albuterol/ipratropium (Rx)

>10%

Bronchitis (2-12%)

1-10%

Upper respiratory tract infection (1-10%)

Lung disease (6%)

Headache (3-6%)

Dyspnea (2-5%)

Nasopharyngitis (4%)

Cough (3-4%)

Pharyngitis (2-4%)

Pain (1-3%)

Chest pain (2.6%)

Sinusitis (2.3%)

Nausea (1-2%)

Diarrhea (1.8%)

Urinary tract infection (1.6%)

Influenza (1.4%)

Leg cramps (1.4%)

Nausea (1.4%)

Pneumonia (1.4%)

Rhinitis (1.1%)

<1%

Allergic-type reactions, such as skin reactions (eg, rash, pruritus, urticaria [including giant urticaria]), angioedema (eg, of tongue, lips, face), laryngospasm, and anaphylaxis

Angina

Arrhythmia

Arthralgia

Dizziness

Dry mouth

Dyspepsia

Dysphonia

Edema

Fatigue

Hypertension

Insomnia

Nervousness

Palpitation

Paresthesia

Tachycardia

Tremor

Vomiting

Postmarketing Reports

Cardiovascular: Palpitations, hypotension, myocardial infarction, decreased diastolic blood pressure (BP), increased systolic BP

General: Anaphylactoid reactions, drowsiness, flushing, alopecia, edema, hypokalemia, mental disorder, hyperhidrosis, metabolic acidosis (with albuterol products), asthenia

Gastrointestinal (GI): Mucosal ulcers, stomatitis, heartburn, distress (diarrhea, nausea, vomiting), GI motility disorder, constipation

Muscular: Muscle spasms, muscular weakness, myalgia

Neurologic and psychiatric: Central nervous system (CNS) stimulation, coordination difficulty

Other: Throat irritation, dry throat, hoarseness

Renal: Urinary retention

Respiratory: Bronchospasm (including paradoxical bronchospasm), nasal congestion, drying of secretions, wheezing, exacerbation of COPD symptoms

Sensory: Mydriasis, precipitation or worsening of narrow-angle glaucoma, glaucoma, increased intraocular pressure (IOP), acute eye pain, halo vision, blurred vision, accommodation disorder, ocular irritation, corneal edema, conjunctival hyperemia

Contraindications

Hypersensitivity to albuterol, ipratropium, atropine and derivatives, soy, or peanut

Cautions

Paradoxical bronchospasm; discontinue immediately, and administer alternative therapy

History of cardiovascular disorders; beta-adrenergic stimulation can result in clinically significant cardiovascular effects, myocardial ischemia, or electrocardiographic (ECG) changes

Avoid spraying into eyes, and contact physician if visual disturbances (eg, blurred vision or halos) occur; monitor patients with narrow-angle glaucoma

May produce clinically important hypokalemia leading to adverse cardiovascular effects in some patients

May cause immediate hypersensitivity reaction (urticaria, angioedema, rash, bronchospasm, anaphylaxis, or oropharyngeal edema); discontinue immediately, and administer alternative therapy

Use cution in patients with convulsive disorders, hyperthyroidism, diabetes mellitus, prostatic hyperplasia, or bladder-neck obstruction

May cause dizziness and blurred vision; patients should use caution when performing tasks requiring mental alertness

Do not exceed recommended dosage; fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma

Keep out of reach of children

Avoid freezing

Pregnancy

There are no randomized clinical studies of the drug combination, or its individual components, ipratropium bromide and albuterol sulfate, in pregnant women; ipratropium is negligibly absorbed systemically following oral inhalation; therefore, maternal use is not expected to result in fetal exposure to drug

Published literature, including cohort studies, case-control studies and case series, over several decades have not identified drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes with ipratropium bromide

Available data from published epidemiological studies and postmarketing case reports of pregnancy outcomes following inhaled albuterol use do not consistently demonstrate a risk of major birth defects or, miscarriage; there are clinical considerations with use of therapy in pregnant women; animal reproduction studies have not been conducted with drug

Because of potential for beta-agonist interference with uterine contractility, use of drug for the treatment of COPD during labor should be restricted to those patients in whom the benefits clearly outweigh risk; serious adverse reactions, including pulmonary edema, have been reported during or following treatment of premature labor with beta2-agonists, including albuterol

Animal data

• Animal studies are available with its individual components, ipratropium bromide and albuterol sulfate
• Based on oral reproduction studies, no evidence of structural alterations was observed when ipratropium bromide was administered to pregnant mice, rats, and rabbits during organogenesis at doses approximately 340, 68,000 and 17,000 times, respectively, the maximum recommended human daily inhalation dose (MRHDID) in adults on a mg/m² basis
• When albuterol was administered to pregnant mice during organogenesis there was evidence of cleft palate at doses approximately equivalent to maximum recommended human daily inhalation

Lactation

There are no available data on presence of drug, or components, ipratropium bromide or albuterol, in human milk, effects on breastfed infant, or on milk production; although lipid-insoluble quaternary cations pass into breast milk, ipratropium concentrations in plasma after inhaled therapeutic doses are low

Plasma levels of albuterol after inhaled therapeutic doses are low in humans; therefore, ipratropium and albuterol concentrations in human breast milk are likely to be correspondingly low; developmental and health benefits of breastfeeding should be considered along with mother’s clinical need for albuterol and any potential adverse effects on breastfed child from albuterol or from underlying maternal condition

Pregnancy Categories

A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.

B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.

C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.

D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.

X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.

NA: Information not available.

Mechanism of Action

Albuterol: Beta2-adrenergic bronchodilator

Ipratropium: Anticholinergic (parasympatholytic) agent; inhibits vagally mediated reflexes by antagonizing acetylcholine action; prevents increase in intracellular calcium concentration caused by interaction of acetylcholine with muscarinic receptors on bronchial smooth muscle

Absorption

Peak plasma time: Albuterol, 3 hr (from portion swallowed)

Peak plasma concentration: Albuterol, 419-802 pg/mL (from portion swallowed)

Distribution

Protein bound: Ipratropium, 0-9%

Metabolism

Albuterol: Conjugatively metabolized to albuterol 4'-O-sulfate

Ipratropium: Partially metabolized to inactive ester hydrolysis products

Elimination

Half-life: Albuterol, 3.6 hr (after 30-min infusion of 1.5 mg); ipratropium, 2 hr (after inhalation or IV administration)

Mean clearance: Albuterol, 439 mL/min/1.73 m²

Excretion: Albuterol, urine (27%); ipratropium, urine (4%)

Instructions

See individual package inserts for instructions on use

Avoid freezing

Aerosol metered-dose inhalers

• Insert cartridge into metered-dose inhaler, and prime unit before initial use; actuate inhaler toward ground until aerosol cloud is visible, then repeat 3 more times
• If inhaler has not been used for >3 days, actuate it once before using it again
• If inhaler has not been used for ≥21 days, repeat priming process for initial use (ie, actuate until aerosol cloud is observed, then repeat 3 more times)

Nebulizer solution

• Administer via jet nebulizer connected to air compressor with adequate air flow
• Equip with mouthpiece or suitable air mask