Pulmozim® (Pulmozyme®)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substanceDornase AlphaDornase Alpha
Similar drugsTo uncover
  • Pulmozim®
    solution d / inhal. 
    Hoffmann-La Roche Ltd.     Switzerland
    • Dosage form: & nbspinhalation solution
    Composition:

    1 ampoule (2.5 ml) solution for inhalation contains:

    active substance: dornase alpha 2.5 mg;

    Excipients: sodium chloride 21.93 mg, calcium chloride dihydrate 0.38 mg, water for injection q.s. up to 2.5 ml.

    * 1 mg of dornase alpha corresponds to 1000 units.

    Description:

    Transparent, colorless or slightly yellowish solution.

    Pharmacotherapeutic group:mucolytic agent
    ATX: & nbsp

    R.05.C.B.13   Dornase alpha (deoxyribonuclease)

    Pharmacodynamics:

    Recombinant human DNase (dornase alpha) is a genetically engineered version of a human natural 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 secret contains very high concentrations of the extracellular DNA-viscous polyanion released from the disintegrating leukocytes that accumulate in response to the infection.

    In vitro dornase alpha hydrolyzes DNA in sputum and drastically reduces the viscosity of sputum in cystic fibrosis.

    Pharmacokinetics:

    Suction

    Systemic absorption of dornase alpha after inhalation of aerosol in humans is low.

    Normally, Dnaz 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 blood serum as compared to normal endogenous levels. Serum concentration of DNase did not exceed 10 ng / ml.

    After the appointment of dronazy alpha to 2500 units (2.5 mg) twice a day for 24 weeks, the mean serum concentrations of DNase did not differ from the mean before treatment (3.5 ± 0.1 ng / ml), indicating a small systemic suction or small cumulation.

    Distribution

    In patients with cystic fibrosis, the mean concentration of dornase alpha in sputum at 15 minutes after inhalation of 2500 U (2.5 mg) is approximately 3 μg / ml. After inhalation, the concentration of dornase alpha at sputum quickly decreases.

    Metabolism

    Expected that dornase alpha metabolized by the action of proteases present in biological fluids.

    Excretion

    After intravenous administration of dornase alpha, the half-life of serum is 3-4 hours.

    Within 2 hours, the concentration of DNase in the sputum is more than halved compared to the value immediately after inhalation,However, the effect on rheology of sputum persists for more than 12 hours.

    Pharmacokinetics in specific patient groups

    Patients aged 3 months to 9 years

    A drug Pulmozyme® was used in children with cystic fibrosis, aged 3 months to 9 years at a dose of 2.5 mg in the form of inhalations once a day for 2 weeks. In the 90 minutes after the first inhalation bronchoalveolar lavage (BAL) was performed. The concentration of DNase in BAL fluid reached the detectable level in all patients, but varied over a wide range from 0.007 to 1.8 μg / ml.

    After applying Pulmozim® for a period of an average of 14 days the concentration of DNase in the blood serum (mean ± SD) was increased by l,l ± l, 6 ng / ml in children from 3 months to 5 years and by 0.8 ± 1.2 ng / ml in children from 5 to 9 years. The relationship between the concentration of DNase concentration in serum or BAL fluid with the development of unwanted reactions or the effectiveness of therapy has not been established.

    Indications:

    Symptomatic therapy in combination with standard cystic fibrosis therapy in patients with the value of forced vital capacity (FVC) is at least 40% of the norm in order to improve lung function.

    Contraindications:

    Hypersensitivity to the active substance of the drug or its components.

    Carefully:

    Pregnancy, the period of breastfeeding.

    Children under 5 years.

    Pregnancy and lactation:

    Pregnancy

    Safety of the drug Pulmozyme for pregnant women is not established. Studies of dornase alpha did not indicate a violation of fertility, teratogenicity or the effect of the drug on fetal development in animals. Pulmozym® should be administered with caution and pregnancy only if the benefit to the mother exceeds the potential risk to the fetus.

