Pulmozyme

Generic Name: Dornase Alfa
Class: Mucolytic Agents
ATC Class: R05CB13
VA Class: RE900
Chemical Name: Deoxyribonuclease
CAS Number: 9003-98-9

Introduction

Mucolytic agent; biosynthetic (recombinant DNA origin) form of human deoxyribonuclease I (DNase I).1 2 33

Uses for Pulmozyme

Cystic Fibrosis

Adjunctive therapy in patients with cystic fibrosis to reduce mucus viscosity and enable the clearance of airway secretions to improve pulmonary function (designated an orphan drug by FDA for this use).1 4 5 8 9 10 11 12 13 14 15 16 17 18 27 36

Slideshow: 2014 Update - First Time Brand-to-Generic Switches

Reduces the frequency of respiratory infections requiring parenteral anti-infective therapy in patients with forced vital capacity (FVC) ≥40%.1 4 5 8 9 10 11 12 14 15 16 17 18 27 36

Pulmozyme Dosage and Administration

Administration

Oral Inhalation

Administer by oral inhalation via nebulization once daily.1

Administer using a recommended nebulizer system; safety and efficacy of dornase alfa inhalation solution administered by a nebulizer system other than those listed below not established.1 1

Use in patients unable to inhale or exhale orally throughout the entire nebulization period.1

Recommended Nebulizer and Compression Systems

Nebulizer

Compressor

Hudson T Up-draft II with

Pulmo-Aide

Marquest Acorn II with

Pulmo-Aide

PARI LC Jet+ with

PARI PRONEB

PARI BABY with

PARI PRONEB

Durable Sidestream with

Porta-Neb

Durable Sidestream with

MOBILAIRE

Oral inhalation solution should not be diluted nor mixed with any other drugs in the nebulizer.1

Empty the entire contents of the single-use ampul of solution into the nebulizer cup; attach the cup to the inhalation apparatus according to the manufacturer’s instructions.1 32

Place the mouthpiece of the nebulizer in the mouth and turn on the compressor.32 Breathe calmly and evenly through the mouth until the nebulizer stops producing a mist (duration of treatment for full dose is approximately 10–15 minutes).32

Clean the nebulizer after use according to the manufacturer’s instructions.b

Oral inhalation solution contains no preservatives; once the single-use ampul is opened, use the entire contents or discard the remainder.1

Dosage

Each single-use ampul delivers 2.5 mg (2.5 mL of undiluted solution) to the nebulizer cup.1 35

Pediatric Patients

Cystic Fibrosis
Oral Inhalation

Children ≥5 years of age: 2.5 mg once daily.1 Some patients (e.g., those with FVC >85%) may benefit from 2.5 mg twice daily.1 35

Adults

Cystic Fibrosis
Oral Inhalation

2.5 mg once daily.1 Some patients (e.g., ≥21 years of age, those with FVC >85%) may benefit from 2.5 mg twice daily.1 35

Prescribing Limits

Pediatric Patients

Cystic Fibrosis
Oral Inhalation

In clinical studies, dosages >2.5 mg twice daily did not provide additional improvement in pulmonary function (e.g., FEV1).1 10

Safety and efficacy of daily administration for >12 months of continuous therapy not established.1

Adults

Cystic Fibrosis
Oral Inhalation

In clinical studies, dosages >2.5 mg twice daily did not provide additional improvement in pulmonary function (e.g., FEV1).1 10

Safety and efficacy of daily administration for >12 months of continuous therapy not established.1

Special Populations

No special population dosage recommendations at this time.a

Cautions for Pulmozyme

Contraindications

Known hypersensitivity to dornase alfa, Chinese hamster ovary cell-derived products, or any ingredient in the formulation.a

Warnings/Precautions

General Precautions

Adjunct to and not a replacement for standard therapies (e.g., chest physical therapy, anti-infectives, bronchodilators, oral enzyme supplements, vitamins, oral and/or inhaled corticosteroids, analgesics); continue such therapies during enzyme therapy.1 31

Specific Populations

Pregnancy

Category B.a

Lactation

Not known whether dornase alfa is distributed into milk; caution if used in nursing women.a

Pediatric Use

Limited experience in patients <5 years of age; use only in those in whom there is a potential for benefit in pulmonary function or in risk of respiratory tract infection.1

Increased incidence of cough, rhinitis, and rash in children <5 years of age compared with children ≥5 years of age.1

Geriatric Use

Insufficient experience in patients ≥65 years of age to determine whether geriatric patients respond differently than younger adults.a

Common Adverse Effects

Pharyngitis, chest pain, voice alteration (e.g., hoarseness), rash, conjunctivitis.a

Interactions for Pulmozyme

No formal drug interaction studies to date; however, the manufacturer states that concomitant administration of dornase alfa and other standard therapies for cystic fibrosis is safe and effective.a

Pulmozyme Pharmacokinetics

Absorption

Bioavailability

Following oral inhalation, serum DNase concentrations were not increased above normal endogenous levels.a

Onset

Following oral inhalation, mean sputum DNase concentrations measurable within 15 minutes.a Improvement in pulmonary function (FEV1) evident within 8 days.a

Distribution

Extent

Not known whether dornase alfa crosses the placenta or is distributed into milk.a

Stability

Storage

Oral

Inhalation Solution

2–8°C; protect from light and excessive heat.a b Store ampuls in protective foil pouch to protect from light until used.a Discard if left at room temperature for ≥24 hours.b

