Avodart, 90 pcs., 0.5 mg, capsules
Dutasteride is absorbed through the skin and therefore women and children should avoid contact with damaged capsules. In case of contact with damaged capsules, immediately wash the affected area of skin with soap and water.
Liver dysfunction.
There are currently no data on the use of Avodart® in patients with impaired liver function. Due to the fact that dutasteride undergoes intensive metabolism, and its T1/2 is 3-5 weeks, caution must be exercised when treating patients with impaired liver function with Avodart®.
Heart failure with the combined use of dutasteride and tamsulosin.
In two 4-year clinical studies, the incidence of heart failure was higher in patients receiving the combination of dutasteride and an α1-blocker, primarily tamsulosin, than in patients not receiving the combination treatment. In these two studies, the incidence of heart failure remained low (≤1%) with some variability between them. But in general, there were no discrepancies in the incidence of cardiovascular side effects. A cause-and-effect relationship between treatment with dutasteride (as monotherapy or in combination with an α1-blocker) and the development of heart failure has not been established.
Impact on the detection of prostate-specific antigen (PSA) and prostate cancer (PCa).
Patients should undergo a digital rectal examination, as well as other methods of examining the prostate gland before starting treatment with dutasteride and periodically repeat them during treatment to exclude the development of prostate cancer.
Determination of serum PSA concentration is an important component of screening for PCa. After 6 months of dutasteride therapy, the mean serum PSA level decreases by approximately 50%. Patients taking dutasteride should have a new baseline PSA level determined after 6 months of therapy. In the future, it is recommended to regularly monitor PSA levels.
The use of dutasteride does not affect the diagnostic value of PSA level as a marker of prostate cancer. Any confirmed increase in PSA levels relative to the nadir during dutasteride treatment may indicate the development of PCa (particularly high-Gleason grade PCa) or non-adherence to dutasteride therapy and should be carefully evaluated, even if these PSA levels remain within the normal range. for this age category of patients not taking 5α-reductase inhibitors.
The total PSA level returns to its original value within 6 months after discontinuation of dutasteride.
The ratio of free PSA to total remains constant even during dutasteride therapy. If the determination of the percentage of free PSA fraction is additionally used to detect prostate cancer in men receiving dutasteride, correction of this value is not required.
The effect of long-term use of dutasteride on the development of breast cancer in men.
No effect of long-term use of dutasteride on the development of breast cancer in men was found.
PCa and high-grade tumors.
The 4-year study (
REDUCE
) compared placebo and dutasteride in 8231 volunteers aged 50 to 75 years with a negative biopsy for PCa and a PSA level of 2.5 to 10 ng/mL at baseline.
During the study, 6,706 patients underwent a puncture biopsy of the prostate gland and, based on the results obtained, the degree of malignancy of prostate cancer was determined according to the Gleason score. 1517 patients were diagnosed with prostate cancer during the study. In the majority of cases, both in the dutasteride group and in the placebo group, well-differentiated prostate cancer was diagnosed (Gleason score 5–6). There was no difference in the number of cases of PCa with a Gleason score of 7–10 between the dutasteride group and the placebo group (p=0.81).
After 4 years, there were more cases of PCa with a Gleason score of 8–10 in the dutasteride group (n=29; 0.9%) compared with placebo (n=19; 0.6%; p=0.15 ). When assessing biopsy data for 1-2 years, the number of patients diagnosed with PCa with a Gleason score of 8-10 was comparable in the dutasteride (n = 17; 0.5%) and placebo (n = 18; 0.5) groups. %). When assessing biopsy data at 3–4 years, more cases of PCa with a Gleason score of 8–10 were diagnosed in the dutasteride group (n=12; 0.5%) compared with the placebo group (n=1; <0). .1%; p=0.0035). The percentage of patients diagnosed with PCa with a Gleason score of 8–10 was stable across all time periods (1–2 and 3–4 years) in the dutasteride group (0.5% in each period), while In the placebo group, the percentage of patients diagnosed with PCa with a score of 8–10 was lower in years 3–4 than in years 1–2 (<0.1% versus 0.5%, respectively).
In a 4-year study ( CombAT
) patients with BPH, in which prostate biopsy was not mandated for all participants by protocol and all PCa diagnoses were based on indicated biopsy, PCa with a Gleason score of 8–10 was diagnosed in 8 patients (<0.5%) at taking dutasteride, in 11 patients (<0.7%) when taking tamsulosin and 5 patients (<0.3%) with combination therapy with dutasteride and tamsulosin. A cause-and-effect relationship between taking dutasteride and the development of high-grade prostate cancer has not been established. Men taking dutasteride should undergo regular screening to assess their risk of developing prostate cancer, including PSA levels.
