Dornase alfa is a biosynthetic (recombinant DNA origin) form of human deoxyribonuclease I (DNase I), an enzyme that selectively cleaves extracellular DNA (e.g., in purulent pulmonary secretions).1, 2, 33
Dornase alfa is used in conjunction with standard therapies in pediatric and adult patients with cystic fibrosis to improve pulmonary function.1, 37, 39, 40, 41 In patients with forced vital capacity ≥40% of the predicted value, daily administration of dornase alfa has been shown to reduce the frequency of respiratory infections requiring parenteral anti-infective therapy.1 Dornase alfa has been designated an orphan drug by FDA to reduce mucous viscosity and enable the clearance of airway secretions in patients with cystic fibrosis.13 Guidelines recommend the use of dornase alfa for patients with asymptomatic, mild, moderate, or severe cystic fibrosis to improve lung function and reduce exacerbations.1000
The current indication for dornase alfa is based principally on data from a randomized, double-blind multicenter study involving 968 patients ≥5 years of age with stable cystic fibrosis and a baseline forced vital capacity of ≥40% of the predicted value and a randomized, controlled study involving 320 patients with stable cystic fibrosis and a baseline forced vital capacity of <40% of the predicted value.1, 37, 39
In the study that evaluated efficacy of dornase alfa as adjunctive therapy for cystic fibrosis when forced vital capacity was ≥40% of the predicted value, patients received placebo, dornase alfa 2.5 mg once daily, or dornase alfa 2.5 mg twice daily for 6 months while continuing standard therapy for cystic fibrosis.1, 39 Doses were administered via a Hudson T Up-draft II® nebulizer with a Pulmo-Aide® compressor.1, 39 Patients receiving dornase alfa 2.5 mg once or twice daily had reductions of 27 or 29%, respectively, in relative risk of developing a respiratory infection compared with patients receiving placebo.1 Patients receiving dornase alfa also possessed an increased mean forced expiratory volume at 1 second (FEV1) and decreased incidence of occurrence of first respiratory tract infection requiring parenteral antibiotics.1 Dornase alfa appears to be less effective in reducing the risk of respiratory tract infection in older patients (e.g., ≥21 years of age) than in younger patients, and twice-daily dosing may be required in such patients.1 When data are adjusted to compensate for age differences in the 3 treatment groups in the multicenter study, once- or twice-daily dosing of dornase alfa resulted in 28-31 or 32-37% reductions in the risk of respiratory infections requiring parenteral anti-infectives.39 Patients with relatively mild disease (e.g., those with a baseline forced vital capacity >85% of the predicted value) also appear to be less responsive to the drug1, 10 and may experience greater benefit with twice-daily dosing of dornase alfa.1
In the study that evaluated efficacy of dornase alfa as adjunctive therapy for cystic fibrosis when forced vital capacity was <40% of the predicted value, patients received dornase alfa 2.5 mg once daily or placebo for 12 weeks.1, 37 The mean change from baseline in FEV1 was an increase of 9.4% with dornase alfa compared with 2.1% with placebo.1, 37 However, dornase alfa was not distinguishable from placebo in relative risk of developing a respiratory infection requiring use of parenteral anti-infectives.1 A secondary measure of efficacy was the mean change from baseline in forced vital capacity, which was an increase of 12.4% with dornase alfa compared with 7.3% with placebo.1, 37
Clinical trials indicate that dornase alfa therapy can be initiated or continued during an acute pulmonary exacerbation.1, 28 The manufacturer reports that short-term studies did not demonstrate a dose-dependent improvement in pulmonary function (FEV1) at dornase alfa dosages exceeding 2.5 mg twice daily.1 Patients who have received the drug on an intermittent regimen (alternating 10 mg of dornase alfa twice daily with no therapy, at 2-week intervals) experienced rapid improvement in FEV1 at initiation of therapy and a return to baseline values following withdrawal of the drug with each cycle.1
