Pulmozyme

Mucolytics for Cystic Fibrosis

For storage information, see the specific product information within How Supplied section.

Intrapleural catheter injection†
NOTE: Dornase Alfa is not FDA-approved for injectable administration.
Preparation
Dilute 5 mg in 10 to 30 mL of 0.9% Sodium Chloride Injection.
 
Intrapleural Instillation
Inject via chest tube followed by 5 mL 0.9% Sodium Chloride flush and clamp chest tube for 1 hour, then allow to drain for 1 hour.

Nebulization Administration:
The manufacturer recommends that 1 of the following jet nebulizers/compressors or nebulizer systems be used to deliver dornase alfa:
Hudson T Up-draft II in conjunction with a Pulmo-Aide or legally marketed compressor of identical pressure and flow rate (max 30 psi, 12 LPM);
Marquest Acorn II in conjunction with a Pulmo-Aide or legally marketed compressor of identical pressure and flow rate (max 30 psi, 12 LPM);
PARI LC Plus in conjunction with a PARI PRONEB or legally marketed compressor of identical pressure and flow rate (max 24 psi, 9 LPM);
PARI BABY nebulizer in conjunction with a PARI PRONEB or legally marketed compressor of identical pressure and flow rate (max 24 psi, 9 LPM); this nebulizer can be used in patients unable to inhale or exhale orally throughout the treatment period;
Durable Sidestream in conjunction with a MOBILAIRE, Porta-NEB, or legally marketed compressor of identical pressure and flow rate (max 45 psi, 7 LPM);
eRapid Nebulizer System consisting of the eRapid Nebulizer Handset with eBase Controller. When used for dornase alfa administration, replace the handset after 90 uses, regardless of whether the EasyCare cleaning aid is used. Delivery data is not available for dornase alfa administered beyond 90 administrations, and appropriate therapeutic dose delivery cannot be assured. Only use in patients who can use a mouthpiece; do not use for patients who require a mask for administration.
Safety and efficacy have been demonstrated with these machines; there are no clinical data to support the use of dornase alfa with other nebulizer systems.
Advise the patient to follow the manufacturer's instructions for use and maintenance of equipment.
In order to avoid adverse physicochemical and/or functional changes, do not dilute or mix dornase alfa with other drugs in the nebulizer.

Oral inhalation via nebulization:
Empty entire contents of the single-use ampule into the nebulizer cup and attach cup to the nebulizer according to the manufacturer's instruction. Discard any unused portions because the inhalation solution contains no preservatives.
Instruct patient on proper inhalation technique (see manufacturer's labeling). Breathe through the mouth; do not breathe through the nose. A nose clip may be used in patients unable to breathe correctly. Continue therapy until nebulizer cup is empty or the nebulizer stops producing a mist.

chest pain (unspecified) / Early / 18.0-25.0
dyspnea / Early / 17.0-17.0
conjunctivitis / Delayed / 1.0-5.0
antibody formation / Delayed / 2.0-4.0

cough / Delayed / 30.0-45.0
pharyngitis / Delayed / 32.0-40.0
headache / Early / 5.0-36.0
rhinitis / Early / 27.0-35.0
fever / Early / 32.0-32.0
hoarseness / Early / 12.0-18.0
rash / Early / 3.0-10.0
laryngitis / Delayed / 3.0-4.0
dyspepsia / Early / 3.0-3.0
urticaria / Rapid / Incidence not known

Pulmozyme

Rx

Recombinant human deoxyribonuclease (rhDNase); selectively cleaves DNA
Used in cystic fibrosis (CF) patients to aid clearance of bronchial secretions
Recommended for use in children and adults with mild, moderate, or severe CF; role in non-CF disease states unclear

2.5 mg inhaled by nebulizer once daily; some persons older than 21 years or with baseline forced vital capacity (FVC) more than 85% may benefit from twice daily administration.[33009] Guidelines recommend use in persons with mild, moderate, and severe disease.

2.5 mg inhaled by nebulizer once daily; some persons with baseline forced vital capacity (FVC) more than 85% may benefit from twice daily administration.[33009] Guidelines recommend use in persons with mild, moderate, and severe disease.

2.5 mg inhaled by nebulizer once daily. Use in this age group is supported by extrapolation of efficacy data in patients 5 years and older; additional safety data is available for 65 pediatric patients aged 3 months to 4 years who received 2.5 mg by nebulizer once daily for 2 weeks.

