Daksas tablets are covered. 0 5 mg 30 pcs. (Roflumylast)

Release form

Film-coated tablets.

Packing

30 pcs

Pharmacological action of

The action of roflumilast is aimed at eliminating the inflammatory processes associated with COPD. The mechanism of action is the inhibition of PDE4, the main cyclic adenosine monophosphate - a metabolizing enzyme contained in cells involved in inflammatory processes, and which is an important link in the pathogenesis of COPD.

The effect of roflumilast is mainly directed at PDE4A, 4B and 4D, with a similar potential in the nanomolar range. The affinity for the type PDE4S is 5-10 times lower. This mechanism of action and selectivity are also applicable to N-oxide, which is the main active metabolite of roflumilast.

Inhibition of PDE4 leads to an increase in intracellular cAMP and a decrease in the dysfunction of leukocytes, smooth muscle cells of the respiratory tract and pulmonary vessels, endothelial cells and epithelial cells of the respiratory tract, as well as fibroblasts in the experiment.

Stimulation of human neutrophils, monocytes, macrophages or lymphocytes (in vitro) showed that roflumilast and roflumilast N-oxide inhibit the release of inflammatory mediators such as leukotriene B4, reactive oxygen species, TNFα, interferon gamma and granzyme B.

In patients with COPD, roflumilast lowers the neutrophil count in mucotrophils and also reduces the influx of neutrophils and eosinophils into the airways of healthy volunteers who received endotoxin.

Roflumilast is actively metabolized in the human body with the formation of the main pharmacodynamically active metabolite of roflumilast N-oxide. Because roflumilast and roflumilast N-oxide are involved in the inhibition of PDE activity (in vivo), pharmacokinetics are described based on the assessment of the total inhibitory effect on PDE4.

Indications

Supportive therapy for the treatment of severe COPD (first bronchodilation volume of forced expiration in the first second (FEV1) should be less than 50% of the calculated proper value) in adult patients with frequent exacerbations in history.

Contraindications

hypersensitivity to roflumilast or to any other component of the drug Daxas

moderate or severe form of liver failure (Child-Pu class B and C)

age under 18 years (efficacy and safety not established) lrdlrd pregnancy due to lack of sufficient experience of use: serious immunodeficiency diseases (HIV infection, multiple sclerosis, systemic lupus erythematosus, progressive multifocal leukoencephalopathy and others), serious acute infectious diseases (such as tuberculosis or acute hepatitis), cancer (except for basal cell carcinoma, a slowly growing type of skin cancer), chronic heart failure functional classes 3 and 4 (NYHA)

due to lack of sufficient experience of use: treatment with immunosuppressive drugs (such as methotrexate, azathioprine, infliximab, etanercept, as well as in individuals receiving ongoing maintenance therapy july by oral corticosteroids)

rare hereditary diseases such as galactose intolerance, lactase deficiency or glucose-galactose malabsorption

depression, associated with the emergence of suicidal ideation and behavior.

Caution: history of mental disorders treatment with a CYP1A2 cytochrome isoenzyme inhibitor fluvoxamine or two CYP3A4 / 1A2 inhibitors enoxacin and cimetidine. A mild form of liver failure (class A according to the Child-Pugh classification).

Use during pregnancy and lactation

Pregnancy. Data on the use of roflumilast by pregnant women are limited. According to preclinical studies, roflumilast crosses the placental barrier. Animal studies have shown reproductive toxicity of the drug. Daxas is not recommended for pregnant women and women of reproductive age who do not use contraceptives.

Lactation. Available pharmacokinetic data obtained in animals showed the release of roflumilast or its metabolites into milk. The risk of a child getting the drug cannot be ruled out. Daxas is not recommended for use during lactation.

Composition of

In 1 coated tablet contains:

Active ingredient:

roflumilast 500 mcg.

Excipients:

lactose monohydrate - 198.64 mg,

corn starch - 53.56 mg,

povidone K90 - 3.9 mg,

magnesium stearate - 2.6 mg.

Shell composition:

hypromellose 2910 - 3 mg,

macrogol 4000 - 4 mg,

titanium dioxide (E171) - 1.25 mg,

dye iron oxide yellow (E172) - 250 mcg.

Dosage and Administration

Inside. The drug Daxas is prescribed in tablets of 0.5 mg 1 time per day. Tablets must be washed down with water and taken daily at the same time, regardless of food intake. To achieve a therapeutic effect, treatment may be required for several weeks.

There is evidence of clinical studies on the duration of Daxas administration for up to one year.

