Duodart caps 0.5mg + 0.4mg #90

Duodart instruction

You can buy Duodart here

Composition

active ingredient: dutasteride, tamsulosin hydrochloride
1 capsule contains dutasteride 0.5 mg and tamsulosin hydrochloride 0.4 mg;
excipients: Caprylic acid monodiglycerides, butylhydroxytoluene (E 321), gelatin, glycerin, titanium dioxide (E171), ferric oxide yellow (E172), medium chain triglycerides, and lecithin; microcrystalline cellulose, methacrylate copolymer dispersion, talc, triethyl citrate; hard capsule shell: carrageenan (E 407), potassium chloride, titanium dioxide (E 171), FD & C Yellow 6 (E 110), hypromellose, carnauba wax, corn starch, ferric oxide red (E 172), SW-9008 Black Ink (shellac, propylene glycol, ferrous oxide black (E172), potassium hydroxide).
Packaging
In packing of 30 and 90 pieces.

pharmachologic effect

Duodart is a combination drug of dutasteride and tamsulosin with a complementary mechanism of action.
Dutasteride, a dual inhibitor of 5α-reductase, inhibits the activity of type 1 and type 2α-reductase isoenzymes, which are responsible for the conversion of testosterone to 5α-dihydrotestosterone. Dihydrotestosterone (DHT) is the main androgen responsible for the hyperplasia of the glandular tissue of the prostate gland. Dutasteride reduces the level of DHT, reduces the size of the prostate gland, reduces the symptoms of the disease, leads to improved urination, reducing the risk of acute urinary retention and the need for surgical treatment.
The maximum effect of dutasteride on a decrease in the concentration of DHT is dose-dependent and is observed 1–2 weeks after the start of treatment. After 1–2 weeks of dutasterid dosing at a dose of 0.5 mg / day, the median serum DHT concentrations are reduced by 85–90%, respectively.
In patients with benign prostatic hyperplasia (BPH) while taking dutasteride at a dose of 0.5 mg / day, the average reduction in the level of DHT was 94% during the first year and 93% during the second year of therapy; average serum testosterone levels increased by 19% during the first and second years of treatment. This effect is due to a decrease in the level of 5α-reductase and does not lead to the development of any known adverse reactions.
Tamsulosin hydrochloride is a blocker of postsynaptic α1a -adrenoreceptors found in the smooth muscles of the prostate gland, bladder neck and prostatic urethra. The blockade of α1a -adrenoretseptor leads to a decrease in the tone of the smooth muscles of the prostate gland, bladder neck and the prostatic part of the urethra and improve urine flow. At the same time, both obstructive symptoms and irritative symptoms due to increased smooth muscle tone and detrusor hyperactivity in BPH are reduced.

Duodart, indications for use

- treatment and prevention of progression of benign prostatic hyperplasia (reducing its size, reducing symptoms of the disease, improving urination, reducing the risk of acute urinary retention and the need for surgical treatment).

Contraindications

- women;
- children and teenagers under the age of 18;
- severe degree of liver failure;
- A history of orthostatic hypotension;
- scheduled cataract surgery;
- known hypersensitivity to tamsulosin hydrochloride, dutasteride, other 5α-reductase inhibitors, or any other ingredient of Duodart.

Dosage and administration

Adult men (including the elderly) are prescribed 1 capsule (0.5 mg / 0.4 mg) by mouth, 1 time / day, 30 minutes after the same meal, with water.
Capsules should be taken whole, without opening and not chewing, since the contact of the contents of the capsule with the mucous membrane of the mouth can cause inflammation from the mucous membrane.
Currently, there is no data on the use of the drug Duodart in patients with impaired renal function.
There is no need for dose adjustment in this cohort of patients.
Currently there are no data on the use of the drug Duodart in patients with impaired liver function.
The drug should be used with caution in patients with mild and moderate liver failure. Duodart is contraindicated in patients with severe liver failure.

