(for MOH te rol)
US labeling:
Asthma: Treatment of asthma (only as concomitant therapy with an inhaled corticosteroid) in patients with reversible obstructive airway disease, including patients with symptoms of nocturnal asthma (Foradil Aerolizer).
Chronic obstructive pulmonary disease (COPD): Maintenance treatment of bronchoconstriction in patients with COPD (Foradil Aerolizer, Perforomist).
Exercise-induced bronchospasm: Prevention of exercise-induced bronchospasm when administered on an as-needed basis (monotherapy may be indicated in patients without persistent asthma) (Foradil Aerolizer).
Canadian labeling:
Asthma: Treatment of asthma (only as concomitant therapy with an inhaled corticosteroid) in patients with reversible obstructive airway disease, including patients with symptoms of nocturnal asthma (Foradil, Oxeze Turbuhaler).
COPD: Maintenance treatment of COPD (Foradil).
Exercise-induced bronchospasm: Prevention of exercise-induced bronchospasm when administered on an as-needed basis (monotherapy may be indicated in patients without persistent asthma) (Oxeze Turbuhaler).
Hypersensitivity to formoterol or any component of the formulation (Foradil Aerolizer only); treatment of status asthmaticus or other acute episodes of asthma or COPD (Foradil Aerolizer only); monotherapy in the treatment of asthma (ie, use without a concomitant long-term asthma control medication, such as an inhaled corticosteroid)
Canadian labeling: Additional contraindications (not in U.S. labeling): Presence of tachyarrhythmias
Long-acting beta-2 adrenergic agonists increase the risk of asthma-related death. Data from a large placebo-controlled US study that compared the safety of another long-acting beta-2 adrenergic agonist (salmeterol) or placebo added to usual asthma therapy showed an increase in asthma-related deaths in patients receiving salmeterol. This finding with salmeterol is considered a class effect of long-acting beta-2 adrenergic agonists. Currently available data are inadequate to determine whether concurrent use of inhaled corticosteroids or other long-term asthma control drugs mitigates the increased risk of asthma-related death from long-acting beta-2 adrenergic agonists.
Because of this risk, use of formoterol inhalation powder for the treatment of asthma without a concomitant long-term asthma control medication, such as an inhaled corticosteroid, is contraindicated. Use formoterol only as additional therapy for patients with asthma who are currently taking but are inadequately controlled on a long-term asthma control medication, such as an inhaled corticosteroid. Once asthma control is achieved and maintained, assess the patient at regular intervals and step down therapy (eg, discontinue formoterol) if possible without loss of asthma control, and maintain the patient on a long-term asthma control medication, such as an inhaled corticosteroid. Do not use formoterol for patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.
The safety and efficacy of formoterol inhalation solution in patients with asthma have not been established.
Pediatric and adolescent patients:Available data from controlled clinical trials suggest that long-acting beta-2 adrenergic agonists increase the risk of asthma-related hospitalization in pediatric and adolescent patients. For pediatric and adolescent patients with asthma who require the addition of a long-acting beta-2 adrenergic agonist to an inhaled corticosteroid, a fixed-dose combination product containing an inhaled corticosteroid and long-acting beta-2 adrenergic agonist should ordinarily be considered to ensure adherence with both drugs. In cases in which use of a separate long-term asthma control medication (eg, inhaled corticosteroid) and long-acting beta-2 adrenergic agonist is clinically indicated, appropriate steps must be taken to ensure adherence with both treatment components. If adherence cannot be ensured, a fixed-dose combination product containing an inhaled corticosteroid and long-acting beta-2 adrenergic agonist is recommended.
Note: Foradil Aerolizer is no longer available in the US.
Asthma treatment: Inhalation: Note: For asthma control, long-acting beta2-agonists (LABAs) should be used in combination with inhaled corticosteroids and not as monotherapy.
US labeling: Foradil Aerolizer: 12 mcg every 12 hours (maximum: 24 mcg daily)
Canadian labeling:
Foradil: 12 mcg every 12 hours; in severe cases, 24 mcg every 12 hours may be given (maximum: 48 mcg daily)
Oxeze Turbuhaler: 6 mcg or 12 mcg every 12 hours (maximum: 48 mcg daily)
Prevention of exercise-induced bronchospasm: Inhalation: Note: If already using for asthma maintenance, then should not use additional doses for exercise-induced bronchospasm. Because LABAs may disguise poorly controlled persistent asthma, frequent or chronic use of LABAs for exercise-induced bronchospasm is discouraged by the Asthma Guidelines (NAEPP 2007).
