Top Drugs in the US: #9 Albuterol

*Disclaimer: This is not intended to be fear mongering. However, people need to be informed of any risk associated with a medication. Sometimes, benefits outweigh the risks and therefore the medication is worth taking. Many times Pharmaceutical companies and doctors rely on the general population to just blindly take medication. FDA inserts are available to anyone, this post serves as an easy breakdown of its contents. Use this information to make an educated decision that is best for you.

Today’s top medication is Albuterol (a bronchodilator). This drug can be prescribe in many formats. For this post, we will specifically be talking about PROAIR HFA Inhalation Aerosol. This formulation of the drug is created for exercise-induced bronchospasm (asthma). This is your classic inhaler medication, although it is also sometimes prescribed in other formats for chest symptoms related to illness. As usual, majority of information will be pulled directly from the FDA label/insert available here. Other supporting sources will be linked throughout.

Definitions for Today:

  • Bronchospasm: spasmodic contraction of the muscular lining of the bronchi, as in asthma, causing difficulty in breathing.
  • Bronchodilator: a substance that acts to dilate constricted bronchial tubes to aid breathing, used especially for relief of asthma.
  • Bronchus: either of the two main branches of the trachea.
  • Tachycardia: excessively rapid heartbeat.
  • Urticaria: a transient condition of the skin, usually caused by an allergic reaction, characterized by pale or reddened irregular, elevated patches and severe itching; hives.
  • Angioedema: swelling that occurs just beneath the surface of the skin or mucous membranes.
  • Anaphylaxis: exaggerated allergic reaction.
  • MRHDID: Maximum Recommended Human Daily Inhalation Dose.

Warnings and Side Effects: As described by the FDA

  • Paradoxical Bronchospasm: This is essentially just a fancy term to describe the drug causing the very symptom/condition it is supposed to treat. The insert states that if this occurs, alternative therapy should be used. Also noted that paradoxical bronchospasm, when associated with inhaled formulations, frequently occurs with the first use of a new canister.
  • Cardiovascular Effects: can produce clinically significant cardiovascular effects in some patients as measured by pulse rate, blood pressure, and/or symptoms. These effects include tachycardia and palpitations. Caution should be used in patients with cardiovascular disorders.
  • Immediate hypersensitivity reaction: occurs immediately after administration of the drug and symptoms include: urticaria, angioedema, rash, bronchospasm, anaphylaxis, and oropharyngeal edema.
  • Hypokalemia: decrease in potassium levels. Usually a transient decrease and does not require supplementation. However, in patients with cardiovascular disorders this could cause worsening of those symptoms.

Other Reactions:

  • Common side effects noted in postmarketing experiences:
    • urticaria, angioedema, rash, bronchospasm, hoarseness, oropharyngeal edema, and arrhythmias (including atrial fibrillation, supraventricular tachycardia extrasystoles).
    • Angina, hypertension or hypotension, palpitations, central nervous system stimulation, insomnia, headache, nervousness, tremor, muscle cramps, drying or irritation of the oropharynx, hypokalemia, hyperglycemia, and metabolic acidosis.
Adverse reaction information obtained from a 6 week blinded study which compared PROAIR HFA Inhalation Aerosol (180 mcg four times daily) with a double-blinded matched placebo HFA-Inhalation
Aerosol and an evaluator-blinded marketed active comparator HFA-134a albuterol inhaler in 172 asthmatic patients 12 to 76 years of age. The table lists the incidence of all adverse events.

Other Data:

  • Pregnancy: It is important to note that there are no randomized clinical studies of albuterol use during pregnancy.
    • Available data from published epidemiological studies and post-marketing case reports of pregnancy outcomes following inhaled albuterol use do not consistently demonstrate a risk of major birth defects or miscarriage.
    • However, in animal reproduction studies subcutaneously administered albuterol sulfate produced cleft palate formation in 5 of 111 (4.5%) mice fetuses at an exposure nine-tenths of the MRHDID for adults.
    • It should also be noted that in a study on pregnant rats, it was found that drug-related material is transferred from the maternal circulation to the fetus.
  • Lactation: There are no available data on the presence of albuterol in human milk, the effects on the breastfed child, or the effects on milk production.
    • However, plasma levels of albuterol after inhaled therapeutic doses are low in humans, and if present in breast milk, albuterol has a low oral bioavailability. This means that essentially it will not be easily absorbed by the baby if transferred through breast milk.
  • Pediatric Use: In my opinion, there is very limited data on the safety of this drug in pediatric patients. Below is the info regarding studies in children from the FDA sheet:
    • The safety and effectiveness of PROAIR HFA Inhalation Aerosol for the treatment or prevention of bronchospasm in children 12 years of age and older with reversible obstructive airway disease is based on one 6-week clinical trial in 116 patients 12 years of age and older with asthma. It compared doses of 180 mcg four times daily with placebo, and one single-dose crossover study comparing doses of 90, 180, and 270 mcg with placebo in 58 patients.
    • The safety of PROAIR HFA Inhalation Aerosol in children 4 to 11 years of age is based on one 3-week clinical trial in 50 patients 4 to 11 years of age with asthma using the same formulation of albuterol as in PROAIR HFA Inhalation Aerosol comparing doses of 180 mcg four times daily with placebo.
  • Geriatric Use: Clinical studies have not included sufficient numbers of geriatric patients to conclude its safety in this population.
    • Other reported clinical experience has not identified differences in responses between elderly and younger patients. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

Non-clinical Toxicology

This section discusses effects noted in animal studies but not found clinically in humans.

