Dornase Alfa (Oral Inhalation) (Monograph)
Brand name: Pulmozyme
Drug class: Mucolytic Agents
Introduction
Mucolytic agent; biosynthetic (recombinant DNA origin) form of human deoxyribonuclease I (DNase I).1 2 33
Uses for Dornase Alfa (Oral Inhalation)
Cystic Fibrosis
Adjunctive therapy in pediatric and adult patients with cystic fibrosis to improve pulmonary function.1 37 39 40 41
Reduces the frequency of respiratory infections requiring parenteral anti-infective therapy in patients with forced vital capacity (FVC) ≥40%.1
Designated an orphan drug by FDA for this use.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
Parapneumonic Effusions and Empyema
Although safety and efficacy not established, limited data suggest dornase alfa may be used intrapleurally in conjunction with alteplase for complicated parapneumonic effusions and empyema† [off-label].42 43 44 45
Chronic Rhinosinusitis Secondary to Cystic Fibrosis
Although safety and efficacy not established, limited data suggest dornase alfa may be used for the treatment of chronic rhinosinusitis secondary to cystic fibrosis in pediatric patients† [off-label] .46
Related/similar drugs
azithromycin, Zithromax, gentamicin, Creon, tobramycin
Dornase Alfa (Oral Inhalation) Dosage and Administration
General
Other General Considerations
-
Only administer dornase alfa with specific jet nebulizers and nebulizer systems listed in the manufacturer’s product labeling.1 Data are not available to support the administration of dornase alfa with other nebulizer systems.1
Administration
Oral Inhalation
Administer by oral inhalation via nebulization.1
Administer using a recommended jet nebulizer/compressor system (see Table) or using the eRapid™ Nebulizer System (consisting of the eRapid™ Nebulizer Handset with eBase™ Controller); safety and efficacy of dornase alfa inhalation solution administered via other nebulizer systems not established.1 If using the eRapid™ Nebulizer System, the handset should be replaced after 90 uses.1
Jet Nebulizer |
Compressor |
---|---|
Hudson T Up-draft II |
Pulmo-Aide or legally marketed compressor of identical pressure and flow rate |
Marquest Acorn II |
Pulmo-Aide or legally marketed compressor of identical pressure and flow rate |
PARI LC Plus |
PARI PRONEBor legally marketed compressor of identical pressure and flow rate |
PARI BABY |
PARI PRONEB or legally marketed compressor of identical pressure and flow rate |
Durable Sidestream |
Porta-Neb ,MOBILAIRE , or legally marketed compressor of identical pressure and flow rate |
Do not dilute or mix the oral inhalation solution with any other drugs in the nebulizer.1
Clean the nebulizer after use according to the manufacturer’s instructions.1 Consult Instructions for Use provided by the manufacturer for detailed information on proper administration techniques via various nebulization systems.1
Oral inhalation solution contains no preservatives; once the single-use ampule is opened, use the entire contents or discard the remainder.1
Dosage
Each single-use ampule delivers 2.5 mg of dornase alfa (2.5 mL of undiluted solution).1
Pediatric Patients
Cystic Fibrosis
Oral Inhalation
2.5 mg once daily.1 Some patients may benefit from twice daily administration.1
Adults
Cystic Fibrosis
Oral Inhalation
2.5 mg once daily.1 Some patients may benefit from twice daily administration.1
Special Populations
Hepatic Impairment
No specific dosage recommendations at this time.1
Renal Impairment
No specific dosage recommendations at this time.1
Geriatric Use
No specific dosage recommendations at this time.1
Cautions for Dornase Alfa (Oral Inhalation)
Contraindications
Known hypersensitivity to dornase alfa, Chinese hamster ovary cell products, or any ingredient in the formulation.1
Warnings/Precautions
Specific Populations
Pregnancy
No adequate and well-controlled studies 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
Lactation
Not known whether dornase alfa distributed into human milk.1 Consider developmental and health benefits of breastfeeding along with mother’s clinical need for the drug and the potential for adverse effects to the breast-fed child.1
Pediatric Use
Safety and efficacy established in pediatric patients.1 Use of dornase alfa in pediatric patients 5–17 years of age supported by evidence from a clinical trial.1 Use of dornase alfa in pediatric patients <5 years of age supported by extrapolated efficacy data from pediatric patients ≥5 years of age and additional safety data.1
Geriatric Use
Clinical studies did not include sufficient numbers of patients ≥65 years of age.1
Hepatic Impairment
Not evaluated in hepatic impairment.1
Renal Impairment
Not evaluated in renal impairment.1
Common Adverse Effects
Adverse effects (≥3%): voice alteration, pharyngitis, rash, laryngitis, chest pain, conjunctivitis, rhinitis, decrease in FVC ≥10%, fever, dyspnea.1
Drug Interactions
Manufacturer states no clinically significant drug-drug interactions.1
Dornase Alfa (Oral Inhalation) Pharmacokinetics
Absorption
Bioavailability
Following oral inhalation, serum DNase concentrations were not increased above normal endogenous levels.1
Onset
After oral inhalation, sputum concentrations measurable within 15 minutes.1
