhibit vagally mediated reflexes by antagonizing the action of acetylcholine, the transmitter agent released at the neuromuscular junctions in the lung.
• Anticholinergics prevent the increases in intracellular concentration of Ca++ which is caused by interaction of acetylcholine with the muscarinic receptors on bronchial smooth muscle.

Albuterol sulfate:

• The sulfate salt of the short-acting sympathomimetic agent albuterol, a 1:1 racemic mixture of (R)-albuterol and (S)-albuterol with bronchodilator activity.
• Albuterol stimulates beta2-adrenergic receptors in the lungs, thereby activating the enzyme adenylate cyclase that catalyzes the conversion of ATP to cyclic-3',5'-adenosine monophosphate (cAMP).
• Increased cAMP concentrations relax bronchial smooth muscle, relieve bronchospasms, and reduce inflammatory cell mediator release, especially from mast cells.
• To a lesser extent albuterol stimulates beta1-adrenergic receptors, thereby increasing the force and rate of myocardial contraction.

Who Should Not Use this medicine ?

This medicine cannot be used in patients with:

• Hypersensitivity to any of the ingredients.
• Hypersensitivity to atropine or any of its derivatives.

What drug interactions can this medicine cause?

• Tell your doctor and pharmacist what other prescription and nonprescription medications, vitamins, nutritional supplements, and herbal products you are taking or plan to take.

Especially tell your doctor if you take:

• beta blockers such as atenolol (Tenormin), labetalol, metoprolol (Lopressor, Toprol XL), nadolol (Corgard), and propranolol (Inderal)
• diuretics ('water pills')
• epinephrine (Epipen, Primatene Mist)
• medications for colds, irritable bowel disease, Parkinson's disease, ulcers, or urinary problems
• other inhaled medications, especially other medications for asthma such as arformoterol (Brovana), formoterol (Foradil, Perforomist), metaproterenol, levalbuterol (Xopenex), and salmeterol (Serevent, in Advair)
• terbutaline (Brethine).

Also tell your doctor if you are taking any of the following medications or if you have stopped taking them within the past 2 weeks:

• antidepressants such as amitriptyline amoxapine
• clomipramine (Anafranil), desipramine (Norpramin), doxepin (Silenor), imipramine (Tofranil), nortriptyline (Pamelor), protriptyline (Vivactil), and trimipramine (Surmontil)
• monoamine oxidase (MAO) inhibitors such as isocarboxazid (Marplan), phenelzine (Nardil), tranylcypromine (Parnate), and selegiline (Eldepryl, Emsam, Zelapar).

Is this medicine FDA approved?

• The combination was approved for medical use in the United States in 1996.

How should this medicine be used?

Recommended dosage:

• The recommended dose of Ipratropium bromide/salbutamol is one inhalation four times a day.
• Patients may take additional inhalations as required; however, the total number of inhalations should not exceed six in 24 hours.
• Safety and efficacy of additional doses of Ipratropium bromide/salbutamol beyond six inhalations/24 hours have not been studied.
• Also, safety and efficacy of extra doses of ipratropium or albuterol in addition to the recommended doses of Ipratropium bromide/salbutamol have not been studied.

Administration:

• The combination of albuterol and ipratropium comes as a solution to inhale by mouth using a nebulizer and as a spray to inhale by mouth using an inhaler.
• It is usually inhaled four times a day.
• Prior to first use, the cartridge is inserted into the Ipratropium bromide/salbutamol inhaler and the unit is primed.
• When using the unit for the first time, patients are to actuate the inhaler toward the ground until an aerosol cloud is visible and then repeat the process three more times.
• The unit is then considered primed and ready for use. If not used for more than 3 days, patients are to actuate the inhaler once to prepare the inhaler for use.
• If not used for more than 21 days, patients are to actuate the inhaler until an aerosol cloud is visible and then repeat the process three more times to prepare the inhaler for use.
• If you are using the inhaler, your medication will come in cartridges. Each cartridge of albuterol and ipratropium inhalation spray is designed to provide 120 inhalations.
• Be careful not to get albuterol and ipratropium inhalation into your eyes. If you get albuterol and ipratropium in your eyes, you may develop narrow angle glaucoma.
• The inhaler that comes with albuterol and ipratropium spray is designed for use only with a cartridge of albuterol and ipratropium. Never use it to inhale any other medication, and do not use any other inhaler to inhale the medication in a cartridge of albuterol and ipratropium.

What are the dosage forms and brand names of this medicine?

This medicine is available in fallowing doasage form:

• As Inhalation spray: 20 mcg ipratropium bromide (monohydrate) and 100 mcg albuterol (equivalent to 120 mcg albuterol sulfate) per actuation.

