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  • CLASSES

    Oral Beta-2 Agonists
    Parenteral Beta-2 Agonists
    Respiratory Short-Acting Beta-2 Agonists (SABA)

    BOXED WARNING

    Premature labor

    Terbutaline has been used systemically off-label to reduce contractions of preterm labor and uterine hyperstimulation. Although, certain acute situations may warrant the use of injectable terbutaline in premature labor, its use is not without risk and a boxed warning addresses the use of terbutaline as tocolysis. Oral terbutaline is contraindicated for acute or maintenance tocolysis as its safety and efficacy have not been established. Terbutaline injection has not been approved and should not be used for prolonged tocolysis (beyond 48 to 72 hours). Do not use for maintenance tocolysis in the outpatient or home setting. Serious adverse reactions, including death, have been reported after administration of terbutaline sulfate to pregnant women. In the mother, these adverse reactions include increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema and myocardial ischemia. Increased fetal heart rate and neonatal hypoglycemia may occur as a result of maternal administration. Therefore, terbutaline administered by injection or by continuous infusion pump is contraindicated for prolonged tocolysis (use beyond 48 to 72 hours).

    DEA CLASS

    Rx

    DESCRIPTION

    Systemic short-acting selective beta-2 agonist (SABA); shorter acting than albuterol
    Used for treating and preventing bronchospasm due to asthma in adult and pediatric patients; also for bronchospasm due to COPD in adults, but inhaled agents are preferred
    Not recommended for use for prolonged tocolysis, off-label use as an acute tocolytic must be approached with caution

    COMMON BRAND NAMES

    Brethine

    HOW SUPPLIED

    Brethine/Terbutaline/Terbutaline Sulfate Oral Tab: 2.5mg, 5mg
    Brethine/Terbutaline/Terbutaline Sulfate Subcutaneous Inj Sol: 1mg, 1mL

    DOSAGE & INDICATIONS

    For asthma maintenance treatment.
    Oral dosage
    Adults

    5 mg PO 3 times daily (given every 6 hours while awake). If side effects occur, reduce to 2.5 mg PO 3 times daily. Max: 15 mg/day. Both NAEPP and GINA generally recommend against the use of oral short-acting beta-2 agonists.

    Adolescents 16 to 17 years

    5 mg PO 3 times daily (given every 6 hours while awake). If side effects occur, reduce to 2.5 mg PO 3 times daily. Max: 15 mg/day. Both NAEPP and GINA generally recommend against the use of oral short-acting beta-2 agonists.

    Children and Adolescents 12 to 15 years

    2.5 mg PO 3 times daily (given every 6 hours while awake). Max: 7.5 mg/day. Both NAEPP and GINA generally recommend against the use of oral short-acting beta-2 agonists.

    For the treatment of bronchospasm (e.g., episodic wheezing) or an asthma exacerbation (e.g., primary care or acute care management).
    Subcutaneous dosage
    Adults

    0.25 mg subcutaneously once; repeat in 15 to 30 minutes if no significant improvement. If the patient fails to respond within another 15 to 30 minutes, consider alternative therapy. Do not exceed 0.5 mg total dose within a 4 hour period. There is no proven advantage of systemic beta-2 agonist therapy over inhalation therapy.

    Children and Adolescents 12 to 17 years

    0.25 mg subcutaneously once; repeat in 15 to 30 minutes if no significant improvement. If the patient fails to respond within another 15 to 30 minutes, consider alternative therapy. Do not exceed 0.5 mg total dose within a 4 hour period. There is no proven advantage of systemic beta-2 agonist therapy over inhalation therapy.

    Children 2 to 11 years†

    0.01 mg/kg/dose (Max: 0.25 mg) subcutaneously every 10 to 20 minutes for 3 doses or until IV infusion is initiated. May repeat intermittent injection every 2 to 6 hours as needed. There is no proven advantage of systemic beta-2 agonist therapy over inhalation therapy.

    For the treatment of bronchospasm due to chronic obstructive pulmonary disease (COPD) (e.g., chronic bronchitis and emphysema).
    Oral dosage
    Adults

    5 mg PO 3 times daily (given every 6 hours while awake). If side effects occur, may reduce to 2.5 mg PO 3 times daily. Max: 15 mg/day PO. According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for COPD, more selective and inhaled short-acting beta agonists (SABAs), such as albuterol or levalbuterol, are generally preferred vs. terbutaline. Inhaled SABAs may be used for therapy in patients with mild COPD (Group A) and in combination with other treatments in those with more severe disease (Groups B, C, and D); inhaled SABAs are preferred for the management of COPD exacerbations, with or without an inhaled antimuscarinic agent. Oral beta agonists (e.g., terbutaline) are not preferred for COPD patients.

