Composition, form of production and packaging
The solution for inhalations is clear, colorless or slightly yellowish.
1 ml of 1 amp.
dornase alpha 1 mg (1000 U) 2.5 mg (2500 U)
Excipients: sodium chloride, calcium chloride dihydrate, water d / and.
2.5 ml - plastic ampoules (6) - aluminum foil multi-layer foil containers (1) - cardboard packs.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2014.
Mucolytic drug used in cystic fibrosis.
Recombinant human DNase (dornase alpha) is a genetically engineered version of a natural human enzyme that cleaves extracellular DNA.
The accumulation of a viscous purulent secretion in the airways plays a role in the disturbance of the function of external respiration and in exacerbations of the infectious process in patients with cystic fibrosis. The purulent secretion contains very high concentrations of extracellular DNA, a viscous polyanion released from collapsing leukocytes, which accumulate in response to infection. In vitro, dornase alpha hydrolyzes DNA in sputum and expresses the viscosity of sputum in cystic fibrosis.
Systemic absorption of dornase alpha after inhalation of aerosol is low.
Normally, DNase is present in human serum. Inhalation of dornase alpha in doses up to 40 mg for up to 6 days did not lead to a significant increase in the concentration of DNase in the serum as compared to normal endogenous levels. The concentration of serum dornase alpha in the serum did not exceed 10 ng / ml.
After the appointment of dornase alpha at a dose of 2500 units (2.5 mg) 2 times / day for 24 weeks, the concentration of DNase in the serum did not differ from the average before treatment (3.5 В± 0.1 ng / ml), which indicates low systemic absorption and low cumulation.
In cystic fibrosis, the mean concentration of dornase alpha in sputum is 15 Ојg after inhalation of the drug at a dose of 2500 U (2.5 mg) of approximately 3 Ојg / ml.
After inhalation, the serum dornase alpha concentration decreases rapidly.
- symptomatic therapy in combination with standard cystic fibrosis therapy in patients with FVC not less than 40% of the norm.
Pulmozyme can be used to treat patients with certain chronic lung diseases (bronchiectasis, COPD, congenital malformation of the lungs in children, chronic pneumonia, immunodeficiency states that occur with lung damage, etc.), if the doctor estimates that the mucolytic effect of dornase alpha provides benefits for patients .
The drug is administered in the form of inhalations, which are carried out with the help of a jet nebulizer.
The dose of the drug is 2.5 mg (corresponds to the content of the drug in 1 ampoule - 2.5 ml of undiluted solution, 2500 IU) 1 time / day. In some patients older than 21 years, the drug may be more effective in appointing 2 times / day.
In most patients, the optimal effect can be achieved with a constant daily use of Pulmozyme. The results of the studies, in which the dornase alpha was administered intermittently, show that after the cessation of therapy, the effect of the drug (improvement in lung function) quickly disappears. Therefore, patients should be advised daily use of the drug without interruption.
It is necessary to continue complex therapy, including physiotherapy of the thorax.
In case of exacerbation of respiratory tract infections with Pulmozym therapy, the use of the drug can be continued without any risk to the patient.
The solution in ampoules is intended only for a single inhalation application.
Pulmonaceous can not be diluted or mixed with other drugs or solutions in the nebulizer tank. Mixing the drug with other drugs can lead to undesirable structural and / or functional changes in the Pulmozyme or other component of the mixture.
All the contents of one ampoule must be poured into a jet-nebulizer / compressor of the type Hudson T Up-draft II / Pulmo-Aide, Airlife Misty / Pulmo-Aide, modifications of Respigard / Pulmo-Aide or Acorn II / Pulmo-Aide. The pelmozyme can be injected with a reusable nebulizer / reusable compressor such as Pari LL / Inhalierboy, Pari LC / Inhalierboy or Master, Aiolos / 2 Aiolos, Side Stream / CR50, Mobil Air or Porta-Neb.
Ultrasonic nebulizers are not suitable for the administration of Pulmozyme, because they can inactivate dornase alpha or have unacceptable aerosol characteristics.
Patients who are unable to breathe through the mouth during the inhalation period through the nebulizer can use a Pari Baby nebulizer with a tight-fitting facial mask.
The patient should be warned about the need to follow the manufacturer's instructions for the operation and care of the nebulizer / compressor.
Unwanted reactions in the treatment with Pulmonzyme occur rarely (<1/1000), in most cases are mild, transient and do not require dose adjustment.
From the hemopoietic system: acute lymphocytic leukemia, aplastic anemia.
