Elase

Dornase Alfa:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• Clinical pharmacology
• Nonclinical toxicology
• Clinical studies
• How supplied/storage and handling
• Patient counseling information
• Instructions for use
• Instructions for use
• Elase (Dornase Alfa) reviews

1 INDICATIONS AND USAGE

Elase (Dornase Alfa)^® (dornase alfa) is indicated for daily administration in conjunction with standard therapies for the management of cystic fibrosis (CF) patients to improve pulmonary function.

In CF patients with an FVC ≥ 40% of predicted, daily administration of Elase (Dornase Alfa) has also been shown to reduce the risk of respiratory tract infections requiring parenteral antibiotics.

Elase (Dornase Alfa) is a recombinant DNase enzyme indicated in conjunction with standard therapies for the management of cystic fibrosis (CF) patients to improve pulmonary function. (1)

2 DOSAGE AND ADMINISTRATION

• The recommended dosage is one 2.5 mg single-use ampule inhaled once daily using a recommended nebulizer.
• Some patients may benefit from twice daily administration. (2.1)

2.1 Recommended Dosage

The recommended dosage for use in most cystic fibrosis patients is one 2.5 mg single-use ampule inhaled once daily using a recommended jet nebulizer/compressor system or eRapid Nebulizer System.

Some patients may benefit from twice daily administration

2.2 Directions for Use

Administer Elase via the eRapid Nebulizer System or via a jet nebulizer connected to an air compressor with an adequate air flow and equipped with a mouthpiece or suitable face mask. No data are currently available to support the administration of Elase (Dornase Alfa) with other nebulizer systems.

Do not dilute or mix Elase (Dornase Alfa) with other drugs in the nebulizer. Mixing of Elase (Dornase Alfa) with other drugs could lead to adverse physicochemical and/or functional changes in Elase (Dornase Alfa) or the admixed compound.

The patient should follow the manufacturer's instructions on the use and maintenance of the equipment, including cleaning and disinfection procedures.

When Elase (Dornase Alfa) is administered with the eRapid Nebulizer System, advise patients to replace the handset after 90 uses, regardless of whether the EasyCare cleaning aid is used. Since delivery data are not available for Elase (Dornase Alfa) administered with the eRapid handset beyond 90 administrations, delivery of the appropriate therapeutic dose of Elase (Dornase Alfa) cannot be assured beyond 90 administrations. The eRapid Nebulizer System should only be used by adults and children who can use a mouthpiece, and not by younger children who need a mask to take Elase (Dornase Alfa).

2.3 Storage and Handling

Store Elase (Dornase Alfa) ampules in their protective foil pouch under refrigeration and protected from light. Refrigerate ampules during transport and do not expose to room temperatures for a total time of 24 hours.

Each Elase (Dornase Alfa) ampule should be squeezed prior to use in order to check for leaks. Discard ampules if the solution is cloudy or discolored. Once opened, the entire contents of the ampule must be used or discarded.

3 DOSAGE FORMS AND STRENGTHS

Inhalation Solution: 2.5 mg/2.5 mL in single-use ampules.

Inhalation Solution: 2.5 mg/2.5 mL in single-use ampules (3)

4 CONTRAINDICATIONS

Elase (Dornase Alfa) is contraindicated in patients with known hypersensitivity to Elase (Dornase Alfa), Chinese Hamster Ovary cell products, or any component of the product.

Elase (Dornase Alfa) is contraindicated in patients with known hypersensitivity to Elase (Dornase Alfa), Chinese Hamster Ovary cell products, or any component of the product. (4)

5 WARNINGS AND PRECAUTIONS

None.

None.

6 ADVERSE REACTIONS

The most common adverse reactions over placebo) seen in clinical trials in CF patients were: voice alteration, pharyngitis, rash, laryngitis, chest pain, conjunctivitis, rhinitis, decrease in FVC of ≥10%, fever, and dyspnea. (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Genentech at 1-888-835-2555 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.

The data described below reflect exposure to Elase (Dornase Alfa) in 902 patients, with exposures ranging from 2 weeks of daily administration up to once or twice daily administration for six months. Elase (Dornase Alfa) was studied in both placebo-controlled and uncontrolled trials (n=804 and n=98). The population of patients in placebo-controlled trials was with FVC ≥ 40% of predicted (n=643) or with more advanced pulmonary disease, FVC < 40% of predicted (n=161). The population in the uncontrolled trial included 98 pediatric patients with CF ranging from 3 months to 10 years of age. More than half of the patients received Elase (Dornase Alfa) 2.5 mg by inhalation once a day (n=581), while the rest of patients (n=321) received Elase (Dornase Alfa) 2.5 mg by inhalation twice a day.