Distribution
Extent
Not known whether distributed into human milk.1
Elimination
Metabolism
Expected to undergo metabolism via proteases in biological fluids.1
Half-life
3-4 hours after IV administration.1
Stability
Storage
Oral Inhalation
Solution for nebulization
Store in protective foil at 2-8ºC; keep refrigerated during transport, and do not expose to room temperature for ≥24 hours total.1
Actions
-
Selectively cleaves extracellular DNA (e.g., in purulent pulmonary secretions);1 2 5 33 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
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Mechanism of action not fully elucidated;6 7 appears to improve the transportability of purulent mucus via ciliary activity and cough.3 19
-
Reduces airflow obstruction, improves pulmonary function (increased FVC and forced expiratory volume at 1 second [FEV1]), and improves mucociliary clearance in patients with cystic fibrosis.1 5 8 9 10 11 12 14 27 29
Advice to Patients
-
Advise patients and caregivers on the proper storage of dornase alfa; must be stored in the refrigerator and protected from heat and light.1 Refrigerate dornase alfa during transport, and do not allow it to be exposed to room temperature for more than 24 hours total.1
-
Instruct patients and caregivers to squeeze ampules prior to each use to check for leaks, and to discard the ampule if the solution appears cloudy or discolored.1 Once the ampule is opened, the contents must be used immediately or discarded.1
-
Inform patients and caregivers that dornase alfa must not be diluted or mixed with other drugs in the nebulizer.1
-
Advise patients and caregivers to perform proper maintenance of the jet nebulizer/compressor system or eRapid™ Nebulizer System.1
-
Instruct patients and caregivers to read and follow the dornase alfa Instructions for Use and the Manufacturer’s eRapid™ Nebulizer System Instruction Booklet.1
-
Instruct patients and caregivers to replace the eRapid™ handset after 90 uses; data are not available for the administration of dornase alfa with the eRapid™ handset beyond 90 administrations.1
-
Advise women to inform their clinician if they are or plan to become pregnant or plan to breast-feed.1
-
Advise patients to inform their clinician of existing or contemplated concomitant therapy, including prescription and OTC drugs and dietary and herbal supplements, as well as any concomitant illnesses.1
-
Advise patients of other important precautionary information.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.
Preparations
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.
Routes |
Dosage Forms |
Strengths |
Brand Names |
Manufacturer |
---|---|---|---|---|
Oral Inhalation |
Solution, for nebulization |
1 mg/mL (2.5 mg) |
Pulmozyme |
Genentech |
AHFS DI Essentials™. © Copyright 2024, Selected Revisions October 26, 2023. American Society of Health-System Pharmacists, Inc., 4500 East-West Highway, Suite 900, Bethesda, Maryland 20814.
† Off-label: Use is not currently included in the labeling approved by the US Food and Drug Administration.
References
1. Genentech, Inc. Pulmozyme (dornase alfa) inhalation solution prescribing information. South San Francisco, CA; 2021 July.
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. http://www.ncbi.nlm.nih.gov/pubmed/2251263?dopt=AbstractPlus
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. http://www.ncbi.nlm.nih.gov/pubmed/1538726?dopt=AbstractPlus
6. Rubin BK. Aerosolized recombinant human deoxyribonuclease I in the treatment of cystic fibrosis. N Engl J Med. 1992; 327:571. http://www.ncbi.nlm.nih.gov/pubmed/1635583?dopt=AbstractPlus
7. Hubbard RC, Shak S, Crystal RG. Aerosolized recombinant human deoxyribonuclease I in the treatment of cystic fibrosis. N Engl J Med. 1992; 327:571.
8. Aitken ML, Burke W, McDonald G et al. Recombinant human DNase inhalation in normal subjects and patients with cystic fibrosis: a phase 1 study. JAMA. 1992; 267:1947-51. http://www.ncbi.nlm.nih.gov/pubmed/1548827?dopt=AbstractPlus
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. http://www.ncbi.nlm.nih.gov/pubmed/8317790?dopt=AbstractPlus
11. Ranasinha C, Assoufi B, Shak S et al. Efficacy and safety of short-term administration of aerosolised recombinant human DNase I in adults with stable stage cystic fibrosis. Lancet. 1993; 342:199-202. http://www.ncbi.nlm.nih.gov/pubmed/8100928?dopt=AbstractPlus
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.
20. Shak S, King M. Effects of rhDNase on cystic fibrosis sputum viscoelasticity in vitro. Pediatr Pulmonol. 1993; Suppl 9:251.
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.
37. McCoy K, Hamilton S, Johnson C. Effects of 12-week administration of dornase alfa in patients with advanced cystic fibrosis lung disease. Chest. 1996; 110:889-95. http://www.ncbi.nlm.nih.gov/pubmed/8874241?dopt=AbstractPlus
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.
1000. Mogayzel PJ Jr, Naureckas ET, Robinson KA, et al. Cystic fibrosis pulmonary guidelines. Chronic medications for maintenance of lung health. Am J Respir Crit Care Med. 2013;187(7):680-689.
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