Levalbuterol Inhalation Solution Concentrate

Levalbuterol inhalation solution is contraindicated in patients with a history of hypersensitivity to levalbuterol or racemic albuterol. Reactions have included urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema [see Warnings and Precautions (5.6)].

Levalbuterol inhalation solution, USP (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 hydrochloride is a relatively selective beta2-adrenergic receptor agonist [see Clinical Pharmacology (12)]. The chemical name for levalbuterol hydrochloride is (R)-α1-[[(1,1dimethylethyl)amino]methyl]-4-hydroxy-1,3-benzenedimethanol hydrochloride, and its established chemical structure is as follows: 

The molecular weight of levalbuterol hydrochloride USP is 275.78, and its molecular formula is C13H21NO3•HCl. It is a white or almost white, crystalline powder, with a melting point of approximately 188 to 195°C and freely soluble in water.

Levalbuterol hydrochloride is the USAN modified name for (R)-albuterol hydrochloride in the United States. 

Levalbuterol inhalation solution, USP (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 hydrochloride USP), edetate disodium, sodium citrate dihydrate, sodium chloride to adjust tonicity and hydrochloric acid to adjust the pH to 4.0 (3.3 to 4.5). 

Carcinogenesis, Mutagenesis, Impairment of Fertility

Although there have been no carcinogenesis studies with levalbuterol hydrochloride, racemic albuterol sulfate has been evaluated for its carcinogenic potential.

In a 2-year study in Sprague-Dawley rats, dietary administration of racemic albuterol sulfate resulted in a significant dose-related increase in the incidence of benign leiomyomas of the mesovarium at doses of 2 mg/kg/day and greater (approximately 4 times the MRDI dose of levalbuterol hydrochloride for adults and approximately 5 times the MRDI dose of levalbuterol hydrochloride for children on a mg/m2 basis). In an 18-month study in CD-1 mice and a 22-month study in the golden hamster, dietary administration of racemic albuterol sulfate showed no evidence of tumorigenicity. Dietary doses in CD-1 mice were up to 500 mg/kg/day (approximately 540 times the MRDI dose of levalbuterol hydrochloride for adults and approximately 630 times the MRDI dose of levalbuterol hydrochloride for children on a mg/m2 basis) and doses in the golden hamster study were up to 50 mg/kg/day (approximately 90 times the MRDI dose of levalbuterol hydrochloride for adults on a mg/m2 basis and approximately 105 times the MRDI dose of levalbuterol hydrochloride for children on a mg/m2 basis).

Levalbuterol hydrochloride was not mutagenic in the Ames test or the CHO/HPRT Mammalian Forward Gene Mutation Assay. Levalbuterol hydrochloride was not clastogenic in the in vivo micronucleus test in mouse bone marrow. Racemic albuterol sulfate was not clastogenic in an in vitro chromosomal aberration assay in CHO cell cultures.

No fertility studies have been conducted with levalbuterol hydrochloride. Reproduction studies in rats using racemic albuterol sulfate demonstrated no evidence of impaired fertility at oral doses up to 50 mg/kg/day (approximately 108 times the maximum recommended daily inhalation dose of levalbuterol hydrochloride for adults on a mg/m2 basis).

See FDA-approved patient labeling (Patient Information and Instructions for Using Levalbuterol 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 levalbuterol inhalation solution more frequently than recommended without consulting their physician. If patients find that treatment with levalbuterol 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 levalbuterol inhalation solution can produce paradoxical bronchospasm. Instruct patients to discontinue levalbuterol inhalation solution if paradoxical bronchospasm occurs.

Concomitant Drug Use

Inform patients using levalbuterol 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 levalbuterol 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 levalbuterol inhalation solution.

General Information on Storage and Use

Advise patients to dilute levalbuterol inhalation solution (concentrate) with sterile normal saline before administration by nebulization.

Advise patients how to store levalbuterol inhalation solution (concentrate). Store in the foil pouch between 20° to 25°C (68° 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 levalbuterol inhalation solution with other drugs in a nebulizer.

To report adverse events, call Aurobindo Pharma USA LLC at 1-866-850-2876.

Rx Only                               NDC 65862-942-50

Levalbuterol
Inhalation Solution, USP
(Concentrate)
1.25 mg/0.5 mL*

*Potency expressed as levalbuterol

One 0.5 mL Sterile Unit-Dose Vial

Open Foil Pouch Just Prior to Administration

Dilute Before Use

Each 0.5 mL unit-dose vial contains 1.25 mg of levalbuterol
(equivalent to levalbuterol hydrochloride USP 1.44 mg) in an
aqueous solution containing edetate disodium, sodium
citrate dihydrate, sodium chloride to adjust tonicity and
hydrochloric acid to adjust the pH to 4.0. Contains no
preservatives.

Keep out of reach of children.

Attention Pharmacist: Detach “Patient’s Information” from
package insert and dispense with product.

Use only as directed by your physician.

Do not exceed recommended dose.

Protect from light. Store at 20° to 25°C (68° to 77°F) [see
USP Controlled Room Temperature]. Discard if solution is
not colorless.

AUROBINDO

Rx Only             NDC 65862-942-03

Levalbuterol
Inhalation Solution, USP
(Concentrate)
1.25 mg/0.5 mL*

*Potency expressed as levalbuterol
Dilution Required
For Oral Inhalation Only. Sterile Unit-Dose Vial
30 x 0.5 mL Sterile Unit-Dose Vials
Open the foil pouch just prior to administration DILUTE BEFORE USE

AUROBINDO