Generic Name: LEVALBUTEROL HYDROCHLORIDE
Brand Name: Xopenex
- Substance Name(s):
- LEVALBUTEROL HYDROCHLORIDE
7 Other short-acting sympathomimetic aerosol bronchodilators and adrenergic drugs: May potentiate effect.
( 7.1 ) Beta-blockers: May block bronchodilatory effects of beta-agonists and produce severe bronchospasm.
Patients with asthma should not normally be treated with beta-blockers.
( 7.2 ) Diuretic: May worsen electrocardiographic changes or hypokalemia associated with diuretic may worsen.
Consider monitoring potassium levels.
( 7.3 ) Digoxin: May decrease serum digoxin levels.
Consider monitoring digoxin levels.
( 7.4 ) Monoamine oxidase inhibitors (MAOs) or tricyclic antidepressants: May potentiate effect of albuterol on the cardiovascular system.
( 7.5 ) 7.1 Short-Acting Bronchodilators Avoid concomitant use of other short-acting sympathomimetic bronchodilators or epinephrine in patients being treated with XOPENEX Inhalation Solution.
If additional adrenergic drugs are to be administered by any route, they should be used with caution to avoid deleterious cardiovascular effects.
7.2 Beta-blockers Beta-adrenergic receptor blocking agents not only block the pulmonary effect of beta-adrenergic agonists such as XOPENEX Inhalation Solution, but may produce severe bronchospasm in asthmatic patients.
Therefore, patients with asthma should not normally be treated with beta-blockers.
However, under certain circumstances, e.g., prophylaxis after myocardial infarction, there may be no acceptable alternatives to the use of beta-adrenergic blocking agents in patients with asthma.
In this setting, cardioselective beta-blockers should be considered, although they should be administered with caution.
7.3 Diuretics The ECG changes or hypokalemia that may result from the administration of non-potassium-sparing diuretics (such as loop and 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 not known, caution is advised in the coadministration of beta-agonists with non-potassium-sparing diuretics.
Consider monitoring potassium levels.
7.4 Digoxin Mean decreases of 16% and 22% in serum digoxin levels were demonstrated after single-dose intravenous and oral administration of racemic albuterol, respectively, to normal volunteers who had received digoxin for 10 days.
The clinical significance of these findings for patients with obstructive airway disease who are receiving XOPENEX Inhalation Solution and digoxin on a chronic basis is unclear.
Nevertheless, it would be prudent to carefully evaluate the serum digoxin levels in patients who are currently receiving digoxin and XOPENEX Inhalation Solution.
7.5 Monoamine Oxidase Inhibitors or Tricyclic Antidepressants XOPENEX Inhalation Solution should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of levalbuterol on the vascular system may be potentiated.
Consider alternative therapy in patients taking MAO inhibitors or tricyclic antidepressants.
10 The expected symptoms with overdosage are those of excessive beta-adrenergic receptor stimulation and/or occurrence or exaggeration of any of the symptoms listed under Adverse Reactions ( 6 ) , e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min., arrhythmias, nervousness, headache, tremor, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, and sleeplessness.
Hypokalemia also may occur.
As with all sympathomimetic medications, cardiac arrest and even death may be associated with the abuse of XOPENEX Inhalation Solution.
Treatment consists of discontinuation of XOPENEX Inhalation Solution together with appropriate symptomatic therapy.
The judicious use of a cardio selective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm.
There is insufficient evidence to determine if dialysis is beneficial for overdosage of XOPENEX Inhalation Solution.
11 XOPENEX Inhalation Solution Concentrate is a sterile, clear, colorless, preservative-free solution of the hydrochloride salt of levalbuterol, the (R)-enantiomer of the drug substance racemic albuterol.
Levalbuterol HCl is a relatively selective beta 2 -adrenergic receptor agonist [see Clinical Pharmacology ( 12 ) ].
The chemical name for levalbuterol HCl is (R)-α 1 -[[(1,1-dimethylethyl)amino]methyl]-4-hydroxy-1,3-benzenedimethanol hydrochloride, and its established chemical structure is as follows: The molecular weight of levalbuterol HCl is 275.8, and its empirical formula is C 13 H 21 NO 3 •HCl.