Both short- and long-term studies indicate that dornase alfa therapy improves pulmonary function in selected patients with cystic fibrosis5, 8, 10, 11, 14, 27, 40, 41 and is associated with decreases in dyspnea, cough frequency and severity, and bacterial counts in sputum.8, 10, 11, 14 Therapy with dornase alfa also is associated with subjective improvements in these patients, including a perceived general increase in feeling of well-being and quality of life.10, 14 However, the drug appears to be useful only in patients with infected (purulent) sputum.2, 5, 8 In several controlled studies involving children and adults with stable cystic fibrosis and a baseline forced vital capacity of ≥40% of the predicted value, dornase alfa was more effective than placebo in improving parameters of pulmonary function (increased forced vital capacity and FEV1) during a 10-day period.10, 11 Response to therapy appeared to be dose dependent and most marked in patients with moderately severe disease (forced vital capacity 40-70% of the predicted value).10
A meta-analysis found that, compared to placebo, dornase alfa improved FEV1 at time frames of 1 month to 2 years and reduced the number of pulmonary exacerbations in trials of up to 2 years' duration.40 The effect of dornase alfa compared to other hyperosmolar agents was unclear.40
The Cystic Fibrosis Foundation recommends chronic use of dornase alfa to improve lung function and reduce exacerbations in patients ≥6 years of age with asymptomatic or mild lung disease, and strongly recommends chronic use of dornase alfa to improve lung function, improve quality of life, and reduce exacerbations in patients ≥6 years of age with moderate to severe lung disease.1000
Although safety and efficacy have not been established, limited data suggest that dornase alfa may be used intrapleurally in conjunction with alteplase for complicated parapneumonic effusions and empyema† .42, 43, 44, 45
Although safety and efficacy have not been established, limited data suggest that dornase alfa may be used for the treatment of chronic rhinosinusitis secondary to cystic fibrosis in pediatric patients†.46
Dornase alfa is administered by oral inhalation via a jet nebulizer or a vibrating mesh nebulizer.1
The manufacturer states that recommended jet nebulizers for use with dornase alfa include: the disposable jet nebulizer Hudson T Up-draft II® or the disposable jet nebulizer Marquest Acorn II®, in conjunction with a Pulmo-Aide® compressor or a legally marketed compressor of identical pressure and flow rate; the reusable PARI LC® Plus or PARI BABY™ nebulizer, in conjunction with the PARI PRONEB® compressor or a legally marketed compressor of identical pressure and flow rate; and the Durable Sidestream® nebulizer with either the MOBILAIRE® or Porta-Neb® compressor or a legally marketed compressor of identical pressure and flow rate.1 The manufacturer states that recommended vibrating mesh nebulizers for use with dornase alfa include the eRapid™ Nebulizer System, consisting of the eRapid™ Nebulizer Handset with eBase™ Controller, Innospire Go, Pulmogine Vibrating Mesh Nebulizer, AireHealth Nebulizer, and Intelligent Mesh Nebulizer.1
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 for dornase alfa inhalation.1 Patients and clinicians should refer to the manufacturer's instruction manual on the use, maintenance, and replacement of equipment,including cleaning and disinfection procedures for the selected nebulizer.1
Dornase alfa oral inhalation solution should not be diluted nor should it be admixed with any other drugs in the nebulizer.1 The manufacturer states that patients or their caregivers should be advised to squeeze each ampule prior to use to check for leaks.1
Store ampules of dornase alfa at 2-8°C and in their protective foil to protect from light and heat; once protective foil pouch is opened, unused ampules must be refrigerated in the foil pouch to protect from light and heat.1 Keep ampules refrigerated during transport in their protective foli pouch and do not expose to room temperature for longer than 60 hours in total.1 Dornase alfa oral inhalation solution contains no preservatives; once the single-use ampule is opened, the manufacturer states that the entire contents must be used or the remainder discarded.1
