Umeclidinium and Vilanterol Inhalation Powder - Indications, Contraindications, Pharmacology Aspects, Warnings and Precautions

Overview:

Umeclidinium and Vilanterol inhalation powder is a type of inhaler used to deliver a combination of two medications, Umeclidinium and Vilanterol, to patients through oral inhalation. Umeclidinium bromide and Vilanterol trifenatate are the active ingredients. Umeclidinium bromide is a white powder that is slightly soluble in water, while Vilanterol trifenatate is also a white powder but is practically insoluble in water. The inhaler itself is made of light gray and red plastic and contains two foil blister strips. Each strip has blisters containing a mix of the medication powder, magnesium stearate, and lactose monohydrate. One blister strip contains Umeclidinium, and the other contains Vilanterol. Once the inhaler is activated, the powder in both blisters is exposed and ready to be inhaled. The Food and Drug Administration approved Umeclidinium and Vilanterol inhalation powder in 2013.

Available Doses and Dosage Forms:

The inhaler for Umeclidinium and Vilanterol Inhalation Powder is a plastic device that is light gray and red. Inside, there are two foil strips with powder meant for breathing in through the mouth. One strip has Umeclidinium powder (62.5 mcg (microgram) per dose), and the other has Vilanterol powder (25 mcg per dose).

For Patients:

How Does Umeclidinium and Vilanterol Inhalation Powder Work in Chronic Obstructive Pulmonary Disease?

Chronic obstructive pulmonary disease (COPD) is a lung condition often linked to smoking or pollution, leading to symptoms like coughing, difficulty breathing, and fatigue. While there is no cure, medications can help manage symptoms. Umeclidinium and Vilanterol are drugs used to treat COPD by improving airflow. Umeclidinium prevents the muscles around the airways from tightening, while Vilanterol relaxes these muscles, making it easier to breathe. Together, these medications work to open up the airways and keep them open, helping people with COPD breathe more easily and feel more comfortable.

What Is the Dosage of Umeclidinium and Vilanterol Inhalation Powder?

Umeclidinium and Vilanterol inhalation powder, a combination medication of Umeclidinium and Vilanterol, should be taken once daily using an inhaler. It is important to use it at the same time every day and not to exceed one dose within 24 hours. There is no need to change the dosage for older patients, those with kidney issues, or those with moderate liver problems.

How Effective Is Umeclidinium and Vilanterol Inhalation Powder?

Umeclidinium and Vilanterol Inhalation Powder medication helps to open up the air passages in the lungs, which makes breathing easier. It contains two types of drugs: an anticholinergic and a bronchodilator. People often refer to it as a controller inhaler because it helps manage and control breathing problems.

What Are the Things to Inform the Doctor Before Taking the Umeclidinium and Vilanterol Inhalation Powder?

• Before starting Umeclidinium and Vilanterol, let the doctor and pharmacist know if the person is allergic to any of its ingredients, including Umeclidinium, Vilanterol, or milk protein. Also, inform them about any other medications, vitamins, or herbal products they are taking.

• If an individual has asthma, the doctor may advise against using Umeclidinium and Vilanterol unless they are also using an inhaled steroid medication.

• Be sure to inform the doctor if the person has a history of certain health conditions like high blood pressure, irregular heartbeat, seizures, diabetes, glaucoma, urinary or prostate issues, or liver disease.

• If the person is pregnant, planning to become pregnant, or breastfeeding, discuss this with the doctor before using this medication.

• Keep in mind that using Umeclidinium and Vilanterol may sometimes cause wheezing or difficulty in breathing after inhalation. If this occurs, contact the doctor immediately and avoid using the medication again unless instructed otherwise.

What Are the Side Effects of Umeclidinium and Vilanterol Inhalation Powder?

• Serious asthma-related events like hospitalizations, needing a ventilator, or even death can occur, especially if LABA (long acting beta agonists) medications like Vilanterol are used alone for asthma. Umeclidinium and Vilanterol Inhalation Powder are not meant to treat asthma.

• Paradoxical bronchospasm, where the airways suddenly tighten instead of opening up.

• Cardiovascular effects could include changes in heart rate, blood pressure, or heart symptoms.

• Worsening of narrow-angle glaucoma, a condition affecting the eyes.

• Worsening of urinary retention, especially in patients with existing bladder issues.

