Perforomist

Drug overview for PERFOROMIST (formoterol fumarate):

Generic name: FORMOTEROL FUMARATE (for-MOW-ter-all)
Drug class: Beta-Adrenergic Agents Long-Acting (Inhaled)
Therapeutic class: Respiratory Therapy Agents

Formoterol fumarate, a synthetic sympathomimetic amine, is a relatively selective, long-acting beta2-agonist.

No enhanced Uses information available for this drug.

DRUG IMAGES

PERFOROMIST 20 MCG/2 ML SOLN

The following indications for PERFOROMIST (formoterol fumarate) have been approved by the FDA:

Indications:
Adjunct maintenance tx for asthma
Bronchospasm prevention with COPD
Exercise-induced bronchospasm prevention

Professional Synonyms:
Adjunct to achieve long-term asthma control
COPD with bronchospasms prophylaxis
Exercise-induced bronchospasm prophylaxis

The following dosing information is available for PERFOROMIST (formoterol fumarate):

Dosing
Administration
PERFOROMIST
FORMOTEROL FUMARATE

Each 2-mL single-dose vial of formoterol fumarate oral inhalation solution contains 20 mcg of formoterol fumarate. The oral inhalation solution does not require dilution prior to administration by nebulization. The actual amount of drug delivered to the lungs will depend on patient factors and the type of nebulization system used and its performance.

Each actuation of the oral aerosol inhaler containing the fixed combination of formoterol fumarate dihydrate and budesonide delivers 5.1 mcg of formoterol fumarate dihydrate and 91 or 181 mcg of budesonide from the valve and delivers 4.5 mcg of formoterol fumarate dihydrate and 80 or 160 mcg of budesonide from the actuator per metered spray, depending on the preparation used.

The strength of formoterol/budesonide preparations and dosage of the fixed combination are expressed in terms of drug delivered from the mouthpiece of the actuator. The actual amount of drug delivered to the lungs depends on factors such as the patient's coordination between the actuation of the inhaler and inspiration through the delivery system. The commercially available formoterol/budesonide aerosol inhaler delivers 60 metered sprays per 6- or 6.9-g

canister and 120 metered sprays per 10.2-g canister.

After priming of the oral aerosol inhaler containing the fixed combination of formoterol fumarate and glycopyrrolate, each actuation of the oral aerosol inhaler (Bevespi(R) Aerosphere(R)) delivers 5.5 mcg of formoterol fumarate and 10.4 mcg of glycopyrrolate (equivalent to 8.3 mcg of glycopyrronium) from the valve.

Dosage is expressed in terms of drug delivered from the mouthpiece; each actuation of the inhaler delivers 4.8 mcg of formoterol fumarate and 9 mcg of glycopyrrolate (equivalent to 7.2 mcg of glycopyrronium) from the actuator. The actual amount of drug delivered to the lungs depends on factors such as the patient's coordination between actuation of the device and inspiration through the delivery system.

Commercially available formoterol/glycopyrrolate aerosol inhaler delivers 28 or 120 metered sprays per 5.9- or 10.7-g canister, respectively.

Each actuation of the oral aerosol inhaler containing the fixed combination of formoterol fumarate dihydrate and mometasone furoate delivers 5.5 mcg of formoterol fumarate dihydrate and 115 or 225 mcg of mometasone furoate from the valve and delivers 5 mcg of formoterol fumarate dihydrate and 100 or 200 mcg of mometasone furoate from the actuator per metered spray, depending on the preparation used. The strength of formoterol/mometasone preparations and dosage of the fixed combination are expressed in terms of drug delivered from the mouthpiece of the actuator.

The actual amount of drug delivered to the lungs may depend on factors such as the patient's coordination between actuation of the device and inspiration through the delivery system. Commercially available formoterol/mometasone aerosol inhaler delivers 60 or 120 metered sprays per 8.8- or 13-g canister, respectively.

Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs. (See Cautions, in Albuterol 12:12.08.12.)

Patients receiving formoterol alone or in fixed combination with budesonide, glycopyrrolate, or mometasone furoate should not use additional formoterol or other long-acting beta2-agonists for any reason.

No enhanced Administration information available for this drug.