    Breastfeeding period

    Considering the minimal systemic absorption of dornase alpha when the recommended dosage regimen is observed, the appearance of measurable concentrations of dornase alpha in breast milk should not be expected in women. Prescribe Pulmozym® to nursing mothers with caution. In lactating Javanese macaques receiving high doses of intravenous dorsal alfa (iv), low concentrations of dornase alpha in human milk (<0.1% of serum concentrations) were found.

    Dosing and Administration:

    The solution in ampoules is intended only for a single inhalation application.

    Pulmozyme preparation® Do not dilute or mix 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 drug Pulmozyme® or other component of the mixture.

    2.5 mg dornase alpha (corresponds to the contents of 1 ampoule - 2.5 ml undiluted solution, 2500 units) once a day, inhalation, without dilution, with the help of jet nebulizer (see the section "Instructions for the treatment of the drug").

    In some patients older than 21 years, the best effect of treatment can be achieved by applying a daily dose of the drug 2 times a day. In most patients, the optimal effect can be achieved with a constant daily use of Pulmozim®.

    Studies in which dornase alpha was administered in intermittent mode show that after the cessation of therapy, the improvement in lung function disappears. Therefore, patients should be advised daily intake of the drug without interruption.

    Patients should continue to take complex therapy, including chest physiotherapy.

    With an exacerbation of respiratory tract infection during the treatment with Pulmozim® its use can continue without any risk to the patient.

    Instructions for handling the drug

    The contents of one ampoule must be poured into a jet-nebulizer / compressor tank, such as Hudson T Up-draft II / Pulmo-Aide, Airlife Misty/ Pulmo-Aide, modifications Respigard/ Pulmo-Aide or Acorn II / Pulmo-Aide.

    The drug Pulmozim® can be injected with a jet-nebulizer / reusable compressor of the type Pari LL/ Inhalierboy, Pari LC/ Inhalierboy or Master, Aiolos/ 2 Aiolos, Side Stream/CR50, Mobil Air or Porta-Neb.

    Patients who are unable to breathe through the mouth during the entire inhalation period through the nebulizer may use a nebulizer Pari Baby with a tight-fitting face mask. Ultrasonic nebulizers are not suitable for the administration of Pulmozyme®, since they can inactivate the drug Pulmozyme® or have unacceptable aerosol characteristics.

    The patient must follow the manufacturer's instructions for the operation and care of the nebulizer / compressor.

    Side effects:

    Undesirable reactions during treatment with Pulmozyme® are rare (<1/1000), in most cases are mild, are of a transient nature and do not require dose adjustment.

    Disorders from the side of the organ of vision: conjunctivitis.

    Disturbances from the respiratory system, chest and mediastinal organs: change in voice, dyspnea, pharyngitis, laryngitis, rhinitis (all non-infectious nature), respiratory infections, including those caused by Pseudomonas, an increase in bronchial secretions.

    Disorders from the gastrointestinal tract; dyspepsia.

    Disturbances from the skin and subcutaneous tissues: rash, hives.

    General disorders: chest pain (pleural / noncardiogenic), pyrexia, headache.

    Impact on laboratory and instrumental research results: decreased respiratory function.

    Patients who develop unwanted events that coincide with the symptoms of cystic fibrosis can, as a rule, continue to use the drug Pulmozyme®. The undesirable effects that led to the complete cessation of Pulmozym® treatment were observed in a very small number of patients, and the frequency of interruption of therapy was similar for placebo (2%) and dornase alpha (3%).

    Antibodies to dornase alpha were found in less than 5% of patients, but none of them were classified as class IgE. Improvement in lung function was noted even after the appearance of antibodies to dornase alpha.