This medicine is available in fallowing brand namesː

• Combivent Metered Dose Inhaler; Combivent Respimat Inhalation Spray; DuoNeb Inhalant Solution

What side effects can this medication cause?

The most common side effects of this medicine include:

• upper respiratory infection, nasopharyngitis, cough, bronchitis, headache, and dyspnea

Less common, but serious side effects may include:

• Paradoxical bronchospasm
• Cardiovascular effects
• Hypersensitivity reactions including anaphylaxis
• Hypokalemia
• Ocular effects
• Urinary retention

What special precautions should I follow?

• Inform patients that Ipratropium bromide/salbutamol Inhalation Spray can produce paradoxical bronchospasm that can be life-threatening. If paradoxical bronchospasm occurs, patients should discontinue using Ipratropium bromide/salbutamol Inhalation Spray.
• Caution patients to avoid spraying the aerosol into their eyes and advise that this may result in precipitation or worsening of narrow‑angle glaucoma, mydriasis, increased intraocular pressure, acute eye pain or discomfort, temporary blurring of vision, visual halos or colored images in association with red eyes from conjunctival and corneal congestion. Patients should also be advised that should any combination of these symptoms develop, they should consult their physician immediately.
• Since dizziness, accommodation disorder, mydriasis, and blurred vision may occur with use of Ipratropium bromide/salbutamol Inhalation Spray, patients should be cautioned about engaging in activities requiring balance and visual acuity such as driving a car or operating appliances or machinery.
• Inform patients that Ipratropium bromide/salbutamol Inhalation Spray may cause urinary retention and advise them to consult their physician if they experience difficulty with urination.
• Inform patients of adverse effects associated with beta2-agonists, such as palpitations, chest pain, rapid heart rate, tremor, or nervousness.
• The action of Ipratropium bromide/salbutamol Inhalation Spray should last 4 to 5 hours or longer. Ipratropium bromide/salbutamol Inhalation Spray should not be used more frequently than recommended. Safety and efficacy of additional doses of COMBIVENT RESPIMAT beyond six inhalations in 24 hours have not been studied.
• Inform patients that hypersensitivity reactions, including urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema, may occur after the administration of Ipratropium bromide/salbutamol Inhalation Spray. Advise patients to immediately discontinue Ipratropium bromide/salbutamol Inhalation Spray and consult a physician
• There are no available data on the presence of ipratropium bromide or albuterol, in human milk, the effects on the breastfed infant, or the effects on milk production.

What to do in case of emergency/overdose?

Symptoms of overdosage may include:

• The effects of overdosage are expected to be related primarily to albuterol sulfate.
• Acute overdosage with ipratropium bromide by inhalation is unlikely since ipratropium bromide is not well absorbed systemically after inhalation or oral administration.

Albuterol sulfate overdose symptoms:

• Anginal pain, hypertension, hypokalemia, tachycardia with rates up to 200 beats per minute, metabolic acidosis.

• As with all beta2-adrenergic agonist aerosol medications, cardiac arrest and even death may be associated with abuse.

Management of overdosage:

• In case of overdose, call the poison control helpline of your country. In the United States, call 1-800-222-1222.

• Overdose related information is also available online at poisonhelp.org/help.
• In the event that the victim has collapsed, had a seizure, has trouble breathing, or can't be awakened, immediately call emergency services. In the United States, call 911.
• Treatment of overdosage consists of discontinuation of Ipratropium bromide/salbutamol Inhalation Spray together with institution of appropriate medical and supportive therapy.
• Dialysis is not appropriate treatment for overdosage of albuterol as an inhalation aerosol; the judicious use of a cardiovascular beta‑receptor blocker, such as metoprolol tartrate, may be indicated.

Can this medicine be used in pregnancy?

• There are no randomized clinical studies of Ipratropium bromide/salbutamol Inhalation Spray, or its individual components, ipratropium bromide and albuterol sulfate, in pregnant women.

Can this medicine be used in children?

• Safety and effectiveness of Ipratropium bromide/salbutamol Inhalation Spray in pediatric patients have not been established.

What are the active and inactive ingredients in this medicine?

Active ingredient:

• IPRATROPIUM BROMIDE
• ALBUTEROL SULFATE

Inactive ingredients:

• none

Who manufactures and distributes this medicine?

Distributed by:

• Boehringer Ingelheim Pharmaceuticals, Inc.
• Ridgefield, CT USA

What should I know about storage and disposal of this medication?

• Store at 20°C to 25°C (68°F to 77°F); excursions permitted to 15°C to 30°C (59°F to 86°F).
• Avoid freezing.

• Dailymed label info on Ipratropium bromide/salbutamol
• FDA Ipratropium bromide/salbutamol

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