Dutasteride-vista

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT DUTASTERIDE-VISTA (DUTASTERIDE-VISTA)

Composition:

Active substance: dutasteride;

1 capsule contains 0.5 mg of dutasteride;

Excipients: glycerol monocaprylocaprate Type 1, butylhydroxytoluene (E 321);

capsule shell: gelatin, glycerin, purified water, titanium dioxide (E 171), iron oxide yellow (E 172), medium-chain triglycerides, soy lecithin (E 322).

Pharmaceutical form. Soft capsules.

Main physicochemical properties: elongated opaque yellow soft gelatin capsules containing a yellowish oily liquid.

Pharmacotherapeutic group. Agents used in benign prostatic hyperplasia. Testosterone 5α-reductase inhibitors. ATC code G04C B02.

Pharmacological Properties.

Pharmacodynamics.

Dutasteride is a dual inhibitor of 5α-reductase, inhibiting both type 1 and type 2 isoenzymes of 5α-reductase, which are responsible for the conversion of testosterone into 5α-dihydrotestosterone. Dihydrotestosterone is an androgen primarily responsible for hyperplasia of prostate tissue. The maximal reduction in dihydrotestosterone levels during dutasteride treatment is dose-dependent and occurs within the first 1–2 weeks. After the 1st and 2nd week of dutasteride administration at a daily dose of 0.5 mg, the mean concentration of dihydrotestosterone decreases by 85% and 90%, respectively.

In patients with benign prostatic hyperplasia receiving 0.5 mg of dutasteride daily, the mean reduction in dihydrotestosterone levels was 94% after 1 year and 93% after 2 years of treatment. Mean testosterone levels increased by 19% after both 1 and 2 years.

Pharmacokinetics.

Dutasteride is administered orally in the form of a solution in soft gelatin capsules. After a single 0.5 mg dose, peak plasma concentration is observed within 1–3 hours. Absolute bioavailability is 60% when administered via a two-hour intravenous infusion. Bioavailability is not affected by food intake.

After single or multiple doses, dutasteride has a large volume of distribution (300–500 L). Plasma protein binding exceeds 99.5%.

With a daily dose of 0.5 mg, 65% of the steady-state plasma concentration of dutasteride is achieved after 1 month of treatment and approximately 90% after 3 months. A steady-state plasma concentration of approximately 40 ng/mL is reached after 6 months of treatment with a daily dose of 0.5 mg. As in plasma, steady-state concentrations of dutasteride in semen are achieved after 6 months. After 52 weeks of treatment, the mean concentration of dutasteride in semen is 3.4 ng/mL (range: 0.4–14 ng/mL). The distribution ratio of dutasteride from plasma to semen is approximately 11.5%.

In vitro, dutasteride is metabolized by the CYP3A4 enzymes of human cytochrome P450 to two monohydroxylated metabolites.

Spectrometric analysis in human plasma reveals unchanged dutasteride, three major metabolites (4´-hydroxydutasteride, 1,2-dihydrodutasteride, and 6-hydroxydutasteride), and two minor metabolites (6,4´-dihydroxydutasteride and 15-hydroxydutasteride).

Dutasteride is extensively metabolized. After oral administration of 0.5 mg/day, 1–15.4% (mean 5.4%) of the administered dose is excreted in feces as unchanged dutasteride. The remainder of the dose is excreted as metabolites.

Only trace amounts of unchanged dutasteride (<0.1% of the administered dose) are detected in urine. The terminal elimination half-life of dutasteride is 3–5 weeks. Residual levels of dutasteride in plasma may be detected 4–6 months after discontinuation of treatment.

Based on pharmacokinetic and pharmacodynamic studies, dose adjustment of dutasteride according to patient age is not required.

The effect of renal impairment on the pharmacokinetics of dutasteride has not been studied. However, less than 0.1% of the dose is excreted in human urine after administration of 0.5 mg dutasteride; therefore, dose adjustment in patients with renal impairment is not necessary.