Overdose:

No instances of overdose have been reported with Umeclidinium and Vilanterol inhalation powder. However, since it contains both Umeclidinium and Vilanterol, the potential risks of overdosing with each component are applicable. If an overdose occurs, Umeclidinium and Vilanterol Inhalation Powder should be stopped, and appropriate supportive treatment should be initiated. A beta-blocker may be considered cautiously, but it can cause bronchospasm. Cardiac monitoring is advised in cases of overdose. High doses of Umeclidinium may cause anticholinergic symptoms, but systemic effects were not seen. Vilanterol overdose may lead to excessive beta-adrenergic stimulation, resulting in symptoms like chest pain, changes in blood pressure or heart rate, nervousness, and more. Severe cases may even lead to cardiac arrest or death.

Storage:

Umeclidinium and Vilanterol Inhalation Powder come in a plastic inhaler with two strips inside, each containing blisters of medication. One strip has Umeclidinium, and the other has Vilanterol. Each dose is prepared by using one blister from each strip. The inhaler is stored in a foil tray with a lid and a drying agent to protect it from moisture. It should be stored at room temperature away from direct sunlight and heat, and out of children's reach. Before using, keep it inside the foil tray and only take it out when ready to use. Once opened, use it within six weeks or when the counter shows zero, whichever comes first. The inhaler is disposable and should not be taken apart or reused.

For Doctors:

Indication:

Umeclidinium and Vilanterol inhalation powder are used to help manage COPD, but it is not meant to provide quick relief for sudden breathing problems or to treat asthma. It has not been proven safe or effective for asthma treatment.

Dose:

For adults with chronic obstructive pulmonary disease (COPD), the usual dose is one inhalation of Umeclidinium (62.5 mcg) and Vilanterol (25 mcg) once a day. A person should not take more than one inhalation every 24 hours. This medication helps with the long-term treatment of breathing difficulties in COPD, which includes chronic bronchitis and emphysema. No dose adjustment required for kidney or liver issues.

What Are the Pharmacological Aspects of Umeclidinium and Vilanterol Inhalation Powder?

• Pharmacodynamics: In studies with healthy individuals, Umeclidinium and Vilanterol inhalation powder caused a slight prolongation of the QTc interval, which indicates a change in heart rhythm, and an increase in heart rate compared to placebo. The higher the dose, the greater the effect on heart rate. However, in people diagnosed with COPD, Umeclidinium and Vilanterol inhalation powder did not show any significant impact on heart rhythm when monitored over 24 hours.

• Mechanism of Action: Umeclidinium and Vilanterol inhalation powder contains two different types of medications: Umeclidinium and Vilanterol, each with its way of working in the body. Umeclidinium is an anticholinergic medication. It blocks certain receptors, called muscarinic receptors, in the airways, which helps relax the muscles around the airways, making breathing easier. Vilanterol, on the other hand, is a type of medication called a long-acting beta-agonist (LABA). It works by stimulating certain receptors, called beta2-receptors, in the airways. This stimulation leads to the relaxation of the muscles around the airways, making it easier to breathe. While beta2-receptors are mainly found in the lungs, there are also some in the heart, which could potentially affect heart function. Both medications, Umeclidinium and Vilanterol, ultimately help to relax the muscles in the airways, making breathing easier for people with conditions like COPD.

• Pharmacokinetics: Both Umeclidinium and Vilanterol show linear pharmacokinetics, meaning that the amount of drug in the body increases proportionally with the dose.

  • Both drugs are absorbed mostly from the lungs into the bloodstream. Umeclidinium and Vilanterol reach their highest blood levels within five to 15 minutes after inhalation. With repeated doses of Umeclidinium and Vilanterol inhalation powder, steady levels of the drugs in the blood are reached within two weeks.

  • Distribution happens after entering the bloodstream. Umeclidinium and Vilanterol mainly bind to proteins in the blood and have large volumes of distribution, meaning they can spread widely.

  • Metabolism occurs when Umeclidinium is primarily broken down by an enzyme called CYP2D6, while Vilanterol is mainly broken down by CYP3A4. These drugs are also substrates for a transporter called P-glycoprotein. Metabolism results in the formation of inactive or less active breakdown products.

