FARMATEKA » Experience with drug therapy with Dalfaz in patients with various urinary disorders

Introduction

Violation of the act of urination is one of the most common complaints that is the basis for contacting a urologist. It should be noted that the prevalence of urinary disorders is directly proportional to age: patients over 50 years of age are most susceptible to them. The changing demographic situation throughout the world and in our country, characterized by an increase in the number of older people, makes urinary disorders a number of priority medical and social problems.

Early 1990s was marked by a sharp increase in the interest of urologists around the world in the problem of drug therapy for urination disorders caused by diseases of the lower urinary tract. With all the variety of drugs for the correction of urinary disorders, the group of selective alpha1-blockers confidently occupies a leading position [2, 3]. Drugs in this group are successfully used for obstructive urination of almost any etiology, not only in men, but also in women.

Currently, there is objective evidence of the effectiveness of treating various urinary disorders with alpha1-blockers. The reasons for the widespread use of drugs of this pharmacological group become obvious when considering the mechanisms of their action. The pathogenesis of urinary dysfunction in most urological patients is based on insufficiency of energy metabolism and detrusor hypoxia in conditions of increased urethral resistance. The work of the staff of our department has proven that in the muscle tissue of the bladder there is a decrease in the arteriovenous difference in partial oxygen tension and metabolic acidosis, as well as a decrease in the activity of enzymes in the detrusor tissue involved in key reactions of aerobic oxidation. In parallel, there is an increase in the activity of glycolytic enzymes and enzymes of the pentose phosphate shunt, indicating the predominance of glycolysis in the detrusor [2].

The causes of disorders of energy metabolism and detrusor function are extremely diverse. In particular, they can accompany increased activity of the sympathetic nervous system, organ circulatory disorders, vitamin deficiency (group B), chronic diseases of the respiratory and cardiovascular systems, and are aggravated by taking a number of pharmacological drugs that inhibit the respiratory chain. Naturally, such disturbances are also observed in obstructive urodynamic disorders [2, 6].

The mechanism of action of alpha1-adrenergic blockers in a patient with urinary disorder is based on blocking the transmission of nerve impulses in the sympathetic nervous system, relaxing the smooth muscles of the affected area, which in turn causes a decrease in intraurethral resistance and improved blood supply to the pelvic organs.

Benign prostatic hyperplasia

In recent years, drug therapy for benign prostatic hyperplasia (BPH) with alpha1-blockers has become an international standard [2, 12, 13]. In popularity, these drugs are noticeably superior to 5-alpha reductase blockers and herbal drugs [18].

Recent studies indicate that in patients with BPH, two parallel processes occur in the lower urinary tract - the formation of urethral obstruction and a violation of the energy metabolism of the detrusor (mitochondrial insufficiency). The cause of obstruction is an increase in the size of the prostate with a gradual narrowing of the lumen of the urethra (mechanical component) and an increase in the tone of the smooth muscle fibers of the prostate and posterior urethra (dynamic component) [2, 5].

In some elderly men with BPH, secondary structural and functional changes in the detrusor obstructive nature are aggravated by stress (direct catecholamine effects) and ischemic (vasospasm) damage to the smooth muscle elements of the bladder. In these cases, the bladder experiences increased exposure to catecholamines, and as a consequence of this process, disorders of bioenergetics and detrusor function occur [2].

Alpha-blockers eliminate the hypertonicity of the smooth muscles of the prostate stroma, which occupies up to 60% of the volume of the hyperplastic prostate, which makes it possible to level out the dynamic component of bladder outlet obstruction [19]. On the other hand, experimentally proven improvement in blood supply to the bladder, which occurs during treatment with alpha-blockers, leads to an improvement in the bioenergetics of the detrusor and the restoration of its contractility.

Many international comparative multicenter studies have proven that during treatment with alpha1-blockers in patients with BPH, symptoms decrease on average by 50%, the maximum volumetric flow rate of urination increases by 30–47%, and the amount of residual urine is halved [6, 13, 16 , 17].