The effect of hepatic impairment on the pharmacokinetics of dutasteride has not been studied (see sections "Dosage and Administration" and "Special Warnings").

Safety and Clinical Studies.

Heart Failure

In a 4-year clinical study evaluating dutasteride in combination with tamsulosin for the treatment of benign prostatic hyperplasia in 4844 men (CombAT study), the incidence of heart failure (composite term) was higher in the combination therapy group (14/1610, 0.9%) than in either monotherapy group receiving dutasteride (4/1623, 0.2%) or tamsulosin (10/1611, 0.6%).

In a separate 4-year placebo-controlled clinical trial of dutasteride chemoprevention involving 8231 patients aged 50 to 75 years with a prior negative prostate biopsy for prostate cancer and baseline PSA levels between 2.5 ng/mL and 10.0 ng/mL in men aged 50–60 years or 3.0 ng/mL and 10.0 ng/mL in men aged 60 years and older (REDUCE study), the incidence of heart failure was higher in patients receiving dutasteride 0.5 mg once daily (30/4105, 0.7%) compared to those receiving placebo (16/4126, 0.4%). In a retrospective analysis of this study, a higher incidence of heart failure was observed in patients receiving dutasteride and an alpha-blocker concurrently (12/1152, 1.0%) compared to those receiving dutasteride without an alpha-blocker (18/2953, 0.6%), placebo with an alpha-blocker (1/1399, <0.1%), or placebo without an alpha-blocker (15/2727, 0.6%). A causal relationship between the use of dutasteride (alone or in combination with alpha-blockers) and the development of heart failure has not been established (see section "Special Warnings").

Prostate Cancer and High-Grade Tumors

In a 4-year placebo-controlled study involving 8231 patients aged 50 to 75 years with a prior negative prostate biopsy for prostate cancer and baseline PSA levels between 2.5 ng/mL and 10.0 ng/mL in men aged 50–60 years or 3.0 ng/mL and 10.0 ng/mL in men aged 60 years and older (REDUCE study), 6706 subjects underwent prostate needle biopsy (mandatory per the original protocol), and data were analyzed using the Gleason grading scale. A total of 1517 patients were diagnosed with prostate cancer in the study. Most prostate tumors (70%) detected by biopsy in both treatment groups were well-differentiated (Gleason score 5–6).

A higher incidence of high-grade prostate cancer (Gleason score 8–10) was observed in the dutasteride group (n = 29, 0.9%) compared to the placebo group (n = 19, 0.6%) (p = 0.15). During years 1–2 of the study, the number of patients diagnosed with Gleason score 8–10 prostate cancer was similar in the dutasteride group (n = 17, 0.5%) and the placebo group (n = 18, 0.5%). During years 3–4, more cases of Gleason score 8–10 prostate cancer were diagnosed in the dutasteride group (n = 12, 0.5%) compared to the placebo group (n = 1, <0.1%) (p = 0.0035). There are no data on the effect of dutasteride use beyond 4 years on the risk of developing prostate cancer. The percentage of patients diagnosed with Gleason score 8–10 prostate cancer remained constant over different periods of the study (years 1–2 and 3–4) in the dutasteride group (0.5% in each period), whereas in the placebo group, the percentage of patients with high-grade prostate cancer (Gleason score 8–10) was lower in years 3–4 than in years 1–2 (<0.1% vs. 0.5%, respectively) (see section "Special Warnings"). There was no difference in the incidence of prostate cancer with Gleason score 7–10 (p = 0.81).

In a 4-year clinical study of benign prostatic hyperplasia treatment (CombAT), where mandatory biopsy was not required by the original protocol and all prostate cancer diagnoses were biopsy-confirmed based on clinical indications, the incidence of Gleason score 8–10 prostate cancer was (n = 8, 0.5%) in the dutasteride group, (n = 11, 0.7%) in the tamsulosin group, and (n = 5, 0.3%) in the combination therapy group.

The relationship between dutasteride use and the development of high-grade prostate cancer remains unclear.

