Pulmozyme

Name: Pulmozyme

Patient information

Instructions for Use

PULMOZYME®
(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 Pulmozyme with the ultras onic eRapid™ Nebulizer System

Read this Instructions for Use before you start taking Pulmozyme 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 Pulmozyme. A nebulizer changes the Pulmozyme liquid medicine into a fine mist you inhale by breathing through a mouthpiece. A compressor gives the nebulizer power and makes the nebulizer work.

Pulmozyme should only be used with the approved nebulizers and compressors listed below, or with the eRapid Nebulizer System (see other side).

Do not use any other inhaled medicines in the nebulizer at the same time. Keep all other inhaled medication systems completely separate from Pulmozyme.

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 Pulmozyme using the following jet nebulizer systems.

Nebulizer Compressor
Hudson T Up-draft II® with Pulmo-Aide®
Marquest Acorn II® with Pulmo-Aide®
PARI LC® Plus with PARI PRONEB®
PARI BABY™ with PARI PRONEB®
Durable Sidestream® with MOBILAIRE™
Durable Sidestream® with Porta-Neb®

Supplies you will need to give a dose of Pulmozyme (See Figure A):

  • 1 ampule of Pulmozyme
  • 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)

Preparing the jet nebulizer and compressor:

Step 1. Clean a flat table surface and wash your hands.

  • Clean a flat table surface.
  • Wash your hands well with soap and water before using the Pulmozyme ampule and nebulizer. This helps prevent infection (See Figure B).

Step 2. Gather the nebulizer and test the compressor.

  • Place the nebulizer parts on a clean, flat table surface within reach.
  • Test the compressor by turning it on and putting your finger in front of the "air out" or "air" port to feel air flowing. Turn off the compressor (See Figure C).
  • For the MOBILAIRE™ compressor only, turn the pressure control knob fully to the right for the highest pressure output.

Step 3. Gather the Pulmozyme ampule and check the expiration date.

  • Remove 1 foil pouch of Pulmozyme from the refrigerator. Open the foil pouch and remove 1 ampule of Pulmozyme. Put the remaining ampules back in the foil pouch and return them to the refrigerator.
  • Check the expiration date printed on the ampule (See Figure D). Do not use the Pulmozyme ampule if the expiration date has passed.

Step 4. Check the Pulmozyme ampule.

  • Check the ampule for leaks by turning it upside down and gently squeezing (See Figure E). Do not use the ampule if it is leaking. Throw it away and get a new one.
  • Check the Pulmozyme liquid in the ampule and make sure it is clear and free of particles. Do not use Pulmozyme if the liquid is cloudy or discolored. Take the Pulmozyme back to the pharmacy, hospital, or clinic that gave you the medicine.

Step 5. Attach the tube to the compressor.

  • Attach the long connecting tube to the "air out" or "air" port on the compressor (See Figure F).

Step 6. Attach the mouthpiece.

  • Skip to Step 7 if you use the Sides tream nebulizer or the PARI BABY nebulizer.
  • Push the mouthpiece into the wider end of the plastic T. Attach the flex tube to the other end of the T (See Figure G).

Step 7. Remove the cap from the cup.

  • Unscrew or unsnap the cap from the nebulizer cup (See Figure H).
  • Put the nebulizer cup on the table face up and place the cap upside down on a clean surface (See Figure I).

Step 8. Open the Pulmozyme ampule.

  • Hold the tab at the bottom of the Pulmozyme ampule firmly. Twist off the top. Do not squeeze the body of the ampule (See Figure J).

Step 9. Pour the full Pulmozyme dose into the nebulizer.

  • Turn the ampule upside down and squeeze gently to empty the medicine into the nebulizer cup. Keep squeezing until the ampule is empty. It is very important you squeeze all of the medicine out of the ampule (See Figure K).
  • Screw or snap the cap onto the nebulizer cup (See Figure L).

Step 10. Connect the plastic T.

  • Connect the plastic T to the nebulizer cap (See Figure M).
  • If you are using the Sides tream nebulizer, attach the mouthpiece to the top of the nebulizer (See Figure N).
  • If you are using the PARI BABY nebulizer, connect the elbow piece and mask to the nebulizer outlet (See Figure O).

