Levalbuterol or Levosalbutamol (Xopenex) is a short-acting beta-adrenergic receptor agonist that acts on the smooth muscles of the airways resulting in rapid bronchodilation. It is used in the acute, short-term treatment of severe asthma/ bronchospasm.

Levalbuterol Uses:

• Bronchospasm:

  • In individuals with reversible obstructive bronchial illness, levalbuterol is used to treat or prevent bronchospasm.

Levalbuterol (Xopenex) Dose in Adults:

Levalbuterol (Xopenex) Dose in the treatment of Bronchospasm:

• Metered-dose inhaler:

  • 2 puffs or inhalations, each equal to 90 mcg, are required every 4 to 6 hours.
  • One inhalation (45 mcg) every four hours may be sufficient for some people.
  • The allowed maximum dose is 2 puffs i.e 90 mcg every 4 hours.

• Nebulization solution:

  • It can be administered initially as 0.63 mg three times daily, spaced six to eight hours apart.
  • With careful monitoring for adverse effects, the dose may be increased to 1.25 mg three times per day.
  • The maximum dose is 1.25 mg three times daily.

Levalbuterol (Xopenex) Dose in the treatment of an acute severe exacerbation of asthma:

• Metered-dose inhaler:

  • When using metered inhalers, take 4 to 8 breaths every 20 minutes for up to 4 hours, then as needed, every 1 to 4 hours.

• Nebulization solution:

  • If used in nebulizers, take 2 to 2.5 mg three times every 20 minutes, then 1.25 to 5 mg as needed every 1 to 4 hours.

Levalbuterol (Xopenex) Dose in Children:

Note: Dosage measured in milligrammes of levalbuterol

Levalbuterol (Xopenex) Dose in the treatment of acute exacerbation of Asthma:

• Nebulization:

  • Infants and Children:
    • For this age range, the dosage is 0.075 mg/kg/dose.
    • The recommended maximum dose is 5 mg/dose given every 1 to 4 hours as specified, with a minimum dose of 1.25 mg/dose every 20 minutes for 3 doses, followed by 0.075 to 0.15 mg/kg/dose.
  • Adolescents:
    • For three doses, take 1.25 to 2.5 mg every 20 minutes; after that, take 1.25 to 5 mg as needed, every 1 to 4 hours.

• Inhalation, aerosol (metered-dose inhaler): 45 mcg/spray:

  • Infants and Children:
    • In infants and children it is given as 4 to 8 puffs every 20 minutes for 3 doses, then every 1 to 4 hours
  • Adolescents:
    • Teenagers receive it as 4 to 8 puffs every 20 minutes for up to 4 hours, then as needed at 1 to 4 hour intervals.

Levalbuterol (Xopenex) Dose in the maintenance treatment of Asthma:

However, it is not advised for daily maintenance or long-term use. Its consistent usage for symptom control beyond two days per week suggests the need for additional long-term control medication, such as inhalational corticosteroids.

• Nebulization:

  • Infants and Children ≤4 years:
    • 31 to 1.25 mg every 4 to 6 hours as indicated.
  • Children 5 to <12 years:
    • 31 to 0.63 mg every 8 hours as indicated.
  • Children ≥12 years and Adolescents:
    • 0.63 to 1.25 mg every 8 hours as indicated

• Inhalation, aerosol (metered-dose inhaler): 45 mcg/spray:

  • Children ≥4 years and Adolescents:
    • Children older than 4 years old should receive 2 inhalations as needed every 4 to 6 hours.
    • According to the literature, some people may only require one inhalation every four hours.
    • Two inhalations every four hours are the maximum dose.

Levalbuterol Pregnancy Category: C

• A mother and her unborn child may be more at risk from asthma exacerbations or poorly controlled asthma than from asthma that is appropriately managed.
• Increased risks of preterm deliveries, perinatal death, preeclampsia, and low birth weight babies are all intimately linked to uncontrolled asthma.
• Acute asthma attacks should be treated with fast-acting beta-2 antagonists to prevent foetal hypoxia (SABA).
• High doses of SABA may cause hypoglycemia in fetuses. Therefore, it is important to check and manage the BSR of newborns as soon as possible.
• It is important to choose a safer agent for treatment during pregnancy. Preterm labor is not managed with Levalbuterol.
• There are still studies ongoing on the effects of levalbuterol on pregnancy outcomes.

Levalbuterol use during breastfeeding:

• It is unknown if it is found in breast milk.
• If levalbuterol is to be administered to a mother who is breastfeeding, it should be evaluated to determine if the benefits outweigh any risks to the baby.
• However, breasts should not be withheld.

Dose in Kidney Disease:

No dose adjustments are given, however as it has a renal clearance that's why its systemic exposure is increased in CKD.

Dose in Liver disease:

Its not yet studied that dose adjustments are required in liver disease.

