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  • CLASSES

    5-Alpha Reductase Inhibitors

    DEA CLASS

    Rx

    DESCRIPTION

    5-alpha-reductase inhibitor; similar to finasteride, but causes a greater reduction in DHT concentrations at equipotent doses
    Used for symptomatic treatment of BPH; may potentially be used for male pattern baldness (i.e., androgenetic alopecia)
    May decrease risk of low-grade prostate cancer; but, may increase risk of more serious high-grade prostate cancer

    COMMON BRAND NAMES

    Avodart

    HOW SUPPLIED

    Avodart/Dutasteride Oral Cap: 0.5mg

    DOSAGE & INDICATIONS

    For the treatment of benign prostatic hyperplasia (BPH) in men with an enlarged prostate to improve urinary symptoms, reduce risk of acute urinary retention, and reduce the risk of the need for BPH-related surgery.
    NOTE: Instruct patient to swallow capsules whole; do not chew or open since contact with the capsule contents may cause irritation of the oropharyngeal mucosa.
    For use in combination with tamsulosin.
    Oral dosage (Avodart capsules)
    Adult males

    0.5 mg PO with tamsulosin (0.4 mg PO) once daily.

    Oral dosage (Avodart capsules)
    Adult males

    0.5 mg PO once daily.

    For the treatment of male pattern hair loss† (i.e., androgenetic alopecia†), in patients with mild to moderate hair loss of the vertex and anterior mid-scalp area.
    Oral dosage (tablets†)
    Adult males

    Doses ranging from 0.5 to 2.5 mg PO once daily have been studied. Published data, however, are lacking. If capsules are used, instruct the patient to swallow them whole; do not chew or open since contact with the capsule contents may cause irritation of the oropharyngeal mucosa.

    †Indicates off-label use

    MAXIMUM DOSAGE

    Adults

    Specific maximum dosage information is not available.

    Elderly

    Specific maximum dosage information is not available.

    Adolescents

    Not recommended.

    Children

    Not recommended.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Dutasteride should be used with caution in patients with hepatic disease, since the drug is extensively metabolized by the liver. Specific guidelines for dosage adjustments are not available.

    Renal Impairment

    No dosage adjustments are needed.

    ADMINISTRATION

    Oral Administration

    May be administered with or without food. Swallow capsules whole; do not chew or open since contact with the capsule contents may cause irritation of the oropharyngeal mucosa.
    Do not administer soft-gelatin capsules that are cracked or leaking; contact a pharmacist for replacements.
    Females who are pregnant or may become pregnant should not handle/administer dutasteride soft-gelatin capsules. If a woman who is pregnant gets enough dutasteride through her skin after handling it, the drug could harm the unborn fetus. If skin contact with a leaking capsule occurs, the affected area should be washed with soap and water immediately.

    STORAGE

    Avodart:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F

    CONTRAINDICATIONS / PRECAUTIONS

    General Information

    Dutasteride is contraindicated in patients with a known hypersensitivity to dutasteride (e.g., angioedema) or any ingredient in the preparation. Cross-sensitivity with other 5-alpha-reductase inhibitors is possible.
     
    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 urine, so no adjustment in dosage is expected for patients with renal impairment.
     
    No overall differences in safety or effectiveness have been observed between elderly (> 65 years of age) and other younger adult patients.

    Pregnancy

    Dutasteride is contraindicated for use in females of childbearing potential and is pregnancy risk category X and is therefore contraindicated during pregnancy. Dutasteride and other 5-alpha-reductase inhibitors inhibit the conversion of testosterone to DHT that can cause abnormalities in the external genitalia of the male fetus. Pregnant women or women trying to conceive should not handle dutasteride capsules because dutasteride is absorbed through the skin and may result in fetal exposure. If skin contact with a leaking capsule occurs, the affected area should be washed with soap and water immediately. Dutasteride is secreted into male semen. The amount of dutasteride in semen that is available for vaginal absorption is estimated to be less than 100 times the concentrations that produces abnormalities in the genitalia of male offspring in animal studies. In addition, dutasteride is more than 96% protein bound in human semen, which may decrease vaginal absorption of the drug.

    Breast-feeding

    Dutasteride is not indicated for use in women. It is not known whether dutasteride is excreted in human milk. Therefore, the effects of dutasteride on infants during breast-feeding cannot be determined.