It is a white to off-white, crystalline solid, with a melting point of approximately 187°C and solubility of approximately 180 mg/mL in water.
Levalbuterol HCl is the USAN modified name for (R)-albuterol HCl in the United States.
XOPENEX Inhalation Solution Concentrate is supplied in 0.5 mL unit-dose vials that must be diluted with normal saline before administration by nebulization.
Each 0.5 mL unit-dose vial contains 1.25 mg of levalbuterol (as 1.44 mg of levalbuterol HCl), sodium chloride to adjust tonicity, and hydrochloric acid to adjust the pH to 4.0 (3.3 to 4.5).
14 Adults and Adolescents ≥12 Years Old The safety and efficacy of XOPENEX Inhalation Solution were evaluated in a 4-week, multicenter, randomized, double-blind, placebo-controlled, parallel-group study in 362 adult and adolescent patients 12 years of age and older, with mild-to-moderate asthma (mean baseline FEV 1 60% of predicted).
Approximately half of the patients were also receiving inhaled corticosteroids.
Patients were randomized to receive XOPENEX 0.63 mg, XOPENEX 1.25 mg, racemic albuterol sulfate 1.25 mg, racemic albuterol sulfate 2.5 mg, or placebo three times a day administered via a PARI LC Plus™ nebulizer and a Dura-Neb ® portable compressor.
Racemic albuterol delivered by a chlorofluorocarbon (CFC) metered-dose inhaler (MDI) was used on an as-needed basis as the rescue medication.
Efficacy, as measured by the mean percent change from baseline FEV 1 , was demonstrated for all active treatment regimens compared with placebo on day 1 and day 29.
On both day 1 (see Figure 1 ) and day 29 (see Figure 2 ), 1.25 mg of XOPENEX demonstrated the largest mean percent change from baseline FEV 1 compared with the other active treatments.
A dose of 0.63 mg of XOPENEX and 2.5 mg of racemic albuterol sulfate produced a clinically comparable mean percent change from baseline FEV 1 on both day 1 and day 29.
Figure 1: Mean Percent Change from Baseline FEV 1 on Day 1, Adults and Adolescents ≥12 years old Figure 2: Mean Percent Change from Baseline FEV 1 on Day 29, Adults and Adolescents ≥12 years old The mean time to onset of a 15% increase in FEV 1 over baseline for levalbuterol at doses of 0.63 mg and 1.25 mg was approximately 17 minutes and 10 minutes, respectively, and the mean time to peak effect for both doses was approximately 1.5 hours after 4 weeks of treatment.
The mean duration of effect, as measured by a >15% increase from baseline FEV 1 , was approximately 5 hours after administration of 0.63 mg of levalbuterol and approximately 6 hours after administration of 1.25 mg of levalbuterol after 4 weeks of treatment.
In some patients, the duration of effect was as long as 8 hours.
Figure 1 Figure 2 Children 6 to 11 Years Old A multicenter, randomized, double-blind, placebo- and active-controlled study was conducted in children with mild-to-moderate asthma (mean baseline FEV 1 73% of predicted) (n=316).
Following a 1-week placebo run-in, subjects were randomized to XOPENEX (0.31 or 0.63 mg), racemic albuterol (1.25 or 2.5 mg), or placebo, which were delivered three times a day for 3 weeks using a PARI LC Plus™ nebulizer and a Dura-Neb ® 3000 compressor.
Efficacy, as measured by mean peak percent change from baseline FEV 1 , was demonstrated for all active treatment regimens compared with placebo on day 1 and day 21.
Time profile FEV 1 curves for day 1 and day 21 are shown in Figure 3 and Figure 4 , respectively.
The onset of effect (time to a 15% increase in FEV 1 over test-day baseline) and duration of effect (maintenance of a >15% increase in FEV 1 over test-day baseline) of levalbuterol were clinically comparable to those of racemic albuterol.
