Olodaterol - Mechanism of Action, Indications, Dosage, and Adverse Drug Reactions

Overview

Olodaterol is a daily inhaled beta2-adrenoceptor agonist for adults with chronic obstructive pulmonary disease (COPD) (a chronic inflammatory lung disease that results in obstructed airflow from the lungs). It improves lung function, reduces rescue medication use, and may improve dyspnea (shortness of breath) and quality of life.

After six weeks, it improves exercise endurance. The US FDA (United States Food and Drug Administration) approved Olodaterol on July 31, 2014, and it can be administered daily due to its quick, 24-hour bronchodilatory action. Nasopharyngitis (an inflammation of the nasal passages and the throat) is the most common adverse effect.

Drug Group

The class of drugs known as long-acting beta2-adrenergic agonists (LABAs), also known as beta2-adrenoceptor agonists, includes Olodaterol. It works by attaching to and activating beta2-adrenergic receptors in the lungs, opening airways, and promoting respiratory passages' relaxation.

Indications

Olodaterol is recommended for individuals with chronic obstructive pulmonary disease (COPD), including chronic bronchitis (long-term inflammation of the bronchi) and/or emphysema (lung diseases that cause damage in the lung air sacs), as a once-daily maintenance bronchodilator therapy for airflow restriction over the long term.

Significant Restrictions:

• Olodaterol is not recommended as a treatment for the acute exacerbation of COPD.

• Asthma (a condition where airways become inflamed, narrow, and swollen, producing extra mucus and making breathing difficult) treatment with Olodaterol is not recommended.

Contraindications

For patients with asthma who are not taking long-term asthma treatment, all LABA is contraindicated. It is not recommended to use Olodaterol to treat asthma.

Dosage Forms and Available Strengths

A dose of Olodaterol is administered through inhalation spray, with a 2.7 mcg (microgram) of Olodaterol hydrochloride per actuation (2.5 mcg) concentration; two actuations provide a single dose.

Warnings and Precautions

• Individuals with COPD who are rapidly worsening should not start Olodaterol.

• Avoid using this to treat sudden symptoms. Concomitant short-acting beta2 agonists might be administered to provide immediate relief.

• Avoid taking more than the suggested amount of Olodaterol. When Olodaterol is used excessively or in combination with other drugs that include LABA, it can have lethal and clinically significant cardiovascular consequences.

• Paradoxical bronchospasm with a life-threatening risk can happen. Stop using Olodaterol right away.

• When administering sympathomimetic medications to patients who have thyrotoxicosis (high thyroid hormones like T3 and T4), cardiovascular or convulsive disorders (a state when the central nervous system exhibits excessive, aberrant neuronal discharge), or who are sensitive to sympathomimetic medications, use caution.

For Patients

What Is Chronic Obstructive Pulmonary Disease (COPD)?

Chronic obstructive pulmonary disease (COPD) is a long-term lung disease defined by breathing difficulties, coughing, mucus production, and wheezing. It is brought on by several progressive lung diseases, with emphysema and chronic bronchitis (explain) being the most common. Symptoms include shortness of breath, chest tightness, a chronic cough, frequent respiratory infections, and weight loss. Causes include long-term exposure to irritating gases or particulate matter, usually from cigarette smoke, or occupational exposure to dust, fumes, or chemicals.

How Does Olodaterol Work?

The lungs beta2-adrenergic receptors, which are normally stimulated by Epinephrine, are triggered by the beta2-adrenergic agonist Olodaterol. These receptors mediate bronchodilation and smooth muscle relaxation. Adenylate cyclase, which is activated by Olodaterol stimulation of a related G protein, catalyzes the production of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA), which relaxes the smooth muscles of the airways and causes bronchodilation.

What Are the Clinical Uses of Olodaterol?

Clinical uses of Olodaterol include the following:

• Long-Term Treatment of COPD: Olodaterol is used as a long-term (maintenance) medication to prevent and reduce wheezing (a high-pitched whistling sound produced during breathing) and dyspnea brought on by respiratory conditions like COPD, which includes emphysema and/or chronic bronchitis.

• Lung Function Improvement: In COPD patients, Olodaterol single doses have been demonstrated to enhance forced expiratory volume in one second (FEV1) for 24 hours, enabling once-daily dosing.

• Reduction of COPD Exacerbations: Although it may lessen exacerbations, it is unlikely to change the individual's life expectancy or the rate at which their lungs deteriorate.

How Is Olodaterol Administered?

The recommended dosage for Olodaterol is two inhalations daily at the same time, with no more than two inhalations every 24 hours. Before use, the cartridge is inserted into the inhaler and primed. Patients should actuate the inhaler toward the ground until an aerosol cloud is visible and repeat the process three times.

If not used for more than three days, patients should actuate the inhaler once. If not used for more than 21 days, patients should actuate the inhaler until an aerosol cloud is visible and repeat the process three times. No dosage adjustment is required for geriatric patients, those with mild and moderate hepatic impairment, or renal-impaired patients.