Impact on the ability to drive vehicles and operate machinery.
Taking dutasteride does not affect driving or operating machinery.
Pharmacological properties of the drug Avodart
Pharmacodynamics . Dutasteride is a 5-α-reductase inhibitor that inhibits both type 1 and type 2 5-α-reductase isoenzymes, which are responsible for the conversion of testosterone to 5-α-dihydrotestosterone. Dihydrotestosterone is an androgen primarily responsible for hyperplasia of prostate tissue. The maximum decrease in dihydrotestosterone while taking Avodart depends on the dose and is observed in the first 1–2 weeks. After the 1st and 2nd weeks of treatment with Avodart at a daily dose of 0.5 mg, the average concentration of dihydrotestosterone decreases by 85 and 90%, respectively. In patients with benign prostatic hyperplasia receiving 0.5 mg dutasteride per day, the average decrease in dihydrotestosterone levels was 94% after 1 year and 93% after 2 years of treatment, the average testosterone level increased by 19% after 1 and 2 years. This is an expected consequence of 5-α-reductase inhibition and does not result in the various known side effects. According to multicenter, placebo-controlled, double-blind clinical studies involving 4,325 men with prostatic hyperplasia (30 cm3), the use of Avodart at a dose of 0.5 mg/day led to the prevention of disease progression both by reducing the risk of acute urinary retention and the need for surgical intervention, and a statistically significant improvement in the condition of the lower urinary tract, an increase in urination rate and a decrease in prostate volume compared to placebo. All of the above changes were noted over a period of 24 months. Pharmacokinetics . Dutasteride is used orally in the form of a solution in soft gelatin capsules. After taking a single dose of 0.5 mg, the maximum concentration of the drug in the blood plasma is observed after 1–3 hours. Absolute bioavailability is 60% and does not depend on food intake. Dutasteride after a single or multiple dose has a large volume of distribution (300–500 l). Binding to blood plasma proteins is 99.5%. When used in a daily dose of 60%, a constant equilibrium concentration of dutasteride in the blood plasma is achieved after 1 month of treatment and about 90% after 3 months. A constant equilibrium concentration of dutasteride of approximately 40 ng/ml in blood plasma is achieved after 6 months of administration at a daily dose of 0.5 mg. Similarly with blood plasma, a constant equilibrium concentration of dutasteride in seminal fluid is achieved after 6 months. After 52 weeks of treatment, the average concentration of dutasteride in seminal fluid is 3.4 ng/ml (range 0.4–14 ng/ml). The distribution ratio of dutasteride from blood plasma to seminal fluid is about 11.5%. In vitro, dutasteride is metabolized by human cytochrome P450 CYP3A4 enzymes to two monohydroxyl metabolites. In blood plasma, according to spectrometric analysis, unchanged dutasteride, 3 major metabolites (4-hydroxydutasteride, 1,2-dihydrodutasteride and 6-hydroxydutasteride) and 2 minor metabolites (6,4-dihydroxydutasteride and 15-hydroxydutasteride) are detected. Dutasteride is extensively metabolized. After oral administration of dutasteride at a dose of 0.5 mg/day, 1–15.4% (on average 5.4%) is excreted in the feces in the form of unchanged dutasteride, the rest in the form of metabolites. Traces of unchanged dutasteride (≤0.1%) are determined in urine. The final half-life of dutasteride is 3–6 weeks. Traces of dutasteride in blood plasma can be detected 4–6 months after the end of treatment.
Indications for use of the drug Avodart
Treatment and prevention of progression of benign prostatic hyperplasia by reducing the size of the prostate gland, reducing the severity of symptoms of the disease, improving urine flow, reducing the risk of acute urinary retention and, if necessary, surgical intervention. In combination with tamsulosin, it treats and prevents the progression of benign prostatic hyperplasia by reducing the size of the prostate gland, reducing the severity of symptoms of the disease and improving urine flow.
Use of the drug Avodart
Avodart can be prescribed as monotherapy or in combination with the α-receptor blocker tamsulosin (0.4 mg). Adult men (including elderly patients) The recommended dose of Avodart is 1 capsule (0.5 mg) per day orally. The capsule is swallowed whole, do not open or chew, since contact with the contents of the capsule may irritate the mucous membrane of the oral cavity and pharynx. Avodart can be taken with or without food. Despite the fact that a decrease in the severity of symptoms of the disease may be noted a short time after taking the drug, to objectively assess the effectiveness of the drug, treatment should be continued for at least 6 months. Renal failure For patients with renal failure, no dose adjustment is necessary. Hepatic impairment The pharmacokinetics of dutasteride have not been studied in patients with hepatic impairment.
