CLASSES

5-Alpha Reductase Inhibitors

DEA CLASS

Rx

DESCRIPTION

Oral 5-alpha-reductase inhibitor
Used for symptomatic treatment of BPH in men with enlarged prostates; used off-label for male-pattern baldness
Pregnant women or women trying to conceive should not handle dutasteride since absorption through the skin may result in fetal exposure and severe adverse outcomes

COMMON BRAND NAMES

Avodart

HOW SUPPLIED

Avodart/Dutasteride Oral Cap: 0.5mg

DOSAGE & INDICATIONS

†Indicates off-label use

MAXIMUM DOSAGE

Specific maximum dosage information is not available.

Specific maximum dosage information is not available.

Not recommended.

Not recommended.

DOSING CONSIDERATIONS

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.

No dosage adjustments are needed.

ADMINISTRATION

Hazardous Drugs Classification
NIOSH 2016 List: Group 3
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating capsules will increase exposure and require additional protective equipment. Oral liquid drugs require double chemotherapy gloves and protective gown. Eye/face and respiratory protection may be needed during preparation and administration.

STORAGE

Avodart:
- Store at 77 degrees F; excursions permitted to 59-86 degrees F

CONTRAINDICATIONS / PRECAUTIONS

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.

Dutasteride is contraindicated for use in females of childbearing potential 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 of childbearing potential and thus is contraindicated for use during breast-feeding. It is not known whether dutasteride is excreted in human milk. Therefore, the effects of dutasteride on infants during breast-feeding cannot be determined.

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.

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

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.

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.

Dutasteride may cause spermatogenesis inhibition or oligospermia, decreased sperm motility, or decreased semen volume. The clinical significance of dutasteride’s effect on semen characteristics for an individual male patient’s fertility is not known; consider the potential effects on semen when assessing a male with infertility. The effects of dutasteride 0.5 mg/day on semen characteristics were evaluated in normal male volunteers aged 18 to 52 (n = 27 dutasteride, n = 23 placebo) throughout 52 weeks of treatment and 24 weeks of post-treatment follow-up. At 52 weeks, the mean percent reductions from baseline in total sperm count, semen volume, and sperm motility were 23%, 26%, and 18%, respectively, in the dutasteride group when adjusted for changes from baseline in the placebo group. Sperm concentration and sperm morphology were unaffected. After 24 weeks of follow-up, the mean percent change in total sperm count in the dutasteride group remained 23% lower than baseline. While mean values for all semen parameters at all time-points remained within the normal ranges and did not meet predefined criteria for a clinically significant change (30%), 2 subjects in the dutasteride group had decreases in sperm count of greater than 90% from baseline at 52 weeks, with partial recovery at the 24-week follow-up.

ADVERSE REACTIONS

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

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

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 / Early / Incidence not known
pruritus / Rapid / Incidence not known
decreased ejaculate volume / Delayed / Incidence not known
spermatogenesis inhibition / Delayed / Incidence not known
oligospermia / Delayed / Incidence not known

DRUG INTERACTIONS

Adagrasib: (Moderate) Monitor for dutasteride-related adverse reactions if coadministration with adagrasib is necessary. Dutasteride is a CYP3A substrate and adagrasib is a strong CYP3A inhibitor. Although the effect of strong CYP3A inhibitors on dutasteride has not been studied, dutasteride exposure may increase.
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.
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 strong CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate.
Ceritinib: (Moderate) Monitor for dutasteride-related adverse reactions if coadministration with ceritinib is necessary. Dutasteride is a CYP3A4 substrate and ceritinib is a strong CYP3A4 inhibitor. Although the effect of strong CYP3A4 inhibitors on dutasteride has not been studied, dutasteride exposure may increase.
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 strong CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate.
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 strong CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (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 strong 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.
Elvitegravir; Cobicistat; 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 strong CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate.
Elvitegravir; Cobicistat; 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 strong CYP3A4 inhibitor, while dutasteride is a CYP3A4 substrate.
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.
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.
Ketoconazole: (Moderate) Monitor for dutasteride-related adverse reactions if coadministration with ketoconazole is necessary due to a potential for increased dutasteride exposure. Dutasteride is extensively metabolized in humans by CYP3A4/3A5 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 dutasteride to patients taking potent, chronic CYP3A4 enzyme inhibitors like ketoconazole, a strong CYP3A4 inhibitor.
Letermovir: (Moderate) An increase in the plasma concentration of dutasteride may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Dutasteride is extensively metabolized by CYP3A4. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor. The effects of strong CYP3A4 inhibitors on dutasteride have not been evaluated.
Levoketoconazole: (Moderate) Monitor for dutasteride-related adverse reactions if coadministration with ketoconazole is necessary due to a potential for increased dutasteride exposure. Dutasteride is extensively metabolized in humans by CYP3A4/3A5 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 dutasteride to patients taking potent, chronic CYP3A4 enzyme inhibitors like ketoconazole, a strong CYP3A4 inhibitor.
Lonafarnib: (Moderate) Monitor for dutasteride-related adverse reactions if coadministration with lonafarnib is necessary. Dutasteride is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor. Although the effect of strong CYP3A4 inhibitors on dutasteride has not been studied, dutasteride exposure may increase.
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.
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.
Nirmatrelvir; 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.
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.
Ribociclib: (Moderate) Monitor for an increase in dutasteride-related adverse reactions if coadministration with ribociclib is necessary. Dutasteride is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
Ribociclib; Letrozole: (Moderate) Monitor for an increase in dutasteride-related adverse reactions if coadministration with ribociclib is necessary. Dutasteride is a CYP3A4 substrate and ribociclib is a strong CYP3A4 inhibitor.
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.
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.
Tucatinib: (Moderate) Monitor for dutasteride-related adverse reactions if coadministration with tucatinib is necessary. Dutasteride is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor. Although the effect of strong CYP3A4 inhibitors on dutasteride has not been studied, dutasteride exposure may increase.
Voriconazole: (Moderate) Monitor for dutasteride-related adverse effects (e.g., impotence, decreased libido, breast enlargement) if coadministered with voriconazole. Dutasteride is a CYP3A4 substrate, and voriconazole is a strong CYP3A4 inhibitor. Although the effect of strong CYP3A4 inhibitors on dutasteride has not been defined, dutasteride exposure may increase.

PREGNANCY AND LACTATION

Dutasteride is not indicated for use in women of childbearing potential and thus is contraindicated for use during breast-feeding. 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