Tudorza Pressair (aclidinium bromide)

For the long-term management of reversible bronchospasm associated with chronic obstructive pulmonary disease (COPD), the usual dosage of aclidinium bromide in adults is 400 mcg (one inhalation) twice daily via the Pressair(R) device. Orally inhaled aclidinium should not be used for the treatment of acute episodes of bronchospasm.

Aclidinium bromide is administered by oral inhalation only using a specific breath-actuated, oral inhalation device (Pressair(R)) that delivers powdered drug.

Prior to use, the inhaler should be removed from the sealed pouch. The protective cap should be removed from the inhaler by lightly squeezing the arrows marked on each side of the cap and pulling outward. The patient should then hold the inhaler with the mouthpiece toward the face, but not inside the mouth, with the green button facing straight up; the inhaler should not be tilted. Before placing the inhaler in the mouth, the patient should completely depress and then release the green button on the inhaler and then check the colored control window to ensure that it has changed from red to green, indicating that the dose is ready for inhalation.

Before inhaling the dose, the patient should exhale as completely as possible, being careful not to exhale into the Pressair(R) device. The patient should then place the mouthpiece of the inhaler tightly between the lips and inhale quickly and deeply through the mouth. The patient should hear a click (indicating that the inhaler is being used correctly) during the inhalation and should continue inhaling. The green button should not be pressed or held down during the inhalation. After a complete inhalation, the patient should remove the inhaler from the mouth and hold their breath for as long as comfortable, then exhale slowly through the nose. While some patients may taste the drug delivered from the Pressair(R) device, they should be instructed not to use another dose even if they do not taste the drug. The patient should check the control window to ensure that it has changed from green to red, indicating that the full dose has been inhaled. If the control window is still green, the patient should attempt to inhale through the device again. If the patient is unable to inhale correctly after several attempts, the patient should contact their clinician. After the control window has turned red, the protective cap should be pressed back onto the mouthpiece of the inhaler.

The inhaler does not need to be cleaned. However, if desired, the outside of the mouthpiece can be wiped with a dry tissue or paper towel; water should not be used to clean the inhaler. The inhaler should be discarded when the dose indicator (showing the number of doses remaining in intervals of ten) reads zero, when the device locks out (i.e., the green button stays depressed), or 45 days after removal of the inhaler from the sealed pouch, whichever comes first. The inhaler also should be discarded if the device appears damaged or the protective cap is lost.

No dosing information is available for this tab.

No formal drug interaction studies have been performed with aclidinium to date. Results of in vitro studies suggest that aclidinium has limited potential to cause metabolic interactions with cytochrome P-450 (CYP) isoenzymes at plasma concentrations achieved clinically.

There are no contraindication interactions for this drug.

Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

Inhaled Anticholinergics/Pramlintide

SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.

MECHANISM OF ACTION: Pramlintide slows gastric emptying. Anticholinergics may result in additive or synergistic effects.(1)

CLINICAL EFFECTS: Concurrent use of pramlintide and anticholinergics may result in additive or synergistic effects.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The manufacturer of pramlintide states that pramlintide therapy should not be considered in patients requiring the use of drugs that stimulate gastrointestinal motility or in patients taking drugs that alter gastrointestinal motility.(1) Patients receiving inhaled anticholinergics should be evaluated for signs of systemic effects, which may include constipation.

DISCUSSION: Patients using drugs that alter gastrointestinal motility have not been studied in clinical trials for pramlintide.(1) Constipation has been reported as a side effect of inhaled anticholinergic agents such as ipratropium(2) and tiotropium.(3)

Moderate Interaction: Assess the risk to the patient and take action as needed.

Beta-Agonists; Anticholinergics; Theophylline/Methacholine

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Beta-agonists, anticholinergics, and theophylline may inhibit the action of methacholine on the airway.(1)

CLINICAL EFFECTS: The result of the methacholine challenge test may not be accurate.(1)

PREDISPOSING FACTORS: None determined.

PATIENT MANAGEMENT: The following drugs should be held before a methacholine challenge for the the duration indicated:(1) - short-acting beta-agonists: 6 hours - long-acting beta-agonists: 36 hours - short-acting anti-cholinergics: 12 hours - long-acting anti-cholinergics: at least 168 hours (7 days) - oral theophylline: 12-48 hours

DISCUSSION: Beta-agonists, anticholinergics, and theophylline may inhibit the action of methacholine on the airway and cause inaccurate test results.

Inhaled Anticholinergics/Solid Oral Potassium Capsules

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16)

CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with inhaled anticholinergics could potentially result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16)

PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21)

PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling.

DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. Some lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17) Constipation has been reported as a side effect of inhaled anticholinergic agents such as ipratropium(22) and tiotropium.(23)

Inhaled Anticholinergics/Solid Oral Potassium Tablets

SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed.

