CAYSTON- aztreonam kit

United States - English - NLM (National Library of Medicine)

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Active ingredient:
aztreonam (UNII: G2B4VE5GH8) (aztreonam - UNII:G2B4VE5GH8)
Available from:
Gilead Sciences, Inc.
INN (International Name):
aztreonam
Composition:
aztreonam 75 mg in 1 mL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
CAYSTON® is indicated to improve respiratory symptoms in cystic fibrosis (CF) patients with Pseudomonas aeruginosa . Safety and effectiveness have not been established in pediatric patients below the age of 7 years, patients with FEV1 <25% or >75% predicted, or patients colonized with Burkholderia cepacia [see Clinical Studies (14)]. To reduce the development of drug-resistant bacteria and maintain the effectiveness of CAYSTON and other antibacterial drugs, CAYSTON should be used only to treat patients with CF known to have Pseudomonas aeruginosa in the lungs. CAYSTON is contraindicated in patients with a known allergy to aztreonam. Risk Summary Available data on CAYSTON use in pregnant women is insufficient to inform a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes; however, systemic absorption of aztreonam following inhaled administration is expected to be minimal [see Clinical Pharmacology (12.3)]. There are risks to the mother associated with cystic fi
Product summary:
Each kit for a 28-day course of CAYSTON contains 84 sterile vials of CAYSTON and 88 ampules of sterile diluent packed in 2 cartons, each carton containing a 14-day supply. The four additional diluent ampules are provided in case of spillage. CAYSTON vials and diluent ampules should be stored in the refrigerator at 2 °C to 8 °C (36 °F to 46 °F) until needed. Once removed from the refrigerator, CAYSTON and diluent may be stored at room temperature (up to 25 °C/77 °F) for up to 28 days. Do not separate the CAYSTON vials from the diluent ampules. CAYSTON should be protected from light. Do not use CAYSTON if it has been stored at room temperature for more than 28 days. Do not use CAYSTON beyond the expiration date stamped on the vial. Do not use diluent beyond the expiration date embossed on the ampule. CAYSTON should be used immediately upon reconstitution. Do not reconstitute more than one dose at a time. Do not use diluent or reconstituted CAYSTON if it is cloudy or if there are particles in the solution.
Authorization status:
New Drug Application
Authorization number:
61958-0901-1

CAYSTON- aztreonam

Gilead Sciences, Inc.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use CAYSTON safely and effectively. See full

prescribing information for CAYSTON.

CAYSTON (aztreonam for inhalation solution), for oral inhalation use

Initial U.S. Approval: 1986

To reduce the development of drug-resistant bacteria and maintain the effectiveness of CAYSTON and other antibacterial

drugs, CAYSTON should be used only to treat patients with cystic fibrosis (CF) known to have Pseudomonas aeruginosa in

the lungs. (1)

INDICATIONS AND USAGE

CAYSTON is a monobactam antibacterial indicated to improve respiratory symptoms in cystic fibrosis (CF) patients with

Pseudomonas aeruginosa. Safety and effectiveness have not been established in pediatric patients below the age of 7

years, patients with FEV <25% or >75% predicted, or patients colonized with Burkholderia cepacia. (1)

DOSAGE AND ADMINISTRATION

Administer one dose (one single use vial and one ampule of diluent) 3 times a day for 28 days. (2.1)

Use dose immediately after reconstitution. (2.2)

Administer only with the Altera

Nebulizer System. Do not administer with any other type of nebulizer. (2.3)

DOSAGE FORMS AND STRENGTHS

Lyophilized aztreonam (75 mg/vial) (3)

Diluent (0.17% sodium chloride): 1 mL/ampule (3)

CONTRAINDICATIONS

Contraindicated in patients with a known allergy to aztreonam. (4)

WARNINGS AND PRECAUTIONS

Allergic reaction to CAYSTON was seen in clinical trials. Stop treatment if an allergic reaction occurs. Use caution when

CAYSTON is administered to patients with a known allergic reaction to beta-lactams. (5.1)

Bronchospasm has been reported with CAYSTON. Stop treatment if chest tightness develops during nebulizer use.

(5.2)

ADVERSE REACTIONS

Common adverse reactions (more than 5%) occurring more frequently in CAYSTON patients are cough, nasal congestion,

wheezing, pharyngolaryngeal pain, pyrexia, chest discomfort, abdominal pain and vomiting. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Gilead Sciences, Inc. at 1-800-GILEAD5, option 3 or

FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 11/2019

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

2.1 Dosing Information

2.2 Instructions for CAYSTON Reconstitution

2.3 Instructions for CAYSTON Administration

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Allergic Reactions

®

®

5.2 Bronchospasm

5.3 Decreases in FEV After 28-Day Treatment Cycle

5.4 Development of Drug-Resistant Bacteria

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.2 Lactation

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Use in Patients with Renal Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.3 Pharmacokinetics

12.4 Microbiology

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

15 REFERENCES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

CAYSTON is indicated to improve respiratory symptoms in cystic fibrosis (CF) patients with

Pseudomonas aeruginosa. Safety and effectiveness have not been established in pediatric patients below

the age of 7 years, patients with FEV <25% or >75% predicted, or patients colonized with

Burkholderia cepacia [see Clinical Studies (14)].