Dosing information for PERFOROMIST
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
PERFOROMIST 20 MCG/2 ML SOLN	Maintenance	Adults inhale 2 milliliters (20 mcg) via nebulizer by inhalation route 2 times per day in the morning and evening

Generic dosing information for FORMOTEROL FUMARATE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
FORMOTEROL 20 MCG/2 ML NEB VL	Maintenance	Adults inhale 2 milliliters (20 mcg) via nebulizer by inhalation route 2 times per day in the morning and evening

The following drug interaction information is available for PERFOROMIST (formoterol fumarate):

Contraindicated
Severe
Moderate

There are 0 contraindications.

There are 4 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Ergot Alkaloids/Sympathomimetics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Concurrent use of ergot alkaloids and sympathomimetics may result in additive or synergistic effect on peripheral blood vessels. CLINICAL EFFECTS: Concurrent use of ergot alkaloids and sympathomimetics may result in increased blood pressure due to peripheral vasoconstriction. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: When possible, avoid the concurrent use of ergot alkaloids and sympathomimetics. If concurrent use is warranted, monitor blood pressure and for signs of vasoconstriction. Decreasing the dose of one or both drugs may be necessary. DISCUSSION: There have been reports of severe vasoconstriction resulting in gangrene in patients receiving intravenous ergonovine with dopamine or norepinephrine.	DIHYDROERGOTAMINE MESYLATE, ERGOLOID MESYLATES, ERGOMAR, ERGOTAMINE TARTRATE, ERGOTAMINE-CAFFEINE, METHYLERGONOVINE MALEATE, METHYSERGIDE MALEATE, MIGERGOT, MIGRANAL, TRUDHESA
Selected Inhalation Anesthetic Agents/Sympathomimetics SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: The exact mechanism is unknown. The anesthetics produce conduction changes that increase impulse re-entry into the myocardial tissue.(1) The anesthetics' ability to precipitate arrhythmias is enhanced by elevated arterial blood pressure, tachycardia, hypercapnia, and/or hypoxia, events that stimulate the release of endogenous catecholamines.(1) CLINICAL EFFECTS: Concurrent use of inhalation anesthetic agents and sympathomimetics may result in ventricular arrhythmias or sudden blood pressure and heart rate increase during surgery.(2) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Monitor blood pressure and avoid use of sympathomimetics in patients being treated with anesthetics on the day of surgery.(2) Intravenous use of epinephrine during surgery with halothane and related halogenated general anesthetics should be strongly discouraged. When intravenous epinephrine is necessary, nitrous oxide anesthesia supplemented with ether, muscle relaxants, or opioids should be used instead of halothane.(3,4) Epinephrine may safely be used subcutaneously with the following precautions: the patient is adequately ventilated to prevent hypoxia or respiratory acidosis; the total dose of epinephrine is limited to 100 mcg/10 minute period or 300 mcg/hour in adults, 3.5 mcg/Kg in infants, 2.5 mcg/Kg in children up to two years of age, and 1.45 mcg/Kg in children over two years of age; a minimum effective concentration of anesthetic is maintained; the drugs are not co-administered in patients with hypertension or other cardiovascular disorders; and the cardiac rhythm is continuously monitored during and after injection.(3-10) If arrhythmias occur after the administration of the epinephrine, the drugs of choice are lidocaine or propranolol, depending on the type of arrhythmia.(1) DISCUSSION: Administration of epinephrine during halothane anesthesia may may lead to serious ventricular arrhythmias.(3-6,11-18) This has occurred when epinephrine was administered intravenously,(6) when it was administered with lidocaine as a dental block,(11,14) or when it was administered supraperiosteally.(5) Norepinephrine has been shown to interact with halothane in a manner similar to epinephrine.(1) In two case reports, patients were given terbutaline (0.25 to 0.35 mg) for wheezing following induction of anesthesia with halothane. One patient's heart rate increased from 68 to 100 beats/minute, and the ECG showed premature ventricular contractions and bigeminy, while the other patient developed multiple unifocal premature ventricular contractions and bigeminy. The arrhythmias resolved in both patients following lidocaine administration.(19) Although not documented, isoproterenol causes effects on the heart similar to terbutaline(20) and would probably interact with halothane in a similar manner. Other inhalation anesthetics that increase the incidence of arrhythmias with epinephrine include chloroform,(20) methoxyflurane,(20) and enflurane.(12) A similar interaction may be expected between the other inhalation anesthetics and sympathomimetics.	DESFLURANE, FORANE, ISOFLURANE, SEVOFLURANE, SUPRANE, TERRELL, ULTANE