Small studies and case reports have utilized a variety of doses administered via nebulization or intratracheally. Pediatric studies most often included infants younger than 6 months of age with a primary diagnosis of congenital heart disease; however, patients up to 16 years and those with varying underlying conditions (e.g., bronchiolitis, pneumonia) have also been studied. Those treated with nebulized dornase alfa received 2.5 mg once or twice daily for up to 3 days or until clinical improvement was noted.[33011] [33010] [58319] [58412] One retrospective study suggested nebulized dornase alfa was most effective within 10 doses of therapy for amelioration of atelectasis in mechanically ventilated patients.[58319] Studies utilizing intratracheal dornase alfa for resolution of atelectasis used 0.1 mg/kg/dose (Max: 1.25 mg) twice daily or 0.25 mg/dose, diluted to 5 mL with 0.9% NaCl Injection, twice daily until clinical improvement and/or extubation.[33010] [58244] Case reports of intratracheal administration have described larger single doses of 2.5 mg or 10 mg, both diluted to 10 to 20 mL with 0.9% NaCl Injection, in children 7 to 8 years of age; in 1 patient, the 10 mg dose was repeated in 8 hours resulting in clinical improvement and no adverse effects.[58326] [58328] [58329] In a study evaluating the use of dornase alfa for the prevention of atelectasis in post-operative cardiac patients, a prophylactic intratracheal dose of 0.2 mg/kg/dose for patients weighing less than 5 kg and 0.1 mg/kg/dose for those weighing more than 5 kg, administered every 12 hours was used.[58245]

Small case series have described the use of dornase alfa for the treatment of severe atelectasis and mucus plugging in premature neonates as young as 25 weeks postmenstrual age. Nebulized doses have ranged from 1.25 mg as a single dose to 2.5 mg twice daily. Intratracheal doses have ranged from 1 mg/m2 as a single dose to 2.5 mg three times daily. One case series of 7 premature infants reported clinical improvement in all patients after the administration of dornase alfa. The initial dose used was 2.5 mg intratracheally twice daily for 3 to 6 days, followed by daily therapy for an additional 3 days in some patients. The clinical condition of 2 infants deteriorated when the dornase alfa was discontinued. No adverse events were reported.

5 mg intrapleurally twice daily for 3 days in combination with alteplase.

5 mg intrapleurally twice daily for 3 days in combination with alteplase.

†Indicates off-label use

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

There are no drug interactions associated with Dornase Alfa products.

Pulmozyme Respiratory (Inhalation) Sol: 1mg, 1mL

2.5 mg via inhalation twice daily.

Safety and efficacy have not been established.

2.5 mg via inhalation twice daily.

2.5 mg via inhalation twice daily.

>= 3 months: 2.5 mg via inhalation twice daily.
< 3 months: Safety and efficacy have not been established; however, doses up to 2.5 mg via inhalation twice daily or 2.5 mg intratracheally 3 times daily have been used off-label.

Safety and efficacy have not been established; however, doses up to 2.5 mg via inhalation twice daily or 2.5 mg intratracheally 3 times daily have been used off-label.

Dornase alfa hydrolyzes extracellular DNA. The exact mechanism of hydrolysis is unknown. There is no effect on intracellular DNA. Patients with CF experience chronic bacterial lung infections and inflammation. One characteristic feature of this inflammation is a significant influx of neutrophils. When these neutrophils degenerate, their DNA is released, increasing the viscosity and decreasing the patient's ability to clear the sputum. In vitro studies show that by cleaving extracellular DNA, dornase alfa decreases the viscosity of the sputum which then improves mucociliary clearance of sputum. Also, in these patients, dornase alfa reduces the incidence of recurrent bacterial infections. Clinical trials report that patients given dornase alfa have an increase in general perception of well-being and a decreased perception of dyspnea, frequency of cough and chest congestion. Beneficial effects subside within several days after discontinuation.

Dornase alfa is administered by inhalation.

Administration of a usual dose to cystic fibrosis patients results in sputum concentrations of approximately 3 mcg/mL within 15 minutes. Mean sputum concentrations declined to an average of 0.6 mcg/ml 2 hours following inhalation. Following 6 months of 2.5 mg twice daily administration in 321 CF patients, no accumulation of serum DNase occurred. However, when 2.5 mg once daily was administered to 98 children (age 3 months to <= 10 years) for 14 days, serum DNase concentrations increased by 1.3 +/- 1.3 ng/mL for the 3 month to < 5 years age group and by 0.8 +/- 1.2 ng/mL in the 5 to <= 10 years age group. In this same study, bronchoalveolar lavage (BAL) fluid concentrations of DNase 90 minutes following the first dose of dornase alfa varied from 0.007—1.8 mcg/mL. Though serum concentrations are not believed to be clinically useful, the relationship between BAL concentrations and clinical outcomes is unknown. Dornase alfa is expected to be metabolized by proteases present in biological fluids. A human intravenous dose study suggested an elimination half-life of 3—4 hours. Dornase alfa has demonstrated improvements in forced expiratory volume (FEV1) and forced vital capacity (FVC) by day 3—8 of administration.

There are no adequate data regarding fetal developmental risks associated with the use of dornase alfa in human pregnancy. Animal studies have revealed no evidence of harm to the mother, harm to the fetus, or effects on development of the fetus when dornase alfa was administered to rats and rabbits at doses up to approximately 600 times the maximum recommended human dose (MRHD).

It is not known whether dornase alfa is distributed into human breast milk. Small amounts of dornase alfa were detected in the milk of cynomolgus monkeys after an intravenous bolus of 100 mcg/kg followed by a 6 hour infusion of 80 mcg/kg/hour. Per the manufacturer, little or no measurable concentrations of dornase alfa would be expected in human milk after chronic dosing at recommended nebulized doses. However, because many drugs are excreted in breast milk, caution should still be used in women who are breast-feeding.