Each film-coated tablet contains: Dutasteride 500 mcg, Excipients q.s.
Pharmacology: Pharmacodynamics: Effect on 5a-Dihydrotestosterone and Testosterone: The maximum effect of daily doses of Dutasteride on the reduction of DHT is dose dependent and is observed within 1 to 2 weeks. After 1 and 2 weeks of daily dosing with Dutasteride 0.5 mg, median serum DHT concentrations were reduced by 85% and 90%, respectively.
Mechanism of Action: Dutasteride inhibits the conversion of testosterone to dihydrotestosterone (DHT). DHT is the androgen primarily responsible for the initial development and subsequent enlargement of the prostate gland. Testosterone is converted to DHT by the enzyme 5a-reductase, which exists as 2 isoforms, type 1 and type 2. The type 2 isoenzyme is primarily active in the reproductive tissues, while the type 1 isoenzyme is also responsible for testosterone conversion in the skin and liver.
Dutasteride is a competitive and specific inhibitor of both type 1 and type 2 5a-reductase isoenzymes, with which it forms a stable enzyme complex.
Pharmacokinetics: Absorption: Following administration of a single 0.5-mg dose of a tablet, time to peak serum concentrations (Tmax) of Dutasteride occurs within 2 to 3 hours.
Absolute bioavailability in 5 healthy subjects is approximately 60% (range, 40% to 94%). When the drug is administered with food, the maximum serum concentrations were reduced by 10% to 15%. This reduction is of no clinical significance.
Distribution: Pharmacokinetic data following single and repeat oral doses show that Dutasteride has a large volume of distribution (300 to 500 L). Dutasteride is highly bound to plasma albumin (99.0%) and alpha-1 acid glycoprotein (96.6%).
Metabolism and Elimination: Dutasteride is extensively metabolized in humans. In vitro studies showed that Dutasteride is metabolized by the CYP3A4 and CYP3A5 isoenzymes. Both of these isoenzymes produced the 4'-hydroxy-dutasteride, 6-HYDROXYDUTASTERIDE, and the 6,4'-dihydroxydutasteride metabolites. In addition, the 15-hydroxydutasteride metabolite was formed by CYP3A4. Dutasteride is not metabolized in vitro by human cytochrome P450 isoenzymes CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, and CYP2E1. In human serum following dosing to steady state, unchanged Dutasteride, 3 major metabolites (4'-hydroxydutasteride, 1,2-dihydrodutasteride, and 6-hydroxydutasteride), and 2 minor metabolites (6,4'-dihydroxydutasteride and 15-hydroxy-dutasteride), as assessed by mass spectrometric response, have been detected.
Dutasteride and its metabolites were excreted mainly in feces. As a percent of dose, there was approximately 5% unchanged Dutasteride (~1% to ~15%) and 40% as Dutasteride-related metabolites (~2% to ~90%). Only trace amounts of unchanged Dutasteride were found in urine (< 1%). Therefore, on average, the dose unaccounted for approximated 55% (range, 5% to 97%).
Dutasteride is indicated in the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to: improve symptoms, reduce the risk of acute urinary retention (AUR), and reduce the risk of the need for BPH-related surgery.
The tablets should be swallowed whole and not chewed or opened, as contact with the tablet contents may result in irritation of the oropharyngeal mucosa. Dutasteride may be administered with or without food, or as prescribed by the physician.
Monotherapy: The recommended dose of Dutasteride is one tablet (500 mcg) taken once daily.
There is no specific antidote for Dutasteride. Therefore, in cases of suspected overdosage, symptomatic and supportive treatment should be given as appropriate, taking the long half-life of Dutasteride into consideration.
Dutasteride is contraindicated for use in: Use in Pregnancy: Dutasteride may cause fetal harm when administered to a pregnant woman. If Dutasteride is used during pregnancy or if the patient becomes pregnant while taking Dutasteride, the patient should be apprised of the potential hazard to the fetus.
Women of childbearing potential.
Pediatric patients.
Patients with previously demonstrated clinically significant hypersensitivity (e.g., serious skin reactions, angioedema) to Dutasteride or other 5-Alpha Reductase Inhibitors.
Effects on Prostate-Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection: Dutasteride reduced serum PSA concentration by approximately 50% within 3 to 6 months of treatment. This decrease was predictable over the entire range of PSA values in subjects with symptomatic BPH, although it may vary in individuals. Dutasteride may also cause decreases in serum PSA in the presence of prostate cancer.