    Subcutaneous dosage
    Adults

    Initially, 0.25 mg subcutaneously. Repeat in 15 to 30 minutes if no significant improvement. If the patient fails to respond within another 15 to 30 minutes, consider alternative therapy. Do not exceed 0.5 mg total dose within a 4-hour period.[46800] According to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines for COPD, more selective and inhaled short-acting beta-agonists (SABAs), such as albuterol or levalbuterol, are generally preferred vs. terbutaline. Inhaled SABAs may be used for therapy in patients with mild COPD (Group A) and in combination with other treatments in those with more severe disease (Groups B, C, and D). Inhaled SABAs are preferred for the management of COPD exacerbations, with or without an inhaled antimuscarinic agent vs. use of systemic beta agonists (e.g., terbutaline).[63765]

    For the treatment of status asthmaticus† in pediatric patients.
    Intravenous dosage
    Children and Adolescents 2 to 17 years

    Typical dose range: 2 to 10 mcg/kg IV load over 5 minutes, then 0.1 to 10 mcg/kg/minute continuous IV infusion. Start low and titrate by 0.1 to 0.2 mcg/kg/minute every 30 to 60 minutes to clinical response and tolerance. Usual maintenance rate: 1 to 5 mcg/kg/minute. Usual Max: 10 mcg/kg/minute. IV terbutaline infusions are typically reserved for patients not responding to conventional therapy. For children 5 years and younger, a 2 mcg/kg IV load over 5 minutes, followed by 5 mcg/kg/hour (0.08 mcg/kg/min) continuous IV infusion has been recommended to be used only when inhalational beta-agonist therapy is not possible. Hemodynamic stability may be compromised; monitor heart rate and blood pressure continuously.

    For the inhibition of uterine contraction in premature labor†.
    For continued suppression of uterine contractions after successful inhibition of acute premature labor†.
    Oral dosage
    Pregnant females

    Not recommended. Per the FDA, oral terbutaline should not be used for prevention or any treatment of preterm labor due to lack of efficacy and serious maternal cardiovascular safety concerns, increased fetal heart rate, and neonatal hypoglycemia. Doses of 5 to 10 mg PO every 4 to 6 hours until 37 weeks gestation have been studied in clinical trials. Meta-analyses have found no benefit in reducing the risk of recurrent preterm labor or preterm delivery from prolonged administration of any tocolytic.

    Subcutaneous continuous infusion dosage†
    Pregnant females

    Not recommended. Do not use for prevention or prolonged treatment (beyond 48 to 72 hours) of preterm labor due to serious maternal CV events and death.[43432] Maternal adverse events have included increased heart rate, hypokalemia, cardiac arrhythmias, pulmonary edema, and myocardial ischemia; in the fetus, increased heart rate and neonatal hypoglycemia may occur as a result of maternal administration.[46800] [46801] During post-marketing surveillance, 16 maternal deaths and 12 cases of serious maternal cardiovascular events were reported to the FDA.[43432] Meta-analyses have found no benefit in reducing the risk of recurrent preterm labor or preterm delivery from prolonged administration of any tocolytic. Historically, doses ranging from 50 to 100 mcg/hour continuous subcutaneous infusion have been studied. Usual MAX basal rate: 100 mcg/hour. Adjust rate to maternal and fetal response. A 250 mcg bolus subcutaneously has been used to control break-through uterine contractions. Requires the use of modified syringe pumps (e.g., insulin or Mini-Med infusion syringe pumps).

    Subcutaneous dosage
    Pregnant females

    Terbutaline should not be used for prolonged tocolysis (beyond 48 to 72 hours) of preterm labor due to the potential for serious maternal cardiovascular events and death.[46800] [46801] [43432] The historical off-label dose is 0.25 mg subcutaneously every 20 minutes to 6 hours. Doses should be held for a pulse of more than 120 beats/minute.[33039] [33598] Although not definitive, the typical duration of tocolysis for acute inhibition of premature labor is 24 to 72 hours. Maternal arrhythmias, pulmonary edema, tachycardia, and myocardial ischemia, as well as fetal tachycardia, neonatal hyperglycemia, and neonatal hypoglycemia, have been reported.[46800] [46801] [43432] The American College of Obstetrics and Gynecology states that a clear-first line drug cannot be recommended. The preterm delivery rate is not reduced by tocolysis. Tocolytics typically prolong pregnancy by approximately 2 to 7 days, which allows for the transfer of the patient to a hospital with appropriate facilities and administration of antenatal corticosteroids to enhance fetal lung maturation.[33039]

    †Indicates off-label use

    MAXIMUM DOSAGE

    Dosage must be individualized and is highly variable depending on the indication, route of administration, and patient response.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    No guidelines for dosage adjustment in patients with hepatic impairment are available.