Currently, several alpha-blockers are available in Russia: alfuzosin, terazosin, doxazosin and tamsulosin. Comparative studies of these drugs, conducted in many urological clinics around the world, have proven their almost equal effectiveness. The issue of selecting optimal therapy within a given pharmacological group in recent years has ceased to be determined by the degree of effect of the drug on the symptoms of BPH, but depends mainly on the ease of use, availability of drugs and the individual preferences of the doctor. Based on the results of a comparison of effectiveness, safety and ease of use, alfuzosin (Dalfaz) occupies a leading position among all alpha-blockers in Russia and European countries. Currently, the Department of Urology of Moscow State Medical University has experience in its use in more than 1,600 patients with BPH.

As mentioned above, the frequency of side effects, of which the most common are low blood pressure, dizziness and headache, are almost the same for all selective alpha1-blockers. The occurrence of side effects of varying intensity during treatment is recorded in 10–16% of patients receiving treatment with these drugs [6, 13]. The mechanism of occurrence of the above side effects is based on the effect of alpha1-blockers on the smooth muscles of the vascular wall, leading to vasodilation and blood deposition in the periphery, especially with a sharp change in body position after a long rest.

Given their high efficiency and low number of side effects, selective alpha1-blockers have become the drugs of choice in the drug therapy of BPH in recent years. They are used in the treatment of patients with mild or moderate symptoms, as well as those awaiting surgery or wishing to avoid surgery.

Obstructive urination in women

One of the manifestations of a violation of the mechanism of urine evacuation during urination in women is obstructive urination, caused by both organic (urethral stenosis) and functional reasons [7, 8]. The fundamental mechanisms for the development of functional obstruction in women include neurogenic urination disorders and impaired detrusor bioenergetics. Similar conditions are often observed against the background of various inflammatory diseases of the urinary tract. Analysis of the most typical complaints presented by patients, as well as the study of the etiology of urinary disorders, often reveal the commonality of the mechanisms of their occurrence in men and women. Common causes of obstructive urination are bladder hypotension, postoperative conditions, urethral instability and detrusor-sphincter dyssynergia. Contraction of the striated muscles of the urethra occurs simultaneously with contractions of the detrusor, which leads to a rise in detrusor pressure to high numbers and the occurrence of intermittent urine flow [9, 10].

The general term that describes the involuntary contractions of the detrusor that cause the clinical symptoms of urinary urgency is detrusor overactivity. Overactive bladder (OAB) is a symptom complex that includes:

the occurrence of a strong, sudden urge to urinate (urgency);
urge urinary incontinence;
nocturia (night urination);
pollakiuria.

The relevance of this problem is proven by the fact that out of 27 thousand urodynamic studies in women conducted at our department over the past 14 years, in 10–15% of cases obstructive urination was noted in the absence of signs of urethral stenosis and other organic changes. Despite the widespread prevalence of OAB, most patients both in our country and abroad do not seek help from specialists, considering their condition a natural consequence of age-related changes or not knowing that this pathology is curable. As a result, it is quite difficult to estimate the true prevalence of urge urinary disorders. Until recently, treatment of patients with such functional disorders was limited to the use of drugs such as oxybutynin and tolterodine, a set of exercises aimed at relaxing the pelvic floor muscles, and training in self-catheterization techniques [14].

At present, there is no consensus on the effectiveness of treatment of imperative urinary disorders. The choice of treatment tactics for a patient depends on the type and severity of bladder dysfunction, the effectiveness of previously used treatments and the presence of concomitant pathology or complications from other organs and systems. The main principle should be to start treatment with the least traumatic methods that give the least number of side effects.

