Aclidinium Bromide

FDA Drug Information • Also known as: Tudorza Pressair

Brand Names: Tudorza Pressair
Route: RESPIRATORY (INHALATION)
Dosage Form: POWDER, METERED
Product Type: HUMAN PRESCRIPTION DRUG

Description

11 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 1-azoniabicyclo[2.2.2]octane, 3-[(hydroxydi-2-thienylacetyl)oxy]-1-(3-phenoxypropyl)-, bromide, (3 R )-. The structural formula is: Aclidinium bromide is a white powder with a molecular formula of C 26 H 30 NO 4 S 2 Br 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 (equivalent to 343 mcg of aclidinium). This results in delivery of 375 mcg aclidinium bromide (equivalent to 322 mcg of aclidinium) 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. Structural Formula

What Is Aclidinium Bromide Used For?

1 INDICATIONS AND USAGE 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)

Dosage and Administration

2 DOSAGE AND ADMINISTRATION The recommended dose of TUDORZA PRESSAIR is one oral inhalation of 400 mcg, twice daily (morning and evening approximately 12 hours apart). For oral inhalation only

One inhalation of TUDORZA PRESSAIR 400 mcg twice daily. (2)

Side Effects (Adverse Reactions)

6 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 . 6.1 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 (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. 6.2 Postmarketing Experience The following adverse reactions have been identified during postapproval use of drug TUDORZA PRESSAIR. Because these reactions are reported...

Drug Interactions

7 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 (12.3) ] . Anticholinergics: May interact additively with concomitantly used anticholinergic medications. Avoid administrations of TUDORZA PRESSAIR with other anticholinergic-containing drugs. ( 7.2 ) 7.1 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 beta 2 agonists), methylxanthines, and oral and inhaled steroids showed no increases in adverse drug reactions. 7.2 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.

Contraindications

4 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)

Pregnancy and Breastfeeding

8.1 Pregnancy 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...

Overdosage

10 OVERDOSAGE 10.1 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

16 HOW SUPPLIED/STORAGE AND HANDLING TUDORZA ® PRESSAIR ® (aclidinium bromide inhalation powder) 400 mcg is supplied in a sealed bag and is available in 60 metered doses (NDC 0310-0800-60) and 30 metered doses (NDC 0310-0800-39). 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. 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] . Do not store the inhaler on a vibrating surface. The PRESSAIR inhaler should be stored inside the sealed bag and only be opened immediately before use. Throw away the bag. Throw away (dispose of) the PRESSAIR inhaler after the marking “0” with a red background shows in the middle of the dose indicator, when the device is empty and locks out, or 45 days after the date you opened the sealed bag that the inhaler comes in, whichever comes first. Keep out of reach of children.

About This Information

This drug information is sourced from FDA-approved labeling via the openFDA database. It is intended for educational and reference purposes only. This is not medical advice. Always consult your healthcare provider before making decisions about medication. Drug information may be updated by the FDA; check with your pharmacist for the most current information.

What are side effects?

Side effects are unwanted reactions that can occur when taking a medication. They range from mild (headache, nausea) to severe (allergic reactions, organ damage). Not everyone experiences side effects, and severity varies. Report any concerning side effects to your doctor.

What are drug interactions?

Drug interactions occur when a medication is affected by another drug, food, or supplement. Interactions can make medications less effective or cause dangerous side effects. Always tell your doctor about all medications and supplements you take.