treatment of symptoms of moderate to severe benign prostatic hyperplasia; reduction of the risk of acute urinary retention and, if necessary, surgical intervention in patients with symptoms of moderate to severe benign prostatic hyperplasia.
The avodart can be administered alone or in combination with an Î±-adrenergic blocker tamsulosin (0.4 mg).
Adult men (including elderly patients). The recommended dose of Avodart is 1 capsule (0.5 mg) per day for oral administration. The capsule should be swallowed whole, without opening and not chewing, because when contacting the contents of the capsule, irritation of the mucous membrane of the mouth and pharynx is possible.
Avodart can be taken regardless of food intake.
Despite the fact that relief from taking the drug is noted at an early stage, for an objective assessment of the effectiveness of the drug, treatment should be continued for at least 6 months.
Renal failure. The pharmacokinetics of dutasteride in patients with renal insufficiency has not been studied, so caution should be given to patients with severe renal insufficiency.
Liver failure. The pharmacokinetics of dutasteride in patients with hepatic insufficiency has not been studied, so with caution should be applied to the drug with mild and moderate hepatic insufficiency. Patients with severe hepatic insufficiency dutasteride is contraindicated.
Children. The use is contraindicated.
hypersensitivity to dutasteride, other 5Î±-reductase inhibitors, soy, peanuts or other components of the drug.
The drug is not used to treat women and children (see Application during pregnancy and lactation). Dutasteride is contraindicated in patients with severe hepatic insufficiency.
monotherapy with Avodart. According to 3 placebo-controlled clinical trials of Phase III with dutasteride compared with placebo, the following adverse reactions were noted, which, according to the researchers' definition, were associated with drug use (at a rate of â‰¥1%).
Post-marketing research data
Immune system: very rarely - allergic reactions, including rash, itching, hives, localized edema and angioedema.
Disorders of the psyche: very rarely - a depressive mood.
Skin and subcutaneous tissue: rarely - alopecia (mainly loss of hair on the body), hypertrichosis.
Reproductive system and breaches from the breast: very rarely - testicular pain and swelling.
Cases of breast cancer in men have been reported in clinical and post-marketing studies (see SPECIAL INSTRUCTIONS).
dutasteride can be absorbed through the skin, so women and children should avoid contact with leaking capsules (see Application during pregnancy and lactation). If the liquid from the capsule has got on the skin, it should be washed off immediately with soap and water.
The effect of hepatic insufficiency on the pharmacokinetics of dutasteride has not been studied. Since dutasteride is extensively metabolized and its TÂ½ is 3-5 weeks, the drug should be administered with caution to patients with mild to moderate hepatic impairment (see APPLICATION and PHARMACOLOGICAL PROPERTIES).
Adverse reactions from the cardiovascular system. Combination therapy can be given after a thorough assessment of the benefit / risk due to a potential increase in the risk of adverse reactions (including heart failure) and after considering alternative treatment options, including monotherapy.
According to 4-year clinical studies, the incidence of heart failure (the combined term for all reports, predominantly heart failure and congestive heart failure) was higher among patients receiving Avodart's combination with an Î±-adrenergic blocker, mainly tamsulosin, not using this combination. According to these two studies, the incidence of heart failure was low (â‰¤1%) and variable within these studies. There is no imbalance in the incidence of cardiovascular side effects in any of the studies. The causal relationship between the use of Avodart (alone or in combination with Î±-adrenoreceptor blockers) and the onset of heart failure has not been established (see PHARMACOLOGICAL PROPERTIES).
Effect on the PSA. The concentration of PSA is an important component of the screening process for detecting prostate cancer.
The avodart is able to reduce the level of plasma PSA in patients by an average of 50% after 6 months of treatment.
In patients taking Avodart, it is necessary to determine a new baseline level of PSA 6 months after treatment with this drug. Subsequently, this level is recommended to be checked regularly. Any confirmed increase in PSA from the lowest value with Avodart can be evidence of prostate cancer or failure to adhere to the Avodart treatment regimen and requires careful study, even if the PSA is within normal limits in men who have not been treated with 5Î±-reductase inhibitors. When interpreting PSA in patients taking Avodart, the previous PSA measures should be taken into account for comparison.
The use of Avodart does not affect the use of the PSA level for the diagnosis of prostate cancer after the establishment of its new baseline value.
The total plasma PSA level returns to baseline within 6 months after discontinuation of treatment.
The ratio of free PSA to total PSA remains constant even with Avodart. Therefore, if the patient, who is taking Avodart, chooses a percentage of free PSA to determine prostate cancer, correction of its significance is not required.
Before the start of the course of treatment with dutasteride and periodically during therapy, it is necessary to perform a digital rectal examination of the patient, as well as to use other methods for detecting prostate cancer.
Prostate cancer and tumors of high degree of graduation according to Gleason (low-grade). In a 4-year clinical trial involving> 8000 men aged 50-75 years with preliminary negative biopsy data for prostate cancer and a baseline PSA level of 2.5-10.0 ng / ml (REDUCE) in 1517 is diagnosed with prostate cancer. The incidence of prostate cancer (8-10 points on the Gleason score) was higher in the group treated with Avodart (n = 29, 0.9%) than in the placebo group (n = 19, 0.6%). An increase in the incidence of prostate cancer in the Gleason score of 5-6 and 7-10 was not observed. The causal relationship between the use of Avodart and the high stages of prostate cancer has not been established. The clinical significance of the numerical imbalance is unknown. Men taking Avodart should be checked regularly for the risk of prostate cancer, including the definition of PSA.