To reduce the development of drug-resistant bacteria and maintain the effectiveness of CAYSTON and

other antibacterial drugs, CAYSTON should be used only to treat patients with CF known to have

Pseudomonas aeruginosa in the lungs.

2 DOSAGE AND ADMINISTRATION

2.1 Dosing Information

The recommended dose of CAYSTON for both adults and pediatric patients 7 years of age and older is

one single-use vial (75 mg of aztreonam) reconstituted with 1 mL of sterile diluent administered 3 times

a day for a 28-day course (followed by 28 days off CAYSTON therapy). Dosage is not based on

weight or adjusted for age. Doses should be taken at least 4 hours apart.

CAYSTON is administered by inhalation using an Altera

Nebulizer System. Patients should use a

bronchodilator before administration of CAYSTON.

Sections or subsections omitted from the full prescribing information are not listed.

2.2 Instructions for CAYSTON Reconstitution

CAYSTON should be administered immediately after reconstitution. Do not reconstitute CAYSTON until

ready to administer a dose.

Take one amber glass vial containing CAYSTON and one diluent ampule from the carton. To open the

glass vial, carefully remove the blue cap and metal ring and remove the gray rubber stopper. Twist the

tip off the diluent ampule and squeeze the liquid into the glass vial. Replace the rubber stopper, then

gently swirl the vial until contents have completely dissolved.

The empty vial, stopper, and diluent ampule should be disposed of properly upon completion of dosing.

2.3 Instructions for CAYSTON Administration

CAYSTON is administered by inhalation using an Altera Nebulizer System. CAYSTON should not be

administered with any other nebulizer. CAYSTON should not be mixed with any other drugs in the

Altera Nebulizer Handset.

CAYSTON is not for intravenous or intramuscular administration.

Patients should use a bronchodilator before administration of CAYSTON. Short-acting bronchodilators

can be taken between 15 minutes and 4 hours prior to each dose of CAYSTON. Alternatively, long-

acting bronchodilators can be taken between 30 minutes and 12 hours prior to administration of

CAYSTON. For patients taking multiple inhaled therapies, the recommended order of administration is

as follows: bronchodilator, mucolytics, and lastly, CAYSTON.

To administer CAYSTON, pour the reconstituted solution into the handset of the nebulizer system. Turn

the unit on. Place the mouthpiece of the handset in your mouth and breathe normally only through your

mouth. Administration typically takes between 2 and 3 minutes. Further patient instructions on how to

administer CAYSTON are provided in the FDA-approved patient labeling. Instructions on testing

nebulizer functionality and cleaning the handset are provided in the Instructions for Use included with

the nebulizer system.

3 DOSAGE FORMS AND STRENGTHS

A dose of CAYSTON consists of a single-use vial of sterile, lyophilized aztreonam (75 mg)

reconstituted with a 1 mL ampule of sterile diluent (0.17% sodium chloride). Reconstituted CAYSTON

is administered by inhalation.

4 CONTRAINDICATIONS

CAYSTON is contraindicated in patients with a known allergy to aztreonam.

5 WARNINGS AND PRECAUTIONS

5.1 Allergic Reactions

Severe allergic reactions have been reported following administration of aztreonam for injection to

patients with no known history of exposure to aztreonam. In addition, allergic reaction with facial rash,

facial swelling, and throat tightness was reported with CAYSTON in clinical trials. If an allergic

reaction to CAYSTON occurs, stop administration of CAYSTON and initiate treatment as appropriate.

Caution is advised when administering CAYSTON to patients if they have a history of beta-lactam

allergy, although patients with a known beta-lactam allergy have received CAYSTON in clinical trials

and no severe allergic reactions were reported. A history of allergy to beta-lactam antibiotics, such as

penicillins, cephalosporins, and/or carbapenems, may be a risk factor, since cross-reactivity may occur.

5.2 Bronchospasm

5.2 Bronchospasm

Bronchospasm is a complication associated with nebulized therapies, including CAYSTON. Reduction

of 15% or more in forced expiratory volume in 1 second (FEV ) immediately following administration

of study medication after pretreatment with a bronchodilator was observed in 3% of patients treated with

CAYSTON.

5.3 Decreases in FEV After 28-Day Treatment Cycle

In clinical trials, patients with increases in FEV during a 28-day course of CAYSTON were sometimes

treated for pulmonary exacerbations when FEV declined after the treatment period. Healthcare

providers should consider a patient's baseline FEV measured prior to CAYSTON therapy and the

presence of other symptoms when evaluating whether post-treatment changes in FEV are caused by a

pulmonary exacerbation.

5.4 Development of Drug-Resistant Bacteria

Prescribing CAYSTON in the absence of known Pseudomonas aeruginosa infection in patients with CF

is unlikely to provide benefit and increases the risk of development of drug-resistant bacteria.

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed

in the clinical trials of drugs cannot be directly compared to rates in the clinical trials of another drug

and may not reflect the rates observed in practice.

