Avodart

5-Alpha Reductase Inhibitors

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.

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.

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

Avodart

Rx

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

0.5 mg PO once daily.

0.5 mg/day PO of dutasteride has been the most commonly evaluated dose. The available data suggest that dutasteride 0.5 mg PO once daily is at least as effective as 1 mg/day of finasteride in hair growth improvement. In one study, dutasteride 0.5 mg/day was superior to 1 mg/day of finasteride in hair growth measures at 24 weeks. A similar finding occurred in one meta-analysis in which dutasteride was found to be more effective than finasteride in all measures of efficacy including the mean change in total hair count, investigator's assessment of global photographs for the vertex and frontal views, panel global photographic assessment for the vertex and frontal views, and the assessment of the subjects. It appears that there is no statistical difference between dutasteride and finasteride in adverse effect profile (e.g., sexual dysfunction). According to one evidence-based guideline, dutasteride 0.5 mg PO daily can be considered for improving or preventing the progression of hair loss in cases of ineffective treatment with finasteride for 12 months.[64978] [64981]

†Indicates off-label use

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.

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.
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.
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.

Avodart/Dutasteride Oral Cap: 0.5mg

Specific maximum dosage information is not available.

Specific maximum dosage information is not available.

Not recommended.

Not recommended.

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.

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
 

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.

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.