Based on knowledge of the mechanisms of action of alpha1-blockers, we hypothesized that they can be successfully used in the treatment of symptoms of obstructive urination not only in men, but also in women. Dalfaz retard was chosen as a classic representative of the pharmacological group of alpha1-adrenergic blockers, prescribed to 130 patients with obstructive urination of various etiologies (except organic obstruction) in a standard dosage of 5 mg 2 times a day. The mechanism of action of Dalfaz in this category of patients, as well as in BPH, is multifaceted - it is a direct adrenergic blocking effect on receptors in the smooth muscles of the bladder neck and an antihypoxic effect as a consequence of normalizing the tone of the vascular wall. In a small group of patients, Dalfaz was prescribed in combination with Picamilon (nicotinoyl-gamma-aminobutyric acid) or Essentiale Forte. In most patients, at the first stage of treatment, drug therapy was combined with intermittent catheterization of the bladder.

The duration of treatment ranged from two months to six months. By the end of the course of treatment, positive changes in the quality of urination, expressed in regression of obstructive and irritative symptoms, were noted by 79 patients (61%). In parallel with the assessment of the quality of urination, data from a combined urodynamic study were monitored, demonstrating the complete absence of influence of Dalfaz on the maximum urethral pressure and functional length of the urethra. The maximum urine flow rate increased from 11.8 to 16.7 ml/s, and the maximum amount of residual urine decreased from 300 to 50 ml.

The above data indicate the high effectiveness of therapy for obstructive urination in women with alpha1-blockers and allow us to recommend it for use in wide clinical practice.

Acute urinary retention

One of the most common and most serious complications of BPH in older men is acute urinary retention (AUR). Data from epidemiological studies indicate an increased risk of developing AUR by 3–4 times due to an increase in prostate volume of more than 40 cm3 and prostate-specific antigen (PSA) above 1.4 ng/ml [21]. The risk of developing AUR is also associated with increasing age and the severity of symptoms of urinary disorders according to various questionnaires (IPSS, AUA, Boyarsky) [22]. The likelihood of developing AUR in men over 70 years of age is 8 times higher than in 40-year-old men [21].

The treatment strategy for these patients depends entirely on the likelihood of restoration of independent urination. The most popular method of combating AUR is bladder drainage with a urethral catheter. According to data published in BJU, 98% of surveyed urologists do this [23], and the duration of drainage is directly proportional to the probability of restoration of independent urination and increases 1.4 times when this period is prolonged from 1 to 7 days [24]. It should be noted that the downside of long-term catheterization is the risk of catheter infection and the development of urethritis.

The outcome of therapy aimed at restoring independent urination in patients with AUR largely depends on the factors that provoked it. Treatment should be comprehensive and aimed at eliminating these factors. Thus, if indicated, antibacterial, antihistamine, antispasmodic and other drugs should be used.

Recent work has proven that the use of alpha1-blockers can increase the likelihood of restoration of spontaneous urination in patients with BPH with new-onset AUR after removal of the urethral catheter and reduce the need for subsequent surgical intervention [23–25].

According to data obtained in recent years on the pharmacodynamics of drugs from the group of alpha1-adrenergic blockers, the effect of their use develops within a few hours after taking the first tablet. Thus, the maximum concentration of alfuzosin in the blood, according to the Synthelabo Groupe laboratory, is achieved within 30 minutes after taking a 5 mg tablet, and when the same amount of the drug is administered intravenously, intraurethral pressure decreases by 50% in 20 minutes [11, 20]. Additional advantages of this drug, which are of key importance in the medical resolution of AUR, are the absence of the need to titrate the dose and the possibility of initial administration at a high therapeutic dosage.

Since 1997, the Department of Urology of the Moscow State Medical University has been working on the relief of AUR by prescribing alpha1-blockers. At the first stage of this study, we were convinced of the inappropriateness of prescribing Dalfaz as the only measure to relieve AUR. Despite the speed and effectiveness of the drug, due to the long stay of the detrusor in a state of overextension, its contractility cannot be restored in full in a short period of time. Simultaneous administration of a daily dose of Dalfaz (10 mg orally) led to the restoration of independent urination in only 15% of patients.

