Composition, form of production and packaging
Solid capsules of hypromellose, oblong, with a size of N00; with a brown case and an orange lid on which the code "GS 7CZ" is printed in black ink; the content of the capsules is a soft gelatin capsule containing dutasteride and pellets containing tamsulosin hydrochloride.
Capsules soft gelatinous, oblong, opaque, matte-yellow color.
dutasteride 500 Ојg
Excipients: caprylic / capric acid mono di-glycerides (MDC) - 299.47 mg, butylhydroxytoluene (BGT) - 0.03 mg.
The total mass of the contents is 300 mg.
The composition of the capsule shell: gelatin - 116.11 mg, glycerol - 66.32 mg, titanium dioxide - 1.29 mg, iron oxide oxide yellow - 0.13 mg.
The total weight of the capsule shell is 184 mg.
Technological additives: medium chain triglycerides (TCS) - qs, lecithin - qs
Total weight is 484 mg.
Pellets are from white to almost white.
tamsulosin hydrochloride 400 Ојg
Auxiliary substances: microcrystalline cellulose - 138.25 mg, copolymer methacrylic acid: ethyl acrylate (1: 1) 30% dispersion * - 8.25 mg, talc - 8.25 mg, triethyl citrate - 0.825 mg.
The mass of the pellet core is 156 mg.
Composition of the shell pellets: copolymer methacrylic acid: ethyl acrylate (1: 1) 30% dispersion * - 10.4 mg, talc - 4.16 mg, triethyl citrate - 1.04 mg.
The mass of the pellet shell is 15.6 mg.
Total weight is 172 mg.
The composition of the brown case of a hard capsule of hypromellose: carrageenan - 0-1.3 mg, potassium chloride - 0-0.8 mg, titanium dioxide ~ 1 mg, iron oxide red ~ 5 mg, water purified ~ 5 mg, hypromellose-2910 - up to 100 mg .
Technological additives: carnauba wax - qs, corn starch - qs
Composition of the orange lid of a hard capsule made of hypromellose: carrageenan - 0-1.3 mg, potassium chloride - 0-0.8 mg, titanium dioxide ~ 6 mg, dye sunset yellow ** ~ 0.1 mg, purified water ~ 5 mg, hypromellose-2910 - 100 mg, black ink ~ 0.05 mg.
Technological additives: carnauba wax - qs, corn starch - qs
Composition of black ink SW-9010: shellac - 24-27% w / w, propylene glycol - 3-7% w / w, iron dye oxide black - 24-28% w / w.
Composition of black ink SW-9008: shellac - 24-27% w / w, propylene glycol - 3-7% w / w, iron dye oxide black - 24-28% w / w, potassium hydroxide 0.05-0.1%.
The theoretical total weight per 1 capsule is 0.05 mg.
30 pcs. - bottles of high-density polyethylene (1) - packs of cardboard.
90 pcs. - bottles of high-density polyethylene (1) - packs of cardboard.
* Mixture of copolymer of methacrylic acid: ethyl acrylate also contains auxiliary substances polysorbate 80 and sodium lauryl sulfate as emulsifiers.
** in the manufacturer's dossier is called "dye FD & C yellow 6".
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
Duodart is a combination of two components with complementary mechanisms of action that help to eliminate symptoms in patients with benign prostatic hyperplasia (BPH): a double inhibitor of 5? -reductase - dutasteride and a blocker? 1a- adrenoreceptors - tamsulosin.
Dutasteride suppresses the activity of the isoenzymes of the 5-reductase of the 1 st and 2 nd types, under the action of which the conversion of testosterone into 5? -dihydrotestosterone (DHT) is the main androgen responsible for the hyperplasia of the glandular tissue of the prostate gland.
Does Tamsulosin Inhibit ? 1a- adrenoreceptors in the smooth muscles of the stroma of the prostate and the neck of the bladder. Approximately 75%? 1- adrenoreceptors in the prostate gland are subtype receptors? 1a .
It is expected that the pharmacodynamic properties of dutasteride and tamsulosin in the form of a combined preparation will not differ from the properties of dutasteride and tamsulosin used simultaneously as separate components.
