Duodart capsules 0.5 mg + 0.4 mg №30

Release form

Capsules

Packaging

30 pieces

Mechanism of action

Duodart^® - 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 the 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 - postsynaptic α blocker_1a-adrenoreceptors located in the smooth muscles of the prostate gland, bladder neck and prostatic urethra. Α blockade_1a-adrenoretseptorov leads to a decrease in the smooth muscle tone of the prostate gland, bladder neck and prostatic 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.

Indications

- treatment and prevention of progression of benign prostatic hyperplasia (reducing its size, reducing the 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 the drug.

Use during pregnancy and lactation

Drug duodart^® 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.

Special notes

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 T_1/2 dutasteride is 3-5 weeks and is metabolized mainly in the liver, the drug 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-adrenergic blocker, mainly tamsulosin hydrochloride, than in patients not receiving the 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 alpha₁-adrenoblocker) and heart failure.

Impact on PSA and prostate cancer

In patients with BPH, a digital rectal examination and other methods of examining the prostate gland should be carried out 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 the drug Douodart^®, a new baseline PSA level should be determined after 6 months of therapy.

Any stable increase in PSA level with respect to the lowest value in the treatment with drug 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 treatment with drug Douodart^® and should be carefully evaluated, even if these PSA levels remain within the normal range 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 any alpha₁-adrenergic blockers, when tamsulosin hydrochloride is used, orthostatic hypotension may occur, in rare cases leading to fainting.

Patients starting treatment with Douodart^®, should be warned about the need to sit down or lie down at the first sign of orthostatic hypotension (dizziness) until dizziness passes.

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 operations in some patients who received alpha₁-blockers, 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 the drug 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 T_1/2 is 3-5 weeks, you need to be careful when treating with Douodart^® 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.

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).

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 are 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^® contraindicated in patients with severe hepatic insufficiency.

Side effects

Adverse events caused by the use of tamsulosin hydrochloride in combination with dutasteride

Very rarely (<1/10 000): impotence, decreased libido, impaired ejaculation, gynecomastia, chest pain, dizziness.

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 <1/1000): alopecia (mainly hair loss on the body), hypertrichosis.

Very rarely (<1/10 000): depression, pain and swelling in the testicles.

Adverse events due to tamsulosin hydrochloride as monotherapy

Often (≥1 / 100 and <1/10): dizziness, impaired ejaculation.

Infrequently (≥1 / 1000 and <1/100): rapid heartbeat, constipation, diarrhea, vomiting, asthenia, rhinitis, rash, pruritus, urticaria, postural hypotension.

Rarely (≥1 / 10 000 and <1/1000): loss of consciousness, angioedema.

Very rarely (<1/10 000): priapism, Stevens-Johnson syndrome.

Postmarketing research

Intraoperative atonic iris syndrome (IFIS, a type of small pupil syndrome) was observed during cataract operations in some patients who received alpha₁-blockers, 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.

Drug 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 cells.