Avodart, Dutasteride An Overiew
Avodart [Dutasteride], marketed by GSK, is a 5-alpha-reductase inhibitor used in the treatment of benign prostatic hypertrophy in men with enlarged prostate. Avodart [Dutasteride], blocks the action of the 5-alpha-reductase enzymes that convert testosterone into dihydrotestosterone (DHT). Avodart [Dutasteride] inhibits both isoforms of 5-alpha reductase [Type 1 and Type 2] unlike finasteride, a drug belonging to the same class of drugs but inhibiting only one form of 5-alpha reductase. It is a competitive and specific inhibitor of 5-alpha-reductase enzyme.
Avodart [Dutasteride] helps improve urinary flow and may also reduce for a prostatic surgery later on.
It also helps in decreasing the chances of carcinoma prostate.
Benign Prostate Hypertrophy:
Benign prostate hypertrophy also known as benign enlargement of prostate is a condition seen in middle aged men and elder men in which there is increase in the size of prostate.
There is hyperplasia of prostatic stromal cells and epithelial cells leading to formation of large nodules in the peri-urethral area of the prostate.
Hence if these nodules are large enough then they can suppress the urethral canal completely or partially leading to obstruction in urine flow leading to
- urinary hesitancy,
- frequent urination
- increased risk of urinary tract infections due to stasis of bacteria in the bladder residue
- incomplete voiding
- Post-urination dribble
- Nocturia– need to urinate during the night
- Dysuria: painful urination
- weak urinary stream,
- Urinary retention which may be acute [inability to void] or chronic in which there is gradual increase in the residual urinary volume, distending the bladder. This may lead to renal failure termed as obstructive uropathy.
- Urinary bladder stone formation.
Dihydrotestosterone, a metabolite of testosterone plays a critical role in the growth of prostate. Dihydrotestosterone is synthesized under the action of the enzyme 5α-reductase, type 2 in the prostate from the circulating testosterone. Since this enzyme is localized primarily in the stromal cells; hence, these cells are the main site for the synthesis of dihydrotestosterone.
Although all men show prostate hypertrophy as they age, especially after 70 years, the incidence of symptomatic prostatic hypertrophy is observed more in men have a western lifestyle than in men from rural areas.
Benign hypertrophy of prostate is associated with increased levels of serum ‘prostate specific antigen [PSA]’ which is a marker for carcinoma prostate, it is not considered to be a pre-malignant condition.
This condition is diagnosed mainly by rectal examination and by ultrasonography.
Indications and dosage:
- Monotherapy: Symptomatic treatment of benign prostatic hyperplasia in men with enlarged prostate by improving symptoms, reducing the risk of acute retention of urine and reduce the risk of benign prostatic hyperplasia related surgery.
- In combination with an alpha blocker: Avodart [Dutasteride] along with tamsulosin is indicated for the treatment of symptomatic BPH in men with an enlarged prostate.
- Clinical trials for dutasteride as a hair loss drug were undertaken, but called off in late 2002. Industry sources speculate that Avodart would have been seen as too similar to Propecia to have proved profitable as a hair loss treatment. However, phase II results indicated that dutasteride 2.5mg generated a superior hair count to finasteride 5mg at 12 and 24 weeks. Phase III trials have been started in Korea, however the future of this drug for male pattern baldness depends upon the clearance by the FDA.
Avodart [Dutasteride] is used to treat urinary symptoms of Enlarging Prostate, and to reduce the risk of acute urinary retention (AUR) and prostate surgery.
Dosage: available in capsule form of 0.5 mg each
- Monotherapy : the recommended daily dose of Avodart [Dutasteride] is 0.5mg
- Along with an alpha blocker: the recommended dose is Avodart [Dutasteride] 0.5 mg once daily and tamsulosin 0.4 mg once daily.
- presence of other urological disorders: especially carcinoma prostate
- Blood donation: patients who were on Avodart [Dutasteride] should refrain from donating blood for 6 months since there is a possibility of the blood being transfused to a pregnant female who might be carrying a male fetus.
- There have not been conclusive studies in the event of taking Avodart [Dutasteride] in the presence of hepatic failure or renal failure. This drug is highly metabolized in the liver and hence advisable to be avoided in hepatic failure.
- Avodart [Dutasteride] can be used safely in geriatric population.
- Avodart [Dutasteride] is secreted in the semen. It does not alter the sperm concentration and sperm morphology. However the clinical significance of its effect on semen characteristics for an individual patient's fertility is not known.
- Patients who present with hypersensitivity to Avodart [Dutasteride] or other 5 alpha reductase inhibitors.
- Pregnancy: Dutasteride inhibits the activity of 5α-reductase, which prevents conversion of testosterone to dihydrotesterone which is necessary for normal development of male genitalia. Hence male fetuses of pregnant females taking Avodart [Dutasteride] are at increased risk of abnormal external genitalia. It is advised that pregnant females should not even touch the capsule of Avodart [Dutasteride] since it is speculated that there may be some absorption through skin. The contact area should be immediately washed with soap and water.
- Women of child bearing age
- decreased libido
- ejaculatory defects
- Breast disorders (like breast enlargement and tenderness)
Long-Term Treatment (Up to 4 Years): Long term treatment with Avodart [Dutasteride] is not found to be associated increased incidence of drug-related sexual adverse reactions (impotence, decreased libido, and ejaculation disorder) or breast disorders. No relationship between long-term use of Avodart [Dutasteride] and male breast neoplasia has been found out till date.
In combination with alpha blocker tamsulosin:
- decreased libido
- defect in ejaculation
- breast disorders (like breast enlargement and tenderness)
Hypersensitivity reactions like uritacaria, rash, pruritis, angioneurotic edema, etc.
- Calcium Channel Antagonists: they decrease the clearance of Avodart [Dutasteride]
- HIV /AIDS medicine such as nelfinavir or ritonavir
- Antibiotics such as clarithromycin, erythromycin, itraconazole, ketoconazole, or troleandomycin.
- Selective serotonin reuptake inhibitor like fluoxetine, fluvoxamine, or paroxetine
- tricyclic antidepressant such as amitriptyline, amoxapine, clomipramine, desipramine, doxepin, imipramine, nortriptyline, protriptyline, or trimipramine
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