Cayston

>25%

Cough (54%)

10-25%

Nasal congestion ( 16%)

Wheezing (16%)

Pharyngolaryngeal pain (12%)

Pyrexia (13%)

1-10%

Chest discomfort (8%)

Abdominal pain (7%)

Vomiting (6%)

Bronchospasm (3%)

Rash (2%)

Before taking Cayston, tell your doctor if you:

• are allergic to any antibiotics
• have liver or kidney problems
• are pregnant or plan to become pregnant
• are breastfeeding or plan to breastfeed. Talk to your doctor about the best way to breastfeed your baby if you take Cayston.

Tell your doctor about all the medicine you take, including prescription and non-prescription medicines, vitamins and herbal supplements.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine

If you take too much Cayston, call your doctor or local Poison Control Center, or seek emergency medical attention right away.

• Each Cayston kit contains enough 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 at 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 (less than 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.

• Tell all of your health care providers that you take Cayston. This includes your doctors, nurses, pharmacists, and dentists.
• Unsafe allergic effects may rarely happen.
• Do not use longer than you have been told. A second infection may happen.
• Tell your doctor if you are pregnant or plan on getting pregnant. You will need to talk about the benefits and risks of using this medicine while you are pregnant.
• Tell your doctor if you are breast-feeding. You will need to talk about any risks to your baby.

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%).

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

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

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 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. Likewise, genetic toxicology studies performed in vivo did not reveal evidence of mutagenic potential.

Aztreonam did not impair the fertility of rats when administered at doses that would provide systemic exposures far in excess of peak plasma levels measured in humans following Cayston therapy.

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 FEV1 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 FEV1 % 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 FEV1 (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 FEV1 (L) was statistically significant at 10% (95% CI: 6%, 14%). Improvements in FEV1 were comparable between adult and pediatric patients. Two weeks after completion of drug treatment, the difference in FEV1 between Cayston and placebo groups had decreased to 6% (95% CI: 2%, 9%).

Figure 1 Adjusted Mean Percent Change in FEV1 from Baseline to Study End (Days 0–42)

See FDA-Approved Patient Labeling

Patients should be advised that Cayston is for inhalation use only and that Cayston should only be administered using the Altera Nebulizer System. Patients should be instructed only to reconstitute Cayston with the provided diluent and not mix other drugs with Cayston in the Altera Nebulizer System.

Patients should be advised to complete the full 28-day course of Cayston even if they are feeling better. 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.

Patients should be advised to use a bronchodilator prior to administration of Cayston. Patients taking several inhaled medications should be advised to use the medications in the following order of administration: bronchodilator, mucolytics, and lastly, Cayston.

Patients should be advised to tell their doctor if they have new or worsening symptoms. Patients who believe they are experiencing an allergic reaction to Cayston should be advised to contact their doctor immediately.

Patients should be counseled 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, patients should be told that although it is common to feel better early in the course of therapy, the medication should be taken 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.

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.

© 2014 Gilead Sciences, Inc. All rights reserved.
50-814-GS-002

FDA-Approved Patient Labeling

PATIENT INFORMATION

Cayston® (kay-stun)
(aztreonam for inhalation solution)

Read this Patient Information before you start taking Cayston and each time you get a refill. This information does not take the place of talking with your doctor about your medical condition or your treatment.

What is Cayston?

Cayston is a prescription inhaled antibiotic. Cayston is used to improve breathing symptoms in people with cystic fibrosis (CF) who have Pseudomonas aeruginosa (P. aeruginosa) in their lungs.

Cayston is only for infections caused by bacteria. It is not for infections caused by viruses, such as the common cold.

Cayston is used only with the Altera® Nebulizer System.

It is not known if Cayston is safe and effective in children under the age of 7.

Who should not take Cayston?

Do not take Cayston if you are allergic to aztreonam (AZACTAM®).

What should I tell my doctor before taking Cayston?

Before taking Cayston, tell your doctor if you:

• are allergic to any antibiotics.
• are pregnant or plan to become pregnant.
• are breast-feeding or plan to breast feed. Talk to your doctor about the best way to breast feed your baby if you take Cayston.

Tell your doctor about all the medicine you take, including prescription and non-prescription medicines, vitamins and herbal supplements.

Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine.

How should I take Cayston?

