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Dutasteride


General


Pronunciation

(doo TAS teer ide)


Brand Names: U.S.

  • Avodart

Indications


Use: Labeled Indications

Benign prostatic hyperplasia: Treatment of symptomatic benign prostatic hyperplasia (BPH) as monotherapy (to improve symptoms, reduce the risk of acute urinary retention, and to reduce the risk of need for BPH-related surgery) or combination therapy with tamsulosin

Limitations of use: Not approved for the prevention of prostate cancer.


Contraindications


Clinically significant hypersensitivity to dutasteride, other 5-alpha-reductase inhibitors (eg, finasteride), or any component of the formulation; use in pediatric patients; women of childbearing potential; pregnancy


Dosing and Administration


Dosing: Adult

Benign prostatic hyperplasia (BPH): Males: Oral: 0.5 mg once daily alone or in combination with tamsulosin


Dosing: Geriatric

Refer to adult dosing.


Dosing: Renal Impairment

No dosage adjustment is necessary


Dosing: Hepatic Impairment

There are no dosage adjustments provided in the manufacturer 's labeling (has not been studied). Dutasteride is extensively hepatically metabolized and exposure could be increased in hepatic impairment, however, higher doses studied did not generally produce additional adverse effects.


Administration

May be administered without regard to meals. Capsule should be swallowed whole; do not chew or open; contact with opened capsule can cause oropharyngeal irritation. Should not be touched or handled by women who are pregnant or are of childbearing age.

Hazardous agent; use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).


Storage

Store at controlled room temperature of 25 ‚ °C (77 ‚ °F); excursions permitted to 15 ‚ °C to 30 ‚ °C (59 ‚ °F to 86 ‚ °F).


Dosage Forms/Strengths


Dosage Forms

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Capsule, Oral:

Avodart: 0.5 mg

Generic: 0.5 mg


Drug Interactions

CYP3A4 Inhibitors (Strong): May increase the serum concentration of Dutasteride. Monitor therapy


Monitoring Parameters

Objective and subjective signs of relief of benign prostatic hyperplasia, including improvement in urinary flow, reduction in symptoms of urgency, and relief of difficulty in micturition; for serial PSA monitoring, establish a new baseline PSA level after 3 months of therapy and monitor PSA periodically thereafter.


Lab Test Interferences


Test Interactions

PSA levels decrease in treated patients. After 3 months of therapy, PSA levels stabilize to a new baseline that is ~50% of pretreatment values. If following serial PSAs in a patient, re-establish a new baseline after ≥3 months of use. If interpreting an isolated PSA value in a patient treated for ≥3 months, then double the PSA value for comparison.


Adverse Reactions


Frequency of most adverse events (except prostate cancer high grade) tends to decrease with continued use (>6 months). Frequency not always defined.

1% to 10%:

Endocrine & metabolic: Decreased libido ( ≤3%; incidence highest during first 6 months of therapy), gynecomastia (including breast tenderness, breast enlargement; ≤1%), increased luteinizing hormone, increased testosterone level, increased thyroid stimulating hormone level

Genitourinary: Impotence ( ≤5%; incidence highest during first 6 months of therapy), ejaculatory disorder ( ≤2%)

Hematologic & oncologic: Prostate cancer high grade ( ≤1%)

<1% (Limited to important or life-threatening): Cardiac failure, depressed mood, dermatological reaction (serious), dizziness, hypersensitivity, localized edema, malignant neoplasm of breast (males), testicular pain, testicular swelling


Warnings/Precautions


Special Populations: Elderly

Dutasteride half-life increases with age.


Warnings/Precautions

Disease-related concerns:

- Diminished urinary flow: Carefully monitor patients with a large residual urinary volume or severely diminished urinary flow for obstructive uropathy; these patients may not be candidates for dutasteride therapy.

- Hepatic impairment: Use with caution in patients with hepatic impairment.