Step 11. Attach the tube to the cup.

  • Connect the open end of the long tube to the port on the bottom of the nebulizer cup by pushing up firmly (See Figure P).

Step 12. Turn on the compressor.

  • Turn on the compressor and check to see that mist is coming out of the nebulizer (See Figure Q).
  • If you are using the MOBILAIRE™ compressor, turn the compressor control knob fully to the right, then turn on the compressor. The pressure gauge should move between 35 psi and 45 psi, the highest pressure output (See Figure R).

Taking your dose of Pulmozyme with a nebulizer:

Step 13. Breathe through the mouthpiece.

  • Skip to Step 14 if you are using the PARI BABY to give Pulmozyme to your child.
  • Place the mouthpiece between your teeth and on top of your tongue (See Figure S).
  • Breathe slowly in and out through your mouth. Do not block the airflow with your tongue.
  • Do not breathe through your nose. If you have problems breathing only through your mouth, use a nose clip (See Figure T).
  • Do not be concerned if liquid droplets form in the long connecting tube during treatment. When the nebulizer begins spitting, gently tap the nebulizer cup and continue breathing until the nebulizer cup is empty or stops making mist (See Figure U).
  • If you need to stop treatment before you are finished, or you begin coughing, turn off the compressor and do not spill any of the medicine.
  • To start treatment again, turn on the compressor and continue breathing slowly in and out through your mouth.
  • The complete treatment usually takes from 10 to 15 minutes for most nebulizers and compressors.
  • If you are using the Sidestream nebulizer with the MOBILAIRE™ or Porta-Neb compressors, treatment usually takes from 2 to 6 minutes.
  • It is important to inhale the full dose of Pulmozyme. If you find a leak or feel any moisture coming from the nebulizer during treatment, turn off the compressor and check to make sure the nebulizer cap is sealed correctly before continuing (See Figure V).
If you are using the PARI BABY nebulizer to give Pulmozyme to your child, follow the instructions below in Step 14. If not, go to Step 15

Step 14. Breathing through the facemask

  • During the treatment your child may sit, lie down or stand.
  • Place the facemask gently but firmly over your child's nose and mouth (See Figure W).
  • Make sure there are no air gaps between the mask and your child's face. This will help make sure that your child will get the full dose of Pulmozyme.
  • It is important that you try to keep the body of the nebulizer upright during the entire treatment (See Figure W). The elbow piece will allow you to move the mask for a good fit while keeping the nebulizer body upright.
  • When the nebulizer begins "spitting," gently tap the nebulizer cup and continue treatment until the nebulizer is empty or stops making a mist (See Figure X).
  • If you need to s top the treatment or your child begins to cough during treatment, turn the compressor off. Do not spill any Pulmozyme.
  • If you have not removed the mask and you want to begin the treatment again, turn on the compressor.
  • If you have removed the mask, repeat the steps above to replace the mask on your child's face and restart the compressor.
  • The complete treatment usually takes from 10 to 15 minutes.

It is important that your child inhale the full dose of Pulmozyme. If you find a leak or feel moisture coming from the nebulizer during the treatment, turn off the compressor and make sure the nebulizer cap is sealed correctly before starting the compressor again (See Figure Y).

After your treatment with Pulmozyme:

Step 15. Prepare the nebulizer for cleaning and storage.

  • Turn off the compressor and take apart the nebulizer system. Set aside the flex tube and the long connecting tube.
    Note: The Sidestream nebulizer does not use a flex tube.
  • Throw away the Pulmozyme ampule in your household trash.
  • Follow the manufacturer's recommendations for care of your nebulizer and compressor.
  

How should I store Pulmozyme?

  • Store Pulmozyme in its foil pouch in the refrigerator between 36°F to 46°F (2°C to 8°C) until you are ready to use it.
  • When traveling, Pulmozyme should be kept cold in its foil pouch.
  • Do not freeze Pulmozyme.
  • Protect Pulmozyme from excessive heat and strong light.
  • Do not use Pulmozyme if it has been left at room temperature for a total time of 24 hours or if it becomes cloudy or discolored.
  • Do not use Pulmozyme past the expiration date printed on the ampule.