    Renal Impairment

    CrCl > 50 ml/min: No dosage adjustment is needed.
    CrCl 10—50 ml/min: Give 50% of the usual systemic dose given at the normal dosage interval.
    CrCl < 10 ml/min: Avoid use.

    ADMINISTRATION

    Oral Administration

    Administer tablets orally.
    For patients with difficulty swallowing, the tablets may be crushed. Alternatively, an extemporaneous oral liquid may be prepared.

    Injectable Administration

    Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

    Intravenous Administration

    Continuous IV Infusion
    Terbutaline is not FDA-approved for continuous intravenous infusion.
    May dilute with 5% Dextrose Injection, 0.9% Sodium Chloride Injection, or 0.2% Sodium Chloride Injection to a maximum concentration of 1 mg/mL.
    ASHP Recommended Standard Concentrations for Pediatric Continuous Infusions: 1 mg/mL.

    Subcutaneous Administration

    Inject terbutaline subcutaneously into the lateral deltoid area.
    Discard unused portion after single patient use; vials or ampules are for single-use only.

    STORAGE

    Brethine:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 degrees F)
    - Store in carton until time of use

    CONTRAINDICATIONS / PRECAUTIONS

    Acute bronchospasm, paradoxical bronchospasm

    Terbutaline sulfate is contraindicated in patients known to be hypersensitive to sympathomimetic amines or any component of this drug product. Immediate hypersensitivity reactions and exacerbations of acute bronchospasm have been reported after terbutaline administration. Paradoxical bronchospasm has been reported in the inhaled use of short-acting beta-agonists and may be life threatening. If paradoxical bronchospasm occurs, discontinue the inhaled beta-agonist immediately give alternative therapy. It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister or vial.

    Deterioration of asthma

    Be alert for deterioration of asthma in patients taking terbutaline in the treatment of asthma, regardless of dosage form used. Increased terbutaline use may indicate asthma destabilization. Asthma may deteriorate acutely over a period of hours or chronically over several days or weeks. If deterioration of asthma occurs during therapy with terbutaline, appropriate evaluation of the patient and the treatment strategy is warranted, giving special consideration to corticosteroid therapy. Terbutaline has no anti-inflammatory activity and is not a substitute for corticosteroid therapy. The use of beta-agonists alone may not be adequate to control asthma in many patients. Early consideration should be given to adding anti-inflammatory agents (e.g., corticosteroids) to the therapeutic regimen. Corticosteroids should not be stopped or reduced when terbutaline therapy is instituted.

    Pheochromocytoma

    Terbutaline should generally be avoided in patients with pheochromocytoma, since sympathomimetic amines may increase blood pressure and heart rate. Pheochromocytoma may also increase the risk of prolonging the QT interval when using terbutaline.

    Apheresis, AV block, bradycardia, cardiac arrhythmias, cardiomyopathy, celiac disease, coronary artery disease, females, fever, heart failure, human immunodeficiency virus (HIV) infection, hyperparathyroidism, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, hypothermia, hypothyroidism, long QT syndrome, myocardial infarction, QT prolongation, rheumatoid arthritis, sickle cell disease, sleep deprivation, stroke, systemic lupus erythematosus (SLE)

    Terbutaline possesses positive inotropic and chronotropic effects; the effects are dose related. Significant changes in systolic and diastolic blood pressures or heart rate may occur in some patients after use of any beta-adrenergic bronchodilator. Periodically monitor pulse rate, blood pressure, and/or symptoms. Although such effects are uncommon after administration of terbutaline sulfate at recommended doses, if they occur, the drug may need to be discontinued. Terbutaline should be used with caution in patients with cardiovascular disorders including coronary artery disease, hypertension, or cardiac arrhythmias; rarely, such conditions can be aggravated by the use of terbutaline. The risk is higher with higher doses of terbutaline. If such patients do not respond adequately to terbutaline, choose alternative therapy. Beta-adrenergic agonist medications may produce hypokalemia in some patients, which has the potential to produce adverse cardiovascular effects, including prolonging the QT interval. The decrease in serum potassium is usually transient, not requiring supplementation. Beta-agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the T wave, QT prolongation, and ST segment depression. Use terbutaline with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.

