Dornase Alfa

FDA Drug Information • Also known as: Pulmozyme

Brand Names: Pulmozyme
Dosage Form: LIQUID
Product Type: DRUG FOR FURTHER PROCESSING

Description

11 DESCRIPTION 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). The product is purified by column chromatography and tangential flow filtration. 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. PULMOZYME (dornase alfa) inhalation solution is administered by inhalation of an aerosol mist produced by a compressed air driven nebulizer or a recommended nebulizer system [see Clinical Studies (14) and Dosage and Administration (2.2) ] . PULMOZYME is a sterile, clear, colorless, highly purified solution in single-dose ampules. Each ampule delivers 2.5 mL of the solution to the nebulizer bowl. Each mL of aqueous solution contains 1 mg 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.

What Is Dornase Alfa Used For?

1 INDICATIONS AND USAGE PULMOZYME ® is indicated, in conjunction with standard therapies, for the management of pediatric and adult patients with cystic fibrosis (CF) to improve pulmonary function. In CF patients with an FVC ≥ 40% of predicted, daily administration of PULMOZYME has also been shown to reduce the risk of respiratory tract infections requiring parenteral antibiotics. PULMOZYME is a recombinant DNase enzyme indicated in conjunction with standard therapies for the management of cystic fibrosis (CF) patients to improve pulmonary function. ( 1 )

Dosage and Administration

2 DOSAGE AND ADMINISTRATION The recommended dosage is 2.5 mg (one single-dose ampule) inhaled once daily using a recommended nebulizer. ( 2.1 ) Some patients may benefit from twice daily administration. ( 2.1 ) See full prescribing information for the recommended nebulizers for use with PULMOZYME. ( 2.2 ) 2.1 Recommended Dosage The recommended dosage, in most cystic fibrosis patients, is 2.5 mg (one single-dose ampule) inhaled once daily using a recommended jet nebulizer connected to an air compressor system or via a vibrating mesh nebulizer [see Dosage and Administration (2.2) ] . Some patients may benefit from twice daily administration [see Clinical Studies (14) ] . 2.2 Administration Instructions Nebulizer Information Administer PULMOZYME via a jet nebulizer connected to an air compressor with an adequate air flow and equipped with a mouthpiece or suitable face mask, or via a vibrating mesh nebulizer. Refer to Table 1 for the recommended Jet Nebulizers or Vibrating Mesh Nebulizers for use with PULMOZYME. No data are currently available to support the administration of PULMOZYME with other nebulizer systems. The eRapid Nebulizer System should only be used by adults and pediatric patients who can use a mouthpiece, and not by younger patients who need a mask to inhale PULMOZYME. Use the selected nebulizer in accordance with the manufacturer's instruction manual. Refer to the manufacturer's instruction manual on the use, maintenance, and replacement of the equipment, including cleaning and disinfection procedures for the selected nebulizer. For additional information, refer to the selected nebulizer manufacturer's instruction manual. Table 1. Recommended Jet Nebulizers or Vibrating Mesh Nebulizers for Use with PULMOZYME Jet Nebulizer Follow the selected nebulizer manufacturer's instruction manual. Compressor Hudson T Up-draft II ® Pulmo-Aide ® or legally marketed compressor of identical pressure and flow rate (maximum 30 psi, 12 LPM). Marquest Acorn II ® PARI LC ® Plus PARI PRONEB ® or legally marketed compressor of identical pressure and flow rate (maximum 24 psi, 9 LPM). PARI BABY™ Patients who are unable to inhale or exhale orally throughout the entire nebulization period may use the PARI BABY™ nebulizer. Durable Sidestream ® MOBILAIRE™, Porta-NEB ® or legally marketed compressor of identical pressure and flow rate (maximum 45 psi, 7 LPM). Vibrating Mesh Nebulizers eRapid ® Nebulizer System Consisting of the eRapid ® Nebulizer Handset with eBase™ Controller. Avoid use in patients who need a mask to inhale PULMOZYME. Innospire Go Pulmogine Vibrating Mesh Nebulizer AireHealth Nebulizer™ Intelligent Mesh Nebulizer PULMOZYME Information Each PULMOZYME 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. Do not dilute or mix PULMOZYME with other drugs in the nebulizer. Mixing of PULMOZYME with other...

Side Effects (Adverse Reactions)

6 ADVERSE REACTIONS The most common adverse reactions (occurring in ≥3% of patients treated with PULMOZYME 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 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 (n=804) and uncontrolled trials (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 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 Single measurement only, does not reflect overall FVC changes. 17% 22% Fever 28% 32% Dyspepsia 0% 3% Dyspnea (when reported as serious) Differences were less than 3% 12% Total reports of dyspnea (regardless of severity or seriousness) had a difference of less than 3% in Trial 2. 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...

Drug Interactions

7 DRUG INTERACTIONS Available data indicate there are no clinically important drug-drug interactions with PULMOZYME.

Contraindications

4 CONTRAINDICATIONS PULMOZYME is contraindicated in patients with known hypersensitivity to dornase alfa, Chinese Hamster Ovary cell products, or any component of the product. PULMOZYME is contraindicated in patients with known hypersensitivity to dornase alfa, Chinese Hamster Ovary cell products, or any component of the product. ( 4 )

Pregnancy and Breastfeeding

8.1 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.

How Supplied

16 HOW SUPPLIED/STORAGE AND HANDLING PULMOZYME (dornase alfa) inhalation solution is a sterile, clear, colorless solution supplied in: 30 unit cartons containing 5 foil pouches of 6 single-dose ampules. Each 2.5 mL ampule contains 2.5 mg of dornase alfa (1 mg/mL): NDC 50242-100-40. Storage and Handling Store PULMOZYME ampules at a refrigerated temperature between 2°C to 8°C (36°F to 46°F) in their protective foil to protect from light and heat. Once the protective foil pouch is opened, the unused ampules must be kept refrigerated in the protective foil pouch to protect from light and heat. Do not use beyond the expiration date stamped on the ampule. During transport, keep the ampules refrigerated in their protective foil pouch to protect from light and heat. Do not use if the ampules are exposed to room temperature (22°C to 28°C [72°F to 82°F]) for more than a total of 60 hours. Avoid excessive heat and light.

About This Information

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

What are side effects?

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

What are drug interactions?

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