The safety of CAYSTON was evaluated in 344 patients from two placebo-controlled trials and one

open-label follow-on trial. In controlled trials, 146 patients with CF received 75 mg CAYSTON 3 times

a day for 28 days.

Table 1 displays adverse reactions reported in more than 5% of patients treated with CAYSTON 3 times

a day in placebo-controlled trials. The listed adverse reactions occurred more frequently in

CAYSTON-treated patients than in placebo-treated patients.

Table 1 Adverse Reactions Reported in more than 5% of

Patients Treated with CAYSTON in the Placebo-

Controlled Trials

Event (Preferred Term)

Placebo

(N=160)

n (%)

CAYSTON

75 mg 3 times

a day

(N=146)

n (%)

Cough

82 (51%)

79 (54%)

Nasal congestion

19 (12%)

23 (16%)

Wheezing

16 (10%)

23 (16%)

Pharyngolaryngeal pain

17 (11%)

18 (12%)

Pyrexia

9 (6%)

19 (13%)

Chest discomfort

10 (6%)

11 (8%)

Abdominal Pain

8 (5%)

10 (7%)

Vomiting

7 (4%)

9 (6%)

Adverse reactions that occurred in less than 5% of patients treated with CAYSTON were bronchospasm

(3%) [see Warnings and Precautions (5.2)] and rash (2%).

1

6.2 Postmarketing Experience

In addition to adverse reactions reported from clinical trials, the following possible adverse reactions

have been identified during post-approval use of CAYSTON. Because these events have been reported

voluntarily from a population of unknown size, estimates of frequency cannot be made.

MUSCULOSKELETAL AND CONNECTIVE TISSUE DISORDERS

Arthralgia, joint swelling

7 DRUG INTERACTIONS

No formal clinical studies of drug interactions with CAYSTON have been conducted.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk Summary

Available data on CAYSTON use in pregnant women is insufficient to inform a drug-associated risk of

major birth defects, miscarriage, or adverse maternal or fetal outcomes; however, systemic absorption

of aztreonam following inhaled administration is expected to be minimal [see Clinical Pharmacology

(12.3)]. There are risks to the mother associated with cystic fibrosis in pregnancy (see Clinical

Considerations). In animal reproduction studies with aztreonam for injection administered parenterally to

pregnant rats and rabbits during organogenesis, there was no evidence of developmental toxicity. A

peri/postnatal study in rats revealed no drug-induced changes in maternal, fetal, or neonatal parameters.

The estimated background risk of major birth defects and miscarriage for the indicated population are

unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. 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.

Clinical Considerations

Disease-Associated Maternal and/or Embryo/Fetal Risk

Cystic fibrosis may increase the risk for preterm delivery.

Data

Animal Data

No reproductive toxicity studies have been conducted with CAYSTON. However, studies were

conducted with aztreonam for injection. No evidence of developmental toxicity has been shown in

studies with pregnant rats and rabbits that received parenteral doses of aztreonam during organogenesis

of up to 1800 and 1200 mg/kg/day, respectively. In rats receiving aztreonam for injection during late

gestation and lactation at up to 1800 mg/kg/day, no drug induced changes in maternal, fetal or neonatal

parameters were observed. These animal reproduction and developmental toxicity studies used

parenteral routes of administration that would provide systemic exposures significantly greater than the

average peak plasma levels measured in humans following CAYSTON therapy.

8.2 Lactation

Risk Summary

Following intravenous administration of aztreonam for injection, aztreonam is excreted in human milk at

concentrations that are less than one percent of those determined in simultaneously obtained maternal

serum. Peak plasma concentrations of aztreonam following administration of CAYSTON (75 mg) are

approximately 1% of peak concentrations observed following IV aztreonam (500 mg). Systemic

absorption of aztreonam following inhaled administration is expected to be minimal [see Clinical

absorption of aztreonam following inhaled administration is expected to be minimal [see Clinical

Pharmacology (12.3)]. There are no data on the effects of aztreonam on the breastfed infant or the

effects on milk production. The developmental and health benefits of breastfeeding should be

considered along with the mother's clinical need for CAYSTON and any potential adverse effects on

the breastfed infant from CAYSTON or from the underlying maternal condition.

8.4 Pediatric Use

Patients 7 years and older were included in clinical trials with CAYSTON. Fifty-five patients under 18

years of age received CAYSTON in placebo-controlled trials. No dose adjustments were made for

pediatric patients. Pyrexia was more commonly reported in pediatric patients than in adult patients.

Safety and effectiveness in pediatric patients below the age of 7 years have not been established.

8.5 Geriatric Use

Clinical trials of CAYSTON did not include CAYSTON-treated patients aged 65 years of age and older

to determine whether they respond differently from younger patients.

8.6 Use in Patients with Renal Impairment

Aztreonam is known to be excreted by the kidney. Placebo-controlled clinical trials with CAYSTON

excluded patients with abnormal baseline renal function (defined as serum creatinine greater than 2 times

the upper limit of normal range). Given the low systemic exposure of aztreonam following

administration of CAYSTON, clinically relevant accumulation of aztreonam is unlikely to occur in

patients with renal impairment. Therefore, CAYSTON may be administered to patients with mild,

moderate and severe renal impairment with no dosage adjustment.