Breast Cancer in Men

Two case-control epidemiological studies—one conducted in the USA (n = 339 breast cancer cases and n = 6780 controls) and another in the UK (n = 398 breast cancer cases and n = 3930 controls)—did not show an increased risk of male breast cancer with the use of 5α-reductase inhibitors. The first study found no association with breast cancer (relative risk for use ≥1 year before diagnosis compared to use <1 year: 0.70; 95% CI 0.34, 1.45). In the second study, the relative risk of breast cancer associated with 5α-reductase inhibitor use compared to non-use was 1.08; 95% CI 0.62, 1.87).

A causal relationship between male breast cancer and long-term use of dutasteride has not been established.

Clinical characteristics.

Indications.

Treatment of symptoms of moderate to severe benign prostatic hyperplasia; reduction of the risk of developing acute urinary retention and the need for surgical intervention in patients with moderate to severe symptoms of benign prostatic hyperplasia.

Contraindications.

DUTASTERIDE-VISTA is contraindicated in patients with hypersensitivity to dutasteride, other 5α-reductase inhibitors, soy, peanuts, or any other component of the product.

DUTASTERIDE-VISTA must not be used for the treatment of women and children (see section "Use during pregnancy or breastfeeding").

DUTASTERIDE-VISTA is contraindicated in patients with severe hepatic impairment.

Interaction with other medicinal products and other forms of interaction.

Information on the reduction of PSA (Prostate-specific antigen) levels in blood serum during treatment with dutasteride, as well as information on the detection of prostate cancer, see section "Special precautions for use".

Effect of other medicinal products on the pharmacokinetics of dutasteride

Concomitant use with CYP3A4 and/or P-glycoprotein inhibitors.

Dutasteride is primarily eliminated by metabolism. In vitro studies show that metabolism is catalyzed by CYP3A4 and CYP3A5. Formal interaction studies with potent CYP3A4 inhibitors have not been conducted. However, in a population pharmacokinetic study, serum concentrations of dutasteride were on average 1.6–1.8 times higher in a small number of patients who were concurrently treated with verapamil or diltiazem (moderate CYP3A4 inhibitors and P-glycoprotein inhibitors) compared to other patients.

Data from studies indicate that the clearance of dutasteride is reduced when co-administered with the CYP3A4 inhibitors verapamil (by 37%) and diltiazem (by 44%). In contrast, the clearance of dutasteride is not reduced when administered with amlodipine, another calcium channel blocker.

Since dutasteride is metabolized by the CYP3A4 isoenzyme, serum concentrations of dutasteride may increase in the presence of CYP3A4 inhibitors. Long-term administration of DUTASTERIDE-VISTA together with medicinal products that are strong inhibitors of the CYP3A4 enzyme (such as ritonavir, indinavir, nefazodone, itraconazole, oral ketoconazole) may lead to increased dutasteride concentrations. Further inhibition of 5α-reductase due to prolonged action of dutasteride is unlikely. However, dose reduction of dutasteride may be considered if adverse effects occur. It should be noted that in the case of enzyme inhibition, the long half-life may become even longer, and concomitant therapy may need to continue for more than 6 months before a new steady-state concentration is achieved.

In vitro, dutasteride is not metabolized by CYP1A2, CYP2A6, CYP2E1, CYP2C8, CYP2C9, CYP2C19, CYP2B6, or CYP2D6 isoenzymes of the human cytochrome P450 system.

Effect of dutasteride on the pharmacokinetics of other medicinal products

Dutasteride does not affect the pharmacokinetics of warfarin or digoxin. This suggests that dutasteride does not inhibit/induce the activity of the CYP2C9 enzyme or the P-glycoprotein transporter. In vitro interaction studies indicate that dutasteride does not inhibit the enzymes CYP1A2, CYP2D6, CYP2C9, CYP2C19, or CYP3A4.