  • Not found to be carcinogenic in rodents.
  • No findings of fertility impairment in rodents.
  • Intravenous studies in rats with albuterol sulfate have demonstrated that albuterol crosses the blood-brain barrier and reaches brain concentrations amounting to approximately 5% of the plasma concentrations. In structures outside the blood-brain barrier (pineal and pituitary glands), albuterol concentrations were found to be 100 times those in the whole brain.
  • Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when Beta-agonists and methylxanthines (most commonly caffeine) were administered concurrently. The clinical significance of these findings is unknown.
    • I would think this would be significant enough to warrant adding a contraindication to methylxanthines. Especially since coffee is such a popular drink choice.

Drug Interactions

  • Beta Blockers – will block the affects of the albuterol.
  • Diuretics – depending on the diuretic used, could cause excessive potassium.
  • Digoxin – there appears to be some affect by the albuterol that causes significant decrease of concentration of the Digoxin drug in the blood stream.
  • Monoamine Oxidase Inhibitors or Tricyclic Antidepressants – when taken with albuterol, cardiovascular affects can be significantly increased.

Mechanism of Action

Albuterol sulfate is a medication that helps relax the muscles in the airways. It does this by targeting specific receptors called beta2-adrenergic receptors. When these receptors are activated, they trigger a series of reactions inside the cells, ultimately leading to the relaxation of the muscles in the airways. This relaxation makes it easier to breathe.

Albuterol works throughout the airways, from the big tubes in the lungs down to the smaller ones, helping to open them up. It’s effective against different things that might make the airways tighten up.

Although it’s mainly focused on the airways, albuterol can sometimes affect the heart too. It tends to have fewer heart-related side effects compared to some other similar medications, but it’s still important to be aware of how it might affect your heart rate, blood pressure, and other heart-related factors.

Ingredients

  • Albuterol Sulfate – a racemic salt
  • HFA-134a (1, 1, 1, 2-tetrafluoroethane) – this serves as a propellant for the albuterol. It is a refrigerant. It is the same as HFC-134a used in fire extinguishers, just a higher level of purity. I will be covering this ingredient in a separate post at a later date. I am honestly appalled by this information.
  • Ethanol – an alcohol, used to dissolve the salt.

Manufacturer/Profitability

PROAIR HFA is manufactured by IVAX Pharmaceuticals Ireland and marketed by Teva Respiratory LLC.

IVAX Pharmaceuticals Ireland: Now also owned by Teva Respiratory LLC. The Ireland branch appears to be focused on the manufacture and development of specifically respiratory drugs. As of November 2023, the 2023 yearly revenue for Teva Pharmaceuticals (which absorbed IVAX) was expected to finish around $15 billion.

If you remember from last week’s post, Teva was also the distributor for Norco.

Cost of PROAIR HFA

Based on data on Drugs.com, PROAIR HFA is more expensive than something like Norco. Especially if you have a chronic condition requiring regular refills. The average cost for one 200-dose inhaler is $86.68. If you consider the possibility of needing on average 4 doses/day, each refill only lasts around a month. As usual, insurance coverages vary and therefore so do out of pocket costs.

According to Cost Plus Drugs, the manufacturing cost for this medication is around $23.

Final Thoughts

Similar to Norco, I definitely feel a medication like Albuterol has a necessary place in the world. Breathing is a requirement to live. However, I am honestly shocked/appalled/disappointed-but-not-surprised to learn it utilizes a refrigerant as a delivery method. I’ve always felt Big Pharma cares more about their bottom line than creating more safe medications. Ingredients like the refrigerant are definitely something I want to deep dive into. Perhaps that will be the next series.

Relating to it being a top prescribed drug, sadly I think this one also makes sense. Many people have breathing issues whether it be asthma, weight induced, regular illness, or toxic environmental exposure. I feel a lot of these could be eliminated by creating an overall less-toxic world. We need less pills and more exercise. Less chemicals and more natural alternatives.

Profitability wise, its not the MOST expensive drug I’ve ever seen. However, like Norco, lifelong users will contribute thousands to the pockets of Big Pharma. Especially with the 273% markup they are charging.

What are your thoughts on Albuterol? Let me know in the comments! Next week we will discuss Drug #8: Metformin.


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