Instructions for Use

PULMOZYME®
(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 Pulmozyme 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 Pulmozyme 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 Pulmozyme.

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 Pulmozyme.

Follow the instructions on this side of the sheet to give Pulmozyme using the eRapid Nebulizer System.

Supplies you will need to give a dose of Pulmozyme (See Figure A):

  • 1 ampule of Pulmozyme
  • 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

Figure A

Preparing the eRapid nebulizer system:

Step 1. Clean a flat table surface and wash your hands.

  • Clean a flat table surface.
  • Wash your hands well with soap and water before using the Pulmozyme ampule and nebulizer. This helps prevent infection (See Figure B).

Step 2. Gather the nebulizer and test it.

  • Place the eRapid system parts on a clean, flat table surface within reach.
  • Make sure the controller batteries are charged or that the unit is plugged into a power outlet (See Figure C).
  • Press and hold the ON/OFF button on the controller for a few seconds to test if the controller will turn on (See Figure D).
  • When controller is turned on, press and hold the ON/OFF button to turn the controller off.

Step 3. Gather the Pulmozyme ampule and check the expiration date.

  • Remove 1 foil pouch of Pulmozyme from the refrigerator. Open the foil pouch and remove 1 ampule of Pulmozyme. Put the remaining ampules back in the foil pouch and return them to the refrigerator.
  • Check the expiration date printed on the ampule (See Figure E).
    Do not use Pulmozyme ampule if expiration date has passed.

Step 4. Check the Pulmozyme ampule.

  • Check the ampule for leaks by turning it upside down and gently squeezing (See Figure F).
    Do not use the ampule if it is leaking. Throw it away and get a new one.
  • Check the Pulmozyme liquid in the ampule and make sure it is clear and free of particles.
    Do not use Pulmozyme if the liquid is cloudy or discolored. Take the Pulmozyme back to the pharmacy, hospital, or clinic that gave you the medicine.

Step 5. Put together the eRapid nebulizer system.

  • The eRapid Nebulizer System has several small parts that must be put together the right way to give your dose of Pulmozyme (Figure G).
  • The parts must be cleaned and disinfected at least 1 time before first use.
  • See the Manufacturer's eRapid Nebulizer System Instruction Booklet for cleaning instructions and step-by-step instructions for how to put together your eRapid Nebulizer System (See Figure G).

Step 6. Open the Pulmozyme ampule.

  • Hold the tab at the bottom of the Pulmozyme ampule firmly. Twist off the top. Do not squeeze the body of the ampule (See Figure H).

Step 7. Pour the full Pulmozyme dose into the nebulizer.

  • Turn the ampule upside-down and squeeze gently to empty the medicine into the medication reservoir. Keep squeezing until the ampule is empty. It is very important that you squeeze out all the medicine in the ampule (See Figure I).

Step 8. Place the cap on the Medication Reservoir.

  • Line up the tabs on medication cap with the slots on medication reservoir (See Figure J).
  • Turn medication cap clockwise until it stops (See Figure J).

Step 9. Turn on the nebulizer.

  • Press and hold ON/OFF button on the controller for a few seconds (See Figure K).
  • The controller will beep and the light will turn green. The nebulizer will start making mist (See Figure L).
Taking your dose of Pulmozyme:  

Step 10. Breathe through the mouthpiece.

  • Place the mouthpiece between your teeth and on top of your tongue (See Figure M).
  • Breathe slowly in and out through your mouth. Do not block medicine flow with your tongue.
  • Do not breathe through your nose. If you have problems breathing only through your mouth, use a nose clip (See Figure N).
  • If you need to stop treatment before you are finished, or you begin coughing, press and hold the ON/OFF button on the controller for 1 second (See Figure O).
  • To restart your treatment, press and hold the ON/OFF button for 1 second.
  • Continue your treatment until the controller beeps twice.
  • The nebulizer will shut off by itself when your dose is complete.
    The complete treatment usually takes from 1 minute to 5 minutes.