Placebo-Controlled Trials

Trial 1: Trial 1 was a randomized, placebo-controlled clinical trial in patients with FVC ≥ 40% of predicted. In this trial, over 600 patients received Elase (Dornase Alfa) once or twice daily for six months. The most common adverse reaction (risk difference ≥5%) was voice alteration. The proportion of most adverse events was similar for patients on Elase (Dornase Alfa) and on placebo, probably reflecting the sequelae of the underlying lung disease. In most cases reactions that were increased were mild, transient in nature, and did not require alterations in dosing. Few patients experienced adverse reactions resulting in permanent discontinuation from Elase (Dornase Alfa), and the proportion of discontinuations were similar for placebo (2%) and Elase (Dornase Alfa) (3%). Adverse reactions occurring in a higher proportion (greater than 3%) of Elase (Dornase Alfa) treated patients than in placebo-treated patients are listed in Table 2.

Trial 2: Trial 2 was a randomized, placebo-controlled trial in patients with more advanced pulmonary disease (FVC < 40% of predicted) who were treated for 12 weeks. In this trial, the safety profile of Elase (Dornase Alfa) was similar to that reported in patients with less advanced pulmonary disease (FVC ≥ 40% of predicted). Adverse reactions that were reported in this trial with a higher proportion (greater than 3%) in the Elase (Dornase Alfa) treated patients are listed in Table 2.

Mortality rates observed in controlled trials were similar for the placebo and Elase (Dornase Alfa) treated patients. Causes of death were consistent with progression of cystic fibrosis and included apnea, cardiac arrest, cardiopulmonary arrest, cor pulmonale, heart failure, massive hemoptysis, pneumonia, pneumothorax, and respiratory failure.

Uncontrolled Trial

Trial 3: The safety of Elase (Dornase Alfa), 2.5 mg by inhalation, was studied with 2 weeks of daily administration in 98 pediatric patients with cystic fibrosis 3 months to 10 years of age (65 aged 3 months to < 5 years, 33 aged 5 to ≤ 10 years). The PARI BABY reusable nebulizer (which uses a facemask instead of a mouthpiece) was utilized in patients unable to demonstrate the ability to inhale or exhale orally throughout the entire treatment period (54/65, 83% of the younger and 2/33, 6% of the older patients). Overall, the nature of adverse reactions was similar to that seen in the placebo-controlled trials. The number of patients reporting cough was higher in the younger age group as compared to the older age group (29/65, 45% compared to 10/33, 30%) as was the number reporting moderate to severe cough (24/65, 37% as compared to 6/33, 18%). The number of patients reporting rhinitis was higher in the younger age group as compared to the older age group (23/65, 35% compared to 9/33, 27%) as was the number reporting rash (4/65, 6% as compared to 0/33).

Allergic Reactions

There have been no reports of anaphylaxis attributed to the administration of Elase (Dornase Alfa). Urticaria, mild to moderate, and mild skin rash have been observed and have been transient. Within all of the studies, a small percentage (average of 2-4%) of patients treated with Elase (Dornase Alfa) developed serum antibodies to Elase (Dornase Alfa). None of these patients developed anaphylaxis, and the clinical significance of serum antibodies to Elase (Dornase Alfa) is unknown.

6.2 Postmarketing Experience

Postmarketing spontaneous reports and prospectively collected safety data from observational studies confirm the safety profile to be as described in clinical trials [see Adverse Reactions (6.1) ].

7 DRUG INTERACTIONS

Available data indicate there are no clinically important drug-drug interactions with Elase (Dornase Alfa).

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Risk summary

There are no adequate and well-controlled studies with Elase in pregnant women. However, animal reproduction studies have been conducted with Elase (Dornase Alfa). In these studies, no evidence of fetal harm was observed in rats and rabbits at doses of Elase (Dornase Alfa) up to approximately 600 times the maximum recommended human dose (MRHD).

The background risk of major birth defects and miscarriage for the cystic fibrosis population is unknown. However, the background risk in the U.S. general population of major birth defects is 2-4% and of miscarriage is 15-20% of clinically recognized pregnancies.

