PULMOZYME
Clinical safety rating: caution
Comprehensive clinical and safety monograph for PULMOZYME (PULMOZYME).
Recombinant human deoxyribonuclease I (rhDNase) cleaves extracellular DNA in sputum, reducing viscosity and improving mucus clearance.
| Metabolism | Not extensively metabolized; eliminated via proteolysis and renal clearance. |
| Excretion | Pulmozyme (dornase alfa) is a recombinant DNase administered via inhalation. Systemic absorption is minimal; most of the drug is locally active in the airways and subsequently cleared by proteolysis and mucociliary clearance. No significant renal or biliary excretion occurs; the small fraction absorbed is likely metabolized by proteases in the plasma. Excretion of the absorbed fraction is not well-characterized in humans. |
| Half-life | The terminal elimination half-life of dornase alfa after inhalation is 6–7 hours, but this reflects slow release from the lung rather than systemic elimination. Clinically, the half-life supports once-daily dosing. |
| Protein binding | Not clinically significant due to minimal systemic absorption. Systemic bioavailability is very low (<1%), and no data on protein binding of the absorbed fraction are available. In vitro, dornase alfa does not bind significantly to plasma proteins. |
| Volume of Distribution | After inhalation, the volume of distribution is not applicable as the drug acts locally in the lungs. For the small absorbed fraction, the volume of distribution is estimated to be 0.6 L/kg, indicating distribution into total body water. This is not clinically relevant. |
| Bioavailability | Bioavailability by inhalation is primarily local; systemic bioavailability is less than 1% due to high molecular weight and metabolism in the lungs. No oral bioavailability as it is administered via inhalation. |
| Onset of Action | After inhalation, clinical improvement in pulmonary function (e.g., FEV1) is observed within 3–7 days of initiation. The drug reduces sputum viscosity by cleaving DNA, with onset of this effect occurring within minutes to hours after inhalation. |
| Duration of Action | The effect on sputum viscosity persists for 24 hours, allowing once-daily dosing. Improvement in lung function is sustained with continued administration. Duration of clinical benefit is prolonged with regular use. |
2.5 mg (one ampule) once daily via inhalation using a jet nebulizer. An approved compressor is recommended.
| Dosage form | VIAL |
| Renal impairment | No dose adjustment required for renal impairment. No pharmacokinetic studies have been conducted in renally impaired patients, but drug action is local. |
| Liver impairment | No dose adjustment required for hepatic impairment. No studies performed; hepatic metabolism is not a significant elimination pathway. |
| Pediatric use | For children ≥5 years with cystic fibrosis: 2.5 mg inhaled once daily. Safety and efficacy in children <5 years have not been established. |
| Geriatric use | No specific geriatric dosage adjustments. Dosing should be cautious due to greater frequency of renal, hepatic, or cardiac dysfunction and concomitant disease or drug therapy. |
| 1st trimester | Consult provider |
| 2nd trimester | Consult provider |
| 3rd trimester | Consult provider |
Clinical note
Comprehensive clinical and safety monograph for PULMOZYME (PULMOZYME).
| Breastfeeding | Unknown excretion in human milk; consider benefits of breastfeeding vs. potential risk. |
| Teratogenic Risk | No evidence of teratogenicity in animal studies; insufficient human data in first trimester. No known fetal risk in second or third trimester. |
| Fetal Monitoring | No specific monitoring required beyond standard obstetrical care. |
■ FDA Black Box Warning
No FDA black box warning.
| Serious Effects |
["Hypersensitivity to dornase alfa or any component of the formulation."]
| Precautions | ["Risk of hemoptysis, especially in patients with FVC <40% of predicted.","Should not be used in patients with known hypersensitivity to dornase alfa or any product components.","Monitor for bronchospasm, laryngeal edema, or urticaria during initial administration."] |
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| Fertility Effects | No known effects on fertility. |