Use during pregnancy and lactation

The drug Duodart is contraindicated for use in women.
No data on the elimination of dutasteride or tamsulosin with breast milk.
The use of dutasteride has not been studied in women, since preclinical data suggest that the suppression of DHT levels in the circulation may disrupt the formation of the external genitalia in male fetuses, if the mother received dutasteride during pregnancy.

Side effects of Duodart

Adverse events caused by the use of tamsulosin hydrochloride in combination with dutasteride
Very rarely (
Disorders of the sexual sphere are associated with the use of the dutasteride component and may persist after discontinuation of therapy.
Adverse events due to the use of dutasteride as monotherapy
Rarely (≥1 / 10 000 and
Very rarely (
Adverse events due to tamsulosin hydrochloride as monotherapy
Often (≥1 / 100 and
Infrequently (≥1 / 1000 and
Rarely (≥1 / 10 000 and
Very rarely (

Postmarketing research

Intraoperative atonic iris syndrome (IFIS, a type of small pupil syndrome) was observed during cataract surgery in some patients who received alpha1-adrenoblockers, including tamsulosin hydrochloride.
Cases of atrial fibrillation, arrhythmia, tachycardia and dyspnea have been identified with tamsulosin. The frequency of adverse reactions and the relationship with taking tamsulosin has not been established.

special instructions

Dutasteride is absorbed through the skin, so women and children should avoid contact with damaged capsules. In case of contact with damaged capsules, it is necessary to immediately wash the corresponding skin area with soap and water.
The combined use of tamsulosin and strong inhibitors of CYP3A4 (ketoconazole), CYP2D6 (paroxetine), as well as their weaker inhibitors leads to an increase in the exposure of tamsulosin. Thus, the use of tamsulosin in combination with strong inhibitors of CYP3A4 is not recommended; The combination of CYP2D6 inhibitors and tamsulosin should be administered with caution.
Since T1 / 2 dutasteride is 3-5 weeks and is metabolized primarily in the liver, Duodart should be used with caution in patients with liver disease.
Combined therapy with tamsulosin hydrochloride and the development of heart failure
In two 4-year clinical studies, the incidence of heart failure (a composite term for the occurring events, mainly heart failure and congestive heart failure) was higher in patients who received the combination of dutasteride and alpha1-adrenoblocker, mainly tamsulosin hydrochloride, than in patients not receiving combined treatment. In two 4-year clinical studies, the incidence of heart failure remained low (≤ 1%) and varied between studies. But in general, there was no discrepancy in the incidence of side effects from the cardiovascular system. No causal link has been established between treatment with dutasteride (alone or in combination with an alpha1-blocker) and heart failure.

Impact on PSA and prostate cancer

In patients with BPH, it is necessary to conduct a digital rectal examination and other methods of examining the prostate gland before starting treatment with Duodart and periodically repeat these studies during treatment to rule out the development of prostate cancer.
The determination of serum PSA concentrations is an important component of the screening process aimed at detecting prostate cancer.
After 6 months of therapy, dutasteride reduces serum PSA levels in patients with BPH by about 50%.
Patients taking Duodart should have a new baseline PSA level determined after 6 months of therapy.
Any stable increase in PSA levels with respect to the smallest value in the treatment with Duodart may indicate the development of prostate cancer (in particular, prostate cancer with a high degree of differentiation on the Gleason scale) or failure to comply with the therapy mode with Duodart and even if these PSA levels remain within normal values ​​in patients not taking 5α-reductase inhibitors.
The overall PSA level returns to its original value within 6 months after dutasteride is discontinued.
The ratio of free PSA to total remains constant even during therapy with dutasteride. When expressing this ratio in fractions to detect prostate cancer in men who receive dutasteride, correction of this value is not required.

Risk of developing breast cancer

In clinical studies in the treatment of BPH, 2 cases of breast cancer have been identified in patients using dutasteride. The first case developed 10 weeks after the start of therapy, the second - 11 months; 1 case of breast cancer was also detected in a patient from the placebo group. The relationship between long-term dutasteride intake and the risk of developing breast cancer is unknown.

