Adverse reactions : תופעות לוואי

4.8     Undesirable effects

AVODART AS MONOTHERAPY
Approximately 19% of the 2167 patients who received dutasteride in the 2 year Phase III placebo-controlled trials developed adverse reactions during the first year of treatment. The majority of events were mild to moderate and occurred in the reproductive system. No change to the adverse event profile was apparent over a further 2 years in open-label extension studies.

The following table shows adverse reactions from controlled clinical trials and post-marketing experience.
The listed adverse events from clinical trials are investigator-judged drug-related events (with incidence more than or equal to 1%) reported with a higher incidence in patients treated with dutasteride compared with placebo during the first year of treatment. Adverse events from post-marketing experience were identified from spontaneous post-marketing reports; therefore the true incidence is not known: 
Very common (≥ 1/10); Common (≥ 1/100 to < 1/10); Uncommon (≥ 1/1,000 to < 1/100); Rare (≥1/10,000 to < 1/1,000); Very rare (< 1/10,000); not known (cannot be estimated from the available data).

Organ system             Adverse reaction                     Incidence from clinical trial data Incidence during year 1    Incidence during year 2 of of treatment (n=2167)      treatment (n=1744)
Impotence*                                 6.0%                            1.7% Reproductive       Altered (decreased) libido*            3.7%                          0.6% system and         Ejaculation disorders*^                1.8%                          0.5% breast disorders   Breast disorders+                      1.3%                          1.3% 
Incidence estimated from post-marketing data
Immune system      Allergic reactions                                Not known disorders          including rash, pruritus,
urticaria, localised oedema, and angioedema
Psychiatric        Depression                                         Not known disorders
Skin and           Alopecia (primarily body                           Uncommon subcutaneous       hair loss), hypertrichosis tissue disorders

Reproductive        Testicular pain and                                  Not known system and          swelling breast disorders
*
These sexual adverse events are associated with dutasteride treatment (including monotherapy and combination with tamsulosin). These adverse events may persist after treatment discontinuation. The role of dutasteride in this persistence is unknown.
^ includes semen volume decreased
+ includes breast tenderness and breast enlargement

AVODART IN COMBINATION WITH THE ALPHA-BLOCKER TAMSULOSIN

Data from the 4 year CombAT Study, comparing dutasteride 0.5mg (n=1623) and tamsulosin 0.4mg (n=1611) once daily alone and in combination (n=1610) have shown that the incidence of any investigator- judged drug-related adverse event during the first, second, third and fourth years of treatment respectively was 22%, 6%, 4% and 2% for dutasteride/tamsulosin combination therapy, 15%, 6%, 3% and 2% for dutasteride monotherapy and 13%, 5%, 2% and 2% for tamsulosin monotherapy. The higher incidence of adverse events in the combination therapy group in the first year of treatment was due to a higher incidence of reproductive disorders, specifically ejaculation disorders, observed in this group.

The following investigator-judged drug-related adverse events have been reported with an incidence of greater than or equal to 1% during the first year of treatment in the CombAT Study; the incidence of these events during the four years of treatment is shown in the table below: 


Incidence during treatment period
System Organ
Class                Adverse Reaction               Year 1          Year 2          Year 3        Year 4 Combinationa (n)            (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) Nervous system       Dizziness disorders
Combinationa                   1.4%            0.1%           <0.1%          0.2% Dutasteride                   0.7%            0.1%           <0.1%         <0.1% Tamsulosin                    1.3%            0.4%           <0.1%           0% Cardiac disorders    Cardiac failure
(composite termb)
Combinationa
0.2%            0.4%           0.2%           0.2%
Dutasteride
<0.1%            0.1%           <0.1%           0%
Tamsulosin
0.1%           <0.1%           0.4%           0.2%
Reproductive         Impotence c system and breast
Combinationa                  6.3%            1.8%           0.9%           0.4% disorders
Dutasteride                   5.1%            1.6%           0.6%           0.3% Tamsulosin                    3.3%            1.0%           0.6%           1.1% Altered (decreased) libido c
Combinationa                  5.3%            0.8%           0.2%            0% Dutasteride                   3.8%            1.0%           0.2%            0% Tamsulosin                    2.5%            0.7%           0.2%          <0.1% Ejaculation disorders c^
Combinationa                  9.0%            1.0%           0.5%          <0.1% Dutasteride                   1.5%            0.5%           0.2%           0.3% Tamsulosin                    2.7%            0.5%           0.2%           0.3% Breast disordersd
Combinationa                  2.1%            0.8%           0.9%           0.6% Dutasteride                   1.7%            1.2%           0.5%           0.7% Tamsulosin                    0.8%            0.4%           0.2%            0% a
Combination = dutasteride 0.5 mg once daily plus tamsulosin 0.4 mg once daily.
b
Cardiac failure composite term comprised of Cardiac failure congestive, cardiac failure, left ventricular failure, cardiac failure acute, cardiogenic shock, left ventricular failure acute, right ventricular failure, right ventricular failure acute, ventricular failure, cardiopulmonary failure, congestive cardiomyopathy.
c
These sexual adverse events are associated with dutasteride treatment (including monotherapy and combination with tamsulosin). These adverse events may persist after treatment discontinuation. The role of dutasteride in this persistence is unknown.
d
Includes breast tenderness and breast enlargement.
^
Includes semen volume decreased.


OTHER DATA

The REDUCE study revealed a higher incidence of Gleason 8-10 prostate cancers in dutasteride treated men compared to placebo (see section 4.4 and 5.1). Whether the effect of dutasteride to reduce prostate volume, or study related factors, impacted the results of this study has not been established.

The following has been reported in clinical trials and post-marketing use: male breast cancer (see section 4.4).


Reporting of suspected adverse reactions
Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form https://sideeffects.health.gov.il
Additionally, you should also report to GSK Israel (il.safety@gsk.com).