Aclidinium

Aclidinium belongs to the Long-acting beta 2 Agonist (LABA) Pharmacological class.

Aclidinium is approved for the treatment of Chronic Obstructive Pulmonary Disease, Chronic Bronchitis, and Emphysema.

An average of about 6% of bioavailability was reported in healthy patients treated with Aclidinium. Aclidinium is rapidly metabolized through hydrolysis. The volume of distribution of Aclidinium was found to be 300L. The intravenously administered radiolabelled Aclidium was found to be excreted in urine about 54%-65% and through feces about 20%to 33% of the dose.

The common side effects associated with Aclidinium are headache, sore throat, sinus pain, stuffy nose, cough, and headache

Aclidinium is available in the form of breath-actuated powdered inhalation.

Aclidinium is available in India, U.K., U.S., Canada, India, E.U., China, Japan, and Australia.

Aclidinium belonging to the pharmacological class of Long-acting beta 2 Agonist (LABA), acts as a Bronchodilator therapeutic agent. Through its action on Beta2-adrenergic receptors, Aclidiniumis found to work by activation of adenylate cyclase, the enzyme which is found to be responsible for the production of cellular mediated cAMP. Aclidinium hence leads to Bronchodilation of the smooth muscles and reverses bronchospasm.

Aclidinium has a quick onset of action is found to be 30 - 45 minutes, and the duration of action is around 3- 6 hours.

Aclidinium is available in breath-actuated powdered dose inhalers.

• Aclidinium comes in a sealed pouch. The pouch should not be used until you are ready to use it. The green button is pressed gently until one is ready to take a dose.
• The cap is removed by squeezing and pulling it off the mouthpiece. The mouthpiece is checked to make sure it is clear.
• Now the inhaler is held with the mouthpiece facing you while the green button is on top. The green button is pressed all the way down and released and the inhaler should not be tilted.
• The control window is checked to make sure the dose is ready for inhalation. Check if the colored control window changed from red to green. If it is still red, the steps should be repeated to prepare the dose.
• This medicine should be inhaled properly, First, breathe out fully and try to get as much air out of your lungs as possible. Now the lips should be tightly circled around the mouthpiece and breathed in quickly and deeply until one hears a "click" sound. Now one must keep breathing in, even after they hear the "click" sound to be sure one gets the full dose.
• The green button should not be held while breathing in.
• The inhaler should be removed from the mouth and the breath should be for as long as it is comfortable, and then the air breathed out slowly through the nose.
• The colored control window should be checked if it has turned red. This means one has inhaled the full dose of the medicine.
• Once the window has turned red, the cap is placed back by pressing it back into the mouthpiece.

Aclidinium can be used in the treatment of:

• COPD (Chronic Obstructive Pulmonary Disease)
• Chronic Bronchitis
• Emphysema

Aclidiniumcan help to relieve symptoms of Chronic Obstructive Pulmonary Disease, Chronic bronchitis, and emphysema.

Aclidinium is approved for use in the following clinical indications:

• COPD (Chronic Obstructive Pulmonary Disease)
• Chronic Bronchitis
• Emphysema

For inhalation aerosol dosage form i.e.powdered dosage form:

For maintenance treatment for Chronic Obstructive Pulmonary Disease:

Adults—One puff 2 twice a day, in the morning and evening which is about 12 hours apart.

Children—Use and dose must be determined by the treating physician.

One inhalation dose of 400mcg

Breath actuated Powdered metered dose inhalation.

Maintaining health and smoking cessation is a must.

Avoid or restrict or limit the usage of caffeine as it might lead to the risk of nausea, palpitations, nervousness, rapid heartbeat, etc.

Diet containing refined and high energy-dense foods, low fiber, food with a high glycemic index, saturated and trans fat food, red and processed meat, added sugar, salt, preservatives, low antioxidants, and vitamins needs to be restricted.

The dietary restrictions should be individualized as per the patient's requirements.

Aclidinium may be contraindicated during the co-administration with the following drugs:

• Hypersensitivity to the ingredients of the medication
• Severe hypersensitivity towards the milk proteins

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

Not for Acute Use

Aclidinium is intended as a twice-a-day maintenance treatment for the treatment of Chronic Obstructive Pulmonary Disease, and it is not indicated for the initial treatment of acute episodes of bronchospasm, i.e., rescue therapy.

