dutasteride

Avodart

Pharmacologic class: Synthetic 4-azasteroid compound

Therapeutic class: 5-alpha-reductase inhibitor, sex hormone

Pregnancy risk category X

Action

Inhibits 5-alpha-reductase, an intracellular enzyme present in liver, skin, and prostate that's required for conversion of testosterone to 5-alpha-dihydrotestosterone (DHT). DHT appears to be the principal androgen responsible for stimulating prostatic growth.

Availability

Capsules: 0.5 mg

Indications and dosages

➣ Symptomatic benign prostatic hypertrophy (alone or in combination with tamsulosin)

Adults: 0.5 mg P.O. daily

Contraindications

• Hypersensitivity to drug, its components, other 5-alpha-reductase inhibitors, xanthines (such as coffee, theobromine), or ethylenediamine

• Women

• Children

Precautions

Use cautiously in:

• hepatic impairment.

Administration

• Don't handle drug if you're pregnant or plan to become pregnant.

• Don't open or crush capsule.

• Give without regard to food.

Adverse reactions

GI: dyspepsia

GU: decreased libido, decreased ejaculatory volume, erectile dysfunction, gynecomastia

Interactions

Drug-drug. Cimetidine, ciprofloxacin, diltiazem, ketoconazole, other drugs metabolized by CYP450-3A4 pathway, ritonavir, verapamil: increased dutasteride blood level

Drug-diagnostic tests. Prostate-specific antigen (PSA): decreased level

Thyroid-stimulating hormone: increased level

Patient monitoring

• Monitor fluid intake and output. Assess for ease of starting urine stream and for urinary urgency or frequency.

• Check baseline PSA level; reevaluate at 3 to 6 months.

Patient teaching

• Tell patient to take drug with full glass of water without crushing or opening capsule.

• Instruct patient not to take capsule if it's cracked or leaking.

• Inform patient that drug decreases testosterone production in prostate.

• Tell patient to report dysuria and urinary urgency.

See Advise patient not to donate blood for at least 6 months after final dose.

• Inform patient that drug may decrease ejaculatory volume.

• Explain that sexual side effects eventually will subside.

• As appropriate, review all other significant adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

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dutasteride

(doo-tas-te-ride) dutasteride,

Avodart

(trade name)

Classification

Therapeutic: benign prostatic hyperplasia bph agents
Pharmacologic: androgen inhibitors
Pregnancy Category: X

Indications

Management of the symptoms of benign prostatic hyperplasia (BPH) in men with an enlarged prostate gland (alone or with tamsulosin).

Action

Inhibits the enzyme 5-alpha-reductase, which is responsible for converting testosterone to its potent metabolite 5-alpha-dihydrotestosterone in the prostate gland and other tissues. 5-Alpha-dihydrotestosterone is partly responsible for prostatic hyperplasia.

Therapeutic effects

Reduced prostate size with associated decrease in urinary symptoms.

Pharmacokinetics

Absorption: Well absorbed (60%) following oral administration; also absorbed through skin.Distribution: 11.5% of serum concentration partitions into semen.Protein Binding: 99% bound to albumin; 96.6% bound to alpha-1 glycoprotein.Metabolism and Excretion: Mostly metabolized by the liver via the CYP3A4 metabolic pathway; metabolites are excreted in feces.Half-life: 5 wk.

Time/action profile (reduction in dihydrotestosterone levels†)

ROUTE	ONSET	PEAK	DURATION
PO	unknown	1–2 wk	unknown

†Symptoms may only improve over 3–12 mo

Contraindications/Precautions

Contraindicated in: Hypersensitivity;Cross-sensitivity with other 5-alpha-reductase inhibitors may occur;Women; Pediatric: Children.Use Cautiously in: Hepatic impairment.

Adverse Reactions/Side Effects

Central nervous system

depressed mood

Genitourinary

prostate cancer (high-grade) (life-threatening)
↓ libido
ejaculation disorders
erectile dysfunction
testicular pain
testicular swelling

Endocrinologic

gynecomastia

Dermatologic

rash
urticaria

Miscellaneous

allergic reactions (life-threatening)
angioedema (life-threatening)

Interactions

Drug-Drug interaction

Blood levels and effects may be ↑ by ritonavir, ketoconazole, verapamil, diltiazem, cimetidine, ciprofloxacin, or other CYP3A4 enzyme inhibitors.

Route/Dosage

Oral (Adults) 0.5 mg once daily (with or without tamsulosin).

Availability (generic available)

Soft gelatin capsules: 0.5 mg In combination with: tamsulosin (Jalyn); see combination drugs.

Nursing implications

Nursing assessment

Assess patient for symptoms of prostatic hyperplasia (urinary hesitancy, feeling of incomplete bladder emptying, interruption of urinary stream, impairment of size and force of urinary stream, terminal urinary dribbling, straining to start flow, dysuria, urgency) before and periodically during therapy.
Digital rectal examinations should be performed before and periodically during therapy for BPH.
Lab Test Considerations: Serum prostate-specific antigen (PSA) concentrations, used to screen for prostate cancer, decrease by about 20% within the 1st mo of therapy and stabilize at about 50% of the pretreatment level within 6 mo. New baseline PSA concentrations should be established at 3 and 6 mo of therapy and evaluated periodically during therapy. Any increase in PSA during dutaseride therapy may be a sign of prostate cancer and should be evaluated, even those within normal limits. Isolated PSA values from men taking dutaseride for 3 mo or more should be doubled for comparison in untreated men.

Potential Nursing Diagnoses

Impaired urinary elimination (Indications)

Implementation

Oral: Administer once daily with or without meals. Do not break, crush, or chew capsule.

Patient/Family Teaching

Instruct patient to take dutasteride at the same time each day as directed, even if symptoms improve or are unchanged. Take missed doses as soon as remembered later in the day or omit dose. Do not make up by taking double doses the next day.
Caution patient that sharing of dutasteride may be dangerous.
Inform patient that the volume of ejaculate may be decreased during therapy but that this will not interfere with normal sexual function.
Advise patient to avoid donating blood for at least 6 mo after last dose of dutasteride to prevent a pregnant female from receiving dutasteride through a blood transfusion.
Inform patient of potential increase risk in high-grade prostate cancer.
Caution patient that dutasteride poses a potential risk to a male fetus. Women who are pregnant or may become pregnant should avoid exposure to semen of a partner taking dutasteride and should not handle dutasteride because of the potential for absorption.
Emphasize the importance of periodic follow-up exams to determine whether a clinical response has occurred.

Evaluation/Desired Outcomes

Decrease in urinary symptoms of BPH.

dutasteride

A drug that reduces production of dihydrotestosterone by inhibiting both types of the enzyme 5-alpha-reductase and is used to control benign prostatic hyperplasia and reduce the risk of acute urinary retention. Dutasteride is said to be more effective in this role than FINASTERIDE (Proscar). Like all testosterone antagonists this drug can cause reduced sexual interest, impotence, ejaculation problems, breast tenderness and breast enlargement (gynecomastia). A brand name is Avodart.