DAXAS PILLS 0,5MG

Indications

- as a maintenance therapy in the treatment of severe COPD (post-bronchodilation FEV1 should be less than 50% of the calculated due indicator) in adult patients with frequent exacerbations in history.

Contraindications

- moderate or severe liver failure (class B and C according to Child-Pugh classification);

- age up to 18 years (efficacy and safety have not been established);

- pregnancy;

- lactation period (breastfeeding);

- hypersensitivity to the drug.

Contraindications due to lack of experience with:

- serious immunodeficiency diseases (including HIV infection, multiple sclerosis, systemic lupus erythematosus, progressive multifocal leukoencephalopathy);

- 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 class 3 and 4 according to the NYHA classification;

- treatment with immunosuppressive drugs (such as Methotrexate, azathioprine, infliximab, etanercept, as well as in patients receiving continuous supportive therapy with oral GCS);

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

- depression associated with the appearance of suicidal thinking and behavior.

WITH caution should use the drug for mental disorders in history; with a mild form of liver failure (class A according to Child-Pugh classification); treatment with CYP1A2 isoenzyme inhibitor fluvoxamine or two CYP3A4 / 1A2 inhibitors enoxacin and cimetidine.

Dosage

The drug is administered orally at a dose of 500 mcg 1 time / day.

Treatment may take several weeks to achieve a therapeutic effect. There are data from clinical studies on the duration of the drug Daxas up to one year.

Have elderly patients (over 65 years) dose adjustment is not required.

Clinical data on the use of the drug Daxas patients with impaired liver function class A according to the Child-Pugh classification not enough to recommend a dose adjustment, so the drug should be used with caution in the treatment of these patients.

Have kidney patients dose adjustment is not required.

Tablets need to be washed down with water and taken daily at the same time, regardless of the meal.

Overdose

During the first phase of clinical studies after taking a single oral dose of 2.5 mg and a single dose of 5 mg (10 times the recommended dose), the following were more common. symptoms: headache, disorders of the gastrointestinal tract, tachycardia, dizziness, clouding of consciousness, sweating and arterial hypotension.

Treatment: in case of overdose, appropriate symptomatic therapy is recommended. Roflumilast largely binds to plasma proteins, so hemodialysis is not an effective method for its elimination. There is no evidence of whether roflumilast is amenable to peritoneal dialysis.

Drug interaction

The main step in the metabolism of roflumilast is N-oxidation with the formation of N-oxide roflumilast with the participation of CYP3A4 and CYP1A2 isoenzymes. Both roflumilast and roflumilast N-oxide possess intrinsic inhibitory activity against PDE4. Therefore, after taking roflumilast, the total inhibitory activity of PDE4 is the cumulative effect of both roflumilast and roflumilast N-oxide. Clinical studies of interactions with CYP3A4 isoenzyme inhibitors, Erythromycin and Ketoconazole showed an increase in the total inhibitory activity of PDE4 by 9%. Studies of interactions with the CYP1A2 isoenzyme inhibitor, fluvoxamine, and CYP3A4 and CYP31A2 inhibitors, enoxacin and cimetidine, showed an increase in the total inhibitory activity of PDE4 - 59%, 25% and 47%, respectively. Combined use of the drug Daxas with these active substances can lead to increased action and the development of intolerance. In this case, it is necessary to reconsider the issue of treatment with Daxas.

Acceptance of the isoenzyme inducer of the cytochrome P450 system of rifampicin resulted in a decrease in the total inhibitory activity of PDE4 by approximately 60%. Therefore, the use of powerful inducers of this enzyme system (for example, phenobarbital, Carbamazepine, phenytoin) can lead to a decrease in the therapeutic effect of roflumilast.

Simultaneous administration with theophylline led to an 8% increase in the total inhibitory activity of PDE4. In the study of interaction with oral contraceptives containing gestodene and ethinyl estradiol, the total inhibitory activity of PDE4 increased by 17%.

There was no interaction with inhaled drugs Salbutamol, salbutamol, formoterol, Budesonide and oral drugs montelukast, Digoxin, Warfarin, Sildenafil and midazolam.

Simultaneous administration with antacid preparations (a combination of aluminum hydroxide and Magnesium hydroxide) did not change the absorption rates or pharmacokinetic properties of roflumilast or roflumilast N-oxide.

Pregnancy and lactation

The use of the drug Daxas during pregnancy and lactation (breastfeeding) is contraindicated.

Data on the use of roflumilast in pregnant women is limited.

It is not recommended to prescribe the drug. women of childbearing agenot using reliable contraceptive methods.

It is possible that the infant will receive the drug during breastfeeding, therefore, if necessary, use of the drug during lactation should decide on the termination of breastfeeding.

In the study of human spermatogenesis, roflumilast at a dose of 500 mcg did not affect sperm parameters or sex hormones during treatment for 3 months and for the next 3 months after cessation of treatment.

AT experimental studies in animals, roflumilast has been shown to penetrate the placental barrier; has reproductive toxicity. Pharmacokinetic data obtained in animals showed the release of roflumilast or its metabolites in breast milk.