Dutasteride reduces the levels of DHT, reduces the size of the prostate gland, helps to eliminate symptoms of lower urinary tract diseases and increases the rate of urination, and also reduces the risk of acute urinary retention and the need for surgery.
The maximum effect of daily dutasteride doses on decreasing concentrations of DHT is dose-dependent and is observed for 1-2 weeks. After 1 and 2 weeks of dutasteride administration at a dose of 500 Ојg / day, the average values вЂ‹вЂ‹of serum DHT concentrations were reduced by 85% and 90%, respectively.
In patients with BPH who received 500 Ојg dutasteride per day, the mean decrease in DHT level was 94% at 1 year and 93% at 2 years, the average increase in serum testosterone levels was 19% at 1 year and 2 years later. This is an expected consequence of inhibition of 5? -reductase and does not lead to any of the known undesirable phenomena.
Tamsulosin increases the maximum rate of urination by reducing the tone of the smooth muscles of the prostate and urethra and, consequently, reduces obstruction.Tamsulosin also reduces the complex of symptoms of filling and emptying, in the development of which a significant role is played by the instability of the bladder and the tone of the smooth muscles of the lower urinary tract. Alpha- 1- adrenoblockers can reduce blood pressure by decreasing peripheral resistance.
The bioequivalence between Duodart and the simultaneous administration of individual dutasteride and tamsulosin capsules was demonstrated.
A single dose bioequivalence study was conducted in patients, both on an empty stomach and after a meal. At the same time, a decrease in C max of tamsulosin in the blood serum was observed by 30% after eating compared to the combination of dutasteride and tamsulosin on an empty stomach. The intake of food had no effect on the AUC of tamsulosin.
After taking a single dose of dutasteride (500 Ојg), C max in the blood serum is reached within 1-3 hours. Absolute bioavailability of dutasteride in men is about 60% with respect to a 2-hour IV infusion. Bioavailability of dutasteride does not depend on food intake.
Pharmacokinetic data obtained after a single and repeated oral administration of dutasteride indicate a large V d (from 300 L to 500 L). Dutasteride has a high degree of binding to plasma proteins (> 99.5%).
With daily intake, serum dutasteride concentration reaches 65% of the stable concentration after 1 month and approximately 90% of the stable concentration level after 3 months. C ss of serum dutasteride, approximately 40 ng / ml, are achieved after 6 months of a single daily dutasteride dose of 500 Ојg. In sperm, as in serum, C ss of dutasteride are also reached after 6 months. After 52 weeks of treatment, the concentrations of dutasteride in the sperm averaged 3.4 ng / ml (0.4 to 14 ng / ml).From serum, about 11.5% of dutasteride enters the semen.
In vitro, dutasteride is metabolized by the CYP3A4 isoenzyme of the human cytochrome P450 system to two small monohydroxylated metabolites; However, the isozymes CYP1A2, CYP2A6, CYP2E1, CYP2C8, CYP2C9, CYP2C19, CYP2B6 or CYP2D6 of this system do not act on it.
After achieving a stable concentration of dutasteride in the serum using a mass spectrometric method
unchanged dutasteride, 3 major metabolites (4'-hydroxydutasteride, 1,2-dihydrodutasteride and 6-hydroxydutasteride) and 2 minor metabolites (6,4'-dihydroxydutasteride and 15-hydroxydutasteride). 5 metabolites of dutasteride found in human serum were detected in the blood serum of rats, and the stereochemistry of hydroxyl groups at positions 6 and 15 of metabolites in humans and rats is unknown.
In the human body, dutasteride undergoes intensive metabolism. To achieve a stable concentration after ingestion of dutasteride in a daily dose of 500 mcg from 1% to 15.4% (an average of 5.4%) of the accepted dose is excreted through the intestine in unchanged form. The rest is excreted through the intestine in the form of 4 major metabolites, accounting for 39%, 21%, 7% and 7%, respectively, and 6 minor metabolites (each accounting for less than 5%). In human urine, only trace amounts of unchanged dutasteride are detected (less than 0.1% of the dose).