Currently, our tactics for managing patients with new-onset AUR involves drainage of the lower urinary tract with a Foley urethral catheter No. 16–18 Ch in parallel with the administration of Dalfaz. Of the 50 patients who received the above treatment for 3 days, spontaneous urination after removal of the urethral catheter was restored in 18 (36%). However, 6 patients (12%) from this group subsequently underwent elective surgery for BPH, and 12 patients (24%) continued drug treatment.

Our data on the high effectiveness of combining therapy with alpha1-blockers with drainage of the lower urinary tract for the purpose of conservative relief of new-onset AUR allows us to recommend this treatment tactic for widespread use.

Combination therapy for BPH

The pathogenesis of urination disorders in patients with BPH is represented by 3 mechanisms: the dynamic component of bladder outlet obstruction and the disorder of detrusor bioenergetics, which were mentioned above, and the mechanical component of bladder outlet obstruction, caused by an increase in the size of the prostate, causing compression of the urethra in the prostatic region. The third component becomes of great importance when the volume of the prostate gland exceeds 50–60 cm3, which is often observed in Russian patients. According to statistics, in Russia, most patients suffering from BPH turn to a urologist quite late, when the prostate gland is already significantly enlarged in size [1]. The fact that the average prostate volume in a patient with BPH in Russia exceeds that in other countries of the world makes the problem of drug reduction of prostate volume especially relevant.

The only drug available in Russia that reliably reduces the volume of the prostate gland is the 5-alpha reductase blocker finasteride, which inhibits cell proliferation at the hormonal level [4]. However, these changes become noticeable after at least 6 months of continuous use of the drug, and they reach significant values after 12–18 months from the start of treatment. The slow-onset effect of treatment and the ability of finasteride to act exclusively on the mechanical component of bladder outlet obstruction became the basis for combination therapy with 5-alpha-reductase blockers and alpha1-blockers [1, 4, 15]. The latter have a rapid effect and neutralize two mechanisms of the pathogenesis of urinary disorders that are not affected by 5-alpha reductase blockers. The high effectiveness of this treatment was proven in a large long-term study of the combined administration of finasteride and doxazosin - MTOPS [26].

In a 3-year study of a similar design, conducted at the Department of Urology of Moscow State Medical University, an improvement in the quality of urination and a reduction in the symptoms of BPH was noted by 96% of patients receiving combination therapy, 74% by finasteride and 84% by alfuzosin. A detailed analysis of the results confirms the higher effectiveness of treatment in the combination therapy group: the IPSS score decreased by 45% versus 41 and 42% in the monotherapy groups. The positive dynamics of the QoL score was also more pronounced in the combination treatment group: 36% versus 33 and 23%. The advantages of combination therapy are obvious when analyzing not only subjective, but also objective parameters. Thus, the maximum urine flow rate after a course of treatment in the combination therapy group increased by 44%, and in the finasteride and alfuzosin monotherapy groups by only 24 and 38%, respectively. The most obvious difference in treatment results becomes when comparing the dynamics of changes in the volume of the prostate gland. During combined treatment with finasteride and alfuzosin, the prostate gradually decreases in volume (by 25% by the end of 3 years of treatment). On the background of alfuzosin monotherapy, prostate volume, on the contrary, increased by 13.3%. The percentage of adverse events reported during treatment was comparable in all three groups.

Thus, combined drug therapy with alpha1-adrenergic blockers and 5-alpha-reductase blockers is pathogenetically justified and effective in patients with BPH with no absolute indications for surgery and severe symptoms of urinary disorders with a significant increase in the volume of the prostate gland [1, 4]. World literature data, confirming the high effectiveness of such treatment, indicate the ability of alpha1-blockers with long-term use to significantly (almost 10 times) reduce the risk of developing AUR [21, 22].

Chronic prostatitis

Therapeutic tactics for patients with urinary disorders caused by chronic prostatitis and prostatodynia have long been the subject of active discussion among urologists.