Paradoxical Bronchospasm

Inhalation medicines, including Aclidinium, may lead to paradoxical bronchospasm. If this occurs, treatment with Aclidinium should be stopped immediately and other treatments should be considered.

Worsening of Narrow-Angle Glaucoma

Aclidinium should be used with caution in patients suffering from narrow-angle glaucoma.

Physicians and patients should be vigilant for signs and symptoms of acute narrow-angle glaucoma. Patients should be advised to consult a physician immediately should any of these signs or symptoms develop.

Worsening of Urinary Retention

Aclidinium should be used with caution in patients suffering from urinary retention. Physicians and patients should be vigilant for signs and symptoms of prostatic hyperplasia or bladder-neck obstruction, e.g., difficulty passing urine, or painful urination. Patients should be advised to consult a physician immediately should any of these signs or symptoms develop.

Immediate Hypersensitivity Reactions

Immediate hypersensitivity reactions which include anaphylaxis, angioedema i.e.including swelling of the lips, tongue, or throat, urticaria, rash, bronchospasm, or itching, has reported having occurred after administration of Aclidinium. If such a reaction occurs, therapy with Aclidinium should be stopped immediately and alternative treatments should be considered.

Avoid alcohol usage while on Aclidinium medication as alcohol can worsen the effects of any underlying disease condition.

It is not known whether Aclidinium is excreted in human milk. Therefore, Aclidinium should be used during nursing only if the potential benefits outweigh the potential risks associated with newborn growth.

Pregnancy Category C.

There is no well-documented experience of clinical studies in pregnant women. Aclidinium should only be used during pregnancy if the potential benefits outweigh the risks associated with the fetus's growth.

No adverse developmental effects were seen with inhalation administration of Aclidinium to pregnant rats and rabbits during organogenesis at doses 15 or 20 times respectively than the maximum recommended human daily inhaled dose (MRHDID). Reduced pup weights were seen when pregnant rats continued inhalation administration through lactation at 5 times the maximum recommended human daily inhaled dose of aclidinium bromide. Adverse developmental effects occurred when observed in rabbits when orally dosed with Aclidinium at approximately 1,400 times the MRHDID.

The adverse reactions related to Aclidinium can be categorized as:

Common

• Sore throat
• Stuffy or runny nose
• Unusual tiredness or weakness
• Fever
• Headache
• Muscle aches

Less common

• Lower back or side pain
• Sneezing
• Tender, swollen glands in the neck
• Tightness in the chest
• Trouble in swallowing
• Voice changes
• Bladder pain
• Bloody or cloudy urine
• Body aches or pain
• Chest pain
• Chills
• Cough
• Difficult, burning, or painful urination
• Difficulty in breathing
• Dry throat
• Ear congestion
• Fainting
• Fast, pounding, or irregular heartbeat or pulse
• Frequent urge to urinate
• Hoarseness
• Loss of voice

Rare

• Increased hunger
• Increased thirst
• Loss of consciousness
• Muscle pain or stiffness
• Nausea
• Pain, swelling, or redness in the joints
• Slow or irregular heartbeat
• Stomachache
• Sweating
• Unexplained weight loss
• Chest discomfort
• Difficulty with moving
• Dilated neck veins
• Dry mouth
• Extreme tiredness or weakness
• Flushed, dry skin
• Fruit-like breath odor

The clinically relevant drug interactions of Aclidiniumis briefly summarized here:

In vitro studies suggest that due to limited potential for CYP450-related metabolic drug interactions, therefore no formal drug interaction studies have been performed and studied with Aclidinium.

Sympathomimetics, Methylxanthines, Steroids

In clinical studies, it has been found that concurrent administration of Aclidinium and other drugs commonly used in the treatment of Chronic Obstructive Pulmonary Disease including sympathomimetics i.e.short-acting beta2 agonists, methylxanthines, and oral and inhaled steroids showed no increase in adverse drug reactions.

Anticholinergics There may be a potential for an additive interaction with concomitantly used anticholinergic medications. Therefore, co-administration of Aclidinium with other anticholinergic-containing drugs should be avoided as this may lead to an increase in anticholinergic effects.