At a low concentration in the blood serum (less than 3 ng / ml), dutasteride is excreted rapidly by both methods, both concentration-dependent and not dependent on concentration. When taking a single dose of dutasteride 5 mg or less, a rapid clearance with a short T 1/2 of 3 to 9 days was observed.
At a serum concentration of more than 3 ng / ml, dutasteride is slowly excreted (0.35 to 0.58 l / h), mostly linearly, with T 1/2 from 3 to 5 weeks. When dutasteride is taken in therapeutic doses, its final T 1/2 is 3-5 weeks and after repeated administration at a dose of 500 Ојg / day, the slower clearance prevails and the overall clearance is linear and independent of concentration. Dutasteride is found in serum (in concentrations above 0.1 ng / ml) up to 4-6 months after discontinuation of its administration.
Pharmacokinetics in specific patient groups
The pharmacokinetics and pharmacodynamics of dutasteride were studied in 36 healthy male volunteers aged 24 to 87 years after receiving a single dose (500 Ојg) of dutasteride. There were no statistically significant differences between the different age groups for such pharmacokinetic parameters as AUC and C max . There were no statistically significant differences in the values вЂ‹вЂ‹of T 1/2 dutasteride between the age groups of men 50-69 years old and over 70 years of age, which include most men with BPH. Between different age groups, there were no significant differences in the degree of decrease in the level of DHT. These results demonstrate that there is no need to correct the dose of dutasteride depending on the age of the patients.
The effect of renal dysfunction on the pharmacokinetics of dutasteride has not been investigated. However, less than 0.1% C ss of dutasteride (when dutasteride is administered at a dose of 500 Ојg 1 time / day) is excreted by the kidney in a person, thus, there is no need for dose correction in case of renal dysfunction.
The effect of a violation of liver function on the pharmacokinetics of dutasteride has not been investigated. Since dutasteride is extensively metabolized in the liver, its exposure in patients with impaired liver function can be increased.
Tamsulosin is absorbed in the intestine and has almost 100% bioavailability. Tamsulosin is characterized by linear pharmacokinetics after a single and multiple administration with the achievement of stable concentrations on day 5 with the administration of 1 time / day. The rate of absorption of tamsulosin slows down after eating. The same level of absorption can be achieved if the patient takes tamsulosin daily, about 30 minutes after the same meal.
The average stable apparent V d of tamsulosin after iv administration to 10 healthy adult males was 16 l, indicating its distribution in the extracellular fluid of the body.
Tamsulosin mostly binds to human plasma proteins (from 94 to 99%), mainly with? 1- acid glycoprotein, binding is linear in a wide range of concentrations (20-600 ng / ml).
In humans, there was no enantiomeric bioconversion of tamsulosin from the R (-) isomer to the S (+) isomer. Tamsulosin is intensively metabolized by isoenzymes of the human cytochrome P450 system in the liver, and less than 10% of the administered dose is excreted unchanged by the kidneys. However, the pharmacokinetic profile of metabolites in humans is not defined. The results obtained in vitro show that the isoenzymes CYP3A4 and CYP2D6 are involved in the metabolism of tamsulosin, and there is also a small amount of other cytochrome P450 isoenzymes. Inhibition of the activity of liver enzymes involved in the metabolism of tamsulosin can lead to an increase in its exposure. Metabolites of tamsulosin undergo intensive conjugation with glucuronides or sulfates before excretion by the kidneys.
T 1/2 of tamsulosin is 5-7 hours. About 10% of tamsulosin is excreted unchanged in kidneys.
Pharmacokinetics in specific patient groups
A cross-sectional study comparing AUC and T 1/2 showed that the pharmacokinetic distribution of tamsulosin may be somewhat longer in older men than in young healthy male volunteers. Own clearance does not depend on the binding of tamsulosin hydrochloride with? 1- acid glycoprotein, but decreases with age, which leads to an increase in AUC by 40% in men aged 55-75 years compared with men aged 20-32 years.