Data

Animal Data

Reproductive studies have been performed in rats and rabbits at intravenous doses of Elase (Dornase Alfa) up to 10 mg/kg/day (approximately 600 times the MRHD in adults). In a combined embryo-fetal development and pre- and post-natal development study, no evidence of maternal toxicity, embryotoxicity, or teratogenicity was observed when Elase (Dornase Alfa) was administered to dams throughout organogenesis (Gestation days 6 to 17). Elase (Dornase Alfa) did not elicit adverse effects on fetal or neonatal growth when administered to dams throughout most of gestation and delivery (Gestation days 6 to 25) and nursing (Post-partum days 6 to 21).

A pharmacokinetic study in Cynomolgus monkeys found no detectable levels of Elase (Dornase Alfa) in fetal blood or amniotic fluid on gestation day 150 (end of gestation) from mothers that were administered an intravenous bolus dose (0.1 mg/kg) followed by an intravenous infusion dose (0.080 mg/kg) over a 6-hour period during pregnancy.

8.2 Lactation

Risk Summary

It is not known whether Elase (Dornase Alfa) is present in human milk. In a pharmacokinetic study in Cynomolgus monkeys, levels of Elase (Dornase Alfa) detected in milk were less than 0.1% of the maternal serum concentration at 24 hours after dosing [intravenous bolus dose (0.1 mg/kg) of Elase (Dornase Alfa) followed by an intravenous infusion (0.080 mg/kg/hr) over a 6-hour period] on post-partum day 14. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for Elase (Dornase Alfa) and any potential adverse effects on the breastfed child from Elase (Dornase Alfa) or from the underlying maternal condition.

8.4 Pediatric Use

The safety and effectiveness of Elase have been established in pediatric patients 5 years of age and older [see Adverse Reactions (6) and Clinical Studies (14)]. The safety of Elase (Dornase Alfa), 2.5 mg by inhalation, was studied with 2 weeks of daily administration in 65 patients with cystic fibrosis aged 3 months to < 5 years . While clinical trial data are limited in pediatric patients younger than 5 years of age, the use of Elase (Dornase Alfa) should be considered for pediatric CF patients who may experience potential benefit in pulmonary function or who may be at risk of respiratory tract infection.

8.5 Geriatric Use

Cystic fibrosis is primarily a disease of children and young adults. Clinical studies of Elase (Dornase Alfa) did not include sufficient numbers of subjects aged 65 or older to determine whether they respond differently from younger subjects.

10 OVERDOSAGE

Single-dose inhalation studies in rats and monkeys at doses up to 180-times higher than doses routinely used in clinical studies are well tolerated. Single dose oral administration of Elase (Dornase Alfa) in doses up to 200 mg/kg are also well tolerated by rats.

Cystic fibrosis patients have received up to 20 mg BID for up to 6 days and 10 mg BID intermittently (2 weeks on/2 weeks off drug) for 168 days. These doses were well tolerated.

11 DESCRIPTION

Elase (Dornase Alfa) is a recombinant human deoxyribonuclease I (rhDNase) an enzyme which selectively cleaves DNA. The protein is produced by genetically engineered Chinese Hamster Ovary (CHO) cells containing DNA encoding for the native human protein, deoxyribonuclease I (DNase). Fermentation is carried out in a nutrient medium containing the antibiotic gentamicin, 100–200 mg/L. However, the presence of the antibiotic is not detectable in the final product. The product is purified by tangential flow filtration and column chromatography. The purified glycoprotein contains 260 amino acids with an approximate molecular weight of 37,000 daltons. The primary amino acid sequence is identical to that of the native human enzyme.

Elase (Dornase Alfa) is administered by inhalation of an aerosol mist produced by a compressed air driven nebulizer or an approved nebulizer system [see Clinical Studies (14) and Dosage and Administration (2) ]. Elase (Dornase Alfa) is a sterile, clear, colorless, highly purified solution in single-use ampules. Each ampule delivers 2.5 mL of the solution to the nebulizer bowl. Each mL of aqueous solution contains 1 mg Elase (Dornase Alfa), calcium chloride dihydrate (0.15 mg) and sodium chloride (8.77 mg). The solution contains no preservative. The nominal pH of the solution is 6.3.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

Elase is recombinant human deoxyribonuclease I (rhDNase), an enzyme which selectively cleaves DNA. In preclinical in vitro studies, Elase (Dornase Alfa) hydrolyzes the DNA in sputum of CF patients and reduces sputum viscoelasticity. In CF patients, retention of viscous purulent secretions in the airways contributes both to reduced pulmonary function and to exacerbations of infection. Purulent pulmonary secretions contain very high concentrations of extracellular DNA released by degenerating leukocytes that accumulate in response to infection.