Step 11. Check that you received your full dose.

  • After your treatment, about 1/5 teaspoon (1mL) of medicine should be left in the medication reservoir (See Figure P).
  • Open the medication cap and check the medication reservoir. If more than 1/5 teaspoon (1 mL) is left in the medication reservoir, put the medication cap back on and continue treatment.
  • When treatment is complete, throw away the 1/5 teaspoon (1 mL) of medicine that is left in the medication reservoir.

After Your Treatment with Pulmozyme:

Step 12. Cleaning the nebulizer

  • If the controller is on, turn off the controller by pressing and holding the ON/OFF button.
  • Take apart the nebulizer system.
  • Throw away the empty Pulmozyme ampule in your household trash.
  • See the Manufacturer's eRapid Nebulizer System Instruction Booklet for cleaning instructions (See Figure Q).
    • The handset, including the medication reservoir, medication cap, aerosol head, and mouthpiece, must be cleaned after each use and disinfected after each day of use.
  • Use of the EasyCare cleaning aid is recommended for cleaning the aerosol head located inside the handset 1 time each week.
  • Replace the handset after you use your eRapid Nebulizer System 90 times. Replace it even if you use the EasyCare cleaning aid.
  • Your handset has been tested for only 90 doses of Pulmozyme. Delivery of the right dose of PULMOZYME cannot be certain after 90 doses.

How should I store Pulmozyme?

  • Store Pulmozyme in its foil pouch in the refrigerator between 36°F to 46°F (2°C to 8°C) until you are ready to use it.
  • When traveling, Pulmozyme should be kept cold.
  • Do not freeze Pulmozyme.
  • Protect Pulmozyme from excessive heat and strong light.
  • Do not use Pulmozyme if it has been left at room temperature for a total time of 24 hours or if it becomes cloudy or discolored.
  • Do not use Pulmozyme past the expiration date printed on the ampule.

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

Pharmacology

Mechanism of Action

Recombinant human DNase 1, digests neutrophil DNA deposited in the pulmonary mucosa thereby reducing mucosal viscoelasticity

Pharmacokinetics

Onset of action: Enzyme activity measured in sputum in 15 min

Duration: Activity declines rapidly

What should i avoid while using dornase alfa (pulmozyme)?

Do not dilute or mix the dornase alfa solution with any other drugs in the nebulizer. Mixing of dornase alfa with other drugs could lead to changes in the actions of the medications.

Pulmozyme Usage

Use Pulmozyme exactly as prescribed. 

Pulmozyme comes as an inhalation and is inhaled once daily using a recommended nebulizer.

  • Pulmozyme must be stored in the refrigerator and protected from light
  • Squeeze each ampule before use to check for leaks
  • Discard the solution if it is cloudy or discolored
  • Once opened, the entire contents of the ampule must be used or discarded
  • Do not dilute or mix Pulmozyme with other drugs in the nebulizer 

Pulmozyme should only be used with the approved nebulizers and compressors. Follow directions carefully when using eRapid Nebulizer System and jet nebulizers.

If you miss a dose, take the missed dose as soon as you remember. If it is almost time for the next dose, skip the missed dose, and take your next dose at the regular time. Do no take two doses of Pulmozyme. 

Pulmozyme Dosage

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully. 

The dose your doctor recommends may be based on the following:

  • your lung function
  • other medications you are taking
  • the stability of your cystic fibrosis

The recommended dose of Pulmozyme for the treatment of cystic fibrosis is one 2.5 mg single-use ampule inhaled by mouth once daily. Some patients may benefit from twice daily usage. 

Other Requirements

  • Store Pulmozyme under refrigeration 36°F to 46°F(2°C to 8°C) in their protective foil to protect from light
  • Do not use beyond the expiration date stamped on the ampule
  • Refrigerate Pulmozyme during transport and do not expose to room temperatures for a total time of 24 hours.
  • Keep this and all medicines out of the reach of children.

