Levalbuterol – Side Effects and Precautions

Background

Levosalbutamol, or levalbuterol, is a short-acting β2 adrenergic receptor agonist used in the treatment of asthma and chronic obstructive pulmonary disease (COPD). Salbutamol has been marketed as a racemic mixture, although beta2-agonist activity resides almost exclusively in the (R)-enantiomer. The enantioselective disposition of salbutamol and the possibility that (S)-salbutamol has adverse effects have led to the development of an enantiomerically pure (R)-salbutamol formulation known as levosalbutamol (levalbuterol).

Properties and Characteristics of Levalbuterol

Drug class	Adrenergic bronchodilators
Brand Names	Xopenex, Xopenex HFA, Xopenex Concentrate
Synonyms	(R)-salbutamol, Levalbuterol, Levosalbutamol, R-salbutamol
Molecular Formula	C13H21NO3
Molecular Weight	239.31 g/mol
IUPAC Name	4-[(1R)-2-(tert-butylamino)-1-hydroxyethyl]-2-(hydroxymethyl)phenol
Structural formula of main components
Pure active ingredient	Levalbuterol tartrate
Appearance	White to off-white, crystalline solid
Melting point	187°C
Solubility	180 mg/mL
Excretion	Excrete through urine
Storage	Store in the protective foil pouch between 20°C and. 258. 25°C (68°F and 77°F)
Available Forms	inhalation aerosol, inhalation solution
Prescription	Doctor prescription is required

Uses of Levalbuterol

Levalbuterol is used to prevent and treat wheezing and shortness of breath caused by breathing problems (such as asthma, chronic obstructive pulmonary disease). It is a quick-relief drug. Levalbuterol belongs to a class of drugs known as bronchodilators. It works by relaxing the muscles around the airways so that they open up and you can breathe more easily. Controlling symptoms of breathing problems can decrease time lost from work or school.

What side effects may I notice from receiving this medication?

Side effects that you should report to your care team as soon as possible:

• Allergic reactions—skin rash, itching, hives, swelling of the face, lips, tongue, or throat
• Heart rhythm changes—fast or irregular heartbeat, dizziness, feeling faint or lightheaded, chest pain, trouble breathing
• Increase in blood pressure
• Low potassium level—muscle pain or cramps, unusual weakness or fatigue, fast or irregular heartbeat
• Wheezing or trouble breathing that is worse after use

Side effects that usually do not require medical attention (report to your care team if they continue or are bothersome):

• Dizziness
• Headache
• Tremors or shaking
• Trouble sleeping

This list may not describe all possible side effects. Call your doctor for medical advice about side effects.

Mechanism of action

β2 adrenergic receptors on airway smooth muscle are Gs coupled and their activation by levosalbutamol leads to activation of adenylate cyclase and to an increase in the intracellular concentration of 3′,5′-cyclic adenosine monophosphate (cyclic AMP). Increased cyclic AMP activates protein kinase A which itself inhibits the phosphorylation of myosin produces lower intracellular ionic calcium concentrations, inducing muscle relaxation. Increased cyclic AMP concentrations are also associated with the inhibition of the release of mediators from mast cells in the airways, potentially contributing to its benefit in asthma attacks.

Interactions between Levalbuterol (Xopenex) and other drugs

Levalbuterol (Xopenex) may interact with certain medications or supplements. Always let your doctor and pharmacist know about any other medications or supplements (including prescribed and over-the-counter medications, vitamins, and dietary or herbal supplements) that you are currently taking. The list below does not include all possible drug interactions with Levalbuterol (Xopenex). Please note that only the generic name of each medication is listed below.

Using this medicine with any of the following medicines is usually not recommended, but may be required in some cases. If both medicines are prescribed together, your doctor may change the dose or how often you use one or both of the medicines.

• Acebutolol
• Befunolol
• Carteolol
• Desipramine
• Epinephrine
• Fenoterol
• Hexoprenaline
• Imipramine
• Labetalol
• Melitracen
• Nadolol
• Opipramol
• Penbutolol
• Sotalol
• Talinolol

Dosing

The dose of this medicine will be different for different patients. Follow your doctor’s orders or the directions on the label. The following information includes only the average doses of this medicine. If your dose is different, do not change it unless your doctor tells you to do so.