Beta-2 Agonists/Non-Cardioselective Beta-Blockers SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Non-cardioselective beta-blockers and beta-2 agonists may antagonize the effects of each other. CLINICAL EFFECTS: Diminished response to either the beta-agonist, beta-blocker, or both may occur. Beta-blockers may also induce bronchospasm. PREDISPOSING FACTORS: Patients receiving beta-2 agonists for the treatment of asthma may be more at risk for bronchospasm. PATIENT MANAGEMENT: If possible, avoid beta-blocker therapy in asthmatic patients requiring beta-2 agonist therapy. If beta-blocker therapy is required, use a cardio-selective beta-blocker. For timolol ophthalmic drops, counsel patients to apply pressure to the inner corner of the eye after administration to prevent systemic absorption. Monitor patients for decreased effects of either agent, such as increased need for/use of beta-2 agonists or increased heart rate or blood pressure. DISCUSSION: Many patients with asymptomatic or mild reactive airways disease tolerate beta-blockers well. Most patients with COPD do not have bronchospastic component to their illness and may be given beta-blockers. Heart failure treatment guidelines recommend beta-blockers in the presence of COPD. Non-selective beta-blockers have been shown to have a negative effect on lung function (FEV1) and airway hyperresponsiveness (AHR) in patients with asthma and COPD.(1) An open-label study using the nonselective beta blocker nadolol showed no effect on salbutamol in 10 patients with mild asthma not on controller therapy.(2) A study in 8 healthy men showed that long acting propranolol (160 mg) only effected airway dilation at the 200 mcg salbutamol dose. The 800 mcg and 1600 mcg dose were unaffected. However, penbutolol prevented any significant airway dilation with all doses of salbutamol.(3) In a double blind, three-way, crossover study, 44% (7/16 patients) of patients taking metoprolol showed a greater than 20% decrease in FEV1 compared to 19% (3 patients) after dilevalol and 6% (1 patient) after placebo. Dilevalol and metoprolol significantly inhibited isoproterenol response compared to placebo.(4) A double-blind, randomized, crossover study in 10 asthmatic patients showed that intravenous propranolol produced marked symptomatic bronchoconstriction. Only a slight but significant inhibition of bronchomotor sensitivity to isoproterenol was noted during esmolol infusion.(5) In 18 patients with reversible bronchial asthma, labetalol caused a significant increase in FEV1 and metoprolol caused a significant decrease in FEV1. Concurrent administration of isoproterenol and labetalol caused a further increase in FEV1. The effect of isoproterenol was decreased by metoprolol (100, 200mg).(6) In one study propranolol (0.06mg/kg IV) was shown to almost completely block the effects of isoproterenol in asthmatics. Metoprolol (0.12mg/kg IV) did not affect isoproterenol.(7) Studies have shown that cardioselective beta-blockers are safe for patients with asthma and COPD.(8,9,10) Nebivolol and celiprolol significantly decreased FEV1. Inhalation of albuterol (up to 800mcg) significantly improved FEV1, but the values after nebivolol and celiprolol administration were lower than the initial values.(11) Administration of metoprolol did not cause any respiratory problems in 9 asthmatic patients. There was no significant difference between the metoprolol and placebo groups in the respiratory response to an isoproterenol aerosol in 24 asthmatic patients.(12) Eight male asthmatic patients were given 10 mg bisoprolol, 20 mg bisoprolol, and 100 mg metoprolol. Both bisoprolol and metoprolol caused bronchoconstriction measured by a significant fall in PEFR (peak expiratory flow rate). Terbutaline was able to reverse bronchoconstriction in all patients.(13) A double blind, placebo-controlled study analyzed the use of atenolol 100mg, metoprolol 100mg, or acebutolol 400 mg in 8 asthmatic patients before and after exercise. All three drugs reduced significantly FEV1 and PEFR. Administration of terbutaline improved all respiratory indices.(14) A double-blind crossover trial in 10 asthmatic patients showed that a single IV dose of atenolol 3mg caused slight impairment of ventilatory function. A dose of salbutamol by inhalation was able to reverse the bronchial effect of atenolol.