In a small 2-week study (N=24) involving healthy men, dutasteride (0.5 mg daily) did not affect the pharmacokinetics of tamsulosin or terazosin. No evidence of pharmacodynamic interaction was observed in this study.

In vitro studies have shown that dutasteride does not displace warfarin, acenocoumarol, phenprocoumon, diazepam, or phenytoin from plasma protein binding, and these compounds do not displace dutasteride either. Interactions between dutasteride and tamsulosin, terazosin, warfarin, digoxin, and cholestyramine have been studied. No clinically significant interactions were observed. Administration of 12 g cholestyramine one hour after a single 5 mg dose of dutasteride did not affect the pharmacokinetics of dutasteride.

Although specific interaction studies with other drugs have not been performed, approximately 90% of all patients in clinical trials of dutasteride received other medicinal products concurrently. No clinically significant adverse reactions were observed when dutasteride was used concomitantly with lipid-lowering agents, angiotensin-converting enzyme inhibitors, beta-blockers, calcium channel blockers, corticosteroids, diuretics, nonsteroidal anti-inflammatory drugs, type V phosphodiesterase inhibitors, or quinolone antibiotics.

Special precautions for use

Cardiovascular adverse reactions

Combined therapy may be prescribed only after careful assessment of benefit/risk due to the potential increased risk of adverse reactions (including heart failure) and after consideration of alternative therapeutic options, including monotherapy (see section "Dosage and administration").

According to data from four-year clinical studies, the incidence of heart failure (a collective term for all reported events, primarily primary heart failure and congestive heart failure) was higher among patients treated with a combination of dutasteride and an alpha-blocker, mainly tamsulosin, compared to patients who did not receive this combination. However, in these two studies, the incidence of heart failure was low (≤1%) and variable across the studies. No imbalance in the incidence of cardiovascular adverse events was observed in any of the studies. A causal relationship between the use of dutasteride (alone or in combination with alpha-blockers) and the occurrence of heart failure has not been established (see section "Pharmacological properties").

A meta-analysis of 12 randomized, placebo-controlled or comparative clinical trials (n = 18,802) evaluated the risk of cardiovascular adverse reactions associated with dutasteride use (compared to the control group). There was no consistent statistically significant increase in the risk of heart failure (RR 1.05; 95% CI 0.71, 1.57), acute myocardial infarction (RR 1.00; 95% CI 0.77, 1.30), or stroke (RR 1.20; 95% CI 0.88, 1.64).

Effect on prostate-specific antigen (PSA)

Serum prostate-specific antigen (PSA) concentration is an important component of the screening process for prostate cancer detection.

DUTASTERIDE-VISTA reduces serum PSA levels in patients by approximately 50% on average after 6 months of treatment.

Patients taking DUTASTERIDE-VISTA should have a new baseline PSA level established 6 months after initiating treatment with this medication. This level should then be monitored regularly. Any confirmed increase in PSA from the lowest level during DUTASTERIDE-VISTA treatment may indicate the presence of prostate cancer or non-adherence to DUTASTERIDE-VISTA therapy and requires careful evaluation, even if PSA values remain within the normal range for men not treated with 5α-reductase inhibitors. When interpreting PSA values in patients treated with DUTASTERIDE-VISTA, previous PSA values should be taken into account for comparison.

The use of DUTASTERIDE-VISTA does not affect the utility of PSA levels for diagnosing prostate cancer after establishing a new baseline level.

Total serum PSA returns to baseline levels within 6 months after discontinuation of treatment.

The ratio of free PSA to total PSA remains constant even during treatment with DUTASTERIDE-VISTA. Therefore, if a physician decides to use the percentage of free PSA to assess prostate cancer in a patient taking DUTASTERIDE-VISTA, no adjustment of the value is required.

Digital rectal examination and other methods for detecting prostate cancer should be performed before starting dutasteride treatment and periodically during therapy.

