Avodart (Dutasteride)
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Avodart (Dutasteride)

AVODART
(dutasteride)

DRUG DESCRIPTION

AVODART is a synthetic 4-azasteroid compound that is a selective inhibitor of both the type 1 and type 2 isoforms of steroid 5 alpha-reductase, an intracellular enzyme that converts testosterone to DHT.

Dutasteride is chemically designated as (5α,17β)-N-{2,5 bis(trifluoromethyl)phenyl}-3oxo-4-azaandrost-1-ene-17-carboxamide. The empirical formula of dutasteride is C27H30F6N2O2, representing a molecular weight of 528.5 with the following structural formula:

AVODART (dutasteride) Structural Formula Illustration

Dutasteride is a white to pale yellow powder with a melting point of 242° to 250°C. It is soluble in ethanol (44 mg/mL), methanol (64 mg/mL), and polyethylene glycol 400 (3 mg/mL), but it is insoluble in water.

Each AVODART Soft Gelatin Capsule, administered orally, contains 0.5 mg of dutasteride dissolved in a mixture of mono-di-glycerides of caprylic/capric acid and butylated hydroxytoluene. The inactive excipients in the capsule shell are ferric oxide (yellow), gelatin (from certified BSE-free bovine sources), glycerin, and titanium dioxide. The soft gelatin capsules are printed with edible red ink.

What are the possible side effects of dutasteride (Avodart)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Less serious side effects may include:

  • decreased libido (sex drive);
  • decreased amount of semen released during sex;
  • impotence (trouble getting or keeping an erection); or
  • breast tenderness or enlargement.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at...

Read All Potential Side Effects and See Pictures of Avodart »

What are the precautions when taking dutasteride (Avodart)?

Before taking dutasteride, tell your doctor or pharmacist if you are allergic to it; or to finasteride; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Do not donate blood while you are taking this medication and for at least 6 months after you stop taking it. This will prevent the possibility of your blood being given to a pregnant woman.

This medication is not usually used in women....

Read All Potential Precautions of Avodart »

Last reviewed on RxList: 7/5/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

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.

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.

Limitations of Use

AVODART is not approved for the prevention of prostate cancer.

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. AVODART may be administered with or without food.

Monotherapy

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

Combination With Alpha Adrenergic Antagonist

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

HOW SUPPLIED

Dosage Forms And Strengths

0.5-mg, opaque, dull yellow, gelatin capsules imprinted with “GX CE2” in red ink on one side.

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 0173-0712-15) and 90 (NDC 0173-0712-04) with child-resistant closures.

Store at 25°C (77°F); excursions permitted to 15-30°C (59-86°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].

GlaxoSmithKline Research, Triangle Park, NC 27709. Manufactured by Catalent Pharma Solutions Somerset, NJ 08873 for GlaxoSmithKline, Research Triangle Park, NC 27709

Last reviewed on RxList: 7/5/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Clinical Trials Experience

Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trial of another drug and may not reflect the rates observed in practice.

From clinical trials with AVODART as monotherapy or in combination with tamsulosin:

  • The most common adverse reactions reported in subjects receiving AVODART were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), and ejaculation disorders. The most common adverse reactions reported in subjects receiving combination therapy (AVODART plus tamsulosin) were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), ejaculation disorders, and dizziness. Ejaculation disorders occurred significantly more in subjects receiving combination therapy (11%) compared with those receiving AVODART (2%) or tamsulosin (4%) as monotherapy.
  • Study withdrawal due to adverse reactions occurred in 4% of subjects receiving AVODART, and 3% of subjects receiving placebo in placebo-controlled trials with AVODART. The most common adverse reaction leading to study withdrawal was impotence (1%).
  • In the clinical trial evaluating the combination therapy, study withdrawal due to adverse reactions occurred in 6% of subjects receiving combination therapy (AVODART plus tamsulosin) and 4% of subjects receiving AVODART or tamsulosin as monotherapy. The most common adverse reaction in all treatment arms leading to study withdrawal was erectile dysfunction (1% to 1.5%).

Monotherapy

Over 4,300 male subjects with BPH were randomly assigned to receive placebo or 0.5-mg daily doses of AVODART in three identical 2-year, placebo-controlled, double-blind, Phase 3 treatment studies, each followed by a 2-year open-label extension. During the double-blind treatment period, 2,167 male subjects were exposed to AVODART, including 1,772 exposed for 1 year and 1,510 exposed for 2 years. When including the open-label extensions, 1,009 male subjects were exposed to AVODART for 3 years and 812 were exposed for 4 years. The population was aged 47 to 94 years (mean age: 66 years) and greater than 90% were Caucasian. Table 1 summarizes clinical adverse reactions reported in at least 1% of subjects receiving AVODART and at a higher incidence than subjects receiving placebo.

Table 1: Adverse Reactions Reported in ≥ 1% of Subjects Over a 24-Month Period and More Frequently in the Group Receiving AVODART Than the Placebo Group (Randomized, Double-Blind, Placebo-Controlled Studies Pooled) by Time of Onset

Adverse Reaction Adverse Reaction Time of Onset
Months 0-6 Months 7-12 Months 13-18 Months 19-24
AVODART (n)
Placebo (n)
(n = 2,167)
(n = 2,158)
(n = 1,901)
(n = 1,922)
(n = 1,725)
(n = 1,714)
(n = 1,605)
(n = 1,555)
Impotence
  AVODART 4.7% 1.4% 1.0% 0.8%
  Placebo 1.7% 1.5% 0.5% 0.9%
Decreased libido
  AVODART 3.0% 0.7% 0.3% 0.3%
  Placebo 1.4% 0.6% 0.2% 0.1%
Ejaculation disorders
  AVODART 1.4% 0.5% 0.5% 0.1%
  Placebo 0.5% 0.3% 0.1% 0.0%
Breast disordersa
  AVODART 0.5% 0.8% 1.1% 0.6%
  Placebo 0.2% 0.3% 0.3% 0.1%
aIncludes breast tenderness and breast enlargement.

