Avodart capsules 0.5 mg, 30 pcs.

Composition

1 capsule contains:

Active ingredient:

dutasteride – 500 mcg.

Auxiliary substances:

mono-and diglycerides of caprylic / capric acid – 349.5 mg,

butylhydroxytoluene-35 mcg.

Capsule shell composition:

gelatin-144.8 mg,

glycerol-70.8 mg,

titanium dioxide-1.78 mg,

iron oxide yellow-127 mcg,

medium-chain triglycerides-q. s.,

lecithin-q. s., red printing ink** – q. s.

Pharmacological action

Dutasteride is a double 5α-reductase inhibitor. Inhibits the activity of 5α-reductase isoenzymes types 1 and 2, which are responsible for the conversion of testosterone to 5α-dihydrotestosterone (DHT).

Dihydrotestosterone is the main androgen responsible for glandular hyperplasia of the prostate.

The maximum effect of dutasteride on reducing DHT concentrations is dose-dependent and is observed 1-2 weeks after the start of treatment. After 1 and 2 weeks of taking dutasteride at a dose of 500 mcg/day, the average serum dihydrotestosterone concentrations decreased by 85% and 90%.

Indications

• As a combination therapy with alpha-1-blockers for the treatment and prevention of the progression of benign prostatic hyperplasia by reducing its size, relieving symptoms, improving urination, reducing the risk of acute urinary retention and the need for surgery. A combination of dutasteride and the alpha-1-blocker tamsulosin was mainly studied.
• As a monotherapy for the treatment and prevention of the progression of benign prostatic hyperplasia by reducing its size, relieving symptoms, improving urination, reducing the risk of acute urinary retention and the need for surgery.

Use during pregnancy and lactation

Pregnancy: dutasteride is contraindicated in women. Dutasteride has not been studied in women, as preclinical evidence suggests that suppression of DHT levels may cause inhibition of the development of the external genitalia in the fetus.

Lactation: there are no data on the penetration of dutasteride into breast milk.

Effect on fertility: the effect of dutasteride in a daily dose of 500 mcg on sperm characteristics was studied in healthy volunteers aged 18-52 years. By the 52nd week of treatment, the average percentage decreases in total sperm count, sperm volume, and sperm motility were 23%,26%, and 18%, respectively, compared to baseline. The concentration of spermatozoa and their morphological characteristics did not change.

After 24 weeks of follow-up, the mean percentage change in total sperm count in the dutasteride group remained 23% lower compared to baseline.

The average value for all sperm parameters at all time points remained within the normal range and did not meet the specified criteria for clinically significant changes (30%). At the 52nd week of treatment, the total sperm count of two volunteers in the dutasteride group decreased by more than 90% compared to the baseline level, with partial recovery at the 24th week of follow-up. Thus, the clinical significance of the effect of dutasteride on semen parameters and on individual patient fertility is unknown.

Contraindications

• Hypersensitivity to dutasteride and other components of the drug.
• Hypersensitivity to other 5α-reductase inhibitors.
• Avodart® is contraindicated in women and children.

With caution: the drug should be prescribed for hepatic insufficiency.

Side effects

The adverse events presented below are listed according to the anatomical and physiological classification and frequency of occurrence. The frequency of occurrence is determined as follows:

• Very often (≥1/10).
• Frequently (≥1/100 and
• Infrequently (≥1/1000 and
• Rarely (≥ 1/10,000 and
• Very rare (

Frequency categories were formed based on clinical studies of the drug and post-marketing surveillance. The frequency of occurrence of adverse events formed on the basis of post-marketing observation.

Immune system disorders: very rarely – allergic reactions (including rash, pruritus, urticaria, localized edema) and angioedema.

From the skin and subcutaneous fat: rarely-alopecia (mainly loss of body hair) or hypertrichosis.

Mental disorders: very rarely – depressive state.

From the reproductive system: very rarely – testicular pain, testicular edema.

Interaction

In vitro dutasteride is metabolized by the CYP3A4 isoenzyme of the cytochrome P450 enzyme system. In the presence of CYP3A4 inhibitors, blood concentrations of dutasteride may increase.

When dutasteride is co-administered with CYP3A4 inhibitors verapamil and diltiazem, there is a decrease in dutasteride clearance. However, amlodipine, another calcium channel blocker, does not reduce dutasteride clearance. A decrease in the clearance of dutasteride and a subsequent increase in its concentration in the blood with simultaneous use of this drug and CYP3A4 inhibitors is not significant due to the wide range of safety limits of dutasteride, so there is no need to reduce its dose.

In vitro, dutasteride is not metabolized by the following human cytochrome P 450 isoenzymes: CYP1A2, CYP2A6, CYP2E1, CYP2C8, CYP2C9, CYP2C19, and CYP2D6.

Dutasteride does not inhibit in vitro human cytochrome P 450 enzymes involved in drug metabolism.

In vitro, dutasteride does not displace warfarin, acenocoumarol, phenprocumone, diazepam, and phenytoin from their plasma protein binding sites, and these drugs, in turn, do not displace dutasteride.

No clinically significant pharmacokinetic or pharmacodynamic interactions were observed in human interaction studies of dutasteride with tamsulosin, terazosin, warfarin, digoxin, and colestyramine.

No significant adverse drug interactions were observed when dutasteride was administered concomitantly with lipid-lowering drugs, ACE inhibitors, beta-blockers, calcium channel blockers, corticosteroids, diuretics, NSAIDs, phosphodiesterase type 5 inhibitors, and quinolone antibiotics.

How to take, course of administration and dosage

The drug can be taken regardless of food intake.