    Hyperthyroidism, thyrotoxicosis

    Terbutaline, as with all sympathomimetic amines, should be used with caution in patients with hyperthyroidism. Patients with hyperthyroidism can be more susceptible to the effects of the sympathomimetic drugs. Systemic sympathomimetics are generally avoided during the treatment of thyrotoxicosis.

    Seizure disorder, seizures

    There have been rare reports of seizures in patients receiving terbutaline; seizures did not recur in these patients after the drug was discontinued. Terbutaline should be used with caution in patients with a history of seizure disorder.

    Diabetes mellitus, diabetic ketoacidosis

    Large doses of intravenous terbutaline have been reported to aggravate pre-existing diabetes mellitus and diabetic ketoacidosis. Use systemic terbutaline with caution in patients with diabetes mellitus.

    Caesarean section, labor, obstetric delivery, pregnancy

    Terbutaline is classified as a pregnancy risk category C drug. It crosses the placenta, but studies have not indicated any teratogenic effects in humans. Fetal tachycardia has followed parenteral use of terbutaline during pregnancy. Terbutaline can inhibit uterine contractions and should be used cautiously during the second and third trimesters. Systemic therapies, such as terbutaline, are not preferred asthma treatments during pregnancy. The 2004 guidelines of the National Asthma Education and Prevention Program (NAEPP) Asthma and Pregnancy Working Group include short-acting inhaled beta-2 agonists, such as albuterol, as first line therapy for mild intermittent asthma during pregnancy, if treatment is required. Albuterol is preferred due to extensive safety-related information during pregnancy. However, there is no evidence of fetal injury with the use of other short-acting inhaled beta-2 agonists, and maintaining a previously established treatment regimen may be more beneficial to the patient. Selection of any pharmacological treatment for asthma control during pregnancy should include the specific needs of the patient, based on an individual evaluation, and consideration of the potential benefits or risks to the fetus. Because of the potential for beta-agonist interference with uterine contractility, use of terbutaline for relief of bronchospasm during labor and obstetric delivery should be restricted to those patients in whom the benefits clearly outweigh the risk. Terbutaline crosses the placenta. After single dose intravenous administration of terbutaline to women in late pregnancy who were delivered by elective Caesarean section due to clinical reasons, umbilical blood levels of terbutaline were found to range from 11% to 48% of the maternal blood levels.

    Premature labor

    Terbutaline has been used systemically off-label to reduce contractions of preterm labor and uterine hyperstimulation. Although, certain acute situations may warrant the use of injectable terbutaline in premature labor, its use is not without risk and a boxed warning addresses the use of terbutaline as tocolysis. Oral terbutaline is contraindicated for acute or maintenance tocolysis as its safety and efficacy have not been established. Terbutaline injection has not been approved and should not be used for prolonged tocolysis (beyond 48 to 72 hours). Do not use for maintenance tocolysis in the outpatient or home setting. Serious adverse reactions, including death, have been reported after administration of terbutaline sulfate to pregnant women. In the mother, these adverse reactions include increased heart rate, transient hyperglycemia, hypokalemia, cardiac arrhythmias, pulmonary edema and myocardial ischemia. Increased fetal heart rate and neonatal hypoglycemia may occur as a result of maternal administration. Therefore, terbutaline administered by injection or by continuous infusion pump is contraindicated for prolonged tocolysis (use beyond 48 to 72 hours).

    Breast-feeding

    Terbutaline is excreted into breast milk in small amounts; based on concentrations in breast milk after oral doses of 7.5 to 15 mg/day, it was estimated that an exclusively breast fed infant would receive 0.2% to 0.7% of the maternal dose. According to the manufacturer, terbutaline should only be used in breast-feeding women if the benefit outweighs the potential risk to the newborn. The American Academy of Pediatrics has previously considered terbutaline to be usually compatible with breast-feeding. Expert panels consider inhaled beta-agonists to be first line over systemic therapy in the lactating mother, due to the low bioavailability and low systemic maternal concentrations. Alternatives to systemic terbutaline would include inhaled albuterol or levalbuterol, for example. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MAOI therapy

    Terbutaline sulfate, like other beta-agonists, should be administered with extreme caution to patients being treated with MAOI therapy or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, since the action of terbutaline sulfate on the vascular system may be potentiated.