Figure 3: Mean Percent Change from Baseline FEV 1 on Day 1, Children 6 to 11 Years of Age Figure 4: Mean Percent Change from Baseline FEV 1 on Day 21, Children 6 to 11 Years of Age Figure 3 Figure 4
16 /STORAGE AND HANDLING XOPENEX (levalbuterol HCl) Inhalation Solution Concentrate ( foil pouch label color red ) is supplied in 0.5 mL unit-dose, low-density polyethylene (LDPE) vials as a clear, colorless, sterile, preservative-free, aqueous solution.
Each vial contains 1.25 mg of levalbuterol (as 1.44 mg of levalbuterol HCl) and is available in cartons of 30 (NDC 17478-171-30) individually pouched vials.
XOPENEX Inhalation Solution is also available in 3 mL vials in three different strengths of levalbuterol: 0.31 mg (NDC 17478-172-24), 0.63 mg (NDC 17478-173-24), and 1.25 mg (NDC 17478-174-24).
Store XOPENEX Inhalation Solution Concentrate in the protective foil pouch at 20º to 25°C (68º to 77°F) [see USP Controlled Room Temperature].
Protect from light and excessive heat.
Open the foil pouch just prior to administration.
Once the foil pouch is opened, the contents of the vial should be used immediately.
Discard any vial if the solution is not colorless.
Dilute XOPENEX (levalbuterol HCl) Inhalation Solution Concentrate with sterile normal saline before administration by nebulization.
8.5 Geriatric Use Clinical studies of XOPENEX Inhalation Solution did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently from younger subjects.
Only 5 patients 65 years of age and older were treated with XOPENEX Inhalation Solution in a 4-week clinical study [see Clinical Pharmacology ( 12 ) and Clinical Studies ( 14 ) ] (n=2 for 0.63 mg and n=3 for 1.25 mg).
In these patients, bronchodilation was observed after the first dose on day 1 and after 4 weeks of treatment.
In general, patients 65 years of age and older should be started at a dose of 0.63 mg of XOPENEX Inhalation Solution.
If clinically warranted due to insufficient bronchodilator response, the dose of XOPENEX Inhalation Solution may be increased in elderly patients as tolerated, in conjunction with frequent clinical and laboratory monitoring, to the maximum recommended daily dose [see Dosage and Administration ( 2 ) ].
DOSAGE FORMS AND STRENGTHS
3 Inhalation Solution Concentrate: 0.5 mL unit-dose vials containing 1.25 mg of levalbuterol that must be diluted before use.
XOPENEX Inhalation Solution Concentrate is available in cartons of 30 individually pouched vials.
Inhalation Solution Concentrate (unit-dose vial for nebulization): 1.25 mg/0.5 mL Dilute before use.
( 3 )
MECHANISM OF ACTION
12.1 Mechanism of Action Activation of beta 2 -adrenergic receptors on airway smooth muscle leads to the activation of adenylate cyclase and to an increase in the intracellular concentration of cyclic-3´, 5´-adenosine monophosphate (cyclic AMP).
The increase in cyclic AMP is associated with the activation of protein kinase A, which in turn inhibits the phosphorylation of myosin and lowers intracellular ionic calcium concentrations, resulting in muscle relaxation.
Levalbuterol relaxes the smooth muscles of all airways, from the trachea to the terminal bronchioles.
Increased cyclic AMP concentrations are also associated with the inhibition of release of mediators from mast cells in the airway.
Levalbuterol acts as a functional antagonist to relax the airway irrespective of the spasmogen involved, thus protecting against all bronchoconstrictor challenges.
While it is recognized that beta 2 -adrenergic receptors are the predominant receptors on bronchial smooth muscle, data indicate that there are beta-receptors in the human heart, 10% to 50% of which are beta 2 -adrenergic receptors.
The precise function of these receptors has not been established [see Warnings and Precautions ( 5.4 ) ].
However, all beta-adrenergic agonist drugs can produce a significant cardiovascular effect in some patients, as measured by pulse rate, blood pressure, symptoms, and/or electrocardiographic changes.
INDICATIONS AND USAGE
1 XOPENEX (levalbuterol HCl) Inhalation Solution Concentrate is indicated for the treatment or prevention of bronchospasm in adults, adolescents, and children 6 years of age and older with reversible obstructive airway disease.
