Avodart Special Precautions

General: Lower urinary tract symptoms of BPH can be indicative of other urological diseases, including prostate cancer. Patients should be assessed to rule out other urological diseases prior to treatment with AVODART. Patients with a large residual urinary volume and/or severely diminished urinary flow may not be good candidates for 5α-reductase inhibitor therapy and should be carefully monitored for obstructive uropathy.
Blood Donation: Men being treated with dutasteride should not donate blood until at least 6 months have passed following their last dose. The purpose of this deferred period is to prevent administration of dutasteride to a pregnant female transfusion recipient.
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 (particularly high grade 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 with BPH prior to initiating therapy with dutasteride 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, children and adolescents must avoid contact with leaking capsules (see Use in Pregnancy & Lactation). If contact is made with leaking capsules the contact area should be washed immediately with soap and water.
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.
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).