FDA

Tudorza Pressair

Approved 23 Jul 2012InhalationPowder, metered

Indications

TUDORZA® PRESSAIR® (aclidinium bromide inhalation powder) is indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). TUDORZA PRESSAIR is an anticholinergic indicated for the maintenance treatment of patients with chronic obstructive pulmonary disease (COPD). (1)

Contraindications

The use of TUDORZA PRESSAIR is contraindicated in the following conditions:

Severe hypersensitivity to milk proteins [see Warnings and Precautions (5.5) ]
Hypersensitivity to aclidinium bromide or any of the excipients [see Warnings and Precautions (5.5) ]
Severe hypersensitivity to milk proteins. (4)
Hypersensitivity to any ingredient. (4)

Warnings and precautions

Not for acute use: Not for use as a rescue medication. (5.1)
Paradoxical bronchospasm: Discontinue TUDORZA PRESSAIR and consider other treatments if paradoxical bronchospasm occurs. (5.2)
Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to consult a physician immediately if this occurs. (5.3)
Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to consult a physician immediately if this occurs. (5.4)
Immediate hypersensitivity reactions: Discontinue TUDORZA PRESSAIR at once and consider alternatives if immediate hypersensitivity reactions, including angioedema, bronchospasm, or anaphylaxis occur. (5.5)

5.1Not 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).

5.2Paradoxical Bronchospasm

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

5.3

At a glance

Brand name: Tudorza Pressair
Active substance: aclidinium bromide
Route: Inhalation
Dosage form: Powder, metered
Applicant: Azurity
Status: Prescription
FDA approval: 23 Jul 2012
Application: NDA202450-001

Indications

Contraindications

The use of TUDORZA PRESSAIR is contraindicated in the following conditions:

Severe hypersensitivity to milk proteins [see Warnings and Precautions (5.5) ]
Hypersensitivity to aclidinium bromide or any of the excipients [see Warnings and Precautions (5.5) ]
Severe hypersensitivity to milk proteins. (4)
Hypersensitivity to any ingredient. (4)

Warnings and precautions

Not for acute use: Not for use as a rescue medication. (5.1)
Paradoxical bronchospasm: Discontinue TUDORZA PRESSAIR and consider other treatments if paradoxical bronchospasm occurs. (5.2)
Worsening of narrow-angle glaucoma may occur. Use with caution in patients with narrow-angle glaucoma and instruct patients to consult a physician immediately if this occurs. (5.3)
Worsening of urinary retention may occur. Use with caution in patients with prostatic hyperplasia or bladder-neck obstruction and instruct patients to consult a physician immediately if this occurs. (5.4)
Immediate hypersensitivity reactions: Discontinue TUDORZA PRESSAIR at once and consider alternatives if immediate hypersensitivity reactions, including angioedema, bronchospasm, or anaphylaxis occur. (5.5)

5.1Not 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).

5.2Paradoxical Bronchospasm

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

5.3

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

There are no adequate and well controlled studies of TUDORZA PRESSAIR in pregnant women to inform drug associated risks. No adverse developmental effects were seen with inhalation administration of aclidinium bromide to pregnant rats and rabbits during organogenesis at 15 or 20 times, respectively, the maximum recommended human daily inhaled dose (MRHDID). However, reduced pup weights were seen when pregnant rats continued inhalation administration through lactation at 5 times the MRHDID of aclidinium bromide.

Adverse developmental effects occurred when rabbits were orally dosed with aclidinium bromide at approximately 1,400 times the MRHDID [ see Data ]. The estimated background risk of major birth defects and miscarriage of the indicated populations is unknown. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.

Data Animal Data In an embryo-fetal development study in pregnant rats dosed during the period of organogenesis from gestation days 6-17, no evidence of structural alterations was observed at approximately 15 times the MRHDID [based on summed AUCs of aclidinium bromide and its metabolites at inhaled doses less than or equal to 5.0 mg/kg/day]. However, in a pre- and post-natal development study, decreased pup weights were observed when pregnant rats were exposed from gestation day 6 and continuing during the lactation period at approximately 5 times the MRHDID [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. In an embryo-fetal development study in pregnant Himalayan rabbits administered inhaled doses of aclidinium bromide during the period of organogenesis from gestation days 6-19, no evidence of structural alterations was observed at approximately 20 times the MRHDID [based on summed AUCs of aclidinium bromide and its metabolites at inhaled doses less than or equal to 3.6 mg/kg/day].

However, in another embryo-fetal development study in pregnant Himalayan rabbits dosed orally from gestation days 6-19, increased incidences of additional liver lobes (3-5%), as compared to 0% in the control group, were observed at approximately 1,400 times the MRHDID [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 MRHDID [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.

Adverse reactions

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

Paradoxical bronchospasm [see Warnings and Precautions (5.2) ]
Worsening of narrow-angle glaucoma [see Warnings and Precautions (5.3) ]
Worsening of urinary retention [see Warnings and Precautions (5.4) ]
Immediate hypersensitivity reactions [see Warnings and Precautions (5.5) ] Most common adverse reactions (≥3% incidence and greater than placebo) are headache, nasopharyngitis and cough. (6.1) To report SUSPECTED ADVERSE REACTIONS, contact Covis Pharma at 1-877-411-2510 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical 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 (FEV 1 ) 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, 1 st 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. Long-Term Trial of up to 3-Years In a long-term safety trial with 3630 moderate to very severe COPD patients with previous major cardiac events or cardiovascular risk factors at baseline, the adverse reactions reported with a frequency ≥2% in the TUDORZA PRESSAIR group in which the exposure-adjusted incidence rate exceeds the placebo group were nausea, back pain, cough, hypertension, sinusitis, constipation, arthralgia, anemia, muscle spasms, cardiac failure congestive, cellulitis, and gastroesophageal reflux disease.

No other new adverse reactions were identified.

6.2Postmarketing 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.

Tudorza Pressair

Indications

Contraindications

Warnings and precautions

5.1Not for Acute Use

5.2Paradoxical Bronchospasm

5.3

At a glance

Two medicines in one question?

Tudorza Pressair

Indications

Contraindications

Warnings and precautions

5.1Not for Acute Use

5.2Paradoxical Bronchospasm

5.3

At a glance

Two medicines in one question?

5.4Worsening of Urinary Retention

5.5Immediate Hypersensitivity Reactions

Interactions

7.1Sympathomimetics, Methylxanthines, Steroids

7.2Anticholinergics

Pregnancy and breastfeeding

8.1Pregnancy Risk Summary

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Official product information