(15) Propranolol (80mg/day), oxprenolol (80mg/day), atenolol (100mg/day), and celiprolol 200mg/day were given to 10 asthmatic patients in a randomized, crossover design with a two week washout period between each drug. The non-beta 1 selective beta blockers (propranolol, oxprenolol) caused a significant reduction in FEV1 and inhibited the bronchodilator response to inhaled salbutamol. Atenolol and celiprolol (beta1 selective beta blockers) did not significantly affect respiratory function or antagonize salbutamol effects.(16) A double blind, randomized, within patient, placebo-controlled study compared the cardioselective beta-blocker atenolol to the non-selective propranolol. Atenolol caused a significantly less drop in FEV1 compared to propranolol. The effect of isoprenaline plus the beta blockers were also studied. Both atenolol and propranolol effected isoprenaline FEV1 dose response curves but the greatest displacement was seen with propranolol.(17) The pulmonary effects of celiprolol 200 mg, celiprolol 400mg, propranolol 40mg, atenolol 100 mg were evaluated in 34 asthmatic patients. Propranolol and atenolol caused significant reductions in pulmonary function. Propranolol pretreatment caused a significant reduction in the effect of the bronchodilator. Celiprolol did not antagonize the bronchodilators.(18) A double-blind, placebo controlled, randomized, crossover design study studied the effects of propranolol 80mg or celiprolol 200 or 400mg on pulmonary function. Propranolol produced a significant decrease in FEV1 and FVC. Celiprolol and placebo had similar results. The effect of aerosolized terbutaline was also measured. Even at supratherapeutic doses, terbutaline was unable to restore pulmonary function parameters to baseline levels after treatment with propranolol. Terbutaline caused further bronchodilation after administration of celiprolol.(19) Eleven asthmatic patients showed significant bronchoconstriction in small airways after propranolol 40mg and pindolol 2.5mg in a double blind, randomized trial. Large airways only showed bronchoconstriction with propranolol. Terbutaline 0.5mg subcutaneous was given after pretreatment with propranolol and pindolol. The bronchodilator effect of terbutaline on large airways was diminished after both propranolol and timolol.(20)	BETAPACE, BETAPACE AF, BETIMOL, BRIMONIDINE TARTRATE-TIMOLOL, CARVEDILOL, CARVEDILOL ER, COMBIGAN, COREG, COREG CR, CORGARD, COSOPT, COSOPT PF, DORZOLAMIDE-TIMOLOL, HEMANGEOL, INDERAL LA, INDERAL XL, INNOPRAN XL, ISTALOL, LABETALOL HCL, LABETALOL HCL-WATER, NADOLOL, PINDOLOL, PROPRANOLOL HCL, PROPRANOLOL HCL ER, PROPRANOLOL-HYDROCHLOROTHIAZID, SOTALOL, SOTALOL AF, SOTALOL HCL, SOTYLIZE, TIMOLOL, TIMOLOL MALEATE, TIMOLOL-BIMATOPROST, TIMOLOL-BRIMONI-DORZOL-BIMATOP, TIMOLOL-BRIMONIDIN-DORZOLAMIDE, TIMOLOL-DORZOLAMIDE-BIMATOPRST, TIMOPTIC OCUDOSE
Iobenguane I 123/Agents that Affect Catecholamines SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Many compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with iobenguane uptake into cells.(1) CLINICAL EFFECTS: Compounds that reduce catecholamine uptake or that deplete catecholamine stores may interfere with imaging completed with iobenguane.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Discuss the use of agents that affect catecholamines. Discontinue drugs that reduce catecholamine uptake or deplete catecholamine stores prior to imaging with iobenguane. Before imaging with iobenguane, discontinue agents that affect catecholamines for at least 5 biological half-lives, as clinically tolerated.(1) DISCUSSION: Many agents may reduce catecholamine uptake or deplete catecholamine stores.(1) Examples include: - CNS stimulants or amphetamines (e.g. cocaine, methylphenidate, dextroamphetamine) - norepinephrine and dopamine reuptake inhibitors (e.g. phentermine) - norepinephrine and serotonin reuptake inhibitors (e.g. tramadol) - monoamine oxidase inhibitors (e.g. phenelzine, linezolid) - central monoamine depleting drugs (e.g. reserpine) - non-select beta adrenergic blocking drugs (e.g. labetalol) - alpha agonists or alpha/beta agonists (e.g. pseudoephedrine, phenylephrine, ephedrine, phenylpropanolamine, naphazoline) - tricyclic antidepressants or norepinephrine reuptake inhibitors (e.g. amitriptyline, bupropion, duloxetine, mirtazapine, venlafaxine) - botanicals that may inhibit reuptake of norepinephrine, serotonin or dopamine (e.g. ephedra, ma huang, St. John's Wort, yohimbine)	ADREVIEW