Side effects

Most often: diarrhea (5.9%), weight loss (3.4%), nausea (2.9%), abdominal pain (1.9%), and headache (1.7%). These adverse reactions mainly occur during the first weeks of treatment and in most cases disappear as the treatment continues; most of them are light or moderate.

Determination of the frequency of adverse reactions: very often (≥1 / 10), often (≥1 / 100 and <1/10), infrequently (≥1 / 1000 and <1/100), rarely (≥1 / 10 000 and <1 / 1000), very rarely (<1/10 000).

Gastrointestinal: often - diarrhea, nausea, abdominal pain; infrequently - gastritis, vomiting, gastroesophageal reflux disease, dyspepsia; rarely - hematochezia, constipation, increased activity of GGT, AST.

From the psyche: often - insomnia; infrequently - anxiety; rarely - nervousness, depression. In clinical trials, reports of rare cases of suicidal thinking and behavior (including completed suicide) were received. Patients should be instructed to inform their physician about all manifestations of suicidal thinking.

Cardiovascular: infrequently - tachycardia.

Respiratory: rarely, respiratory tract infections (other than pneumonia).

Nervous system: often - headache; infrequently - tremor, vertigo, dizziness; rarely - dysgeusia.

On the part of the endocrine system: rarely - gynecomastia.

Metabolism and nutrition: often - weight loss, loss of appetite.

Dermatologic: infrequently - rash.

Allergic reactions: infrequently - hypersensitivity; rarely - urticaria, angioedema.

Musculoskeletal system: infrequently - muscle spasms and muscle weakness, myalgia, back pain; rarely, an increase in blood CPK.

Other: Infrequently - malaise, asthenia, fatigue.

Terms and conditions of storage

Keep out of the reach of children at a temperature not exceeding 30 ° C. Shelf life - 3 years.

special instructions

Daxas is a non-steroidal anti-inflammatory agent intended for the maintenance treatment of patients with severe COPD with frequent exacerbations. Due to the fact that in the general population of COPD, patients over the age of 40 years predominate significantly, when prescribing the drug to patients under 40 years of age, spirometric confirmation of the diagnosis of COPD is required.

According to the indications for use of the drug, it is necessary that the value of post-bronchodilation FEV1 should be less than 50% of the calculated proper indicator.

Daxas is not intended to treat an acute attack of shortness of breath (acute bronchospasm).The patient should be warned that in order to relieve an acute attack, it is important to always have a medicine prescribed by a doctor in order to stop the attack. Daksas in this case is not effective.

In the course of studies conducted during the year, there was more often a decrease in body weight in patients who received Daxas, compared with patients who received placebo. After discontinuing the drug, Daxas in most patients was restored to body weight within 3 months.

In patients with underweight should be monitored at each visit to the doctor. Patients should be advised to regularly monitor their body weight. In the case of an unexplained or clinically significant weight loss, you must stop taking Daxas and monitor the dynamics.

Due to the lack of sufficient experience, it is not advisable to start treatment with Daxas for patients receiving continuous maintenance therapy with oral GCS, with the exception of short-term courses of systemic GCS.

Experience with the use of the drug Daxas in patients with latent infections, such as tuberculosis, viral hepatitis, viral herpes and shingles, is limited.

The use of Daxas is associated with an increased risk of mental disorders such as insomnia, anxiety, nervousness, and depression. In clinical studies, rare cases of suicidal thinking and behavior have been identified.Therefore, if patients report previously manifested symptoms from the psyche or such symptoms are presently present, or if concomitant therapy with other drugs is planned, related to the likelihood of mental disorders, a careful assessment of the risks and benefits associated with the onset or continuation of drug treatment Daxas. Patients should be instructed to notify the physician prescribing the treatment of any changes in the behavior, mood or occurrence of suicidal thoughts of any nature.

Despite the fact that adverse reactions such as diarrhea, nausea, abdominal pain and headache occur mainly in the first weeks of treatment and in most cases go away with continued treatment, if these symptoms persist, the issue of treatment with Daxas should be reconsidered.

Intolerance can occur in the case of special populations of patients, in particular, in non-smoking black women or patients receiving treatment with a CYP1A2 inhibitor fluvoxamine or two inhibitors of CYP3A4 / 1A2 enoxacin and cimetidine.

There is no clinical data regarding concomitant treatment with theophylline as maintenance therapy. Therefore, concomitant therapy with theophylline is not recommended.

Influence on ability to drive motor transport and control mechanisms

Because of the possibility of adverse reactions, patients should be careful when driving and doing other potentially hazardous activities,requiring increased concentration and speed of psychomotor reactions.

In case of impaired renal function

Have kidney patients dose adjustment is not required.

With abnormal liver function

Clinical data on the use of the drug Daxas patients with impaired liver function class A according to the Child-Pugh classification not enough to recommend a dose adjustment, so the drug should be used with caution in the treatment of these patients.

WITH caution should be used in the mild form of liver failure (Child-Pugh class A).

Use in old age

Elderly patients (over 65 years) do not require dose adjustment.

Use in childhood

Contraindicated in children and adolescents under 18 years of age.