Each single-use ampule delivers 2.5 mg of dornase alfa (2.5 mL of undiluted solution).1
For adjunctive therapy in the management of cystic fibrosis in adults, the usual oral inhalation dosage of dornase alfa is 2.5 mg once daily using a recommended jet nebulizer system connected to an air compressor system or via a vibrating mesh nebulizer.1 The manufacturer states that some patients may benefit from twice daily administration of dornase alfa.1 Data indicate that dornase alfa may be continued or initiated during an acute respiratory exacerbation.1
For adjunctive therapy in the management of cystic fibrosis in pediatric patients, the usual oral inhalation dosage of dornase alfa is 2.5 mg once daily using a recommended jet nebulizer system connected to an air compressor system or via a vibrating mesh nebulizer.1 The manufacturer states that some patients may benefit from twice daily administration of dornase alfa.1 Data indicate that dornase alfa may be continued or initiated during an acute respiratory exacerbation.1
The manufacturer makes no specific dosage recommendations in hepatic impairment.1
The manufacturer makes no specific dosage recommendations in renal impairment.1
The manufacturer makes no specific dosage recommendations in geriatric patients.1
There are no adequate and well-controlled studies of dornase alfa in pregnant women.1 Animal reproductive data have shown no evidence of fetal harm at doses up to 600 times the maximum recommended human dose.1
It is not known whether dornase alfa is distributed into human milk.1 Consider the developmental and health benefits of breastfeeding along with the mother's clinical need for dornase alfa and the potential for adverse effects on the breast-fed child.1
Safety and efficacy of dornase alfa as adjunctive therapy in cystic fibrosis have been established in pediatric patients.1 The use of dornase alfa in pediatric patients 5-17 years of age is supported by evidence from a trial including 303 clinically stable patients with cystic fibrosis; use of dornase alfa in pediatric patients <5 years of age is supported by extrapolated efficacy data from pediatric patients ≥5 years of age, and additional safety data in 65 patients, 3 months to 5 years of age, who received dornase alfa 2.5 mg daily via inhalation for a 2-week period.1
Because cystic fibrosis is a condition that primarily affects children and young adults, clinical studies of dornase alfa did not include sufficient numbers of patients ≥65 years of age to determine whether geriatric patients respond differently from younger patients.1
Pharmacokinetics have not been evaluated in patients with hepatic impairment.1
Pharmacokinetics have not been evaluated in patients with renal impairment.1
Adverse effects in clinical studies of dornase alfa occurring in ≥3% of patients and more commonly than with placebo include voice alteration, pharyngitis, rash, laryngitis, chest pain, conjunctivitis, rhinitis, a decrease in forced vital capacity ≥10%, fever, and dyspnea.1
The manufacturer states that there are no clinically significant drug-drug interactions with dornase alfa.1
Dornase alfa is a biosynthetic (recombinant DNA origin) form of human deoxyribonuclease I (DNase I, pancreatic DNase, human DNase, thymonuclease), an enzyme that selectively cleaves DNA.1, 2, 33 Deoxyribonuclease I is present in a variety of animal and plant tissues.2, 14 Dornase alfa is prepared from cultures of genetically modified Chinese hamster ovary cells using recombinant DNA technology.1 These cells have been modified by the addition of plasmids that incorporate the human deoxyribonuclease gene, which was isolated from human pancreas cells.1, 2