Dose adjustment based on patient age (over 65) is not required. Clinical data on the use of the drug Daxas in patients with impaired grade A liver function according to the Child-Pugh classification are insufficient to recommend dose adjustment, therefore, the drug should be used with caution in the treatment of such patients. Patients with kidney disease do not need dose adjustment.

Side effects

The most common complaints are diarrhea (5.9%), weight loss (3.4%), nausea (2.9%), abdominal pain (1.9%) and headache (1, 7%). Most of these adverse side reactions are mild or moderate. Such adverse reactions mainly occur during the first weeks of treatment and in most cases disappear as treatment continues.

Side effects are classified according to frequency of occurrence: most frequent - 1/10 frequent - 1/100 and

Immune system disorders: infrequent - hypersensitivity.

Disorders from the endocrine system: rare - gynecomastia.

Disorders from metabolism and nutrition: frequent - weight loss, loss of appetite.

Mental disorders: frequent - insomnia infrequent - rare anxiety - nervousness, depression. During clinical trials, reports of rare cases of suicidal thinking and behavior (including completed suicide) were received. Patients should be instructed to inform their doctor of all manifestations of suicidal ideation.

Disorders of the nervous system: frequent - headache infrequent - tremors, vertigo, dizziness rare - dysgeusia.

Violations by the CCC: infrequent - tachycardia.

Disorders of the respiratory system, chest and mediastinal organs: rare - respiratory tract infections (except pneumonia).

Disorders from the gastrointestinal tract: frequent - diarrhea, nausea, abdominal pain infrequent - gastritis, vomiting, gastroesophageal reflux disease, rare dyspepsia - hematochesia, constipation.

Disorders from the liver and biliary tract: rare - increased activity of GGT, increased activity of AST.

Disorders of the skin and subcutaneous tissue: infrequent - rare rash - urticaria.

Disorders from the musculoskeletal and connective tissue: infrequent - muscle spasms and muscle weakness, myalgia, back pain rare - increased creatine phosphokinase in the blood.

Complications of a general nature and reactions at the injection site: infrequent - malaise, asthenia, fatigue.

Drug Interaction

A major step in the metabolism of roflumilast is the N-oxidation of roflumilast into roflumilast N-oxide by cytochrome CYP3A4 and CYP1A2. Both roflumilast and N-oxide roflumilast have PDE4 inhibitory activity. Therefore, after administration of roflumilast, the total PDE4 inhibitory activity is a total effect of both roflumilast and roflumilast N-oxide. Clinical studies of interactions with cytochrome CYP3A4 inhibitors erythromycin and ketoconazole have shown a 9% increase in PDE4 total inhibitory activity.

Interaction studies with the cytochrome CYP1A2 inhibitor fluvoxamine, and CYP3A4 and CYP31A2 inhibitors enoxacin and cimetidine showed an increase in PDE4 total inhibitory activity of 59%, 25%, and 47%, respectively. The combined use of Daxas with these active substances may lead to increased action and the development of intolerance. In this case, it is necessary to reconsider the issue of treatment with the drug Daxas.

Reception of the cytochrome P450 inducer rifampicin resulted in a 60% reduction in total PDE4 inhibitory activity. Therefore, the use of potent inducers of cytochrome P450 (eg, phenobarbital, carbamazepine, phenytoin) may lead to a decrease in the therapeutic effect of roflumilast.

Co-administration with theophylline resulted in an 8% increase in total PDE4 inhibitory activity. In a study of interaction with oral contraceptives containing gestodene and ethinylestradiol, the total PDE4 inhibitory activity increased by 17%. No interaction was observed with inhalation (salbutamol, formoterol, budesonide) and oral preparations (montelukast, digoxin, warfarin, sildenafil, and midazolam). Co-administration with antacid drugs (combination of aluminum hydroxide and magnesium hydroxide) did not change the absorption rates or pharmacokinetic properties of roflumilast or roflumilast N-oxide.

Overdose

During the first phase of clinical studies, following the single oral dose of 2.5 mg and a single dose of 5 mg (10 times the recommended dose), the following symptoms were most commonly observed: headache, gastrointestinal disorders, tachycardia, head , clouding of consciousness, sweating and hypotension.

In case of overdose, it is recommended to carry out appropriate symptomatic therapy. Since roflumilast is highly bound to plasma proteins, hemodialysis is not an effective method of its removal. No data, Is roflumilast amenable to peritoneal dialysis.

Storage conditions

At a temperature not exceeding 30 ° C.

D ystvuyushtee substance

Roflumilast

Conditions of release from drugstores

Prescription

Dosage PMA



Appointment

Appointment

Adults doctor's prescription

Takeda GmbH, Japan



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