12.3 Pharmacokinetics

When 2.5 mg Elase (Dornase Alfa) was administered by inhalation to eighteen CF patients, mean sputum concentrations of 3 µg/mL DNase were measurable within 15 minutes. Mean sputum concentrations declined to an average of 0.6 µg/mL two hours following inhalation. Inhalation of up to 10 mg TID of Elase (Dornase Alfa) by 4 CF patients for six consecutive days, did not result in a significant elevation of serum concentrations of DNase above normal endogenous levels. After administration of up to 2.5 mg of Elase (Dornase Alfa) twice daily for six months to 321 CF patients, no accumulation of serum DNase was noted. Elase (Dornase Alfa) is expected to be metabolized by proteases present in biological fluids. A human intravenous dose study suggested an elimination half-life of 3-4 hours for dornase alpha.

Elase (Dornase Alfa), 2.5 mg by inhalation, was administered daily to 98 patients aged 3 months to ≤ 10 years, and bronchoalveolar lavage (BAL) fluid was obtained within 90 minutes of the first dose. BAL DNase concentrations were detectable in all patients but showed a broad range, from 0.007 to 1.8 µg/mL. Over an average of 14 days of exposure, serum DNase concentrations (mean ± s.d.) increased by 1.1 ± 1.6 ng/mL for the 3 months to < 5 year age group and by 0.8 ± 1.2 ng/mL for the 5 to ≤ 10 year age group. The relationship between BAL or serum DNase concentration and adverse experiences and clinical outcomes is unknown.

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

Elase (Dornase Alfa) produced no treatment-related increases in the incidence of tumors in a lifetime study in Sprague Dawley rats that were administered inhaled doses up to 0.246 mg/kg/day (approximately 30 times the MRHD in adults). There was no increase in the development of benign or malignant neoplasms and no occurrence of unusual tumor types in rats after lifetime exposure.

Elase (Dornase Alfa) tested negative in the following genotoxicity assays: the in vitro Ames assay, in vitro mouse lymphoma assay, and in vivo mouse bone marrow micronucleus assay. No evidence of impairment of fertility was observed in male and female rats that received intravenous doses up to 10 mg/kg/day (approximately 600 times the MRHD in adults).

14 CLINICAL STUDIES

Trial in CF Patients with FVC >40% of Predicted

Elase (Dornase Alfa) has been evaluated in a randomized, placebo-controlled trial of clinically stable cystic fibrosis patients, 5 years of age and older, with baseline forced vital capacity (FVC) greater than or equal to 40% of predicted and receiving standard therapies for cystic fibrosis. Patients were treated with placebo (325 patients), 2.5 mg of Elase (Dornase Alfa) once a day (322 patients), or 2.5 mg of Elase (Dornase Alfa) twice a day (321 patients) for six months administered via a Hudson T Up-draft II^® nebulizer with a Pulmo-Aide^® compressor.

Both doses of Elase (Dornase Alfa) resulted in significant reductions in the number of patients experiencing respiratory tract infections requiring use of parenteral antibiotics compared with the placebo group. Administration of Elase (Dornase Alfa) reduced the relative risk of developing a respiratory tract infection by 27% and 29% for the 2.5 mg daily dose and the 2.5 mg twice daily dose, respectively. The data suggest that the effects of Elase (Dornase Alfa) on respiratory tract infections in older patients ( > 21 years) may be smaller than in younger patients, and that twice daily dosing may be required in the older patients. Patients with baseline FVC > 85% may also benefit from twice a day dosing. The reduced risk of respiratory infection observed in Elase (Dornase Alfa) treated patients did not directly correlate with improvement in FEV₁ during the initial two weeks of therapy.

Within 8 days of the start of treatment with Elase (Dornase Alfa), mean FEV₁ increased 7.9% in those treated once a day and 9.0% in those treated twice a day compared to the baseline values. The overall mean FEV₁ during long-term therapy increased 5.8% from baseline at the 2.5 mg daily dose level and 5.6% from baseline at the 2.5 mg twice daily dose level. Placebo recipients did not show significant mean changes in pulmonary function testing.

For patients 5 years of age or older, with baseline FVC greater than or equal to 40%, administration of Elase (Dornase Alfa) decreased the incidence of occurrence of first respiratory tract infection requiring parenteral antibiotics, and improved mean FEV₁, regardless of age or baseline FVC.

