Aclidinium Bromide

Name: Aclidinium Bromide

Stability

Storage

Inhalation

Powder for Oral Inhalation

25°C (may be exposed to 15–30°C) in a dry place.1 Do not store inhaler on a vibrating surface.1

Keep inhaler in sealed pouch until immediately before use.1 Discard inhaler when dose indicator reads zero, when device locks out (green button stays depressed), or 45 days after removal from sealed pouch, whichever comes first.1

Actions

  • Long-acting, orally inhaled bronchodilator.1 14

  • Competitively and reversibly inhibits actions of acetylcholine and other cholinergic stimuli at M3 receptors in the smooth muscle of the respiratory tract leading to bronchodilation.1 14

  • Tolerance not observed with long-term administration; improvement in lung function (as measured by FEV1) consistently maintained over 12 or 24 weeks in clinical studies.1 14

Description

TUDORZA PRESSAIR consists of a dry powder formulation of aclidinium bromide for oral inhalation only.

Aclidinium bromide, the active component of TUDORZA PRESSAIR is an anticholinergic with specificity for muscarinic receptors. Aclidinium bromide is a synthetic, quaternary ammonium compound, chemically described as 1Azoniabicyclo[2.2.2]octane, 3-[(hydroxydi-2-thienylacetyl)oxy]-1-(3-phenoxypropyl)-, bromide, (3R)-. The structural formula is:

Aclidinium bromide is a white powder with a molecular formula of C26H30NO4S2Br and a molecular mass of 564.56. It is very slightly soluble in water and ethanol and sparingly soluble in methanol.

TUDORZA PRESSAIR is a breath-actuated multi-dose dry powder inhaler. Each actuation of TUDORZA PRESSAIR provides a metered dose of 13 mg of the formulation which contains lactose monohydrate (which may contain milk proteins) as the carrier and 400 mcg of aclidinium bromide. This results in delivery of 375 mcg aclidinium bromide from the mouthpiece, based on in vitro testing at an average flow rate of 63 L/min with constant volume of 2 L. The amount of drug delivered to the lungs will vary depending on patient factors such as inspiratory flow rate and inspiratory time. The PRESSAIR inhaler delivers the target dose at flow rates as low as 35 L/min. Based on a study in adult patients with moderate (N=24) and severe (N=24) COPD the mean peak inspiratory flow (PIF) was 95.3 L/min (range: 54.6 to 129.4 L/min) and 88.7 L/min (range: 72.0 to 106.4 L/min) respectively.

Indications

TUDORZA® PRESSAIR® (aclidinium bromide inhalation powder) is indicated for the long-term, maintenance treatment of bronchospasm associated with chronic obstructive pulmonary disease (COPD), including chronic bronchitis and emphysema.

Side effects

The following adverse reactions are described in greater detail in other sections:

  • Paradoxical bronchospasm [see WARNINGS AND PRECAUTIONS]
  • Worsening of narrow-angle glaucoma [see WARNINGS AND PRECAUTIONS]
  • Worsening of urinary retention [see WARNINGS AND PRECAUTIONS]
  • Immediate hypersensitivity reactions [see WARNINGS AND PRECAUTIONS]

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.

3-Month And 6-Month Trials

TUDORZA PRESSAIR was studied in two 3-month (Trials B and C) and one 6-month (Trial D) placebo-controlled trials in patients with COPD. In these trials, 636 patients were treated with TUDORZA PRESSAIR at the recommended dose of 400 mcg twice daily.

The population had a mean age of 64 years (ranging from 40 to 89 years), with 58% males, 94% Caucasian, and had COPD with a mean pre-bronchodilator forced expiratory volume in one second (FEV1) percent predicted of 48%. Patients with unstable cardiac disease, narrow-angle glaucoma, or symptomatic prostatic hypertrophy or bladder outlet obstruction were excluded from these trials.

Table 1 shows all adverse reactions that occurred with a frequency of greater than or equal to 1% in the TUDORZA PRESSAIR group in the two 3-month and one 6-month placebo-controlled trials where the rates in the TUDORZA PRESSAIR group exceeded placebo.

Table 1: Adverse Reactions (% Patients) in Placebo-Controlled Clinical Trials

Adverse Reactions
Preferred Term
Treatment
TUDORZA PRESSAIR
(N=636)
n (%)
Placebo
(N=640)
n (%)
Headache 42 (6.6) 32 (5.0)
Nasopharyngitis 35 (5.5) 25 (3.9)
Cough 19 (3.0) 14 (2.2)
Diarrhea 17 (2.7) 9 (1.4)
Sinusitis 11 (1.7) 5 (0.8)
Rhinitis 10 (1.6) 8 (1.2)
Toothache 7 (1.1) 5 (0.8)
Fall 7 (1.1) 3 (0.5)
Vomiting 7 (1.1) 3 (0.5)

In addition, among the adverse reactions observed in the clinical trials with an incidence of less than 1% were diabetes mellitus, dry mouth, 1st degree AV block, osteoarthritis, cardiac failure, and cardio-respiratory arrest.

Long-term Safety Trials

TUDORZA PRESSAIR was studied in three long term safety trials, two double blind and one open label, ranging from 40 to 52 weeks in patients with moderate to severe COPD. Two of these trials were extensions of the 3-month trials, and one was a dedicated long term safety trial. In these trials, 891 patients were treated with TUDORZA PRESSAIR at the recommended dose of 400 mcg twice daily. The demographic and baseline characteristics of the long term safety trials were similar to those of the placebo-controlled trials. The adverse events reported in the long term safety trials were similar to those occurring in the placebo-controlled trials of 3 to 6 months. No new safety findings were reported compared to the placebo controlled trials.

Postmarketing Experience

The following adverse reactions have been identified during postapproval use of drug TUDORZA PRESSAIR. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

In postmarketing experience with TUDORZA PRESSAIR, immediate hypersensitivity reactions, including anaphylaxis, angioedema (including swelling of the lips, tongue, or throat), urticaria, rash, bronchospasm, or itching have been reported. Additionally, nausea, dysphonia, blurred vision, urinary retention, tachycardia and stomatitis have been observed.

  • Albuterol Sulfate
  • Incruse Ellipta
  • Proventil
  • Serevent Diskus
  • Stiolto Respimat
  • Striverdi Respimat
  • Theophylline in 5% Dextrose
  • Uniphyl
  • Utibron Neohaler
  • Ventolin HFA

© Tudorza Pressair Patient Information is supplied by Cerner Multum, Inc. and Tudorza Pressair Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.

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