XOPENEX (levalbuterol hydrochloride) Inhalation Solution Concentrate is a beta 2 -adrenergic agonist indicated for: Treatment or prevention of bronchospasm in adults, adolescents, and children 6 years of age and older with reversible obstructive airway disease.
( 1 )
8.4 Pediatric Use Pediatric Patients 6 Years of Age and Older The safety and efficacy of XOPENEX Inhalation Solution have been established in pediatric patients 6 years of age and older in an adequate and well-controlled clinical trial [see Adverse Reactions ( 6 ) and Clinical Studies ( 14 ) ].
Pediatric Patients less than 6 Years of Age XOPENEX Inhalation Solution is not indicated for pediatric patients less than 6 years of age.
Clinical trials with XOPENEX Inhalation Solution in this age group failed to meet the primary efficacy endpoint and demonstrated an increased number of asthma-related adverse reactions following chronic XOPENEX treatment.
XOPENEX Inhalation Solution was studied in 379 pediatric patients less than 6 years of age with asthma or reactive airway disease – (291patients 2 to 5 years of age, and 88 patients from birth to less than 2 years of age).
Efficacy and safety data for XOPENEX Inhalation Solution in this age group are primarily available from one 3-week, multicenter, randomized, double-blind, placebo-controlled study (Study 1) in 211 pediatric patients between the ages of 2 and 5 years, of whom 119 received XOPENEX Inhalation Solution.
Over the 3 week treatment period, there were no significant treatment differences in the Pediatric Asthma Questionnaire (PAQ) total score between groups receiving XOPENEX Inhalation Solution 0.31 mg, XOPENEX Inhalation Solution 0.63 mg, racemic albuterol, and placebo.
Additional safety data following chronic dosing is available from a 4-week, multicenter, randomized, modified-blind, placebo-controlled study (Study 2) of 196 patients between the ages of birth and 3 years, of whom 63 received open-label XOPENEX Inhalation Solution.
In these two studies, treatment-emergent asthma exacerbations or asthma-related adverse reactions and treatment discontinuations due to asthma occurred at a higher frequency in XOPENEX Inhalation-treated subjects compared to control ( Table 5 ).
Other adverse reactions were consistent with those observed in the clinical trial population of patients 6 years of age and older [see Adverse Reactions ( 6.1 )].
Asthma-related Adverse Reactions in 3- and 4-Week Clinical Trials in Children Birth to <6 Years of Age *Asthma exacerbation defined as worsening of asthma symptoms or pulmonary function that required any of the following: emergency department visit, hospitalization, therapeutic intervention with oral or parenteral steroids, unscheduled clinic visit to treat acute asthma symptoms **Includes the following Preferred Terms (whether considered by the investigator to be related or unrelated to drug): asthma, cough, hypoxia, status asthmaticus, tachypnea Asthma Exacerbations* n (%) Treatment Discontinuations due to Asthma n (%) Asthma-related Adverse Reactions** n (%) Study 1 XOPENEX 0.31 mg, n=58 6 (10) 4 (7) — XOPENEX 0.63 mg, n=51 7 (14) 6 (12) — Racemic albuterol, n=52 3 (6) 2 (4) — Placebo, n=50 2 (4) 2 (4) — Study 2 XOPENEX 0.31 mg, n=63 — 2 (3) 6 (10) Levalbuterol HFA inhalation aerosol, n=65 — 1 (2) 8 (12) Placebo, n=68 — 0 3 (4)
8.1 Pregnancy Pregnancy Exposure Registry There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to asthma medication, including XOPENEX during pregnancy.
To enroll in MotherToBaby Pregnancy Studies’ Asthma & Pregnancy Study or for more information about the registry, call 1-877-311-8972 or visit www.mothertobaby.org/ongoing-study/asthma.
Risk Summary There are no adequate and well-controlled studies of XOPENEX Inhalation Solution Concentrate in pregnant women.
There are clinical considerations with the use of XOPENEX Inhalation Solution Concentrate in pregnant women [see Clinical Considerations ].
