Drug for the treatment of benign prostatic hyperplasia (BPH). The competitive and specific inhibitor of 5-alpha-reductase type II – an intracellular enzyme that converts testosterone into the more potent androgen – dihydrotestosterone (DHT). It is a synthetic 4-azasteroidnoe connection. Effectively reduces the level of DHT in the blood and in cancer tissue.
Suppression of DHT formation is accompanied by a decrease in the size of the prostate gland, increase in maximum urinary flow rate and decrease severity of symptoms associated with benign prostatic hyperplasia.
Finasteride has no affinity for the androgen receptor. The drug has no effect on lipid profile, as well as the maintenance of plasma levels of cortisol, estradiol, prolactin, thyroid-stimulating hormone and thyroxine.
Acute administration of finasteride at a dose of 5 mg leads to a rapid decrease in the concentration of DHT in the blood serum with maximum effect after 8 h. Although the level of finasteride in plasma exposed to fluctuations over 24 h, the level of DHT remains constant. This means that the concentration of finasteride in plasma was not correlated with the concentration of DHT in the blood plasma. In patients with BPH who Proscar 5 mg / day given for 4 years, decreased concentration of DHT in the blood by about 70% and a decrease in prostate volume by approximately 20%. In addition, approximately 50% decreased level of prostate-specific antigen (PSA) compared to its initial level, which implies a reduction in the growth of epithelial cells of the prostate gland. The level of testosterone in the blood increased by about 10-20%.
When using Proscar for 7-10 days in patients who were shown prostatectomy, there was a reduction of DHT in prostate tissue by approximately 80% and increase testosterone levels in prostate tissue of 10 times compared to their levels before treatment.
Found that long-term (more than 4 years) use of Proscar patients with benign prostatic hyperplasia (with moderate and severe symptom) reduced the risk of urological complications, and surgery (transurethral resection of the prostate or prostatectomy, acute urinary retention requiring catheterization) in 51% and accompanied by a marked and persistent decrease in prostate volume, and persistent increase in maximum urinary flow rate and improvement of symptoms (Study PLESS).
Patients who took Proscar for 3 months and achieved reduction of prostate volume by approximately 20%, upon termination of treatment prostate volume was returning to the original size within three months.
Thus, Proscar causes a decrease in the size of enlarged prostate, improves the current urine and reduces the symptoms associated with BPH
Indications
Treatment of benign prostatic hyperplasia in order to:
- Prevention of urological complications (risk reduction of acute urinary retention) and reducing the need for surgical operations (including transurethral resection of the prostate and prostatectomy).
- Reduce the size of enlarged prostate, improving the current urine and reduce the severity of symptoms associated with benign prostatic hyperplasia.
Proscar therapy for patients with enlarged prostate gland.
Dosage regimen
The recommended dose is 5 mg (1 tablet) 1 times / day regardless of meals.
Proscar can be used as monotherapy or in combination with doxazosin.
For patients with renal insufficiency of varying severity (with a decrease in QA> = 10 ml / min) did not require individual selection of doses, since pharmacokinetic studies have not revealed any changes in the distribution of finasteride in this category of patients.
For older patients there is also no need for dosage, although pharmacokinetic studies indicate that the removal of finasteride in patients older than 70 years is somewhat reduced.
Side effects
The study PLESS safety assessment was conducted in 1524 patients treated with Proscar 5 mg / day, and in 1516 patients who received placebo for 4 years. At 4.9% (74) patients, treatment was withdrawn because of side effects attributed to Proscar, compared with 3.3% (50) of patients receiving placebo. Thus at 3.7% (57) patients taking Proscar, and 2.1% (32) of patients receiving placebo, treatment was withdrawn because of violation of sexual function, which was the most frequently reported adverse events.
In the first year of treatment of impotence, decreased libido and ejaculation disorder found more frequently in patients taking Proscar compared with placebo. When using Proscar for 2-4 year study of the frequency of the above side effects in patients taking Proscar, did not differ from that of patients taking placebo.
On the part of the reproductive system: sore testicles, impotence, decreased libido, abnormal ejaculation, reduced volume of ejaculate.
On the part of the endocrine system: an increase in pain and breast tenderness.
Allergic reactions: hives, itchy skin, hives, angioedema of the lips and face.
Prolonged use Proscar is not observed to increase the frequency and severity of side effects, and the number of violations of sexual function associated with the medication, if prolonged therapy is reduced.
The safety profile and tolerability of combination therapy in the treatment of finasteride at a dose of 5 mg / day and doxazosin 4 or 8 mg / day is comparable to the safety and tolerability of each of these drugs individually.
