Dutasteride: Package Insert and Label Information (Page 3 of 3)

13.2 Animal Toxicology and/or Pharmacology

Central Nervous System Toxicology Studies

In rats and dogs, repeated oral administration of dutasteride resulted in some animals showing signs of non-specific, reversible, centrally-mediated toxicity without associated histopathological changes at exposures 425- and 315-fold the expected clinical exposure (of parent drug), respectively.

Rabbit Dermal Absorption

In a rabbit dermal pharmacokinetics study, dermal absorption of dutasteride in CAPMUL (glyceryl oleate) in rabbits resulted in serum concentrations of 2.7 to 40.5 mcg/h/mL for doses of 1 to 20 mg/mL, respectively, or 56% to 100% of applied dutasteride to be absorbed under occluded and prolonged conditions. Dutasteride capsules administered orally contain 0.5 mg dutasteride dissolved in a mixture of mono-di-glycerides of caprylic/capric acid and butylated hydroxytoluene. Dutasteride in water was minimally absorbed in rabbits (2,000 mg/kg).

14 CLINICAL STUDIES

14.1 Monotherapy

Dutasteride 0.5 mg/day (n = 2,167) or placebo (n = 2,158) was evaluated in male subjects with BPH in three 2-year multicenter, placebo-controlled, double-blind trials, each with 2-year open-label extensions (n = 2,340). More than 90% of the trial population was white. Subjects were aged at least 50 years with a serum PSA ≥1.5 ng/mL and <10 ng/mL and BPH diagnosed by medical history and physical examination, including enlarged prostate (≥30 cc) and BPH symptoms that were moderate to severe according to the American Urological Association Symptom Index (AUA-SI). Most of the 4,325 subjects randomly assigned to receive either dutasteride or placebo completed 2 years of double-blind treatment (70% and 67%, respectively). Most of the 2,340 subjects in the trial extensions completed 2 additional years of open-label treatment (71%).

Effect on Symptom Scores

Symptoms were quantified using the AUA-SI, a questionnaire that evaluates urinary symptoms (incomplete emptying, frequency, intermittency, urgency, weak stream, straining, and nocturia) by rating on a 0 to 5 scale for a total possible score of 35, with higher numerical total symptom scores representing greater severity of symptoms. The baseline AUA-SI score across the 3 trials was approximately 17 units in both treatment groups.

Subjects receiving dutasteride achieved statistically significant improvement in symptoms versus placebo by Month 3 in 1 trial and by Month 12 in the other 2 pivotal trials. At Month 12, the mean decrease from baseline in AUA-SI total symptom scores across the 3 trials pooled was -3.3 units for dutasteride and -2.0 units for placebo with a mean difference between the 2 treatment groups of -1.3 (range: -1.1 to -1.5 units in each of the 3 trials, P <0.001) and was consistent across the 3 trials. At Month 24, the mean decrease from baseline was -3.8 units for dutasteride and -1.7 units for placebo with a mean difference of -2.1 (range: -1.9 to -2.2 units in each of the 3 trials, P <0.001). See Figure 1. The improvement in BPH symptoms seen during the first 2 years of double-blind treatment was maintained throughout an additional 2 years of open-label extension trials.

These trials were prospectively designed to evaluate effects on symptoms based on prostate size at baseline. In men with prostate volumes ≥40 cc, the mean decrease was -3.8 units for dutasteride and -1.6 units for placebo, with a mean difference between the 2 treatment groups of -2.2 at Month 24. In men with prostate volumes <40 cc, the mean decrease was -3.7 units for dutasteride and -2.2 units for placebo, with a mean difference between the 2 treatment groups of -1.5 at Month 24.

Fig 1
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Effect on Acute Urinary Retention and the Need for BPH-Related Surgery

Efficacy was also assessed after 2 years of treatment by the incidence of AUR requiring catheterization and BPH-related urological surgical intervention. Compared with placebo, dutasteride was associated with a statistically significantly lower incidence of AUR (1.8% for dutasteride versus 4.2% for placebo, P <0.001; 57% reduction in risk, [95% CI: 38% to 71%]) and with a statistically significantly lower incidence of surgery (2.2% for dutasteride versus 4.1% for placebo, P <0.001; 48% reduction in risk, [95% CI: 26% to 63%]). See Figures 2 and 3.