The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.

For preventing or treating bronchospasm

For inhalation aerosol dosage form:

• Adults and children 4 years of age and older—Two puffs every 4 to 6 hours. In some patients one puff every 4 hours may be enough.
• Children younger than 4 years of age—Use and dose must be determined by your doctor.

For inhalation solution dosage form (used with a nebulizer):

• Adults and children 12 years of age and older—At first, 0.63 milligrams (mg) in the nebulizer 3 times a day, every 6 to 8 hours per day. Some patients may need to start at 1.25 mg in the nebulizer 3 times a day.
• Children 6 to 11 years of age—0.31 mg in the nebulizer 3 times a day. Your doctor may increase your dose as needed. However, the dose is usually not more than 0.63 mg 3 times a day.
• Children younger than 6 years of age—Use and dose must be determined by your doctor.

Overdosage

The expected symptoms with overdosage are those of excessive beta-adrenergic receptor stimulation and/or occurrence or exaggeration of any of the symptoms are 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 Levalbuterol Inhalation Solution, USP. Treatment consists of discontinuation of Levalbuterol Inhalation Solution, USP together with appropriate symptomatic therapy. The judicious use of a cardioselective 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 Levalbuterol Inhalation Solution, USP.

What are warnings and precautions for Levalbuterol?

Cautions

• Risk of paradoxical bronchospasm; this should be distinguished from inadequate response; discontinue and treat with alternate therapy if it occurs
• Has a higher affinity for beta1- and beta2-adrenergic receptors than racemic albuterol has
• Risk of hypersensitivity reactions
• Use caution in hyperthyroidism; may increase thyroid activity
• Use with caution in diabetes mellitus (beta2 agonists may increase glucose)
• Risk of hypokalemia (usually transient); use with caution in hypokalemia
• Use with caution in patients with a history of seizure disorders; therapy may increase CNS activity/excitation
• Exceeding the recommended dose may result in serious adverse effects, including fatalities

Cardiovascular effects

• Use with caution in cardiovascular disorders (eg, arrhythmias, hypertension, coronary insufficiency)
• May cause elevation in blood pressure and heart rate; may cause CNS stimulation or excitation
• May increase the risk of arrhythmia and electrocardiogram changes, including ST-segment depression, prolongation of the QTc interval, or flattening of the T wave

Drug interaction overview

• Short-acting bronchodilators
• Avoid use
• If additional adrenergic drugs are to be administered by any route, use with caution to avoid deleterious additive cardiovascular effects

Beta-blockers

• Beta-adrenergic receptor blocking agents not only block the pulmonary effect of beta-adrenergic agonists but may produce severe bronchospasm in asthmatic patients.
• Therefore, patients with asthma should not normally be treated with beta-blockers.
• Under certain circumstances, cardioselective beta-blockers should be considered and may be used with caution

Diuretics

• ECG changes or hypokalemia that may result from the administration of non-potassium-sparing diuretics can be acutely worsened by beta-agonists, especially when the recommended dose of the beta-agonist is exceeded

Digoxin

• Mean decreases of 16% and 22% in serum digoxin levels were demonstrated after single-dose IV and oral administration of racemic albuterol, respectively, to normal volunteers who had received digoxin for 10 days

Monoamine oxidase inhibitors or tricyclic antidepressants

• Use 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

Pregnancy and Lactation

• There are no adequate and well-controlled studies on pregnant women; there are clinical considerations with use in pregnant women

Pregnancy exposure registry

• Monitors pregnancy outcomes in women exposed to asthma medication 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

Clinical considerations

• 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 gestational age in neonate
• Closely monitor and adjust medication as necessary to maintain optimal control

Lactation

• There are no available data on the presence of levalbuterol in human milk, its effects on the breastfed child, or effects on milk production
• Developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for therapy and any potential adverse effects on the breastfed child from therapy or underlying maternal condition