    Hepatic disease

    Dutasteride should be used with caution in patients with hepatic disease; data are limited regarding the incidence of adverse effects or drug accumulation in these patients. The drug is extensively metabolized by the liver and has a half-life of about 5 weeks at steady state. The effect of potent hepatic CYP3A4 isoenzyme inhibitors on the metabolism of dutasteride has not been studied. Care should be taken when administering dutasteride to patients taking potent CYP3A4 inhibitors chronically.

    Children, infants, neonates

    Dutasteride is contraindicated for use in neonates, infants, children, and adolescents. Safety and effectiveness have not been established in these age groups.

    Prostate cancer, urinary tract obstruction

    Dutasteride reduces total serum prostate specific antigen (PSA) by about 40% after 3 months of treatment and 50% after 6, 12, and 24 months of treatment. This decrease is predictable over the entire range of PSA values, but may vary in individual patients. It is recommended that a new baseline PSA concentration be established after 3—6 months for interpretation of serial PSAs in men taking dutasteride. This new baseline PSA should be used to assess potentially cancer-related changes in PSA. To interpret an isolated PSA value in a man treated with dutasteride for 6 months or more, the PSA value should be doubled for comparison with normal values in untreated men. Increased PSA levels from nadir during dutasteride treatment may indicate possible prostate cancer and should be carefully evaluated regardless of whether or not the levels fall within the normal range for men not taking a 5-alpha reductase inhibitor. The free-to-total PSA ratio (percent free PSA) remains constant at month 12, even under the influence of dutasteride. If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men receiving dutasteride, no adjustment to its value appears necessary. In June 2011, a review of two large, randomized controlled trials, the Prostate Cancer Prevention Trial (PCPT) and the Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial prompted the FDA to alert healthcare professionals of the potential risk of an increased incidence of high-grade prostate cancer in patients receiving finasteride or dutasteride treatment. Results from the REDUCE trial showed that men receiving dutasteride had a 23% decreased risk of being diagnosed with prostate cancer when compared to placebo (p < 0.0001); however, the risk reduction was limited to Gleason score (GS) <= 6 cancers. There was an increased incidence of GS 8—10 prostate cancers with dutasteride compared to placebo (1% vs. 0.5%, respectively). Therefore, in initiating or continuing treatment with dutasteride, clinicians should weigh the known benefits of treatment against the potential risk and be aware that dutasteride may increase the risk of high-grade prostate cancer. Lower urinary tract symptoms of BPH can be indicative of other urological diseases, including prostate cancer. Patients should be assessed to rule out other urological diseases prior to treatment with dutasteride and periodically thereafter. Patients with a large residual urinary volume and/or severely diminished urinary flow may not be good candidates for 5-alpha-reductase inhibitor therapy and should be carefully monitored for urinary tract obstruction.

    Blood donation

    Males treated with dutasteride should not undergo blood donation 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 receiving a blood transfusion. Serum levels of dutasteride are detectable for 4—6 months following termination of therapy.

    ADVERSE REACTIONS

    Severe

    heart failure / Delayed / 0-1.0
    angioedema / Rapid / Incidence not known
    teratogenesis / Delayed / Incidence not known

    Moderate

    impotence (erectile dysfunction) / Delayed / 0-5.0
    ejaculation dysfunction / Delayed / 0-2.0
    edema / Delayed / Incidence not known

    Mild

    libido decrease / Delayed / 0-3.0
    gynecomastia / Delayed / 0-2.0
    mastalgia / Delayed / 0-1.1
    breast enlargement / Delayed / 0-1.0
    dizziness / Early / 0-1.0
    urticaria / Rapid / Incidence not known
    rash (unspecified) / Early / Incidence not known
    pruritus / Rapid / Incidence not known
    decreased ejaculate volume / Delayed / Incidence not known
    oligospermia / Delayed / Incidence not known
    spermatogenesis inhibition / Delayed / Incidence not known

