Umeclidinium - Uses, Warnings, and Pharmacology

Overview:

Umeclidinium is a long-acting muscarinic antagonist drug that can be used for long-term maintenance and treatment of airflow obstruction in patients suffering from a chronic obstructive pulmonary disease (COPD). The drug is available as an inhalation therapy which should be used once daily or as a fixed-dose combination with the long-acting beta 2-agonist Vilanterol. Umeclidinium inhibits the binding of acetylcholine and thus opens up the airway by preventing bronchoconstriction in cases of COPD (chronic pulmonary disease). Umeclidinium is clinically significant and also sustains improvements in lung function. It is also used in the treatment of bronchitis and emphysema.

Warnings for the Use of Umeclidinium:

• The drug should be avoided if the patient is allergic to it or severely allergic to milk protein.

• Umeclidinium is not a fast-acting inhalation drug for bronchospasm and does not work immediately after administration. Thus in cases of acute bronchospasm, it is important to take a fast acting drug.

• Umeclidinium should not be taken if the breathing problem does not improve after taking a few initial doses.

What Is Chronic Obstructive Pulmonary Disease?

The symptoms of COPD are difficulty breathing, sputum (mucus) production, cough, and wheezing. Patients suffering from chronic obstructuve pulmonary disease (COPD) develop an increased risk of diseases to the heart, lungs, and some other organs.

Causes of Chronic Obstructive Pulmonary Disease

• The most common cause of chronic obstructive pulmonary disease is long-term exposure to irritating gasses or particulate matter.

• Diseases that can lead to chronic obstructive pulmonary disease are emphysema and chronic bronchitis. Emphysema is a lung disorder in which the air sacs of the lungs are damaged, leading to shortness of breath. Chronic bronchitis is prolonged inflammation in the bronchi of the lungs. Emphysema and chronic bronchitis occur together and lead to chronic obstructive pulmonary obstruction.

Symptoms Seen in Chronic Obstructive Pulmonary Disease

• Wheezing: Coarse rattle or shrill whistle is heard when the airway is partially blocked.

• Shortness of breath, particularly during physical activities.

• Chest tightness or stiffness.

• Lack of energy and fatigue.

• Respiratory infections are frequent.

• Chronic cough produces clear, white, greenish, or yellow mucus.

• In later stages, the chronic obstructive pulmonary disease may lead to unintentional weight loss.

• Swellings in the ankles, feet, or legs.

More About the Drug:

For Patients:

Before Starting the Drug Umeclidinium:

Some of the conditions which should be mentioned to the doctor or the pharmacist before starting the drug are:

• Allergies due to any drug or Umeclidinium.

• Allergies to milk proteins such as whey or casein.

• Glaucoma: It is an eye disease that leads to vision loss in one or both eyes. It is caused due to fluid build-up behind the eye, which puts pressure on the optic nerve and damages it. There are two types of glaucoma which are open angle and closed angle. Open-angle glaucoma is when the blockage due to fluid is not seen in the tests, whereas closed-angle glaucoma is when the blockage is seen in the tests.

• Heart diseases such as heart attack or congestive heart failure.

• Urination problems may make it difficult to excrete the drug outside the body.

• Enlarged prostate due to an increase in the number of prostate cells. This condition generally occurs in older adults.

• Pregnant or breastfeeding mothers should inform the doctor before starting the consumption of Umeclidinium.

• Age of the individual as the drug should not be given to anyone less than 18 years of age.

How Is the Drug Umeclidinium Taken?

• The instructions given by the doctor should be followed strictly while taking the drug. The prescription label should also be read properly before starting the drug.

• The drug should be taken every day at the same time and not more than once in 24 hours.

• The dose should be taken strictly, as the healthcare professional advice; overdosing should be avoided.

• Umeclidinium should not be considered a rescue medicine for bronchospasm attacks. It is not a fast-acting inhalation medicine so it should not be used in cases of acute breathing attacks.

• The inhaler device should not be cleaned or opened apart as it may damage the drug.

Storage and Disposal: The drug should be stored at room temperature away from moisture and away from the reach of children. The inhaler device should be in a sealed foil tray before it is used. The inhaler should be thrown away after six weeks of opening or when the dose indicator shows a zero on the inhaler.

What if a Dose of Umeclidinium Is Missed?