Long-Term Treatment (Up to 4 Years)

High-grade Prostate Cancer: The REDUCE trial was a randomized, double-blind, placebo-controlled trial that enrolled 8,231 men aged 50 to 75 years with a serum PSA of 2.5 ng/mL to 10 ng/mL and a negative prostate biopsy within the previous 6 months. Subjects were randomized to receive placebo (N = 4,126) or 0.5-mg daily doses of AVODART (N = 4,105) for up to 4 years. The mean age was 63 years and 91% were Caucasian. Subjects underwent protocol-mandated scheduled prostate biopsies at 2 and 4 years of treatment or had “for-cause biopsies” at non-scheduled times if clinically indicated. There was a higher incidence of Gleason score 8-10 prostate cancer in men receiving AVODART (1.0%) compared with men on placebo (0.5%) [see INDICATIONS AND USAGE, WARNINGS AND PRECAUTIONS]. 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%).

No clinical benefit has been demonstrated in patients with prostate cancer treated with AVODART.

Reproductive and Breast Disorders

In the 3 pivotal placebo-controlled BPH trials with AVODART, each 4 years in duration, there was no evidence of increased sexual adverse reactions (impotence, decreased libido, and ejaculation disorder) or breast disorders with increased duration of treatment. Among these 3 trials, there was 1 case of breast cancer in the dutasteride group and 1 case in the placebo group. No cases of breast cancer were reported in any treatment group in the 4-year CombAT trial or the 4-year REDUCE trial.

The relationship between long-term use of dutasteride and male breast neoplasia is currently unknown.

Combination With Alpha-Blocker Therapy (CombAT)

Over 4,800 male subjects with BPH were randomly assigned to receive 0.5-mg AVODART, 0.4-mg tamsulosin, or combination therapy (0.5-mg AVODART plus 0.4-mg tamsulosin) administered once daily in a 4-year double-blind study. Overall, 1,623 subjects received monotherapy with AVODART; 1,611 subjects received monotherapy with tamsulosin; and 1,610 subjects received combination therapy. The population was aged 49 to 88 years (mean age: 66 years) and 88% were Caucasian. Table 2 summarizes adverse reactions reported in at least 1% of subjects in the combination group and at a higher incidence than subjects receiving monotherapy with AVODART or tamsulosin.

Table 2: Adverse Reactions Reported Over a 48-Month Period in ≥ 1% of Subjects and More Frequently in the Coadministration Therapy Group than the Groups Receiving Monotherapy With AVODART or Tamsulosin (CombAT) by Time of Onset

Adverse Reaction Adverse Reaction Time of Onset
Year 1 Year 2 Year 3 Year 4
Months 0-6 Months 7-12
Combinationa
AVODART
Tamsulosin
(n = 1,610)
(n = 1,623)
(n = 1,611)
(n = 1,527)
(n = 1,548)
(n = 1,545)
(n = 1,428)
(n = 1,464)
(n = 1,468)
(n = 1,283)
(n = 1,325)
(n = 1,281)
(n = 1,200)
(n = 1,200)
(n = 1,112)
Ejaculation disordersb
  Combination 7.80% 1.60% 1.00% 0.50% < 0.1%
  AVODART 1.00% 0.50% 0.50% 0.20% 0.30%
  Tamsulosin 2.20% 0.50% 0.50% 0.20% 0.30%
Impotencec
  Combination 5.40% 1.10% 1.80% 0.90% 0.40%
  AVODART 4.00% 1.10% 1.60% 0.60% 0.30%
  Tamsulosin 2.60% 0.80% 1.00% 0.60% 1.10%
Decreased libidod
  Combination 4.50% 0.90% 0.80% 0.20% 0.00%
  AVODART 3.10% 0.70% 1.00% 0.20% 0.00%
  Tamsulosin 2.00% 0.60% 0.70% 0.20% < 0.1%
Breast disorderse
  Combination 1.10% 1.10% 0.80% 0.90% 0.60%
  AVODART 0.90% 0.90% 1.20% 0.50% 0.70%
  Tamsulosin 0.40% 0.40% 0.40% 0.20% 0.00%
Dizziness
  Combination 1.10% 0.40% 0.10% < 0.1% 0.20%
  AVODART 0.50% 0.30% 0.10% < 0.1% < 0.1%
  Tamsulosin 0.90% 0.50% 0.40% < 0.1% 0.00%
aCombination = AVODART 0.5 mg once daily plus tamsulosin 0.4 mg once daily.
bIncludes anorgasmia, retrograde ejaculation, semen volume decreased, orgasmic sensation decreased, orgasm abnormal, ejaculation delayed, ejaculation disorder, ejaculation failure, and premature ejaculation.
cIncludes erectile dysfunction and disturbance in sexual arousal.
dIncludes libido decreased, libido disorder, loss of libido, sexual dysfunction, and male sexual dysfunction.
eIncludes breast enlargement, gynecomastia, breast swelling, breast pain, breast tenderness, nipple pain, and nipple swelling.

Cardiac Failure: In CombAT, after 4 years of treatment, the incidence of the composite term cardiac failure in the combination therapy group (12/1,610; 0.7%) was higher than in either monotherapy group: AVODART, 2/1,623 (0.1%) and tamsulosin, 9/1,611 (0.6%). Composite cardiac failure was also examined in a separate 4-year placebo-controlled trial evaluating AVODART in men at risk for development of prostate cancer. The incidence of cardiac failure in subjects taking AVODART was 0.6% (26/4,105) compared with 0.4% (15/4,126) in subjects on placebo. A majority of subjects with cardiac failure in both studies had co-morbidities associated with an increased risk of cardiac failure. Therefore, the clinical significance of the numerical imbalances in cardiac failure is unknown. No causal relationship between AVODART, alone or in combination with tamsulosin, and cardiac failure has been established. No imbalance was observed in the incidence of overall cardiovascular adverse events in either study.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of AVODART. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to AVODART.