US labeling: Foradil Aerolizer: 12 mcg at least 15 minutes before exercise on an occasional as needed" basis; additional doses should not be used for another 12 hours
Canadian labeling: Oxeze Turbuhaler: 6 mcg or 12 mcg at least 15 minutes before exercise on an occasional as needed" basis (maximum: 48 mcg/24-hour period)
COPD maintenance treatment: Inhalation:
US labeling:
Foradil Aerolizer: 12 mcg every 12 hours (maximum: 24 mcg daily)
Perforomist: 20 mcg twice daily (maximum dose: 40 mcg daily)
Canadian labeling: Foradil: 12 mcg or 24 mcg twice daily (maximum dose: 48 mcg daily)
Refer to adult dosing.
Note: Foradil Aerolizer is no longer available in the US.
Asthma treatment: Inhalation: Note: For asthma control, long-acting beta2-agonists (LABAs) should be used in combination with inhaled corticosteroids and not as monotherapy.
US labeling: Foradil Aerolizer: Children ≥5 years and Adolescents: Refer to adult dosing.
Canadian labeling:
Foradil:
Children 6 to 16 years: 12 mcg every 12 hours (maximum: 24 mcg daily)
Adolescents ≥17 years: Refer to adult dosing.
Oxeze Turbuhaler:
Children 6 to 16 years: 6 mcg or 12 mcg every 12 hours (maximum: 24 mcg daily)
Adolescents ≥17 years: Refer to adult dosing.
Prevention of exercise-induced bronchospasm:Note: If already using for asthma maintenance, then should not use additional doses for exercise-induced bronchospasm. Because LABAs may disguise poorly controlled persistent asthma, frequent or chronic use of LABAs for exercise-induced bronchospasm is discouraged by the Asthma Guidelines (NAEPP 2007).
US labeling: Foradil Aerolizer: Children ≥5 years and Adolescents: Refer to adult dosing.
Canadian labeling: Oxeze Turbuhaler: Children ≥6 years and Adolescents: 6 mcg or 12 mcg at least 15 minutes before exercise on an occasional as needed" basis (maximum: 24 mcg/24-hour period)
No dosage adjustment provided in manufacturers labeling (has not been studied).
No dosage adjustment provided in manufacturers labeling (has not been studied).
Foradil Aerolizer: Remove capsule from foil blister immediately before use. Place capsule in the capsule-chamber in the base of the Aerolizer Inhaler. Capsules must not be swallowed whole; must only use the Aerolizer Inhaler. Press both buttons once only and then release. Keep inhaler in a level, horizontal position. Exhale fully. Do not exhale into inhaler. Tilt head slightly back and inhale (rapidly, steadily, and deeply). Hold breath as long as possible. If any powder remains in capsule, exhale and inhale again. Repeat until capsule is empty. Throw away empty capsule; do not leave in inhaler. Do not use a spacer with the Aerolizer Inhaler. Always keep capsules and inhaler dry.
Perforomist: Remove unit-dose vial from foil pouch immediately before use. Solution does not require dilution prior to administration; do not mix other medications with formoterol solution. Place contents of unit-dose vial into the reservoir of a standard jet nebulizer connected to an air compressor; assemble nebulizer based on the manufacturer 's instructions and turn nebulizer on; breathe deeply and evenly until all of the medication has been inhaled. Discard any unused medication immediately; do not ingest contents of vial. Clean nebulizer after use.
Oxeze Turbuhaler [Canadian product]: Hold inhaler upright. Turn colored grip as far as it will go in one direction and then turn back to original position; a clicking sound should be heard which means the inhaler is ready for use. Exhale fully. Do not exhale into mouthpiece of inhaler. Place mouthpiece to lips and inhale forcefully and deeply. Do not chew or bite on mouthpiece. Clean outside of mouthpiece once weekly with a dry tissue. Avoid getting inhaler wet. If the inhaler is accidently dropped or shaken, or if the patient exhales into the inhaler, the dose will be lost and a new dose should be loaded.
Foradil Aerolizer: Prior to dispensing, store in refrigerator at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F). After dispensing, store at room temperature at 20 ‚ °C to 25 ‚ °C (68 ‚ °F to 77 ‚ °F). Protect from heat and moisture. Capsules should always be stored in the blister and only removed immediately before use.