Although there is no consensus on the etiology of CP/CPPS, most urologists recognize the high incidence of neurogenic disorders leading to obstructive urination in these patients. Incomplete opening of the bladder neck during urination, accompanied by increased urethral tone with its narrowing at the level of the external sphincter, leads to a significant increase in urethral closure pressure, the occurrence of turbulent urine flow, and a decrease in the maximum and average urine flow rate (Qmax and Qmean). All of the above leads to reflux of urethral contents into the ducts of the prostatic glands [27]. The ensuing inflammatory reaction causes increased activity of alpha-adrenergic receptors, which, in turn, leads to an increase in the tone of the smooth muscles of the bladder neck, sphincter, prostate and posterior urethra, resulting in poor drainage of the prostatic acini, activation of the arachidonic acid cascade and worsening urodynamic disorders , provoking repeated reflux.

The complaints made by patients with chronic prostatitis are in many ways similar to those of patients with BPH.

For 3 years, the Department of Urology of Moscow State Medical University has been working to study the effectiveness of therapy with alpha1-blockers in order to eliminate urinary disorders in chronic prostatitis. All patients undergo a preliminary examination, during which the presence or absence of signs of bacterial inflammation in the prostate tissue is determined. If the presence of bacterial inflammation is confirmed, patients undergo complex antibacterial and anti-inflammatory therapy in combination with alpha1-adrenergic receptor blockers and multivitamin preparations. In the absence of bacterial inflammation, alpha1-blockers are the main active principle.

Treatment was carried out using various drugs from the group of selective alpha1-blockers, but the most numerous was the group of patients receiving Dalfaz. Over the past 3 years, 140 patients suffering from chronic nonbacterial prostatitis have undergone treatment with this drug. The vast majority of patients had a history of multiple attempts at treatment with antibacterial and anti-inflammatory drugs that did not give the desired effect. More than half of the patients had received various physiotherapeutic procedures or prostate massage courses in the past. 3 months after the start of Dalfaz therapy, a subjective improvement in the quality of urination and a decrease in the severity of urination disorders was noted by 127 (90.8%) of 140 patients. The average IPSS total score decreased from 18.6 to 12.4.

Work on studying the effectiveness of treating urinary disorders in chronic prostatitis by prescribing selective alpha1-blockers continues, but even the above preliminary data indicate the feasibility of such treatment.

The effect of alpha1-blockers on sexual function in patients with BPH

Sexual dysfunction is often not an independent disease, but a manifestation of various disorders in a man’s body. The prevalence and severity of erectile dysfunction clearly correlates with age and is about 50% at 50 years old, 60% at 60 years old, and 70% at 70 years old. At the same time, symptoms of urinary dysfunction are present in 72.2% of patients with erectile dysfunction [28]. Within one age group, the incidence of sexual disorders is directly proportional to the severity of symptoms of urinary disorders [29].

Data from several international studies of the effectiveness of the use of alpha1-blockers indicate that, along with a decrease in the severity of symptoms of urinary dysfunction, many patients note an improvement in sexual function. It is assumed that this effect is based on the polyvalent mechanism of action of alpha1-adrenergic blockers, which helps improve blood circulation in the pelvic organs and generally improve the patient’s quality of life. Since 1990, the Department of Urology of Moscow State Medical University has been working to study the effectiveness and safety of treating symptoms of urinary disorders in men. The total number of patients who received alpha1-blockers for this purpose is about 2200 people. The average improvement in quality of life, as measured by the QoL questionnaire, was 32%. Positive changes in the patient’s general status, a decrease in the severity of symptoms of urinary disorders and an improvement in the quality of life indicators result from an improvement in the patients’ sexual activity indicators. Research in this direction continues.

Conclusion

Research into the pathogenesis of urinary disorders in various diseases of the lower urinary tract and advances in pharmacology in recent years have led to an increase in the popularity of drug treatment for these conditions, with selective alpha1-blockers taking the leading positions in all European countries and the United States. Every year, many clinical studies are conducted, the purpose of which is to expand the boundaries of the use of this most numerous and promising group of drugs. This article summarizes the experience of the Department of Urology at Moscow State Medical University over the past few years, demonstrating the expansion of indications for the use of selective alpha1-blockers in urology. Work is underway to study the possibilities of drug treatment of urinary disorders in the early and late postoperative period, with various neurogenic disorders, the effect of alpha1-blocker therapy on copulatory function, giving good preliminary results.