Fig 2
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Fig 3
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Effect on Prostate Volume

A prostate volume of at least 30 cc measured by transrectal ultrasound was required for trial entry. The mean prostate volume at trial entry was approximately 54 cc.

Statistically significant differences (dutasteride versus placebo) were noted at the earliest post-treatment prostate volume measurement in each trial (Month 1, Month 3, or Month 6) and continued through Month 24. At Month 12, the mean percent change in prostate volume across the 3 trials pooled was -24.7% for dutasteride and -3.4% for placebo; the mean difference (dutasteride minus placebo) was -21.3% (range: -21.0% to -21.6% in each of the 3 trials, P <0.001). At Month 24, the mean percent change in prostate volume across the 3 trials pooled was -26.7% for dutasteride and -2.2% for placebo with a mean difference of -24.5% (range: -24.0% to -25.1% in each of the 3 trials, P <0.001). See Figure 4. The reduction in prostate volume seen during the first 2 years of double-blind treatment was maintained throughout an additional 2 years of open-label extension trials.

Fig 4
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Effect on Maximum Urine Flow Rate

A mean peak urine flow rate (Qmax ) of ≤15 mL/sec was required for trial entry. Qmax was approximately 10 mL/sec at baseline across the 3 pivotal trials.

Differences between the 2 groups were statistically significant from baseline at Month 3 in all 3 trials and were maintained through Month 12. At Month 12, the mean increase in Qmax across the 3 trials pooled was 1.6 mL/sec for dutasteride and 0.7 mL/sec for placebo; the mean difference (dutasteride minus placebo) was 0.8 mL/sec (range: 0.7 to 1.0 mL/sec in each of the 3 trials, P <0.001). At Month 24, the mean increase in Qmax was 1.8 mL/sec for dutasteride and 0.7 mL/sec for placebo, with a mean difference of 1.1 mL/sec (range: 1.0 to 1.2 mL/sec in each of the 3 trials, P <0.001). See Figure 5. The increase in maximum urine flow rate seen during the first 2 years of double-blind treatment was maintained throughout an additional 2 years of open-label extension trials.

Fig 5
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Summary of Clinical Trials

Data from 3 large, well-controlled efficacy trials demonstrate that treatment with dutasteride (0.5 mg once daily) reduces the risk of both AUR and BPH-related surgical intervention relative to placebo, improves BPH-related symptoms, decreases prostate volume, and increases maximum urinary flow rates. These data suggest that dutasteride arrests the disease process of BPH in men with an enlarged prostate.

14.2 Combination with Alpha-blocker Therapy (CombAT)

The efficacy of combination therapy (dutasteride 0.5 mg/day plus tamsulosin 0.4 mg/day, n = 1,610) was compared with dutasteride alone (n = 1,623) or tamsulosin alone (n = 1,611) in a 4-year multicenter, randomized, double-blind trial. Trial entry criteria were similar to the double-blind, placebo-controlled monotherapy efficacy trials described in section 14.1. Eighty-eight percent (88%) of the enrolled trial population was white. Approximately 52% of subjects had previous exposure to 5 alpha-reductase-inhibitor or alpha-adrenergic-antagonist treatment. Of the 4,844 subjects randomly assigned to receive treatment, 69% of subjects in the combination group, 67% in the group receiving dutasteride, and 61% in the tamsulosin group completed 4 years of double-blind treatment.

