Sign Out
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 to 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 Duodart 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 Avodart 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): PSA concentration is an important component of the screening process to detect prostate cancer. Duodart causes a decrease in mean serum PSA levels by approximately 50% after 6 months of treatment.
Patients receiving Duodart should have a new PSA baseline established after 6 months of treatment with Duodart. It is recommended to monitor PSA values regularly thereafter. Any confirmed increase from lowest PSA level while on DUODART may signal the presence of prostate cancer or non-compliance to therapy with Duodart and should be carefully evaluated, even if those values are still within the normal range for men not taking a 5-ARI (see Clinical Studies under Actions). In the interpretation of a PSA value for a patient taking DUODART, previous PSA values should be sought for comparison.
Treatment with Duodart 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 Duodart. If clinicians elect to use percent-free PSA as an aid in the detection of prostate cancer in men undergoing Duodart 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 Duodart 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 thecombination 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 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. Prescribers should instruct their patients to promptly report any changes in their breast tissue such as lumps or nipple discharge.
Hypotension: As with other alpha-1 adrenergic blockers, orthostatic hypotension can occur in patients treated with tamsulosin, which in rare cases can result in syncope. Patients beginning treatment with Duodart should be cautioned to sit or lie down at the first signs of orthostatic hypotension (dizziness and vertigo) until the symptoms have resolved.
Caution is advised when alpha adrenergic blocking agents including tamsulosin are co-administered with PDE5 inhibitors. Alpha adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two drug classes can potentially cause symptomatic hypotension (see Interactions).
Intraoperative Floppy Iris Syndrome: Intraoperative Floppy Iris Syndrome (IFIS, a variant of small pupil syndrome) has been observed during cataract surgery in some patients treated with alpha-1 adrenergic blockers, including tamsulosin. IFIS may increase the risk of eye complications during and after the operation.
During pre-operative assessment, cataract surgeons and ophthalmic teams should consider whether patients scheduled for cataract surgery are being or have been treated with Duodart in order to ensure that appropriate measures will be in place to manage IFIS if it occurs during surgery.
Discontinuing tamsulosin 1 to 2 weeks prior to cataract surgery is anecdotally considered helpful, but the benefit and duration of stopping of therapy prior to cataract surgery has not yet been established.
Leaking capsules: 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 Use in Pregnancy & Lactation).
Inhibitors of CYP3A4 and CYP2D6: Concomitant administration of tamsulosin hydrochloride with strong inhibitors of CYP3A4 (e.g. ketoconazole), or to a lesser extent, with strong inhibitors of CYP2D6 (e.g. paroxetine) can increase tamsulosin exposure (see Interactions). Tamsulosin hydrochloride is therefore not recommended in patients taking a strong CYP3A4 inhibitor and should be used with caution in patients taking a moderate CYP3A4 inhibitor (e.g. erythromycin), a strong or moderate CYP2D6 inhibitor, a combination of both CYP3A4 and CYP2D6 inhibitors, or in patients known to be poor metabolisers of CYP2D6.
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 three to five weeks, caution should be used in the administration of Duodart to patients with liver disease (see Dosage & Administration and Pharmacokinetics under Actions).
Effects on Ability to Drive and Use Machines: There have been no studies to investigate the effect of Duodart on the ability to perform tasks that require judgement, motor or cognitive skills. However, patients should be informed about the possible occurrence of symptoms related to orthostatic hypotension such as dizziness when taking Duodart.