Perforomist: Prior to dispensing, store in refrigerator at 2 ‚ °C to 8 ‚ °C (36 ‚ °F to 46 ‚ °F). After dispensing, store at 2 ‚ °C to 25 ‚ °C (36 ‚ °F to 77 ‚ °F) for up to 3 months. Protect from heat. Unit-dose vials should always be stored in the foil pouch and only removed immediately before use.
Oxeze Turbuhaler [Canadian product]: Store at 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F). Protect from moisture.
Excipient information presented when available (limited, particularly for generics); consult specific product labeling. [DSC] = Discontinued product
Capsule, Inhalation, as fumarate:
Foradil Aerolizer: 12 mcg [DSC] [contains milk protein]
Nebulization Solution, Inhalation, as fumarate dihydrate:
Perforomist: 20 mcg/2 mL (2 mL)
AtoMOXetine: May enhance the tachycardic effect of Beta2-Agonists. Monitor therapy
AtoMOXetine: May enhance the hypertensive effect of Sympathomimetics. AtoMOXetine may enhance the tachycardic effect of Sympathomimetics. Monitor therapy
Atosiban: Beta2-Agonists may enhance the adverse/toxic effect of Atosiban. Specifically, there may be an increased risk for pulmonary edema and/or dyspnea. Monitor therapy
Beta-Blockers (Beta1 Selective): May diminish the bronchodilatory effect of Beta2-Agonists. Of particular concern with nonselective beta-blockers or higher doses of the beta1 selective beta-blockers. Monitor therapy
Beta-Blockers (Nonselective): May diminish the bronchodilatory effect of Beta2-Agonists. Avoid combination
Betahistine: May diminish the therapeutic effect of Beta2-Agonists. Monitor therapy
Caffeine and Caffeine Containing Products: May enhance the adverse/toxic effect of Formoterol. Caffeine and Caffeine Containing Products may enhance the hypokalemic effect of Formoterol. Monitor therapy
Cannabinoid-Containing Products: May enhance the tachycardic effect of Sympathomimetics. Exceptions: Cannabidiol. Monitor therapy
Doxofylline: Sympathomimetics may enhance the adverse/toxic effect of Doxofylline. Monitor therapy
Highest Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Highest Risk QTc-Prolonging Agents. Management: Avoid such combinations when possible. Use should be accompanied by close monitoring for evidence of QT prolongation or other alterations of cardiac rhythm. Consider therapy modification
Inhalational Anesthetics: May enhance the arrhythmogenic effect of Formoterol. Monitor therapy
Iobenguane I 123: Sympathomimetics may diminish the therapeutic effect of Iobenguane I 123. Avoid combination
Linezolid: May enhance the hypertensive effect of Sympathomimetics. Management: Reduce initial doses of sympathomimetic agents, and closely monitor for enhanced pressor response, in patients receiving linezolid. Specific dose adjustment recommendations are not presently available. Consider therapy modification
Long-Acting Beta2-Agonists: May enhance the adverse/toxic effect of other Long-Acting Beta2-Agonists. Avoid combination
Loop Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Loop Diuretics. Monitor therapy
Loxapine: Agents to Treat Airway Disease may enhance the adverse/toxic effect of Loxapine. More specifically, the use of Agents to Treat Airway Disease is likely a marker of patients who are likely at a greater risk for experiencing significant bronchospasm from use of inhaled loxapine. Management: This is specific to the Adasuve brand of loxapine, which is an inhaled formulation. This does not apply to non-inhaled formulations of loxapine. Avoid combination
MAO Inhibitors: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy
MiFEPRIStone: May enhance the QTc-prolonging effect of QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying). Management: Though the drugs listed here have uncertain QT-prolonging effects, they all have some possible association with QT prolongation and should generally be avoided when possible. Consider therapy modification
Moderate Risk QTc-Prolonging Agents: QTc-Prolonging Agents (Indeterminate Risk and Risk Modifying) may enhance the QTc-prolonging effect of Moderate Risk QTc-Prolonging Agents. Monitor therapy
Sympathomimetics: May enhance the adverse/toxic effect of other Sympathomimetics. Monitor therapy
Tedizolid: May enhance the hypertensive effect of Sympathomimetics. Tedizolid may enhance the tachycardic effect of Sympathomimetics. Monitor therapy
Theophylline Derivatives: May enhance the adverse/toxic effect of Formoterol. Theophylline Derivatives may enhance the hypokalemic effect of Formoterol. Monitor therapy