Common Side Effects of Levalbuterol (Xopenex):

• Central nervous system:

  • Headache

• Gastrointestinal:

  • Vomiting

• Infection:

  • Viral infection

• Respiratory:

  • Rhinitis

Less Common Side Effects of Levalbuterol (Xopenex):

• Cardiovascular:

  • Tachycardia

• Central nervous system:

  • Nervousness
  • Dizziness
  • Migraine
  • Anxiety
  • Pain

• Dermatologic:

  • Skin rash
  • Urticaria

• Gastrointestinal:

  • Diarrhea
  • Dyspepsia

• Hematologic & oncologic:

  • Lymphadenopathy

• Neuromuscular & skeletal:

  • Tremor
  • Leg cramps
  • Weakness
  • Myalgia

• Respiratory:

  • Pharyngitis
  • Asthma
  • Cough
  • Sinusitis
  • Flu-like symptoms
  • Bronchitis
  • Nasal mucosa swelling

• Miscellaneous:

  • Fever
  • Accidental injury

• Endocrine & metabolic:

  • Decreased serum potassium
  • Increased heart rate
  • Increased serum glucose
  • Paradoxical bronchospasm

• Hypersensitivity:

  • Hypersensitivity reaction (including bronchospasm, oropharyngeal edema)

Contraindications to Levalbuterol (Xopenex):

Hypersensitivity is a serious contraindication.

Warnings and precautions

• Bronchospasm

  • It is rare to cause bronchospasm, so it should be distinguished from the appropriate response.
  • In such cases, it is best to stop the therapy immediately and use an alternative agent.
  • Paradoxical bronchospasm can be attributed to the first use of a brand new vial or canister.

• Hypersensitivity reactions

  • There have been reports of immediate hypersensitivity reactions such as rash, angioedema and anaphylaxis.

• Cardiovascular disease

  • Patients with heart disease should be cautious about using beta-agonists as they can cause hypertension, cardiac insufficiency and life-threatening arrhythmias. 
  • CNS stimulation may be caused by beta-agonists, which can cause an increase in blood pressure and heart beat.
  • The electrocardiogram (ECG) modifications such as flattening the T wave, prolonging or lengthening of the QTc interval, and ST-segment depression symptoms have also been linked to beta-2 agonists.

• Diabetes:

  • Beta-agonists may cause hyperglycemia, which can lead to diabetic ketoacidosis.

• Hyperthyroidism:

  • It can stimulate thyroid activity, so patients with hyperthyroidism should be cautious about using it.

• Hypokalemia

  • It can also lead to hypokalemia.

• Renal impairment

  • Increased systemic exposure can be caused by renal disease.

• Seizures:

  • Beta-agonists can make seizures worse as they can stimulate the CNS.

Levalbuterol: Drug Interaction

Monitoring parameters:

• Asthma symptoms.
• FEV, peak flow, and pulmonary function tests.
• heart rate and blood pressure.
• CNS stimulation.
• arterial blood gases (if condition warrants).
• serum potassium levels.
• serum glucose in diabetic patients.

How to administer Levalbuterol (Xopenex)?

Inhalation: For oral inhalation only.

Metered-dose inhaler:

• Shake thoroughly before using, and keep spray away from your eyes.
• When using the inhaler for the first time or after more than three days, prime with four test sprays.
• Weekly cleaning with warm water and thorough air drying of the actuator (mouthpiece).
• When utilising a metered-dose inhaler, a spacer or valved holding chamber is advised.
• 200 actuations are in each inhaler; discard when the display window reads 0.

Nebulization solution:

• Its  Safety and efficacy were established when administered with the following nebulizers:
  • PARI LC Jet,
  • PARI LC Plus, as well as the following compressors:
    • PARI Master,
    • Dura-Neb 2000, and
    • Dura-Neb 3000.
• The concentrated solution should be diluted prior to use.
• Blowby administration is not recommended, use a mask device if the patient unable to hold the mouthpiece in the mouth for administration.

Mechanism of action of Levalbuterol (Xopenex):

Action on beta-2 receptors relaxes the bronchial smooth muscles with little effect on the heart rate

The beginning of action(as measured using a 15% increase FEV-1)

• Inhaler with metered dose: 5.5-10.2 minutes; Peak effect 76-78 minutes
• The solution to nebulization takes 10-17 minutes. Peak effect can be seen in about 1.5 hours

Time(as measured using a 15% increase FEV)

• Metered-dose inhaler: 3–4 hours; for some people, up to 6 hours
• Some patients may require up to 8 hours for the nebulization solution, which takes 5 to 6 hours.

Absorption:

• The systemic circulation absorbs a portion of the inhaled dose

Metabolism:

• SULT1A3 is largely used for gastrointestinal tract metabolism (sulfotransferase)

Half-life elimination:

• 3.3 to 4 hours

Time to peak, serum: Nebulization solution:

• Children: 0.3 to 0.6 hours,
• Adults: 0.2 hours

Excretion:

• Urine (80% to 100%),
• feces (<20%)

International Brand Names of Levalbuterol:

• Xopenex
• Xopenex Concentrate
• Xopenex HFA
• Albulair
• Inhawell
• Lebusal
• Levalin
• Levodose
• Levolin
• Seramar
• Ventoplus

Levalbuterol Brand Names in Pakistan:

No Brands Available in Pakistan.