The pharmacokinetics of tamsulosin were compared in 6 volunteers with an easy-intermediate (30 <KK <70 ml / min / 1.73 m 2 ) or medium-heavy (10 <KK <30 ml / min / 1.73 m 2 ) degree of renal dysfunction and 6 healthy volunteers (KK> 90 ml / min / 1.73 m 2 ). While there was a change in the total concentration of tamsulosin in the blood plasma as a result of a binding disorder with? 1- acid glycoprotein, the concentration of unbound (active) tamsulosin, as well as its own clearance, remained relatively constant. Consequently, in patients with impaired renal function, dose adjustment of tamsulosin is not required. However, patients with terminal stage of kidney disease (CC <10 ml / min / 1.73 m 2 ) were not investigated.
The pharmacokinetics of tamsulosin was compared in 8 volunteers with an average degree of impaired liver function (classes A and B on the Child-Pugh scale) and 8 healthy volunteers. While as a result of a violation of binding with? 1- acid glycoprotein, changes in the total concentration of tamsulosin in the blood plasma were observed, the unbound (active) concentration of tamsulosin did not change significantly, only a moderate (32%) change in the intrinsic clearance of unbound tamsulosin occurred. Therefore, in patients with an average degree of impaired liver function, dose adjustment of tamsulosin is not required. However, patients with a severe degree of impaired liver function were not investigated.
There were no pharmacokinetic studies of the use of Duodart in specific groups of patients.
- treatment and prevention of BPH progression by reducing its size, eliminating symptoms, increasing the rate of urination, reducing the risk of acute urinary retention, and the need for surgery.
The drug is taken orally. Capsules should be taken whole, not liquid and without opening, washing down with water. Contact of the contents of a soft gelatin capsule containing dutasteride, which is contained within a hard capsule, with the oral mucosa may cause inflammatory effects on the mucosal side.
In adult men (including elderly patients), the recommended dose of Duodart is 1 caps. 1 time / day, about 30 minutes after the same meal.
Currently, there is no data on the use of Duodart in patients with impaired renal function , however, when Duodart is used, dose adjustment is not required.
Currently, there is no data on the use of Duodart in patients with impaired liver function .
Clinical studies of the Duodart drug have not been conducted, however, information on the combination is available from a clinical study of CombAT (comparison of dutasteride 500 Ојg and tamsulosin 400 Ојg 1 time / day for 4 years in combination or as a monotherapy).
Information on the profiles of adverse reactions to individual components (dutasteride and tamsulosin) is also provided.
The use of a combination of dutasteride and tamsulosin
Clinical Trials Data
The following undesirable reactions evaluated by the researchers (with a cumulative frequency of 1%) were recorded during the CombAT study.
Undesired reaction Frequency of occurrence of undesirable reaction
Year 1 Year 2 Year 3 Year 4 Year
The combination a (n = 1610) (n = 1428) (n = 1283) (n = 1200)
Dutasteride (n = 1623) (n = 1464) (n = 1325) (n = 1200)
Tamsulosin (n = 1611) (n = 1468) (n = 1281) (n = 1112)
Erectile dysfunction b
The combination of 6% 2% <1% <1%
Dutasteride 5% 2% <1% <1%
Tamsulosin 3% 1% <1% 1%
Violation (decrease) of libido b
The combination of 5% <1% <1% 0%
Dutasteride 4% 1% <1% 0%
Tamsulosin 2% <1% <1% <1%
Violation of ejaculation b
Combination 9% 1% <1% <1%
Dutasteride 1% <1% <1% <1%
Tamsulosin 3% <1% <1% <1%
Breast disorders in the
The combination of 2% <1% <1% <1%
Dutasteride 2% 1% <1% <1%
Tamsulosin <1% <1% <1% 0%
The combination of 1% <1% <1% <1%
Dutasteride <1% <1% <1% <1%
Tamsulosin 1% <1% <1% 0%
a - combination: dutasteride 0.5 mg 1 time / day + tamsulosin 0.4 mg 1 time / day.
b - unwanted reactions from the reproductive system are associated with the use of dutasteride (both in monotherapy and in combination with tamsulosin). These adverse reactions may persist after discontinuation of treatment. The effect of dutasteride on the preservation of these unwanted reactions is unknown.
in - including soreness and enlargement of the mammary glands.
