Tudorza Pressair: Indications, Dosage, Precautions, Adverse Effects
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Tudorza Pressair - Product Information

Manufacture: Forest Laboratories, Inc.
Country: United States
Condition: COPD, Maintenance
Class: Anticholinergic bronchodilators
Form: Inhaler
Ingredients: aclidinium bromide, lactose monohydrate

Indications and Usage

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.

Dosage and Administration

The recommended dose of TUDORZA PRESSAIR is one oral inhalation of 400 mcg, twice daily.

Dosage Forms and Strengths

Inhalation Powder. TUDORZA PRESSAIR is a breath-actuated multi-dose dry powder inhaler metering 400 mcg of aclidinium bromide per actuation.

Contraindications

None.

Warnings and Precautions

Not for Acute Use

TUDORZA PRESSAIR is intended as a twice-daily maintenance treatment for COPD and is not indicated for the initial treatment of acute episodes of bronchospasm (i.e., rescue therapy).

Paradoxical Bronchospasm

Inhaled medicines, including TUDORZA PRESSAIR, may cause paradoxical bronchospasm. If this occurs, treatment with TUDORZA PRESSAIR should be stopped and other treatments considered.

Worsening of Narrow-Angle Glaucoma

TUDORZA PRESSAIR should be used with caution in patients with narrow-angle glaucoma. Prescribers and patients should be alert for signs and symptoms of acute narrow-angle glaucoma (e.g., eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema). Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

Worsening of Urinary Retention

TUDORZA PRESSAIR should be used with caution in patients with urinary retention. Prescribers and patients should be alert for signs and symptoms of prostatic hyperplasia or bladder-neck obstruction (e.g., difficulty passing urine, painful urination). Instruct patients to consult a physician immediately should any of these signs or symptoms develop.

Immediate Hypersensitivity Reactions

Immediate hypersensitivity reactions, including anaphylaxis, angioedema (including swelling of the lips, tongue, or throat), urticaria, rash, bronchospasm, or itching, have occurred after administration of TUDORZA PRESSAIR. If such a reaction occurs, therapy with TUDORZA PRESSAIR should be stopped at once and alternative treatments should be considered. Given the similar structural formula of atropine to aclidinium, patients with a history of hypersensitivity reactions to atropine should be closely monitored for similar hypersensitivity reactions to TUDORZA PRESSAIR. In addition, TUDORZA PRESSAIR should be used with caution in patients with severe hypersensitivity to milk proteins.

Adverse Reactions

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
  Treatment
Adverse Reactions TUDORZA PRESSAIR Placebo
Preferred Term (N=636) (N=640)
  n (%) 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.

Drug Interactions

In vitro studies suggest limited potential for CYP450-related metabolic drug interactions, thus no formal drug interaction studies have been performed with TUDORZA PRESSAIR[see Clinical Pharmacology].

Sympathomimetics, Methylxanthines, Steroids

In clinical studies, concurrent administration of aclidinium bromide and other drugs commonly used in the treatment of COPD including sympathomimetics (short-acting beta2 agonists), methylxanthines, and oral and inhaled steroids showed no increases in adverse drug reactions.

Anticholinergics

There is a potential for an additive interaction with concomitantly used anticholinergic medications. Therefore, avoid coadministration of TUDORZA PRESSAIR with other anticholinergic-containing drugs as this may lead to an increase in anticholinergic effects.

Use in Specific Populations

Pregnancy

Teratogenic effects: Pregnancy Category C: There are no adequate and well controlled studies in pregnant women. Adverse development effects were observed in rats and rabbits exposed to aclidinium bromide. TUDORZA PRESSAIR should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus.

Effects of aclidinium bromide on embryo-fetal development were examined in rats and rabbits. No evidence of structural alterations was observed in rats exposed during the period of organogenesis at approximately 15 times the recommended human daily dose (RHDD) [based on summed AUCs of aclidinium bromide and its metabolites at inhaled doses less than or equal to 5.0 mg/kg/day]. However, decreased pup weights were observed from dams exposed during the lactation period at approximately 5 times the RHDD [based on summed AUCs of aclidinium bromide and its metabolites at inhaled doses greater than or equal to 0.2 mg/kg/day]. Maternal toxicity was also observed at inhaled doses greater than or equal to 0.2 mg/kg/day.

No evidence of structural alterations was observed in Himalayan rabbits exposed during the period of organogenesis at approximately 20 times the RHDD [based on summed AUCs of aclidinium bromide and its metabolites at inhaled doses less than or equal to 3.6 mg/kg/day]. However, increased incidences of additional liver lobes (3-5%), as compared to 0% in the control group, were observed at approximately 1,400 times the RHDD [based on summed AUCs of aclidinium bromide and its metabolites at oral doses greater than or equal to 150 mg/kg/day], and decreased fetal body weights were observed at approximately 2,300 times the RHDD [based on summed AUCs of aclidinium bromide and its metabolites at oral doses greater than or equal to 300 mg/kg/day]. These fetal findings were observed in the presence of maternal toxicity.

Labor and Delivery

The effect of TUDORZA PRESSAIR on labor and delivery is unknown. TUDORZA PRESSAIR should be used during labor and delivery only if the potential benefit to the patient justifies the potential risk to the fetus.