Deoxyribonuclease I is an enzyme involved in endonucleolytic cleavage of extracellular DNA to 5'-phosphodinucleotide and 5'-phosphooligonucleotide end products;14, 33 deoxyribonuclease I has no effect on DNA within intact cells.1, 14, 34 In patients with cystic fibrosis, retention of viscous purulent secretions in the airways contributes to both reduced pulmonary function and exacerbations of infection.1 Purulent pulmonary secretions contain high concentrations of extracellular DNA, an extremely viscous polyanion, which is released by degeneration of leukocytes that accumulate during the inflammatory response to infection.1, 2, 5 In vitro, dornase alfa hydrolyzes the DNA in sputum of patients with cystic fibrosis;1, 2, 5 optimal enzymatic activity depends on the presence of divalent cations (e.g., calcium, magnesium).2 The enzyme does not appear to affect sputum in the absence of an inflammatory response to infection (i.e., in those with nonpurulent sputum),2, 5, 8 nor does it affect pulmonary function in healthy individuals.8 While most evidence suggests that this effect on extracellular DNA reduces sputum viscosity and viscoelasticity,1, 2, 3, 15, 20 limited evidence indicates that the enzyme may instead reduce the adhesiveness and elasticity of purulent sputum with little effect on its viscosity per se.19 Trypsin, chymotrypsin, and/or other proteolytic contaminants, which were present in early formulations of bovine DNase I, do not appear to contribute to the viscosity-reducing effect of deoxyribonuclease I, including dornase alfa.2
Although the mechanism of dornase alfa has not been elucidated fully,6, 7 the enzyme appears to improve the transportability of purulent mucus via ciliary activity and cough.3, 19 Alteration of purulent sputum by dornase alfa is associated with reduced airflow obstruction, improved pulmonary function (increased forced vital capacity and forced expiratory volume at 1 second [FEV1]), and more effective mucociliary clearance in patients with cystic fibrosis.1, 5, 8, 9, 10, 11, 12, 14, 27, 29 The beneficial effects of dornase alfa in these patients involve a mechanism(s) distinct from the mucolytic action of acetylcysteine.2
After administration of dornase alfa 2.5 mg by inhalation to cystic fibrosis patients, sputum concentrations were measurable within 15 minutes.1 When up to 10 mg of dornase alfa was inhaled 3 times daily in patients with cystic fibrosis for 6 consecutive days, significant elevations in DNase above normal endogenous levels were not observed.1 When 2.5 mg of dornase alfa was administered 2 times daily to patients with cystic fibrosis for 6 months, no accumulation of serum DNase was observed.1 Dornase alfa is expected to undergo metabolism via proteases present in biological fluids.1 The elimination half-life of IV administered dornase alfa is 3-4 hours.1
Additional Information
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information. The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.
Please refer to the ASHP Drug Shortages Resource Center for information on shortages of one or more of these preparations.
1. Genentech, Inc. Pulmozyme® (dornase alfa) inhalation solution prescribing information. South San Francisco, CA; 2024 Feb.
2. Shak S, Capon DJ, Hellmiss R et al. Recombinant human DNase I reduces the viscosity of cystic fibrosis sputum. Proc Natl Acad Sci USA . 1990; 87:9188-92. [PubMed 2251263]
3. Zahm JM, de Bentzmann S, Deneuville E et al. Recombinant human DNase I improves the transport of cystic fibrosis respiratory mucus ex vivo. Pediatr Pulmonol . 1993; Suppl 9:250.
5. Hubbard RC, McElvaney NG, Birrer P et al. A preliminary study of aerosolized recombinant human deoxyribonuclease I in the treatment of cystic fibrosis. N Engl J Med . 1992; 326:812-5. [PubMed 1538726]
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9. Fuchs HJ, Borowitz D, Christiansen D et al. Aerosolized recombinant human DNase reduces pulmonary exacerbations and improves pulmonary function in patients with cystic fibrosis. Presented at the 36th Annual Conference on Chest Disease, Intermountain Thoracic Society. Snowbird, UT: 1993 Jan 26.
10. Ramsey BW, Astley SJ, Aitken ML et al. Efficacy and safety of short-term administration of aerosolized recombinant human deoxyribonuclease in patients with cystic fibrosis. Am Rev Respir Dis . 1993; 148:145-51. [PubMed 8317790]
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12. Ramsey B for the Pulmozyme® (rhDNase) Study Group. A summary of the results of the phase III multicenter clinical trial: aerosol administration of recombinant human DNase reduces the risk of respiratory tract infections and improves pulmonary function in patients with cystic fibrosis. Pediatr Pulmonol . 1993; Suppl 9:152-3.