10 OVERDOSAGE

No overdoses have been reported with CAYSTON in clinical trials to date. In clinical trials, 225 mg

doses of CAYSTON via inhalation were associated with higher rates of drug-related respiratory

adverse reactions, particularly cough. Since the peak plasma concentration of aztreonam following

administration of CAYSTON (75 mg) is approximately 0.6 mcg/mL, compared to a serum concentration

of 54 mcg/mL following administration of aztreonam for injection (500 mg), no systemic safety issues

associated with CAYSTON overdose are anticipated.

11 DESCRIPTION

A dose of CAYSTON consists of a 2 mL amber glass vial containing lyophilized aztreonam (75 mg) and

lysine (46.7 mg), and a low-density polyethylene ampule containing 1 mL sterile diluent (0.17% sodium

chloride). The reconstituted solution is for inhalation. The formulation contains no preservatives or

arginine.

The active ingredient in CAYSTON is aztreonam, a monobactam antibacterial. The monobactams are

structurally different from beta-lactam antibiotics (e.g., penicillins, cephalosporins, carbapenems) due to

a monocyclic nucleus. This nucleus contains several side chains; sulfonic acid in the 1-position

activates the nucleus, an aminothiazolyl oxime side chain in the 3-position confers specificity for

aerobic Gram-negative bacteria including Pseudomonas spp., and a methyl group in the 4-position

enhances beta-lactamase stability.

Aztreonam is designated chemically as (Z)-2-[[[(2-amino-4-thiazolyl)[[(2S,3S)-2-methyl-4-oxo-1-sulfo-

3-azetidinyl]carbamoyl]methylene]amino]oxy]-2-methylpropionic acid. The structural formula is

presented below:

CAYSTON is a white to off-white powder. CAYSTON is sterile, hygroscopic, and light sensitive.

Once reconstituted with the supplied diluent, the pH range is 4.5 to 6.0.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Aztreonam is an antibacterial drug [see Clinical Pharmacology (12.4)].

12.3 Pharmacokinetics

Sputum Concentrations

Sputum aztreonam concentrations exhibited considerable variability between patients receiving

CAYSTON (75 mg) in clinical trials. The mean sputum concentration 10 minutes following the first

dose of CAYSTON (n = 195 patients with CF) was 726 mcg/g. Mean sputum concentrations of

aztreonam in patients receiving CAYSTON 3 times a day for 28 days were 984 mcg/g, 793 mcg/g, and

715 mcg/g 10 minutes after dose administration on Days 0, 14, and 28, respectively, indicating no

accumulation of aztreonam in sputum.

Plasma Concentrations

Plasma aztreonam concentrations exhibited considerable variability between patients receiving

CAYSTON (75 mg) in the clinical trials. The mean plasma concentration one hour following the first

dose of CAYSTON (at approximately the peak plasma concentration) was 0.59 mcg/mL. Mean peak

plasma concentrations in patients receiving CAYSTON 3 times a day for 28 days were 0.55 mcg/mL,

0.67 mcg/mL, and 0.65 mcg/mL on Days 0, 14, and 28, respectively, indicating no systemic

accumulation of aztreonam. In contrast, the serum concentration of aztreonam following administration

of aztreonam for injection (500 mg) is approximately 54 mcg/mL.

Absorption

Evaluation of plasma and urine aztreonam concentrations following administration of CAYSTON

indicates low systemic absorption of aztreonam. Approximately 10% of the total CAYSTON dose is

excreted in the urine as unchanged drug, as compared to 60–65% following intravenous administration

of aztreonam for injection.

Distribution

The protein binding of aztreonam in plasma is approximately 77% within the clinical dose range of

concentrations achieved following CAYSTON administration.

Metabolism

Following intramuscular administration of aztreonam for injection 500 mg every 8 hours for 7 days,

approximately 6% of the dose was excreted as a microbiologically inactive open β-lactam ring

hydrolysis product in an 8-hour urine collection on the last day of multiple dosing.

Excretion

The elimination half-life of aztreonam from plasma is approximately 2.1 hours following administration

of CAYSTON to adult patients with CF, similar to what has been reported for aztreonam for injection.

Approximately 10% of the total CAYSTON dose is excreted in the urine as unchanged drug.

Systemically absorbed aztreonam is eliminated about equally by active tubular secretion and glomerular

filtration. Following administration of a single intravenous dose of radiolabeled aztreonam for injection,

about 12% of the dose was recovered in the feces.

12.4 Microbiology

Mechanism of Action

Aztreonam exhibits activity in vitro against Gram-negative aerobic pathogens including P. aeruginosa.

Aztreonam binds to penicillin-binding proteins of susceptible bacteria, which leads to inhibition of

bacterial cell wall synthesis and death of the cell. Aztreonam activity is not decreased in the presence of

CF lung secretions.

Susceptibility Testing

A single sputum sample from a patient with CF may contain multiple morphotypes of P. aeruginosa and

each morphotype may have a different level of in vitro susceptibility to aztreonam. There are no in vitro

susceptibility test interpretive criteria for isolates of P. aeruginosa obtained from the sputum of CF

patients.