The use of dutasteride as a monotherapy
Clinical Trials Data
In three placebo-controlled Phase III studies, aimed at comparing dutasteride (n = 2167) with placebo (n = 2158), the undesirable reactions evaluated by the investigators after the first and second year of dutasteride monotherapy were similar in type and frequency to those observed in patients who received dutasteride as a monotherapy in a CombAT study (see table above).
Changes in the profile of adverse events over the next 2 years of open phase of the study was observed.
These observations post-registration
Adverse reactions shown below are listed in accordance with a lesion of organs and organ systems, and frequency of occurrence. The frequency of occurrence is defined as follows: very common (1/10?), Often, infrequently, rarely (1/10 000 and <(1/100 and <1/10?) (1/1000 and <1/100?)? 1/1000), very rare (<1/10 000, including isolated cases). Frequency categories were formed on the basis of post-marketing surveillance, based on the frequency of reports of adverse reactions, and not on their true frequency.
From the immune system
Very rarely allergic reactions (including rash, pruritus, urticaria, localized edema) and angioedema
Skin and subcutaneous tissue
Rare alopecia (mostly loss of hair on the body), hypertrichosis
Very rare worsening of mood
of the reproductive organs and breast
very rarely, testicular pain, testicular swelling
Application tamsulosin as monotherapy
These clinical studies and observations post-marketing
Adverse reactions and frequency of occurrence of specified below are based on the information from publicly available sources. In the table below, frequent and infrequent adverse reactions are consistent with reports of clinical trials, and the incidence of generally reflect those as compared to placebo. The rare and very rare adverse reactions, as well as their frequency, correspond to the data of the post-marketing reports observations.
Adverse reactions shown below are listed in accordance with a lesion of organs and organ systems, and frequency of occurrence. The frequency of occurrence is defined as: common (? 1/100 and <1/10), uncommon, rare, very rare (<(1/1000 and <1/100?) (1/10 000 and <1/1000?) 1/10 000, including isolated cases).
From the side of the cardiovascular system
Infrequently, palpitations, postural hypotension
From the gastrointestinal tract
Infrequently, constipation, diarrhea, vomiting
From the nervous system
of the reproductive organs and breast
often ejaculation disorder
Very rarely, priapism
From the respiratory system
From the immune system
Infrequently a rash, pruritus, urticaria
Very rare Stevens-Johnson syndrome
During post-marketing observational cases of intraoperative iris syndrome atonic syndrome as a variant of a narrow pupil during cataract surgery have been identified, which was associated with the reception? 1a adrenoblokatorov, including tamsulosin.
during use of tamsulosin the following adverse reactions were recorded: atrial fibrillation, arrhythmia, tachycardia, dyspnea, epistaxis, blurred vision, visual disturbances, erythema multiforme, exfoliative dermatitis, and dry mouth.
- hypersensitivity to dutasteride, other inhibitors of 5-reductase, tamsulosin or any other components that make up the drug;?
- orthostatic hypotension (including history);
- severe hepatic impairment;
- age up to 18 years;
- use of the drug is contraindicated in women and children.
With caution should be prescribed to patients with chronic renal failure (creatinine clearance less than 10 mL / min), an arterial hypotension, a planned surgery for cataract, coupled with a strong or moderately active inhibitors isoenzyme CYP3A4 (ketoconazole varikonazol and others).
PREGNANCY AND LACTATION
No studies on the use of the drug Duodart during pregnancy, breastfeeding and its impact on fertility. The following data reflect the information available to the individual components.
Effect dutasteride receiving a dose of 500 mg / day sperm characteristics evaluated in healthy volunteers aged 18 to 52 years throughout the 52 weeks of treatment and 24 weeks of observation after completion of therapy. After 52 weeks, the average deviation from baseline total sperm count, semen volume and sperm motility in dutasteride group was 23%, 26% and 18% respectively, considering the deviation from baseline values вЂ‹вЂ‹in the placebo group. The concentration and sperm morphology were not changed. After 24 weeks of observation mean deviation of the total number of spermatozoa in dutasteride group was 23% below baseline.Whereas the mean values вЂ‹вЂ‹for all semen parameters at all time points stayed within normal values вЂ‹вЂ‹and did not meet a predetermined criteria for clinically meaningful change (30%), two patients in the group dutasteride sperm count after 52 weeks decreased by more than 90 % of baseline values вЂ‹вЂ‹with partial recovery after 24 weeks of observation. The clinical significance of the effect of dutasteride on the fertility of sperm parameters in individual patients is not known.