From the side of the central nervous system: epileptic seizures, migraines.
From the sense organs: conjunctivitis, imbalance.
From the cardiovascular system: tachycardia, bradycardia, cardiac arrest.
From the respiratory system: pneumonia, bronchitis, respiratory tract infections, incl. Pseudomonas, pharyngitis, laryngitis, voice change (hoarseness), dyspnea, rhinitis, impaired lung function, decreased respiratory function, respiratory failure, hemoptysis, pneumothorax, pulmonary bleeding, laryngeal polyps, cough, bronchial secretion, alveolitis, hypoxia, bronchospasm , productive cough.
On the part of the digestive system: dyspepsia, abdominal pain, bloody vomiting, liver failure.
Dermatological reactions: rash, itching, dermatitis, purpura, urticaria, angioedema.
On the part of the reproductive system: premature birth, complications of pregnancy, spontaneous abortion, medical abortion.
On the part of the body as a whole: fever, weakness, malaise, death, pleural pain in the chest.
Patients who develop adverse events that coincide with the symptoms of cystic fibrosis may, as a rule, continue to use Pulmozyma. The undesirable effects that led to the complete cessation of treatment with Pulmozyme were observed in a very small number of patients, and the frequency of discontinuation of therapy was the same for placebo (2%) and dornase alpha (3%).
Antibodies to dornase alpha were found in less than 5% of patients, but none of them belonged to the IgE class. Improvement in lung function was noted even after the appearance of antibodies to dornase alpha.
- Hypersensitivity to the active substance or other components of the drug.
Caution should be used during pregnancy, lactation (breastfeeding), in children under 5 years.
PREGNANCY AND LACTATION
The safety of the use of Pulmozyme in pregnancy is not established. The drug should be used with caution and only in cases where the intended benefit to the mother exceeds the potential risk to the fetus.
It is not known whether dornase alpha is excreted in human breast milk. With caution should be used during the lactation (breastfeeding). Given the minimal systemic absorption of dornase alpha, do not expect measured concentrations of dornase alpha in breast milk in women.
In experimental animal studies, no evidence of impaired fertility, teratogenic properties, or the effect of the drug on fetal development has been obtained. Lactating monkeys of cynomolgus who received high doses of alveolar alfa IV showed low concentrations of dornase alpha in breast milk (<0.1% of serum concentrations).
APPLICATION FOR CHILDREN
With caution should be used in children under 5 years.
Against the backdrop of the use of Pulmonase, it is necessary to continue regular medical supervision of the patient.
After the beginning of Pulmozim therapy, as with any aerosol, the lung function may decrease slightly, and the sputum discharge will increase.
The efficacy and safety of dornase alpha in patients with FVC less than 40% of the norm are not established.
A single short-term effect of elevated temperatures (not more than 24 hours at a temperature of up to 30 В° C) does not affect the stability of the drug.
Use in Pediatrics
Experience in the use of Pulmonase in children under 5 years of age is limited. There were no differences in the safety profile in children under 5 years old and in the older age group from 5 to 9 years. After the end of treatment, there was no increase in the incidence of serious adverse events in children under 5 years of age who received Pulmozym В® . Prescribe Pulmozyme В® for infants under 5 years of age should only be given if the potential benefit of improving lung function exceeds the risk of respiratory tract infection.
Impact on the ability to drive vehicles and manage mechanisms
There is no information on the effect of the drug on the patient's ability to drive vehicles and other potentially dangerous activities.
No cases of drug overdose Pulmozim В® have been reported.
In experimental studies in laboratory animals, it was shown that a single inhalation of the drug at doses much higher than that usually used in humans (up to 180 times) was tolerated well. Oral administration of Pulmozyme to rats at doses up to 200 mg / kg was also tolerated well.
In clinical trials, the drug was administered to patients with cystic fibrosis in a dose of 20 mg 2 times / day for 6 days or 10 mg 2 times / day by intermittent schedule (a two-week reception, a two-week break) for 168 days. Both dosing regimens were well tolerated.
The drug is compatible with standard drugs for the treatment of cystic fibrosis (antibiotics, bronchodilators, digestive enzymes, vitamins, analgesics, GCS for systemic and inhalation use).
Pulmozyme is an aqueous solution without buffer properties. It can not be diluted or mixed with other drugs or solutions in the nebulizer tank. Mixing can lead to undesirable structural and / or functional changes in the Pulmonase or other component of the mixture.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored in a place protected from light, inaccessible to children at a temperature of 2 В° to 8 В° C. Shelf life - 2 years.