Immune System Disorders

Hypersensitivity reactions, including rash, pruritus, urticaria, localized edema, serious skin reactions, and angioedema.

Neoplasms

Male breast cancer.

Read the Avodart (dutasteride) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

Cytochrome P450 3A Inhibitors

Dutasteride is extensively metabolized in humans by the CYP3A4 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].

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.

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].

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].

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].

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].

Last reviewed on RxList: 7/5/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

AVODART®
(av' o dart)
(dutasteride) Capsules

AVODART is for use by men only.

Read this patient information before you start taking AVODART and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is AVODART?

AVODART is a prescription medicine that contains dutasteride. AVODART 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

Who should NOT take AVODART?

Do Not Take AVODART if you are:

  • pregnant or could become pregnant. AVODART may harm your unborn baby. Pregnant women should not touch AVODART Capsules. If a woman who is pregnant with a male baby gets enough AVODART in her body by swallowing or touching AVODART, the male baby may be born with sex organs that are not normal. If a pregnant woman or woman of childbearing potential comes in contact with leaking AVODART Capsules, the contact area should be washed immediately with soap and water.
  • a child or a teenager.
  • allergic to dutasteride or any of the ingredients in AVODART. See the end of this leaflet for a complete list of ingredients in AVODART.
  • allergic to other 5 alpha-reductase inhibitors, for example, PROSCAR (finasteride) Tablets.

What should I tell my healthcare provider before taking AVODART?

Before you take AVODART, tell your healthcare provider if you:

  • have liver problems

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. AVODART and other medicines may affect each other, causing side effects. AVODART may affect the way other medicines work, and other medicines may affect how AVODART 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 AVODART?

  • Take 1 AVODART capsule once a day.
  • Swallow AVODART capsules whole. Do not crush, chew, or open AVODART capsules because the contents of the capsule may irritate your lips, mouth, or throat.
  • You can take AVODART 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 AVODART?

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

What are the possible side effects of AVODART?

AVODART may cause serious side effects, including:

  • Rare and serious allergic reactions, including:
    • swelling of your face, tongue, or throat
    • 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 AVODART 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.

AVODART has been shown to reduce sperm count, semen volume, and sperm movement. However, the effect of AVODART 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 AVODART. A blood test called PSA (prostate-specific antigen) is sometimes used to see if you might have prostate cancer. AVODART 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 AVODART (even if the PSA levels are in the normal range) should be evaluated by your healthcare provider.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects with AVODART. For more information, ask you healthcare provider or pharmacist.

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 AVODART?

  • Store AVODART Capsules at room temperature (59°F to 86°F or 15°C to 30°C).
  • AVODART Capsules may become deformed and/or discolored if kept at high temperatures.
  • Do not use AVODART if your capsules are deformed, discolored, or leaking.
  • Safely throw away medicine that is no longer needed.

Keep AVODART and all medicines out of the reach of children.

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

This patient information leaflet summarizes the most important information about AVODART. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about AVODART that is written for health professionals.

For more information, go to www.AVODART.com or call1-888-825-5249.

What are the ingredients in AVODART?

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, and edible red ink.

How does AVODART work?

Prostate growth is caused by a hormone in the blood called dihydrotestosterone (DHT). AVODART 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 AVODART, a treatment period of at least 6 months is usually necessary to see if AVODART will work for you.

Last reviewed on RxList: 7/5/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

In volunteer studies, single doses of dutasteride up to 40 mg (80 times the therapeutic dose) for 7 days have been administered without significant safety concerns. In a clinical study, daily doses of 5 mg (10 times the therapeutic dose) were administered to 60 subjects for 6 months with no additional adverse effects to those seen at therapeutic doses of 0.5 mg.

There is no specific antidote for dutasteride. Therefore, in cases of suspected overdosage, symptomatic and supportive treatment should be given as appropriate, taking the long half-life of dutasteride into consideration.

CONTRAINDICATIONS

AVODART is contraindicated for use in:

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

Last reviewed on RxList: 7/5/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Dutasteride inhibits the conversion of testosterone to dihydrotestosterone (DHT). DHT is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. Testosterone is converted to DHT by the enzyme 5 alpha-reductase, which exists as 2 isoforms, type 1 and type 2. The type 2 isoenzyme is primarily active in the reproductive tissues, while the type 1 isoenzyme is also responsible for testosterone conversion in the skin and liver.

Dutasteride is a competitive and specific inhibitor of both type 1 and type 2 5 alpha-reductase isoenzymes, with which it forms a stable enzyme complex. Dissociation from this complex has been evaluated under in vitro and in vivo conditions and is extremely slow. Dutasteride does not bind to the human androgen receptor.

Pharmacodynamics

Effect on 5 Alpha-Dihydrotestosterone and Testosterone

The maximum effect of daily doses of dutasteride on the reduction of DHT is dose dependent and is observed within 1 to 2 weeks. After 1 and 2 weeks of daily dosing with dutasteride 0.5 mg, median serum DHT concentrations were reduced by 85% and 90%, respectively. In patients with BPH treated with dutasteride 0.5 mg/day for 4 years, the median decrease in serum DHT was 94% at 1 year, 93% at 2 years, and 95% at both 3 and 4 years. The median increase in serum testosterone was 19% at both 1 and 2 years, 26% at 3 years, and 22% at 4 years, but the mean and median levels remained within the physiologic range.

In patients with BPH treated with 5 mg/day of dutasteride or placebo for up to 12 weeks prior to transurethral resection of the prostate, mean DHT concentrations in prostatic tissue were significantly lower in the dutasteride group compared with placebo (784 and 5,793 pg/g, respectively, P < 0.001). Mean prostatic tissue concentrations of testosterone were significantly higher in the dutasteride group compared with placebo (2,073 and 93 pg/g, respectively, P < 0.001).

