The speed and intensity of the effect of dutasteride on dihydrotestosterone directly depends on the prescribed dose of the drug. In most cases, the effect becomes noticeable 1-2 weeks after the first dose.
For example, when taking 0.5 mg of dutasteride per day, after a week the amount of dihydrotestosterone decreases by 85%, after 2 weeks of treatment - by 90%.
Therapy promotes:
- reduction in the size of the prostate gland;
- improving urination;
- reducing the risk of developing acute urinary retention.
The maximum concentration of the active substance is observed 2-3 hours after taking one dose. Bioavailability is around 60% (levels vary from 40 to 94%), but food intake reduces bioavailability by 10-15%.
As a result of daily therapy, after a month of treatment, the concentration of dutasteride is about 65% of the equilibrium concentration, after 3 months - 90%.
About 11.5% of the active substance penetrates from blood serum into sperm.
Indications for use
Preparations based on dutasteride are prescribed if necessary, prevention and treatment of progression of benign prostatic hyperplasia(prescribe monotherapy or combination therapy in combination with α-blockers).
Mode of application
The effect of food intake on the bioavailability of the drug at a level of 10-15% is considered clinically insignificant. Therefore, you can take the product regardless of food.
In most cases, men are prescribed 1 capsule (500 mcg) per day. The effect of therapy is noticeable after 1-2 weeks, but treatment should not be stopped. The recommended course is 6 months.
If renal function is impaired, there is no need to reduce the dose, since less than 0.1% of the dose taken is excreted in the urine. But there is no data on taking the drug by patients who have impaired liver function. The half-life of the drug varies from 3 to 5 weeks, so if you have liver problems, you should be careful during treatment.
Composition and release form
The release form depends on the specific drug that contains dutasteride.
If treatment with dutasteride is necessary, Avodart is prescribed..
It comes in the form of opaque oblong yellow gelatin capsules.
They are marked with the code "GX CE2".
Capsules are packed in blisters of 10 pieces.
A cardboard box contains from 3 to 9 blisters.
Interaction with other tools
During the experiments it was found that the metabolism of the substance dutasteride occurs under the influence of the CYP3A4 isoenzyme. This means that in the presence of these isoenzymes, the concentration of dutasteride may increase.
Concomitant use of dutasteride-based drugs and CYP3A4 inhibitors (for example, Verapamil or Diltiazem) leads to decreased clearance of dutasteride. But calcium channel blockers, including Amlodipine, do not lead to a decrease in the clearance of dutasteride.
But the decrease in clearance and increase in its concentration under the influence of CYP3A4 inhibitors is not clinically significant due to the wide range of safety limits of drugs based on dutasteride. Because of this, there is no need to adjust its dose.
In vitro experiments revealed that dutasteride does not replace Phenytoin, Diazepam, Warfarin, Phenprocoumon, Acenocoumarol from sites where binding to plasma proteins occurs. These drugs do not replace dutasteride.
Checking the pharmacological interaction with Warfarin, Terazosin, Digoxin, Tamsulosin, Kolestyramine showed that there are no significant interactions.
There are also no undesirable effects when using dutasteride in combination with quinolone antibiotics, NSAIDs, corticosteroids, calcium channel blockers, ACE inhibitors, diuretics, beta-blockers.
Video: "Prostate adenoma"
Side effects
Some patients experience undesirable effects while taking dutasteride-based drugs.
In rare cases it is possible:
- development of alopecia (hair loss mainly on the body);
- the occurrence of hypertrichosis.
In very rare cases, such side effects are observed:
- allergies (manifested in the form of urticaria, itching, localized swelling, rash), angioedema;
- development of a depressive state;
- the appearance of testicular swelling and testicular pain.
In addition, erectile dysfunction, ejaculation disorders, decreased libido and the occurrence of disorders of the mammary glands are possible. During the studies, the number of such complaints was higher than in the group of patients taking placebo.
Overdose
A slight one-time overdose is not dangerous for patients. Studies have found that even taking 40 mg of dutasteride, which is 80 times the recommended dose, for 7 days does not lead to clinically significant side effects.