Effect on Symptom Score

Symptoms were quantified using the first 7 questions of the International Prostate Symptom Score (IPSS) (identical to the AUA-SI). The baseline score was approximately 16.4 units for each treatment group. Combination therapy was statistically superior to each of the monotherapy treatments in decreasing symptom score at Month 24, the primary time point for this endpoint. At Month 24 the mean changes from baseline (±SD) in IPSS total symptom scores were -6.2 (±7.14) for combination, -4.9 (±6.81) for dutasteride, and -4.3 (±7.01) for tamsulosin, with a mean difference between combination and dutasteride of -1.3 units (P <0.001; [95% CI: -1.69, -0.86]), and between combination and tamsulosin of -1.8 units (P <0.001; [95% CI: -2.23, -1.40]). A significant difference was seen by Month 9 and continued through Month 48. At Month 48 the mean changes from baseline (±SD) in IPSS total symptom scores were -6.3 (±7.40) for combination, -5.3 (±7.14) for dutasteride, and -3.8 (±7.74) for tamsulosin, with a mean difference between combination and dutasteride of -0.96 units (P <0.001; [95% CI: -1.40, -0.52]), and between combination and tamsulosin of -2.5 units (P <0.001; [95% CI: -2.96, -2.07]). See Figure 6.

Fig 6
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Effect on Acute Urinary Retention or the Need for BPH-Related Surgery

After 4 years of treatment, combination therapy with dutasteride and tamsulosin did not provide benefit over monotherapy with dutasteride in reducing the incidence of AUR or BPH-related surgery.

Effect on Maximum Urine Flow Rate

The baseline Qmax was approximately 10.7 mL/sec for each treatment group. Combination therapy was statistically superior to each of the monotherapy treatments in increasing Qmax at Month 24, the primary time point for this endpoint. At Month 24, the mean increases from baseline (±SD) in Qmax were 2.4 (±5.26) mL/sec for combination, 1.9 (±5.10) mL/sec for dutasteride, and 0.9 (±4.57) mL/sec for tamsulosin, with a mean difference between combination and dutasteride of 0.5 mL/sec (P = 0.003; [95% CI: 0.17, 0.84]), and between combination and tamsulosin of 1.5 mL/sec (P <0.001; [95% CI: 1.19, 1.86]). This difference was seen by Month 6 and continued through Month 24. See Figure 7.

The additional improvement in Qmax of combination therapy over monotherapy with dutasteride was no longer statistically significant at Month 48.

Fig 7
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Effect on Prostate Volume

The mean prostate volume at trial entry was approximately 55 cc. At Month 24, the primary time point for this endpoint, the mean percent changes from baseline (±SD) in prostate volume were -26.9% (±22.57) for combination therapy, -28.0% (±24.88) for dutasteride, and 0% (±31.14) for tamsulosin, with a mean difference between combination and dutasteride of 1.1% (P = NS; [95% CI: -0.6, 2.8]), and between combination and tamsulosin of -26.9% (P <0.001; [95% CI: -28.9, -24.9]). Similar changes were seen at Month 48: -27.3% (±24.91) for combination therapy, -28.0% (±25.74) for dutasteride, and +4.6% (±35.45) for tamsulosin.

16 HOW SUPPLIED/STORAGE AND HANDLING

NDC: 63629-8207-1: 30 Capsules in a BOTTLE

NDC: 63629-8207-2: 90 Capsules in a BOTTLE

NDC: 63629-8207-3: 180 Capsules in a BOTTLE

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information).

PSA Monitoring

Inform patients that dutasteride reduces serum PSA levels by approximately 50% within 3 to 6 months of therapy, although it may vary for each individual. For patients undergoing PSA screening, increases in PSA levels while on treatment with dutasteride may signal the presence of prostate cancer and should be evaluated by a healthcare provider [see Warnings and Precautions (5.1)].

Increased Risk of High-grade Prostate Cancer

Inform patients that there was an increase in high-grade prostate cancer in men treated with 5 alpha-reductase inhibitors (which are indicated for BPH treatment), including dutasteride, compared with those treated with placebo in trials looking at the use of these drugs to reduce the risk of prostate cancer [see Indications and Usage (1.3), Warnings and Precautions (5.2), Adverse Reactions (6.1)].

Transdermal Exposure of Dutasteride in Pregnant or Potentially Pregnant Women—Risk to Male Fetus

Inform patients that dutasteride capsules should not be handled by women who are pregnant or may potentially be pregnant because of the potential for absorption of dutasteride and the subsequent potential risk to a developing male fetus. Dutasteride can be absorbed through the skin and could result in unintended fetal exposure. If a pregnant or potentially pregnant woman comes in contact with leaking dutasteride capsules, the contact area should be washed immediately with soap and water [see Warnings and Precautions (5.4), Use in Specific Populations (8.1)].