Adult males with genetically inherited type 2 5 alpha-reductase deficiency also have decreased DHT levels. These 5 alpha-reductase deficient males have a small prostate gland throughout life and do not develop BPH. Except for the associated urogenital defects present at birth, no other clinical abnormalities related to 5 alpha-reductase deficiency have been observed in these individuals.

Effects on Other Hormones

In healthy volunteers, 52 weeks of treatment with dutasteride 0.5 mg/day (n = 26) resulted in no clinically significant change compared with placebo (n = 23) in sex hormone-binding globulin, estradiol, luteinizing hormone, follicle-stimulating hormone, thyroxine (free T4), and dehydroepiandrosterone. Statistically significant, baseline-adjusted mean increases compared with placebo were observed for total testosterone at 8 weeks (97.1 ng/dL, P < 0.003) and thyroid-stimulating hormone at 52 weeks (0.4 mcIU/mL, P < 0.05). The median percentage changes from baseline within the dutasteride group were 17.9% for testosterone at 8 weeks and 12.4% for thyroid-stimulating hormone at 52 weeks. After stopping dutasteride for 24 weeks, the mean levels of testosterone and thyroid-stimulating hormone had returned to baseline in the group of subjects with available data at the visit. In patients with BPH treated with dutasteride in a large randomized, double-blind, placebo-controlled study, there was a median percent increase in luteinizing hormone of 12% at 6 months and 19% at both 12 and 24 months.

Other Effects

Plasma lipid panel and bone mineral density were evaluated following 52 weeks of dutasteride 0.5 mg once daily in healthy volunteers. There was no change in bone mineral density as measured by dual energy x-ray absorptiometry compared with either placebo or baseline. In addition, the plasma lipid profile (i.e., total cholesterol, low density lipoproteins, high density lipoproteins, and triglycerides) was unaffected by dutasteride. No clinically significant changes in adrenal hormone responses to ACTH stimulation were observed in a subset population (n = 13) of the 1-year healthy volunteer study.

Pharmacokinetics

Absorption

Following administration of a single 0.5-mg dose of a soft gelatin capsule, time to peak serum concentrations (Tmax) of dutasteride occurs within 2 to 3 hours. Absolute bioavailability in 5 healthy subjects is approximately 60% (range: 40% to 94%). When the drug is administered with food, the maximum serum concentrations were reduced by 10% to 15%. This reduction is of no clinical significance.

Distribution

Pharmacokinetic data following single and repeat oral doses show that dutasteride has a large volume of distribution (300 to 500 L). Dutasteride is highly bound to plasma albumin (99.0%) and alpha-1 acid glycoprotein (96.6%).

In a study of healthy subjects (n = 26) receiving dutasteride 0.5 mg/day for 12 months, semen dutasteride concentrations averaged 3.4 ng/mL (range: 0.4 to 14 ng/mL) at 12 months and, similar to serum, achieved steady-state concentrations at 6 months. On average, at 12 months 11.5% of serum dutasteride concentrations partitioned into semen.

Metabolism and Elimination

Dutasteride is extensively metabolized in humans. In vitro studies showed that dutasteride is metabolized by the CYP3A4 and CYP3A5 isoenzymes. Both of these isoenzymes produced the 4'-hydroxydutasteride, 6-hydroxydutasteride, and the 6,4 '-dihydroxydutasteride metabolites. In addition, the 15-hydroxydutasteride metabolite was formed by CYP3A4. Dutasteride is not metabolized in vitro by human cytochrome P450 isoenzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1. In human serum following dosing to steady state, unchanged dutasteride, 3 major metabolites (4 '-hydroxydutasteride, 1,2-dihydrodutasteride, and 6-hydroxydutasteride), and 2 minor metabolites (6,4'-dihydroxydutasteride and 15-hydroxydutasteride), as assessed by mass spectrometric response, have been detected. The absolute stereochemistry of the hydroxyl additions in the 6 and 15 positions is not known. In vitro, the 4 '-hydroxydutasteride and 1,2-dihydrodutasteride metabolites are much less potent than dutasteride against both isoforms of human 5 alpha-reductase. The activity of 6β-hydroxydutasteride is comparable to that of dutasteride.

Dutasteride and its metabolites were excreted mainly in feces. As a percent of dose, there was approximately 5% unchanged dutasteride (~1% to ~15%) and 40% as dutasteride-related metabolites (~2% to ~90%). Only trace amounts of unchanged dutasteride were found in urine ( < 1%). Therefore, on average, the dose unaccounted for approximated 55% (range: 5% to 97%).

The terminal elimination half-life of dutasteride is approximately 5 weeks at steady state. The average steady-state serum dutasteride concentration was 40 ng/mL following 0.5 mg/day for 1 year. Following daily dosing, dutasteride serum concentrations achieve 65% of steady-state concentration after 1 month and approximately 90% after 3 months. Due to the long half-life of dutasteride, serum concentrations remain detectable (greater than 0.1 ng/mL) for up to 4 to 6 months after discontinuation of treatment.

Specific Populations

Pediatric: Dutasteride pharmacokinetics have not been investigated in subjects younger than 18 years.

Geriatric: No dose adjustment is necessary in the elderly. The pharmacokinetics and pharmacodynamics of dutasteride were evaluated in 36 healthy male subjects aged between 24 and 87 years following administration of a single 5-mg dose of dutasteride. In this single-dose study, dutasteride half-life increased with age (approximately 170 hours in men aged 20 to 49 years, approximately 260 hours in men aged 50 to 69 years, and approximately 300 hours in men older than 70 years). Of 2,167 men treated with dutasteride in the 3 pivotal studies, 60% were age 65 and over and 15% were age 75 and over. No overall differences in safety or efficacy were observed between these patients and younger patients.