  • Elimination happens when both drugs have an effective half-life of about 11 hours, meaning it takes about 11 hours for half of the drug to be removed from the body. Umeclidinium is eliminated mostly through feces (solid waste), while Vilanterol is eliminated through urine (liquid waste).

Toxicity:

Carcinogenicity, mutagenicity, and effects on fertility were not specifically studied for Umeclidinium and Vilanterol inhalation powder as a combination product. However, studies have been conducted on its components, Umeclidinium and Vilanterol.

Umeclidinium:

In studies on rats and mice, Umeclidinium did not cause an increase in tumors at doses up to 20 and 25 times the maximum recommended human dose. Umeclidinium did not show any genotoxic (DNA (deoxyribonucleic acid)-damaging) effects in various tests. There was no evidence of fertility problems in male and female rats at doses up to 100 and 50 times the maximum recommended human dose.

Vilanterol:

In studies on mice and rats, Vilanterol caused some tumors in the ovaries and pituitary glands at very high doses, much higher than the recommended human dose. Vilanterol did not show any genotoxic effects in most tests, but there was some uncertainty in one test. No fertility issues were observed in male and female rats at doses much higher than the recommended human dose. Overall, while some tumor findings were observed in animal studies with Vilanterol, it is uncertain how relevant these findings are to human use. Umeclidinium did not show any signs of causing tumors or fertility issues in animal studies.

Clinical Studies:

The safety and effectiveness of Umeclidinium and Vilanterol Inhalation Powder were evaluated through various trials involving thousands of participants with COPD. These trials assessed lung function and the frequency of COPD exacerbations.

• Dose-ranging Trials: Before Umeclidinium and Vilanterol Inhalation Powder was finalized, its components, Umeclidinium and Vilanterol, underwent dose-ranging trials to determine the most effective doses. These trials helped establish the once-daily doses used in the final product.

• Confirmatory Trials: Several trials were conducted to confirm the effectiveness of Umeclidinium and Vilanterol inhalation powder. These trials compared Umeclidinium and Vilanterol Inhalation Powder with its components and placebos. The results showed that Umeclidinium and Vilanterol inhalation powder significantly improved lung function compared to placebos and its components.

• Exacerbations: In one important trial, Umeclidinium and Vilanterol Inhalation Powder were compared with other COPD treatments to see how well they reduced the frequency of COPD exacerbations (worsening of symptoms). Results showed that Umeclidinium and Vilanterol inhalation powder reduced exacerbations significantly compared to other treatments.

Overall, these trials demonstrated that Umeclidinium and Vilanterol Inhalation Powder effectively improves lung function and reduces the frequency of COPD exacerbations, providing valuable relief to COPD patients.

What Are the Contraindications of Umeclidinium and Vilanterol Inhalation Powder?

If someone is severely allergic to milk proteins or has shown strong allergic reactions to Umeclidinium, Vilanterol, or any ingredients in Umeclidinium and Vilanterol Inhalation Powder, they should not use it. Also, using a long-acting beta2-adrenergic agonist (LABA) without an inhaled corticosteroid (ICS) is not recommended for asthma patients. Umeclidinium and Vilanterol Inhalation powder are not meant for treating asthma.

Warnings and Precautions:

• Umeclidinium and Vilanterol inhalation powder have not been proven safe or effective for treating asthma. Using medications with the active ingredient Vilantero alone without a corticosteroid for asthma may increase the risk of severe asthma-related events like hospitalizations or even death. However, when combined with a corticosteroid, this risk does not seem to increase significantly based on large studies.

• Umeclidinium and Vilanterol inhalation powder should not be started when someone's COPD is rapidly worsening or during severe episodes. It is not meant to be used for immediate relief during acute breathing problems. Patients already taking frequent short-acting inhalers should use them only as needed for sudden symptoms, not regularly alongside Umeclidinium and Vilanterol Inhalation Powder.

• If COPD symptoms worsen despite using Umeclidinium and Vilanterol Inhalation Powder, if short-acting inhalers become less effective, or if they are needed more often, it could indicate a decline in the condition. In such cases, a doctor should reevaluate the treatment plan instead of increasing the dosage of Umeclidinium and Vilanterol Inhalation Powder.

• Umeclidinium and Vilanterol inhalation powder should not be used more often or at higher doses than directed. It also should not be used with other medications containing similar ingredients, as it could lead to serious side effects especially related to the heart, or even death.