At 7-year placebo-controlled study (which included 18882 healthy men) on the results of the biopsy (in 9060 men), prostate cancer was detected in 18.4% of patients treated with Proscar and 24.4% of patients receiving placebo. In 280 men (6.4%) in group Proscar and 237 men (5.1%) in the placebo group on the basis of the results of a biopsy revealed a prostate cancer, estimated at 7-10 points on the Gleason score. Approximately 98% of all cases of cancer tumor was intracapsular (stage T1 or T2).
From the laboratory parameters: reduction of prostate-specific antigen.
Contraindications
- Hypersensitivity to the drug.
Proscar is not shown for use in women and children.
With care prescribe medication for patients with large volume of residual urine and / or significantly reduced current urine (should be carefully monitored for obstructive uropathy).
Pregnancy and lactation
Women of childbearing age and pregnant women should avoid contact with crushed or have lost the integrity of the drug Proscar tablets because of the possibility of penetration of finasteride in pregnant women and subsequent risk for developing male fetus.
In connection with the ability of inhibitors of 5-alpha-reductase type II inhibit the conversion of testosterone to dihydrotestosterone, these drugs, including finasteride, may cause the formation of intrauterine pathology of the external genitalia in male fetus.
Proscar tablets are coated, and it prevents contact with finasteride, provided that the pill does not crushed and did not lose integrity.
Cautions
Impact on the level of prostate-specific antigen and the diagnosis of prostate cancer
So far not shown a positive clinical effect of Proscar patients with prostate cancer. In patients with BPH and elevated PSA in controlled clinical trials (with a few definitions of PSA and biopsy of the prostate gland) Proscar therapy did not affect the frequency of prostate cancer. The overall incidence of prostate cancer were not significantly different in groups of patients treated with Proscar or a placebo.
Before treatment Proscar and periodically during treatment should be carried out rectal examination, and investigation of other methods to determine the presence of prostate cancer. Determination of serum PSA is also used to detect prostate cancer. In general, the baseline PSA above 10 ng / ml required a more extensive examination of the patient, including, if necessary, the appointment of a biopsy. At the level of PSA in the range 4.10 ng / ml recommended further examination of the patient. There is substantial overlap between PSA levels in patients with prostate cancer and patients without the disease. Therefore, in men with BPH and normal values of PSA does not allow to exclude prostate cancer, regardless of treatment Proscar. Source PSA level below 4 ng / ml does not preclude the presence of prostate cancer.
Proscar causes a decrease in serum PSA by approximately 50% of patients with BPH, even in the presence of prostate cancer. In this connection it should be borne in mind that the reduction of PSA levels in patients with BPH receiving treatment Proscar, does not exclude concomitant prostate cancer.
Shown that in patients treated with Proscar for 6 months or more, PSA values should be doubled for comparison with normal values of this indicator in patients not receiving treatment. This adjustment preserves the sensitivity and specificity analysis of PSA and the possibility of prostate cancer.
Any prolonged increase in PSA levels in patients receiving finasteride therapy requires careful examination to determine the cause, which may be in noncompliance of Proscar.
Proscar did not significantly reduce the percentage of free PSA (ratio of free PSA to total). This figure remains constant even under the influence of Proscar. If the diagnosis of prostate cancer using the percentage of free PSA, the adjustment values for this parameter is optional.
Influence on laboratory parameters
The concentration of PSA in the blood serum correlates with patient’s age and prostate volume and prostate volume, in turn, depends on the age of the patient. In determining the level of PSA should be borne in mind that this figure is reduced in patients taking Proscar. In most patients, rapid decrease in PSA levels observed in the first months of therapy, after which it is stabilized at a new level, which is usually half the value measured before the start of therapy. Therefore, patients taking Proscar for 6 months or more, you should double the PSA value for comparison with the normal rates for men not taking Proscar.
Overdose
Patients were treated with Proscar in a single dose to 400 mg and multiple doses of 80 mg / day for 3 months, with no adverse effects were found.
Recommendations for specific treatment of overdose Proscar no.
Drug Interactions
Not detected clinically significant interactions with other drugs Proscar.
Apparently, Proscar has no appreciable effect on the activity of cytochrome P450 isoenzymes and the pharmacokinetics of drugs in the metabolism of which these isozymes prinimyut participation. The combined use of Proscar with propranolol, digoxin, glyburide, warfarin, theophylline, with ACE inhibitors, acetaminophen, acetylsalicylic acid, alpha-blockers, beta-blockers, calcium channel blockers, nitrates, diuretics, blockers, histamine H2-receptor inhibitors of HMG-KoA -reductase inhibitors, NSAIDs, quinolones and benzodiazepines were found clinically significant manifestations of drug interactions.
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