Effect of tamsulosin on sperm count and sperm functional characteristics are not evaluated.
Pregnancy and lactation
The drug is contraindicated Duodart for use in women.
No data on the allocation of dutasteride or tamsulosin with breast milk.
Use of dutasteride has not been studied in women because preclinical data have shown that the suppression of circulating levels of DHT can retard or inhibit the formation of external genitalia in male fetuses, if a woman during pregnancy received dutasteride.
Assignment tamsulosin pregnant female rats and rabbits at doses higher than the therapeutic showed no signs of damage to the fetus.
APPLICATION FOR FUNCTIONS OF THE LIVER
With caution should be prescribed to patients with chronic renal failure (creatinine clearance less than 10 mL / min).
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Use of the drug is contraindicated in severe hepatic impairment.
APPLICATION FOR CHILDREN
Use of the drug is contraindicated in children.
Dutasteride is absorbed through the skin, therefore, women and children should avoid contact with damaged capsules. In case of contact with damaged capsules should immediately rinsed with water corresponding portion of the skin with soap.
The simultaneous use of tamsulosin with potent inhibitors isoenzyme CYP3A4 (e.g., ketoconazole), or, to a lesser extent, with potent inhibitors isoenzyme CYP2D6 (e.g., paroxetine) may increase the exposure of tamsulosin. Therefore tamsulosin is not recommended for patients receiving potent inhibitor of isozyme CYP3A4, and should be used with caution in patients taking a medium strength inhibitor isoenzyme CYP3A4 (e.g., erythromycin), strong or medium strong inhibitor of isozyme CYP2D6, combination isoenzyme inhibitors CYP3A4 and CYP2D6, or patients with known low CYP2D6 metabolism.
Effect of human liver pharmacokinetics dutasteride not investigated. Because dutasteride is extensively metabolized in the liver and its T 1/2is from 3 to 5 weeks, should be used with caution in preparation Duodart patients with impaired liver function.
Heart failure is the combined use of tamsulosin and dutasteride
The two 4-year clinical trials, the incidence of heart failure (the term composite mark events, mainly heart failure and congestive heart failure) was higher for
patients receiving combination dutasteride and alpha 1 -adrenoblocker mainly tamsulosin, than patients who did not
treated with combination therapy. In these two clinical trials, the incidence of heart failure has remained low (<1%) and ranged between studies. But in general, discrepancies between the frequency of side effects with the cardiovascular system were noted. It has not been established a causal relationship between the reception dutasteride (alone or in combination with an alpha 1 adrenoblokatorom) and cardiac insufficiency.
The effect on detection of prostate-specific antigen (PSA) and prostate cancer (PCa)
patients with prostatic hyperplasia necessary digital rectal examination and other diagnostic methods for prostate cancer prior to treatment with Duodart and periodically repeating them during treatment.
PSA serum level is an important component of the screening aimed at identifying prostate cancer. After 6 months therapy dutasteride mean PSA in serum is reduced by about 50%.
Patients taking the drug Duodart new PSA baseline after 6 months of treatment should be determined. After that, we recommend regular monitoring of PSA levels. Any confirmed increase in PSA with respect to the smallest of its value in the treatment of drug Duodart could indicate or non-compliance with drug therapy, or on the development of prostate cancer (particularly prostate cancer with a high degree of differentiation by Gleason score) and should be carefully evaluated, even if these PSA levels remain in the normal range for men not taking inhibitors of 5? -reductase. In interpreting the results of measurements of PSA in patients taking the drug Duodart must be used to compare previous results of the evaluation of PSA levels.
Application Duodart product has no effect on the diagnostic value of PSA as a marker of prostate cancer after it set a new baseline PSA. Total PSA level returns to baseline within 6 months after discontinuation of dutasteride.