Development of Resistance

No changes in the susceptibility of P. aeruginosa to aztreonam were observed following a 28-day

course of CAYSTON in the placebo-controlled trials.

Cross-Resistance

No cross-resistance to other classes of antibiotics, including aminoglycosides, quinolones, and beta-

lactams, was observed following a 28-day course of CAYSTON in the Phase 3 placebo-controlled

trials or in an open-label follow-on trial of up to nine 28-day courses of 75 mg CAYSTON 3 times a

day.

Other

No trends in the treatment-emergent isolation of other bacterial respiratory pathogens (Burkholderia

cepacia, Stenotrophomonas maltophilia, Achromobacter xylosoxidans, and Staphylococcus aureus) were

observed in clinical trials. There was a slight increase in the isolation of Candida spp. following up to

nine 28-day courses of CAYSTON therapy.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

A 104-week rat inhalation toxicology study to assess the carcinogenic potential of aztreonam

demonstrated no drug-related increase in the incidence of tumors. Rats were exposed to aerosolized

aztreonam for up to 4 hours per day. Peak plasma levels of aztreonam averaging approximately 6.8

mcg/mL were measured in rats at the highest dose level. This is approximately 12-fold higher than the

average peak plasma level measured in humans following CAYSTON therapy.

Genetic toxicology studies performed in vitro demonstrated that aztreonam did not induce structural

chromosome aberrations in CHO cells and did not induce mutations at the TK locus in mouse lymphoma

L5178Y TK cells. In vivo, aztreonam was not clastogenic in mouse bone marrow cells.

Aztreonam did not impair the fertility of rats when administered parenterally at doses up to 2400

mg/kg/day that would provide systemic exposures significantly higher than peak plasma levels measured

in humans following CAYSTON therapy.

14 CLINICAL STUDIES

CAYSTON was evaluated over a period of 28 days of treatment in a randomized, double-blind,

placebo-controlled, multicenter trial that enrolled patients with CF and P. aeruginosa. This trial was

designed to evaluate improvement in respiratory symptoms. Patients 7 years of age and older and with

FEV of 25% to 75% predicted were enrolled. All patients received CAYSTON or placebo on an

outpatient basis administered with the Altera Nebulizer System. All patients were required to take a

dose of an inhaled bronchodilator (beta-agonist) prior to taking a dose of CAYSTON or placebo.

Patients were receiving standard care for CF, including drugs for obstructive airway diseases.

The trial enrolled 164 patients with CF and P. aeruginosa. The mean age was 30 years, and the mean

baseline FEV % predicted was 55%; 43% were females and 96% were Caucasian. These patients were

randomized in a 1:1 ratio to receive either CAYSTON (75 mg) or volume-matched placebo administered

by inhalation 3 times a day for 28 days. Patients were required to have been off antibiotics for at least

28 days before treatment with study drug. The primary efficacy endpoint was improvement in

respiratory symptoms on the last day of treatment with CAYSTON or placebo. Respiratory symptoms

were also assessed two weeks after the completion of treatment with CAYSTON or placebo. Changes

in respiratory symptoms were assessed using a questionnaire that asks patients to report on symptoms

like cough, wheezing, and sputum production.

Improvement in respiratory symptoms was noted for CAYSTON-treated patients relative to placebo-

treated patients on the last day of drug treatment. Statistically significant improvements were seen in both

adult and pediatric patients but were substantially smaller in adult patients. Two weeks after completion

of treatment, a difference in respiratory symptoms between treatment groups was still present, though

the difference was smaller.

Pulmonary function, as measured by FEV (L), increased from baseline in patients treated with

CAYSTON (see Figure 1). The treatment difference at Day 28 between CAYSTON-treated and

placebo-treated patients for percent change in FEV (L) was statistically significant at 10% (95% CI:

6%, 14%). Improvements in FEV were comparable between adult and pediatric patients. Two weeks

after completion of drug treatment, the difference in FEV between CAYSTON and placebo groups had

decreased to 6% (95% CI: 2%, 9%).

Figure 1 Adjusted Mean Percent Change in FEV from Baseline to Study End (Days 0–42)

1

15 REFERENCES

1. Clinical and Laboratory Standards Institute (CLSI). Methods for Dilution Antimicrobial

Susceptibility Tests for Bacteria that Grow Aerobically—Eighth Edition; Approved Standard. CLSI

Document M7-A8. CLSI, Wayne, PA 19087. January 2009.

16 HOW SUPPLIED/STORAGE AND HANDLING

Each kit for a 28-day course of CAYSTON contains 84 sterile vials of CAYSTON and 88 ampules of

sterile diluent packed in 2 cartons, each carton containing a 14-day supply. The four additional diluent

ampules are provided in case of spillage.

Package

Configuration

Dosage Strength

NDC

28-Day Kit

75 mg

61958-0901-1

CAYSTON vials and diluent ampules should be stored in the refrigerator at 2 °C to 8 °C (36 °F to 46

°F) until needed. Once removed from the refrigerator, CAYSTON and diluent may be stored at room

temperature (up to 25 °C/77 °F) for up to 28 days. Do not separate the CAYSTON vials from the diluent

ampules. CAYSTON should be protected from light.