Following oral administration of levalbuterol HCl to pregnant rabbits, there was no evidence of teratogenicity at doses up to 25 mg/kg/day [approximately 108 times the maximum recommended human daily inhalation dose (MRHDID) of levalbuterol HCl for adults on a mg/m 2 basis]; however, racemic albuterol sulfate was teratogenic in mice (cleft palate) and rabbits (cranioschisis) at doses slightly higher than the human therapeutic range ( see Data ).
The estimated background risk of major birth defects and miscarriage for the indicated populations(s) are unknown.
In the U.S.
general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20% respectively.
Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk In women with poorly or moderately controlled asthma, there is an increased risk of preeclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate.
Pregnant women should be closely monitored and medication adjusted as necessary to maintain optimal control.
Labor or Delivery Because of the potential for beta-adrenergic agonists to interfere with uterine contractility, the use of XOPENEX Inhalation Solution for the treatment of bronchospasm during labor should be restricted to those patients for whom the benefits clearly outweigh the risk.
XOPENEX Inhalation Solution has not been approved for the management of preterm labor.
The benefit-risk ratio when XOPENEX is administered for tocolysis has not been established.
Serious adverse reactions, including maternal pulmonary edema, have been reported during or following treatment of premature labor with beta 2 -agonists, including racemic albuterol.
Data Animal Data The oral administration of levalbuterol HCl to pregnant New Zealand White rabbits during the period of organogenesis found no evidence of teratogenicity at doses up to 25 mg/kg/day (approximately 108 times the MRHDID of levalbuterol HCl for adults on a mg/m 2 basis).
In a rat development study, racemic albuterol sulfate administered by inhalation did not produce any teratogenic effects at exposure approximately 63 times the MRHDID (on a mg/m 2 basis at a maternal dose of 10.5 mg/kg).
However, other developmental studies with the racemic albuterol sulfate, did result in teratogenic effects in mice and rabbits at doses slightly higher than the human therapeutic range.
In a rabbit developmental study, orally administered albuterol sulfate induced cranioschisis in 7 of 19 fetuses (37%) at approximately 215 times the MRHDID for adults (on a mg/m 2 basis at a maternal dose of 50 mg/kg).
In a mouse developmental study, subcutaneously administered albuterol sulfate produced cleft palate formation in 5 of 111 (4.5%) fetuses at an exposure approximately 0.3 times the MRHDID for adults (on a mg/m 2 basis at a maternal dose of 0.25 mg/kg/day) and in 10 of 108 (9.3%) fetuses at approximately 3 times the MRHDID (on a mg/m 2 basis at a maternal dose of 2.5 mg/kg/day).
Similar effects were not observed at approximately 0.03 times the MRHDID for adults on a mg/m 2 basis at maternal dose of 0.025 mg/kg/day (i.e., less than the therapeutic dose).
Cleft palate also occurred in 22 of 72 (30.5%) fetuses from females treated subcutaneously with isoproterenol (positive control).
WARNING AND CAUTIONS
5 WARNINGS AND PRECAUTIONS Life-threatening paradoxical bronchospasm may occur.
Discontinue XOPENEX Inhalation Solution immediately and treat with alternative therapy.
( 5.1 ) Need for more doses of XOPENEX Inhalation Solution than usual may be a sign of deterioration of asthma and requires reevaluation of treatment.
( 5.2 ) XOPENEX Inhalation Solution is not a substitute for corticosteroids.
( 5.3 ) Cardiovascular effects may occur.
Consider discontinuation of XOPENEX Inhalation Solution if these effects occur.
Use with caution in patients with underlying cardiovascular disorders.
( 5.4 ) Excessive use may be fatal.
Do not exceed recommended dose.
( 5.5 ) Immediate hypersensitivity reactions may occur.
Discontinue XOPENEX Inhalation Solution immediately.
( 5.6 ) Hypokalemia and changes in blood glucose may occur.
( 5.7 , 5.8 ) 5.1 Paradoxical Bronchospasm XOPENEX Inhalation Solution can produce paradoxical bronchospasm, which may be life-threatening.
If paradoxical bronchospasm occurs, XOPENEX Inhalation Solution should be discontinued immediately and alternative therapy instituted.
It should be recognized that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new vial.