    Geriatric

    Geriatric patients may be more sensitive to the side effects of systemic beta-agonists such as terbutaline, especially tremor and tachycardia. Elderly patients may also be at increased risk for QT prolongation. Inhaled bronchodilators are generally preferred over systemic agents. The federal Omnibus Budget Reconciliation Act (OBRA) regulates medication use in residents of long-term care facilities (LTCFs). The OBRA guidelines caution that beta-agonists such as terbutaline can cause restlessness, increased heart rate, and anxiety.

    ADVERSE REACTIONS

    Severe

    seizures / Delayed / 0-1.0
    vasculitis / Delayed / 0-1.0
    pulmonary edema / Early / Incidence not known
    arrhythmia exacerbation / Early / Incidence not known

    Moderate

    palpitations / Early / 5.0-22.9
    sinus tachycardia / Rapid / 1.3-3.5
    dyspnea / Early / 2.0-2.0
    chest pain (unspecified) / Early / 1.3-1.5
    hallucinations / Early / 0-1.0
    hypertonia / Delayed / 0-1.0
    elevated hepatic enzymes / Delayed / 0-1.0
    ST-T wave changes / Rapid / Incidence not known
    premature ventricular contractions (PVCs) / Early / Incidence not known
    hypokalemia / Delayed / Incidence not known
    QT prolongation / Rapid / Incidence not known
    hyperglycemia / Delayed / Incidence not known
    hypoglycemia / Early / Incidence not known

    Mild

    tremor / Early / 8.0-38.0
    drowsiness / Early / 5.5-11.7
    dizziness / Early / 1.3-10.2
    headache / Early / 7.5-8.8
    vomiting / Early / 1.3-3.9
    nausea / Early / 1.3-3.9
    injection site reaction / Rapid / 0.5-2.6
    hyperhidrosis / Delayed / 1.0-2.4
    asthenia / Delayed / 2.0-2.0
    insomnia / Early / 1.5-1.5
    xerostomia / Early / 0.5-1.5
    weakness / Early / 0.5-1.3
    muscle cramps / Delayed / 0-1.0
    paresthesias / Delayed / 0-1.0
    anxiety / Delayed / 1.0-1.0
    rash / Early / 0-1.0