Do not use CAYSTON if it has been stored at room temperature for more than 28 days. Do not use

CAYSTON beyond the expiration date stamped on the vial. Do not use diluent beyond the expiration

date embossed on the ampule.

CAYSTON should be used immediately upon reconstitution. Do not reconstitute more than one dose at a

time.

Do not use diluent or reconstituted CAYSTON if it is cloudy or if there are particles in the solution.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for

Use).

Allergic Reactions

Advise patients to tell their healthcare provider immediately if they believe they are experiencing new

or worsening symptoms or believe they are having an allergic reaction to CAYSTON [see Warnings and

Precautions (5.1)].

Development of Drug-Resistant Bacteria

Counsel patients that antibacterial drugs including CAYSTON should only be used to treat bacterial

infections. They do not treat viral infection (e.g., the common cold). When CAYSTON is prescribed to

treat a bacterial infection, inform patients that although it is common to feel better early in the course of

therapy, the medication should be taken exactly as directed. Skipping doses or not completing the full

course of therapy may (1) decrease the effectiveness of the immediate treatment and (2) increase the

likelihood that bacteria will develop resistance and will not be treatable by CAYSTON or other

antibacterial drugs in the future [see Warnings and Precautions (5.4)].

Reconstitution and Administration

Advise patients that:

CAYSTON is for inhalation use only and should only be administered using the Altera Nebulizer

System.

CAYSTON should only be reconstituted with the provided diluent. Instruct patients not to mix other

drugs with CAYSTON in the Altera Nebulizer System.

Advise patients to:

use a bronchodilator prior to administration of CAYSTON.

complete the full 28-day course of CAYSTON even if they are feeling better.

Advise patients taking several inhaled medications to use the medications in the following order:

bronchodilator, mucolytics, and lastly, CAYSTON.

Missed Dose

Inform the patient that if they miss a dose, they should take all 3 daily doses as long as the doses are at

least 4 hours apart.

CAYSTON is a trademark of Gilead Sciences, Inc. All other trademarks referenced herein are the

property of their respective owners.

© 2019 Gilead Sciences, Inc. All rights reserved.

50-814-GS-004

PATIENT INFORMATION

CAYSTON (kay-stun)

(aztreonam for inhalation solution)

for oral inhalation use

What is CAYSTON?

CAYSTON is a prescription medicine that is used to improve breathing symptoms in people with cystic

fibrosis (CF) who have a lung infection caused by a bacterium called Pseudomonas aeruginosa.

CAYSTON contains an antibacterial medicine called aztreonam.

CAYSTON is only for infections caused by bacteria. It is not for infections caused by viruses, such

as the common cold.

It is not known if CAYSTON is safe and effective:

in children under 7 years of age

in people who have an FEV less than 25% or greater than 75% predicted

in people who are colonized with a bacterium called Burkholderia cepacia

Do not take CAYSTON if you are allergic to aztreonam, or any of the ingredients in CAYSTON.

See the end of this Patient Information for a complete list of ingredients in CAYSTON.

®

Before you take CAYSTON, tell your healthcare provider about all of your medical conditions,

including if you:

are allergic to any antibiotics.

are pregnant or plan to become pregnant. It is not known if CAYSTON can harm your unborn baby.

are breastfeeding or plan to breastfeed. CAYSTON can pass into your breastmilk. Talk with your

healthcare provider about the best way to feed your baby while you are taking CAYSTON.

Tell your healthcare provider about all the medicines you take, including prescription and over-the-

counter medicines, vitamins, and herbal supplements.

Some medicines may affect how CAYSTON works.

How should I take CAYSTON?

See the step-by-step Instructions for Use about the right way to take your CAYSTON.

Take CAYSTON exactly as your healthcare provider tells you. Do not change your dose or stop

taking CAYSTON unless your healthcare provider tells you to.

The dose for both adults and children 7 years of age and older is:

1 single-use vial of CAYSTON, mixed with 1 ampule of saline (diluent) inhaled 3 times a day

using a hand-held Altera Nebulizer System.

Each dose of CAYSTON should be taken at least 4 hours apart (for example: morning, after school,

and before bed).

CAYSTON should be taken for 28 days.

CAYSTON is taken as a breathing treatment (inhalation) with the Altera Nebulizer System. Do not

use any other nebulizer for your CAYSTON treatment.

Do not mix or dilute CAYSTON with any other medicines in your Altera Nebulizer System.

Do not mix CAYSTON with the saline until right before you are ready to use it.

Do not mix more than 1 dose of CAYSTON at a time.

Each treatment should take about 2 to 3 minutes.

If you miss a dose of CAYSTON, you can still take all 3 daily doses as long as they are at least 4

hours apart.

You should use an inhaled bronchodilator (a type of medicine used to relax and open your airways)

before taking a dose of CAYSTON. If you do not have an inhaled bronchodilator, ask your

healthcare provider to prescribe one for you.