Gender: AVODART is contraindicated in pregnancy and women of childbearing potential and is not indicated for use in other women [see CONTRAINDICATIONS, WARNINGS AND PRECAUTIONS]. The pharmacokinetics of dutasteride in women have not been studied.

Race: The effect of race on dutasteride pharmacokinetics has not been studied.

Renal Impairment: The effect of renal impairment on dutasteride pharmacokinetics has not been studied. However, less than 0.1% of a steady-state 0.5-mg dose of dutasteride is recovered in human urine, so 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. Because dutasteride is extensively metabolized, exposure could be higher in hepatically impaired patients.

Drug Interactions

Cytochrome P450 Inhibitors: No clinical drug interaction studies have been performed to evaluate the impact of CYP3A enzyme inhibitors on dutasteride pharmacokinetics. However, based on in vitro data, blood concentrations of dutasteride may increase in the presence of inhibitors of CYP3A4/5 such as ritonavir, ketoconazole, verapamil, diltiazem, cimetidine, troleandomycin, and ciprofloxacin.

Dutasteride does not inhibit the in vitro metabolism of model substrates for the major human cytochrome P450 isoenzymes (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) at a concentration of 1,000 ng/mL, 25 times greater than steady-state serum concentrations in humans.

Alpha Adrenergic Antagonists: In a single-sequence, crossover study in healthy volunteers, the administration of tamsulosin or terazosin in combination with AVODART had no effect on the steady-state pharmacokinetics of either alpha adrenergic antagonist. Although the effect of administration of tamsulosin or terazosin on dutasteride pharmacokinetic parameters was not evaluated, the percent change in DHT concentrations was similar for AVODART alone compared with the combination treatment.

Calcium Channel Antagonists: In a population pharmacokinetics analysis, a decrease in clearance of dutasteride was noted when coadministered with the CYP3A4 inhibitors verapamil (-37%, n = 6) and diltiazem (-44%, n = 5). In contrast, no decrease in clearance was seen when amlodipine, another calcium channel antagonist that is not a CYP3A4 inhibitor, was coadministered with dutasteride (+7%, n = 4).

The decrease in clearance and subsequent increase in exposure to dutasteride in the presence of verapamil and diltiazem is not considered to be clinically significant. No dose adjustment is recommended.

Cholestyramine: Administration of a single 5-mg dose of AVODART followed 1 hour later by 12 g cholestyramine did not affect the relative bioavailability of dutasteride in 12 normal volunteers.

Digoxin: In a study of 20 healthy volunteers, AVODART did not alter the steady-state pharmacokinetics of digoxin when administered concomitantly at a dose of 0.5 mg/day for 3 weeks.

Warfarin: In a study of 23 healthy volunteers, 3 weeks of treatment with AVODART 0.5 mg/day did not alter the steady-state pharmacokinetics of the S- or R-warfarin isomers or alter the effect of warfarin on prothrombin time when administered with warfarin.

Other Concomitant Therapy: Although specific interaction studies were not performed with other compounds, approximately 90% of the subjects in the 3 randomized, double-blind, placebo-controlled safety and efficacy studies receiving AVODART were taking other medications concomitantly. No clinically significant adverse interactions could be attributed to the combination of AVODART and concurrent therapy when AVODART was coadministered with anti-hyperlipidemics, angiotensin-converting enzyme (ACE) inhibitors, beta-adrenergic blocking agents, calcium channel blockers, corticosteroids, diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), phosphodiesterase Type V inhibitors, and quinolone antibiotics.

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.

Clinical Studies

Monotherapy

AVODART 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 studies, each with 2-year open-label extensions (n = 2,340). More than 90% of the study population was Caucasian. Subjects were at least 50 years of age 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 study 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 studies was approximately 17 units in both treatment groups.

Subjects receiving dutasteride achieved statistically significant improvement in symptoms versus placebo by Month 3 in 1 study and by Month 12 in the other 2 pivotal studies. At Month 12, the mean decrease from baseline in AUA-SI total symptom scores across the 3 studies 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 studies, P < 0.001) and was consistent across the 3 studies. 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 studies, 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 studies.

These studies 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.

Figure 1: AUA-SI Scorea Change From Baseline (Randomized, Double-Blind, Placebo-Controlled Studies Pooled

AUA-SI Score Change From Baseline - Illustration

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, AVODART was associated with a statistically significantly lower incidence of AUR (1.8% for AVODART vs. 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 AVODART vs. 4.1% for placebo, P < 0.001; 48% reduction in risk, [95% CI: 26% to 63%]). See Figures 2 and 3.

Figure 2: Percent of Subjects Developing Acute Urinary Retention Over a 24-Month Period (Randomized, Double-Blind, Placebo-Controlled Studies Pooled

Percent of Subjects Developing Acute Urinary Retention - Illustration

Figure 3: Percent of Subjects Having Surgery for Benign Prostatic Hyperplasia Over a 24-Month Period (Randomized, Double-Blind, Placebo-Controlled Studies Pooled)

Percent of Subjects Having Surgery for Benign Prostatic Hyperplasia - Illustration

Effect on Prostate Volume

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

Statistically significant differences (AVODART versus placebo) were noted at the earliest post-treatment prostate volume measurement in each study (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 studies 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 studies, P < 0.001). At Month 24, the mean percent change in prostate volume across the 3 studies 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 studies, 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 studies.

Figure 4: Prostate Volume Percent Change From Baseline (Randomized, Double-Blind, Placebo-Controlled Studies Pooled)

Prostate Volume Percent Change From Baseline -  Illustration

Effect on Maximum Urine Flow Rate

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

Differences between the 2 groups were statistically significant from baseline at Month 3 in all 3 studies and were maintained through Month 12. At Month 12, the mean increase in Qmax across the 3 studies pooled was 1.6 mL/sec for AVODART 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 studies, 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 studies, 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 studies.