13. Food and Drug Administration. Orphan designations pursuant to Section 526 of the Federal Food and Cosmetic Act as amended by the Orphan Drug Act (P.L. 97-414), to August 31, 1993. Rockville, MD; 1993 September.
14. Quan MP. Manufacturer letter regarding product information on Pulmozyme® (dornase alfa). South San Francisco, CA: Genentech, Inc; 1993 Aug 6.
15. Boucher RC. Drug therapy in the 1990s: what can we expect for cystic fibrosis? Drugs . 1992; 43:431-9.
19. Rubin BK, Ramirez OE, Baharav AL. The physical and transport properties of CF sputum after treatment with rhDNase. Pediatr Pulmonol . 1993; Suppl 9:251.
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27. Shah PL, Scott S, Geddes D et al. A preliminary report on using aerosolised recombinant human DNase I in the treatment of patients with stable stage cystic fibrosis for six months. Pediatr Pulmonol . 1993; Suppl 9:247.
28. Wilmott R, DNase Multicenter Study Group, Genentech Staff. A phase II, double-blind, multicenter study of the safety and efficacy of aerosolized recombinant human DNase I (rhDNase) in hospitalized patients with CF experiencing acute pulmonary exacerbations. Pediatr Pulmonol . 1993; Suppl 9:154.
29. Laube BL, Auci RM, Shields DE et al. A randomized, placebo-controlled trial of the effect of recombinant human DNase I (rhDNase) on the deposition homogeneity and mucociliary clearance of radioaerosol in patients with cystic fibrosis. Pediatr Pulmonol . 1993; Suppl 9:155-6.
33. Webb EC, preparer. Enzyme nomenclature 1992: recommendations of the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology on the nomenclature and classification of enzymes. San Diego, CA: Academic Press, Inc; 1992:339. ECC 3.1.21.1.
34. Armstrong JB, White JC. Liquefaction of viscous purulent exudates by deoxyribonuclease. Lancet . 1950; 1:739-42.
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39. Fuchs HJ, Borowitz DS, Christiansen DH, et al. Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group. N Engl J Med. 1994;331(10):637-642.
40. Yang C, Montgomery M. Dornase alfa for cystic fibrosis. Cochrane Database Syst Rev. 2021;3(3):CD001127. Published 2021 Mar 18.
41. Voldby C, Green K, Philipsen L, et al. Withdrawal of dornase alfa increases ventilation inhomogeneity in children with cystic fibrosis. J Cyst Fibros. 2021;20(6):949-956.
42. Rahman NM, Maskell NA, West A, et al. Intrapleural use of tissue plasminogen activator and DNase in pleural infection. N Engl J Med. 2011;365(6):518-526.
43. Piccolo F, Pitman N, Bhatnagar R, et al. Intrapleural tissue plasminogen activator and deoxyribonuclease for pleural infection. An effective and safe alternative to surgery. Ann Am Thorac Soc. 2014;11(9):1419-1425.
44. Majid A, Kheir F, Folch A, et al. Concurrent Intrapleural Instillation of Tissue Plasminogen Activator and DNase for Pleural Infection. A Single-Center Experience. Ann Am Thorac Soc. 2016;13(9):1512-1518.
45. Jiang C, Xie M, Cervellione K, Thurm C. Clinical efficacy and bleeding outcomes of tissue plasminogen activator and dornase alfa in pleural space infection with once daily concurrent administration: a retrospective cohort study. BMC Res Notes. 2020;13(1):368. Published 2020 Aug 3.
46. Mainz JG, Schien C, Schiller I, et al. Sinonasal inhalation of dornase alfa administered by vibrating aerosol to cystic fibrosis patients: a double-blind placebo-controlled cross-over trial. J Cyst Fibros. 2014;13(4):461-470.
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