Dornase alpha

When ATH:
R05CB13

Characteristic.

Recombinant human DNase I - enzyme, which selectively cleaves DNA. Dornase alfa is a protein, produced by genetic engineering using Chinese hamster ovary cells. Ochishtennыy product - glycoprotein, comprising 260 amino acids, primary sequence which is identical to that of natural human enzyme - DNase I (DNase), an approximate molecular weight 37 kd.

Pharmacological action.
Mucolytic.

Application.

Improving lung function in cystic fibrosis patients aged over 5 years with an index of at least FVC 40% from the norm (in the complex therapy). It can be used to treat patients with certain chronic lung diseases (incl. bronchiectasis, COPD, congenital lung development in children, chronic pneumonia, immunodeficiency states, proceeding with pulmonary), if a doctor to assess the mucolytic effect of dornase alfa provides benefits to patients.

Contraindications.

Hypersensitivity, allergic reactions to drugs from Chinese hamster ovary cells.

Restrictions apply.

Children up to age 5 years, and patients with FVC index less 40%. Safety and efficacy have not been proved.

Pregnancy and breast-feeding.

If pregnancy should be prescribed only if absolutely indicated, if the benefit to the mother outweighs the risk to the child (adequate and well-controlled studies in humans have not held). Studies of dornase alfa in rats and rabbits with on / in at dosages up to 10 mg / kg / day (systemic exposure than in 600 times higher than expected after taking the recommended daily human dose) They did not indicate impairment of fertility, teratogenicity or effects on fetal development.

Category actions result in FDA - B. (The study of reproduction in animals revealed no risk of adverse effects on the fetus, and adequate and well-controlled studies in pregnant women have not done.)

Unknown, Whether drugs penetrate the breast milk of women. Small amounts of dornase alfa was determined in breast milk in monkeys Cynomolgus bolus at a dose (100 mg / kg) dornase alfa after 6 h / Infusion (80 mg / kg / day). When used in accordance with the recommendations of dornase alpha ingress into the systemic circulation is minimal, However, the use in nursing mothers is not recommended.

Side effects.

In clinical trials, patients were used to dornase alpha 12 Months.

In a randomized placebo-controlled trial compared dornase alfa with placebo in patients with an index of at least FVC 40% from the norm over 600 patients received dornase alfa 1 or 2 twice a day every day for 6 Months; Most of the observed adverse events, perhaps, is a manifestation of the underlying disease or complications. In most cases, these side effects were mild, transitory, and did not require discontinuation PM. Adverse events, leading to the complete cessation of treatment dornase alfa, We observed in a very small number of patients, and discontinuation rates were similar in the placebo group (2%) and the group, receiving dornase alfa (3%). Side effects, observed more frequently (more 3%) in patients with cystic fibrosis, receiving dornase alfa, compared to placebo, are presented in Table.

In a randomized placebo-controlled trial in patients with symptomatic cystic fibrosis (FVC less 40% from the norm) the adverse event profile was similar to that noted in trials in patients with cystic fibrosis mild to moderate severity. In this study, the side effects, which have been marked with a higher frequency (more 3%) patients, treated with dornase alfa, as shown in Table.

Table

Side effects, occurs with a frequency more 3% in cystic fibrosis patients in clinical trials of dornase alfa

* Only a single change, It does not reflect all changes in FVC

Adverse events, observed with equal frequency in patients with cystic fibrosis at least index FVC 40% from the norm when inhaled dornase alfa and placebo

Body as a Whole: abdominal pain, asthenia, fever, flu-like symptoms, malaise, sepsis.

Digestive system: ileus, gallbladder disease, liver, pancreas.

Metabolism: diabetes, gipoksiya, weight loss.

Respiratory system: apnea, ʙronxoektaz, bronchitis, changes in the characteristics of sputum, increased cough, dyspnoea, hemoptysis, reduced lung function, nasal polyps, pneumonia, pneumothorax, rhinitis, sinusitis, increased sputum, wheezing.

In controlled trials, mortality was similar in the group of patients, taking dornase alfa, and placebo. Causes of deaths were associated with progression of cystic fibrosis and included apnea, cardiac arrest, cardiopulmonary failure, pulmonary heart, heart failure, massive hemoptysis, pneumonia, pneumothorax, respiratory failure.

Portability dornase alfa 2,5 mg inhalation was studied at two weeks of daily administration at 98 Patients with cystic fibrosis (65 aged 3 Months before 5 years, 33 aged 5 years before 10 years). We used the reusable nebulizer. Number of patients, who celebrated cough, It was higher in the younger age group (29/65, 45% compared to 10/33, 30%) same, as well as the number of cases of moderate and severe cough severity (24/65, 37% compared to 6/33, 18%).

Other side effects were mild or moderate severity. Number of patients, who celebrated rhinitis, It was higher in the younger age group (23/65, 35% compared to 9/33, 27%) same, as the number of patients, who noted rash (4/65, 6% compared to 0/33).

Allergic reactions

There were no reported cases of anaphylaxis, which could be related to the appointment of dornase alfa. There were transient rash mild or moderate severity and weakly expressed in skin rashes. For all studies in approximately 2-4% of patients have antibodies to dornase alfa. None of these patients developed clinical importance anaphylaxis and serum antibodies to dornase alpha unknown.

Cooperation.

Compatible with other drugs, primenyayushtimisya in lechenii CF. (including antibiotics, bronchodilators, digestive enzymes, vitamins, Inhaled and systemic corticosteroids, analgesics).

Pharmaceutical incompatibility: an aqueous solution of dornase alfa has not buffered and should not be divorced or mixed in with other systems inhaled drugs (possible undesirable structural and / or functional changes).

Overdose.

Symptoms: overdoses have been recorded. In studies in rats and monkeys show, that a single inhalation formulation in doses, higher than commonly used in clinical trials up to 180 time, well tolerated. Single oral administration to rats at doses of dornase alfa to 200 mg / kg are also well tolerated.

In clinical studies, patients with cystic fibrosis received up to 20 mg dornase alfa 2 twice a day for 6 days and 10 mg 2 twice a day for a broken circuit (a two-week reception / two-week break) for 168 days. Both dosing regimens were well tolerated.

Dosing and Administration.

Inhalation. The solution in the ampoules is only intended for a single use of the inhalation, It is introduced by the air compressor nebulizer (jet nebuliser); the recommended dose - 2500 ED (2,5 mg) dornase alfa 1 once a day, which corresponds to the content 1 ampoule (2,5 mg undiluted solution). Some patients older 21 , the better the treatment effect can be achieved with use of the drug 2 once a day.

In most patients, the optimal effect can be achieved with continuous daily use of dornase alfa. Research, wherein dornase alfa administered intermittently, show, that after the cessation of therapy improvement in lung function is rapidly disappearing, it is recommended that the daily intake of the drug. Currently, the recommendations on the optimal time of day for administration of the drug is not.

The safety and efficacy of daily use over a period of time 12 months have not been established.

During exacerbation of respiratory tract infection during treatment with use of the drug can be continued without any risk for the patient.