Ipratropium-Albuterol (ipratropium bromide/albuterol sulfate)

Dosage of albuterol sulfate is expressed in terms of albuterol. Dosage of levalbuterol hydrochloride or tartrate is expressed in terms of levalbuterol. Dosage of albuterol sulfate and levalbuterol must be carefully adjusted according to individual requirements and response. The albuterol oral aerosol inhalers deliver 90 mcg of albuterol from the mouthpiece per metered spray. The levalbuterol tartrate oral aerosol inhaler delivers 45 mcg of levalbuterol from the mouthpiece per metered spray. The oral aerosol inhaler containing albuterol sulfate and ipratropium bromide delivers 18 mcg of ipratropium bromide and 103 mcg of albuterol sulfate (equivalent to 90 mcg of albuterol) from the mouthpiece per metered spray. Using in vitro testing at an average flow rate of 3.6 L/minute for an average of 15 minutes, the Pari-LC Plus(R) nebulizer delivered at the mouthpiece approximately 46 or 42% of the original dosage of albuterol or ipratropium bromide, respectively. Using in vitro testing at an average flow rate of 3.6 L/minute for an average of 15 minutes or less, the Pari-LC Plus(R) nebulizer delivered at the mouthpiece approximately 43 or 39% of the original dosage of albuterol at the 1.25- or 0. 63-mg strength, respectively.

Commercially available albuterol sulfate aerosol with a hydrofluoroalkane (HFA) propellant delivers at least 200 metered sprays per 18-g (Ventolin(R) HFA), 6.7-g (Proventil(R) HFA), or 8.5-g (ProAir(R) HFA) canister, respectively. The commercially available aerosol inhaler containing albuterol sulfate in fixed combination with ipratropium bromide delivers 200 metered sprays per 14.7-g canister. The commercially available levalbuterol aerosol inhaler delivers 200 metered sprays per 15-g canister. The canister should be discarded after the labeled number of actuations have been used.

Albuterol sulfate is administered orally or by oral inhalation via a metered-dose inhaler or nebulization. Albuterol sulfate is administered in fixed combination with ipratropium bromide via a metered-dose aerosol inhaler or via nebulization. Levalbuterol hydrochloride is administered by oral inhalation via nebulization. Levalbuterol tartrate with hydrofluoroalkane (HFA) propellant is administered by oral inhalation via a metered-dose inhaler. To avoid microbial contamination, proper aseptic technique should be used when albuterol or levalbuterol is administered via nebulization. Albuterol sulfate extended-release tablets should not be chewed or crushed.

Ipratropium bromide is administered by oral inhalation using an oral aerosol inhaler or via nebulization. Ipratropium bromide is administered in fixed combination with albuterol sulfate via a metered-dose aerosol inhaler or via nebulization. Patients should be advised that ipratropium must be used consistently throughout the course of therapy for maximum benefit. In addition, patients should be advised that the drug will not provide immediate symptomatic relief and should not be used for the relief of acute bronchospasm.

No dosing information is available for this tab.

No dosing information is available for this tab.

The manufacturer states that because of the limited systemic absorption and low plasma drug concentrations associated with oral inhalation of ipratropium, it is unlikely that the drug would interact with systemically administered drugs. The manufacturer states that patients taking ipratropium bromide in fixed combination with albuterol sulfate should not use other inhaled agents unless directed by a clinician.

Adverse drug interactions have not been reported with concomitant administration of orally inhaled ipratropium and a beta-adrenergic agonist bronchodilator (e.g., albuterol, fenoterol (currently not commercially available in the US), isoproterenol, metaproterenol), theophylline derivatives, oral or inhaled corticosteroids, or cromolyn sodium in clinical studies in patients with chronic obstructive pulmonary disease (COPD) or asthma.

While concomitant inhalation of ipratropium and a beta2-adrenergic agonist may not always result in substantial additional bronchodilation compared with inhalation of either agent alone, such combined therapy usually increases the duration of bronchodilation. Concomitant administration of ipratropium and albuterol via nebulization has been reported to increase intraocular pressure (IOP) and precipitate acute angle-closure glaucoma in susceptible individuals (i.e., individuals with untreated or undiagnosed angle-closure glaucoma), probably as a result of inadvertent contact of the drugs with the eyes. (See Cautions: Ocular Effects.) Caution is advised if the fixed combination of albuterol and ipratropium inhalation aerosol is used concomitantly with other beta2-adrenergic agents since the risk for adverse cardiovascular effects increases.

Although ipratropium inhalation aerosol is minimally absorbed into the systemic circulation, there is some potential for additive interaction with concomitantly used antimuscarinic agents. Therefore, caution is advised when ipratropium aerosol is used concomitantly with other antimuscarinic agents.

For further information on drug interactions reported with antimuscarinics, see Drug Interactions in the Antimuscarinics/Antispasmodics General Statement 12:08.08.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

There is no enhanced messaging for this drug.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

There is no enhanced messaging for this drug.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

No enhanced messaging available.

