Continuing Education Activity

Dornase alfa is a medication used in the management and treatment of cystic fibrosis. It is in the category B class of drugs. This activity outlines the indications, action, and contraindications for dornase alfa as a valuable agent in the therapy of cystic fibrosis as well as pleural effusion and emphysema.

Objectives:

• Describes the mechanism of action and administration of dornase alfa.
• Identifies the common adverse effects and contraindications of dornase alfa.
• Summarizes the monitoring needs and toxicity of dornase alfa.
• Outline the importance of improving collaboration and communication amongst the interprofessional team to improve outcomes for patients receiving dornase alfa.

Indications

Dornase alfa is utilized in the treatment and management of cystic fibrosis (CF) in conjunction with standard therapies. Dornase alfa was discovered in 1992 as a mucolytic agent for the treatment of hyper viscous mucous produced in patients with CF, after noticing in the 1950s that the use of bovine deoxyribonuclease decreased the thickness of the sputum in CF patients.[1]

There are also several studies performed in demonstrating the use of dornase alfa in non-CF patients.  It is used off-label for the treatment of parapneumonic pleural effusions and empyemas. In 2015, Bobeck and colleagues showed that Dornase alfa could be used in patients with pleural empyema to improve drainage of hyper viscous pus when used in combination with tissue plasminogen activator (tPA). However, first, it should be confirmed that the drainage is hyper-viscous by using a drop rate count from the syringe.[2] In 2016, another study demonstrated that the use of dornase alfa was beneficial in patients with atelectasis and was routinely used without any safety concerns.[3] In 2017, there was a pilot study performed in assessing the efficacy of using dornase alfa in premature patients with ventilator-associated pulmonary infection (VAPI) compared to the standard treatment. The conclusion that deoxyribonuclease uses in preterm infants with VAPI increased fraction of inspired oxygen (FiO2) without any side effects.[4]

Mechanism of Action

Normally, the cilia that line the respiratory tract are responsible for continuously pushing the thin film of mucus which traps different invaders and duct particle upwards for excretion via cough. Due to the abnormally thick mucus produced in the lungs of a patient with CF, the mucociliary escalator is significantly affected. This condition leads to the colonization of bacterial infection, especially, pseudomonas, which induces inflammation and accumulation of neutrophils in the affected area. After the initial response, neutrophils die, and that leads to an increased amount of highly polymerized DNA in the mucous that leads to even further thickening of the mucous. The presence of DNA material in the mucous results in the plugging of the patient’s airway and also further increases the risk of infection. Repeated endobacterial infection and damage due to the neutrophils’ oxidants lead to irreversible damage and, eventually, respiratory failure, which is the most common cause of death in patients with CF.[1]

Dornase alfa cleaves the DNA released from the neutrophils and reduce mucous viscosity and further prevent airway infections and damage to the lung parenchyma. Overall, improving the pulmonary function.

Administration

For adults: inhale 2.5 mg once a day daily via a selected nebulizer system.

For pediatrics: 

• For infants and children under 2: inhale 2.5 mg once a day daily via selected nebulizer system [1]
• For children 2 to 5: inhale 2.5 mg once a day daily via a selected nebulizer system [5]
• For children over 5 and adolescents: inhale 2.5 mg once a day daily via selected jet nebulizer along with compressor system or a nebulizer system [6] 

For parapneumonic pleural effusion and emphysema (off label use):

Intrapleural (off label use): dornase alfa is administered intrapleural 5 mg twice per day for a total of three days. For sequential dosing, (tPa) and dornase alfa is diluted in 30 mL of sterile water and instilled into the chest tube. Dornase alfa must be administered more than 2 hours after administration of intrapleural (tPA) and allowed dwell time of one hour. The chest tube is clamped and released after one hour, and the suction is turned on.[7] For concurrent administration, tPA and dornase, each is diluted in 50 mL of normal saline. Dornase alfa is instilled right after the tPA, followed by 60 mL of normal saline flush. Then the chest tube is clamped and released after two hours of dwell time.[8]

Adverse Effects

Most common: > 10%

• Voice alteration
• Pharyngitis, 
• Rhinitis
• Rash
• Chest pain

Less common: 1 to 10%

• Laryngitis
• Antibody development against Dornase alfa in up to 4%
• Conjunctivitis
• Dyspepsia

<1%

• Urticaria
• Headache

Even though rash and urticaria have been observed in some patients, there have been o reports of anaphylaxis.[9]

Contraindications

It is contraindicated in patients who have had hypersensitivity reactions or with the use of Chinese hamster ovary cell products, or any product containing these ingredients.

Monitoring

Due to the poor systemic absorption of dornase alfa, there is no required hepatic or renal monitoring; however, it is important to follow up with the patients for any side effects and to ensure administration of the proper dose.

Additionally, a preliminary study done by the Cystic Fibrosis Foundation in 2013 focused on improving the FEV1 of the patient with CF. They provided strict guidelines for the use of dornase alfa and hypertonic saline for patients older than six years of age and prescribing inhaled tobramycin and oral azithromycin in patients older than six years of age with Pseudomonas aeruginosa infection. They monitored the adherence to the guidelines every quarter for one year. According to the early results, it demonstrated that adherence to the guidelines by clinicians increased the FEV1 in patients with CF.[10]

Toxicity

The likelihood of Dornase alfa related to systematic toxicity is rare due to its short half-life and poor systemic absorption. In isolated incidences of overdose where patients used 16 times the maximum daily dose tolerated the medication well.

Enhancing Healthcare Team Outcomes

Even though dornase alfa is safe due to its short half-life and poor systemic absorption, the healthcare team, including the physicians, pharmacists, and nurses, need to follow up with the patients to ensure the correct use of the drug. Since dornase alfa is used with a nebulizer compression system, it is crucial to assist patients in understanding how to use the medication to achieve its fullest effects properly. Physicians need to ensure that the patient is using a nebulizer with a mouthpiece to ensure the maximum drug delivery to the lungs. A patient that is unable to breathe in and out properly should not be using a mouthpiece. Instead, the recommendation should be to use a device that utilizes a face mask. Nurses and home aid healthcare personals also need to educate the patients not to combine dornase alfa with any other CF medications since it will decrease the efficacy of the drug. Interprofessional communication is essential in the care of CF patients with dornase alfa to make sure that the patient is receiving the most benefit with the least amount of side effects.