What Are the Side Effects of Olodaterol?

Inhaling Olodaterol may have unfavorable effects. If any of the following symptoms are severe or persistent, let the physician know:

• Runny nose, cough, and fever.

• Joint pain.

• Nervousness.

• Uncontrollably shaking a bodily portion.

• Cramps.

• Unable to fall or remain asleep.

• Constipation.

Certain adverse effects of Olodaterol may be dangerous.

Call the physician right away if patients have any of these symptoms or seek emergency care:

• Rapid, hammering, or erratic heartbeat in the chest.

• Chest pain.

• Itching, rashes, and hives

• Breathing and swallowing difficulties.

• Tongue, lip, or cheek swelling.

• Frequent or painful urination.

Inhaling Olodaterol may result in additional adverse effects. If patients have any odd side effects while taking Olodaterol, contact the physician who prescribed it.

What Are the Things to Inform the Doctor Before Taking Olodaterol?

• If patients are allergic to any of the substances in Olodaterol inhalation, other drugs, or Olodaterol itself, let the physician and pharmacist know before inhaling. For an ingredient list, read the medication guide or ask the pharmacist.

• Inform the doctor about using any other LABA, such as Vilanterol, Indacaterol, Salmeterol, Arformoterol, or Formoterol. The doctor will determine which medications patients should take and which ones they should quit.

• Inform the doctor and pharmacist about any additional prescription and over-the-counter drugs, vitamins, dietary supplements, and herbal remedies patients now take or intend to use. Make sure to bring up any of these: Aminophylline; Amiodarone; antidepressants such as Amitriptyline, Amoxapine, Clomipramine, Desipramine, Doxepin, Imipramine, Nortriptyline, Protriptyline, and Trimipramine; beta-blockers such as Atenolol, Labetalol, Metoprolol, Nadolol, Propranolol, and Sotalol; diet pills; diuretics; Epinephrine; Erythromycin; medications for colds such as Phenylephrine and Pseudoephedrine; monoamine oxidase (MAO) inhibitors, including Isocarboxazid, Linezolid, Phenelzine, Rasagiline, Selegiline, and Tranylcypromine; Moxifloxacin; steroids such as Dexamethasone, Methylprednisolone, and Prednisone; Pentoxifylline, and Theophylline. The physician might need to carefully monitor patients for any negative effects or adjust the dosages of the medications. Tell the physician about all the medications patients use, including those not on this list, as many other medications may also interact with Olodaterol inhalation.

• Inform the physician if patients have asthma. If patients are not utilizing Olodaterol inhalation with an inhaled steroid medicine, the doctor will advise against using it.

• Inform the physician if patients have now or previously suffered from high blood pressure, diabetes (high blood sugar), seizures (an unexpected, uncontrollable rise in brain activity), QT prolongation (an abnormal heart rhythm that can cause convulsions, fainting, loss of consciousness, or abrupt death), irregular heartbeat, or diseases of the heart, liver, or thyroid.

• Inform the doctor if patients are nursing a baby, intend to get pregnant, or are already pregnant. Contact the doctor if patients become pregnant while using Olodaterol inhalation.

• Patients should be aware that breathing difficulties and wheezing might occasionally be experienced after inhaling Olodaterol. Make a quick call to the physician if this occurs. Reusing Olodaterol inhalation is not advised unless specifically instructed by the physician.

Dietary Considerations:

Maintain the normal diet unless instructed by the doctor.

Missed Dose:

As soon as patients remember, take an inhalation of the missed dose. On the other hand, if the next dose of Olodaterol is almost here, skip the missed one and stick to the usual dosage plan. Take only a single dose of Olodaterol in 24 hours.

Overdose:

Call the poison control helpline in the event of Olodaterol overdose. Call emergency services right away if an individual has passed out, is having a seizure, is having difficulty breathing, or cannot be made to wake up.

An Olodaterol overdose may manifest as any of the following symptoms:

• Chest discomfort.

• Heart pounding.

• Lightheadedness.

• Nervousness.

• Unable to stop a body part from shaking.

• Difficulty falling asleep or staying asleep.

• Anxiety (feeling of fear and uneasiness).

• Headache.

• Xerostomia (dry mouth).

• Nausea.

• Exhaustion.

Storage and Disposal:

Olodaterol medication should be kept at 77°F (degree Fahrenheit) (25°C (degree Celsius)); exceptions are allowed between 15°C and 30°C (59°F and 86°F), out of children's reach, and in its original container. Avoid inhalers and cartridges from freezing. Throw away the inhaler three months from the date of purchase or when the cartridge locks after all medication is used, whichever occurs first. Make use of a medicine take-back program to eliminate unnecessary Olodaterol medications.

