Prostate
cancer: In a 4-year study of
over 8,000 men aged 50 to 75, with a prior negative biopsy for prostate cancer
and baseline PSA between 2.5 ng/mL and 10.0 ng/mL (the Reduce study), 1,517 men
were diagnosed with prostate cancer. There was a higher incidence of Gleason 8-10 prostate cancers in the Avodart group (n=29, 0.9%) compared to the placebo group (n=19, 0.6%). There
was no increased incidence in Gleason 5-6 or 7-10 prostate cancers. No causal
relationship between Avodart and high grade prostate cancer has been
established. The clinical significance of the numerical imbalance is
unknown. Men taking Avodart should be
regularly evaluated for prostate cancer risk including PSA testing.
In
an additional 2-year follow-up study with the original patients from the
dutasteride chemoprevention study (Reduce), a low rate of new prostate cancers
were diagnosed (dutasteride [n=14, 1.2%] and placebo [n=7, 0.7%]), with no new
identified cases of Gleason 8–10 prostate cancers.
Long-term
follow up (up to 18 years) of another 5-ARI (finasteride) in a chemoprevention
study showed no statistically significant difference between finasteride and
placebo in the rates of overall survival (HR 1.02, 95% CI 0.97-1.08) or
survival after prostate cancer diagnoses (HR 1.01, 95% CI 0.85-1.20).
Prostate specific antigen (PSA): Serum prostate-specific
antigen (PSA) concentration is an important component of the screening process
to detect 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 non-compliance 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-ARI. 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 is necessary.
Digital rectal
examination, as well as other evaluations for prostate cancer, should 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 higher among
subjects taking the combination of Avodart and an alpha blocker, primarily
tamsulosin, than it was among subjects not taking the combination. In these two trials, the incidence of cardiac
failure was low (≤1%) and variable between the studies. No imbalance was
observed in the incidence of cardiovascular adverse events overall in either
trial. No causal relationship between
Avodart (alone or in combination with an alpha blocker) and cardiac failure has
been established (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
In a meta-analysis of
12-randomised, placebo- or comparator-controlled clinical studies (n=18,802)
that evaluated the risks of developing cardiovascular adverse events from the
use of Avodart (by comparison with controls), 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) were found.
Breast cancer: There have been rare reports of male breast cancer reported
in men taking Avodart 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-ARIs (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). Prescribers
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 and children must avoid contact with leaking
capsules (see Pregnancy & Lactation).
If contact is made with leaking capsules the contact area should be washed
immediately with soap and water.
Hepatic
impairment: The effect of hepatic
impairment on dutasteride pharmacokinetics has not been studied. Because
dutasteride is extensively metabolised and has a half-life of 3 to 5 weeks,
caution should be used in the administration of dutasteride to patients with
liver disease (see Dosage & Administration and Pharmacology: Pharmacokinetics under Actions).
Effects on ability to drive and use machines: Based
on the pharmacokinetic and pharmacodynamic properties of dutasteride treatment
with dutasteride would not be expected to interfere with the ability to drive
or operate machinery.