5.2 Deterioration of Asthma Asthma may deteriorate acutely over a period of hours or chronically over several days or longer.
If the patient needs more doses of XOPENEX Inhalation Solution than usual, this may be a marker of destabilization of asthma and requires reevaluation of the patient and treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids.
5.3 Use of Anti-Inflammatory Agents XOPENEX Inhalation Solution is not a substitute for corticosteroids.
The use of beta-adrenergic agonist 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.
5.4 Cardiovascular Effects XOPENEX Inhalation Solution, like other beta-adrenergic agonists, can produce clinically significant cardiovascular effects in some patients, as measured by heart rate, blood pressure, and symptoms.
Although such effects are uncommon after administration of XOPENEX Inhalation Solution at recommended doses, if they occur, the drug may need to be discontinued.
In addition, beta-agonists have been reported to produce electrocardiogram (ECG) changes, such as flattening of the t-wave, prolongation of the QTc interval, and ST segment depression.
The clinical significance of these findings is unknown.
Therefore, XOPENEX Inhalation Solution, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, cardiac arrhythmias, and hypertension.
5.5 Do Not Exceed Recommended Dose Do not exceed the recommended dose.
Fatalities have been reported in association with excessive use of inhaled sympathomimetic drugs in patients with asthma.
The exact cause of death is unknown, but cardiac arrest following an unexpected development of a severe acute asthmatic crisis and subsequent hypoxia is suspected.
5.6 Immediate Hypersensitivity Reactions Immediate hypersensitivity reactions may occur after administration of levalbuterol or racemic albuterol.
Reactions have included urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.
The potential for hypersensitivity must be considered in the clinical evaluation of patients who experience immediate hypersensitivity reactions while receiving XOPENEX Inhalation Solution.
5.7 Coexisting Conditions XOPENEX Inhalation Solution, like all sympathomimetic amines, should be used with caution in patients with cardiovascular disorders, especially coronary insufficiency, hypertension, and cardiac arrhythmias; in patients with convulsive disorders, hyperthyroidism, or diabetes mellitus; and in patients who are unusually responsive to sympathomimetic amines.
Clinically significant changes in systolic and diastolic blood pressure have been seen in individual patients and could be expected to occur in some patients after the use of any beta-adrenergic bronchodilator.
Changes in blood glucose may occur.
Large doses of intravenous racemic albuterol have been reported to aggravate preexisting diabetes mellitus and ketoacidosis.
5.8 Hypokalemia As with other beta-adrenergic agonist medications, XOPENEX Inhalation Solution may produce significant hypokalemia in some patients, possibly through intracellular shunting, which has the potential to produce adverse cardiovascular effects.
The decrease is usually transient, not requiring supplementation.
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION See FDA-approved patient labeling ( Patient Information and Instructions for Using XOPENEX Inhalation Solution Concentrate ).
Patients should be given the following information: Hypersensitivity Query patients about previously experienced hypersensitivity to levalbuterol or racemic albuterol and counsel patients to report any hypersensitivity reactions to their physician.
Frequency of Use Inform patients not to increase the dose or use XOPENEX Inhalation Solution more frequently than recommended without consulting their physician.
If patients find that treatment with XOPENEX Inhalation Solution becomes less effective for symptomatic relief, symptoms become worse, or they need to use the product more frequently than usual, they should seek medical attention immediately.
Paradoxical Bronchospasm Inform patients that XOPENEX Inhalation Solution can produce paradoxical bronchospasm.
Instruct patients to discontinue XOPENEX Inhalation Solution if paradoxical bronchospasm occurs.
Concomitant Drug Use Inform patients using XOPENEX Inhalation Solution, that other inhaled drugs and asthma medications should be taken only as directed by their physician.
Common Adverse Reactions Advise patients of the common adverse reactions of treatment with XOPENEX Inhalation Solution include palpitations, chest pain, fast heart rate, headache, dizziness, tremor and nervousness.
Pregnancy Advise patients who are pregnant or nursing to contact their physician about the use of XOPENEX Inhalation Solution.
There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to asthma medication, including XOPENEX, during pregnancy.