Selective alpha1-blockers are the most popular drugs for the treatment of urinary disorders in various urological diseases, and the scope of their use will increase in proportion to the accumulated experience, knowledge of the pharmacodynamics and mechanism of action.

Dalfaz® SR

Orthostatic hypotension is usually transient and is observed, as a rule, at the beginning of taking the drug and usually does not require discontinuation of treatment.

During post-marketing use of the drug in patients with risk factors for lowering blood pressure (such as heart disease or concomitant therapy with antihypertensive drugs), a pronounced decrease in blood pressure has been reported. The risk of excessive reduction in blood pressure and associated adverse reactions may be higher in elderly patients.

Before starting treatment, the patient should be warned about the possibility of the reactions described above.

- Caution should be exercised when using alfuzosin in patients with orthostatic hypotension with clinical symptoms or in patients taking antihypertensive drugs or nitrates: more careful monitoring of blood pressure is necessary, including when moving from a horizontal to a vertical position, especially at the beginning of treatment.

- Caution should be exercised when using alfuzosin in patients with a history of significant hypotensive reactions in response to other alpha1-adrenergic blockers.

— Patients with coronary insufficiency while taking alfuzosin should continue antianginal therapy. If angina recurs or worsens, treatment with alfuzosin should be discontinued.

- Caution should be exercised when using alfuzosin in patients with congenital or acquired QT prolongation or in patients taking medications that can prolong the QT interval.

— During ophthalmic surgery for cataracts, some patients taking or previously taking certain alpha1-blockers developed intraoperative floppy iris syndrome (a variant of small pupil syndrome). Although the risk of developing such a complication when taking Dalfaz® SR seems to be very low, before performing cataract surgery, the ophthalmologist should be informed that the patient is taking or has previously taken alpha1-blockers, since the development of intraoperative floppy iris syndrome may increase the number of complications with this surgical intervention. Ophthalmologists must be prepared for possible changes in surgical techniques.

— Patients should be warned that it is prohibited to crush, crush, chew, or grind the tablet into powder. Such actions can lead to excessive release and absorption of the drug, as a result of which the rapid development of side effects is possible, which is especially dangerous in patients with cerebrovascular disorders that occur with corresponding symptoms, as well as in those patients in whom cerebrovascular disorders are asymptomatic, since in such patients patients with a sharp decrease in blood pressure may increase cerebral ischemia.

— There are reports of cases of the development of priapism (prolonged painful erection of the penis, not associated with sexual activity) during therapy with alpha-g blockers. If priapism therapy is not carried out immediately, it can lead to damage to the tissue of the penis and irreversible loss of potency. Patients should be informed of the seriousness of this condition (see Side Effects section) and the need to seek immediate medical attention if an erection persists for more than 4 hours.

DALFAZ RETARD

special instructions

- Within a few hours after taking alfuzosin (as after taking any other alpha1-blockers), some people, especially patients taking antihypertensive drugs, may develop orthostatic hypotension with clinical symptoms (dizziness, severe weakness, cold sweats) or without her.
When these phenomena develop, the patient must remain in a horizontal position until they completely disappear. Orthostatic hypotension is usually transient and is observed, as a rule, at the beginning of taking the drug and usually does not require discontinuation of treatment.

Before starting treatment, the patient should be warned about the possibility of the reactions described above.

- Caution should be exercised when using alfuzosin in patients with a history of significant hypotensive reactions in response to other alpha1-adrenergic blockers.

— Patients with coronary insufficiency while taking alfuzosin should continue antianginal therapy. If angina recurs or worsens, treatment with alfuzosin should be discontinued.

- Caution should be exercised when using alfuzosin in patients with congenital or acquired QT prolongation or in patients taking medications that can prolong the QT interval.