Prostate cancer and high-grade Gleason tumors (poorly differentiated)

In a 4-year clinical study involving over 8,000 men aged 50 to 75 years with prior negative prostate biopsy for cancer and baseline PSA levels between 2.5 ng/mL and 10.0 ng/mL (the REDUCE study), prostate cancer was diagnosed in 1,517 patients. The incidence of high-grade prostate cancer (Gleason score 8–10) was higher in the group treated with dutasteride (n = 29, 0.9%) compared to the placebo group (n = 19, 0.6%). No increase in the incidence of prostate cancer with Gleason scores 5–6 or 7–10 was observed. A causal relationship between dutasteride use and high-grade prostate cancer has not been established. The clinical significance of this numerical imbalance is unknown. Men treated with DUTASTERIDE-VISTA should be regularly monitored for the risk of prostate cancer, including PSA testing.

In an additional sequential two-year follow-up study of patients from the dutasteride chemoprevention trial (REDUCE study), the incidence of new prostate cancer cases was low (dutasteride group [n = 14, 1.2%] vs. placebo group [n = 7, 0.7%]), with no new cases of Gleason score 8–10 prostate cancer identified.

Long-term follow-up (up to 18 years) of patients from a clinical trial using another 5α-reductase inhibitor (finasteride) for chemoprevention showed no statistically significant difference between the finasteride and placebo groups in overall survival (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

Rare cases of male breast cancer have been reported during clinical trials and in the post-marketing period. However, epidemiological studies indicate no increased risk of male breast cancer with the use of 5α-reductase inhibitors. Patients should promptly report any changes in breast tissue, such as nipple discharge or swelling.

Non-intact capsules

Dutasteride is absorbed through the skin; therefore, women and children should avoid contact with non-intact capsules. If capsule contents come into contact with the skin, the area should be washed immediately with soap and water.

Hepatic impairment

The effect of hepatic impairment on the pharmacokinetics of dutasteride has not been studied. Due to the extensive metabolism of dutasteride and its long elimination half-life (3–5 weeks), dutasteride treatment in patients with mild to moderate hepatic impairment should be undertaken with caution (see sections "Dosage and administration", "Contraindications", and "Pharmacological properties").

Use during pregnancy or breastfeeding.

Fertility

Effects of dutasteride on semen parameters (reduced sperm count, ejaculate volume, and sperm motility) have been reported in healthy men. A risk of reduced male fertility cannot be excluded.

Pregnancy

Dutasteride is contraindicated for use in women.

Like other 5α-reductase inhibitors, dutasteride inhibits the conversion of testosterone to dihydrotestosterone, which may impair the development of external genitalia in male fetuses. Small amounts of dutasteride have been detected in the semen of subjects taking 0.5 mg dutasteride daily. It is unknown whether dutasteride transferred from semen of a treated male to a pregnant woman may affect a male fetus (this risk is highest during the first 16 weeks of pregnancy).

As with other 5α-reductase inhibitors, the use of condoms is recommended if the patient's partner is pregnant or could potentially become pregnant, to prevent exposure of the woman to semen.

Breastfeeding

It is unknown whether dutasteride passes into human breast milk.

Ability to influence reaction rate when driving or operating machinery

Due to the pharmacokinetic and pharmacodynamic properties of dutasteride, it does not affect the ability to drive or operate machinery.

Administration and Dosage

Dutasteride-Vista can be prescribed alone or in combination with the alpha-blocker tamsulosin (0.4 mg).

Adult men (including elderly patients)

The recommended dose of Dutasteride-Vista is 1 capsule (0.5 mg) daily for oral administration. The capsule should be swallowed whole and not opened or chewed, as contact with the capsule contents may cause irritation of the mucous membranes of the mouth and throat.

Dutasteride-Vista can be taken independently of food intake.

Although symptom improvement may be observed early during treatment, treatment should be continued for at least 6 months to allow for an objective assessment of the drug's efficacy.

Renal impairment

The pharmacokinetics of dutasteride in patients with renal impairment have not been studied; therefore, caution should be exercised when prescribing the drug to patients with severe renal impairment.

