Pharmacological action Avodart 0.5 mg
Avodart Drug for the treatment of benign prostatic hyperplasia. Inhibits the activity of 5α-reductase isozymes types 1 and 2, are responsible for the conversion of testosterone to 5α-dihydrotestosterone (DHT). DHT is the primary androgen responsible for hyperplasia of the glandular tissue of the prostate.
The maximum effect of dutasteride on the reduction of the concentration of DHT is dose-dependent and occurs within 1-2 weeks. after starting treatment. After 1 and 2 weeks. receiving dutasteride at a dose of 0.5 mg / day average concentrations of DHT in serum is reduced by 85% and 90%.
The drug reduces the size of the prostate, improves urination and reduces the risk of acute urinary retention and the need for surgical treatment.
Pharmacokinetics Avodart 0.5 mg
Absorption
After receiving single a dose of 500 mg of dutasteride in Cmax serum obtained within 1-3 h. The 2-hour in / infusion absolute bioavailability of approximately 60%. The bioavailability of dutasteride is independent of food intake.
Distribution
Plasma protein binding is high – more than 99.5%. Vd – 300-500 hp.
With daily dosing of dutasteride in the serum concentration reaches 65% of Css in 1 month and approximately 90% of this level in 3 months.
Css dutasteride in serum were approximately 40 ng / ml, achieved after 6 months of daily administration of the drug at a dose of 500 mcg. In sperm, as well as in serum, Css dutasteride also achieved at 6 months. Through 52 weeks. treatment concentration of dutasteride in the sperm are on average 3.4 ng / ml (0.4-14 ng / ml). Of serum in the sperm enters approximately 11.5% of dutasteride.
Metabolism
In vitro dutasteride is metabolized by isoenzyme CYP3A4 to form two secondary metabolites monogidroksilirovannyh, however, it does not act isoenzymes CYP2C9, CYP2C19 and CYP2D6. After reaching the Css of dutasteride in serum by mass-spectrometric method detected unchanged dutasteride, 3 major metabolites (4 “gidroksidutasterid, 1,2 -, and 6 digidrodutasterid – gidroksidutasterid) and two minor metabolites.
Breeding
Dutasteride is subjected to intensive metabolism. After oral administration at a dose of 500 mg / day until reaching the equilibrium state 1-15.4% (average 5.4%) of the dose is excreted in the feces unchanged. The remainder of the dose excreted as 4 major metabolites, constituting 39%, 21%, 7% and 7%, respectively, and 6 small metabolites (the share of each of which represents less than 5%).
A urine output in humans, trace amounts of unchanged dutasteride (less than 0.1% of dose).
When administered at therapeutic doses of dutasteride his final T1 / 2 at 3-5 weeks.
Dutasteride is found in serum (at concentrations higher than 0.1 ng / ml) up to 4-6 months after cessation of administration.
The pharmacokinetics of dutasteride can be described as a process of absorption and first order elimination of two parallel processes, one saturable (ie, dependent on the concentration) and an unsaturated (ie, not dependent on the concentration).
At low concentrations in serum (less than 3 ng / ml), dutasteride is rapidly excreted by the two processes of elimination. After a single oral doses of 5 mg or less dutasteride rapidly excreted from the body and has a short T1 / 2 of 3-5 days.
At concentrations in the serum of more than 3 ng / ml less than the clearance of dutasteride – 0.35-0.58 l / h, with excretion occurs mainly through the unsaturated linear process with a finite T1 / 2 of 3-5 weeks. At therapeutic concentrations, on the background of daily administration of the drug at a dose of 500 mcg dominates the slower clearance of dutasteride, the total clearance is linear and not dependent on the concentration of character.
Pharmacokinetics in special clinical situations Avodart 0.5 mg
Pharmacokinetics and pharmacodynamics of dutasteride were studied in 36 healthy men aged 24 to 87 years after taking the drug in a single dose of 5 mg. Between age groups was not statistically significant differences in pharmacokinetic parameters such dutasteride as AUC and Cmax. There was no statistically significant differences in T1 / 2 of dutasteride between the age group 50-69 years age group older than 70 years, which includes the majority of men with benign prostatic hyperplasia.
Between age groups was not significant difference in the degree of reduction of the levels of DHT. These results indicate that there is no need to reduce the dose of dutasteride in the elderly
Statement Avodart 0.5 mg
- Treatment of benign prostatic hyperplasia (to reduce prostate size, improve urine flow, reduce the risk of acute urinary retention and need surgery).
Dosage regimen Avodart 0.5 mg
For adult men, including elderly patients, the recommended dose for ingestion of 500 mg (1 cap.) 1 times / day. The capsules should be taken as a whole. The drug can be taken irrespective of food intake.