There are 2 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Inhaled Direct-Acting Sympathomimetics/Tricyclic Compounds SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Unknown. However, it is speculated that direct-acting sympathomimetic amines have an enhanced effect due to tricyclic blockage of norepinephrine reuptake. CLINICAL EFFECTS: Increased effect of direct acting sympathomimetics. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The concurrent use of inhaled sympathomimetics and tricyclic compounds or the use of these agents within 14 days of each other should be approached with extreme caution. DISCUSSION: Epinephrine and other direct-acting sympathomimetic amines exert enhanced cardiovascular effects (e.g., arrhythmias, hypertension, and tachycardia) in individuals concurrently receiving or previously treated with tricyclic antidepressants. Protriptyline, amitriptyline, and desipramine have also been reported to interact with direct-acting sympathomimetics. Similarity between cyclobenzaprine and the tricyclic antidepressants consideration of tricyclic antidepressant interactions for cyclobenzaprine.	AMITRIPTYLINE HCL, AMOXAPINE, AMRIX, ANAFRANIL, CHLORDIAZEPOXIDE-AMITRIPTYLINE, CLOMIPRAMINE HCL, CYCLOBENZAPRINE HCL, CYCLOBENZAPRINE HCL ER, CYCLOPAK, CYCLOTENS, DESIPRAMINE HCL, DOXEPIN HCL, FEXMID, IMIPRAMINE HCL, IMIPRAMINE PAMOATE, NORPRAMIN, NORTRIPTYLINE HCL, PAMELOR, PERPHENAZINE-AMITRIPTYLINE, PROTRIPTYLINE HCL, SILENOR, TRIMIPRAMINE MALEATE
Methacholine/Beta-Agonists; Anticholinergics; Theophylline SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Beta-agonists, anticholinergics, and theophylline may inhibit the action of methacholine on the airway.(1) CLINICAL EFFECTS: The result of the methacholine challenge test may not be accurate.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The following drugs should be held before a methacholine challenge for the the duration indicated:(1) - short-acting beta-agonists: 6 hours - long-acting beta-agonists: 36 hours - short-acting anti-cholinergics: 12 hours - long-acting anti-cholinergics: at least 168 hours (7 days) - oral theophylline: 12-48 hours DISCUSSION: Beta-agonists, anticholinergics, and theophylline may inhibit the action of methacholine on the airway and cause inaccurate test results.	METHACHOLINE CHLORIDE, PROVOCHOLINE