In an additional sequential 2-year study involving patients who participated in the dutasteride-as-chemoprevention (REDUCE) study, a low incidence of new prostate cancer cases (dutasteride group [n = 14, 1.2%] and placebo group [n = 7, 0.7%]) with the absence of new identified cases of prostate cancer with differentiation of 8-10 points on the Gleason scale.
Long-term follow-up (up to 18 years) of patients from a clinical trial using another 5Î±-reductase inhibitor (finasteride) as a chemoprophylaxis did not show a statistically significant difference between the finasteride and placebo groups in the overall survival rate (HR 1.02, 95% CI 0, 97-1.08) or survival after diagnosis of prostate cancer (HR 1.01, 95% CI 0.85-1.20).
Breast cancer. There have been reports of rare cases of breast cancer in men during clinical trials and in the postmarketing period. At the same time, epidemiological studies indicate a lack of an increased risk of developing breast cancer in men with 5Î±-reductase inhibitors. Patients should immediately report any changes in breast tissue, for example, discharge from the nipple or swelling.
Unsealed capsules. Dutasteride is absorbed through the skin, so women and children should avoid contact with unsealed capsules. If the liquid from the capsule has got on the skin, it should be washed off immediately with soap and water.
Liver failure. The effect of hepatic insufficiency on the pharmacokinetics of dutasteride has not been studied. Due to the active metabolism of dutasteride and 3-5 weeks of TÂ½, treatment with dutasteride in patients with mild or moderate hepatic insufficiency should be conducted with caution (see APPLICATION, CONTRAINDICATIONS, PHARMACOLOGICAL PROPERTIES).
Use during pregnancy and lactation
Fertility. A study of the effect of dutasteride at a dose of 0.5 mg / day on the characteristics of ejaculate in 27 healthy volunteers aged 18-52 years (n = 27 in the dutasteride group, n = 23 in the placebo group) for 52 weeks and 24 weeks after observations showed a decrease in the total number of spermatozoa, ejaculate volume and motility of spermatozoa by 23; 26 and 18% compared with changes in the placebo group. The concentration of sperm and its morphology remained unchanged. After 24 weeks of follow-up, the average percentage of changes in total sperm count in the dutasteride group remained 23% below baseline. While the mean values â€‹â€‹for all the sperm parameters remained within the normal range and did not meet certain criteria for clinically significant changes (30%), in two patients of the dutasteride group there was a decrease in the number of spermatozoa by more than 90% compared with the baseline 52nd week of treatment and with a partial restoration of their number after 24 weeks of follow-up. The clinical significance of the effect of dutasteride on sperm characteristics for individual patient fertility is unknown.
Pregnancy. Dutasteride is contraindicated for the treatment of women. The use of dutasteride for the treatment of women was not studied, because, according to the preclinical study, it was suggested that suppression of the level of circulating dihydrotestosterone may inhibit the development of the external genitalia in the male fetus that the female is bearing.
Lactation. It is not known whether dutasteride penetrates the breast milk of a woman.
The ability to influence the reaction rate when driving vehicles or working with other mechanisms. Given the pharmacokinetic and pharmacodynamic properties of dutasteride does not affect the ability to drive and other mechanisms.
since dutasteride is metabolized by the CYP 3A4 isoenzyme, the plasma dutasteride concentration may increase with CYP 3A4 inhibitors. Prolonged administration of dutasteride with preparations that are potent inhibitors of the CYP 3A4 enzyme (such as ritonavir, indinavir, nefazodone, itraconazole, ketoconazole orally) may increase dutasteride concentration. According to the study, the clearance of dutasteride decreases with simultaneous application with inhibitors of CYP 3A4 verapamil (37%) and diltiazem (44%). However, the clearance of dutasteride does not decrease when used with amlodipine, another antagonist of calcium channels.
The decrease in clearance and the corresponding increase in the effect of dutasteride in the presence of inhibitors of CYP 3A4 is not of great clinical significance due to the wide spectrum of drug safety.
In vitro, dutasteride is not metabolized by CYP 1A2, CYP 2A6, CYP 2E1, CYP 2C8, CYP 2C9, CYP 2C19, CYP 2B6 and CYP 2D6 - isoenzymes of the cytochrome P450 system in humans.
Dutasteride does not inhibit the isoenzymes of the cytochrome P450 system in humans in vitro and does not induce isoenzymes of CYP 1A, CYP 2B and CYP 3A rats and dogs in vivo.
In vitro studies have shown that dutasteride does not displace warfarin, acenocoumarol, fenprocumone, diazepam or phenytoin from the association with blood plasma proteins, as these components do not replace dutasteride. The interaction of dutasteride with tamsulosin, terazocine, warfarin, digoxin, and colestyramine was studied. Clinically significant interaction was not revealed.
Although no specific studies were conducted on the interaction with other drugs, about 90% of all patients received other drugs during the clinical trials of dutasteride. Clinically significant adverse reactions were not observed with the simultaneous use of dutasteride with antihyperlipidemic drugs, ACE inhibitors, Î²-adrenoreceptor blockers, calcium channel blockers, GCS, diuretics, NSAIDs, PDE type V inhibitors and quinoline antibiotics.
According to clinical studies, in volunteers, single dutasteride doses up to 40 mg / day (80 times higher than therapeutic) for 7 days did not cause concern in terms of safety of their use. During clinical trials, dutasteride doses of 5 mg / day for 6 months without additional side effects compared with dutasteride at a dose of 0.5 mg / day.
There is no specific antidote, therefore, in case of a possible overdose, symptomatic and supportive therapy is performed.
at a temperature not exceeding 30 Â° C.