Capsules should be swallowed whole, not chewed or opened, as the contents of the capsule may cause irritation of the oropharyngeal mucosa.

Benign prostatic hyperplasia (BPH)

Adult men (including the elderly) the recommended dose of Avodart® is 1 capsule (500 mcg) 1 time/day. Capsules should be taken whole.

Although improvement with the drug occurs quite quickly, treatment should be continued for at least 6 months in order to objectively assess the therapeutic effect.

For the treatment of BPH, Avodart® can be prescribed as monotherapy or in combination with alpha-1-blockers.

Special patient groups

At 500 mcg/day, less than 0.1% of the dose is excreted through the kidneys, so there is no need to reduce the dose in patients with impaired renal function.

Currently, there are no data on the use of Avodart® in patients with impaired liver function. Since dutasteride undergoes intensive metabolism and its half-life is 3-5 weeks, caution should be exercised when treating patients with impaired liver function with Avodart®.

Overdose

Symptoms: when prescribing dutasteride up to 40 mg / day once (80 times higher than the therapeutic dose) for 7 days, no significant side effects were observed.

In clinical trials, patients received dutasteride at a dose of 5 mg daily for 6 months, while no additional side effects were found to those observed against the background of taking 500 mcg of dutasteride.

Treatment: There is no specific antidote for dutasteride, so if an overdose is suspected, it is sufficient to conduct symptomatic and supportive treatment.

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 area of the skin with soap and water.

Impaired liver function

Currently, there are no data on the use of Avodart® in patients with impaired liver function. Since dutasteride undergoes intensive metabolism and its half-life is 3-5 weeks, caution should be exercised when treating patients with impaired liver function with Avodart®.

Heart failure with combined use of dutasteride and tamsulosin

In two 4-year clinical trials, the incidence of heart failure was higher in patients treated with a combination of dutasteride and an alpha-1-blocker, mainly tamsulosin, than in patients who did not receive 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 frequency of side effects from the cardiovascular system. No causal relationship has been established between treatment with dutasteride (as monotherapy or in combination with an alpha-1 blocker) and the development of heart failure.

Effect on detection of prostate-specific antigen (PSA) and prostate cancer (PCA)

Patients should have a digital rectal examination, as well as other methods of prostate examination, before starting treatment with dutasteride and periodically repeat them during treatment to exclude the development of prostate cancer.

Determination of serum PSA concentrations is an important component of prostate cancer screening. After 6 months of dutasteride therapy, the average 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 the PSA level.

The use of dutasteride does not affect the diagnostic value of PSA as a marker of prostate cancer. Any confirmed increase in PSA relative to its lowest value during dutasteride treatment may indicate the development of prostate cancer (in particular, prostate cancer with a high degree of differentiation on the Gleason scale) or non-compliance with the dutasteride therapy regimen and should be carefully evaluated, even if these PSA levels remain within normal values for this age category of patients not taking 5α-reductase inhibitors.

Total PSA levels return to baseline within 6 months of dutasteride discontinuation.

The ratio of free PSA to total PSA 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, no correction of this value is required.

Effect of long-term dutasteride intake on the development of breast cancer in men

There was no effect of long-term dutasteride administration on the development of breast cancer in men.

Prostate cancer and high-grade tumors

The 4-year study (REDUCE) compared placebo and dutasteride use in 8231 volunteers aged 50 to 75 years, with a negative biopsy result for the presence of prostate cancer and PSA levels from 2.5 ng/ml to 10 ng/ml at the initial examination.

During the study,6706 patients underwent a puncture biopsy of the prostate gland and, based on the results obtained, the degree of prostate cancer malignancy was determined on the Gleason scale.1,517 patients were diagnosed with prostate cancer during the study. In most cases, both the dutasteride and placebo groups were diagnosed with highly differentiated prostate cancer (Gleason score 5-6). There were no differences in the number of cases of prostate cancer with a score of 7-10 on the Gleason scale in the dutasteride group and the placebo group (p = 0.81).

After 4 years, there were more cases of prostate cancer with a score of 8-10 on the Gleason scale in the dutasteride group (n = 29; 0.9%) compared to the placebo group (n = 19; 0.6%) (p = 0.15). When evaluating biopsy data for 1-2 years, the number of patients diagnosed with prostate cancer with a score of 8-10 on the Gleason scale was comparable in the dutasteride (n = 17; 0.5%) and placebo (n = 18; 0.5%) groups. When evaluating biopsy data for 3-4 years, more cases of prostate cancer were diagnosed with a score of 8-10 on the Gleason scale in the dutasteride group (n = 12; 0.5%) compared to the placebo group (n = 1;

In a 4-year study (CombAT) of patients with BPH, in which prostate biopsy was not determined by protocol for all participants, and all diagnoses of prostate cancer were based on biopsy according to indications, prostate cancer with a score of 8-10 on the Gleason scale was diagnosed in 8 patients (

No causal relationship has been established between the use of dutasteride and the development of high-grade prostate cancer.

Men taking dutasteride should be regularly screened for prostate cancer risk assessment, including PSA levels.

Influence on the ability to drive motor vehicles and manage mechanisms

Taking dutasteride does not affect driving or working with mechanisms.

Form of production

Capsules.

Storage conditions

At a temperature not exceeding 30 °C

Shelf life

4 years

Active ingredient

Dutasteride

Conditions of release from pharmacies

By prescription

Dosage form

of the capsule

Purpose

Adults as prescribed by a doctor

Indications

Prostatic Hyperplasia

Weight

Weight: 38 gr.