Dornase Alpha

Dornase Alpha belongs to the pharmacological class of Mucolytic, a synthetic form of human deoxyribonuclease I.

Dornase Alpha is completely absorbed through the inhalation route. The onset of action of Dornase Alpha is achieved within 3 to 7 days, whereas the peak concentrations are achieved after nine days. A human intravenous dose study had suggested an elimination half-life of about 3-4 hours for dornase alpha.

The common side effects of Dornase Alpha are rash, laryngitis, sore/dry throat and hoarseness, eye inflammation, runny or stuffy nose, eye redness, and irritation.

Dornase Alpha is found to be available in the form of inhalation Solution.

Dornase Alpha is available in the U.S., Canada, E.U., India, Australia, and Japan.

Dornase Alpha belongs to the pharmacological class of Mucolytic, which is a synthetic form of human deoxyribonuclease I.

A dornase alfa is a biosynthetic form of human DNase I. The enzyme is involved in the endonucleolytic cleavage of an extracellular DNA to 5´-phosphodinucleotide as well as 5´-phosphooligonucleotide end products. It had no effect on the intracellular DNA. The optimal activity is dependent on the presence of some divalent cations such as calcium as well as magnesium. Extracellular DNA is said to be a viscous anionic polymer, as well as its breakdown appears to improve the viscosity and viscoelasticity of the purulent sputum of individuals with Cystic Fibrosis, thus reducing the airflow obstruction.

Dornase Alpha has been approved for relieving symptoms as well as also for the treatment and maintenance of episodes of Cystic Fibrosis and Parapneumonic effusions, complicated and empyema (off-label use).

The onset of action of Dornase alpha is achieved after 3-7 days, and peak action of Dornase alpha is achieved in 9 days.

Dornase Alpha is available in Inhalation Solution.

Dornase Alpha can be used in the treatment of the following conditions:

• Cystic Fibrosis
• Parapneumonic effusions, complicated and empyema (off-label use)

Dornase Alpha can help to relieve symptoms and also for the treatment and maintenance of cystic fibrosis and Parapneumonic effusions, complicated and empyema (off-label use).

Dornase Alpha is approved for the treatment in the following clinical indications/conditions:

• Cystic fibrosis
• Parapneumonic effusions, complicated and empyema (off-label use)

Inhalation Solution

1. Dornase alfa inhalation solution comes in the form of small plastic containers called ampules and each ampule contains one full dose of dornase alfa. Already used ampules should not be used. Cloudy or discolored inhalation solution should not be used.
2. The ampule should be removed from the pouch. The inhalation solution should be placed in the medicine reservoir or the nebulizer cup on the machine.
3. The nebulizer should be connected to the face mask or mouthpiece, then the nebulizer should be connected to the compressor.
4. Use the mouthpiece of the nebulizer for breathing in Dornase Alpha. The face mask should not be used with the nebulizer because less medicine will get into the lungs.
5. Patients who are not able to breathe in or breathe out by mouth might use the PARI BABY nebulizer with the supplied face mask. Make sure the patient or the person who administers understands exactly how to use this medicine in the nebulizer.( PARI BABY masks are designed specifically for the low inspiratory flow rate and small tidal volumes of babies and young children because babies and young children don’t stay in one position. Compatible with all PARI reusable nebulizers, the PARI Baby mask and rotating elbow offer efficient aerosol delivery in almost any position as well as they are available in four different sizes).
6. The nebulizer should be used for about 10 to 15 minutes or until the medicine in the nebulizer cup is used.
7. Follow the manufacturer's directions for the care and cleaning of the nebulizer and compressor.
8. Do not mix any other medicine in the nebulizer with dornase alfa.

Inhalation Solution

1mg/mL (2.5mL)

Inhalation Solution

Smoking cessation and maintaining health are a must.

Caffeine should be avoided or limited to use as it might lead to the risk of nausea, palpitations, nervousness, rapid heartbeat, etc.

Alcohol intake should be avoided in patients, especially those with an underlying liver disorder or liver dysfunction.

The dietary restrictions should be individualized as per the patient's requirements.

Dornase Alpha may be contraindicated under the following conditions:

• Hypersensitive to the ingredients of the medication

Dornase alfa should be used in conjunction with standard therapies for cystic fibrosis (CF).