Trial in CF Patients with FVC <40% of Predicted

Elase (Dornase Alfa) has also been evaluated in a second randomized, placebo-controlled trial in clinically stable patients with baseline FVC < 40% of predicted. Patients were enrolled and treated with placebo (162 patients) or Elase (Dornase Alfa) 2.5 mg QD (158 patients) for twelve weeks. In patients who received Elase (Dornase Alfa), there was an increase in mean change (as percent of baseline) compared to placebo in FEV₁ (9.4% vs. 2.1%, p < 0.001) and in FVC (12.4% vs. 7.3%, p < 0.01). Elase (Dornase Alfa) did not significantly reduce the risk of developing a respiratory tract infection requiring parenteral antibiotics (54% of Elase (Dornase Alfa) patients vs. 55% of placebo patients had experienced a respiratory tract infection by 12 weeks, relative risk =.93, p = 0.62).

The effect of Elase (Dornase Alfa) on exercise tolerance has not been established in adult and pediatric patients.

Other Studies

Clinical trials have indicated that Elase (Dornase Alfa) therapy can be continued or initiated during an acute respiratory exacerbation.

Short-term dose ranging studies demonstrated that doses in excess of 2.5 mg BID did not provide further improvement in FEV₁. Patients who have received drug on a cyclical regimen (i.e., administration of Elase (Dornase Alfa) 10 mg BID for 14 days, followed by a 14 day wash out period) showed rapid improvement in FEV₁ with the initiation of each cycle and a return to baseline with each Elase (Dornase Alfa) withdrawal.

16 HOW SUPPLIED/STORAGE AND HANDLING

Elase (Dornase Alfa) is supplied in:

• 30 unit cartons containing 5 foil pouches of 6 single-use ampules. Each 2.5 mL ampule contains 2.5 mg of dornase alpha (1 mg/mL): NDC 50242-100-40.

Storage and Handling

Store Elase (Dornase Alfa) under refrigeration (2°C to 8°C/36°F to 46°F) in their protective foil to protect from light. Do not use beyond the expiration date stamped on the ampule. Store unused ampules in their protective foil pouch under refrigeration. Refrigerate Elase (Dornase Alfa) during transport and do not expose to room temperatures for a total time of 24 hours.

17 PATIENT COUNSELING INFORMATION

Advise patients to read the FDA-approved Patient Labeling (Instructions for Use)

Storage and Handling Information

Instruct patients on the proper techniques to store and handle Elase (Dornase Alfa). Elase (Dornase Alfa) must be stored in the refrigerator at 2 to 8°C (36 to 46°F) and protected from light. It should be kept refrigerated during transport and should not be exposed to room temperatures for a total time of 24 hours.

Advise patients to squeeze each ampule prior to use in order to check for leaks. The solution should be discarded if it is cloudy or discolored. Once opened, the entire contents of the ampule must be used or discarded.

Instruct patients in the proper use and maintenance of the jet nebulizer/compressor system or eRapid Nebulizer System used in Elase (Dornase Alfa) delivery.

Instruct patients not to dilute or mix Elase (Dornase Alfa) with other drugs in the nebulizer. Mixing of Elase (Dornase Alfa) with other drugs could lead to adverse physicochemical and/or functional changes in Elase (Dornase Alfa) or the admixed compound.

Use with the eRapid Nebulizer System

Instruct patients and caregivers to read and follow the directions in both the Elase (Dornase Alfa) Instructions for Use and in the Manufacturer's eRapid Nebulizer System Instruction Booklet.

Instruct patients and caregivers to clean the handset, including the medication reservoir, medicine cap, aerosol head, and mouthpiece, after each use. Instruct patients and caregivers to disinfect the handset, including the medication reservoir, medicine cap, aerosol head, and mouthpiece, after each day of use.

Instruct patients to replace the handset after 90 uses, regardless of whether the EasyCare cleaning aid is used. Since delivery data are not available for Elase (Dornase Alfa) administered with the eRapid handset beyond 90 administrations, delivery of the appropriate therapeutic dose of Elase (Dornase Alfa) cannot be assured beyond 90 administrations.

Elase (Dornase Alfa)^® (dornase alfa)

Inhalation Solution

Manufactured by:

Genentech, Inc.

A Member of the Roche Group

1 DNA Way

South San Francisco, CA 94080-4990

US License No. 1048

©2014 Genentech, Inc. All rights reserved

©2014 Genentech, Inc.