- Due to the fact that after taking alfuzosin, a decrease in blood pressure is possible, there is a risk of developing ischemic cerebrovascular accident in patients predisposed to this (both those with corresponding symptoms and those in whom previous cerebrovascular disorders are asymptomatic).

— During ophthalmic surgery for cataracts, some patients taking or previously taking certain alpha1-blockers developed intraoperative floppy iris syndrome (a variant of small pupil syndrome). Although the risk of developing such a complication when taking Dalfaz® retard seems to be very low, before performing cataract surgery, the ophthalmologist should be informed that the patient is taking or has previously taken alpha1-blockers, since the development of intraoperative floppy iris syndrome may increase the number of complications with this surgical intervention.

Ophthalmologists must be prepared for possible changes in surgical techniques

— There are reports of cases of the development of priapism (prolonged painful erection of the penis, not associated with sexual activity) during therapy with alpha1-blockers. If priapism therapy is not carried out immediately, it can lead to damage to the tissue of the penis and irreversible loss of potency. Patients should be informed of the seriousness of this condition (see Side Effects section) and the need to seek immediate medical attention if an erection persists for more than 4 hours.

Dalfaz sr 10 mg 10 pcs. extended-release tablets

Composition and release form Dalfaz sr 10 mg 10 pcs. extended-release tablets

Dalfaz® SR Extended-release tablets - 1 tablet. (three-layer):

First layer: hypromellose - 79.75 mg; hydrogenated castor oil - 13.5 mg; ethylcellulose 20 - 5 mg; iron dye yellow oxide (E172) - 0.25 mg; colloidal silicon dioxide aqueous - 0.5 mg; magnesium stearate - 1 mg;
Second layer: alfuzosin hydrochloride - 10 mg; mannitol - 10 mg; hypromellose - 10 mg; MCC - 65 mg povidone - 3.2 mg; colloidal silicon dioxide aqueous - 1.25 mg; magnesium stearate - 1 mg;
Third layer: hypromellose - 114.01 mg; hydrogenated castor oil - 27.9 mg; povidone - 4.72 mg; iron dye yellow oxide (E172) - 0.15 mg; colloidal silicon dioxide aqueous - 1.05 mg; magnesium stearate - 2.17 mg.

In a blister pack 10 pcs.; in a cardboard pack 1 or 3 packs.

Dalfaz® retard Film-coated tablets, prolonged action - 1 tablet:

Active ingredients: alfuzosin hydrochloride - 5 mg;
Excipients: MCC - 42 mg; calcium hydrogen phosphate dihydrate - 65 mg; hydrogenated castor oil - 19.6 mg; povidone - 7 mg; magnesium stearate - 1.4 mg;
Film shell composition: hypromellose - 4.158 mg; propylene glycol - 0.416 mg; titanium dioxide (E171) - 0.416 mg; red iron oxide dye (E172) - 0.1765 mcg and yellow iron oxide dye (E172) - 9.8235 mcg (in the form of a suspension).

There are 14 pcs in a blister; There are 4 blisters in a box.

Description of the dosage form

Extended-release tablets (Dalfaz® SR): round, biconvex, three-layer tablets, one white layer between two yellow layers with varying color intensities. Inclusions are allowed. Film-coated tablets, prolonged release (Dalfaz® retard): round, biconvex, film-coated tablets, pale yellow in color.

Directions for use and doses

Orally prescribed in a daily dose of 5-7.5-10 mg in 2-3 doses.

Pharmacodynamics

Alfuzosin is a quinazoline derivative that is orally active. It is a selective antagonist of postsynaptic alpha1-adrenergic receptors located in the prostate gland, bladder triangle and urethra. Clinical manifestations of benign prostatic hypertrophy are expressed in bladder outlet obstruction of the urinary tract, caused by both anatomical (static) and functional (dynamic) factors. The functional component of obstruction is caused by stimulation of alpha1-adrenergic receptors, leading to contraction of the smooth muscle of the prostate gland, its membrane, the triangle of the bladder and the prostatic urethra, which leads to an increase in resistance to the outflow of urine from the bladder and to secondary instability of the bladder. Due to its direct effects on the smooth muscle of prostate tissue associated with alpha1-adrenergic receptor blockade, alfuzosin reduces bladder outlet obstruction, urethral pressure, and resistance to urinary flow during urination. Due to this, alfuzosin improves the flow of urine and facilitates emptying the bladder. These beneficial effects on urodynamics lead to a reduction in symptoms of urinary tract irritation and symptoms associated with urinary outflow disorders in patients with benign prostatic hyperplasia. In patients with maximum urine outflow rate (Qmax)