To enroll in the Asthma & Pregnancy Study or for more information about the registry, call 1-877-311-8972 or visit www.mothertobaby.org/ongoing-study/asthma [see Use in Specific Populations ( 8.1 ) ].
General Information on Storage and Use Advise patients to dilute XOPENEX Inhalation Solution Concentrate with sterile normal saline before administration by nebulization.
Advise patients how to store XOPENEX Inhalation Solution Concentrate.
Store in the foil pouch between 20°C to 25°C (68°F to 77°F) protected from light and excessive heat.
Do not use after the expiration date stamped on the container.
Open the foil pouch just prior to administration.
Once the foil pouch is opened, use the contents of the vial immediately.
Discard any vial if the solution is not colorless.
Advise patients not to mix XOPENEX Inhalation Solution with other drugs in a nebulizer.
AKORN Distributed by: Akorn, Inc.
Lake Forest, IL 60045 Manufactured for: Oak Pharmaceuticals, Inc.
For customer service, call 1-800-932-5676.
To report adverse events, call 1-800-932-5676.
For medical information, call 1-800-932-5676.
XOPENEX is a registered trademark of Sunovion Pharmaceuticals Inc.
and is used under license.
XPA0N December 2018 PHARMACIST — DETACH HERE AND GIVE LEAFLET TO PATIENT ————————————————————————————————————
DOSAGE AND ADMINISTRATION
2 XOPENEX Inhalation Solution Concentrate is for oral inhalation only.
Dilute with sterile normal saline before administration.
Administer by nebulization using with a standard jet nebulizer (with a face mask or mouthpiece) connected to an air compressor.
Do not exceed recommended dose.
For dosages less than 1.25 mg, the non-concentrate (i.e., XOPENEX Inhalation Solution, 3 mL) formulation must be used.
FOR ORAL INHALATION ONLY ( 2 ) Dilute XOPENEX (levalbuterol hydrochloride) Inhalation Solution Concentrate with sterile normal saline before administration by nebulization.
Children 6 to 11 years old: 0.31 mg administered three times a day, by nebulization.
Routine dosing should not exceed 0.63 mg three times a day.
( 2 ) Adults and Adolescents ≥ 12 years old: 0.63 mg administered three times a day, every 6 to 8 hours, by nebulization.
The maximum recommended dose is 1.25 mg three times a day.
( 2 ) For use with a standard jet nebulizer (with a face mask or mouthpiece) connected to an air compressor.
( 2 ) Children 6 to 11 years old: The recommended dosage of XOPENEX Inhalation Solution for patients 6 to 11 years old is 0.31 mg administered three times a day, by nebulization.
Routine dosing should not exceed 0.63 mg three times a day.
Adults and Adolescents ≥ 12 years old: The recommended starting dosage of XOPENEX Inhalation Solution for patients 12 years of age and older is 0.63 mg administered three times a day, every 6 to 8 hours, by nebulization.
Patients 12 years of age and older with more severe asthma or patients who do not respond adequately to a dose of 0.63 mg of XOPENEX Inhalation Solution may benefit from a dosage of 1.25 mg three times a day.
Patients receiving the highest dose of XOPENEX Inhalation Solution should be monitored closely for adverse systemic effects, and the risks of such effects should be balanced against the potential for improved efficacy.
The use of XOPENEX Inhalation Solution can be continued as medically indicated to help control recurring bouts of bronchospasm.
During this time, most patients gain optimal benefit from regular use of the inhalation solution.
If a previously effective dosage regimen fails to provide the usual response this may be a marker of destabilization of asthma and requires reevaluation of the patient and the treatment regimen, giving special consideration to the possible need for anti-inflammatory treatment, e.g., corticosteroids.
The drug compatibility (physical and chemical), efficacy, and safety of XOPENEX Inhalation Solution when mixed with other drugs in a nebulizer have not been established.
The safety and efficacy of XOPENEX Inhalation Solution have been established in clinical trials when administered using the PARI LC Jet™ and PARI LC Plus™ nebulizers, and the PARI Master ® Dura-Neb ® 2000 and Dura-Neb ® 3000 compressors.
The safety and efficacy of XOPENEX Inhalation Solution when administered using other nebulizer systems have not been established.