Avodart Special Precautions

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 Dutasteride (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 Dutasteride (Avodart) and high grade prostate cancer has been established. The clinical significance of the numerical imbalance is unknown. Men taking Dutasteride (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.
Dutasteride (Avodart) causes a decrease in mean serum PSA levels by approximately 50% after 6 months of treatment. Patients receiving Dutasteride (Avodart) should have a new PSA baseline established after 6 months of treatment with Dutasteride (Avodart). It is recommended to monitor PSA values regularly thereafter. Any confirmed increase from lowest PSA levels while on Dutasteride (Avodart) may signal the presence of prostate cancer or non-compliance to therapy with Dutasteride (Avodart) and should be carefully evaluated, even if those values are still within the normal range for men not taking a-ARI. In the interpretation of a PSA value for a patient taking Dutasteride (Avodart), previous PSA values should be sought for comparison.
Treatment with Dutasteride (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 Dutasteride (Avodart). If clinicians elect to use percent-free PSA as an aid in the detection of prostate cancer in men undergoing Dutasteride (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 Dutasteride (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 Dutasteride (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 Dutasteride (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 Dutasteride (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 Dutasteride (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 Use in Pregnancy and 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 and 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.
Use in Pregnancy & Lactation: Dutasteride is contraindicated for use by women. Dutasteride has not been studied in women because pre-clinical data suggests that the suppression of circulating levels of dihydrotestosterone may inhibit the development of the external genital organs in a male foetus carried by a woman exposed to dutasteride.
It is not known whether dutasteride is excreted in breast milk.