Take short-acting bronchodilators between 15 minutes and 4 hours before you take your dose of

CAYSTON

Take long-acting bronchodilators between 30 minutes and 12 hours before you take your dose

of CAYSTON

If you are taking several medicines or treatments to treat your cystic fibrosis, you should take your

medicines or other treatments in this order:

After taking CAYSTON for 28 days, you should stop taking it and wait 28 days. Complete the full

28-day course of CAYSTON even if you are feeling better. It is important that you keep to the 28-

day on, 28 day off cycle.

If you skip doses or do not finish the full 28-day course of CAYSTON, your infection may not be

fully treated and CAYSTON may not work as well as a treatment for infections in the future.

What are the possible side effects of CAYSTON?

CAYSTON may cause serious side effects, including:

Severe allergic reactions. Stop your treatment with CAYSTON and call your healthcare provider

bronchodilator

mucolytics (medicines to help clear mucus from your lungs)

CAYSTON

This Patient Information has been approved by the U.S.

Rev November 2019

right away if you have any symptoms of an allergic reaction, including:

Rash or swelling of your face

Throat tightness

Trouble breathing right after treatment with CAYSTON (bronchospasm). Tell your healthcare

provider right away if you get any of these symptoms of bronchospasm with using CAYSTON:

shortness of breath with wheezing

coughing and chest tightness

To decrease the chance of this happening, be sure to use your inhaled bronchodilator medicine

before each treatment with CAYSTON. See "How should I take CAYSTON?"

The most common side effects of CAYSTON include:

cough

nasal congestion

wheezing

sore throat

fever. Fever may be more common in

children than in adults.

chest discomfort

stomach area (abdominal) pain

vomiting

Other possible side effects of CAYSTON include swelling or pain in joints.

Tell your healthcare provider if you have any new or worsening symptoms while taking CAYSTON.

Tell your healthcare provider about any side effect that bothers you or that does not go away.

These are not all the possible side effects of CAYSTON.

Call your healthcare provider for medical advice about side effects. You may report side effects to

FDA at 1-800-FDA-1088.

How should I store CAYSTON?

Each CAYSTON kit contains enough single-use vials of CAYSTON and ampules of saline for 28

days of treatment. There are 4 extra saline ampules in case some saline spills.

Always keep your CAYSTON and saline together.

Store CAYSTON and saline in the refrigerator between 36 °F to 46 °F (2 °C to 8 °C) until needed.

When you remove CAYSTON and saline from the refrigerator, they may be stored at room

temperature (up to 77 °F) for up to 28 days. Do not use any CAYSTON that has been stored at room

temperature for more than 28 days.

Keep CAYSTON away from light.

Do not use CAYSTON after the expiration date on the vial. Do not use the saline after the expiration

date on the ampule.

Keep CAYSTON and all medicines out of the reach of children.

General information about the safe and effective use of CAYSTON

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information

leaflet. Do not use CAYSTON for a condition for which it was not prescribed. Do not give CAYSTON

to other people, even if they have the same symptoms that you have. It may harm them. You can ask your

pharmacist or healthcare provider for information about CAYSTON that is written for health

professionals.

What are the ingredients in CAYSTON?

Active ingredient: aztreonam

Inactive ingredient: lysine, sodium chloride (diluent)

Manufactured and distributed by: Gilead Sciences, Inc. Foster City, CA 94404

CAYSTON is a registered trademark of Gilead Sciences, Inc. ©2019 Gilead Sciences, Inc. All rights

reserved.

50-814-GS-004

For more information, call 1-877-7CAYSTON (1-877-722-9786).

Food and Drug Administration

Rev November 2019

PATIENT INSTRUCTIONS FOR USE

CAYSTON

(aztreonam for inhalation solution)

for oral inhalation use

Be sure that you read, understand and follow the Patient Instructions for Use below for the right way to

take CAYSTON. If you have any questions, ask your healthcare provider or pharmacist.

You will need the following supplies (Figure 1):

1 amber colored CAYSTON vial covered by a metal seal with a blue cap

1 ampule of saline (diluent)

Altera Nebulizer System

Fig ure 1

Check to make sure that your Altera Nebulizer System works properly before starting your

treatment with CAYSTON. See the manufacturer's instructions for use that comes with your

Altera Nebulizer System. This should have complete information about how to put together

(assemble), prepare, use, and care for your Altera Nebulizer System.

Preparing your CAYSTON for Inhalation

®

Step 1. Mix (reconstitute) CAYSTON with the saline only when ready to take a dose. Take 1

amber vial of CAYSTON and 1 ampule of saline from the carton. Separate the saline ampules by

gently pulling apart.

Step 2. Look at the ampule of saline. If it looks cloudy do not use it. Throw away this ampule and

get another ampule of saline.

Step 3. Gently tap the vial so that the powder settles to the bottom of the vial. This helps you get

the proper dose of medicine. Follow Step A to Step D in Figure 2 below to open the vial:

Step A: With the blue cap tab facing

toward you, place the vial on a flat

surface. Using one hand to hold

the vial steady, use the other hand

to slowly flip up the blue cap.

Step B: Pull the blue cap down to a

flat (horizontal) position (where the

bottom of the blue cap faces up), to

prepare the metal seal for removal.

Do not completely tear through the

metal seal.