The common side effects of Aclidinium include the following:

• Headache
• Stuffy nose
• Sore throat
• Cough
• Sinus pain

Pregnancy

Pregnancy Category C

There is no well-documented experience of clinical studies in pregnant women. Aclidinium should only be used during pregnancy if the potential benefits outweigh the risks associated with the fetus's growth.

No adverse developmental effects were seen with inhalation administration of Aclidinium to pregnant rats and rabbits during organogenesis at doses 15 or 20 times respectively than the maximum recommended human daily inhaled dose (MRHDID). Reduced pup weights were seen when pregnant rats continued inhalation administration through lactation at 5 times the maximum recommended human daily inhaled dose of aclidinium bromide. Adverse developmental effects occurred when observed in rabbits when orally dosed with Aclidinium at approximately 1,400 times the MRHDID.

Nursing Mothers

It is not known whether Aclidinium is excreted in human milk. Therefore, Aclidinium should be used during nursing only if the potential benefits outweigh the potential risks associated with newborn growth.

Pediatric Use

Aclidinium is approved for use in the maintenance treatment of bronchospasm associated with Chronic ObstructivePulmonary Disease. The chronic obstructive pulmonary disease does not normally occur in children. The safety and effectiveness of Aclidinium in pediatric patients have not been established.

Geriatric Use

The pharmacokinetic profile of Aclidinium and its main metabolites was assessed in 12 elderly Chronic ObstructivePulmonary Disease patients aged 70 years or older and compared to a younger cohort of 12 Chronic ObstructivePulmonary Disease patients aged 40-59 years that were administered with 400 mcg Aclidinium once daily for 3 days via inhalation. No clinically significant differences in systemic exposure such as AUC and Cmax were observed when the two groups were compared. Hence, No dosage adjustment is necessary for elderly patients

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

No case of overdose had been reported in clinical studies carried out with Aclidinium. There were found to be no systemic anticholinergic or other adverse effects following a single inhaled dose of up to 6,000 mcg aclidinium bromide in 16 healthy volunteers.

Pharmacodynamics

Aclidinium is found to not prolong the QTc interval or have significant effects on cardiac rhythm.

Pharmacokinetics

• Absorption

Bioavailability of Aclidinium in healthy subjects was found at 6%, T max in healthy patients was found at 10 minutes, and the Time to steady state in healthy subjects was found to be 2 days.

• Volume of Distribution

Followed by the Intravenous administration, the volume of distribution of Aclidinium was found to be 300 L.

• Metabolism

The major route of metabolism of aclidinium is found to be hydrolysis This occurs both chemically and enzymatically by esterases in the plasma. Aclidinium is rapidly and extensively hydrolyzed to its derivatives such as alcohol and dithienylglycolic acid Neither of them is found to be binding to muscarinic receptors and is pharmacologically inactive.

• Excretion

When Intravenously administered radiolabelled Aclidinium was administered to healthy volunteers and it was found to be extensively metabolized with 1% excreted as unchanged Aclidinium. Approximately 54% to 65% of the radioactivity was found to be excreted in urine and 20% to 33% of the dose was reported to be excreted in feces. The combined results indicated that almost the entire Aclidinium dose was eliminated mainly by hydrolysis. After dry powder inhalation, urinary excretion of Aclidinium was reported to be about 0.09% of the dose.

• https://www.drugs.com/mtm/aclidinium.html
• https://www.mayoclinic.org/drugs-supplements/aclidinium-inhalation-route/side-effects/drg-20075736?p=1
• https://medlineplus.gov/druginfo/meds/a613001.html
• https://go.drugbank.com/drugs/DB08897
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• https://www.sciencedirect.com/topics/medicine-and-dentistry/aclidinium-bromide
• https://www.accessdata.fda.gov/drugsatfda_docs/psg/aclidinium bromide_inhalation powder_202450_rc09-15.pdf
• https://pubchem.ncbi.nlm.nih.gov/compound/Aclidinium
• https://www.accessdata.fda.gov/drugsatfda_docs/label/2019/202450s012lbl.pdf
• https://www.gnhindia.com/products/us-ndc/aclidinium-bromide-tudorza-pressair-0310-0800/