    DRUG INTERACTIONS

    Abarelix: (Major) Since abarelix can cause QT prolongation, abarelix should be used cautiously, if at all, with other drugs that are associated with QT prolongation. Prescribers need to weigh the potential benefits and risks of abarelix use in patients with prolonged QT syndrome or in patients taking other drugs that may prolong the QT interval. Agents associated with a lower, but possible risk for QT prolongation and torsade de pointes (TdP) based on varying levels of documentation include the beta-agonists. Beta-agonists may cause cardiovascular effects, particularly when used in high doses and/or when associated with hypokalemia.
    Acebutolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Acetaminophen; Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Acetaminophen; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Acetaminophen; Caffeine; Magnesium Salicylate; Phenyltoloxamine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Acetaminophen; Caffeine; Phenyltoloxamine; Salicylamide: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Acetaminophen; Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Acetaminophen; Chlorpheniramine; Phenylephrine : (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Acetaminophen; Chlorpheniramine; Phenylephrine; Phenyltoloxamine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Acetaminophen; Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Acetaminophen; Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Acetaminophen; Dextromethorphan; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Acetaminophen; Dextromethorphan; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Acetaminophen; Dichloralphenazone; Isometheptene: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Acetaminophen; Guaifenesin; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Acetaminophen; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Acrivastine; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Amphetamine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Amphetamine; Dextroamphetamine Salts: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Amphetamine; Dextroamphetamine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Articaine; Epinephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Aspirin, ASA; Butalbital; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Aspirin, ASA; Butalbital; Caffeine; Codeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Aspirin, ASA; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Aspirin, ASA; Caffeine; Dihydrocodeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Aspirin, ASA; Caffeine; Orphenadrine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Atenolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Atenolol; Chlorthalidone: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Bendroflumethiazide; Nadolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Benzphetamine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Beta-adrenergic blockers: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Betaxolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Bisoprolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Brimonidine; Timolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Brompheniramine; Carbetapentane; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Brompheniramine; Dextromethorphan; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Brompheniramine; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Brompheniramine; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Brompheniramine; Pseudoephedrine; Dextromethorphan: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Bumetanide: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored.
    Bupivacaine; Epinephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Butalbital; Acetaminophen; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Caffeine; Sodium Benzoate: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Carbetapentane; Chlorpheniramine; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Carbetapentane; Diphenhydramine; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Carbetapentane; Guaifenesin; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Carbetapentane; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Carbetapentane; Phenylephrine; Pyrilamine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Carbetapentane; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Carbinoxamine; Dextromethorphan; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Carbinoxamine; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Carbinoxamine; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Carteolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Carvedilol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Cetirizine; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Chlophedianol; Dexchlorpheniramine; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Chlophedianol; Guaifenesin; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Chlorpheniramine; Dextromethorphan; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Chlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Chlorpheniramine; Dihydrocodeine; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Chlorpheniramine; Ibuprofen; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Chlorpheniramine; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Chlorpheniramine; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Cisapride: (Contraindicated) QT prolongation and ventricular arrhythmias, including torsade de pointes (TdP) and death, have been reported with cisapride. Because of the potential for TdP, use of other drugs that might increase the QT interval is contraindicated with cisapride. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Cocaine: (Moderate) Additive effects and increased toxicity might be observed when using cocaine with beta-agonists, which are sympathomimetic agents. The combined use of these agents may have the potential for additive adrenergic stimulation and side effects, such as nervousness, insomnia, palpitations, or adverse cardiovascular effects.
    Codeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Codeine; Phenylephrine; Promethazine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Desloratadine; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Dexbrompheniramine; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Dexchlorpheniramine; Dextromethorphan; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Dextroamphetamine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Dextromethorphan; Diphenhydramine; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Dextromethorphan; Guaifenesin; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Dextromethorphan; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Diethylpropion: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Dihydrocodeine; Guaifenesin; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Diphenhydramine; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Dobutamine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Dopamine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Dorzolamide; Timolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Ephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Ephedrine; Guaifenesin: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Epinephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Ergotamine; Caffeine: (Moderate) Caffeine may enhance the cardiac inotropic effects of beta-agonists.
    Esmolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Ethacrynic Acid: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored.
    Fexofenadine; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Furosemide: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored.
    Green Tea: (Moderate) Some, but not all, green tea products contain caffeine. Caffeine should be avoided or used cautiously with terbutaline. CNS stimulants are associated with adverse effects such as nervousness, irritability, insomnia, and cardiac arrhythmias.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Guaifenesin; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Guaifenesin; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Halofantrine: (Contraindicated) Halofantrine is considered to have a well-established risk for QT prolongation and torsade de pointes (TdP). Halofantrine should be avoided in patients receiving drugs which may induce QT prolongation. These drugs include the beta-agonists. Beta-agonists may be associated with cardiovascular effects, usually at higher doses and/or when associated with hypokalemia.
    Hydrocodone; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Hydrocodone; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Ibuprofen; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Isocarboxazid: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate.
    Isoproterenol: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Labetalol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Levobetaxolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Levobunolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Levomethadyl: (Contraindicated) Levomethadyl is associated with an established risk of QT prolongation and/or torsade de pointes, particularly at high drug concentrations. Levomethadyl is contraindicated in combination with other agents that may prolong the QT interval. Agents with potential to prolong the QT interval include the beta agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Levothyroxine: (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
