Dosage Forms
Excipient information presented when available (limited, particularly for generics); consult specific product labeling.
Solution, Inhalation:
Pulmozyme: 1 mg/mL (2.5 mL)
Pharmacology
Mechanism of Action
The hallmark of cystic fibrosis lung disease is the presence of abundant, purulent airway secretions composed primarily of highly polymerized DNA. The principal source of this DNA is the nuclei of degenerating neutrophils, which is present in large concentrations in infected lung secretions. The presence of this DNA produces a viscous mucous that may contribute to the decreased mucociliary transport and persistent infections that are commonly seen in this population. Dornase alfa is a deoxyribonuclease (DNA) enzyme produced by recombinant gene technology. Dornase selectively cleaves DNA, thus reducing mucous viscosity and as a result, airflow in the lung is improved and the risk of bacterial infection may be decreased.
Pharmacokinetics/Pharmacodynamics
Onset of Action
Nebulization: Enzyme levels are measured in sputum in ~15 minutes and decline rapidly thereafter
Duration of Action
Sputum concentrations decline within 2 hours of inhalation
Use: Labeled Indications
Cystic fibrosis: Management of cystic fibrosis patients, in conjunction with standard therapies, to improve pulmonary function; reduce the risk of respiratory tract infections requiring parenteral antibiotics in patients with a forced vital capacity (FVC) ≥40% of predicted.
Use: Off Label
Parapneumonic pleural effusions and empyemasb
Use of dornase alfa with alteplase in the treatment of complicated parapneumonic effusions or empyemas in adults has been evaluated in controlled and noncontrolled settings, demonstrating reductions in effusion volume, the need for surgical intervention, and hospital stay.
British Thoracic Society guidelines state that there is no indication for the routine use of intrapleural fibrinolytics in the management of pleural infection. However, fibrinolytics may be considered for use in patients with pleural infection refractory to traditional therapy and who are not candidates for surgery. The guidelines mention the potential use of alteplase in combination with dornase but provide no recommendations, as the guidelines were published prior to full publication of the controlled trial evaluating the combination.
Contraindications
Hypersensitivity to dornase alfa, Chinese hamster ovary cell products, or any component of the formulation
Dosage and Administration
Dosing: Adult
Cystic fibrosis: Inhalation: 2.5 mg daily through selected jet nebulizers in conjunction with a Pulmo-Aide, Pari-Proneb, Mobilaire, or Porta-Neb compressor system or eRapid Nebulizer System
Patients unable to inhale or exhale orally throughout the entire treatment period may use Pari-Baby nebulizer. Some patients may benefit from twice daily administration.
Parapneumonic pleural effusions and empyemas (off-label use): Intrapleural: 5 mg twice daily. Administer >2 hours after each intrapleural alteplase dose (with a 1-hour dwell time for each drug) for a total of 3 days (Rahman 2011). Data from a single center study suggest that concurrent administration of alteplase and dornase alfa (with a 2-hour dwell time) is safe and effective (Majid 2016).
Dosing: Geriatric
Refer to adult dosing.
Dosing: Pediatric
Cystic fibrosis:
Infants and Children <2 years; Symptomatic patients: Limited data available (Borowitz 2009; McKenzie 2007): Inhalation: Nebulization: 2.5 mg/day through selected nebulizers in conjunction with Pulmo-Aide, Pari-Proneb, Mobilaire, Porta-Neb, or Pari Baby compressor system or eRapid Nebulizer System (Berge 2003)
Children 2 to <5 years; Acute exacerbations or chronic use in select patients: Limited data available (Lahiri 2016; McKenzie 2007): Inhalation: Nebulization: 2.5 mg/day through selected nebulizers in conjunction with Pulmo-Aide, Pari-Proneb, Mobilaire, Porta-Neb, or Pari Baby compressor system or eRapid Nebulizer System (Nasr 2001)
Children ≥5 years and Adolescents; Chronic therapy: Inhalation: Nebulization: 2.5 mg/day through selected nebulizers in conjunction with a Pulmo-Aide, Pari-Proneb, Mobilaire, Porta-Neb, or Pari Baby compressor system or the eRapid Nebulizer System; chronic daily use in cystic fibrosis patients ≥6 years of age (Mogayzel 2013). Some patients may benefit from twice daily dosing.