Pharmacokinetics

The average relative bioavailability of Dalphase® SR is 104.4% compared to the immediate release form (2.5 mg twice daily) in healthy middle-aged volunteers. Cmax is achieved after 9 hours (Dalfaz® SR), 3 hours (Dalfaz® retard) after oral administration. T1/2 is 9.1 hours (Dalfaz® SR), 8 hours (Dalfaz® retard). The bioavailability of retard tablets is approximately 15% less compared to 2.5 mg alfuzosin. Food intake does not affect the pharmacokinetic profile of the drug. Plasma protein binding is about 90%. Alfuzosin undergoes significant metabolism in the liver, mainly via CYP3A4, with only 11% of the drug excreted unchanged in the urine. Metabolites do not have pharmacological activity. Most metabolites are excreted in feces (75-90%). Pharmacokinetics in special groups of patients In persons over 75 years of age, absorption is faster and Cmax is higher. In some patients, the bioavailability of the drug may increase and the volume of distribution may decrease. T1/2 does not change. In patients with severely impaired liver function, elimination T1/2 and bioavailability increase compared to healthy volunteers. Compared with patients with normal renal function, T1/2 does not change, and the average values of Cmax and AUC in patients with renal failure are moderately increased. These changes in the pharmacokinetic profile of the drug (Dalfaz® SR) are not clinically significant and do not require dose adjustment. In patients with impaired renal function, both requiring and not requiring hemodialysis, due to an increase in the free fraction of the drug (Dalfaz® retard), the volume of distribution and clearance of alfuzosin increases. In chronic heart failure, the pharmacokinetic profile of alfuzosin does not change.

Indications for use Dalfaz sr 10 mg 10 pcs. extended-release tablets

Treatment of prostate adenoma.

Contraindications

fainting when standing up abruptly in the past;
hypersensitivity to the drug.

Application of Dalfaz sr 10 mg 10 pcs. extended-release tablets during pregnancy and breastfeeding

Not applicable.

Overdose

Symptoms: arterial hypotension, reflex tachycardia. Treatment: hospitalization of the patient, constant monitoring of blood pressure. When blood pressure decreases, it is recommended to administer vasoconstrictors and plasma expanders (to increase blood volume). After blood pressure is restored (hypotension is eliminated), it should be monitored for at least another day. Hemodialysis is not effective (due to the high degree of binding of alfuzosin to plasma proteins).

Side effects of Dalfaz sr 10 mg 10 pcs. extended-release tablets

abdominal pain, nausea, diarrhea;
dizziness, headache, malaise;
dry mouth, drowsiness;
palpitations, chest pain, swelling;
skin rash, itching.

Drug interactions

Contraindicated combinations: - alpha1-adrenergic receptor blockers (prazosin, urapidil) - risk of severe orthostatic hypotension and increased hypotensive effect (see section "Contraindications"). Interactions that should be taken into account (for both drugs): - antihypertensive drugs, including CCBs - increased hypotensive effect and the risk of developing orthostatic hypotension (additive effect) (see section "Special instructions"); - CYP3A4 inhibitors (ketoconazole, itraconazole and ritonavir) - it is possible to increase the concentration of alfuzosin (when combined with ketoconazole, the Cmax of alfuzosin increases by 2.1-2.3 times). Dalfaz® retard Additionally: - nitrates - increase the risk of developing reflex tachycardia and lowering blood pressure; — drugs for anesthesia — instability of blood pressure during anesthesia is possible.