Metaproterenol

Brand name: Alupent
Drug class: Selective beta-2-Adrenergic Agonists
VA class: RE102
CAS number: 5874-97-5

Introduction

Bronchodilator; less selective than relatively selective β₂-adrenergic agonists (e.g., albuterol).

Uses for Metaproterenol

Bronchospasm in Asthma

Symptomatic management of bronchospasm in patients with reversible, obstructive airway disease (e.g., asthma). Manufacturer recommends against use with other β-adrenergic bronchodilators. (See Specific Drugs under Interactions.)

Current asthma management guidelines and most clinicians recommend anti-inflammatory therapy with an orally inhaled corticosteroid as first-line therapy for long-term control of persistent asthma, supplemented by intermittent, as-needed use of a short-acting, inhaled β₂-agonist.

The National Asthma Education and Prevention Program (NAEPP) does not recommend nonselective β-adrenergic agonists, including metaproterenol, for treatment of asthma because of the associated potential for excessive cardiac stimulation, particularly in high doses.

Bronchospasm in COPD

Symptomatic management of reversible bronchospasm in patients with COPD, including chronic bronchitis and emphysema. Manufacturer recommends against use with other β-adrenergic bronchodilators. (See Specific Drugs under Interactions.)

Metaproterenol Dosage and Administration

General

• Adjust dosage carefully according to individual requirements and response.

Administration

Administer orally or by oral inhalation via metered-dose inhaler or nebulizer.

Oral Inhalation

Metered-dose Inhaler

Oral inhalation aerosol delivers approximately 0.65 mg from mouthpiece per metered spray; 7-g or 14-g canister delivers 100 or 200 metered sprays, respectively.

Administer inhalation aerosol only with actuator provided by manufacturer.

Shake the inhaler well before use.

Avoid spraying aerosol into eyes.

Place the mouthpiece of the inhaler well into the mouth with lips closed around it. Exhale through nose as completely as possible. Inhale slowly and deeply through mouth. Actuate aerosol inhaler, hold breath for few seconds, withdraw mouthpiece, and exhale slowly.

Allow ≥2 minutes to elapse between inhalations from aerosol inhaler.

Clean inhalation aerosol inhaler by removing metal canister and running warm water through plastic mouthpiece. If soap used, rinse thoroughly with plain water.

Dosage

Available as metaproterenol sulfate; dosage expressed in terms of metaproterenol sulfate.

Pediatric Patients

Bronchospasm in Asthma

Oral

Oral solution in children <6 years of age (limited experience): 1.3–2.6 mg/kg daily.

Oral solution in children 6–9 years of age or those weighing <27.3 kg: Usually, 10 mg 3 or 4 times daily.

Conventional tablets in children 6–9 years of age or those weighing <27.3 kg: Usually, 10 mg 3 or 4 times daily.

Oral solution in children >9 years of age or those weighing >27.3 kg: Usually, 20 mg 3 or 4 times daily.

Conventional tablets in children >9 years of age or those weighing >27.3 kg: Usually, 20 mg 3 or 4 times daily.

Oral Inhalation

Inhalation aerosol in children ≥12 years of age: 1.3 or 1.95 mg (2 or 3 inhalations). Usually no need to repeat dosing more often than every 3–4 hours. If necessary, additional inhalations may be used, with dosage not exceeding 7.8 mg (12 inhalations) in any 24-hour period.

0.4 or 0.6% inhalation solution for nebulization in children ≥12 years of age: 10 or 15 mg (contents of 1 vial of 0.4 or 0.6% solution for nebulization, respectively) 3 or 4 times daily. Usually no need to repeat dosing more often than every 4 hours.

Adults

Bronchospasm in Asthma

Oral

Usually, 20 mg 3 or 4 times daily.

Oral Inhalation

Inhalation aerosol: 1.3 or 1.95 mg (2 or 3 inhalations). Usually no need to repeat dosing more often than every 3–4 hours. If necessary, additional inhalations may be used, with dosage not exceeding 7.8 mg (12 inhalations) in any 24-hour period.

0.4 or 0.6% inhalation solution for nebulization: 10 or 15 mg (contents of 1 vial of 0.4 or 0.6% solution for nebulization, respectively) 3 or 4 times daily. Usually no need to repeat dosing more often than every 4 hours.

Bronchospasm in COPD

Oral Inhalation

Inhalation aerosol: 1.3 or 1.95 mg (2 or 3 inhalations). Usually no need to repeat dosing more often than every 3–4 hours. If necessary, additional inhalations may be used, with dosage not exceeding 7.8 mg (12 inhalations) in any 24-hour period.

0.4 or 0.6% inhalation solution for nebulization: 10 or 15 mg (contents of 1 vial of 0.4 or 0.6% solution for nebulization, respectively) 3 or 4 times daily. Usually no need to repeat dosing more often than every 4 hours.

Prescribing Limits

Pediatric Patients

Bronchospasm

Asthma

Oral Inhalation

Inhalation aerosol in children ≥12 years of age: Maximum ≤7.8 mg (≤12 inhalations) total daily dosage.

Adults

Bronchospasm in Asthma

Oral Inhalation

Inhalation aerosol: Maximum ≤7.8 mg (≤12 inhalations) total daily dosage.

Bronchospasm in COPD

Oral Inhalation

Inhalation aerosol: Maximum ≤7.8 mg (≤12 inhalations) total daily dosage.

Cautions for Metaproterenol

Contraindications

Arrhythmias associated with tachycardia.

Known hypersensitivity to metaproterenol or any ingredients in formulation.

Warnings/Precautions

Warnings

Acute or Worsening Asthma

Oral inhalation therapy intended for acute symptomatic relief of bronchospasm.

