WARNINGS
None.
PRECAUTIONS
General
Pulmozyme should be used in conjunction with standard therapies for CF.
Information for Patients
Pulmozyme must be stored in the refrigerator at 2—8°C (36—46°F) and protected from strong light. It should be kept refrigerated during transport and should not be exposed to room temperatures for a total time of 24 hours. The solution should be discarded if it is cloudy or discolored. Pulmozyme contains no preservative and, once opened, the entire contents of the ampule must be used or discarded. Patients should be instructed in the proper use and maintenance of the nebulizer and compressor system used in its delivery.
Pulmozyme should not be diluted or mixed with other drugs in the nebulizer. Mixing of Pulmozyme with other drugs could lead to adverse physicochemical and/or functional changes in Pulmozyme or the admixed compound.
Drug Interactions
Clinical trials have indicated that Pulmozyme can be effectively and safely used in conjunction with standard cystic fibrosis therapies including oral, inhaled and/or parenteral antibiotics, bronchodilators, enzyme supplements, vitamins, oral or inhaled corticosteroids, and analgesics. No formal drug interaction studies have been performed.
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis: Lifetime studies in Sprague Dawley rats showed no carcinogenic effect when Pulmozyme was administered at doses up to 246 µg/kg body weight per day. Pulmozyme was administered to rats as an aerosol for up to 30 minutes per day, daily for two years, with resulting lower respiratory tract doses of up to 246 µg/kg per day, which represents up to a 28.8-fold multiple of the clinical dose. There was no increase in the development of benign or malignant neoplasms and no occurrence of unusual tumor types in rats after lifetime exposure.
Mutagenesis: Ames tests using six different tester strains of bacteria (4 of S. typhimurium and 2 of E. coli) at concentrations up to 5000 µg/plate, a cytogenetic assay using human peripheral blood lymphocytes at concentrations up to 2000 µg/plate, and a mouse lymphoma assay at concentrations up to 1000 µg/plate, with and without metabolic activation, revealed no evidence of mutagenesis potential. Pulmozyme was tested in a micronucleus (in vivo) assay for its potential to produce chromosome damage in bone marrow cells of mice following a bolus intravenous dose of 10 mg/kg on two consecutive days. No evidence of chromosomal damage was noted.
Impairment of Fertility: In studies with rats receiving up to 10 mg/kg/day, a dose representing systemic exposures greater than 600 times that expected following the recommended human dose, fertility and reproductive performance of both males and females was not affected.
Pregnancy (Category B)
Reproduction studies have been performed in rats and rabbits with intravenous doses up to 10 mg/kg/day, representing systemic exposures greater than 600 times that expected following the recommended human dose. These studies have revealed no evidence of impaired fertility, harm to the fetus, or effects on development due to Pulmozyme. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproductive studies are not always predictive of the human response, this drug should be used during pregnancy only if clearly needed.
Nursing Mothers
It is not known whether Pulmozyme is excreted in human milk. Small amounts of dornase alfa were detected in maternal milk of cynomolgus monkeys when administered a bolus dose (100 µg/kg) of dornase alfa followed by a six hour intravenous infusion (80 µg/kg/hr). Little or no measurable dornase alfa would be expected in human milk after chronic aerosol administration of recommended doses. Because many drugs are excreted in human milk, caution should still be exercised when Pulmozyme is administered to a nursing woman.
Pediatric Use
Because of the limited experience with the administration of Pulmozyme to patients younger than 5 years of age, its use should be considered only for those patients in whom there is a potential for benefit in pulmonary function or in risk of respiratory tract infection.
Geriatric Use
Cystic fibrosis is primarily a disease of pediatrics and young adults. Clinical studies of Pulmozyme did not include sufficient numbers of subjects aged 65 or older to determine whether they respond differently from younger subjects.
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