    Levothyroxine; Liothyronine (Porcine): (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
    Levothyroxine; Liothyronine (Synthetic): (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
    Lidocaine; Epinephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Linezolid: (Moderate) Linezolid may enhance the hypertensive effect of beta-agonists. Closely monitor for increased blood pressure during coadministration. Linezolid is an antibiotic that is also a weak, reversible nonselective inhibitor of monoamine oxidase (MAO). Therefore, linezolid has the potential for interaction with adrenergic agents, such as the beta-agonists.
    Liothyronine: (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
    Loop diuretics: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored.
    Loratadine; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Mesoridazine: (Contraindicated) Mesoridazine is associated with an established risk of QT prolongation and/or torsade de pointes (TdP). Agents that prolong the QT interval could lead to torsade de pointes are contraindicated with mesoridazine and include the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Methacholine: (Major) Discontinue use of short-acting beta-agonists 6 hours before a methacholine challenge test. Beta-agonists inhibit the airway response to methacholine.
    Methamphetamine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Metoprolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Midodrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Mobocertinib: (Minor) QT/QTc prolongation can occur with concomitant use of mobocertinib and short-acting beta-agonists although the risk of developing torsade de pointes (TdP) is low. Additional steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, may be considered in patients with additional risk factors for TdP. The risk for QT/QTc prolongation may be greater with long-acting beta-agonists than short-acting beta-agonists.
    Monoamine oxidase inhibitors: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate.
    Nadolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Naproxen; Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Nebivolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Nebivolol; Valsartan: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Norepinephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Norfloxacin: (Minor) Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during post-marketing surveillance of norfloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Norfloxacin should be used cautiously with other agents that may prolong the QT interval such as the beta-agonists. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Penbutolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Phendimetrazine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Phenelzine: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate.
    Phentermine: (Moderate) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Phentermine; Topiramate: (Moderate) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Pindolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Prilocaine; Epinephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Procarbazine: (Major) Procarbazine has MAOI activity and the cardiovascular effects of beta-2 agonists may be potentiated by concomitant use of MAOIs. Although no data are available, procarbazine may interact similarly. Close observation for such effects is prudent, particularly if beta-agonists are administered within two weeks of stopping the MAOI.
    Promethazine; Phenylephrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Propranolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Pseudoephedrine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Pseudoephedrine; Triprolidine: (Major) Concomitant use of sympathomimetics with beta-agonists might result in additive cardiovascular effects such as increased blood pressure and heart rate.
    Racepinephrine: (Major) Racepinephrine is a sympathomimetic drug with agonist actions at both the alpha and beta receptors. Patients using prescription beta-agonists for the treatment of asthma should generally avoid the concurrent use of racepinephrine inhalation since additive cardiovascular and nervous system adverse effects are possible, some which may be undesirable.
    Rasagiline: (Moderate) The concomitant use of rasagiline and sympathomimetic agents was not allowed in clinical studies; therefore, caution is advised during concurrent use of rasagiline and respiratory adrenergic agents (e.g., the beta-agonists). Although sympathomimetic agents are contraindicated for use with traditional non-selective monoamine oxidase inhibitors (MAOIs), hypertensive reactions generally are not expected to occur during concurrent use with rasagiline because of the selective monoamine oxidase-B (MAO-B) inhibition of rasagiline at manufacturer recommended doses. However, the cardiovascular effects of beta-2 agonists may be potentiated by concomitant use of MAOIs. At least one case of hypertension occurred in a patient with previous episodes of high blood pressure who was receiving albuterol and selegiline, a selective MAOI related to rasagiline, concurrently. Close observation for such effects is prudent, particularly if beta-2 agonists are administered during or within 2 weeks of use of an MAOI.
    Succinylcholine: (Moderate) Concomitant use of succinylcholine and terbutaline may prolong neuromuscular blockade.
    Theophylline, Aminophylline: (Moderate) Beta-agonists are commonly used in conjunction with aminophylline or theophylline therapy. Concomitant use can cause additive CNS stimulation; some patients may experience tremor or nervousness with combined use. More serious effects are rare, but may result in additive cardiovascular effects such as increased blood pressure and heart rate. Methylxanthine derivatives, ((e.g., theophylline and aminophylline) may rarely aggravate the hypokalemic effect seen with beta-agonists. Consider checking potassium levels if clinically indicated. (Moderate) Beta-agonists are commonly used in conjunction with aminophylline or theophylline therapy. Concomitant use can cause additive CNS stimulation; some patients may experience tremor or nervousness with combined use. More serious effects are rare, but may result in additive cardiovascular effects such as increased blood pressure and heart rate. Methylxanthine derivatives, (e.g., theophylline, aminophylline) may rarely aggravate the hypokalemic effect seen with beta-agonists. Consider checking potassium levels if clinically indicated.
    Thiazide diuretics: (Minor) Hypokalemia associated with thiazide diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded. Although the clinical significance of these effects is unknown, use caution when coadministering beta-agonists with thiazide diuretics and monitor serum potassium as clinically indicated.
    Thyroid hormones: (Moderate) Based on the cardiovascular stimulatory effects of beta-agonists and other sympathomimetics, concomitant use with thyroid hormones might enhance the effects on the cardiovascular system. Concurrent use may increase the effects of sympathomimetics or thyroid hormone. Thyroid hormones may increase the risk of coronary insufficiency when sympathomimetic agents are administered to patients with coronary artery disease.
    Timolol: (Moderate) Use of a beta-1-selective (cardioselective) beta blocker is recommended whenever possible when this combination of drugs must be used together. Monitor the patients lung and cardiovascular status closely. Beta-agonists and beta-blockers are pharmacologic opposites, and will counteract each other to some extent when given concomitantly, especially when non-cardioselective beta blockers are used. Beta-blockers will block the pulmonary effects of inhaled beta-agonists, and in some cases may exacerbate bronchospasm in patients with reactive airways. Beta-agonists can sometimes increase heart rate or have other cardiovascular effects, particularly when used in high doses or if hypokalemia is present.
    Torsemide: (Moderate) Loop diuretics may potentiate hypokalemia and ECG changes seen with beta agonists. Hypokalemia due to beta agonists appears to be dose related and is more likely with high dose therapy. Caution is advised when loop diuretics are coadministered with high doses of beta agonists; potassium levels may need to be monitored.
    Tranylcypromine: (Major) Beta-agonists should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors (MAOIs) due to their sympathomimetic effects. Weigh the risks of coadministration, and where possible, allow a washout period after discontinuation of the MAOI before instituring beta-agonist treatment or vice-versa. The cardiovascular effects of beta-agonists may be potentiated by concomitant use of MAOIs. Close observation for such effects is prudent, particularly if beta-agonists are administered within 2 weeks of stopping the MAOI. Monitor blood pressure and heart rate.