If the dose of the drug is missed, it is advised to take it as soon as possible, but if the time is almost for the next dose, it is advised to avoid the dose and take the next dose. Two doses of the drug should not be taken at a time.

What Should Be Avoided While Using Umeclidinium?

Any other bronchodilator which may contain Aclidinium, Arformoterol, Indacaterol, Olodaterol, Tiotropium, or Salmeterol should not be used while using Umeclidinium.

Side Effects of Umeclidinium:

Some of the common side effects shown by Umeclidinium are:

• Cold symptoms include a stuffy nose, sore throat, sneezing, and cough.

• Bruised or darkened skin color.

• Irregular and fast heartbeats.

• Pain in muscles or joints.

• Stomach pain.

• Changed senses of taste.

Some of the serious side effects caused by Umeclidinium are:

• Choking or wheezing or any other breathing issue after using Umeclidinium.

• Blurred vision, eye pain, vomiting, and nausea.

• Seeing halos or bright colors around lights.

• Frequent urination which can be painful and difficult.

• Allergic reactions leading to hives, rashes, difficulty in breathing, swelling of the face, tongue, or lip, and itching.

It is advised to call the doctor immediately if there are any of these serious side effects seen after taking Umeclidinium.

Some of the less common side effects of Umeclidinium are:

• Chest pain.

• Chills.

• Body pain.

• Cough.

• Bladder pain.

• Dryness or soreness of the throat.

• Ear congestion.

• Fever.

• Burning sensation while urinating.

• Loss of voice.

• Trouble swallowing.

• Tender and swollen glands in the neck.

• Voice changes

• Tightness or stiffness in the chest.

Dosage of Umeclidinium: The adult dose for Umeclidinium for the maintenance of chronic obstructive pulmonary disease is one inhalation of 62.5 mcg orally once a day. The maximum dose which can be taken is one inhalation every 24 hours.

What Drugs Can Affect Umeclidinium?

• Medications that treat depression, anxiety, mental illness, and mood disorders.

• Medicines for colds and allergies, such as Benadryl.

• Medications that treat Parkinson’s disease.

• Drugs that treat stomach problems, motion sickness, or irritable bowel syndrome.

• Drugs that treat overactive bladder.

• Any other bronchodilators such as Aclidinium or Tiotropium.

For doctors:

Indication: Umeclidinium is a long-acting muscarinic antagonist used to treat and maintain chronic obstructive pulmonary disease (COPD). Umeclidinium is either used as once-daily inhalation monotherapy or as a fixed-dose combination product with long-acting beta2-agonist Vilanterol.

Mechanism of Action:

Umeclidinium is a long-acting antimuscarinic agent which can also be referred to as anticholinergic. The drug has a similar affinity to the subtypes of muscarinic receptor M1 to M5. In case of airways, it shows pharmacological effects by inhibiting the M3 receptor in the smooth muscle leading to bronchodilation.

Absorption:

Cmax for Umeclidinium occurred at 5 minutes to 15 minutes with concentrations in 14 days with 1.8 fold accumulations.

Protein Binding:

The plasma protein binding capacity of Umeclidinium is almost 89 %.

Metabolism:

Umeclidinium is primarily metabolized by the enzyme cytochrome P450 2D6 (CYP2D6). It is a substrate for the P-glycoprotein transporter. The primary route of the metabolites of Umeclidinium is oxidative (including hydroxylation or O-dealkylation) followed by conjugation (glucuronidation). This results in a range of metabolites with either reduced pharmacological activity or for which the pharmacological activity is not established. The systemic exposure to the metabolites of Umeclidinium is low.

Route of Elimination:

The elimination of the drug was traced by radiolabeling which showed that 58 % of the drugs were eliminated in the feces and 22 % in the urine.

Half-Life of Umeclidinium:

The effective half-life of Umeclidinium after one dose every day is 11 hours.

Toxicity:

The most common adverse effects seen by Umeclidinium are nasopharyngitis, arthralgia, upper respiratory tract infection, and cough. The drug should be used safely in patients with narrow-angle glaucoma or those suffering from prostatic hyperplasia or bladder neck obstruction. Sometimes the inhaled medication can lead to bronchospasm, which can be fatal.

Drug Interactions:

• Acebutolol: It is a selective beta-1 receptor antagonist used to manage ventricular premature beats and hypertension in adults. The metabolism of Umeclidinium reduces when it is combined with Acebutolol.