Failure to respond to previously effective dosage of metaproterenol may indicate seriously worsening asthma. Contact a clinician if control of mild asthma deteriorates. Reevaluate asthma therapy and institute alternative regimens or therapy.

Excessive Doses

Fatalities have been associated with excessive use of inhaled sympathomimetic drugs; cardiac arrest occurred in several cases.

Paradoxical Bronchospasm

Possible life-threatening, acute paradoxical bronchospasm. Occasionally occurs after repeated or excessive use of orally inhaled sympathomimetic amines.

Discontinue therapy immediately if bronchoconstriction occurs and institute alternative therapy.

Cardiovascular Effects

Possible clinically important cardiovascular effects, including cardiac arrhythmias (e.g., tachycardia), changes in BP, and related symptoms.

Cautious use recommended in patients with cardiovascular disorders (e.g., ischemic heart disease, CAD, cardiac arrhythmias, hypertension, CHF).

Sensitivity Reactions

Rarely, immediate hypersensitivity reactions can occur.

Possible acute bronchospasm. (See Paradoxical Bronchospasm under Cautions.)

General Precautions

Nervous System Effects

In high doses, possible CNS stimulation.

Cautious use recommended in patients with seizure disorders and those with sensitivity to sympathomimetic amines.

Metabolic Effects

Possible hypokalemia, which may increase risk of adverse cardiovascular effects.

Cautious use recommended in patients with diabetes mellitus or hyperthyroidism.

Specific Populations

Pregnancy

Category C.

Lactation

Not known whether metaproterenol is distributed into milk. With oral inhalation solution, use caution. Administer oral solution or inhalation aerosol to nursing women only if potential benefits to the woman outweigh the possible risk to infant.

Pediatric Use

Safety and efficacy of oral inhalation aerosol or solution for nebulization not established in children <12 years of age.

Safety and efficacy of oral tablets not established in children <6 years of age. Safety and efficacy of oral solution demonstrated in limited number of pediatric patients <6 years of age.

Common Adverse Effects

Inhalation aerosol: Nervousness, headache, dizziness, palpitations, GI distress, tremor, throat irritation, nausea, vomiting, cough, asthma exacerbation.

Inhalation solution: Nervousness, tachycardia, tremor, nausea.

Oral tablets: Nervousness, tachycardia, tremor, headache, palpitations, nausea, GI distress, dizziness, asthma exacerbation, insomnia, fatigue, diarrhea, bad taste, vomiting, drowsiness, syncope, hypertension, pruritus, appetite changes, dry throat, fever.

Oral solution: Tachycardia, nervousness, tremor, nausea, headache.

Interactions for Metaproterenol

Specific Drugs

Metaproterenol Pharmacokinetics

Absorption

Bioavailability

Oral bioavailability about 10%.

Onset

Oral inhalation aerosol: ≤1 minute.

Oral: ≤15–30 minutes.

Oral inhalation solution: ≤5–30 minutes.

Oral or oral inhalation: Peak effect ≤1 hour.

Duration

Oral: ≤4 hours for oral solution and ≥4 hours for tablets.

Oral inhalation aerosol: About 1–2.5 hours.

Oral inhalation solution: 4–6 hours.

Bronchodilating effect of metaproterenol persists for ≥1 hour longer than that of equipotent doses of isoproterenol.

Distribution

Extent

Not known if metaproterenol is distributed into milk.

Plasma Protein Binding

Approximately 10–15%.

Elimination

Metabolism

Following oral administration, extensively metabolized in GI tract to sulfate conjugate. Following oral inhalation, may be excreted as glucuronic acid conjugates.

Elimination Route

Oral: Excreted in urine (approximately 40%) mostly as sulfate metabolite.

Half-life

Biphasic: Terminal half-life 1.5–6 hours.

Stability

Storage

Oral

Solution and Tablets

Tight, light-resistant containers at 15–30°C. Protect from moisture.

Oral Inhalation

Oral inhalation aerosol: 15–25°C; avoid excessive humidity.

Oral inhalation solution: ≤25°C. Discard solution if pinkish or darker than slightly yellow in color or if it contains a precipitate.

Actions

• Stimulates β-adrenergic receptors with little or no effect on α-adrenergic receptors.

• Less selectivity for β₂-receptors than albuterol. More selectivity for β₂-receptors than isoproterenol.

• Stimulates the production of cyclic adenosine-3′,5′-monophosphate (cAMP), which mediates bronchial smooth muscle relaxation and inhibition of release of proinflammatory mediators from mast cells in airways.

• Decreases airway resistance.

• In high doses, may cause CNS stimulation and some cardiostimulatory effects, which may result in tachycardia and hypertension.

• Possible development of tolerance to bronchodilatory effects with prolonged therapy exceeding recommended dosages.

Advice to Patients

• Importance of adherence to dosing schedules of metaproterenol and concomitant therapy, including not exceeding recommended dosage or frequency of use unless otherwise instructed by a clinician.

• Importance of using extreme care when considering administration of additional sympathomimetic agents. Importance of allowing a sufficient interval of time to elapse before administering another sympathomimetic agent. (See Specific Drugs under Interactions.)

• Importance of contacting clinician if asthmatic symptoms worsen or adverse reactions or diminished response occurs with usual dosage; do not increase dose or frequency of administration.

• Importance of women informing clinicians if they are or plan to become pregnant or plan to breast-feed.

• Importance of informing clinicians of existing or contemplated concomitant therapy, including prescription and OTC drugs.

• Importance of advising patients of other important precautionary information. (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.

* available from one or more manufacturer, distributor, and/or repackager by generic (nonproprietary) name

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