    DRUG INTERACTIONS

    Amiodarone: (Moderate) Dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors, such as amiodarone.
    Amprenavir: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Atazanavir: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Atazanavir; Cobicistat: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together. (Moderate) The plasma concentrations of dutasteride may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as impotence or libido decrease, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate.
    Boceprevir: (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like boceprevir are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Cimetidine: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors, such as cimetidine.
    Cobicistat: (Moderate) The plasma concentrations of dutasteride may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as impotence or libido decrease, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of dutasteride may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as impotence or libido decrease, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate.
    Cobicistat; Elvitegravir; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of dutasteride may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as impotence or libido decrease, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate.
    Conivaptan: (Moderate) According to the manufacturer, concomitant use of conivaptan (a strong CYP3A4 inhibitor) and CYP3A substrates (such as dutasteride) should be avoided. Coadministration of conivaptan with other CYP3A substrates (midazolam, simvastatin, amlodipine) has resulted in increased mean AUC values (2 to 3 times). Theoretically, similar pharmacokinetic effects could be seen with dutasteride. Treatment with dutasteride may be initiated no sooner than 1 week after completion of conivaptan therapy.
    Darunavir: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Darunavir; Cobicistat: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together. (Moderate) The plasma concentrations of dutasteride may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as impotence or libido decrease, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Delavirdine: (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like delavirdine are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Diltiazem: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme and the clearance of dutasteride may be reduced when co-administered with the CYP3A4 inhibitor diltiazem.
    Erythromycin: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme and CYP3A5 isoenzymes. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors, such as erythromycin.
    Erythromycin; Sulfisoxazole: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme and CYP3A5 isoenzymes. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors, such as erythromycin.
    Fluconazole: (Moderate) Dutasteride is metabolized by the CYP3A4/5 hepatic enzyme. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors including fluconazole.
    Fosamprenavir: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Idelalisib: (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like idelalisib are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Imatinib: (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like imatinib are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Indinavir: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Itraconazole: (Moderate) Monitor for increased dutasteride adverse effects if coadministration of itraconazole is necessary. No clinical drug interaction trials 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 such as itraconazole.
    Ivacaftor: (Moderate) Use caution when administering ivacaftor and dutasteride concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as dutasteride, can increase dutasteride exposure leading to increased or prolonged therapeutic effects and adverse events.
    Ketoconazole: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme. CYP3A4 inhibitors, such as ketoconazole, may decrease the clearance of dutasteride.
    Lopinavir; Ritonavir: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and dutasteride concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as dutasteride, can increase dutasteride exposure leading to increased or prolonged therapeutic effects and adverse events.
    Nefazodone: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme. The clearance of dutasteride may be reduced when co-administered with CYP3A4 inhibitors including nefazodone.
    Nelfinavir: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Ombitasvir; Paritaprevir; Ritonavir: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Posaconazole: (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like posaconazole are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Protease inhibitors: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Ritonavir: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Saquinavir: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Saw Palmetto, Serenoa repens: (Moderate) Saw palmetto may inhibit 5 alpha-reductase, preventing the conversion of testosterone to dihydrotestosterone. This action is similar to the action of 5-alpha reductase inhibitors, such as dutasteride and finasteride. Co-use is likely to be common by patients, but the effects of co-use are not known. In theory, the effects could be additive, but it is not known if the added effects would be beneficial or harmful. Clinicians should be alert for any unusual effects if patients ingest saw palmetto supplements while taking 5-alpha reductase inhibitors.
    Soy Isoflavones: (Minor) Theoretically, because the soy isoflavones appear to inhibit type II 5-alpha-reductase, the soy isoflavones may have additive effects with other 5-alpha reductase inhibitors.
    Telithromycin: (Moderate) Monitor for common side effects of dutasteride, such as libido decrease, breast tenderness, or erectile dysfunction when chronic, potent inhibitors of CYP3A4 like telithromycin are used concomitantly. The effect of potent CYP3A4 inhibitors on the metabolism of dutasteride has not been studied. However, because dutasteride is metabolized by CYP3A4 and CYP3A5 isoenzymes, chronic coadministration with potent CYP3A4 enzyme inhibitors may result in elevated concentrations of dutasteride.
    Tipranavir: (Moderate) Concurrent administration of dutasteride with protease inhibitors may result in elevated dutasteride plasma concentrations. Dutasteride is metabolized by the hepatic isoenzyme CYP3A4; protease inhibitors are potent inhibitors of this enzyme. Caution and close monitoring are advised if these drugs are administered together.
    Trandolapril; Verapamil: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme. The clearance of dutasteride may be reduced when co-administered with the CYP3A4 inhibitor verapamil.
    Verapamil: (Moderate) Dutasteride is metabolized by CYP3A4 enzyme. The clearance of dutasteride may be reduced when co-administered with the CYP3A4 inhibitor verapamil.
    Voriconazole: (Moderate) CYP3A4 inhibitors, such as voriconazole, may theoretically reduce the metabolism of dutasteride, which is metabolized by CYP3A4 enzyme. Reduced clearance of dutasteride may increase the risk of side effects.