Figure 5: Qmax Change From Baseline (Randomized, Double-Blind, Placebo-Controlled Studies Pooled)

Qmax Change From Baseline - Illustration

Summary of Clinical Studies

Data from 3 large, well-controlled efficacy studies demonstrate that treatment with AVODART (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 AVODART arrests the disease process of BPH in men with an enlarged prostate.

Combination With Alpha-Blocker Therapy (CombAT)

The efficacy of combination therapy (AVODART 0.5 mg/day plus tamsulosin 0.4 mg/day, n = 1,610) was compared with AVODART alone (n = 1,623) or tamsulosin alone (n = 1,611) in a 4-year multicenter, randomized, double-blind study. Study entry criteria were similar to the double-blind, placebo-controlled monotherapy efficacy trials described above in section 14.1. Eighty-eight percent (88%) of the enrolled study population was Caucasian. 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 AVODART, 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 AVODART, and -4.3 (±7.01) for tamsulosin, with a mean difference between combination and AVODART 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 AVODART, and -3.8 (±7.74) for tamsulosin, with a mean difference between combination and AVODART 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.

Figure 6: International Prostate Symptom Score Change From Baseline Over a 48-Month Period (Randomized, Double-Blind, Parallel Group Study [CombAT Study])

International Prostate Symptom Score Change From Baseline - Illustration

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

After 4 years of treatment, combination therapy with AVODART and tamsulosin did not provide benefit over monotherapy with AVODART 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 AVODART, and 0.9 (±4.57) mL/sec for tamsulosin, with a mean difference between combination and AVODART 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 AVODART was no longer statistically significant at Month 48.

Figure 7: Qmax Change From Baseline Over a 24-Month Period (Randomized, Double- Blind, Parallel Group Study [CombAT Study])

Qmax Change From Baseline - Illustration

Effect on Prostate Volume

The mean prostate volume at study 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 AVODART, and 0% (±31.14) for tamsulosin, with a mean difference between combination and AVODART 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 AVODART, and +4.6% (±35.45) for tamsulosin.

Last reviewed on RxList: 7/5/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

AVODART®
(av' o dart)
(dutasteride) Capsules

AVODART is for use by men only.

Read this patient information before you start taking AVODART and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is AVODART?

AVODART is a prescription medicine that contains dutasteride. AVODART 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

Who should NOT take AVODART?

Do Not Take AVODART if you are:

  • pregnant or could become pregnant. AVODART may harm your unborn baby. Pregnant women should not touch AVODART Capsules. If a woman who is pregnant with a male baby gets enough AVODART in her body by swallowing or touching AVODART, the male baby may be born with sex organs that are not normal. If a pregnant woman or woman of childbearing potential comes in contact with leaking AVODART Capsules, the contact area should be washed immediately with soap and water.
  • a child or a teenager.
  • allergic to dutasteride or any of the ingredients in AVODART. See the end of this leaflet for a complete list of ingredients in AVODART.
  • allergic to other 5 alpha-reductase inhibitors, for example, PROSCAR (finasteride) Tablets.

What should I tell my healthcare provider before taking AVODART?

Before you take AVODART, tell your healthcare provider if you:

  • have liver problems

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. AVODART and other medicines may affect each other, causing side effects. AVODART may affect the way other medicines work, and other medicines may affect how AVODART 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 AVODART?

  • Take 1 AVODART capsule once a day.
  • Swallow AVODART capsules whole. Do not crush, chew, or open AVODART capsules because the contents of the capsule may irritate your lips, mouth, or throat.
  • You can take AVODART 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 AVODART?

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

What are the possible side effects of AVODART?

AVODART may cause serious side effects, including:

  • Rare and serious allergic reactions, including:
    • swelling of your face, tongue, or throat
    • 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 AVODART 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.

AVODART has been shown to reduce sperm count, semen volume, and sperm movement. However, the effect of AVODART 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 AVODART. A blood test called PSA (prostate-specific antigen) is sometimes used to see if you might have prostate cancer. AVODART 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 AVODART (even if the PSA levels are in the normal range) should be evaluated by your healthcare provider.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects with AVODART. For more information, ask you healthcare provider or pharmacist.

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 AVODART?

  • Store AVODART Capsules at room temperature (59°F to 86°F or 15°C to 30°C).
  • AVODART Capsules may become deformed and/or discolored if kept at high temperatures.
  • Do not use AVODART if your capsules are deformed, discolored, or leaking.
  • Safely throw away medicine that is no longer needed.

Keep AVODART and all medicines out of the reach of children.

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

This patient information leaflet summarizes the most important information about AVODART. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about AVODART that is written for health professionals.

For more information, go to www.AVODART.com or call1-888-825-5249.

What are the ingredients in AVODART?

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, and edible red ink.

How does AVODART work?

Prostate growth is caused by a hormone in the blood called dihydrotestosterone (DHT). AVODART 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 AVODART, a treatment period of at least 6 months is usually necessary to see if AVODART will work for you.

Last reviewed on RxList: 7/5/2012
This monograph has been modified to include the generic and brand name in many instances.

>

PATIENT INFORMATION

AVODART®
(av' o dart)
(dutasteride) Capsules

AVODART is for use by men only.

Read this patient information before you start taking AVODART and each time you get a refill. There may be new information. This information does not take the place of talking with your healthcare provider about your medical condition or your treatment.

What is AVODART?

AVODART is a prescription medicine that contains dutasteride. AVODART 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

Who should NOT take AVODART?