For Doctors

Pharmacodynamics:

With significantly lower levels of activity at the beta1- and beta3-adrenergic receptors, which are frequently found in cardiac, smooth muscle, and adipose tissue, respectively, Olodaterol is a strong agonist of the human beta2-adrenergic receptor in vitro and is highly selective for this receptor. Bronchodilation and smooth muscle relaxation in the lungs are brought on by binding to the receptor. Moreover, it has been demonstrated to reverse active bronchoconstriction effectively.

Mechanism of Action

Olodaterol is a beta2-adrenergic agonist that activates beta2-adrenergic receptors in the lungs, causing smooth muscle relaxation and bronchodilation. Its activation triggers the formation of cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA), which relax airway smooth muscles, thereby promoting bronchodilation.

Pharmacokinetics

Absorption: After inhaling Olodaterol, Olodaterol typically reaches its maximal plasma concentration 10 to 20 minutes later. The primary factor influencing the systemic availability of Olodaterol following inhalation is lung absorption, with ingested doses having a negligible impact on systemic exposure.

Distribution: Olodaterol binds to human plasma proteins in vitro with a 60 percent binding rate that is concentration-independent.

Metabolism: Olodaterol is metabolized through direct glucuronidation and O-demethylation, with the unconjugated demethylation product being active at β2-adrenoceptors but not detectable in plasma after chronic inhalation of the therapeutic dose of 5 micrograms.

Excretion: After receiving [14C]-labeled Olodaterol intravenously, 38 percent and 53 percent of the radioactive dose were found in the urine and feces, respectively. Following intravenous treatment, 19 percent of the unmodified Olodaterol was found in the urine. Merely nine percent of Olodaterol and/or its metabolites were found in urine after oral treatment; the majority, 84 percent, were found in feces. After intravenous administration, the terminal half-life is 22 hours.

Drug Interactions

• The action of other adrenergic medications may be amplified. Use with caution when using.

• Hypokalemia (low blood potassium level) or ECG (electrocardiogram) abnormalities may be exacerbated by xanthine derivatives, steroids, diuretics, or non-potassium-sparing diuretics. Use carefully when using.

• Tricyclic antidepressants, MAO inhibitors, and medications that lengthen the QTc interval may have a greater effect on the cardiovascular system. Use with the utmost care.

• Beta-blockers may make treatment less effective. Use only if medically necessary and with caution.

Clinical Studies

The Olodaterol clinical development program involved eight confirmatory trials for COPD patients, four dose-ranging trials for asthma patients, and three dose-ranging trials for COPD patients. Four asthmatic patients participated in randomized, double-blind, placebo-controlled dose-ranging trials that assessed dosages ranging from 2 to 20 mcg.

The outcomes of asthma patients aligned with the findings of dose-ranging trials conducted on individuals with COPD. For asthma, Olodaterol is not recommended. Confirmatory COPD experiments were conducted to assess 5- and 10-mcg dosages based on the outcomes of the dose-ranging trials.

There was no discernible advantage to the 10 mcg dosage over the 5 mcg dose. Compared to those treated with a placebo, patients treated with Olodaterol 5 mcg required less rescue albuterol. After 12 weeks of treatment, serial spirometric evaluations were carried out pre-dose and up to 12 hours post-dosing in a subgroup of 562 patients. Two sets of replicate, placebo- and active-controlled, 6-week cross-over trials including 199 and 230 patients with moderate to very severe COPD were conducted to assess the bronchodilatory profile of Olodaterol 5 mcg. After six weeks, the main objectives for FEV1 AUC0 to 12 hours and FEV1 AUC12 to 24 hours were altered from the pre-treatment baseline.

Specific Considerations

• Pregnancy: The pregnancy labeling rule for prescription drug products has been amended by the US FDA. Now, healthcare providers must provide women with information about drug use during pregnancy and make decisions about prescriptions by providing a summary of the risks, a discussion of the data supporting that summary, and other pertinent information. The pregnancy category, according to the US FDA for Olodaterol is not allocated. Olodaterol should only be used during pregnancy if the benefits to the mother outweigh the risks to the unborn child.

• Breastfeeding: There is no evidence of Olodaterol's presence in human milk, how it affects a breastfed infant, or how much milk it produces, and the manufacturer does not advise using it during breastfeeding.

• Pediatric Use: Olodaterol is not recommended for pediatric use due to its safety and effectiveness in this age group.

• Geriatric Use: According to the study, elderly patients did not require Olodaterol dosage adjustments. 485 of the 876 patients were younger than 65, and 44.6 percent were older. There were no discernible variations in overall efficacy, and the adverse drug reaction profiles of the elderly and general patient populations were comparable.

• Hepatic Impairment: No research was done on severe hepatic impairment, and the study identified no significant differences in Cmax, AUC, or protein binding between mild and moderately hepatically impaired patients and healthy controls.

• Renal Impairment: Severe renal impairment did not result in any significant clinical changes in Cmax or AUC compared to healthy controls.