• Take Cayston exactly as prescribed by your doctor.
• The dose of Cayston for both adults and children 7 years of age and older is one vial of Cayston, mixed with one ampule of saline (diluent) 3 times a day.
• Doses 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.
• 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 doctor to prescribe one for you.
• If you are taking several medicines or treatments to treat your cystic fibrosis, you should take your medicines or other treatments in this order: 1) bronchodilator 2) mucolytics (medicines to help clear mucus from your lungs) 3) Cayston
• You should take Cayston as prescribed, in courses of 28 days on Cayston, followed by at least 28 days off Cayston, as directed by your doctor.
• Do not mix 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 one 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.
• It is important for you to finish taking the full 28-day course of Cayston even if you are feeling better. 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.
• See the end of this Patient Information leaflet for the Patient Instructions for Use on how to take Cayston the right way.

What are the possible side effects of Cayston?

Cayston can cause serious side effects, including:

• Severe allergic reactions. Stop your treatment with Cayston and call your doctor 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). 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?"

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 of joints

Tell your doctor if you have any new or worsening symptoms while taking Cayston. Tell your doctor about any side effect that bothers you or that does not go away.

These are not all the possible side effects of Cayston. For more information, ask your doctor or pharmacist.

Call your doctor 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 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 at 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 (less than 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 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.

This Patient Information leaflet summarizes the most important information about Cayston. If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Cayston that is written for health professionals.

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

What are the ingredients in Cayston?

Active ingredient: aztreonam

Inactive ingredient: lysine, sodium chloride (diluent)

 

PATIENT INSTRUCTIONS FOR USE

Cayston®
(aztreonam for inhalation solution)

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 doctor or pharmacist.

You will need the following supplies (Figure 1):

• 1 amber colored Cayston vial covered by a metal seal with a blue cap or a metal seal only
• 1 ampule of saline (diluent)
• Altera Nebulizer System

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.

Step 1 Preparing your Cayston for inhalation

1. Mix (reconstitute) Cayston with the saline only when ready to take a dose. Take one amber vial of Cayston and one ampule of saline from the carton. Separate the saline ampules by gently pulling apart. 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. 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. Open the amber drug vial by lifting up the metal flap or blue cap on the top (Figure 2) and pulling down (Figure 3) to carefully remove the entire metal ring from the vial (Figure 4). Safely dispose of the ring in household garbage. Carefully remove the rubber stopper (Figure 5).
4. Open the ampule of saline by twisting off the tip. Squeeze out the contents completely into the vial (Figure 6). Next, close the vial with the rubber stopper and gently swirl the vial until the powder has completely dissolved and the liquid is clear.
5. 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. 6. Use Cayston right away after you mix with the saline.

Step 2 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 Handset.

7. Make sure the handset is on a flat, stable surface. 8. Remove the rubber stopper from the vial, then pour all of the mixed Cayston and saline into the Medication Reservoir of the handset (Figure 7). 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 8).
9. 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 9).
10. 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. 11. The empty vial, stopper and saline ampule should be disposed of in household garbage upon completion of dosing.

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.

© 2014 Gilead Sciences, Inc. All rights reserved.
50-814-GS-002

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

Rx only

Cayston  aztreonam kit

Product Information Product Type HUMAN PRESCRIPTION DRUG LABEL Item Code (Source) NDC:61958-0901

Packaging # Item Code Package Description 1 NDC:61958-0901-1 2 CARTON in 1 PACKAGE 1 1 KIT in 1 CARTON

Quantity of Parts Part # Package Quantity Total Product Quantity Part 1 42 VIAL 42 mL Part 2 44 AMPULE 44 mL

Part 1 of 2 AZTREONAM  aztreonam powder, for solution

Product Information Route of Administration RESPIRATORY (INHALATION) DEA Schedule

Active Ingredient/Active Moiety Ingredient Name Basis of Strength Strength aztreonam (aztreonam) aztreonam 75 mg  in 1 mL

Inactive Ingredients Ingredient Name Strength lysine monohydrate

Product Characteristics Color WHITE (white to off-white powder) Score      Shape Size Flavor Imprint Code Contains

Packaging # Item Code Package Description 1 1 mL in 1 VIAL

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA050814 02/22/2010

Part 2 of 2 STERILE DILUENT  sodium chloride solution

Product Information Route of Administration RESPIRATORY (INHALATION) DEA Schedule

Inactive Ingredients Ingredient Name Strength sodium chloride 1.7 mg  in 1 mL water

Packaging # Item Code Package Description 1 1 mL in 1 AMPULE

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA050814 02/22/2010

Marketing Information Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date NDA NDA050814 02/22/2010

Labeler - Gilead Sciences, Inc. (185049848)

Revised: 05/2014   Gilead Sciences, Inc.