Elase (Dornase Alfa)^® is a trademark of Genentech, Inc.

Instructions for Use

Elase (Dornase Alfa)^® (PULL-muh-zyme)

(dornase alfa)

Inhalation Solution

Instructions for Use with Jet Nebulizers and Compressors

See the other side of this Instructions for Use for information on use of Elase (Dornase Alfa) with the ultrasonic eRapid Nebulizer System

Read this Instructions for Use before you start taking Elase (Dornase Alfa) and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment.

A nebulizer and a compressor are used together to give a dose of Elase (Dornase Alfa). A nebulizer changes the Elase (Dornase Alfa) liquid medicine into a fine mist you inhale by breathing through a mouthpiece. A compressor gives the nebulizer power and makes the nebulizer work.

Elase (Dornase Alfa) should only be used with the approved nebulizers and compressors listed below, or with the eRapid Nebulizer System.

Do not use any other inhaled medicines in the nebulizer at the same time. Keep all other inhaled medication systems completely separate from Elase (Dornase Alfa).

Do not use a mask. Use the mouthpiece provided with each nebulizer kit.

If your child cannot breathe in or breathe out by mouth, you may use the PARI BABY reusable nebulizer, but you should discuss it with your doctor first. The PARI BABY nebulizer is the same as the PARI LC Plus Jet system, except the mouthpiece is replaced by a tight fitting face mask connected to an elbow piece.

Follow the steps on this side of the sheet to administer Elase (Dornase Alfa) using the following jet nebulizer systems.

Supplies you will need to give a dose of Elase (Dornase Alfa) :

• 1 ampule of Elase (Dornase Alfa)
• Compressor
• Nebulizer cup and screw-on or snap-on cap
• Plastic T connector (not needed for Sidestream nebulizer or PARI BABY)
• Flexible aerosol tube (not needed for Sidestream nebulizer or PARI BABY)
• Clean mouthpiece or PARI BABY facemask
• Long connecting tube
• Nose clip (optional, not needed for PARI BABY)

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

Genentech, Inc.

A Member of the Roche Group

1 DNA Way

South San Francisco, CA 94080-4990

US License No. 1048

Approved: December 2014

Figure A Figure B Figure C Figure D Figure E Figure F Figure G Figure H Figure I Figure J Figure K Figure L Figure M Figure N Figure O Figure P Figures Q Figures R Figure S Figure T Figure U Figure V Figure W Figure X Figure Y Figure A Figure B Figure C Figure D Figure E Figure F Figure G Figure H Figure I Figure J Figure K Figure L Figure M Figure N Figure O Figure P Figure Q

Instructions for Use

Elase (Dornase Alfa)^® (PULL-muh-zyme)

(dornase alfa)

Inhalation Solution

Instructions for Use with the eRapid Nebulizer System

See the other side of this Instructions for Use for information on use with Jet Nebulizers and Compressors

Read this Instructions for Use before you start taking Elase (Dornase Alfa) and each time you get a refill. There may be new information. This information does not take the place of talking to your healthcare provider about your medical condition or your treatment.

This information does not take the place of the Manufacturer's eRapid Nebulizer System Instruction Booklet. This information is needed to show you the right way to use the eRapid Nebulizer System.

The eRapid Nebulizer System changes the Elase (Dornase Alfa) liquid medicine into a fine mist you inhale by breathing through a mouthpiece.

Do not use any other inhaled medicines in the nebulizer at the same time. Keep all other inhaled medication systems completely separate from Elase (Dornase Alfa).

The eRapid Nebulizer System should only be used by adults and children who can use a mouthpiece, and not by younger children who need a mask to take Elase (Dornase Alfa).

Follow the instructions on this side of the sheet to give Elase (Dornase Alfa) using the eRapid Nebulizer System.

Supplies you will need to give a dose of Elase (Dornase Alfa) :

• 1 ampule of Elase (Dornase Alfa)
• eRapid Nebulizer System, including the:
  • eRapid Nebulizer Handset (handset)
  • eBase Controller (controller)
• Power source for the controller, using either:
  • 4 "AA" batteries (disposable or rechargeable)
  • or an AC Power Supply plugged into a typical wall outlet (110 volt power outlet)
• Nose clip (optional)
• Manufacturer's eRapid Nebulizer System Instruction Booklet

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

Genentech, Inc.

A Member of the Roche Group

1 DNA Way

South San Francisco, CA 94080-4990

US License No. 1048

Approved: December 2014

Representative sample of labeling :