Avodart: instructions for using the medicine, structure, Contraindications
Active material: dutasterid
When ATH: G04CB02
CCF: Drug for the treatment of benign prostatic hyperplasia. Ингибитор 5a-редуктазы
ICD-10 codes (testimony): N40
Manufacturer: GlaxoSmithKline Pharmaceuticals (Britain)
Avodart: dosage form, composition and packaging
Capsules gelatin, yellow color, oblong, opaque, marked in red ink “GX CE2” one side.
| 1 caps. | |
| dutasterid | 500 g |
Excipients: mono- and diglycerides Caprylic/kaprinovoj acid, butylhydroksytoluol.
Ingredients of the capsule shell: gelatin, glycerol (glycerol), titanium dioxide E171 (Cl77891), e 172 iron oxide yellow (Cl77492).
10 PC. – blisters (3) – cardboard boxes.
10 PC. – blisters (9) – cardboard boxes.
Avodart: pharmachologic effect
Drug for the treatment of benign prostatic hyperplasia. Inhibits the activity of isoenzymes 5α-reductase 1 and 2 type, which are responsible for the conversion of testosterone to 5α-dihydrotestosterone (DGT). DHT is the primary androgenic, responsible for hyperplasia of prostate glandular tissue.
Maximum impact dutasterida on reduction of dihydrotestosterone is reversible and can be observed through 1-2 Sun. after treatment. Through 1 and 2 Sun. admission dutasterida dose 0.5 mg/day average concentrations of dihydrotestosterone in the serum is reduced by 85% and 90%.
The drug reduces prostate size, improves urination and reduces the risk of acute urinary retention and the need for surgical treatment.
Avodart: pharmacokinetics
Absorption
After receiving a single dose 500 µg Cmax dutasterida in serum obtained during 1-3 no. When the 2-hour in/infusion in the absolute bioavailability is about 60%. The bioavailability of dutasterida does not depend on the meals.
Distribution
Plasma protein binding is high – more 99.5 %. Vd – 300-500 l.
Daily admission dutasterida concentration in the serum of reaches 65% from Css through 1 months and approximately 90% from this level through 3 Months.
Css dutasterida in serum, component of approximately 40 ng / ml, achieved through 6 month daily dose in a dose 500 g. In sperm, as in serum, Css dutasterida also achieved through 6 Months. Through 52 Sun. treatment of dutasterida in the sperm concentration averaged 3.4 ng / ml (0.4-14 ng / ml). From whey in sperm comes around 11.5% dutasterida.
Metabolism
In vitro dutasteride izofermentom CYP3A4 metabolized into two small monogidroksilirovannyh metabolites; However, it can not operate isoenzymes CYP2C9, CYP2C19 and CYP2D6. After reaching Css dutasterida, in serum using mass-spectrometric method to detect unchanged dutasteride, 3 the major metabolite of (4′ gidroksidutasterid, 1,2 – digidrodutasterid and 6 – gidroksidutasterid) and 2 small metabolite.
Deduction
Dutasteride is subjected to intense metabolism. After taking the drug orally at a dose 500 µg/day to achieve equilibrium 1-15.4% (average 5.4%) of the dose excreted in the feces, unedited. The remainder of the dose is excreted in the form of 4 major metabolites, components 39%, 21%, 7% and 7% respectively, and 6 small metabolites (each of which account for less than 5%).
With human urine excreted trace amounts of unchanged dutasterida (less 0.1% dose).
When taken therapeutic doses dutasterida end T1/2 is 3-5 Sun.
Dutasteride is detected in serum (at concentrations of more than 0.1 ng / ml) to 4-6 months after his admission.
Pharmacokinetics of dutasterida can be described as first-order absorption and elimination of two parallel processes, one saturated (ie. concentration-dependent) and one nenasyshhaemyj (t. it is. not dependent on concentration).
At low concentrations in serum (less 3 ng / ml) dutasteride quickly through both processes of elimination. After receiving a single dose 5 mg and less dutasteride quickly withdrawn from the body and has a short T1/2, component 3-5 d.
When concentrations in the serum of more than 3 ng/ml klirens dutasterida less 0.35-0.58 l /, When the excretion is performed mainly by linear nenasyshhaemogo the process of with an end T1/2 3-5 Sun. At therapeutic concentrations against the backdrop of daily dose in a dose 500 mcg is dominated by slower clearance dutasterida; total clearance is linear and is not dependent on the concentration of nature.
Pharmacokinetics in special clinical situations
Farmakokinetiku and pharmacodynamic dutasterida studied at the 36 healthy men aged 24 to 87 years after taking the drug in a single dose 5 mg. Between different age groups was not statistically significant differences on such farmakokineticski dutasterida settings, both the AUC and Cmax. Also there was no statistically significant difference T1/2 dutasterida between the age group 50-69 years and older age group 70 years, that includes most men with benign prostate hyperplasia.
Between age groups had no significant differences in the degree of reduction of the levels of DHT. These results indicate that there is no need to reduce the dose of dutasterida in elderly patients
Avodart: testimony
-treatment and prevention of progression of benign prostatic hyperplasia (in order to reduce the size of the prostate gland, relieve symptoms, improve urination and reduce the risk of acute urinary retention and the need for surgical treatment);
is combination therapy with alpha1-adrenoblokatorami for the treatment and prevention of progression of benign prostatic hyperplasia (in order to reduce the size of the prostate gland, relieve symptoms, improve urination). Combination of dutasterida and tamsulosin (alpha1-adrenoblocker) has been studied.
Avodart: dosing regimen
Dutasteride can be used as monotherapy, as well as in combination with alpha1-adrenoblokatorami.
