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Avodart [Dutasteride], marketed by GSK, is a 5-alpha-reductase inhibitor usedin the treatment of benign prostatic hypertrophy in men with enlarged prostate.Avodart [Dutasteride], blocks the action of the 5-alpha-reductase enzymes thatconvert testosterone into dihydrotestosterone (DHT). Avodart [Dutasteride]inhibits both isoforms of 5-alpha reductase [Type 1 and Type 2] unlikefinasteride, a drug belonging to the same class of drugs but inhibiting onlyone form of 5-alpha reductase. It is a competitive and specific inhibitor of5-alpha-reductase enzyme.
Avodart [Dutasteride] helps improve urinary flow and may also reduce for aprostatic 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 acondition seen in middle aged men and elder men in which there is increase inthe size of prostate.
There is hyperplasia of prostatic stromal cells and epithelial cells leading toformation of large nodules in the peri-urethral area of the prostate.
Hence if these nodules are large enough then they can suppress the urethralcanal 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 thebladder residue
- incomplete voiding
- Post-urination dribble
- Nocturia? need to urinate during the night
- Intermittency
- Dysuria: painful urination
- weak urinary stream,
- straining
- Urinary retention which may be acute [inability to void] or chronic in whichthere is gradual increase in the residual urinary volume, distending thebladder. This may lead to renal failure termed as obstructive uropathy.
- Urinary bladder stone formation.
Dihydrotestosterone, a metabolite of testosterone plays a critical role in thegrowth of prostate. Dihydrotestosterone is synthesized under the action of theenzyme 5α-reductase, type 2 in the prostate from the circulating testosterone.Since this enzyme is localized primarily in the stromal cells; hence, thesecells are the main site for the synthesis of dihydrotestosterone.
Although all men show prostate hypertrophy as they age, especially after 70years, the incidence of symptomatic prostatic hypertrophy is observed more inmen 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, itis not considered to be a pre-malignant condition.
This condition is diagnosed mainly by rectal examination and byultrasonography.
Indications and dosage:
Indications:
- Monotherapy: Symptomatic treatment of benign prostatic hyperplasia in menwith enlarged prostate by improving symptoms, reducing the risk of acuteretention of urine and reduce the risk of benign prostatic hyperplasia relatedsurgery.
- In combination with an alpha blocker: Avodart [Dutasteride] along withtamsulosin is indicated for the treatment of symptomatic BPH in men with anenlarged prostate.
- Clinical trials for dutasteride as a hair loss drug were undertaken, butcalled off in late 2002. Industry sources speculate that Avodart would havebeen seen as too similar to Propecia to have proved profitable as a hair losstreatment. However, phase II results indicated that dutasteride 2.5mg generateda superior hair count to finasteride 5mg at 12 and 24 weeks. Phase III trialshave been started in
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.
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Special precautions:
- presence of other urological disorders: especially carcinoma prostate
- Blood donation: patients who were on Avodart [Dutasteride] should refrainfrom donating blood for 6 months since there is a possibility of the bloodbeing 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 ishighly metabolized in the liver and hence advisable to be avoided in hepaticfailure.
- Avodart [Dutasteride] can be used safely in geriatric population.
- Avodart [Dutasteride] is secreted in the semen. It does not alter the spermconcentration and sperm morphology. However the clinical significance of itseffect on semen characteristics for an individual patient's fertility is notknown.
Contraindications:
- Patients who present with hypersensitivity to Avodart [Dutasteride] or other5 alpha reductase inhibitors.
- Pregnancy: Dutasteride inhibits the activity of 5α-reductase, which preventsconversion of testosterone to dihydrotesterone which is necessary for normaldevelopment of male genitalia. Hence male fetuses of pregnant females takingAvodart [Dutasteride] are at increased risk of abnormal external genitalia. Itis advised that pregnant females should not even touch the capsule of Avodart[Dutasteride] since it is speculated that there may be some absorption throughskin. The contact area should be immediately washed with soap and water.
- Women of child bearing age
- Children
Side Effects:
On Monotherapy:
- impotence
- 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-relatedsexual adverse reactions (impotence, decreased libido, and ejaculationdisorder) 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:
- impotence
- decreased libido
- defect in ejaculation
- breast disorders (like breast enlargement and tenderness)
- dizziness
Hypersensitivity reactions like uritacaria, rash, pruritis, angioneuroticedema, etc.
Drug interactions:
- 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, orparoxetine
- tricyclic antidepressant such as amitriptyline, amoxapine, clomipramine,desipramine, doxepin, imipramine, nortriptyline, protriptyline, or trimipramine