Effects on Semen Parameters

Advise men that dutasteride may affect sperm characteristics but the effect on fertility is unknown [see Warnings and Precautions (5.6), Use in Specific Populations (8.3)].

Blood Donation

Inform men treated with dutasteride that they should not donate blood until at least 6 months following their last dose to prevent pregnant women from receiving dutasteride through blood transfusion [see Warnings and Precautions (5.5)]. Serum levels of dutasteride are detectable for 4 to 6 months after treatment ends [see Clinical Pharmacology (12.3)].

Trademarks are the property of their respective owners.

Manufactured by:

Ascent Pharmaceuticals, Inc.

Central Islip, NY 11722

Manufactured for:

Camber Pharmaceuticals, Inc.

Piscataway, NJ 08854

Rev: 09/21

Patient Information

PATIENT INFORMATION

Dutasteride Capsules

(doo tas’ ter ide)

Dutasteride capsules are for use by men only.

What is Dutasteride?

Dutasteride capsules are a prescription medicine that contains dutasteride. Dutasteride is used to treat the symptoms of benign prostatic hyperplasia (BPH) in men with an enlarged prostate to:

• improve symptoms,

• reduce the risk of acute urinary retention (a complete blockage of urine flow),

• reduce the risk of the need for BPH-related surgery.

Prostate growth is caused by a hormone in the blood called dihydrotestosterone (DHT). Dutasteride lowers DHT production in the body, leading to shrinkage of the enlarged prostate in most men. While some men have fewer problems and symptoms after 3 months of treatment with dutasteride, a treatment period of at least 6 months is usually necessary to see if dutasteride will work for you.

Do not take dutasteride capsules if you are:

• pregnant or may be pregnant. Dutasteride capsules may harm your unborn baby. Pregnant women should not touch dutasteride capsules. If a woman who is pregnant with a male baby gets enough dutasteride in her body by swallowing or touching dutasteride, the male baby may be born with sex organs that are not normal. If a pregnant woman comes in contact with leaking dutasteride capsules, the contact area should be washed immediately with soap and water.

• allergic to dutasteride or any of the ingredients in dutasteride capsules. See the end of this leaflet for a complete list of ingredients in dutasteride capsules.

• allergic to other 5 alpha-reductase inhibitors, for example, PROSCAR (finasteride) tablets.

Before you take dutasteride capsules, tell your healthcare provider about all of your medical conditions, including if you:

• have liver problems

Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements. Dutasteride capsules and other medicines may affect each other, causing side effects. Dutasteride capsules may affect the way other medicines work, and other medicines may affect how dutasteride capsules works.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine.

How should I take dutasteride capsules?

• Take 1 dutasteride capsule once a day.

• Swallow dutasteride capsules whole. Do not crush, chew, or open dutasteride capsules because the contents of the capsule may irritate your lips, mouth, or throat.

• You can take dutasteride with or without food.

• If you miss a dose, you may take it later that day. Do not make up the missed dose by taking 2 doses the next day.

What should I avoid while taking dutasteride capsules?

• You should not donate blood while taking dutasteride capsules or for 6 months after you have stopped dutasteride capsules. This is important to prevent pregnant women from receiving dutasteride capsules through blood transfusions.

What are the possible side effects of dutasteride capsules?

Dutasteride capsules may cause serious side effects, including:

Rare and serious allergic reactions, including:

o Swelling of your face, tongue, or throat

o Serious skin reactions, such as skin peeling

Get medical help right away if you have these serious allergic reactions.

Higher chance of a more serious form of prostate cancer.

The most common side effects of dutasteride capsules include:

• trouble getting or keeping an erection (impotence)*

• a decrease in sex drive (libido)*

• ejaculation problems*

• enlarged or painful breasts. If you notice breast lumps or nipple discharge, you should talk to your healthcare provider.

*Some of these events may continue after you stop taking dutasteride capsules.