Thiazide and Thiazide-Like Diuretics: Beta2-Agonists may enhance the hypokalemic effect of Thiazide and Thiazide-Like Diuretics. Monitor therapy
Tricyclic Antidepressants: May enhance the adverse/toxic effect of Beta2-Agonists. Monitor therapy
FEV1, peak flow, and/or other pulmonary function tests; blood pressure, heart rate; CNS stimulation; serum glucose, serum potassium
1% to 10%:
Cardiovascular: Chest pain (2% to 3%)
Central nervous system: Anxiety (2%), dizziness (2%), insomnia (2%), voice disorder (1%), headache
Dermatologic: Pruritus (2%), skin rash (1%)
Gastrointestinal: Diarrhea (5%), nausea (5%), xerostomia (1% to 3%), vomiting (2%), abdominal pain, dyspepsia, gastroenteritis
Neuromuscular & skeletal: Muscle cramps (2%), tremor
Respiratory: Respiratory tract infection (3% to 7%), exacerbation of asthma (ages 5 to 12 years: 5% to 6%; age >12 years: <4%; acute deterioration: <1%), bronchitis (5%), pharyngitis (3% to 4%), sinusitis (3%), dyspnea (2%), tonsillitis (1%)
Miscellaneous: Fever (2%)
<1% (Limited to important or life-threatening): Agitation, anaphylaxis (including severe hypotension/angioedema), angina pectoris, atrial fibrillation, behavioral changes, cardiac arrhythmia, decreased glucose tolerance, dermatitis, disturbed sleep, dysgeusia, hyperglycemia, hypertension, hypokalemia, metabolic acidosis, muscle spasm, nervousness, palpitations, paradoxical bronchospasm, prolonged Q-T interval on ECG, restlessness, tachycardia, variable blood pressure, ventricular premature contractions
Concerns related to adverse effects:
- Asthma-related deaths: [US Boxed Warning]: Long-acting beta2-agonists (LABAs) increase the risk of asthma-related deaths. Formoterol should only be used in asthma patients as adjuvant therapy in patients who are currently receiving but are not adequately controlled on a long-term asthma control medication (ie, an inhaled corticosteroid). Monotherapy with an LABA is contraindicated in the treatment of asthma. In a large, randomized, placebo-controlled U.S. clinical trial (SMART, 2006), salmeterol was associated with an increase in asthma-related deaths (when added to usual asthma therapy); risk is considered a class effect among all LABAs. Data are not available to determine if the addition of an inhaled corticosteroid lessens this increased risk of death associated with LABA use. Assess patients at regular intervals once asthma control is maintained on combination therapy to determine if step-down therapy is appropriate and the LABA can be discontinued (without loss of asthma control), and the patient can be maintained on an inhaled corticosteroid. LABAs are not appropriate in patients whose asthma is adequately controlled on low- or medium-dose inhaled corticosteroids.
- Bronchospasm: Rarely, paradoxical bronchospasm may occur with use of inhaled bronchodilating agents; this should be distinguished from inadequate response.
- Hypersensitivity reactions: Immediate hypersensitivity reactions (urticaria, angioedema, rash, bronchospasm) have been reported.
- Serious effects/fatalities: Do not exceed recommended dose or frequency; serious adverse events, including fatalities, have been associated with excessive use of inhaled sympathomimetics.
Disease-related concerns:
- Asthma: Appropriate use:
Foradil Aerolizer: Do not use for acute bronchospasm. Short-acting beta2-agonist (eg, albuterol) should be used for acute symptoms and symptoms occurring between treatments. Do not initiate in patients with significantly worsening or acutely deteriorating asthma; reports of severe (sometimes fatal) respiratory events have been reported when formoterol has been initiated in this situation. Corticosteroids should not be stopped or reduced when formoterol is initiated. Formoterol is not a substitute for inhaled or systemic corticosteroids and should not be used as monotherapy. During initiation, watch for signs of worsening asthma.
Perforomist: Not FDA approved for the treatment of asthma; safety and efficacy in asthma patients have not been established.
- Cardiovascular disease: Use with caution in patients with cardiovascular disease (arrhythmia, coronary insufficiency, hypertension, HF, or aneurysm); beta-agonists may cause elevation in blood pressure and heart rate and result in CNS stimulation/excitation. Beta2-agonists may also increase risk of arrhythmias and prolong QTc interval.