Step C: While continuing to hold

the vial steady with one hand, use

the other hand to slowly pull the

blue cap in a counterclockwise

direction. Do not twist the blue cap.

Step D: When the metal seal opens,

continue to slowly pull the blue cap

in a counterclockwise direction

until the metal seal is completely

removed.

Figure 2

Step 4. Safely throw away (dispose of) the metal seal in household garbage. Carefully remove

(but do not yet discard) the rubber stopper.

Step 5. Open the ampule of saline by twisting off the tip. Squeeze out the contents completely into

the vial (Figure 3). Next, close the vial with the rubber stopper and gently swirl the vial until the

powder has completely dissolved and the liquid is clear.

Taking your CAYSTON Treatment

See the manufacturer's instructions for use that comes with your Altera Nebulizer System for

complete instructions on taking a treatment, and how to clean and disinfect your Altera Nebulizer

Hands et.

Fig ure 3

Step 6. After mixing CAYSTON with the saline, check to make sure the diluted medicine is clear.

If it is cloudy or has particles in it, do not use this medicine. Throw away this dose of medicine

and start over again with a new vial of CAYSTON and a new ampule of saline.

Step 7. Use CAYSTON right away after you mix with the saline.

Step 8. Make sure the handset is on a flat, stable surface.

Step 9. Remove the rubber stopper from the vial, then pour all of the mixed CAYSTON and saline

into the Medication Reservoir of the handset (Figure 4). Be sure to completely empty the vial,

gently tapping the vial against the side of the Medication Reservoir if necessary. Close the

Medication Reservoir (Figure 5).

Fig ure

4

Fig ure

5

Step 10. Begin your treatment by sitting in a relaxed, upright position. Hold the handset level, and

place the Mouthpiece in your mouth. Close your lips around the Mouthpiece (Figure 6).

This Instructions for Use has been approved by the U.S. Food and Drug Administration.

Manufactured by: Gilead Sciences, Inc., Foster City, CA 94404

CAYSTON is a trademark of Gilead Sciences, Inc. All other trademarks referenced herein are the

property of their respective owners.

© 2019 Gilead Sciences, Inc. All rights reserved.

50-814-GS-004

Revised: November 2019

Principal Display Panel - Cayston 28 Day Carton - Representative Label

NDC 61958-0901-1

GILEAD

Cayston

(aztreonam for

inhalation solution)

75 mg/vial

For Oral Inhalation Only

Store Refrigerated, 2 °C to 8 °C (36 °F to 46 °F)

Contains:

84 Single-Use Vials of Aztreonam for Inhalation Solution

88 Diluent Ampules of Sodium Chloride 0.17%, 1 mL

(4 extra ampules provided in case of spillage)

For use only with the Altera

Nebulizer System

28-Day Supply

Fig ure 6

Step 11. Breathe in and out normally (inhale and exhale) through the Mouthpiece. Avoid

breathing through your nose. Continue to inhale and exhale comfortably until the treatment is

finished.

Step 12. The empty vial, stopper and saline ampule should be disposed of in household garbage

upon completion of dosing.

®

R only

x

CAYSTON

aztreonam kit

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:6 19 58 -0 9 0 1

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:6 19 58 -0 9 0 1-1

2 in 1 PACKAGE

0 2/22/20 10

1

1 in 1 CARTON

Quantity of Parts

Part #

Package Quantity

Total Product Quantity

Pa rt 1

42 VIAL

42 mL

Pa rt 2

44 AMPULE

44 mL

Part 1 of 2

AZTREONAM

aztreonam powder, for solution

Product Information

Route of Administration

RESPIRATORY (INHALATION)

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

a ztreo na m (UNII: G2B4VE5GH8 ) (aztreo nam - UNII:G2B4VE5GH8 )

a z tre o na m

75 mg in 1 mL

Inactive Ingredients

Ingredient Name

Stre ng th

lysine mo no hydra te (UNII: F76 25B9 74U)

Product Characteristics

Color

WHITE (white to o ff-white po wder)

S core

S hap e

S iz e

Flavor

Imprint Code

Contains

Packag ing

#

Item

Co de

Package Description

Marketing Start

Date

Marketing End

Date

1

1 mL in 1 VIAL; Type 7: Separate Pro ducts Requiring Cro ss

La be ling

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 50 8 14

0 2/22/20 10

Part 2 of 2

STERILE DILUENT

sodium chloride solution

Product Information

Route of Administration

RESPIRATORY (INHALATION)

Inactive Ingredients

Ingredient Name

Stre ng th

so dium chlo ride (UNII: 451W47IQ8 X)

1.7 mg in 1 mL

wa ter (UNII: 0 59 QF0 KO0 R)

Packag ing

#

Item

Co de

Package Description

Marketing Start

Date

Marketing End

Date

1

1 mL in 1 AMPULE; Type 7: Separate Pro ducts Requiring Cro ss

La be ling

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 50 8 14

0 2/22/20 10

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

NDA0 50 8 14

0 2/22/20 10

Gilead Sciences, Inc.

Labeler -

Gilead Sciences, Inc. (185049848)

Revised: 11/2019

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