    PREGNANCY AND LACTATION

    Pregnancy

    Terbutaline is excreted into breast milk in small amounts; based on concentrations in breast milk after oral doses of 7.5 to 15 mg/day, it was estimated that an exclusively breast fed infant would receive 0.2% to 0.7% of the maternal dose. According to the manufacturer, terbutaline should only be used in breast-feeding women if the benefit outweighs the potential risk to the newborn. The American Academy of Pediatrics has previously considered terbutaline to be usually compatible with breast-feeding. Expert panels consider inhaled beta-agonists to be first line over systemic therapy in the lactating mother, due to the low bioavailability and low systemic maternal concentrations. Alternatives to systemic terbutaline would include inhaled albuterol or levalbuterol, for example. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally ingested drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    Mechanism of Action: Terbutaline stimulates beta-adrenergic receptors. Unlike isoproterenol, terbutaline is more selective for beta-2 receptors than beta-1 receptors. It has insignificant effects on alpha-receptors. Since the lung contains large quantities of beta-2 receptors (located on bronchiolar smooth muscle), terbutaline causes bronchodilation. Stimulation of beta-2 receptors causes relaxation of bronchial smooth muscle, which, in turn, increases bronchial airflow. Terbutaline probably stimulates activation of the enzyme adenyl cyclase, increasing production of cyclic adenosine monophosphate. The increase in cAMP produces vasodilation and muscle relaxation in vascular and smooth muscle. Increased cAMP may lower intracellular calcium by enhancing the efflux of calcium from vascular smooth muscle cells and preventing calcium transmembrane influx. Cyclic AMP may inactivate myosin kinase, reducing phosphorylation of myosin, resulting in smooth muscle relaxation. Intracellular calcium concentrations and cyclic adenosine monophosphate (cAMP) are interdependent. Tolerance to terbutaline can occur just as it does to other drugs that exert their effects via receptor stimulation. In addition, it has been shown that continuous use of beta-2 agonists for a period of 12 months can accelerate the decline in lung function in asthmatic patients.Beta-receptors, including the beta-2 subtype, also are found in the heart. As a result, all beta-adrenergic bronchodilators are also cardiostimulatory, but terbutaline is less so than isoproterenol. Other effects of beta-2 stimulation include hyperglycemia, uterine relaxation, and vasodilation of systemic arterioles, although beta-adrenergic agonists are poor antihypertensive agents. Terbutaline is specifically used to treat recurrent attacks of bronchial asthma and acute bronchospasm.

    PHARMACOKINETICS

    Terbutaline can be administered orally, parenterally, or via inhalation. Small concentrations are distributed into breast milk and cross the placenta, but studies have not indicated any teratogenic effects in humans. Systemic terbutaline undergoes partial metabolism in the liver and is excreted in the urine, about 60% as unchanged drug and the rest as metabolites, with a small amount excreted via the bile in the feces. The possibility of some GI or first-pass metabolism is indicated by a smaller percentage of unchanged drug excreted following oral administration.

    Oral Route

    Following oral administration, about 30—70% is absorbed from the GI tract. Food reduces the bioavailability by about one-third. Improvement in pulmonary function occurs in 1—2 hours following oral administration. Bronchodilation lasts from 3—8 hours, depending on the route of administration. The possibility of some GI or first-pass metabolism is indicated by a smaller percentage of unchanged drug excreted following oral administration.

    Subcutaneous Route

    Improvement in pulmonary function occurs in 30—60 minutes following subcutaneous injection. Bronchodilation lasts from 3—8 hours, depending on the route of administration.

    Inhalation Route

    Improvement in pulmonary function occurs within 5—30 minutes following aerosol administration. Bronchodilation lasts from 3—8 hours, depending on the route of administration. With continuous daily use of the aerosol, there is a reduction in duration of effectiveness.