Avodart Special Precautions

Combination therapy should be prescribed after careful benefit risk assessment due to the potential increased risk of adverse events and after consideration of alternative treatment options including monotherapies (see Dosage & Administration).
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 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 Clinical Studies under Actions).
Digital rectal examination, as well as other evaluations for prostate cancer, must be performed on patients with BPH prior to initiating therapy with Avodart and periodically thereafter.
Dutasteride is absorbed through the skin; therefore, women, children and adolescents must avoid contact with leaking capsules (see Use in pregnancy & lactation under Contraindication). If contact is made with leaking capsules, the contact area should be washed immediately with soap and water.
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 Dosage & Administration, Contraindications, and Pharmacokinetics under Actions).
Serum prostate-specific antigen (PSA) concentration is an important component in the detection of prostate cancer. Generally, a total serum PSA concentration >4 ng/mL (Hybritech) requires further evaluation and consideration of prostate biopsy. Physicians should be aware that a baseline PSA <4 ng/mL in patients taking Avodart does not exclude a diagnosis of prostate cancer. Avodart causes a decrease in serum PSA levels by approximately 50% after 6 months, in patients with BPH, even in the presence of prostate cancer. Although there may be individual variation, the reduction in PSA by approximately 50% is predictable as it was observed over the entire range of baseline PSA values (1.5-10 ng/mL). Therefore, to interpret an isolated PSA value in a man treated with Avodart for ≥6 months, PSA values should be doubled for comparison with normal ranges in untreated men. This adjustment preserves the sensitivity and specificity of the PSA assay and maintains its ability to detect prostate cancer.
Any sustained increases in PSA levels while on Avodart should be carefully evaluated, including consideration of non-compliance to therapy with Avodart.
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.
Effects on the Ability to Drive or Operate Machinery: Based on the pharmacokinetic and pharmacodynamic properties of dutasteride, treatment 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 morphology were unaffected. After 24 weeks of follow-up, the mean percentage 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 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.