Experts from the National Asthma Education and Prevention Program (NAEPP) state that maintaining adequate control of asthma during pregnancy is important for the health and well-being of the mother and the fetus. Because of the risks associated with asthma symptoms and exacerbations (e.g., increased perinatal mortality, preeclampsia, preterm birth, low birth weight during pregnancy, such experts consider use of antiasthmatic agents to be safer than the complications of inadequately controlled asthma. Albuterol is the preferred short-acting inhaled beta2-agonist because more data are available on use of albuterol in pregnant women than on use of other short-acting inhaled beta2-agonists, and such data indicate an excellent safety profile.

The manufacturers of albuterol or levalbuterol state that the drugs should be used during pregnancy only if the possible benefits outweigh the potential risks. During marketing experience with the drug, various congenital anomalies, including cleft palate and limb defects, have been reported in the children of patients being treated with albuterol; however, some women were receiving multiple medications during their pregnancies. Because no consistent pattern of congenital abnormality development can be discerned, a relationship between albuterol use and the development of congenital anomalies cannot be established. Large IV doses of albuterol have reportedly inhibited uterine contractions, and the drug has reportedly delayed preterm labor following oral administration. Serious adverse effects, including maternal pulmonary edema, have been reported during or following treatment of premature labor with beta2-agonists, including albuterol. There are currently no well-controlled studies to show that albuterol will stop preterm labor or prevent labor at term, and the risks versus benefits of tocolytic therapy with levalbuterol or albuterol have not been established. Albuterol or orally inhaled levalbuterol should be used with caution in pregnant women when needed for relief of bronchospasm during labor and only when the potential benefits are expected to clearly outweigh the possible risks, since the drugs may interfere with uterine contractility.

Albuterol has been shown to be teratogenic in mice and rabbits. Reproduction studies in mice given subcutaneous albuterol doses of 0.025, 0.25, or 2.5 mg/kg (approximately 0.003, 0.03, or 0.3 times, respectively, the maximum recommended daily oral dosage for adults; 0.125, 1.25, and 12.5 times the maximum recommended human albuterol single-use inhalation solution via nebulization; less than the maximum recommended adult daily inhalation solution dosage on a mg/m2 basis; and up to 8 times the maximum recommended daily inhalation aerosol dosage on a mg/m2 basis) showed cleft palate formation in 4.5% of fetuses at 0.25 mg/kg and in 9.3% of fetuses at 2.5 mg/kg (approximately equal to the maximum daily nebulized levalbuterol, albuterol sulfate, or albuterol sulfate/ipratropium bromide dosage in adults on a mg/m2 basis); cleft palate did not occur in mice receiving 0.025 mg/kg of albuterol (representing less than the maximum daily adult inhalation dosage of albuterol sulfate alone via metered-dose inhalation or nebulization or in fixed combination with ipratropium bromide via nebulization on a mg/m2 basis). Cleft palate also occurred in 30.5% of fetuses treated with 2.5 mg/kg of isoproterenol (positive control). A reproduction study with oral albuterol in rabbits revealed cranioschisis in 37% of fetuses at 50 mg/kg (approximately 25, 55, 60 or 80 times the maximum recommended daily adult oral albuterol sulfate dosage, albuterol sulfate/ipratropium bromide nebulized adult dosage, nebulized pediatric albuterol dosage or nebulized albuterol sulfate adult dosage, respectively, on a mg/m2 basis; 630-680 times the maximum daily adult inhalation aerosol dosage; or 250 times the maximum albuterol inhalation solution dosage via nebulization for a 50-kg human). In a reproduction study in rats given albuterol sulfate aerosol containing a hydrofluoroalkane propellant by oral inhalation, the drug did not exhibit any teratogenic effects at 10.5 mg/kg daily (approximately 60-65 times the maximum recommended human daily inhalation dosage on a mg/m2 basis). Safe use of the drug in pregnant women has not been established. A reproduction study in rabbits given oral levalbuterol dosages of up to 25 mg/kg (approximately 110 times the maximum recommended daily adult oral inhalation dosage on a mg/m2 basis) revealed no evidence of teratogenicity.

Reproduction studies in mice, rats, and rabbits receiving oral ipratropium bromide dosages of 10, 1000, and 125 mg/kg daily (approximately 200, 40,000, and 10,000 times the maximum recommended human daily inhalation dosage on a mg/m2 basis), respectively, and in rats or rabbits receiving orally inhaled ipratropium bromide dosages of 1.5 or 1.8 mg/kg (approximately 60 or 140 times the maximum recommended human daily inhalation dosage on a mg/m2 basis), respectively, have not revealed evidence of harm to the fetus. There are no adequate and controlled studies to date using orally inhaled ipratropium in pregnant women, and the drug should be used during pregnancy only when clearly needed.

It is not known whether albuterol, albuterol sulfate, or levalbuterol is distributed into milk. Because of the potential for tumorigenicity shown for albuterol in animal studies, a decision should be made whether to discontinue nursing or albuterol or levalbuterol, taking into account the importance of the drug to the woman.

It is not known whether ipratropium is distributed into milk in humans, but highly lipophobic quaternary bases are distributed slowly and at low concentrations into milk. Because ipratropium is not well absorbed systemically following oral inhalation, the manufacturer states that ingestion of substantial amounts of the drug by an infant during breast-feeding is unlikely. The manufacturer recommends that orally inhaled ipratropium be used with caution in nursing women.

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