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30 X 0.5 mg
Avodart can be administered alone or in combination with the alpha-blocker tamsulosin (0.4mg).
Adults (including elderly): The recommended dose of Avodart is one capsule (0.5 mg) taken orally once a day. The capsules should be swallowed whole and not chewed or opened as contact with the capsule contents may result in irritation of the oropharyngeal mucosa. The capsules may be taken with or without food. Although an improvement may be observed at an early stage, it can take up to 6 months before a response to the treatment can be achieved. No dose adjustment is necessary in the elderly.
Renal Impairment: The effect of renal impairment on dutasteride pharmacokinetics has not been studied. No adjustment in dosage is anticipated for patients with renal impairment.
Hepatic Impairment: The effect of hepatic impairment on dutasteride pharmacokinetics has not been studied so caution should be used in patients with mild to moderate hepatic impairment. In patients with severe hepatic impairment, the use of dutasteride is contraindicated.
Treatment of moderate to severe symptoms of benign prostatic hyperplasia (BPH). Prevention of acute urinary retention and surgery in patients with BPH.
Women and children. Patients with known hypersensitivity to dudasteride, other 5-alpha reductase inhibitors, or any component of the preparation.
Combination therapy should be prescribed after careful benefit risk assessment due to the potential increased risk of adverse events (including cardiac failure) and after consideration of alternative treatment options including monotherapies.
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 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.
Effects on prostate specific antigen (PSA) and prostate cancer detection: Digital rectal examination, as well as other evaluations for prostate cancer, must be performed on patients prior to initiating therapy with Avodart and periodically thereafter. Serum prostate-specific antigen (PSA) concentration is an important component in the detection of 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 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 5-reductase inhibitor. In the interpretation of a PSA value for a patient taking Avodart, previous PSA values while on Avodart treatment 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 appears necessary.
Prostate cancer & high grade tumours: Results of one clinical study (the REDUCE study) in men at increased risk of prostate cancer revealed a higher incidence of Gleason 8–10 prostate cancers in dutasteride treated men compared to placebo. The relationship between dutasteride and high grade prostate cancer is not clear. Men taking Avodart should be regularly evaluated for prostate cancer risk including PSA testing.
Leaking Capsules: Dutasteride is absorbed through the skin, therefore, women, children and adolescents must avoid contact with leaking capsules. If contact is made with leaking capsules, the contact area should be washed immediately with soap and water.
Hepatic impairment 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. Breast neoplasia Breast cancer has been reported in men taking dutasteride in clinical trials and during the post-marketing period. Physicians should instruct their patients to promptly report any changes in their breast tissue such as lumps or nipple discharge. Currently it is not clear if there is a causal relationship between the occurrence of male breast cancer and long term use of dutasteride.
For full details see prescribing information.
Avodart as Monotherapy: Approximately 19% of the 2167 patients who received dutasteride in the 2 year Phase III placebo-controlled trials developed adverse reactions during the first year of treatment. The majority of events were mild to moderate and occurred in the reproductive system. No change to the adverse event profile was apparent over a further 2 years in open-label extension studies. Impotence, decreased libido, ejaculation disorders, gynecomastia.
For full details see prescribing information.
For information on the decrease of serum PSA levels during treatment with dutasteride and guidance concerning prostate cancer detection, please see precautions.
Effects of other drugs on the pharmacokinetics of dutasteride Use together with CYP3A4 and/or P-glycoprotein-inhibitors: Dutasteride is mainly eliminated via metabolism. In vitro studies indicate that this metabolism is catalysed by CYP3A4 and CYP3A5. No formal interaction studies have been performed with potent CYP3A4 inhibitors. However, in a population pharmacokinetic study, dutasteride serum concentrations were on average 1.6 to 1.8 times greater, respectively, in a small number of patients treated concurrently with verapamil or diltiazem (moderate inhibitors of CYP3A4 and inhibitors of P-glycoprotein) than in other patients. Long-term combination of dutasteride with drugs that are potent inhibitors of the enzyme CYP3A4 (e.g. ritonavir, indinavir, nefazodone, itraconazole, ketoconazole administered orally) may increase serum concentrations of dutasteride. Further inhibition of 5-alpha reductase at increased dutasteride exposure, is not likely. However, a reduction of the dutasteride dosing frequency can be considered if side effects are noted. It should be noted that in the case of enzyme inhibition, the long half-life may be further prolonged and it can take more than 6 months of concurrent therapy before a new steady state is reached.
Administration of 12g cholestyramine one hour after a 5mg single dose of dutasteride did not affect the pharmacokinetics of dutasteride.
Effects of dutasteride on the pharmacokinetics of other drugs: Dutasteride has no effect on the pharmacokinetics of warfarin or digoxin. This indicates that dutasteride does not inhibit/induce CYP2C9 or the transporter P-glycoprotein. In vitro interaction studies indicate that dutasteride does not inhibit the enzymes CYP1A2, CYP2A6, CYP2E1, CYP2C8, CYP2D6, CYP2C9, CYP2C19, CYP2B6 or CYP3A4. In vitro, dutasteride is not metabolized by human cytochrome P450 isoenzymes CYP1A2, CYP2A6, CYP2E1, CYP2C8, CYP2C9, CYP2C19, CYP2B6 and CYP2D6. In a small study (N=24) of two weeks duration in healthy men, dutasteride (0.5 mg daily) had no effect on the pharmacokinetics of tamsulosin or terazosin. There was also no indication of a pharmacodynamic interaction in this study.
For full details see prescribing information.
Pregnancy and Lactation
Contraindicated for use by women:
Fertility: Dutasteride has been reported to affect semen characteristics (reduction in sperm count, semen volume, and sperm motility) in healthy men. The possibility of reduced male fertility cannot be excluded.
Pregnancy: As with other 5 alpha reductase inhibitors, dutasteride inhibits the conversion of testosterone to dihydrotestosterone and may, if administered to a woman carrying a male foetus, inhibit the development of the external genitalia of the foetus. Small amounts of dutasteride have been recovered from the semen in subjects receiving Avodart 0.5 mg day. It is not known whether a male foetus may be adversely affected if his mother is exposed to the semen of a patient being treated with dutasteride (the risk of which is greatest during the first 16 weeks of pregnancy). As with all 5 alpha reductase inhibitors, when the patient’s partner is or may potentially be pregnant it is recommended that the patient avoids exposure of his partner to semen by use of a condom.
Lactation: It is not known whether dutasteride is excreted in human milk.
In volunteer studies, single daily doses of dutasteride up to 40 mg/day (80 times the therapeutic dose) have been administered for 7 days without significant safety concerns. In clinical studies, doses of 5 mg daily have been administered to subjects for 6 months with no additional adverse effects to those seen at therapeutic doses of 0.5 mg. There is no specific antidote, therefore, in suspected overdose symptomatic and supportive treatment should be given as appropriate.