Taking 5 mg of the drug for six months does not provoke the appearance of additional side effects.
If necessary, in case of overdose, supportive and symptomatic therapy is prescribed. There is no specific antidote.
Contraindications
Dutasteride should not be prescribed if there is an established intolerance to this substance or hypersensitivity to it. Contraindications also include hypersensitivity to other 5α-reductase inhibitors.
It is contraindicated for women and children.
Use during pregnancy
The issue of using dutasteride during pregnancy should not even be considered due to the fact that women are not prescribed drugs based on this substance.
Preclinical studies have shown that as a result of suppression of dihydrotestosterone levels in a male fetus, the development of the external genitalia may be inhibited.
special instructions
Through damaged capsules, the active substance can be absorbed through the skin, so women and children should avoid contact with them. If they touch the contents of the capsule, the area must be washed with soap.
The substance finasteride is contained in such drugs:
- "Adenosteride";
- "Prostan";
- "Prosteride";
- "Urofin";
- "Finpros";
- "Finistère."
But only a doctor should select the appropriate means.
Although finasteride and dutasteride reduce the overall risk of developing prostate cancer, they also increase the likelihood of developing high-grade cancer, as published by the FDA. The authors add that although the risk is low, doctors should be aware of it. The FDA indicates that now the annotations of all drugs in this group in the Warnings section must contain information about the risk of developing high-grade prostate cancer.
Drugs in this class include finasteride, dutasteride, turosteride, etc. They have antiandrogenic activity and are used to treat prostate adenoma and androgenetic alopecia.
The FDA evaluated two randomized studies - PCPT, which compared finasteride 5 mg versus placebo for 7 years, and REDUCE, which compared dutasteride 0.5 mg versus placebo for 4 years. Both studies showed a reduction in the risk of prostate cancer in men over 50 years of age, with a simultaneous increase in the risk of high-grade prostate cancer. This type of prostate cancer (Gleason score 8-10) causes the greatest mortality, as it grows aggressively and quickly invades the prostate capsule. Cancer cells are large, and the tumor itself is difficult to treat and often recurs. Another feature of high-grade cancer is that its recurrence after treatment in some cases is not accompanied by an increase in PSA levels, which makes its early diagnosis difficult. The FDA emphasizes that doctors should discuss with patients the issue of changing or stopping taking 5-a reductase inhibitors.
Dutasteride is a medication that is used to treat benign prostate adenoma. In addition, the drug is used in medical practice to prevent the pathological process. During the period of therapy, it is necessary to regularly undergo a rectal digital examination to prevent the development of cancerous degeneration of a benign neoplasm.
Other names and classification
ATX code: G04CB02.
Russian name
Dutasteride.
Latin name
Trade names
Avodart, Duodart (modified release capsules).
CAS code
Composition and dosage forms
The drug is available in the dosage form of yellow capsules. The outer hard shell is opaque. Consists of gelatin, titanium dioxide, glycerol, yellow dye based on iron oxide. The capsules have an oblong cylindrical shape with “GX CE2” engraved in red dye on one side. Oblong units of the drug contain 0.5 mg of the active substance dutasteride and other additional components:
- di- and monoglycerides of caprylic (carboxylic acid derivative);
- food antioxidant E321.
The drug is packaged in contour cell blisters of 10 units.
Pharmacological group
The medication belongs to the group of dual 5α-reductase inhibitors. The drug belongs to the class of drugs that affect metabolism in the prostate gland. The drug belongs to the group of urodynamic correctors.
pharmachologic effect
The mechanism of action of the drug is based on suppressing the activity of 5α-reductase isoenzymes type 1 and 2, responsible for the transformation of the male sex hormone into DHT (5α-dihydrotestosterone). The latter is the main hormone in men, which takes part in hyperplasia of the endocrine part of the prostate gland.
The maximum therapeutic effect (decrease in dihydrotestosterone concentrations) depends on the amount of dutasteride taken and is observed during the first 1-2 weeks after the start of therapy.
After this period of time, the average serum concentration of the active substance decreases by 85 (after the first 7 days of therapy) and 90% (within 2 weeks).
