Dornase Alfa

Pronunciation

(DOOR nase AL fa)

U.S. Brand Names

Pulmozyme®

Synonyms

DNase; Recombinant Human Deoxyribonuclease

Generic Available

No

Canadian Brand Names

Pulmozyme™

Use

Management of cystic fibrosis patients to reduce the frequency of respiratory infections that require parenteral antibiotics, and to improve pulmonary function

Use - Unlabeled/Investigational

Treatment of chronic bronchitis

Pregnancy Risk Factor

B

Lactation

Excretion in breast milk unknown

Contraindications

Hypersensitivity to dornase alfa, Chinese hamster ovary cell products (eg, epoetin alfa), or any component of the formulation

Warnings/Precautions

No clinical trials have been conducted to demonstrate safety and effectiveness of dornase in patients with pulmonary function <40% of normal or in patients for longer treatment periods >12 months; no data exists regarding safety during lactation

Adverse Reactions

>10%:

Respiratory: Pharyngitis

Miscellaneous: Voice alteration

1% to 10%:

Cardiovascular: Chest pain

Dermatologic: Rash

Ocular: Conjunctivitis

Respiratory: Laryngitis, cough, dyspnea, hemoptysis, rhinitis, hoarse throat, wheezing

Drug Interactions

Dornase alfa can be effectively and safely used in conjunction with standard CF therapies including oral, inhaled, and parenteral antibiotics, bronchodilators, enzyme supplements, vitamins, oral and inhaled corticosteroids, and analgesics. No formal drug interaction studies have been performed.

Stability

Must be stored in the refrigerator at 2°C to 8°C (36°F to 46°F) and protected from strong light; should not be exposed to room temperature for a total of 24 hours

Compatibility

Should not be diluted or mixed with any other drugs in the nebulizer, this may inactivate the dornase alfa.

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.

Pharmacodynamics/Kinetics

Onset of action: Nebulization: Enzyme levels are measured in sputum in ~15 minutes

Duration: Rapidly declines

Dosage

Inhalation:

Children >3 months to Adults: 2.5 mg once daily through selected nebulizers; experience in children <5 years is limited

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.

Administration

Nebulization: Should not be diluted or mixed with any other drugs in the nebulizer, this may inactivate the drug

Patient Education

Inform prescriber of any allergies you have. Use exactly as directed by prescriber (see following administration information). Report any signs of adverse response, skin rash, sore throat, respiratory wheezing, cough, or respiratory difficulty. Breast-feeding precaution: Consult prescriber if breast-feeding.

Self-administered nebulizer: Store in refrigerator, away from light. Do not combine with any other medications in the nebulizer. Wash hands before and after treatment. Wash and dry nebulizer after each treatment. Twist open the top of one unit dose vial and squeeze contents into nebulizer reservoir. Connect nebulizer reservoir to the mouthpiece or face mask. Connect nebulizer to compressor. Sit in comfortable, upright position. Put on face mask and turn on compressor. Avoid leakage around the mask to avoid mist getting into eyes. Breathe calmly and deeply until no more mist is formed in nebulizer (about 5 minutes). At this point treatment is finished.

Dental Health: Effects on Dental Treatment

Key adverse event(s) related to dental treatment: Pharyngitis.

Dental Health: Vasoconstrictor/Local Anesthetic Precautions

No information available to require special precautions

Mental Health: Effects on Mental Status

None reported

Mental Health: Effects on Psychiatric Treatment

None reported

Dosage Forms

Solution for nebulization: 1 mg/mL (2.5 mL)

References

Albertson TE, Walby WF, Allen RP, et al, "The Pharmacology and Toxicology of Three New Biologic Agents Used in Pulmonary Medicine,"J Toxicol Clin Toxicol, 1995, 33(5):427-38.

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,"N Engl J Med, 1994, 331(10):637-42.

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(12):812-5.

Mueller GA, Rubins G, Wessel D, et al, "Effects of Dornase Alfa on Pulmonary Function Tests in Infants with Cystic Fibrosis,"Am J Respir Crit Care Med, 1996, 153:A70.

Rock M, Kirchner K, McCubbin M, et al, "Aerosol Delivery and Safety of rhDNASE in Young Children With Cystic Fibrosis: A Bronchoscopic Study,"Pediatr Pulmonol, 1996, 13(Suppl):A268.

International Brand Names

Pulmozyme® (AR, AT, AU, BE, BR); Pulmozyme™ (CA); Pulmozyme® (CH, CZ, DE, DK, ES, FI, FR, GB, HR, HU, IE, IL, IT, LU, MX, NL, NO, NZ, PL, PT, RO, RU, SE, SI, TR, ZA); Pulmozymev® (CO, PL); Viscozyme® (CL)