• When considering using Umeclidinium and Vilanterol Inhalation Powder alongside strong inhibitors like Ketoconazole, Clarithromycin, or others, caution is advised due to the potential increased risk of heart problems.

• Umeclidinium and Vilanterol inhalation powder, like other inhalers, could cause sudden tightening of the airways (bronchospasm), which can be dangerous. If this happens, stop using Umeclidinium and Vilanterol inhalation powder immediately and use a quick-relief inhaler.

• Allergic reactions such as severe swelling, rash, or difficulty breathing might occur after using Umeclidinium and Vilanterol Inhalation Powder. If these reactions happen, stop using it.

• Vilanterol, one of the components of Umeclidinium and Vilanterol Inhalation Powder, might affect the heart and blood pressure. If a person experiences any unusual changes in heart rate or blood pressure, the doctor might stop Umeclidinium and Vilanterol Inhalation Powder.

• Patients with heart conditions should be cautious when using Umeclidinium and Vilanterol Inhalation Powder. In a study, there were slightly more heart-related problems in patients using Umeclidinium and Vilanterol Inhalation Powder compared to other similar treatments.

• Umeclidinium and Vilanterol Inhalation Powder should be used carefully in patients with certain conditions like seizures, overactive thyroid, or extreme sensitivity to similar medications.

• Patients with narrow-angle glaucoma or difficulty urinating should use Umeclidinium and Vilanterol inhalation powder cautiously and watch for worsening symptoms.

• Umeclidinium and Vilanterol inhalation powder might cause low potassium levels or temporarily raise blood sugar levels in some patients, but this was not a common problem in studies involving COPD patients.

What Are the Drug Interactions of Umeclidinium and Vilanterol Inhalation Powder?

• Vilanterol, one of the components in Umeclidinium and Vilanterol Inhalation Powder, is affected by certain medications that impact the CYP3A4 enzyme. Using strong inhibitors like Ketoconazole alongside Umeclidinium and Vilanterol Inhalation Powder can increase the levels of Vilanterol in the body, so it is important to use caution when considering these combinations.

• Additionally, when patients are taking medications like Monoamine oxidase inhibitors, tricyclic antidepressants, or drugs known to prolong the QTc interval, Vilanterol should be used cautiously due to potential cardiovascular effects.

• Beta-blockers can counteract the effects of Vilanterol and may cause severe breathing problems in COPD patients, so they are generally avoided unless there are no other options. If necessary, cardioselective beta-blockers may be considered but with caution.

• Non-potassium-sparing diuretics can interact with Vilanterol, possibly causing electrolyte imbalances or heart-related issues, so their coadministration should be approached carefully.

• Using Umeclidinium and Vilanterol Inhalation Powder with other medications containing anticholinergics may lead to increased side effects, so it is best to avoid combining them if possible.

Specific Considerations:

• Pregnancy: There is limited data on the use of Umeclidinium and Vilanterol Inhalation Powder during pregnancy. Animal studies showed no adverse effects on fetal development, but human studies are lacking. The risks to pregnant women are uncertain, so caution is advised.

• Labor and Delivery: Umeclidinium and Vilanterol Inhalation Powder's effects during labor are not well-studied. Due to potential effects on uterine contractions, its use during labor should be limited to cases where benefits outweigh risks.

• Breastfeeding: It is unknown if Umeclidinium and Vilanterol Inhalation Powder components pass into human milk. Umeclidinium was detected in the offspring of lactating rats, suggesting it may transfer into maternal milk. The decision to breastfeed should consider both the benefits and potential risks.

• Pediatric Use: Umeclidinium and Vilanterol Inhalation Powder is not recommended for children as its safety and effectiveness have not been established in this population.

• Geriatric Use: Dosage adjustments are not necessary for elderly patients, but some individuals may be more sensitive to the medication. Clinical trials included older adults, showing similar safety and effectiveness compared to younger patients.

• Hepatic Impairment: Moderate liver impairment does not significantly affect Umeclidinium and Vilanterol Inhalation Powder levels in the body. However, studies on severe liver impairment have not been conducted.

• Renal Impairment: Severe kidney impairment does not significantly increase the levels of Umeclidinium and Vilanterol components in the body. No dosage adjustment is needed for patients with renal impairment.