MECHANISM OF ACTION: Concentrated potassium may damage the lining of the GI tract. Anticholinergics delay gastric emptying, resulting in the potassium product remaining in the gastrointestinal tract for a longer period of time.(1-16)

CLINICAL EFFECTS: Use of solid oral dosage forms of potassium in patients treated with inhaled anticholinergics could potentially result in gastrointestinal erosions, ulcers, stenosis and bleeding.(1-16)

PREDISPOSING FACTORS: Diseases or conditions which may increase risk for GI damage include: preexisting dysphagia, strictures, cardiomegaly, diabetic gastroparesis, elderly status, or insufficient oral intake to allow dilution of potassium.(1-10,21) Other drugs which may add to risk for GI damage include: nonsteroidal anti-inflammatory drugs (NSAIDs), bisphosphonates, or tetracyclines.(21)

PATIENT MANAGEMENT: Regulatory agency and manufacturer recommendations regarding this interaction: - In the US, all solid oral dosage forms (including tablets and extended release capsules) of potassium are contraindicated in patients receiving anticholinergics at sufficient dosages to result in systemic effects.(2-8) Patients receiving such anticholinergic therapy should use a liquid form of potassium chloride.(2) - In Canada, solid oral potassium is contraindicated in any patient with a cause for arrest or delay in tablet/capsule passage through the gastrointestinal tract and the manufacturers recommend caution with concurrent anticholinergic medications.(1,9-10) Evaluate each patient for predisposing factors which may increase risk for GI damage. In patients with multiple risk factors for harm, consider use of liquid potassium supplements, if tolerated. For patients receiving concomitant therapy, assure any potassium dose form is taken after meals with a large glass of water or other fluid. To decrease potassium concentration in the GI tract, limit each dose to 20 meq; if more than 20 meq daily is required, give in divided doses.(2) If concurrent therapy is warranted, monitor patients receiving concurrent therapy for signs of blood loss, including decreased hemoglobin, hematocrit, fecal occult blood, and/or decreased blood pressure and promptly evaluate patients with any symptoms. Patients should be instructed to immediately report any difficulty swallowing, abdominal pain, distention, severe vomiting, or gastrointestinal bleeding. Instruct patients to report any signs and symptoms of bleeding, such as unusual bleeding from the gums or nose; unusual bruising; red or black, tarry stools; red, pink or dark brown urine; acute abdominal or joint pain and/or swelling.

DISCUSSION: In clinical trials, there was a higher incidence of gastric and duodenal lesions in patients receiving a high dose of a wax-matrix controlled-release formulation with a concurrent anticholinergic agent. Some lesions were asymptomatic and not accompanied by bleeding, as shown by a lack of positive Hemoccult tests.(1-17) Several studies suggest that the incidence of gastric and duodenal lesions may be less with the microencapsulated formulation of potassium chloride.(14-17) Constipation has been reported as a side effect of inhaled anticholinergic agents such as ipratropium(22) and tiotropium.(23)

The manufacturer states that there are no known contraindications to the use of aclidinium.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

• Angle-closure glaucoma
• Benign prostatic hyperplasia
• Bladder outflow obstruction
• Cardiac arrhythmia
• Urinary retention

Adverse events occurring in at least 3% of patients receiving aclidinium and at an incidence greater than with placebo include headache, nasopharyngitis, and cough.

Less Frequent

• Chronic heart failure
• Hypertension
• Paradoxical bronchospasm

Rare or Very Rare

• Aggravated glaucoma
• Anaphylaxis
• Angioedema
• Diabetes mellitus
• First degree atrioventricular heart block
• Ocular pain
• Pharyngeal edema
• Skin rash
• Stomatitis
• Urticaria

More Frequent

• Cough
• Dyspnea
• Flu-like symptoms
• Headache disorder
• Pharyngitis
• Upper respiratory infection

Less Frequent

• Anemia
• Arthralgia
• Back pain
• Cellulitis
• Constipation
• Diarrhea
• Gastroesophageal reflux disease
• Muscle spasm
• Rhinitis
• Sinusitis
• Toothache
• Urinary tract infection
• Vomiting

Rare or Very Rare

• Arthritis
• Blurred vision
• Edema
• Hypotension
• Laryngismus
• Mydriasis
• Nausea
• Pruritus of skin
• Tachycardia
• Urinary retention
• Visual changes
• Voice change
• Xerostomia

No enhanced messaging available.

Safety and efficacy of oral inhalation of aclidinium have not been established in children. However, COPD does not generally occur in children.

Category C. (See Users Guide.)

Aclidinium is distributed into milk in rats; it is not known whether the drug is distributed into milk in humans. The manufacturer recommends that orally inhaled aclidinium be used with caution in nursing women.

No overall differences in safety and efficacy were observed in geriatric patients relative to younger adults, but increased sensitivity cannot be ruled out. Dosage adjustment is not necessary in geriatric patients.