The effect is quite fast, but treatment should continue for at least 6 months in order to objectively evaluate the effect of the drug.
Renal impairment dose reduction is required (because while taking the drug at a dose of 500 mg / day in the urine is allocated less than 0.1% of dose).
Must be used with caution on patients with impaired liver function, as dutasteride is subjected to intensive metabolism in the liver, and its T1 / 2 at 3-5 weeks.
Side effect Avodart 0.5 mg
Part of the reproductive system: erectile dysfunction, a change (decrease) in libido, ejaculation disorder, gynecomastia (includes tenderness and breast enlargement).
Allergic reactions: in some cases – a rash, itching, urticaria, localized edema.
Contraindications Avodart 0.5 mg
- Hypersensitivity to dutasteride, and other components of the drug;
- Increased sensitivity to other inhibitors of 5α-reductase.
Avodart is contraindicated for women and children.
Use in hepatic dysfunction Avodart 0.5 mg
Must be used with caution on patients with impaired liver function, t.k.dutasterid subjected to intensive metabolism in the liver, and its T1 / 2 at 3-5 weeks.
Use in renal impairment Avodart 0.5 mg
Renal impairment dose reduction is required (because while taking the drug at a dose of 500 mg / day in the urine is allocated less than 0.1% of dose).
Cautions
Dutasteride is absorbed through the skin, so women and children should avoid contact with damaged capsules. In case of contact with damaged capsules should immediately wash the skin area corresponding with soap and water.
In patients with benign prostatic hyperplasia, should conduct a digital rectal examination and other methods of investigation of the prostate before treatment with Avodart and periodically repeat these studies in the treatment process to prevent prostate cancer.
Determination of the concentration of prostate-specific antigen in serum is an important component of the complex studies aimed at identifying prostate cancer. Typically, an additional examination is carried out in patients with a concentration of prostate-specific antigen greater than 4 ng / ml, in such cases can be shown to a biopsy of the prostate. Baseline prostate-specific antigen less than 4 ng / ml in patients receiving dutasteride does not exclude the diagnosis of prostate cancer.
After therapy Avodart for 6 months a decrease in serum prostate-specific antigen in patients with benign prostatic hyperplasia by approximately 50%, even in the presence of prostate cancer. Despite individual variability, the decline in prostate-specific antigen by approximately 50% observed over the entire range of initial values of concentrations of prostate-specific antigen (from 1.5 to 10 ng / ml). Therefore, when interpreting the level of prostate-specific antigen in men who received Avodart for 6 months or more, the measured level should be multiplied by 2, and then compare it to normal levels in men not receiving Avodart.
Effects on ability to drive and control mechanisms
Receiving Avodart no effect on ability to drive a car and operate machinery.
Overdose Avodart 0.5 mg
In case of overdose (the dose 80 times higher than therapeutic) side effects were noted.
Avodart no specific antidote, and so if you suspect an overdose rather spend symptomatic and supportive treatment.
Drug Interactions Avodart 0.5 mg
Because dutasteride is metabolized by isoenzyme CYP3A4, CYP3A4 inhibitors in the presence of concentrations of dutasteride may increase in the blood.
With the simultaneous use of dutasteride with CYP3A4 inhibitors verapamil and diltiazem have declined clearance. However, amlodipine, another calcium channel blocker, does not reduce the clearance of dutasteride.
With simultaneous use of Avodart and inhibitors of CYP3A4 reduced clearance of dutasteride and the subsequent increase of its concentration in the blood is not significant because of the wide therapeutic range for this drug, so there is no need to reduce the dose.
In vitro CYP1A2, CYP2C9, CYP2C19 and CYP2D6 isoenzymes are not involved in the metabolism of dutasteride in humans dutasteride does not inhibit cytochrome P450 enzymes, a person involved in the metabolism of drugs.
When applied simultaneously with dutasteride lipid-lowering drugs, ACE inhibitors, beta-blockers, calcium channel blockers, corticosteroids, diuretics, NSAIDs, inhibitors of PDE 5 and antibiotic derivatives of quinolone, any significant drug interactions can be identified.
In the application within 2 weeks of dutasteride or tamsulosin in conjunction with terazosin did not reveal any pharmacokinetic or pharmacodynamic interaction.
With the simultaneous use of dutasteride and tamsulosin for 9 months demonstrated good tolerability of this combination.
Dutasteride does not displace warfarin, diazepam and phenytoin in sections of their binding to plasma proteins, and these drugs are, in turn, do not displace dutasteride. Warfarin, digoxin, and kolestiramin not interact with dutasteride.