    Patients aged 3 months to 9 years

    Safety of inhalation 2.5 mg of Pulmozim® was tested once a day for 2 weeks in children with cystic fibrosis in two age groups - from 3 months to <5 years and from 5 to 9 years. Adverse events were similar to those observed in other clinical trials involving children. In the younger group of patients, cough (as a side effect) (45% and 30%, respectively), including severe and moderate severity (37% and 18%, respectively) was more frequent than in older children. The remaining adverse reactions were mild to moderate in severity. Also in the younger group of patients, rhinitis (35% vs. 27%) and rash (6% vs. 0%) were observed more often than in the older group.

    Overdose:

    Cases of an overdose of Pulmozym® are not registered. Patients with cystic fibrosis received 20 mg of Pulmozym® inhalation twice daily (which exceeds the recommended daily dose by 16 times) for 6 days or 10 mg twice daily (which exceeds the recommended daily dose by 8 times) by a discontinuous schedule (2 weeks treatment with Pulmozim® followed by a 2-week period without therapy) for 168 days.Six adult patients without cystic fibrosis patients, were obtained Pulmozim® drug intravenously once in a dose of 125 .mu.g / kg body weight, followed by 7 days of these patients received 125 ug / kg drug Pulmozyme® in the form of a subcutaneous injection for two consecutive 5-day periods. There was no formation of neutralizing antibodies to DNase and changes in the concentration of antibodies to double-stranded DNA in the blood serum. All the above dosing regimens were well tolerated.

    Systemic toxicity of Pulmozym® is not detected and is not expected due to low absorption and short half-life of dornase alpha. Thus, in case of an overdose of Pulmozyme® systemic therapy is not required.

    Interaction:

    Compatible with standard drugs for the treatment of cystic fibrosis: antibiotics, bronchodilators, digestive enzymes, vitamins, inhalation and systemic glucocorticosteroids and analgesics.

    Pulmozim® is an aqueous solution without buffer properties and should not be diluted or mixed with other drugs or solutions in the nebulizer vessel.Mixing the drug with other drugs can lead to undesirable structural and / or functional changes in the preparation Pulmozym® or another component of the mixture.

    Special instructions:

    In the patient's medical records, the trade name of the drug should be indicated (Pulmozyme®). Replacement of the drug with any other similar biological medicinal product requires agreement with the attending physician. The information provided in this manual applies only to Pulmozim®.

    When using Pulmozim®, regular medical supervision of the patient and standard physiotherapy should be continued.

    After the beginning of therapy with Pulmozim®, as with any aerosol, the lung function may decrease slightly, and the sputum discharge will increase.

    Experience with Pulmozym® in children under 5 years of age is limited. The effectiveness of Pulmozym ® in children under the age of 5 years has not been studied.

    Prescribe Pulmozym® to children under 5 years of age only if there is a possible improvement in lung function or a reduced risk of respiratory infections.

    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 ° C) does not affect the stability of the drug.

    Effect on the ability to drive transp. cf. and fur:

    The influence of dornase alpha on the ability of the patient to drive vehicles and work with the mechanisms of communication has not been reported.

    Form release / dosage:

    Solution for inhalation, 2.5 mg / 2.5 ml.

    Packaging:

    By 2.5 ml of the drug in colorless plastic ampoules, manufactured by thermo-punching.

    6 ampoules are placed in a protective container of aluminum foil laminated.

    1 a protective container together with an instruction for use is placed in a cardboard box.
    Storage conditions:

    Store at 2-8 ° C, in a place protected from light.

    Keep out of the reach of children.

    Shelf life:

    2 of the year.

    The drug should not be used after the expiry date indicated on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:П N014614 / 01
    Date of registration:10.09.2008
    The owner of the registration certificate:Hoffmann-La Roche Ltd.Hoffmann-La Roche Ltd. Switzerland
    Manufacturer: & nbsp
    Representation: & nbspF.Hoffmann-La Roche Ltd. F.Hoffmann-La Roche Ltd. Switzerland
    Information update date: & nbsp20.01.2016
    Illustrated instructions
      Instructions
      Up