Depressed mood has been reported in patients receiving dutasteride capsules.

Dutasteride capsules has been shown to reduce sperm count, semen volume, and sperm movement. However, the effect of dutasteride capsules on male fertility is not known.

Prostate-Specific Antigen (PSA) Test: Your healthcare provider may check you for other prostate problems, including prostate cancer, before you start and while you take dutasteride capsules. A blood test called PSA (prostate-specific antigen) is sometimes used to see if you might have prostate cancer. Dutasteride capsules will reduce the amount of PSA measured in your blood. Your healthcare provider is aware of this effect and can still use PSA to see if you might have prostate cancer. Increases in your PSA levels while on treatment with dutasteride capsules (even if the PSA levels are in the normal range) should be evaluated by your healthcare provider.

These are not all the possible side effects of dutasteride capsules. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

How should I store dutasteride capsules?

• Store dutasteride capsules at room temperature (20° to 25°C or 68°F to 77°F).

• Dutasteride capsules may become deformed and/or discolored if kept at high temperatures.

• Do not use dutasteride capsules if your capsules are deformed, discolored, or leaking.

• Safely throw away medicine that is no longer needed.

Keep dutasteride capsules and all medicines out of the reach of children.

General information about the safe and effective use of dutasteride capsules.

Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use dutasteride capsules for a condition for which it was not prescribed. Do not give dutasteride capsules to other people, even if they have the same symptoms that you have. It may harm them.

You can ask your healthcare provider or pharmacist for information about dutasteride capsules that is written for health professionals.

For more information call 1-866-495-8330.

What are the ingredients in dutasteride capsules?

Active ingredient: dutasteride

Inactive ingredients: butylated hydroxytoluene, ferric oxide (yellow), gelatin (from certified BSE-free bovine sources), glycerin, mono-di-glycerides of caprylic/capric acid, titanium dioxide. The capsules are printed with edible black ink containing black iron oxide, hypromellose and propylene glycol.

Manufactured by:

Ascent Pharmaceuticals, Inc.

Central Islip, NY 11722

Manufactured for:

Camber Pharmaceuticals, Inc.

Piscataway, NJ 08854

Medication Guide available at http://camberpharma.com/medication-guides

Trademarks are the property of their respective owners.

This Patient Information has been approved by the U.S. Food and Drug Administration. Rev: 09/21

Dutasteride 0.5mg Capsule

Label
(click image for full-size original)
DUTASTERIDE
dutasteride capsule, liquid filled
Product Information
Product Type HUMAN PRESCRIPTION DRUG Item Code (Source) NDC:63629-8207(NDC:31722-131)
Route of Administration ORAL DEA Schedule
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
DUTASTERIDE (DUTASTERIDE) DUTASTERIDE 0.5 mg
Inactive Ingredients
Ingredient Name Strength
FERRIC OXIDE YELLOW
BUTYLATED HYDROXYTOLUENE
GELATIN, UNSPECIFIED
GLYCERYL MONO AND DICAPRYLOCAPRATE
GLYCERIN
TITANIUM DIOXIDE
FERROSOFERRIC OXIDE
HYPROMELLOSE, UNSPECIFIED
PROPYLENE GLYCOL
Product Characteristics
Color yellow Score no score
Shape OVAL (oblong) Size 17mm
Flavor Imprint Code AT131
Contains
Packaging
# Item Code Package Description Multilevel Packaging
1 NDC:63629-8207-1 30 CAPSULE, LIQUID FILLED in 1 BOTTLE None
2 NDC:63629-8207-2 90 CAPSULE, LIQUID FILLED in 1 BOTTLE None
3 NDC:63629-8207-3 180 CAPSULE, LIQUID FILLED in 1 BOTTLE None
Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA206574 10/24/2016
Labeler — Bryant Ranch Prepack (171714327)
Registrant — Bryant Ranch Prepack (171714327)
Establishment
Name Address ID/FEI Operations
Bryant Ranch Prepack 171714327 REPACK (63629-8207), RELABEL (63629-8207)

Revised: 05/2022 Bryant Ranch Prepack

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