- Prostate cancer: When compared to placebo, 5-alpha-reductase inhibitors (5-ARIs) have been shown to reduce the overall incidence of prostate cancer, although an increase in the incidence of high-grade prostate cancers has been observed; 5-ARIs are not approved in the US or Canada for the prevention of prostate cancer.

Concurrent drug therapy issues:

- CYP3A4 inhibitors: Use with caution with concurrent use of potent, chronic CYP3A4 inhibitors.

Special handling:

- Hazardous agent: Use appropriate precautions for handling and disposal (NIOSH 2014 [group 3]).

- Women/pregnancy: Active ingredient can be absorbed through the skin; women should always use caution whenever handling. Pregnant women or women trying to conceive should not handle the product; if contact with a leaking capsule occurs, wash area immediately with soap and water; dutasteride may negatively impact fetal development.

Other warnings/precautions:

- Appropriate use: Other urological diseases, including prostate cancer, should be ruled out before initiating therapy.

- Blood donation: Avoid donating blood during or for 6 months following treatment cessation due to risk of administration to a pregnant female transfusion recipient.

- PSA monitoring: Reduces prostate specific antigen (PSA) by ~50% within 3-6 months of use. If following serial PSAs, re-establish a new baseline ≥3 months after treatment initiation; monitor PSA periodically thereafter. If interpreting an isolated PSA value in a patient treated for ≥3 months, then double the PSA value for comparison to a normal PSA value in an untreated man. PSA increases while on dutasteride should be considered suspicious; obtain serial PSA measurements and evaluate (Andriole, 2006). Patients on a 5-ARI with any increase in PSA levels, even if within normal limits, should be evaluated; may indicate presence of prostate cancer.


Pregnancy Risk Factor

X


Pregnancy Considerations

Abnormalities of external male genitalia were reported in animal reproduction studies. Use is not indicated in women. Pregnant women are advised to avoid contact with crushed or broken tablets and the semen from a male partner exposed to dutasteride.


Actions


Pharmacology

Dutasteride is a 4-azo analog of testosterone and is a competitive, selective inhibitor of both reproductive tissues (type 2) and skin and hepatic (type 1) 5α-reductase. This results in inhibition of the conversion of testosterone to dihydrotestosterone and markedly suppresses serum dihydrotestosterone levels.


Absorption

Absorbed via skin when handling capsules


Distribution

Vd: 300 to 500 L, ~12% of serum concentrations partitioned into semen


Metabolism

Hepatic via CYP3A4 and CYP3A5 isoenzymes (extensive); forms metabolites: 6-hydroxydutasteride has activity similar to parent compound, 4 " ²-hydroxydutasteride and 1,2-dihydrodutasteride are much less potent than parent in vitro


Excretion

Feces (40% as metabolites, ~5% as unchanged drug); urine (<1% as unchanged drug); ~55% of dose unaccounted for


Time to Peak

2-3 hours


Half-Life Elimination

Terminal: ~5 weeks


Protein Binding

99% to albumin; ~97% to alpha1-acid glycoprotein; >96% to semen protein


Patient and Family Education


Patient Education

- Discuss specific use of drug and side effects with patient as it relates to treatment. (HCAHPS: During this hospital stay, were you given any medicine that you had not taken before? Before giving you any new medicine, how often did hospital staff tell you what the medicine was for? How often did hospital staff describe possible side effects in a way you could understand?)

- Patient may experience dizziness, sexual dysfunction, or decreased libido. Have patient report immediately to prescriber lump in breast, breast pain or soreness, enlarged breasts, or depression (HCAHPS).

- Educate patient about signs of a significant reaction (eg, wheezing; chest tightness; fever; itching; bad cough; blue skin color; seizures; or swelling of face, lips, tongue, or throat). Note: This is not a comprehensive list of all side effects. Patient should consult prescriber for additional questions.

Intended Use and Disclaimer: Should not be printed and given to patients. This information is intended to serve as a concise initial reference for healthcare professionals to use when discussing medications with a patient. You must ultimately rely on your own discretion, experience and judgment in diagnosing, treating and advising patients.

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