Drug Interaction

Drug Names

Inhaled Direct-Acting Sympathomimetics/Tricyclic Compounds

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Unknown. However, it is speculated that direct-acting sympathomimetic amines have an enhanced effect due to tricyclic blockage of norepinephrine reuptake.

CLINICAL EFFECTS: Increased effect of direct acting sympathomimetics.

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The concurrent use of inhaled sympathomimetics and tricyclic compounds or the use of these agents within 14 days of each other should be approached with extreme caution.

DISCUSSION: Epinephrine and other direct-acting sympathomimetic amines exert enhanced cardiovascular effects (e.g., arrhythmias, hypertension, and tachycardia) in individuals concurrently receiving or previously treated with tricyclic antidepressants. Protriptyline, amitriptyline, and desipramine have also been reported to interact with direct-acting sympathomimetics. Similarity between cyclobenzaprine and the tricyclic antidepressants consideration of tricyclic antidepressant interactions for cyclobenzaprine.

AMITRIPTYLINE HCL, AMOXAPINE, AMRIX, ANAFRANIL, CHLORDIAZEPOXIDE-AMITRIPTYLINE, CLOMIPRAMINE HCL, CYCLOBENZAPRINE HCL, CYCLOBENZAPRINE HCL ER, CYCLOPAK, CYCLOTENS, DESIPRAMINE HCL, DOXEPIN HCL, FEXMID, IMIPRAMINE HCL, IMIPRAMINE PAMOATE, NORPRAMIN, NORTRIPTYLINE HCL, PAMELOR, PERPHENAZINE-AMITRIPTYLINE, PROTRIPTYLINE HCL, SILENOR, TRIMIPRAMINE MALEATE

Methacholine/Beta-Agonists; Anticholinergics; Theophylline

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Beta-agonists, anticholinergics, and theophylline may inhibit the action of methacholine on the airway.(1)

CLINICAL EFFECTS: The result of the methacholine challenge test may not be accurate.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The following drugs should be held before a methacholine challenge for the the duration indicated:(1) - short-acting beta-agonists: 6 hours - long-acting beta-agonists: 36 hours - short-acting anti-cholinergics: 12 hours - long-acting anti-cholinergics: at least 168 hours (7 days) - oral theophylline: 12-48 hours

DISCUSSION: Beta-agonists, anticholinergics, and theophylline may inhibit the action of methacholine on the airway and cause inaccurate test results.

METHACHOLINE CHLORIDE, PROVOCHOLINE

The following contraindication information is available for PERFOROMIST (formoterol fumarate):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

Formoterol fumarate and fixed combinations containing formoterol fumarate are contraindicated in patients hypersensitive to the drug or any ingredient in the formulation. Because of the risk of asthma-related death and hospitalization, use of formoterol for the treatment of asthma without concomitant use of long-term asthma controller therapy, such as inhaled corticosteroids, is contraindicated. (See Asthma-related Death and Serious Asthma-related Events under Warnings/Precautions: Warnings, in Cautions and also see Uses: Bronchospasm.) Formoterol fumarate in fixed combination with budesonide (formoterol/budesonide; Symbicort(R)) and formoterol fumarate in fixed combination with mometasone furoate (formoterol/mometasone; Dulera(R)) are contraindicated as primary treatment of status asthmaticus or other acute episodes of asthma or chronic obstructive pulmonary disease (COPD) when intensive measures are required. Formoterol fumarate in fixed combination with glycopyrrolate (formoterol/glycopyrrolate; Bevespi(R) Aerosphere(R)) is not indicated for the treatment of asthma.

There are 1 contraindications. Absolute contraindication.

Contraindication List
Acute asthma attack

There are 3 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Congenital long QT syndrome
Hypokalemia
Prolonged QT interval

There are 6 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Cardiac arrhythmia
Chronic myocardial ischemia
Diabetes mellitus
Hypertension
Seizure disorder
Thyrotoxicosis

The following adverse reaction information is available for PERFOROMIST (formoterol fumarate):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects occurring in 2% or more of adults in clinical trials receiving formoterol fumarate oral inhalation solution for the treatment of COPD include diarrhea, nausea, vomiting, nasopharyngitis, dry mouth, dizziness, and insomnia. Adverse effects occurring in 3% or more of patients receiving formoterol fumarate in fixed combination with budesonide for the treatment of asthma include nasopharyngitis, headache, upper respiratory tract infection, pharyngolaryngeal pain, sinusitis, influenza, back pain, nasal congestion, stomach discomfort, vomiting, and oral candidiasis. Adverse effects occurring in 3% or more of patients receiving formoterol fumarate in fixed combination with budesonide for the treatment of COPD include nasopharyngitis, oral candidiasis, bronchitis, sinusitis, and upper respiratory tract infection.

Adverse effects occurring in 2% or more of patients receiving formoterol fumarate in fixed combination with glycopyrrolate for the treatment of COPD and more frequently than in those receiving placebo include urinary tract infection and cough. Adverse effects occurring in 3% or more of patients receiving formoterol fumarate in fixed combination with mometasone furoate for the treatment of asthma and more frequently than in those receiving placebo include nasopharyngitis, sinusitis, and headache.

There are 17 severe adverse reactions.

More Frequent	Less Frequent
None.	Chest pain Tremor

Rare/Very Rare
Anaphylaxis Angina Angioedema Asthma exacerbation Atrial fibrillation Cardiac arrhythmia Hyperglycemia Hypertension Hypokalemia Hypotension Malaise Metabolic acidosis Paradoxical bronchospasm Tachycardia Ventricular premature beats

There are 18 less severe adverse reactions.

