Pulmozyme Inhalation 2.5 mg/1.0 mg Solution

Management of cystic fibrosis (CF) patients, with a forced vital capacity (FVC) of greater than 40 % of predicted value, and over 5 years of age.

PULMOZYME is recommended to be administered daily at a dose of 2,5 mg, once a day to CF patients u00b3 5 years of age. Inhale the contents of one ampoule (2,5 mu2113 of solution) undiluted using a recommended jet nebuliser/compressor system. See Instructions for use/handling. Some patients over the age of 21 may benefit from twice daily administration. Most patients gain optimal benefit from continued daily use of PULMOZYME. Studies demonstrating the reduction in the rate of exacerbations of respiratory tract infections have involved chronic, daily administration of dornase alfa. Therefore, patients should be instructed to take their medications every day, without a break. For patients on PULMOZYME therapy who experience exacerbation of respiratory tract infection, administration of PULMOZYME can be safely continued. The patient should continue his/her standard medical care including their standard regimen of chest physiotherapy. Safety and efficacy have not been demonstrated in patients with forced vital capacity less than 40 % of predicted. There is no clinical experience in the use of PULMOZYME in patients under the age of 5 years.

PULMOZYME should not be administered to patients with known hypersensitivity to the product or its constituents. Pregnancy and lactation. Safety and efficacy in children younger than 5 years has not been established.

Standard cystic fibrosis therapies, such as antibiotics, bronchodilators, pancreatic enzymes, vitamins, inhaled and systemic corticosteroids and analgesics can be used safely in conjunction with PULMOZYME. However, PULMOZYME should not be mixed in the nebuliser with these therapies.

Pregnancy: The safety of dornase alfa has not been established in pregnant women. Lactation: When PULMOZYME is administered to humans according to the dosage recommendation, there is minimal systemic absorption. Nevertheless, dornase alfa should not be administered to a breast-feeding woman.

Side effects reported in clinical trials have been listed below according to system organ class and frequency of occurrence according to the following convention: Rare (u2265 1/10 000 < 1/1 000) In most cases, the adverse reactions are mild and transient in nature and do not require alterations in PULMOZYME dosing. Eye disorders: Rare: Conjunctivitis. Respiratory, thoracic and mediastinal disorders: Rare: Dysphonia, dyspnoea, pharyngitis, laryngitis, rhinitis (all non-infectious), cough. Gastrointestinal disorders: Rare: Dyspepsia. Skin and subcutaneous tissue disorders: Rare: Rash, urticaria. General disorders and administration site conditions: Rare: Chest pain (pleuritic/non-cardiac), pyrexia. Investigations: Rare: Pulmonary function tests decreased. Upon initiation of dornase alfa therapy, pulmonary function may decline and expectoration of sputum may increase. Less than 5 % of patients treated with dornase alfa have developed antibodies to dornase alfa. Improvement in pulmonary function tests has still occurred even after the development of antibodies to dornase alfa.

The effect of PULMOZYME overdosage has not been established. Results of clinical studies and preclinical inhalation studies in rats and monkeys have shown there is minimal systemic absorption of dornase alfa. Cystic fibrosis patients have inhaled up to 20 mg PULMOZYME twice daily (16 times the recommended daily dose) for up to 6 days and 10 mg twice daily (8 times the recommended dose) intermittently (2 weeks on/2 weeks off drug) for 168 days. Six adult non-cystic fibrosis patients received a single intravenous dose of 125 u03bcg/kg of dornase alfa, followed 7 days later by 125 u03bcg/kg subcutaneously for two consecutive 5-day periods, without either neutralising antibodies to DNase or any change in serum antibodies against double-stranded DNA being detected. All of these doses were well tolerated. Systemic toxicity of PULMOZYME has not been observed and is not expected due to the poor absorption and short serum half-life of dornase alfa. Systemic treatment of overdose is therefore unlikely to be necessary. See Pharmacokinetic properties.