Dutasteride

DUTASTERIDE- dutasteride capsule, liquid filled
Intergel Pharmaceuticals Inc

1 INDICATIONS AND USAGE

1.1 Monotherapy

Dutasteride Capsules are indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to:

• improve symptoms,
• reduce the risk of acute urinary retention (AUR), and
• reduce the risk of the need for BPH-related surgery.

1.2 Combination With Alpha Adrenergic Antagonist

Dutasteride Capsules in combination with the alpha-adrenergic antagonist, tamsulosin, is indicated for the treatment of symptomatic BPH in men with an enlarged prostate.

1.3 Limitations of Use

Dutasteride Capsules are not approved for the prevention of prostate cancer.

2 DOSAGE AND ADMINISTRATION

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. Dutasteride Capsules may be administered with or without food.

2.1 Monotherapy

The recommended dose of Dutasteride Capsules is 1 capsule (0.5 mg) taken once daily.

2.2 Combination With Alpha Adrenergic Antagonist

The recommended dose of Dutasteride Capsules is 1 capsule (0.5 mg) taken once daily and tamsulosin 0.4 mg taken once daily.

3 DOSAGE FORMS AND STRENGTHS

0.5-mg, opaque, light yellow, gelatin capsules imprinted with “IPI 068” in black ink on one side.

4 CONTRAINDICATIONS

Dutasteride is contraindicated for use in:

• Pregnancy. In animal reproduction and developmental toxicity studies, dutasteride inhibited development of male fetus external genitalia. Therefore, dutasteride may cause fetal harm when administered to a pregnant woman. If dutasteride is used during pregnancy or if the patient becomes pregnant while taking dutasteride, the patient should be apprised of the potential hazard to the fetus [see Warnings and Precautions ( 5.4), Use in Specific Populations ( 8.1)] .
• Women of childbearing potential [see Warnings and Precautions ( 5.4), Use in Specific Populations ( 8.1)] .
• Pediatric patients [see Use in Specific Populations ( 8.4)] .
• Patients with previously demonstrated, clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to dutasteride or other 5 alpha-reductase inhibitors [see Adverse Reactions ( 6.2)] .

5 WARNINGS AND PRECAUTIONS

5.1 Effects on Prostate-Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection

In clinical trials, dutasteride reduced serum PSA concentration by approximately 50% within 3 to 6 months of treatment. This decrease was predictable over the entire range of PSA values in subjects with symptomatic BPH, although it may vary in individuals. Dutasteride may also cause decreases in serum PSA in the presence of prostate cancer. To interpret serial PSAs in men taking dutasteride, a new PSA baseline should be established at least 3 months after starting treatment and PSA monitored periodically thereafter. Any confirmed increase from the lowest PSA value while on dutasteride may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5 alpha-reductase inhibitor. Noncompliance with dutasteride may also affect PSA test results.

To interpret an isolated PSA value in a man treated with dutasteride for 3 months or more, the PSA value should be doubled for comparison with normal values in untreated men.The free-to-total PSA ratio (percent free PSA) remains constant, even under the influence of dutasteride. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men receiving dutasteride, no adjustment to its value appears necessary.

Coadministration of dutasteride and tamsulosin resulted in similar changes to serum PSA as dutasteride monotherapy.

5.2 Increased Risk of High-Grade Prostate Cancer

In men aged 50 to 75 years with a prior negative biopsy for prostate cancer and a baseline PSA between 2.5 ng/mL and 10.0 ng/mL taking dutasteride in the 4-year Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, there was an increased incidence of Gleason score 8-10 prostate cancer compared with men taking placebo (dutasteride 1.0% versus placebo 0.5%) [see Indications and Usage ( 1.3), Adverse Reactions ( 6.1)] . In a 7-year placebo-controlled clinical trial with another 5 alpha-reductase inhibitor (finasteride 5 mg, PROSCAR ^®), similar results for Gleason score 8-10 prostate cancer were observed (finasteride 1.8% versus placebo 1.1%).

5 alpha-reductase inhibitors may increase the risk of development of high-grade prostate cancer. Whether the effect of 5 alpha-reductase inhibitors to reduce prostate volume or trial-related factors impacted the results of these trials has not been established.

5.3 Evaluation for Other Urological Diseases

Prior to initiating treatment with dutasteride, consideration should be given to other urological conditions that may cause similar symptoms. In addition, BPH and prostate cancer may coexist.

5.4 Exposure of Women—Risk to Male Fetus

Dutasteride capsules should not be handled by a woman who is pregnant or who could become pregnant. Dutasteride is absorbed through the skin and could result in unintended fetal exposure. If a woman who is pregnant or who could become pregnant comes in contact with leaking dutasteride capsules, the contact area should be washed immediately with soap and water [see Use in Specific Populations ( 8.1)] .

5.5 Blood Donation

Men being treated with dutasteride should not donate blood until at least 6 months have passed following their last dose. The purpose of this deferred period is to prevent administration of dutasteride to a pregnant female transfusion recipient.

5.6 Effect on Semen Characteristics

The effects of dutasteride 0.5 mg/day on semen characteristics were evaluated in normal volunteers aged 18 to 52 (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 reductions 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 greater than 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.