Avodart Special Precautions

Dutasteride is absorbed through the skin, therefore women and children must avoid contact with leaking capsules. If contact is made with leaking capsules, the contact area should be washed immediately with soap and water (see Contraindications).
The effect of hepatic impairment on dutasteride pharmacokinetics has not been studied. Because dutasteride is extensively metabolized and has a t½ of 3-5 weeks, caution should be used in the administration of dutasteride to patients with liver disease (see Pharmacology: Pharmacokinetics under Actions and Dosage & Administration).
Combination Therapy with Tamsulosin and Cardiac Failure: 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 α-blocker, primarily tamsulosin, than it was among subjects not taking the combination. In these 2 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 α-blocker) and cardiac failure has been established (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
Effects on Prostate-Specific Antigen (PSA) and Prostate Cancer Detection: Digital rectal examination, as well as other evaluations for prostate cancer, should be performed on patients prior to initiating therapy with dutasteride and periodically thereafter.
Serum 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 of 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 5α-reductase inhibitor (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions). 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 (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions).
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 dutasteride therapy, no adjustment to its value is necessary.
Increased Risk of High-Grade Prostate Cancer: In a 4-year study of over 8000 men 50-75 years, with a prior negative biopsy for prostate cancer and baseline PSA between 2.5 ng/mL and 10 ng/mL (the REDUCE study), 1517 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 (see Pharmacology: Pharmacodynamics under Clinical Studies under Actions).
5α-reductase inhibitors may increase the risk of development of high-grade prostate cancer. Whether the effect of 5α-reductase inhibitors to reduce prostate volume, or study-related factors, impacted the results of these studies has not been established.
Breast Cancer in Men: Breast cancer has been reported in men taking dutasteride in clinical trials (see Pharmacology: Pharmacodynamics: Clinical Studies under Actions) and during the post-marketing period. Prescribers should instruct their patient to promptly report any changes in their breast  tissue such as lumps or nipple discharge. It is not clear if there is a casual relationship between the occurence of male breast cancer and long term use of dutasteride.
Effects on the Ability to Drive or Operate Machinery: 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.
Impairment of Fertility: The effects of dutasteride 0.5 mg/day on semen characteristics were evaluated in normal volunteers 18-52 years (n=27 dutasteride, n=23 placebo) throughout 52 weeks of treatment and 24 weeks of post-treatment follow-up. At 52 weeks, the mean percent reduction from baseline in total sperm count, semen volume and sperm motility were 23, 26 and 18%, respectively, in the dutasteride group when adjusted for changes from baseline in the placebo group. Sperm concentration and sperm morphology were unaffected. After 24 weeks of follow-up, the mean percent change in total sperm count in the dutasteride group remained 23% lower than baseline. While mean values for all semen parameters at all time points remained within the normal ranges and did not meet predefined criteria for a clinically significant change (30%), 2 subjects in the dutasteride group had decreases in sperm count of >90% from baseline at 52 weeks, with partial recovery at the 24-week follow-up. The clinical significance of dutasteride's effect on semen characteristics for an individual patient's fertility is not known.
Use in lactation: It is not known whether dutasteride is excreted in breast milk.