Rhinosinusitis, chronic; secondary to cystic fibrosis: Limited data available: Children ≥5 years and Adolescents: Inhalation: Intranasal: 2.5 mg/day nebulized intranasal with the Pari Sinus; dosing based in double-blind, placebo-controlled cross-over trial in 23 subjects (age range: 5 to 67 years) which showed improvement of primary nasal symptoms compared to placebo (isotonic saline); treatments were well tolerated, nasal bleeding reported in two patients (Mainz 2014).
Administration
Nebulization: Prior to use, squeeze each ampul to check for leaks. Should not be diluted or mixed with any other drugs in the nebulizer, this may inactivate the drug. When administered with the eRapid Nebulizer System, replace handset after 90 uses to ensure delivery of appropriate dose; the eRapid Nebulizer System should only be used by patients who can use a mouthpiece. Follow the manufacturer’s instructions on use and maintenance of the equipment.
Parapneumonic pleural effusions and empyemas (off-label use): Intrapleural: For sequential administration of alteplase and dornase alfa, dilute each dose in 30 mL sterile water. Stability of dornase alfa diluted in sterile water has not been formally evaluated; use immediately after preparation. Instill dose into chest tube and clamp drain. After 1-hour dwell time, release clamp and connect chest tube to continuous suction (Rahman 2011). For concurrent administration of alteplase and dornase alfa, using separate syringes, dilute each dose in 50 mL normal saline. Instill each dose into chest tube, one immediately after the other, followed by a 60 mL normal saline flush. Clamp drain; after 2-hour dwell time, release clamp (Majid 2016).
Storage
Store at 2°C to 8°C (36°F to 46°F) in protective foil to protect from light. Refrigerate during transport and do not expose to room temperatures for ≥24 hours.
Drug Interactions
There are no known significant interactions.
Adverse Reactions
Adverse events were similar in children using the PARI BABY nebulizer (facemask as opposed to mouthpiece) with the addition of cough.
>10%:
Cardiovascular: Chest pain (18% to 25%)
Central nervous system: Voice disorder (12% to 18%)
Dermatologic: Skin rash (3% to 12%)
Respiratory: Cough (PARI-BABY nebulizer facemask: children 3 months to <5 years: 45%; children 5 to ≤10 years: 30%), pharyngitis (32% to 40%), rhinitis (30%; in patients with FVC: <40%), decrease in forced vital capacity (≥10% decrease of predicted: 22%; in patients with FVC: <40%), dyspnea (17%; in patients with FVC: <40%)
Miscellaneous: Fever (32% in patients with FVC <40%)
1% to 10%:
Gastrointestinal: Dyspepsia (≤3%)
Immunologic: Antibody development (to dornase alfa: 2% to 4%)
Ophthalmic: Conjunctivitis (1% to 5%)
Respiratory: Laryngitis (3% to 4%)
<1%, postmarketing and/or case reports: Headache, urticaria
Warnings/Precautions
Disease-related concerns:
- Decreased pulmonary function: In patients with pulmonary function <40% of normal, dornase alfa does not significantly reduce the risk of respiratory infections that require parenteral antibiotics.
Special populations:
- Pediatric: Safety studies included children ≥3 months, however experience is limited in children <5 years of age.
Pregnancy
Pregnancy Considerations
Adverse events have not been observed in animal reproduction studies.
Patient Education
What is this drug used for?
- It is used to lower the number of lung infections and help lung function in cystic fibrosis.
Frequently reported side effects of this drug
- Change in voice
- Runny nose
- Sore throat
- Eye irritation
Other side effects of this drug: Talk with your doctor right away if you have any of these signs of:
- Chest pain
- Shortness of breath
- Signs of a significant reaction like wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat.
Note: This is not a comprehensive list of all side effects. Talk to your doctor if you have questions.
Consumer Information Use and Disclaimer: This information should not be used to decide whether or not to take this medicine or any other medicine. Only the healthcare provider has the knowledge and training to decide which medicines are right for a specific patient. This information does not endorse any medicine as safe, effective, or approved for treating any patient or health condition. This is only a brief summary of general information about this medicine. It does NOT include all information about the possible uses, directions, warnings, precautions, interactions, adverse effects, or risks that may apply to this medicine. This information is not specific medical advice and does not replace information you receive from the healthcare provider. You must talk with the healthcare provider for complete information about the risks and benefits of using this medicine.
