Vilanterol

Vilanterol is a Bronchodilating agent belonging to the Pharmacological Class of Ultra Long-Acting Beta 2 Receptor Agonists (LABA).The drug is approved for treating COPD (Chronic Obstructive Pulmonary Disease), Chronic Bronchitis, and Emphysema.

In Vilanterol , Cmax was achieved in about 5 to 15 minutes. The mean volume of distribution at steady state of Vilanterol was found to be 165 L.The in-vitro data showed that Vilanterol is metabolized essentially by CYP3A4 and is a substrate for the P-gp transporter. Following oral administration of radio-labeled vilanterol, mass balance showed 70% of the radio-label Vilanterol in the urine and 30% in the feces.

The common side effects associated with Vilanterol include increased blood pressure, runny or stuffy nose, sore throat, cough, hoarseness in voice, headache, back pain, joint pain, fever, and flu symptoms.

Vilanterol is available in the form of inhalation powder

Vilanterol is available in Europe, Japan and New Zealand.

Vilanterol, belonging to the pharmacological class Ultra Long-Acting Beta 2 Adrenergic Receptor Agonist, acts as a Bronchodilator therapeutic agent (LABA).It acts via agonistic action on beta 2 adrenergic receptor which in turn stimulates adenyl cyclase following the conversion of ATP to cAMP. This conversion in turn causes an increase in cAMP and leads to the relaxation of the smooth muscles in the airways. Vilanterol also leads to the inhibition of the release of hypersensitivity mediators from mast cells in the lungs.Vilanterol causes bronchial smooth muscle relaxation, which is helpful in relieving the patient from COPD, Emphysema, or Chronic Bronchitis.The drug has an onset of action upto 16 minutes, and the duration of action lasts up to more than 12 hours, approximately 24 hours.

The inhalation powder is enclosed inside a hard gelatin capsule.

The capsule should be used with Neohaler Device only

The capsules should be used once a day after 24 hours’ time interval.

Steps to use:

• Open the cover.
• Breathe out (exhale) fully while holding the inhaler away from your mouth, and . Do not breathe out into the mouthpiece.
• Inhale the medicine.The mouthpiece of the inhaler put between your lips, and close your lips firmly around it. Your lips should fit over the curve shape of the mouthpiece.Take one long, steady, deep breath in through your mouth. Do not breathe in through your nose.
• The inhaler is removed from the mouth and hold your breath for about 3 to 4 seconds.
• Breathe out slowly. It might not taste or feel the medicine taste, even when one are using the inhaler correctly. It is advised not take another dose from the inhaler even if you do not feel or taste the medicine.
• Close the inhaler
• Rinse your mouth

Vilanterol can be used to treat diseases which are as follows:

• Chronic bronchitis
• Emphysema
• Maintain airflow obstruction in patients suffering from Chronic Obstructive Pulmonary Disease.

Vilanterol is approved for use in the following clinical indications:

• COPD (Chronic Obstructive Pulmonary Disease)
• Chronic Bronchitis
• Emphysema
• Once-daily maintenance treatment of asthma in patients aged 18 or older with reversible obstructive airway disease

Vilanterol administration dose is 25 mcg along with other drug combinations which is inhaled once daily.

The duration and dosage of treatment should be as per the clinical judgment of the treating physician.

Vilanterol may be contraindicated in the following as per the innovator:

• Vilanterol is not indicated in the treatment of Asthma as a monotherapy (can be used along with inhaled corticosteroids)
• Vilanterol has been contraindicated in patients with a history of Hypersensitivity towards Vilanterol or any ingredients of the medication.

The treating physician must closely monitor the patient and keep pharmacovigilance as follows:

• Deterioration of Asthmatic Condition, including death:

There might be a deterioration of the asthma condition over a period of time. The increased usage of Vilanterol is a noted marker for the destabilization of the condition. Therefore a re-evaluation of the patient's condition should be considered, and the usage of anti-inflammatory agents such as corticosteroids should be considered. Serious asthma-related events, including deaths, have been reported in clinical trials.