With a single dose of Dutasteride at a dosage of 0.5 mg, the gelatin shell of the capsules disintegrates under the action of esterases and the active component begins to be absorbed by the villi in the small intestine. When the drug enters the systemic circulation, it reaches maximum levels in plasma within 1-3 hours. Bioavailability is 60%. Eating slows down the rate of absorption and reduces the bioavailability of the drug.
Due to the high degree of binding to plasma proteins (about 99.5%), the active substance penetrates into the tissue structure.
The distribution volume varies from 300 to 500 l. The drug is transformed in liver cells under the influence of the cytochrome p450 system and the CYP450-3A2 isoenzyme. As a result, 3 large and 2 small metabolic products are formed.
The drug is excreted in feces 24 hours after administration by 1-15.5% in its original form. About 1% of the substance leaves the body through the kidneys. With repeated administration of a therapeutic dose, the half-life is 21-35 days. In this case, Dutasteride can be detected during laboratory tests in the blood serum within 4-6 months after treatment.
Indications for use of Dutasteride
The medication helps eliminate or prevent the development of benign prostatic hyperplasia. The drug helps normalize the natural process of urination, reduces the risk of developing acute urine retention, and reduces the size of the prostate. Taking medication is a conservative treatment if the patient refuses to undergo surgery or the procedure is impossible for some reason.
Method of application and dosage of Dutasteride
The therapeutic effect occurs quickly, but the duration of therapy should be at least 6 months. This time is necessary for an objective assessment of the effect of the medication on the condition of the prostate.
special instructions
The active substance of the drug can diffuse through the skin, so women and children are not recommended to come into contact with damaged or opened capsules. If the powder contents come into contact with the skin, wash off the medication from the area with clean water and soap.
In the presence of benign prostatic hyperplasia, internal palpation of the anus and rectum (rectal examination with a finger) and other examinations of the prostate gland are performed before starting drug therapy with Dutasteride. The studies carried out must be repeated regularly during the treatment process. This is necessary to exclude cancerous degeneration of a benign adenoma.
The main method for examining for the presence of a malignant neoplasm in the prostate is the screening process. A key component of the procedure is determining the serum level of prostate-specific antigen. A prostate biopsy is performed as an additional examination when the antigen level is above 4 ng/ml.
It is important to remember that an antigen value below 4 ng/ml does not exclude the presence of cancer.
After drug therapy for 6 months, the serum concentration of prostate-specific antigen decreases by 50%, returning to the original values - from 1.5 to 10 ng/ml. Therefore, the dosage of Dutasteride is doubled.
During pregnancy and breastfeeding
The drug is not intended for use by women, therefore taking the drug during pregnancy and breastfeeding is prohibited. There is a possibility of penetration of the active ingredient through the barrier of the placenta with the mother's blood. The medicine may cause intrauterine abnormalities during embryonic development. There are no data on the effect of the drug on fertility.
In childhood
Clinical studies on the effect of the drug on the development of the body in childhood and adolescence have not been conducted. In the absence of data, taking the drug under 18 years of age is prohibited.
For liver dysfunction
If the liver does not function properly, Dutasteride undergoes active transformation in hepatocytes with the formation of metabolites. The half-life increases to 6 weeks, so patients with renal failure should be careful.
For impaired renal function
For patients with renal failure, when taking a standard daily dose of 0.5 mg, only 0.1% of the Dutasteride taken is allocated, which is why there is no reason to reduce the daily dose.
Side effects of Dutasteride
Negative reactions from taking the drug occur in relation to the genitourinary system in men:
- decreased libido;
- complete erectile dysfunction - impotence;
- ejaculation disorder;
- gynecomastia - pain in the mammary glands with subsequent enlargement.
In rare cases, allergic reactions begin, which manifest themselves in the form of hives, skin rashes, itching, and swelling.
Predisposed patients may develop anaphylactic shock and angioedema. Therefore, patients prone to anaphylactoid reactions are given allergy tests to determine the tolerability of Dutasteride before taking capsules.