Prostate cancer

In a clinical study of 4 years, 1517 out of more than 8,000 men with preliminary negative biopsy results and PSA levels of 2.5-10 ng / ml were diagnosed with prostate cancer. A higher incidence of cancer was observed in patients from the dutasterid group (n = 29, 0.9%) compared with the placebo group (n = 19, 0.6%). There was no interaction between taking dutasteride and the degree of prostate cancer. Men taking dutasteride should be regularly screened for the risk of prostate cancer, including a PSA test.

Hypotension

As with the use of any alpha1-blockers, when tamsulosin hydrochloride is used, orthostatic hypotension can occur, in rare cases leading to fainting.
Patients starting treatment with Duodart should be warned to sit or lie down at the first sign of orthostatic hypotension (dizziness) until dizziness subsides.
To avoid the development of symptomatic hypotension, caution should be exercised when co-prescribing alpha1-blockers and PDE5 inhibitors, since These drugs belong to the group of vasodilators and can lead to a decrease in blood pressure.

Floppy iris syndrome

Intraoperative atonic iris syndrome (IFIS, a type of small pupil syndrome) was observed during cataract surgery in some patients who received alpha1-adrenoblockers, including tamsulosin hydrochloride. Syndrome atonic iris can lead to an increase in the number of complications during operations.
During the preoperative examination, the ophthalmosurgeon should clarify whether the patient is taking a combination of dutasteride with tamsulosin hydrochloride to be able to prepare for the operation, and taking adequate measures when the iris atony occurs intraoperatively.
Canceling tamsulosin hydrochloride 1-2 weeks before cataract surgery is considered beneficial, but the benefits and time period for discontinuing Duodart before cataract surgery have not been established.

Liver dysfunction

Currently there are no data on the use of the drug Duodart in patients with impaired liver function. Since Dutasteride undergoes intensive metabolism, and its T1 / 2 is 3-5 weeks. Care must be taken when Duodart treats patients with impaired liver function.

Influence on ability to drive motor transport and control mechanisms

No studies have been conducted that studied the effect on driving a car and working with machinery.
Patients should be informed about the possibility of symptoms associated with orthostatic hypotension, such as dizziness. Care must be taken when driving vehicles or potentially dangerous machinery.

Interaction

No studies have been conducted to study drug interactions for the combination of dutasteride with tamsulosin hydrochloride. The data below reflects the available information about the individual components.

Dutasteride

Dutasteride is metabolized by the CYP3A4 isoenzyme of the cytochrome P450 enzyme system. In the presence of CYP3A4 inhibitors, dutasteride concentrations in the blood may increase.
With the simultaneous use of dutasteride with CYP3A4 inhibitors verapamil and diltiazem, there is a decrease in the clearance of dutasteride by 37% and 44%, respectively. However, amlodipine, another calcium channel blocker, does not reduce the clearance of dutasteride.
The decrease in clearance of dutasteride and the subsequent increase in its concentration in the blood while using this drug and inhibitors of CYP3A4 is not significant due to the wide range of safety limits of this drug, so there is no need to reduce its dose.
In vitro, dutasteride is not metabolized by the following human cytochrome P450 isoenzymes: CYP1A2, CYP2A6, CYP2E1, CYP2C8, CYP2C9, CYP2C19, CYP2B6 and CYP2D6.
Dutasteride does not inhibit in vitro enzymes of the human cytochrome P450 system involved in the metabolism of drugs.
Dutasterid does not displace warfarin, acenocoumarol, fenprokumon, diazepam and phenytoin from their sites of binding to plasma proteins, and these drugs, in turn, do not displace dutasteride.
There was no effect on the pharmacokinetics and pharmacodynamics of the combined use of dutasteride in combination with tamsulosin, terazosin, warfarin, digoxin and holisteramin.
When using dutasteride simultaneously with lipid-lowering drugs, ACE inhibitors, beta-blockers, calcium channel blockers, corticosteroids, diuretics, NSAIDs, PDE5 inhibitors and quinolone antibiotics, there is no significant drug interaction.