More Frequent	Less Frequent
Diarrhea Dizziness Headache disorder Insomnia Nausea Pharyngitis Vomiting Xerostomia	Cough Cramps Dyspnea

Rare/Very Rare
Fatigue Nervousness Palpitations Pruritus of skin Skin rash Symptoms of anxiety Urticaria

The following precautions are available for PERFOROMIST (formoterol fumarate):

Pediatric
Pregnant
Lactation
Geriatric

Formoterol fumarate oral inhalation solution (Perforomist(R)) and formoterol fumarate in fixed combination with glycopyrrolate (Bevespi(R) Aerosphere(R)) are not indicated for use in children. Safety and efficacy of these preparations in children have not been established. Safety and efficacy of formoterol fumarate in fixed combination with budesonide (Symbicort(R)) in pediatric patients 12 years of age or older with asthma have been established in studies of up to 12 months' duration.

Safety and efficacy of formoterol/budesonide in pediatric patients 6 to less than 12 years of age with asthma have been established in studies of up to 12 weeks' duration; however, the manufacturer states that safety and efficacy of the fixed-combination preparation in children younger than 6 years of age with asthma have not been established. Safety and efficacy of formoterol fumarate in fixed combination with mometasone furoate (Dulera(R)) in pediatric patients 12 years of age or older with asthma have been established in studies of up to 12 months' duration. Available data from controlled clinical trials suggest that monotherapy with long-acting beta2-adrenergic agonists increases the risk of asthma-related hospitalization in pediatric and adolescent patients. (See Asthma-related Death and Serious Asthma-related Events under Warnings/Precautions: Warnings, in Cautions.)

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Category C. (See Users Guide.) Formoterol may interfere with uterine contractility; carefully weigh benefit versus risk in labor. There is an increased risk of adverse perinatal outcomes (e.g., preeclampsia, premature birth, low birth weight, and neonates small for gestational age) in women with poorly or moderately controlled asthma.

Pregnant women with asthma should be closely monitored and therapy adjusted as necessary to maintain optimal asthma control. The effects of formoterol fumarate in fixed combination with budesonide, glycopyrrolate, or mometasone furoate during labor and delivery are not known. Because of the potential for beta-agonist interference with uterine contractility, use of formoterol in fixed combination with budesonide, glycopyrrolate, or mometasone during labor should be restricted to those patients in whom the benefits clearly outweigh the risk.

Formoterol is distributed into milk in rats; it is not known whether formoterol is distributed into human milk. Effects of formoterol fumarate on breast-fed infants or milk production also are not known. The benefits of breast-feeding and the woman's clinical need for formoterol fumarate alone or in fixed combination with budesonide or mometasone should be considered along with any potential adverse effects on the breast-fed infant from the drug or from the underlying maternal condition.

Because many drugs are distributed into human milk, caution should be exercised when formoterol fumarate in fixed combination with glycopyrrolate is administered to nursing women. Since there are no data from controlled clinical studies, the manufacturer of formoterol/glycopyrrolate states that a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

No substantial differences in safety and efficacy of formoterol alone or in fixed combination with budesonide, glycopyrrolate, or mometasone furoate have been observed in geriatric patients relative to younger adults. However, the manufacturers state that the possibility that some geriatric patients may exhibit increased sensitivity to formoterol or fixed combinations containing formoterol cannot be ruled out. (See Dosage and Administration: Special Populations.)

The following icd codes are available for PERFOROMIST (formoterol fumarate)'s list of indications:

Adjunct maintenance tx for asthma
J45.40	Moderate persistent asthma, uncomplicated
J45.50	Severe persistent asthma, uncomplicated
J45.909	Unspecified asthma, uncomplicated
J45.991	Cough variant asthma
J45.998	Other asthma
Bronchospasm prevention with COPD
J44	Other chronic obstructive pulmonary disease
J44.8	Other specified chronic obstructive pulmonary disease
J44.89	Other specified chronic obstructive pulmonary disease
J44.9	Chronic obstructive pulmonary disease, unspecified
Exercise-induced bronchospasm prevention
J45.990	Exercise induced bronchospasm