Increased Risk of High-Grade Prostate Cancer: In men aged 50 to 75 years with a prior negative biopsy for prostate cancer and a baseline PSA between 2.5 ng/mL and 10.0 ng/mL taking Dutasteride in the 4-year Reduction by Dutasteride of Prostate Cancer Events (REDUCE) trial, there was an increased incidence of Gleason score 8-10 prostate cancer compared with men taking placebo (Dutasteride 1.0% versus placebo 0.5%). 5-Alpha Reductase Inhibitors may increase the risk of development of high-grade prostate cancer.
Evaluation for Other Urological Diseases: Prior to initiating treatment with Dutasteride, consideration should be given to other urological conditions that may cause similar symptoms. In addition, BPH and prostate cancer may coexist.
Exposure of Women-Risk to Male Fetus: Dutasteride should not be handled by a woman who is pregnant or who could become pregnant. Dutasteride is absorbed through the skin and could result in unintended fetal exposure. If a woman who is pregnant or who could become pregnant comes in contact with leaking Dutasteride capsules, the contact area should be washed immediately with soap and water.
Blood Donation: Men being treated with Dutasteride should not donate blood until at least 6 months have passed following their last dose. The purpose of this deferred period is to prevent administration of Dutasteride to a pregnant female transfusion recipient.
Effect on Semen Characteristics: The effects of Dutasteride 500 mcg/day on semen characteristics for an individual patient's fertility is not known.
Renal Impairment: No dose adjustment is necessary for Dutasteride in patients with renal impairment.
Hepatic Impairment: The effect of hepatic impairment on Dutasteride pharmacokinetics has not been studied. Because Dutasteride is extensively metabolized, exposure could be higher in hepatically impaired patients.
Use in Children: Dutasteride is contraindicated for use in pediatric patients. Safety and effectiveness in pediatric patients have not been established.
Use in Elderly: No overall differences in safety or efficacy were observed between these subjects and younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out.
Use in Pregnancy: Pregnancy Category X. Dutasteride is contraindicated for use in women of childbearing potential and during pregnancy. Dutasteride is a 5-Alpha Reductase Inhibitor that prevents conversion of testosterone to dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia. Dutasteride may cause fetal harm when administered to a pregnant woman. If Dutasteride is used during pregnancy or if the patient becomes pregnant while taking Dutasteride, the patient should be apprised of the potential hazard to the fetus.
Abnormalities in the genitalia of male fetuses is an expected physiological consequence of inhibition of the conversion of testosterone to DHT by 5-Alpha Reductase Inhibitors. These results are similar to observations in male infants with genetic 5 alpha-reductase deficiency. Dutasteride is absorbed through the skin. To avoid potential fetal exposure, women who are pregnant or could become pregnant should not handle Dutasteride. Dutasteride is secreted into semen. The highest measured semen concentration of Dutasteride in treated men was 14 ng/mL. Assuming exposure of a 50-kg woman to 5 mL of semen and 100% absorption, the woman's Dutasteride concentration would be about 0.0175 ng/mL. This concentration is more than 100 times less than concentrations producing abnormalities of male genitalia in animal studies. Dutasteride is highly protein bound in human semen (greater than 96%), which may reduce the amount of Dutasteride available for vaginal absorption.
Use in Lactation: Dutasteride is contraindicated for use in women of childbearing potential, including nursing women. It is not known whether dutasteride is excreted in human milk.
The most common adverse reactions reported in subjects receiving Dutasteride were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), and ejaculation disorders. The most common adverse reactions reported in subjects receiving combination therapy (Dutasteride plus Tamsulosin) were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), ejaculation disorders, and dizziness. Ejaculation disorders occurred significantly more in subjects receiving combination therapy (11%) compared with those receiving Dutasteride (2%) or Tamsulosin (4%) as monotherapy.
The most common adverse reaction leading to trial withdrawal was impotence (1%).
Cytochrome P450 3A Inhibitors: Dutasteride is extensively metabolized in humans by the CYP3A4 and CYP3A5 isoenzymes. Because of the potential for drug-drug interactions, use caution when prescribing Dutasteride to patients taking potent, chronic CYP3A4 enzyme inhibitors (e.g., ritonavir).
Calcium Channel Antagonists: Coadministration of verapamil or diltiazem decreases Dutasteride clearance and leads to increased exposure to Dutasteride. The change in Dutasteride exposure is not considered to be clinically significant. No dose adjustment is recommended.
Cholestyramine: Administration of a single 500-mcg dose of Dutasteride followed 1 hour later by 12 g of cholestyramine does not affect the relative bioavailability of Dutasteride.
Store at temperatures not exceeding 30°C. Protect from light and moisture.
Shelf Life: 36 Months.
G04CB02 - dutasteride ; Belongs to the class of testosterone-5-alpha reductase inhibitors. Used in the treatment of benign prostatic hypertrophy.
Dutasia 0.5 FC tab 500 mcg
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