dornase alfa (DNase I)
Brand: Pulmozyme
Prototype Drug
Drug Class: mucolytic enzyme
Drug Family: mucolytic/expectorant
Subclass: recombinant human deoxyribonuclease I
Organ Systems: respiratory
Mechanism of Action
Recombinant human deoxyribonuclease I that selectively cleaves extracellular DNA in airway secretions; in cystic fibrosis, dying neutrophils release DNA that increases sputum viscosity — dornase alfa reduces DNA polymer chain length, decreasing sputum viscosity and facilitating airway clearance.
extracellular DNA (in sputum)
Indications
- cystic fibrosis (daily management to improve pulmonary function and reduce respiratory infections)
Contraindications
- hypersensitivity to dornase alfa, Chinese hamster ovary cell products, or any excipient
Adverse Effects
Common
- voice alteration (hoarseness)
- pharyngitis
- laryngitis
- rhinitis
- rash
Serious
- rare hypersensitivity reactions
Pharmacokinetics (ADME)
| Absorption | inhaled via nebulizer; systemic absorption minimal; acts locally in airways |
| Distribution | confined to airway secretions; negligible systemic levels |
| Metabolism | digested by proteases in the airway; products are amino acids |
| Excretion | local metabolic breakdown in airways |
| Half-life | N/A (local enzyme action) |
| Onset | improvement in sputum viscosity within hours; FEV1 improvement over weeks |
| Peak | N/A |
| Duration | requires daily use for sustained benefit |
| Protein Binding | N/A |
| Vd | N/A |
Drug Interactions
| Drug / Agent | Mechanism | Severity |
|---|---|---|
| no significant drug interactions identified | acts locally in airway; minimal systemic absorption | minor |
Nursing Considerations
- Administer via recommended jet nebulizers (Hudson T Up-draft II, Marquest Acorn II, or Pari LC Plus with compressors); do not dilute or mix with other nebulizer solutions.
- Single-use ampules (2.5 mg/2.5 mL) should be refrigerated and protected from light; once removed from refrigerator, use within 24 hours; discard unused portions.
- Dornase alfa is typically administered once daily in the morning; timing in relation to airway clearance physiotherapy should be individualized — current CF guidelines suggest administration before or after airway clearance based on patient response.
- Instruct patients and families that voice changes and throat irritation are common, usually mild, and transient; persistent or worsening symptoms should be reported.
Clinical Pearls
- Dornase alfa was the first orphan drug approved specifically for cystic fibrosis (1993) and remains a cornerstone of CF maintenance therapy; in clinical trials it reduced pulmonary exacerbations by 22% and improved FEV1 by approximately 6% in moderate-to-severe CF.
- The therapeutic target of dornase alfa is neutrophil-derived extracellular DNA, not mucus glycoproteins — this distinguishes it from non-specific mucolytics like acetylcysteine and explains its specific efficacy in CF, where airway neutrophilia is a defining pathological feature.
Safety Profile
Pregnancy generally-safe
Lactation insufficient-data
Renal Adjustment Not required
Hepatic Adjustment Not required
TDM Not required
Concordance Terms
Cross-referenced clinical concepts — click any term to see all content where it appears.