The drug can be taken regardless of meals.
The effect is pretty fast, but treatment should continue for at least 6 months in order, to assess the effects of the drug.
To adult males, including elderly patients, the recommended dose of ingestion is 500 g (1 caps.) 1 time / day. The capsules should be swallowed whole, do not chew or open, because the contents of the capsules can cause irritation of the mucous membrane of the oropharynx.
At renal impairment correction dose is not required (tk. When taking the drug in a dose 500 g/day of urine excreted less 0.1% dose).
You need to be wary of preparation patients impaired liver function, tk. dutasteride is subjected to intense metabolism in liver, but his T1/2 is 3-5 weeks.
Avodart: side effects
Data from clinical studies
Monotherapy dutasteridom: impotence, change (reduction) libido, abnormal ejaculation, gynecomastia (includes pain and mammary glands).
Combination Therapy dutasteridom and tamsulozinom: impotence, change (reduction) libido, abnormal ejaculation, gynecomastia (includes pain and mammary glands), dizziness.
Data monitoring in clinical practice: rarely – allergic reactions (rash, itch, hives, limited swelling, angioedema.
Avodart: Contraindications
-hypersensitivity to dutasteridu and other components of the drug;
-hypersensitivity to other 5α-reductase inhibitors.
This is contraindicated in women and children.
Avodart: Pregnancy and lactation
The influence on fertility
Application of dutasterida in daily dose 500 mcg on sperm characteristics studied in healthy volunteers between the ages 18-52 years. The 52-week treatment averages per cent drop in the total number of sperm, sperm volume and locomotor activity of spermatozoa were 23%, 26% and 18% respectively, compared to the baseline. The concentration of sperm and their morphological characteristics have not changed. 30% is considered clinically significant-reduction, thus, the clinical significance of dutasterida influence on individual fertility is unknown.
Avodart: Special instructions
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 area of skin with SOAP and water.
Influence on detection of prostate-specific antigen and prostate cancer
In patients with benign hyperplasia of the prostate digital rectal examination should be conducted, and other methods of examination of the prostate before treatment Avodartom and periodically repeat these studies in the treatment process to exclude prostate cancer.
Determination of the concentrations of prostate-specific antigen in serum is an important component of complex research, to identify prostate cancer. Normally conduct additional examination in patients with prostate-specific antigen concentration, more 4 ng / ml; in such cases, it may be shown prostate biopsy. Baseline prostate-specific antigen in less 4 ng/ml in patients, receiving dutasteride, does not exclude the diagnosis of prostate cancer.
After therapy for Avodartom 6 months, a decrease of serum level of prostate-specific antigen in patients with benign hyperplasia of prostate cancer by about 50%, even if you have prostate cancer. Despite individual differences, decrease in the level of prostate-specific antigen approximately 50% observed throughout the range of the original values of the prostate-specific antigen concentrations (from 1.5 to 10 ng / ml). Thus, When interpreting the prostate-specific antigen levels in men, who gets This for 6 months or more, measured level, you need to multiply 2, and then compare it with normal levels without therapy dutasteridom. Such a calculation of prostate-specific antigen allows you to save the specificity and reliability analysis, as well as the ability to detect prostate cancer.
Any stable increase in the level of prostate-specific antigen in dutasteridom therapy should be carefully evaluated, including the possibility of non-compliance regime therapy dutasteridom.
The level of prostate-specific antigen reverts to its original for 6 months after the cancellation dutasterida.
The ratio of free prostate-specific antigen to the total remains constant even in the face of therapy dutasteridom. In terms of the ratio of shares to detect prostate cancer in men, receiving dutasteride, the correction of this magnitude is not required.
Effects on ability to drive vehicles and management mechanisms
Reception not Branded affects the ability to drive a car and working with machinery.
Avodart: overdose
In case of overdose (dose in 80 times higher than the therapeutic) There have been no reported side effects.
Specific antidote no dutasterida, and so with suspected overdose hold enough symptomatic and supportive treatment.
Avodart: drug interaction
As dutasteride is metabolized by CYP3A4 izofermentom, in the presence of CYP3A4 inhibitors dutasterida concentration in the blood may increase.
If you are applying to dutasterida with CYP3A4 inhibitors, Verapamil and diltiazem, there was a reduction in clearance dutasterida. At the same time, amlodipine, Another calcium channel blocker, does not reduce clearance dutasterida.
While applying Branded and CYP3A4 inhibitors dutasterida clearance reduction and subsequent increase in its concentration in the blood is not clinically significant, owing to the wide therapeutic index this drug, so correction doses not required.
CYP1A2 in vitro, CYP2C9, CYP2D6 and CYP2C19 isoenzymes are not involved in the metabolism of dutasterida in humans; dutasteride inhibits not isozyme cytochrome p 450 system, involved in metabolism of drugs.
Dutasteride does not displace warfarin, diazepam and phenytoin from their connection with the plasma protein, and these drugs, in turn, not displace dutasteride.
When applied simultaneously with dutasterida lipid drugs, ACE inhibitors, beta-blockers, calcium channel blockers, kortikosteroidami, Diuretics, NSAIDs, PDE5 inhibitors 5 and antibiotics derived quinolone, any significant drug interactions are not indicated.
Not detected clinically meaningful interaction dutasterida with tamsulozinom, terazozinom, varfarinom, Digoxin and kolestiraminom.
Avodart: terms of dispensing from pharmacies
The drug is released under the prescription.
Avodart: terms and conditions of storage
The drug should be stored out of reach of children at or above 30 ° C. Shelf life – 4 year.