Nursing Mothers

Aclidinium bromide is excreted into the milk of lactating female rats, and decreased pup weights were observed. Excretion of aclidinium into human milk is probable. There are no human studies that have investigated the effects of TUDORZA PRESSAIR on breast-fed infants. Caution should be exercised when TUDORZA PRESSAIR is administered to nursing women.

Pediatric Use

TUDORZA PRESSAIR is approved for use in the maintenance treatment of bronchospasm associated with COPD. COPD does not normally occur in children. The safety and effectiveness of TUDORZA PRESSAIR in pediatric patients have not been established.

Geriatric Use

Of the 636 COPD patients exposed to TUDORZA PRESSAIR 400 mcg twice daily for up to 24 weeks in three placebo-controlled clinical trials, 197 were less than 60 years, 272 were greater than or equal to 60 to less than 70 years, and 167 were greater than or equal to 70 years of age. No overall differences in safety or effectiveness were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. Based on available data for TUDORZA PRESSAIR, no adjustment of dosage in geriatric patients is warranted[see Clinical Pharmacology].

Renal Impairment

The pharmacokinetics of TUDORZA PRESSAIR were investigated in subjects with normal renal function and in subjects with mild, moderate and severe renal impairment[see Clinical Pharmacology]. No clinically significant differences in aclidinium pharmacokinetics were noted between these populations. Based on available data for TUDORZA PRESSAIR, no adjustment of dosage in renally impaired subjects is warranted.

Hepatic Impairment

The effects of hepatic impairment on the pharmacokinetics of TUDORZA PRESSAIR were not studied [see Clinical Pharmacology].

Overdosage

Human Experience

No case of overdose has been reported in clinical studies with TUDORZA PRESSAIR. There were no systemic anticholinergic or other adverse effects following a single inhaled dose of up to 6,000 mcg aclidinium bromide (7.5 times the RHDD) in 16 healthy volunteers.

How Supplied/Storage and Handling

How Supplied

TUDORZA PRESSAIR(aclidinium bromide inhalation powder) 400 mcg is supplied in a sealed labeled aluminum pouch and is available in 60 metered doses (NDC 0456-0800-60) and 30 metered doses (NDC 0456-0800-31).

The active ingredient is administered using a multi-dose dry powder inhaler, PRESSAIR, which delivers 60 doses or 30 doses of aclidinium bromide powder for oral inhalation. The PRESSAIR inhaler is a white and green colored device and is comprised of an assembled plastic dosing mechanism with a dose indicator, a drug-product storage unit containing the drug-product formulation, and a mouthpiece covered by a green protective cap. The inhaler should be discarded when the marking “0” with a red background shows in the middle of the dose indicator or when the device locks out, whichever comes first.

Storage and Handling

Store TUDORZA PRESSAIR in a dry place at 25 °C (77 °F); excursions permitted to 15-30 °C (59-86 °F) [see USP Controlled Room Temperature].

The PRESSAIR inhaler should be stored inside the sealed pouch and only be opened immediately before use.

Discard the PRESSAIR inhaler 45 days after opening the pouch, after the marking “0” with a red background shows in the middle of the dose indicator, or when the device locks out, whichever comes first.

Keep out of reach of children.

Patient Counseling Information

See FDA-approved Patient Labeling (Patient Information and Instructions for Use)

Acute Bronchospasm

Instruct patients that TUDORZA PRESSAIR is a twice daily maintenance bronchodilator and should not be used for immediate relief of breathing problems (i.e., as a rescue medication)[see Warnings and Precautions].

Paradoxical Bronchospasm

Inform patients that TUDORZA PRESSAIR can cause paradoxical bronchospasm. Advise patients that if paradoxical bronchospasm occurs, patients should discontinue TUDORZA PRESSAIR[see Warnings and Precautions].

Visual Effects

Eye pain or discomfort, blurred vision, visual halos or colored images in association with red eyes from conjunctival congestion and corneal edema may be signs of acute narrow-angle glaucoma. Inform patients to consult a physician immediately should any of these signs and symptoms develop. Advise patients that miotic eyedrops alone are not considered to be effective treatment[see Warnings and Precautions].

Inform patients that care must be taken not to allow the powder to enter into the eyes as this may cause blurring of vision and pupil dilation.

Urinary Retention

Difficulty passing urine and dysuria may be symptoms of new or worsening prostatic hyperplasia or bladder outlet obstruction. Patients should be instructed to consult a physician immediately should any of these signs or symptoms develop [see Warnings and Precautions].

Immediate Hypersensitivity Reactions

Inform patients that anaphylaxis, angioedema (including swelling of the lips, tongue, or throat), urticaria, rash, bronchospasm, or itching, may occur after administration of TUDORZA PRESSAIR. Advise patient to immediately discontinue treatment and consult a physician should any of these signs or symptoms develop [see Warnings and Precautions].

Instructions for Administering TUDORZA PRESSAIR

It is important for patients to understand how to correctly use TUDORZA PRESSAIR.

Inform patients that if they miss a dose, they should take their next dose at the usual time; they should not take 2 doses at one time.

Distributed By

Forest Pharmaceuticals, Inc.
Subsidiary of Forest Laboratories, LLC
Cincinnati, Ohio 45209