    PREGNANCY AND LACTATION

    Pregnancy

    Dutasteride is contraindicated for use in females of childbearing potential and is pregnancy risk category X and is therefore contraindicated during pregnancy. Dutasteride and other 5-alpha-reductase inhibitors inhibit the conversion of testosterone to DHT that can cause abnormalities in the external genitalia of the male fetus. Pregnant women or women trying to conceive should not handle dutasteride capsules because dutasteride is absorbed through the skin and may result in fetal exposure. If skin contact with a leaking capsule occurs, the affected area should be washed with soap and water immediately. Dutasteride is secreted into male semen. The amount of dutasteride in semen that is available for vaginal absorption is estimated to be less than 100 times the concentrations that produces abnormalities in the genitalia of male offspring in animal studies. In addition, dutasteride is more than 96% protein bound in human semen, which may decrease vaginal absorption of the drug.

    Dutasteride is not indicated for use in women. It is not known whether dutasteride is excreted in human milk. Therefore, the effects of dutasteride on infants during breast-feeding cannot be determined.

    MECHANISM OF ACTION

    Dutasteride inhibits the conversion of testosterone to 5-alpha-dihydrotestosterone (DHT), the primary androgen that stimulates the development of prostate tissue. The intracellular enzyme 5-alpha-reductase is responsible for this conversion and exists in two isoforms, type I and II. The type II isoenzyme is primarily active in reproductive tissues (i.e., prostate, seminal vesicles, epididymides) and is responsible for two-thirds of circulating DHT. The type I isoenzyme is mostly active in the skin and liver. In the treatment of benign prostatic hyperplasia, dutasteride reduces circulating DHT which leads to a reduction in prostate hypertrophy and improvement in urine flow. In male pattern hair loss, the balding scalp contains miniaturized hair follicles and increased amounts of DHT compared with hairy scalp. Dutasteride decreases scalp and serum DHT concentrations, thus interrupting a key factor in the development of androgenetic alopecia in those patients genetically predisposed. Dutasteride does not bind to androgen receptors in humans.
     
    The pharmcodynamic effects of dutasteride include decrease in serum DHT, increase in total testosterone, increase in thyroid-stimulating hormone (TSH), and a decrease in total serum prostate specific antigen (PSA). The reduction of serum DHT is dose dependent and is observed within 1 to 2 weeks. Dutasteride does not appear to alter circulating concentrations of sex hormone binding globulin, estradiol, luteinizing hormone, follicle-stimulating hormone, thyroxine (free T4), and dehydroepiandrosterone in healthy volunteers. Dutasteride does not affect the hypothalamic-pituitary-testicular-axis.

    PHARMACOKINETICS

    Dutasteride is administered orally. Once in the systemic circulation, approximately 99% is highly bound to albumin and alpha1-acid glycoprotein. It is distributed widely throughout the body. Dutasteride is metabolized in the liver via CYP3A4 enzyme. Two minor mono-hydroxylated metabolites and 3 major metabolites have been identified. Of these metabolites, the 6-beta-hydroxydutasteride is the only one to have activity comparable to that of dutasteride. Dutasteride and its metabolites are primarily excreted in feces (5% unchanged drug and 40% as metabolites). Only trace amounts of unchanged drug were found in urine (< 1%). The dose unaccounted for was approximately 55%. The terminal elimination half-life is about 5 weeks at steady state (average 40 ng/ml). Following daily dosing of 0.5 mg, 65% of steady-state concentration is achieved after 1 month and approximately 90% after 3 months. Steady-state serum and semen concentrations are achieved at about 6 months. On average, semen concentrations are 11.5% of serum concentrations in healthy patients at 1 year. Because of the long half-life, serum concentrations remain detectable (> 0.1 ng/ml) for up to 4 to 6 months after stopping therapy.
     
    Affected cytochrome P450 isoenzymes: CYP3A4
     

    Oral Route

    After oral administration, dutasteride is absorbed rapidly with a short distribution phase. It's bioavailability is estimated to be about 60% (range 40% to 94%). Peak serum concentrations occur within 2—3 hours. When administered with food, the Cmax was reduced by 10—15%, however, this is of no clinical significance.