Avodart overdose, symptoms and treatment
According to clinical studies, in volunteers a single dose of dutasteride up to 40 mg/day (80 times higher than the therapeutic dose) for 7 days did not cause undesirable manifestations, taking into account the safety of their use. In clinical studies, a dose of dutasteride was used at a dose of 5 mg/day for 6 months without the occurrence of additional adverse reactions compared to the use of dutasteride at a dose of 0.5 mg/day. There is no specific antidote, so in case of possible overdose, symptomatic therapy is carried out.
Side effects of Avodart
According to clinical studies Monotherapy with Avodart When used, the following adverse reactions were observed according to clinical studies with an incidence of 1% compared to placebo
Adverse reaction | Frequency of occurrence during the 1st year of treatment, % | Frequency of occurrence during the 2nd year of treatment, % | ||
Placebo (n=2158) | Avodart (n=2167) | Placebo (n=1736) | Avodart (n=1744) | |
| Impotence | 3 | 6 | 1 | 2 |
| Change (decrease) in libido | 2 | 4 | ≤1 | ≤1 |
| Ejaculation disorder | ≤1 | 2 | ≤1 | ≤1 |
| Gynecomastia* | ≤1 | 1 | ≤1 | 1 |
* including soreness and hypertrophy of the mammary glands.
According to subsequent two-year clinical studies, the side effect profile of the drug did not change. Combination therapy (Avodart + tamsulosin) The following adverse reactions were noted in clinical studies with an incidence of 1% when comparing the combination of Avodart and tamsulosin and monotherapy with these drugs
Adverse reaction | Frequency of occurrence during the 1st year of treatment, % | Frequency of occurrence during the 2nd year of treatment, % | ||||
Avodart+ tamsulosin (n=1610) | Avodart (n=1623) | Tamsulosin (n=1611) | Avodart+ tamsulosin (n=1424) | Avodart (n=1457) | Tamsulosin (n=1468) | |
| Impotence | 7% | 5% | 3% | 1% | 1% | ≤1% |
| Change (decrease) in libido | 5 | 4 | 3 | ≤1 | ≤1 | ≤1 |
| Ejaculation disorder | 9 | 2 | 3 | ≤1 | ≤1 | ≤1 |
| Gynecomastia * | 2 | 2 | ≤1 | ≤1 | 1 | ≤1 |
| Dizziness | 1 | ≤1 | 1 | ≤1 | ≤1 | ≤1 |
* including soreness and hypertrophy of the mammary glands.
Data from post-marketing studies. From the immune system: very rarely - allergic reactions, including rash, itching, urticaria, localized edema and angioedema.
Avodart drug interactions
Since dutasteride is metabolized by the CYP3A4 isoenzyme, plasma concentrations of dutasteride may be increased in the presence of CYP3A4 inhibitors, and the clearance of dutasteride is decreased when administered concomitantly with the CYP3A4 inhibitors verapamil (37%) and diltiazem (44%). However, the clearance of dutasteride is not reduced when used with another calcium channel antagonist, amlodipine. The decrease in clearance and corresponding increase in the effect of dutasteride in the presence of CYP3A4 inhibitors is not of great clinical significance due to the wide range of safety of the drug. In vitro, the isoenzymes CYP 1A2, CYP 2C9, CYP2 C19 and CYP 2D6 do not take part in the metabolism of dutasteride in humans; dutasteride does not inhibit enzymes of the cytochrome P450 system in humans involved in the metabolism of drugs. In vitro studies have shown that dutasteride does not displace warfarin, diazepam or phenytoin from binding to plasma proteins, nor do these components replace dutasteride. The interaction of dutasteride with tamsulosin, terazocin, warfarin, digoxin and cholestyramine was studied. No clinically significant interaction was identified. Although specific drug interaction studies have not been conducted, approximately 90% of all patients in clinical trials of dutasteride received other concomitant therapy. No clinically significant adverse reactions were observed with the simultaneous use of dutasteride with antihyperlipidemic drugs, ACE inhibitors, β-adrenergic receptor blockers, calcium channel blockers, corticosteroids, diuretics, NSAIDs, phosphodiesterase type V inhibitors and quinolone antibiotics. According to a study examining the interaction of tamsulosin or terazocin in combination with Avodart for 2 weeks, no signs of pharmacokinetic or pharmacodynamic interaction were identified.