Hepatic impairment

The pharmacokinetics of dutasteride in patients with hepatic impairment have not been studied; therefore, caution is advised when using the drug in patients with mild to moderate hepatic impairment. Dutasteride-Vista is contraindicated in patients with severe hepatic impairment.

Children

Use is contraindicated.

Overdose

Clinical trial data indicate that single doses of dutasteride up to 40 mg/day (80 times higher than the therapeutic dose) administered for 7 days in volunteers did not raise safety concerns. During clinical trials, doses of dutasteride of 5 mg/day administered for 6 months did not result in additional adverse reactions compared to the use of dutasteride at 0.5 mg/day.

There is no specific antidote; therefore, in the event of potential overdose, symptomatic and supportive therapy should be administered.

Adverse reactions

Dutasteride monotherapy

Adverse reactions occurred in approximately 19% of 2167 patients treated with dutasteride during the first year of two-year, placebo-controlled Phase III studies. Most of the observed adverse events were mild or moderate in severity and involved the reproductive system. During the subsequent 2 years of open-label extension studies, no changes in the adverse event profile were observed.

Table 1 lists adverse reactions identified during controlled clinical trials and in the post-marketing period. The adverse reactions listed below, observed during clinical trials and considered by investigators to be drug-related (with an incidence ≥1%), occurred more frequently in patients receiving dutasteride compared to placebo during the first year of treatment. Adverse reactions reported during the post-marketing period were identified from spontaneous post-approval reports; therefore, their actual frequency is unknown.

Frequency classification: very common (> 1/10), common (≥ 1/100 to < 1/10), uncommon (≥ 1/1000 to < 1/100), rare (≥ 1/10,000 to < 1/1000), very rare (< 1/10,000), frequency not known (cannot be estimated from available data).

Table 1

System organ	Adverse reaction	Incidence from clinical studies
		Incidence during 1 year of treatment (n=2167)	Incidence during 2 years of treatment (n=1744)
Reproductive system and breast	Impotence*	6.0%	1.7%
	Changed (decreased) libido*	3.7%	0.6%
	Ejaculation disorders*^	1.8%	0.5%
	Breast disorders+	1.3%	1.3%
Immune system	Allergic reactions, including rash, pruritus, urticaria, localized edema, and angioedema	Incidence estimated from post-marketing data
		Frequency unknown
Psychiatric disorders	Depression	Frequency unknown
Skin and subcutaneous tissue	Alpecia (mainly loss of body hair), hypertrichosis	Uncommon
Reproductive system and breast	Testicular pain and swelling	Frequency unknown

* Adverse reactions related to sexual function disturbances are associated with dutasteride treatment (including monotherapy and combination with tamsulosin). These adverse reactions may persist after discontinuation of treatment. The effect of dutasteride on their duration is unknown.

^ Includes decreased semen volume.

+ Including breast tenderness and breast enlargement.

Combination therapy (dutasteride + tamsulosin)

Data from the 4-year CombAT study, which compared once-daily administration of dutasteride 0.5 mg (n = 1,623) and tamsulosin 0.4 mg (n = 1,611) as monotherapies and in combination (n = 1,610), showed that the incidence of drug-related adverse events during the first, second, third, and fourth year of treatment was 22%, 6%, 4%, and 2%, respectively, for combination therapy with dutasteride/tamsulosin; 15%, 6%, 3%, and 2% for dutasteride monotherapy; and 13%, 5%, 2%, and 2% for tamsulosin monotherapy. The higher incidence of adverse reactions in the combination therapy group during the first year of treatment was due to a higher frequency of reproductive system disorders, particularly ejaculation disorders, observed in this group.

During the first year of treatment in the CombAT study, the adverse reactions listed below, considered by investigators to be related to drug administration, were reported at an incidence of ≥1%; the incidence of these reactions over 4 years of treatment is presented in Table 2.