• Deterioration of the acute and severe conditions of COPD:

Vilanterol should not be administered in the conditions of acute and severe COPD, as it might lead to a life-threatening condition.

In the acute symptoms of bronchospasm, Vilanterol should not be used. The use of short-acting beta 2 agonists should be considered in this situation.

While starting the administration of Vilanterol, the patients must be advised to withdraw the regular usage of short-acting beta 2 agonists and to only use it for symptomatic relief from acute respiratory symptoms.

During the episodes of the deterioration of the COPD condition, the use of Vilanterol must be withdrawn, and a re-evaluation of the patient's condition must be considered. The markers for the deterioration of the condition include an increased dose of Vilanterol or increased usage of Vilanterol or less effectiveness of the short-acting beta 2 agonists.

• Hypersensitivity events:

In the rare events of Hypersensitivity such as swelling of tongue, lips, and face, urticaria of the skin, difficulty in breathing or swallowing, rashes. Vilanterol should be withdrawn, and other alternate therapy must be considered.

• Paradoxical bronchospasm:

Paradoxical bronchospasm might be a life-threatening condition; therefore, Vilanterol should be immediately withdrawn during such a condition.

• Cardiovascular events:

Vilanterol has the potential of causing Myocardial Ischemia, Cardiac Arrest, changes in the ECG curve such as flattening of the T segment, prolongation of Q-Tc segment, and ST segment depression has been found to be associated with the beta 2 adrenergic agonist.

• Hypokalemia:

Vilanterol causes a decrease in potassium levels which potentially produces adverse cardiac events.

• Xanthine, Steroids, and Diuretics:

In acute asthma conditions, the use of Xanthine, Steroids, and Diuretics should be avoided or closely monitored as it may lead to hypoxia

• Diabetes Mellitus:

During Vilanterol usage, a patient with Diabetes Mellitus condition might suffer from hyperglycemia and will be unable to compensate in the condition of ketoacidosis

Vilanterol or the components of the medication have not been known to be excreted in milk.Yet decision should be made by the treating physician whether to continue or discontinue this medication and should be only used if the benefits outweigh the risks.

Pregnancy Category C

There were found to be no teratogenic effects in rats and rabbits at approximately 13,000 and 70 times, respectively, the MRHD (Maximum Recommended Human Dose) in adults. It is based on a mcg/m2 basis at maternal inhaled doses up to 33,700 mcg/kg/day in rats and on an AUC basis at maternal inhaled doses up to 591 mcg/kg/day in rabbits. However, fetal skeletal variations have been observed in rabbits at approximately 450 times the MRHD (Maximum Recommended Human Dose) in adults (on an AUC basis at maternal inhaled or subcutaneous doses of 5,740 or 300 mcg/kg/day, respectively). The skeletal variations included decreased or absent ossification in cervical vertebral centrum and metacarpals..

No known interactions with food is noted.

The adverse reactions related to Vilanterol can be categorized as:

Common:

• Difficulty with breathing
• Muscle aches
• Sneezing
• Sore throat
• Stuffy or runny nose
• Unusual tiredness or weakness
• Ear congestion
• Fever
• Headache
• Loss of voice
• Body aches or pain
• Chills
• Cough

Less Common:

• Diarrhea
• Dizziness
• General feeling of discomfort or illness
• Joint or muscle pain
• Tingling of the hands or feet
• Trouble sleeping
• Troubled breathing
• Unusual weight gain or loss
• Vomiting
• Loss of appetite
• Nausea
• Nervousness
• Pain or tenderness around the cheekbones and eyes
• Pounding in the ears
• Slow or fast heartbeat
• Sweating
• Tightness of the chest
• Bloating or swelling of the lower legs, or feet,face, arms or hands.
• Blurred vision
• Chest pain

Rare:

• Irregular, pounding, or racing heartbeat or pulse
• Noisy breathing
• Tremor
• Muscle spasms

The physician should be vigilant about the knowledge pertaining to the identification and treatment of overdosage of Vilanterol.