Pulmozyme Side Effects

Along with its needed effects, a medicine may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor immediately if any of the following side effects occur:

More common
  • Body aches or pain
  • chest pain
  • congestion
  • cough
  • dryness or soreness of the throat
  • fever
  • hoarseness
  • runny nose
  • tender, swollen glands in the neck
  • trouble breathing
  • trouble swallowing
  • voice changes

Some side effects may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

More common
  • Acid or sour stomach
  • belching
  • heartburn
  • indigestion
  • rash
  • sneezing
  • stomach discomfort, upset, or pain
  • stuffy nose
Less common
  • Burning, dry, or itching eyes
  • discharge or excessive tearing
  • redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid

Other side effects not listed may also occur in some patients. If you notice any other effects, check with your healthcare professional.

Call your doctor for medical advice about side effects. You may report side effects to the FDA at 1-800-FDA-1088.

Adverse Reactions

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 Pulmozyme in 902 patients, with exposures ranging from 2 weeks of daily administration up to once or twice daily administration for six months. Pulmozyme 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 Pulmozyme 2.5 mg by inhalation once a day (n=581), while the rest of patients (n=321) received Pulmozyme 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 Pulmozyme 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 Pulmozyme 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 Pulmozyme, and the proportion of discontinuations were similar for placebo (2%) and Pulmozyme (3%). Adverse reactions occurring in a higher proportion (greater than 3%) of Pulmozyme 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 Pulmozyme 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 Pulmozyme treated patients are listed in Table 2.

Table 2. Adverse Reactions Increased 3% or More in Pulmozyme Treated Patients Over Placebo in CF Clinical Trials
Adverse Reactions
(of any severity or seriousness)		 Trial 1
CF Patients with FVC ≥ 40% of predicted treated for 24 weeks		 Trial 2
CF Patients with FVC <40% of predicted treated for 12 weeks
Placebo
n=325		 Pulmozyme QD
n=322		 Pulmozyme BID
n=321		 Placebo
n=159		 Pulmozyme QD
n=161
* Single measurement only, does not reflect overall FVC changes. † Total reports of dyspnea (regardless of severity or seriousness) had a difference of less than 3% in Trial 2.
Voice alteration 7% 12% 16% 6% 18%
Pharyngitis 33% 36% 40% 28% 32%
Rash 7% 10% 12% 1% 3%
Laryngitis 1% 3% 4% 1% 3%
Chest Pain 16% 18% 21% 23% 25%
Conjunctivitis 2% 4% 5% 0% 1%
Rhinitis Differences were less than 3% 24% 30%
FVC decrease of ≥ 10% of predicted* 17% 22%
Fever 28% 32%
Dyspepsia 0% 3%
Dyspnea (when reported as serious) Differences were less than 3% 12%† 17%†

Mortality rates observed in controlled trials were similar for the placebo and Pulmozyme 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 Pulmozyme, 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 Pulmozyme. 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 Pulmozyme developed serum antibodies to Pulmozyme. None of these patients developed anaphylaxis, and the clinical significance of serum antibodies to Pulmozyme is unknown.

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)].

Use in specific populations

Pregnancy

Risk summary

There are no adequate and well-controlled studies with Pulmozyme in pregnant women. However, animal reproduction studies have been conducted with dornase alfa. In these studies, no evidence of fetal harm was observed in rats and rabbits at doses of 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 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 dornase alfa was administered to dams throughout organogenesis (Gestation days 6 to 17). 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 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.

Lactation

Risk Summary

It is not known whether Pulmozyme is present in human milk. In a pharmacokinetic study in Cynomolgus monkeys, levels of 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 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 Pulmozyme and any potential adverse effects on the breastfed child from Pulmozyme or from the underlying maternal condition.

Pediatric Use

The safety and effectiveness of Pulmozyme have been established in pediatric patients 5 years of age and older [see Adverse Reactions (6) and Clinical Studies (14)]. The safety of Pulmozyme, 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 [see Adverse Reactions (6.1)]. While clinical trial data are limited in pediatric patients younger than 5 years of age, the use of Pulmozyme 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.

Geriatric Use

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

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 Pulmozyme 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.

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