Do Not Take AVODART if you are:

  • pregnant or could become pregnant. AVODART may harm your unborn baby. Pregnant women should not touch AVODART Capsules. If a woman who is pregnant with a male baby gets enough AVODART in her body by swallowing or touching AVODART, the male baby may be born with sex organs that are not normal. If a pregnant woman or woman of childbearing potential comes in contact with leaking AVODART Capsules, the contact area should be washed immediately with soap and water.
  • a child or a teenager.
  • allergic to dutasteride or any of the ingredients in AVODART. See the end of this leaflet for a complete list of ingredients in AVODART.
  • allergic to other 5 alpha-reductase inhibitors, for example, PROSCAR (finasteride) Tablets.

What should I tell my healthcare provider before taking AVODART?

Before you take AVODART, tell your healthcare provider if you:

  • have liver problems

Tell your healthcare provider about all the medicines you take, including prescription and non-prescription medicines, vitamins, and herbal supplements. AVODART and other medicines may affect each other, causing side effects. AVODART may affect the way other medicines work, and other medicines may affect how AVODART 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 AVODART?

  • Take 1 AVODART capsule once a day.
  • Swallow AVODART capsules whole. Do not crush, chew, or open AVODART capsules because the contents of the capsule may irritate your lips, mouth, or throat.
  • You can take AVODART 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 AVODART?

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

What are the possible side effects of AVODART?

AVODART may cause serious side effects, including:

  • Rare and serious allergic reactions, including:
    • swelling of your face, tongue, or throat
    • 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 AVODART 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.

AVODART has been shown to reduce sperm count, semen volume, and sperm movement. However, the effect of AVODART 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 AVODART. A blood test called PSA (prostate-specific antigen) is sometimes used to see if you might have prostate cancer. AVODART 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 AVODART (even if the PSA levels are in the normal range) should be evaluated by your healthcare provider.

Tell your healthcare provider if you have any side effect that bothers you or that does not go away.

These are not all the possible side effects with AVODART. For more information, ask you healthcare provider or pharmacist.

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 AVODART?

  • Store AVODART Capsules at room temperature (59°F to 86°F or 15°C to 30°C).
  • AVODART Capsules may become deformed and/or discolored if kept at high temperatures.
  • Do not use AVODART if your capsules are deformed, discolored, or leaking.
  • Safely throw away medicine that is no longer needed.

Keep AVODART and all medicines out of the reach of children.

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

This patient information leaflet summarizes the most important information about AVODART. If you would like more information, talk with your healthcare provider. You can ask your pharmacist or healthcare provider for information about AVODART that is written for health professionals.

For more information, go to www.AVODART.com or call1-888-825-5249.

What are the ingredients in AVODART?

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, and edible red ink.

How does AVODART work?

Prostate growth is caused by a hormone in the blood called dihydrotestosterone (DHT). AVODART 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 AVODART, a treatment period of at least 6 months is usually necessary to see if AVODART will work for you.

Last reviewed on RxList: 7/5/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Avodart Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

DUTASTERIDE - ORAL

(due-TAST-er-ide)

COMMON BRAND NAME(S): Avodart

USES: This medication is used in men to treat the symptoms of an enlarged prostate (benign prostatic hyperplasia-BPH). It works by reducing the size of the enlarged prostate. This helps to relieve symptoms of BPH such as difficulty in beginning the flow of urine, weak stream, and the need to urinate frequently or urgently (including during the middle of the night). It may also reduce the need for surgery to treat BPH.

Dutasteride is not approved for prevention of prostate cancer. It may slightly increase the risk of developing a very serious form of prostate cancer. Talk to your doctor about the benefits and risks.

This medication should not be used by women or children.

HOW TO USE: Read the Patient Information Leaflet if available from your pharmacist before you start taking this medication and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth with or without food as directed by your doctor, usually once daily. Swallow the medication whole. Do not crush or chew the capsules.

Use this medication regularly to get the most benefit from it. To help you remember, take it at the same time each day.

Since this drug can be absorbed through the skin and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication.

It may take 3 to 6 months to notice an improvement in symptoms. Tell your doctor if your symptoms do not improve or if they worsen.

Disclaimer

Avodart Consumer (continued)

SIDE EFFECTS: Sexual problems (such as decreased sexual interest/ability, decrease in the amount of semen/sperm), increased breast size, or breast tenderness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

A very serious allergic reaction to this drug is rare. However, get medical help right away if you notice any symptoms of a serious allergic reaction, including: rash, itching/swelling (especially of the face/tongue/throat), severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

In the US -

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Avodart (dutasteride) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before taking dutasteride, tell your doctor or pharmacist if you are allergic to it; or to finasteride; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history.

Before having surgery, tell your doctor or dentist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products).

Do not donate blood while you are taking this medication and for at least 6 months after you stop taking it. This will prevent the possibility of your blood being given to a pregnant woman.

This medication is not usually used in women. Therefore, it is unlikely to be used during pregnancy or breast-feeding. Consult your doctor if you have any questions about this medication.

Disclaimer

Avodart Consumer (continued)

DRUG INTERACTIONS: The effects of some drugs can change if you take other drugs or herbal products at the same time. This can increase your risk for serious side effects or may cause your medications not to work correctly. These drug interactions are possible, but do not always occur. Your doctor or pharmacist can often prevent or manage interactions by changing how you use your medications or by close monitoring.

To help your doctor and pharmacist give you the best care, be sure to tell your doctor and pharmacist about all the products you use (including prescription drugs, nonprescription drugs, and herbal products) before starting treatment with this product. While using this product, do not start, stop, or change the dosage of any other medicines you are using without your doctor's approval.

Keep a list of all the products you use. Share the list with your doctor and pharmacist to reduce your risk for serious medication problems.

OVERDOSE: If overdose is suspected, contact a poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (such as prostate exams, prostate-specific antigen-PSA) should be performed periodically to monitor your progress or check for side effects. Consult your doctor for more details.

MISSED DOSE: If you miss a dose, take it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store at room temperature away from light and moisture. Do not store in the bathroom. Keep all medications away from children and pets.