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 35 nor does it affect pulmonary function in healthy individuals.8

  • Reduces sputum viscosity and viscoelasticity.1 2 3 15 20

  • 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 forced vital capacity 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

  • Importance of providing patient a copy of manufacturer’s patient information.b

  • Importance of adequate understanding of proper storage, preparation, and inhalation techniques, including use of the nebulization delivery system.b

  • Importance of thoroughly washing hands with soap and water before handling drug and nebulizer to avoid microbial contamination.b

  • Importance of adhering to daily dosing schedule and concomitant therapies, including not exceeding the recommended dose or frequency of use unless otherwise instructed by a clinician.b

  • Importance of not diluting or mixing with other drugs in the nebulizer.1

  • Importance of women informing their clinician if they are or plan to become pregnant or plan to breast-feed.1

  • Importance of informing patients of other important precautionary information.a (See Cautions.)

Preparations

Excipients in commercially available drug preparations may have clinically important effects in some individuals; consult specific product labeling for details.

Dornase Alfa

Routes

Dosage Forms

Strengths

Brand Names

Manufacturer

Oral Inhalation

Solution, for nebulization

1 mg/mL (2.5 mg)

Pulmozyme

Genentech

Comparative Pricing

This pricing information is subject to change at the sole discretion of DS Pharmacy. This pricing information was updated 02/2014. Actual costs to patients will vary depending on the use of specific retail or mail-order locations and health insurance copays.

Pulmozyme 1MG/ML Solution (GENENTECH): 75/$2,325.11 or 150/$4,546.85

AHFS DI Essentials. © Copyright, 2004-2014, Selected Revisions April 1, 2010. American Society of Health-System Pharmacists, Inc., 7272 Wisconsin Avenue, Bethesda, Maryland 20814.

References

1. Genentech, Inc. Pulmozyme (dornase alfa) inhalation solution prescribing information. South San Francisco, CA; 2001 Jan.

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.

4. Collins FS. Cystic fibrosis: molecular biology and therapeutic implications. Science. 1992; 256:774-9. [PubMed 1375392]

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. [IDIS 293048] [PubMed 1538726]

6. Rubin BK. Aerosolized recombinant human deoxyribonuclease I in the treatment of cystic fibrosis. N Engl J Med. 1992; 327:571. [IDIS 300805] [PubMed 1635583]

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. [IDIS 294316] [PubMed 1548827]

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. [IDIS 316737] [PubMed 8317790]

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. [IDIS 318293] [PubMed 8100928]

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.

16. Wallace CS, Hall M, Kuhn RJ. Pharmacologic management of cystic fibrosis. Clin Pharm. 1993; 12:657-74. [IDIS 319124] [PubMed 8306566]

17. Fiel SB. Clinical management of pulmonary disease in cystic fibrosis. Lancet. 1993; 341:1070-4. [IDIS 313065] [PubMed 8096969]

18. Gibaldi M. Understanding and treating some genetic diseases. Ann Pharmacother. 1992; 26:1589-94. [IDIS 306629] [PubMed 1482818]

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.

21. Mucolytics. In: Goodman LS, Gilman A, Gilman AG et al, eds. Goodman and Gilman’s the pharmacological basis of therapeutics. 5th ed. New York: Macmillan Publishing Company; 1975:955-6.

22. Lieberman J. Dornase aerosol effect on sputum viscosity in cases of cystic fibrosis. JAMA. 1968; 205:114-5. [PubMed 5694890]

23. Lieberman J. The appropriate use of mucolytic agents. Am J Med. 1970; 49:1-4. [PubMed 4246985]

24. Puckett WH Jr. The pharmacist and inhalation therapy. Am J Hosp Pharm. 1972; 29:556-63. [PubMed 5052020]

25. Raskin P. Bronchospasm after inhalation of pancreatic dornase. Am Rev Respir Dis. 1968; 98:697-8. [PubMed 4877872]

26. Morice AH. Which DNase in cystic fibrosis? Lancet. 1993; 342:624-5. Letter.

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.

30. Shah PL, Scott SF, Hodson ME. Report on a multicentre study using aerosolised recombinant human DNase I in the treatment of cystic fibrosis patients with severe pulmonary disease. Pediatr Pulmonol. 1993; Suppl 9:157.

31. Magnuson DE. Dear hospital pharmacist letter regarding the use of Pulmozyme in the management of patients with cystic fibrosis. South San Francisco, CA: Genentech, Inc; 1994 Jan 5.

32. Genentech, Inc. Patient information booklet: your guide to Pulmozyme (dornase alfa) therapy for cystic fibrosis (CF). South San Francisco, CA; 1994.

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.

35. Genentech, South San Francisco, CA: Personal communication.

36. Genentech, Inc. Pulmozyme (dornase alfa) recombinant inhalation solution prescribing information. South San Francisco, CA; 1996 Nov.

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. [IDIS 373898] [PubMed 8874241]

38. Kanga JF. Dornase alfa therapy in cystic fibrosis: who should get it? Chest. 1996; 110:871-2. Editorial.

a. Genentech, Inc. Pulmozyme (dornase alfa) inhalation solution prescribing information. South San Francisco, CA; 2005 Apr.

b. Genentech, Inc. Pulmozyme (dornase alfa) inhalation solution information for the patient/parent. South San Francisco, CA; 2001 Jan.

Hide
(web4)