An increase in pulse rate, systolic blood pressure, and QTc interval was found in COPD patients.Signs and symptoms for e.g., nervousness, headache, tremor, dry mouth, palpitation, muscle cramps, angina, hypertension or hypotension, tachycardia, hypokalemia, hyperglycemia, metabolic acidosis with heart rate up to 200 bpm, arrhythmias, nausea, dizziness, fatigue, malaise, and insomnia. With all inhaled sympathomimetic medications along with Vilanterol overdose, cardiac arrest and even death may be associated.

Treatment of overdosage consists of:

• Withdrawing of Vilanterol together with institution of appropriate symptomatic and supportive therapy.
• The use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm.
• Monitoring heart rate is recommended in cases of overdosage.

Pharmacodynamics

Vilanterol, belonging to the pharmacological class Ultra Long-Acting Beta 2 Adrenergic Receptor Agonist, acts as a Bronchodilator therapeutic agent.

Vilanterol acts via stimulating the beta 2 adrenergic receptor and causes relaxation of the smooth muscles in the airways and was recently approved for use in the United States. The duration of action of Vilanterol is approximately 24 hours, which allows once-in-a-day administration. Vilanterol is used in the combination of the drugs

Pharmacokinetics

• Absorption

Vilanterol plasma levels may be able predict therapeutic effect. After inhaled administration of Vilanterol in healthy subjects, Cmax was achieved in about 5 to 15 minutes. Vilanterol is found to be mostly absorbed from the lung after inhalation dosage. Following repeated dosing of inhaled Vilanterol, steady state was achieved within 14 days with up to 1.7-fold accumulation.

• Volume of distribution

After intravenous administration in healthy subjects, the mean volume of distribution at steady state was found to be 165 L.

• Protein Binding

In the in vitro plasma protein binding in human plasma during Vilanterol usage was found to be 94% on an average.

• Metabolism

The in-vitro data showed that Vilanterol is metabolized essentially by CYP3A4 and is a substrate for the P-gp transporter. Vilanterol is metabolized to a wide range of metabolites with significantly reduced β1- and β2-agonist activity.

• Route of elimination

Following oral administration of radio-labeled vilanterol, mass balance showed 70% of the radio-label in the urine and 30% in the feces. The effective half-life for Vilanterol, as determined from inhalation administration after multiple doses was found to be is 11 hours.

There are some clinical studies mentioned below for vilanterol:

• Bateman ED, Ferguson GT, Barnes N, et.al. Dual bronchodilation with QVA149 versus single bronchodilator therapy: the SHINE study. Eur Respir J. 2013;42:1484–94.
• Donohue JF, Jones PW, et.al. Correlations between FEV1 and patient-reported outcomes: a pooled analysis of 23 clinical trials in patients with chronic obstructive pulmonary disease. Pulm Pharmacol Ther. 2018;49:11–9.
• Oba Y, Sarva ST, Dias S. Efficacy and safety of long-acting beta-agonist/long-acting muscarinic antagonist combinations in COPD: a network meta-analysis. Thorax. 2016;71:15–25.
• Donohue JF, Singh D, Munzu C, Kilbride S, Church A. Magnitude of umeclidinium/vilanterol lung function effect depends on monotherapy responses: results from two randomised controlled trials. Respir Med. 2016;112:65–74.
• Donohue JF, Maleki-Yazdi MR, et.al. Efficacy and safety of once-daily umeclidinium/vilanterol 62.5/25 mcg in COPD. Respir Med. 2013;107:1538–46.
• Maleki-Yazdi MR, Singh D, Anzueto A, et.al. Assessing short-term deterioration in maintenance-naive patients with COPD receiving Umeclidinium/Vilanterol and Tiotropium: a pooled analysis of three randomized trials. Adv Ther. 2017;33:2188–99.
• Calverley PMA, Anzueto Ar, et.al. Tiotropium and olodaterol in the prevention of chronic obstructive pulmonary disease exacerbations (DYNAGITO): a double-blind, randomised, parallel-group, active-controlled trial. Lancet Respir Med. 2018;6:337–44.