Dutasteride capsules may soften and leak if stored at high temperatures. If your capsules crack and leak, do not use them. If your skin comes in contact with the leaking capsules, wash the area immediately with soap and water. Contact your pharmacist for more information.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

Information last revised March 2012. Copyright(c) 2012 First Databank, Inc.

Avodart Patient Information Including Side Effects

Brand Names: Avodart

Generic Name: dutasteride (Pronunciation: doo TAS ter ide)

What is dutasteride (Avodart)?

Dutasteride prevents the conversion of testosterone to dihydrotestosterone (DHT) in the body. DHT is involved in the development of benign prostatic hyperplasia (BPH).

Dutasteride is used to treat benign prostatic hyperplasia (BPH) in men with an enlarged prostate. Dutasteride helps improve urinary flow and may also reduce your need for prostate surgery later on.

Dutasteride is sometimes given with another medication called tamsulosin (Flomax). Be sure to read the medication guide or patient instructions provided with each of your medications.

Dutasteride may also be used for purposes not listed in this medication guide.

Avodart 0.5 mg

yellow, imprinted with GX CE2

What are the possible side effects of dutasteride (Avodart)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Less serious side effects may include:

  • decreased libido (sex drive);
  • decreased amount of semen released during sex;
  • impotence (trouble getting or keeping an erection); or
  • breast tenderness or enlargement.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Avodart (dutasteride) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about dutasteride (Avodart)?

Dutasteride should never be taken by a woman or a child. Dutasteride can be absorbed through the skin, and women or children should not be permitted to handle dutasteride capsules.

Although dutasteride is not for use by women, this medication can cause birth defects if a woman is exposed to it during pregnancy. Dutasteride capsules should not be handled by a woman who is pregnant or who may become pregnant.

Do not chew, crush, or open a dutasteride capsule. Swallow the capsule whole. Dutasteride can irritate your lips, mouth, or throat if the capsule has been broken or opened before you swallow it.

If a woman accidentally comes into contact with this medication from a leaking capsule, wash the area with soap and water right away.

Before taking dutasteride, tell your doctor if you have ever had an allergic reaction to this medication, or to a similar medicine called finasteride (Propecia, Proscar).

Do not donate blood while taking dutasteride and for at least 6 months after your treatment ends. Dutasteride can be carried in the blood and could cause birth defects if a pregnant women receives a transfusion with blood that contains dutasteride.

Side Effects Centers

Avita Patient Information including How Should I Take

What should I discuss with my healthcare provider before using tretinoin topical?

FDA pregnancy category C. It is not known whether tretinoin topical is harmful to an unborn baby. Before taking this medication, tell your doctor if you are pregnant or plan to become pregnant during treatment.

Tretinoin topical can pass into breast milk and may harm a nursing baby. Do not use this medication without telling your doctor if you are breast-feeding a baby.

How should I use tretinoin topical?

Use tretinoin topical exactly as your doctor has prescribed it for you. Using more medicine or applying it more often than prescribed will not make it work any faster, and may increase side effects. Do not use this medication for longer than your doctor has prescribed.

Wash your hands before and after applying tretinoin topical. Before applying, clean and dry the skin area to be treated.

Applying tretinoin topical to wet skin may cause skin irritation. If you use Renova, wait at least 20 minutes after washing your face before applying a thin layer of the medication.

Do not wash the treated area for at least 1 hour after applying tretinoin topical. Avoid the use of other skin products on the treated area for at least 1 hour following application of tretinoin topical.

Applying an excessive amount of tretinoin gel may result in "pilling" of the medication. If this occurs, use a thinner layer of gel with the next application.

Tretinoin topical should be used as part of a complete skin care program that includes avoiding sunlight and using an effective sunscreen and protective clothing.

Use this medication for as many days as it has been prescribed for you even if you think it is not working. It may take weeks or months of use before you notice improvement in your skin. If you are using tretinoin topical to treat acne, your condition may get slightly worse for a short time when you first start using the medication. Call your doctor if skin irritation becomes severe or if your acne does not improve within 8 to 12 weeks.

Store tretinoin topical at room temperature away from moisture and heat. The gel formulations of Retin-A are flammable, keep them away from open flame.

Avodart Patient Information including If I Miss a Dose

What happens if I miss a dose (Avodart)?

Take the missed dose as soon as you remember. Skip the missed dose if it is almost time for your next scheduled dose. Do not take extra medicine to make up the missed dose.

What happens if I overdose (Avodart)?

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

What should I avoid while taking dutasteride (Avodart)?

Do not donate blood while taking dutasteride and for at least 6 months after your treatment ends. Dutasteride can be carried in the blood and could cause birth defects if a pregnant women receives a transfusion with blood that contains dutasteride.

What other drugs will affect dutasteride (Avodart)?

Tell your doctor about all other medicines you use, especially:

  • conivaptan (Vaprisol);
  • imatinib (Gleevec);
  • isoniazid (for treating tuberculosis);
  • an antibiotic such as clarithromycin (Biaxin), erythromycin (E.E.S., EryPed, Ery-Tab, Erythrocin, Pediazole), or telithromycin (Ketek);
  • an antifungal medication such as itraconazole (Sporanox), ketoconazole (Nizoral), miconazole (Oravig), or voriconazole (Vfend);
  • an antidepressant such as nefazodone;
  • heart or blood pressure medication such as nicardipine (Cardene) or quinidine (Quin-G); or
  • HIV/AIDS medicine such as atazanavir (Reyataz), delavirdine (Rescriptor), indinavir (Crixivan), nelfinavir (Viracept), saquinavir (Invirase), or ritonavir (Norvir, Kaletra).

This list is not complete and other drugs may interact with dutasteride. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about dutasteride.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 9.01. Revision date: 6/14/2011.

Your use of the content provided in this service indicates that you have read,understood and agree to the End-User License Agreement,which can be accessed by clicking on this link.

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