PRINCIPAL DISPLAY PANEL

NDC 80725-712-04

AVODART**®**

(dutasteride)

Soft Gelatin Capsules

0.5 mg

RX only

GX CE2

90 Capsules

WARNING: AVODART should not be used by women or children. Women who are or may potentially be pregnant should not use or handle AVODART Soft Gelatin Capsules (see prescribing information). If contact is made with leaking capsule, wash immediately with soap and water.

Each capsule contains 0.5 mg dutasteride.

Usual Dosage: 0.5 mg once a day.

Capsules should be swallowed whole and not chewed or opened. See prescribing information for further dosing information.

Store at 25oC (77oF); excursions permitted to 15-30oC (59-86oF) [see USP Controlled Room Temperature].

Dispense in a well-closed container as defined in the USP.

Do not use if printed safety seal under cap is broken or missing.

Manufactured for:
Waylis Therapeutics LLC
Wixom, MI 48393

Rev. 10/23


1 INDICATIONS AND USAGE

1.1 Monotherapy

AVODART (dutasteride) soft gelatin 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

AVODART 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

AVODART is not approved for the prevention of prostate cancer.

5 WARNINGS AND PRECAUTIONS

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

Prostate Cancer Detection

In clinical trials, AVODART 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. AVODART may also cause decreases in serum PSA in the presence of prostate cancer. To interpret serial PSAs in men taking AVODART, 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 AVODART 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 AVODART may also affect PSA test results.

To interpret an isolated PSA value in a man treated with AVODART 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 AVODART. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men receiving AVODART, 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 AVODART 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 (AVODART 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 AVODART, consideration should be given to other urological conditions that may cause similar symptoms. In addition, BPH and prostate cancer may coexist.

5.4 Transdermal Exposure of AVODART in Pregnant Women—Risk to Male Fetus

AVODART capsules should not be handled by women who are pregnant or may be pregnant. Dutasteride can be absorbed through the skin and could result in unintended fetal exposure and potential risk to a male fetus. If a pregnant woman 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)]. Dutasteride can be absorbed through the skin based on animal studies [see Nonclinical Toxicology (13.2)].

5.5 Blood Donation

Men being treated with AVODART 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 healthy men throughout 52 weeks of treatment and 24 weeks of post‑treatment follow‑up. At 52 weeks, compared with placebo, dutasteride treatment resulted in mean reduction in total sperm count, semen volume, and sperm motility; the effects on total sperm count were not reversible after 24 weeks of follow-up. Sperm concentration and sperm morphology were unaffected and mean values for all semen parameters remained within the normal range at all timepoints. The clinical significance of the effect of dutasteride on semen characteristics for an individual patient’s fertility is not known [see Use in Specific Populations (8.3)].

7 DRUG INTERACTIONS

7.1 Cytochrome P450 3A Inhibitors

Dutasteride is extensively metabolized in humans by the cytochrome P450 (CYP)3A4 and CYP3A5 isoenzymes. The effect of potent CYP3A4 inhibitors on dutasteride has not been studied. Because of the potential for drug‑drug interactions, use caution when prescribing AVODART to patients taking potent, chronic CYP3A4 enzyme inhibitors (e.g., ritonavir) [see Clinical Pharmacology (12.3)].

7.2 Alpha-adrenergic Antagonists

The administration of AVODART in combination with tamsulosin or terazosin has no effect on the steady-state pharmacokinetics of either alpha-adrenergic antagonist. The effect of administration of tamsulosin or terazosin on dutasteride pharmacokinetic parameters has not been evaluated.

7.3 Calcium Channel Antagonists

Coadministration of verapamil or diltiazem decreases dutasteride clearance and leads to increased exposure to dutasteride. The change in dutasteride exposure is not considered to be clinically significant. No dose adjustment is recommended [see Clinical Pharmacology (12.3)].

7.4 Cholestyramine

Administration of a single 5-mg dose of AVODART followed 1 hour later by 12 g of cholestyramine does not affect the relative bioavailability of dutasteride [see Clinical Pharmacology (12.3)].

7.5 Digoxin

AVODART does not alter the steady-state pharmacokinetics of digoxin when administered concomitantly at a dose of 0.5 mg/day for 3 weeks [see Clinical Pharmacology (12.3)].

7.6 Warfarin

Concomitant administration of AVODART 0.5 mg/day for 3 weeks with warfarin does not alter the steady-state pharmacokinetics of the S- or R-warfarin isomers or alter the effect of warfarin on prothrombin time [see Clinical Pharmacology (12.3)].

16 HOW SUPPLIED/STORAGE AND HANDLING

AVODART soft gelatin capsules 0.5 mg are oblong, opaque, dull yellow, gelatin capsules imprinted with “GX CE2” with red edible ink on one side, packaged in bottles of 30 (NDC 80725-712-15) and 90 (NDC 80725-712-04) with child- resistant closures.

Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature].

Dutasteride is absorbed through the skin. AVODART capsules should not be handled by women who are pregnant or who could become pregnant because of the potential for absorption of dutasteride and the subsequent potential risk to a developing male fetus [see Warnings and Precautions (5.4)].

17 PATIENT COUNSELING INFORMATION

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

PSA Monitoring

Inform patients that AVODART 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 AVODART 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 AVODART, 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 AVODART in Pregnant or Potentially Pregnant Women—Risk to Male Fetus

Inform patients that AVODART 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 AVODART 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 AVODART 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 AVODART 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)].

AVODART is a trademark used under license by Waylis Therapeutics LLC.

The other brands listed are trademarks owned by or licensed to their respective owners and are not owned by or licensed to Waylis Therapeutics LLC. The makers of these brands are not affiliated with and do not endorse Waylis Therapeutics LLC or its products.

Manufactured for:

Waylis Therapeutics LLC
Wixom, MI 48393

PHARMACIST-DETACH HERE AND GIVE INSTRUCTIONS TO PATIENT

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