Table 2

Organ system class	Adverse reaction	Incidence during treatment
		1st year	2nd year	3rd year	4th year
	Combinationa (n) Dutasteride Tamsulosin	(n = 1610) (n = 1623) (n = 1611)	(n = 1428) (n = 1464) (n = 1468)	(n = 1283) (n = 1325) (n = 1281)	(n = 1200) (n = 1200) (n = 1112)
Reproductive system and breast disorders	Impotencyb Combinationa Dutasteride Tamsulosin	6.3 % 5.1 % 3.3 %	1.8 % 1.6 % 1.0 %	0.9 % 0.6 % 0.6 %	0.4 % 0.3 % 1.1 %
	Change (decrease) in libido b Combinationa Dutasteride Tamsulosin	5.3 % 3.8 % 2.5 %	0.8 % 1 % 0.7 %	0.2 % 0.2 % 0.2 %	0 % 0 % < 0.1 %
	Ejaculation disorder b^ Combinationa Dutasteride Tamsulosin	9 % 1.5 % 2.7 %	1 % 0.5 % 0.5 %	0.5 % 0.2 % 0.2 %	<0.1 % 0.3 % 0.3 %
	Breast disordersc Combinationa Dutasteride Tamsulosin	2.1 % 1.7 % 0.8 %	0.8 % 1.2 % 0.4 %	0.9 % 0.5 % 0.2 %	0.6 % 0.7 % 0 %
Cardiac disorders	Heart failure d Combinationa Dutasteride Tamsulosin	0.2 % < 0.1 % < 0.1 %	0.4 % 0.1 % <0.1 %	0.2 % <0.1 % 0.4 %	0.2 % 0 % 0.2 %

From the nervous system

Dizziness Combinationa Dutasteride Tamsulosin

1.4% 0.7% 1.3%

<0.1% <0.1% <0.4%

<0.1% <0.1% <0.1%

0.2% <0.1% 0%

a combination – dutasteride 0.5 mg once daily plus tamsulosin 0.4 mg once daily.

b Adverse reactions related to sexual function are associated with dutasteride treatment (including monotherapy and combination with tamsulosin). These adverse reactions may persist after discontinuation of treatment. The effect of dutasteride on their duration is unknown.

c Including tenderness and breast enlargement.

d The term heart failure includes congestive heart failure, heart failure, left ventricular failure, acute left ventricular failure, cardiogenic shock, acute heart failure, right ventricular failure, acute right ventricular failure, congestive cardiomyopathy, cardiopulmonary failure, ventricular failure, cardiopulmonary failure, congestive cardiomyopathy.

^ Includes decreased semen volume.

Clinical trial data

The REDUCE trial revealed a higher incidence of prostate cancer with Gleason score 8–10 in men receiving dutasteride compared to placebo. It is unknown whether the results of this trial were influenced by prostate volume reduction or other factors related to dutasteride use.

Immune system disorders

Very rare: allergic reactions, including rash, pruritus, urticaria, localized edema, and angioedema.

Psychiatric disorders

Very rare: depression.

Skin and subcutaneous tissue disorders

Rare: alopecia (mainly loss of body hair), hypertrichosis.

Reproductive system and breast disorders

Very rare: testicular pain and swelling.

Cases of male breast cancer have been reported in clinical and postmarketing studies (see section "Special precautions").

Shelf life. 4 years.

Storage conditions.

Store in the original packaging to protect from moisture at temperatures not exceeding 30 °C. Keep out of reach and sight of children.

Packaging. 10 capsules per blister pack, 3 or 9 blister packs per cardboard box.

Prescription category. Prescription only.

Manufacturers.

GALENICUM HEALTH S.L.U.

CINDEA PHARMA, S.L.

SAG MANUFACTURING, S.L.U.

Manufacturer's address and place of business.

Carrer de Sant Gabriel 50, Esplugues de Llobregat, 08950, Spain.

Polígono Industrial Emilianos Revilla Sánchez, Avenida de Agreda, 31, Olvega, Soria, 42110, Spain.

Carretera Nacional 1 Km 36, San Agustín del Guadalix, 28750, Madrid, Spain.