The ratio of free to total PSA remains constant background dutasteride therapy. If the detection of prostate cancer in men receiving dutasteride, is additionally used determination of percent free PSA content of the fraction of this quantity of correction is not required.
As with any alpha 1 adrenoblokatorov when applying tamsulosin orthostatic hypotension may occur in rare cases, leading to fainting. Patients starting treatment with Duodart should be
alerted about the need to sit or lie down at the first signs of orthostatic hypotension (dizziness and imbalance feelings) as long as the symptoms do not go away.
Caution is recommended with the use of alpha 1 adrenoblokatorov, including tamsulosin, together with inhibitors of phosphodiesterase type 5. Alpha 1adrenoblokatory and inhibitors of phosphodiesterase type 5 are vasodilators and can lead to a reduction in blood pressure. The simultaneous use of these two classes of drugs can potentially cause symptomatic hypotension.
Intraoperative atonic iris syndrome
Intraoperative atonic iris syndrome (ISAR, the kind of small pupil syndrome) has been observed during cataract surgery in some patients treated with alpha 1adrenoblokatory including tamsulosin. ISAR may lead to an increased risk of complications during ophthalmic surgery and after it.
At the preoperative examination of ophthalmic surgery should check with the patient, which is scheduled cataract surgery, it takes or took earlier combination of dutasteride with tamsulosin for the provision of adequate measures in the event of ISAR during surgery.
It is considered a legitimate cancellation tamsulosin 1-2 weeks prior to cataract surgery, but the benefits, as well as the exact time discontinuation before cataract surgery have not been established.
PCa and high gradation tumors
at the 4-year study involving more than 8,000 men aged 50 to 75 years with negative biopsies for the presence of prostate cancer, and PSA level between 2.5 ng / ml and 10 ng / ml (study REDUCE) at the initial examination . At the same time 1517 of them were diagnosed with prostate cancer. It was observed more cases of prostate cancer with an estimate 8-10 Gleason dutasteride group (n = 29; 0.9%) compared with the placebo group (n = 19; 0.6%). There was no increase in the incidence of prostate cancer with an estimate of 5-6 and 7-10 points on the Gleason score.
The causal connection between the reception and the development of prostate cancer dutasteride high gradation is not established. The clinical significance of the numerical imbalance is unknown. Men taking dutasteride, should be regularly monitored for assessing the risk of developing prostate cancer, including a PSA level.
Breast cancer in men
in clinical trials and in the post-registration period reported in men taking dutasteride development of breast cancer. Patients should be instructed that they should immediately report any changes in the breasts, such as sealing in the gland or discharge from the nipple. It is unclear whether there is a causal relationship between the occurrence of breast cancer in men and the long-term use of dutasteride.
Impact on the ability to drive vehicles and manage mechanisms
Studies examining the effect of the drug on Duodart ability to perform activities requiring quick decision-making, special motor and cognitive skills, not spent.
It should inform the patient about the possibility of the occurrence of symptoms associated with orthostatic hypotension such as dizziness, Duodart when applying the preparation.
Data regarding overdose when receiving a combination of tamsulosin and dutasteride absent. The data below reflects information on the individual components.
Dutasteride When applying the dose to 40 mg / day (80 times higher than the therapeutic dose) for 7 days significant adverse reactions were noted. In clinical studies, the appointment dutasteride 5 mg / day for 6 months undesirable reactions other than those enumerated for the therapeutic dose (500 ug / day) were observed.
specific antidote dutasteride is not, so should be symptomatic and supportive treatment in cases of suspected overdose.
Symptoms: an overdose of tamsulosin may develop acute hypotension.
Treatment:in the case of arterial hypotension must be symptomatic therapy. AD can be restored when making the patient horizontal position. In the absence of the effect can be applied means increasing bcc, and, if necessary, decongestants. It is necessary to monitor and, if necessary, to maintain renal function. It is unlikely that dialysis would be effective, since tamsulosin is associated with plasma proteins at 94-99%.
Studies on the interaction of the combination of tamsulosin and dutasteride with another