Tamsulosin hydrochloride

There is a theoretical risk of enhancing the hypotensive effect when using tamsulosin hydrochloride in conjunction with drugs that can reduce blood pressure, including anesthetics, alpha1-blockers and PDE5 inhibitors. Doodart® should not be used in combination with other alpha1-adrenergic blockers.
The combined use of tamsulosin and ketoconazole (a strong inhibitor of CYP3A4) leads to an increase in Cmax and AUC of tamsulosin hydrochloride to 2.2 and 2.8, respectively. Combined administration of tamsulosin and paroxetine (a strong inhibitor of CYP2D6) leads to an increase in Cmax and AUC of tamsulosin hydrochloride to 1.3 and 1.6, respectively. The combined use of CYP2D6 and CYP3A4 inhibitors with tamsulosin has not been studied, but with this combination a significant increase in tamsulosin exposure is expected.
The simultaneous use of tamsulosin hydrochloride (0.4 mg) and cimetidine (400 mg every 6 hours) for 6 days resulted in a decrease in clearance (by 26%) and an increase in the AUC of tamsulosin hydrochloride (by 44%). Care must be taken when using the drug Duodart and cimetidine together.
Exhaustive studies of drug interactions between tamsulosin hydrochloride and warfarin have not been conducted. Caution should be exercised with the simultaneous use of warfarin and tamsulosin hydrochloride.
In three studies in which tamsulosin hydrochloride (0.4 mg for 7 days, then 0.8 mg for the next 7 days) was taken along with atenolol, enalapril or nifedipine for 3 months, there was no interaction, therefore, there is no need for dose adjustment when using these drugs together with the drug Duodart.
Simultaneous use of tamsulosin hydrochloride (0.4 mg / day for 2 days, then 0.8 mg / day for 5-8 days) and a single IV administration of theophylline (5 mg / kg) did not change the pharmacokinetics of theophylline, therefore, is not required dose adjustments.
Simultaneous use of tamsulosin hydrochloride (0.8 mg / day) and a single dose of furosemide (20 mg) resulted in a decrease from 11 to 12% of Cmax and AUC of tamsulosin hydrochloride, however, it is expected that these changes are clinically insignificant and dose adjustment is not required.

Combined use of dutasteride and tamsulosin hydrochloride

In two 4-year clinical studies, the incidence of heart failure (a composite term for the occurring events, mainly heart failure and congestive heart failure) was higher in patients who received the combination of dutasteride and alpha1-adrenoblocker, mainly tamsulosin hydrochloride, than in patients not receiving combined treatment. In two 4-year clinical studies, the incidence of heart failure remained low (≤ 1%) and varied between studies. But in general, there was no discrepancy in the incidence of side effects from the cardiovascular system. No causal link has been established between treatment with dutasteride (alone or in combination with an alpha1-blocker) and heart failure.

Overdose

There is no data regarding overdose when taking a combination of dutasteride with tamsulosin hydrochloride. The data below reflects information available on individual components.

Dutasteride

Symptoms: When using dutasteride at a dose of up to 40 mg / day (80 times higher than the therapeutic dose), no adverse events were observed within 7 days. In clinical studies with the appointment of 5 mg / day for 6 months, no adverse reactions other than those listed for the therapeutic dose (0.5 mg / day) were noted.
Treatment: there is no specific antidote for dutasteride; therefore, if overdose is suspected, symptomatic and supportive treatment is sufficient.

Tamsulosin hydrochloride

Symptoms: An overdose of tamsulosin hydrochloride may develop acute hypotension.
Treatment: symptomatic therapy. Blood pressure can recover when a person assumes a horizontal position. In the absence of effect, it is possible to apply agents that increase the bcc and, if necessary, vasoconstrictor agents. It is necessary to monitor the function of the kidneys. It is unlikely that dialysis will be effective, because tamsulosin hydrochloride is 94-99% bound to plasma proteins.

Terms of sell

You can buy Duodart without a prescription.