• Acetazolamide: It is a carbonic anhydrase inhibitor that can be used in edema due to heart failure or some types of medications. The drug has the tendency to increase the central nervous system depressant activities of Umeclidinium.

• Amitriptyline: It is a tricyclic antidepressant which is used for the treatment of endogenous or psychotic depressive illness. The chances of adverse effects of Umeclidinium increase when it is used with Amitriptyline.

• Castor Oil: The therapeutic efficiency of castor oil reduces when it is used along with Umeclidinium.

• Cocaine: It is an ester local anesthesia that is used in diagnostic procedures or surgeries in or through the nasal cavities.The risk of developing adverse effects due to Umeclidinium increases when it is combined with cocaine.

• Dobutamine: It is a beta-1 agonist which is used to treat cardiac decompression in patients with cardiac surgery or organic heart disease. The risk of tachycardia increases when Dobutamine is combined with Umeclidinium.

• Fostemsavir: It is an antiretroviral HIV-1 attachment inhibitor. The serum concentration of Fostemsavir increases when it is combined with Umeclidinium.

• Levocetirizine: It is an H1-receptor antagonist which is used to treat symptoms that are associated with chronic allergic rhinitis and urticaria. Levocetirizine increases the central nervous system activities of Umeclidinium.

• Lovastatin: It is a drug used to lower down low-density lipids (LDL) and reduce the risk of cardiovascular disease. The metabolism of Umeclidinium may reduce when it is combined with Lovastatin.

Clinical Trials of Umeclidinium:

• Study done to evaluate the effect of Umeclidinium as a combination therapy in subjects suffering from chronic obstructive pulmonary disease (COPD).

Description: It is a multicenter, randomized, parallel, and double-blind group study done to evaluate the efficacy and safety of the addition of Umeclidinium when it is given once daily by dry powder inhaler (DPI) to long acting beta-2-agonist twice daily compared to placebo by dry powder inhaler added to long acting beta2-agonist/ inhaled corticosteroids therapy over a treatment period of 12 weeks in patients suffering from chronic obstructive pulmonary disease.

Process of Study: The subjects who match the eligibility criteria will be randomly assigned one of the following blinded study regimens for treatment in equal proportion (1:1) Umeclidinium 62.5 mcg once daily and placebo once daily. About 230 subjects will be randomized to complete around 206 evaluable subjects. The total duration of the studies will be about 14 weeks for each patient.

Actual Enrollment: 236

Allocation: Randomized.

• Study done to see the efficacy of Umeclidinium or Vilanterol with Tiotropium or Olodaterol in chronic obstructive pulmonary disease (COPD).

Brief Summary: The main objective of the study is to assess the effect of Umeclidinium or Vilanterol versus Tiotropium or Olodateral in patients suffering from moderate chronic obstructive pulmonary disease. This study is a multicenter, randomized, two period crossover complete block design, and open-label.

Process of Study: Eligible patients who completed a two week run-in period will be randomly given sequence containing Umeclidinium or Vilanterol inhalation powder (62.5/25 mcg once daily) which is administered as one inhalation by the ELLIPTA inhaler and Tiotropium or Olodaterol is given in 5/5 mcg dose via inhaler as two inhalations by the RESPIMAT inhaler for eight weeks each. This is followed by a three-week washout and then one week follow-up period. The total duration of the study is 22 weeks.

ELLIPTA is a registered trademark of the GlaxoSmithKline group of companies, and RESPIMAT is a registered trademark of Boehringer Ingelheim.

Actual Enrollment: 236 participants.

Allocation: Randomized.

Umeclidinium and Pregnancy: Animal studies showed no signs of teratogenicity in them at approximately 200 times the inhalation of human daily inhaled dose of Umeclidinium during organogenesis. Thus no studies are present to prove any adverse effects of Umeclidinium during pregnancy.

Umeclidinium and Breastfeeding: There is no published data about the use of Umeclidinium during breastfeeding; however, it produces low systemic maternal serum levels, and any drugs in the breast milk are not likely to be absorbed by the baby. Thus the risk to the breastfed baby of maternal Umeclidinium inhalation is very small.

Umeclidinium and Geriatric Patients: The doses of Umeclidinium are the same for geriatric patients as for younger individuals. There is no adverse effect of Umeclidinium used in older patients.