- Chronic obstructive pulmonary disease (COPD): Appropriate use: Do not use for acute episodes of COPD. Do not initiate in patients with significantly worsening or acutely deteriorating COPD. Data are not available to determine if LABA use increases the risk of death in patients with COPD.
- Diabetes: Use with caution in patients with diabetes mellitus; beta2-agonists may increase serum glucose. The effect is usually transient.
- Exercise-induced bronchospasm: Because LABAs may disguise poorly controlled persistent asthma, frequent or chronic use of LABAs for exercise-induced bronchospasm is discouraged by the NIH Asthma Guidelines (NIH, 2007).
- Hyperthyroidism: Use with caution in hyperthyroidism; may stimulate thyroid activity.
- Hypokalemia: Use with caution in patients with hypokalemia; beta2-agonists may decrease serum potassium, possibly through intracellular shunting.
- Pheochromocytoma: Use with caution in patients with pheochromocytoma; may worsen symptoms.
- Seizures: Use with caution in patients with seizure disorders; beta-agonists may result in CNS stimulation/excitation.
Special populations:
- Pediatric: Foradil Aerolizer: [US Boxed Warning]: LABAs may increase the risk of asthma-related hospitalization in pediatric and adolescent patients. In general, a combination product containing a LABA and an inhaled corticosteroid is preferred in patients <18 years of age to ensure adherence.
Dosage form specific issues:
- Foradil Aerolizer: The contents of the capsules are for inhalation only via the Aerolizer device. There have been reports of incorrect administration (swallowing of the capsules).
- Lactose: Powder for oral inhalation contains lactose; very rare anaphylactic reactions have been reported in patients with severe milk protein allergy.
Other warnings/precautions:
- Patient information: Patients using inhaled, short-acting beta2-agonists should be instructed to discontinue routine use of these medications prior to beginning treatment; short-acting agents should still be provided to patients; however, use should be reserved for symptomatic relief of acute symptoms. Patients must be instructed to seek medical attention in cases where acute symptoms are not relieved or a previous level of response is diminished. The need to increase frequency of use of short-acting beta2-agonists may indicate deterioration of asthma or COPD, and medical evaluation must not be delayed.
- Tolerance/Tachyphylaxis: Tolerance to the bronchodilator effect, measured by FEV1, has been observed in studies.
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Adverse events were observed in some animal reproduction studies. Formoterol has the potential to affect uterine contractility if administered during labor.
Uncontrolled asthma is associated with adverse events on pregnancy (increased risk of perinatal mortality, pre-eclampsia, preterm birth, low birth weight infants). Although data related to its use in pregnancy is limited, formoterol may be used as an alternative agent when a long-acting beta agonist is needed to treat moderate persistent or severe persistent asthma in pregnant women (NAEPP, 2005).
Relaxes bronchial smooth muscle by selective action on beta2 receptors with little effect on heart rate. Formoterol has a long-acting effect.
Rapidly into plasma
Hepatic via direct glucuronidation and O-demethylation; CYP2D6, CYP2C19, CYP2C8/9, CYP2A6 involved in O-demethylation
Children 5-12 years: Urine (6% as unchanged drug, 7% to 9% as direct glucuronide metabolites)
Adults: Urine (15% to 18% as direct glucuronide metabolites, 2% to 10% as unchanged drug)
Powder for inhalation: Within 3 minutes
Peak effect: Powder for inhalation: 80% of peak effect within 15 minutes; Solution for nebulization: 2 hours
Maximum improvement in FEV1 in 1-3 hours
Improvement in FEV1 observed for 12 hours in most patients
Powder: ~10-14 hours; Nebulized solution: ~7 hours
61% to 64% in vitro at higher concentrations than achieved with usual dosing
- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)
- Patient may experience diarrhea. Have patient report immediately to prescriber signs of high blood sugar (confusion, feeling sleepy, more thirst, hunger, passing urine more often, flushing, fast breathing, or breath that smells like fruit), signs of low potassium (muscle pain or weakness, muscle cramps, or an abnormal heartbeat), angina, tachycardia, anxiety, severe dizziness, passing out, fast breathing, chills, pharyngitis, severe headache, severe nausea, vomiting, severe abdominal pain, change in voice, or difficulty breathing, wheezing, or coughing after use (HCAHPS).
- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.
Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.