Patients should be instructed in the proper use and maintenance of the nebulizer and compressor system used in its delivery.

Avoid alcohol usage while on Dornase Alpha medication, as alcohol can worsen the effects of any underlying disease condition, including conditions such as dizziness, blurred vision, etc.

Safety and efficacy have not been established.

Data has not been established.

No sufficient scientific evidence is traceable regarding the use and safety of Dornase Alpha in concurrent use with any particular food.

The adverse reactions related to Dornase Alpha can be categorized as follows:

More common

• Dryness or soreness of the throat
• Fever
• Chest pain
• Congestion
• Hoarseness
• Runny nose
• Tender, swollen glands in the neck
• Body aches or pain
• Cough
• Trouble breathing
• Trouble swallowing
• Voice changes

Less common

• Discharge or excessive tearing
• Heartburn
• Acid or sour stomach
• Burning, dry, or itching eyes
• Indigestion
• Belching
• Redness, pain, or swelling of the eye, eyelid, or inner lining of the eyelid
• Stomach discomfort, upset, or pain

No formal drug interaction studies have been performed.

The common side effects of Dornase Alpha include the following:

• Rash
• Laryngitis
• Sore/dry throat and hoarseness
• Eye inflammation
• Runny or stuffy nose
• Eye redness and irritation

Pregnancy

Data has not been established

Nursing Mothers

Safety and efficacy have not been established

Pediatric Use

Safety and efficacy for less than five years old have not been established.

Geriatric Use

Cystic fibrosis is said to be primarily a disease of children as well as young adults. Clinical studies of Dornase Alpha did not include sufficient numbers of subjects who were aged 65 or older in order to determine whether they respond differently from younger subjects.

Physicians should be knowledgeable and vigilant about the treatment pertaining to the treatment and identification of overdosage of Dornase Alpha.

Single-dose inhalation studies in rats as well as monkeys at doses up to one hundred and eighty times higher than doses which are routinely used in clinical studies are well tolerated. Single-dose oral administration of Dornase Alpha in doses up to 200 mg/kg is also well tolerated by rats.

Cystic fibrosis patients had received up to 20 mg BID for up to 6 days and 10 mg BID intermittently (2 weeks on/2 weeks off drug) for 168 days. These doses were well tolerated.

Pharmacodynamics

Cystic fibrosis (CF) is said tom be a disease which is characterized by the retention of viscous purulent secretions in the airways. These thick secretions therefore contributes both to reduced pulmonary function as well as to frequent pulmonary infection. Purulent pulmonary secretions of individuals suffering from cystic fibrosis contain a high concentrations of extracellular DNA which when released by degenerating leukocytes that accumulate in response to such infections. Dornase alfa is said to hydrolyze the DNA in the sputum of Cystic Fibrosis patients and reduces sputum viscosity as well as viscoelasticity. The enzyme does not appear to have affected the sputum in the absence of an inflammatory response to the infection, nor does it affect the sputum of healthy individuals.

Pharmacokinetics

• Absorption

Studies in rats as well as monkeys after the inhalation of dornase alfa shows very little systemic absorption i.e.less than 15% for rats and less than 2% for monkeys. The results were also witnessed in humans. Dornase alfa is also said to be associated with a very low accumulation, with no serum concentration which is greater than 10ng/mL has been observed no matter the dose administered. Bioavailability which is mean sputum concentrations of dornase alfa can be measured after 15 minutes. Onset of action is achieved within 3 to 7 days. Peak concentrations are achieved after nine days.

• Volume of distribution

In studies in rats as well as in monkeys, the initial volume of distribution is found to be similar to the serum volume. Concentrations in sputum decline rapidly after inhalation.

• Metabolism

As no conclusive studies have yet been published, dornase alfa might be metabolized by proteases in biofluids.

1. https://www.mayoclinic.org/drugs-supplements/dornase-alfa-inhalation-route/proper-use/drg-20063509
2. https:/https://go.drugbank.com/drugs/DB00003/
3. www.accessdata.fda.gov/drugsatfda_docs/label/2014/103532s5175lbl.pdf
4. https://www.Dornase Alpha.com/patient/about-Dornase Alpha/how-it-works.html