Avodart (Dutasteride) inhibits the activation of testosterone. It is used in the treatment of benign prostatic hyperplasia and baldness in men (androgenic alopecia).

Dutasteride (Avodart) Uses:

• Benign Prostatic Hyperplasia (BPH):

  • It is used in the symptomatic treatment of benign prostatic hyperplasia (BPH) as monotherapy or in combination with tamsulosin to improve the lower urinary tract obstructive symptoms, prevent the development of acute urinary retention, and to reduce the risk of need for prostatic surgery.
• Limitations of use: It is not approved for the prevention of prostate cancer.

• Off-Label Use of Dutasteride in Adults:

  • Male pattern baldness

Adult dose:

Dutasteride (Avodart) Dose in the treatment of Benign prostatic hyperplasia (BPH):

• Dutasteride 0.5 mg capsules once a day orally alone or in combination with tamsulosin

Use in Children:

It's use is contraindicated in children.

Pregnancy Risk Factor X

• Pregnant women should not use it.
• Pregnant women are advised to avoid handling and touching the drug.
• It can be seen through the skin intact and may cause abnormalities in the genitalia external to the fetus.
• Barrier contraception should be used by men who have a female partner who is pregnant.
• Seminal fluid can cause malformations in the genitalia of the fetus.

Dutasteride use during breastfeeding:

• It is unknown if the drug will be excreted into breastmilk.
• It is not recommended for women who are pregnant.

Renal dose:

Dutasteride (Avodart) Dose in Kidney disease:

Adjustment in the dose is not necessary in patients with kidney disease (as the drug is metabolized in the liver). [/bg_collapse]   

Dutasteride (Avodart) Dose in Liver disease:

The manufacturer has not recommended any adjustments in the dose. However, since dutasteride is extensively metabolized in the liver, drug exposure in patients with liver disease may be increased. Higher doses in patients with hepatic impairment should be avoided. 

Side Effects of Dutasteride (Avodart):

• Endocrine & Metabolic:

  • Decreased Libido
  • Gynecomastia Including
    • Breast Tenderness
    • Breast Enlargement
  • Increased Luteinizing Hormone
  • Increased Testosterone Level
  • Increased Thyroid Stimulating Hormone Level

• Genitourinary:

  • Impotence
  • Ejaculatory Disorder

• Hematologic & Oncologic:

  • Prostate Cancer High Grade

Contraindications to Dutasteride (Avodart):

• Severe allergic reactions to the dutasteride, other 5-alpha-reductase inhibitors (eg, finasteride), or any component of the formulation
• use in children
• females of childbearing potential;
• pregnancy

Warnings and Precautions

• Diminished urinary flow:

  • Patients with large residual urinary volume and markedly reduced urinary flow should be closely monitored. These patients may not be candidates for dutasteride therapy.

• Hepatic impairment:

  • Use the drug with caution in patients with liver disease.

• Prostate cancer:

  • Dutasteride reduces the overall incidence of prostatic cancer, however, the incidence of high-grade prostate cancers has been observed to increase.
  • It is not approved for the prevention of prostatic cancer in the US and Canada.

Dutasteride: Drug Interaction

Note: Drug Interaction Categories:

• Risk Factor C: Monitor When Using Combination
• Risk Factor D: Consider Treatment Modification
• Risk Factor X: Avoid Concomitant Use

Monitoring parameters:

• Monitor the clinical features of BPH (benign prostatic hyperplasia) both subjectively and objectively.
• Monitor for the symptomatic relief in urinary urgency, dysuria (difficulty in micturition), and improvement in urinary flow.
• Monitor PSA levels serially at baseline and three months thereafter (and periodically as indicated).

How to administer Dutasteride (Avodart)?

• It may be administered orally without regard to meals.
• The capsules should not be opened, crushed, or chewed and swallowed whole.
• It may cause local irritation if the opened capsule comes in contact with the oropharynx.
• The drug should not be handled or touched by women of childbearing age especially those who are pregnant.

Mechanism of action of Dutasteride (Avodart):

• Dutasteride inhibits the competitive and selectively inhibited enzyme 5 - alpha reductase. 
• It inhibits Type 1 and Type 2 enzymes, which are found in the skin, liver, and reproductive tissues.
• The inhibition of the enzyme 5 beta-reductase prevents testosterone from being converted to dihydrotestosterone (the active version of testosterone).

Absorption:

• While handling, absorption via the skin may occur.

Distribution:

• About 12% of the serum concentration is partitioned into semen

Protein binding:

• 99% of the drug is bound to albumin
• About 97% to alpha -acid glycoprotein and >96% to semen protein

Metabolism:

• It is metabolized via the liver enzymes CYP3A4 and CYP3A5 isoenzymes. It forms the following metabolites:
  • 6hydroxydutasteride (Similar activity as the parent compound)
  • 4′-hydroxydutasteride and 1,2dihydrodutasteride (These are much less potent than the parent compound in vitro)

Bioavailability:

• About 60% (range: 40% to 94%)

Terminal Half-life elimination:

• About five weeks

Time to peak:

• 2-3 hours

Excretion:

• Feces (40% as metabolites, about 5% as unchanged drug);
• Urine (<1% as unchanged drug);

International Brands of Dutasteride:

• ACT Dutasteride
• APO-Dutasteride
• AURO-Dutasteride
• MED-Dutasteride
• MINT-Dutasteride
• PMS-Dutasteride
• RIVA-Dutasteride
• SANDOZ Dutasteride
• TEVA-Dutasteride
• Armonia
• Avidart
• Avodart
• Avolve
• Bengiride
• Duagen
• Duavo
• Duprost
• Dutagen
• Dutamax
• Dutamex
• Dutasia
• Dutaslow
• Dutesmol
• Neodart
• Prostasil
• Prostatex
• Quedute
• Terod
• Urodart
• Zagallo

Dutasteride Brand Names in Pakistan: