Special Warning : אזהרת שימוש

4.4     Special warnings and precautions for use

Combination therapy should be prescribed after careful benefit risk assessment due to the potential increased risk of adverse events (including cardiac failure) and after consideration of alternative treatment options including monotherapies (see section 4.2).

Prostate cancer and high grade tumours

The REDUCE study, a 4-year, multicentre, randomised, double-blind, placebo controlled study investigated the effect of dutasteride 0.5 mg daily on patients with a high risk for prostate cancer (including men 50 to 75 years of age with PSA levels of 2.5 to 10 ng/ml and a negative prostate biopsy 6 months before study enrolment) compared to placebo. Results of this study revealed a higher incidence of Gleason 8 – 10 prostate cancers in dutasteride treated men (n=29, 0.9%) compared to placebo (n=19, 0.6%). The relationship between dutasteride and Gleason 8 - 10 prostate cancers is not clear. Thus, men taking Avodart should be regularly evaluated for prostate cancer (see section 5.1).


Prostate specific antigen (PSA)
Serum prostate-specific antigen (PSA) concentration is an important component in the detection of prostate cancer. Avodart causes a decrease in mean serum PSA levels by approximately 50%, after 6 months of treatment.

Patients receiving Avodart should have a new PSA baseline established after 6 months of treatment with Avodart. It is recommended to monitor PSA values regularly thereafter. Any confirmed increase from lowest PSA level while on Avodart may signal the presence of prostate cancer or noncompliance to therapy with Avodart and should be carefully evaluated, even if those values are still within the normal range for men not taking a 5 alpha reductase inhibitor (see section 5.1). In the interpretation of a PSA value for a patient taking Avodart, previous PSA values should be sought for comparison.

Treatment with Avodart does not interfere with the use of PSA as a tool to assist in the diagnosis of prostate cancer after a new baseline has been established.

Total serum PSA levels return to baseline within 6 months of discontinuing treatment. The ratio of free to total PSA remains constant even under the influence of Avodart. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men undergoing Avodart therapy, no adjustment to its value appears necessary.

Digital rectal examination, as well as other evaluations for prostate cancer, must be performed on patients prior to initiating therapy with Avodart and periodically thereafter.


Cardiovascular adverse events
In two 4-year clinical studies, the incidence of cardiac failure (a composite term of reported events, primarily cardiac failure and congestive cardiac failure) was marginally higher among subjects taking the combination of Avodart and an alpha blocker, primarily tamsulosin, than it was among subjects not taking the combination. However, the incidence of cardiac failure in these trials was lower in all actively treated groups compared to the placebo group, and other data available for dutasteride or alpha-blockers do not support a conclusion on increased cardiovascular risks (see section 5.1).
Breast neoplasia

There have been rare reports of male breast cancer reported in men taking dutasteride in clinical trials and during the post-marketing period. However, epidemiological studies showed no increase in the risk of developing male breast cancer with the use of 5-alpha reductase inhibitors (see section 5.1). Physicians should instruct their patients to promptly report any changes in their breast tissue such as lumps or nipple discharge.

Leaking capsules

Dutasteride is absorbed through the skin, therefore, women, children and adolescents must avoid contact with leaking capsules (see section 4.6). If contact is made with leaking capsules, the contact area should be washed immediately with soap and water.

Hepatic impairment

Dutasteride was not studied in patients with liver disease. Caution should be used in the administration of dutasteride to patients with mild to moderate hepatic impairment (see section 4.2, section 4.3 and section 5.2).

Effects on Driving

4.7     Effects on ability to drive and use machines
Based on the pharmacodynamic properties of dutasteride, treatment with dutasteride would not be expected to interfere with the ability to drive or operate machinery.