Impact on the ability to drive vehicles and other mechanisms
The drug does not affect the activity of the central nervous system. Therefore, during the treatment period, driving vehicles, operating complex devices, playing extreme sports and other activities that require concentration and speed of physical reaction are allowed.
Contraindications
The medicine is prohibited or not recommended for use in the presence of increased tissue sensitivity to additional substances and active components of the medicine. 5α-reductase inhibitors are contraindicated for use by women and children.
Overdose
Overdose is theoretically possible with a single dose of 80 times the standard daily dose. Cases of clinical manifestations have not been recorded, so a specific counteracting agent has not been developed.
If the drug is abused, it may worsen or increase the likelihood of side effects. If negative reactions occur in a hospital setting, treatment is prescribed aimed at eliminating side effects.
Interoperability and Compatibility
Transformation of the drug in hepatocytes occurs under the influence of CYP3A4 isoenzymes and the cytochrome P450 enzyme complex. Therefore, drugs that are isoenzyme inhibitors of CYP3A4 help increase the plasma concentration of the active substance in an unchanged form. When taking the drug in parallel with Verapamil and Diltiazem, a decrease in the clearance of Dutasteride is observed, while Amlodipine, a calcium channel blocker, does not reduce the clearance of the active component.
A subsequent increase in the concentration of the chemical compound in the blood when taking CYP3A4 blockers in parallel does not exhibit toxicity and is a safe combination for the body. Therefore, there is no need to adjust drug dosages.
When taking lipid-lowering drugs, angiotensin-converting enzyme and phosphodiesterase V inhibitors, beta-blockers, diuretics, corticosteroids, non-steroidal anti-inflammatory drugs, calcium channel blockers and antibiotics from the quinolone group with Dutasteride, no chemical interaction is observed. In addition, during clinical studies (medicine taken by volunteers for 9 months), no pharmacological reactions of the drug for the treatment of prostate adenoma with Terazosin, Tamsulosin were identified.
The active substance of the drug does not suppress the enzymatic activity of cytochrome P450, which is involved in the transformation and breakdown of drugs.
Dutasteride does not displace Diazepam, Digoxin, Cholestyramine, Warfarin and Phenytoin from plasma proteins. When taking these drugs in parallel, no chemical interaction is observed.
With alcohol
During drug therapy, you should not drink alcoholic beverages. Alcohol products contain ethanol, which has a negative effect on the central, circulatory and hepatobiliary systems. Ethyl alcohol reduces the therapeutic effect of the drug and exacerbates side effects.
Manufacturer
CJSC GlaxoSmithKline Trading, Russia.
Conditions for dispensing from pharmacies
The drug is dispensed at certified pharmacological outlets strictly according to a prescription if there are direct medical indications.
Price
The average cost of the drug varies from 2080 to 4300 rubles.
Conditions and shelf life
The drug can be stored for 4 years from the date of release indicated on the packaging at a temperature not exceeding +30°C. It is necessary to keep the medication in a place with low humidity, protected from sunlight.
Analogs
Drug substitutes with similar chemical composition and pharmacological effects include:
- Avodart;
- Adenosteride;
- Penester;
- Dutasteride Bacter;
- Prosteride;
- Finasteride.
The transition to another drug is carried out by the attending physician in the absence of a therapeutic effect.
Dutasteride is a medicine for treating prostate adenoma and stopping hair loss in men. Unlike finasteride, it binds to type 1 and type 5 alpha reductase. It affects the root cause of baldness, but does not stimulate new hair growth, so it is used together with minoxidil. Retains existing hair and slows down further hair loss. The drug is available in tablet form and is taken orally every day.
Questions and answers about dutasteride:
If you intend to take drugs based on dutasteride to treat baldness, then first you should definitely consult your therapist and trichologist. Dutasteride should not be taken by women and children.
How is dutasteride different from finasteride?
Finasteride inhibits type 2 5-alpha reductase, while type 1 remains unaffected. Dutasteride inhibits both types of 5-alpha reductase, which can significantly improve the therapeutic effect, since the first type accounts for approximately 30% of all 5-alpha reductase. If in a particular person the first type of 5-alpha reductase is more active than the second type or if the sensitivity of the receptors is high, then even this 30% percent can play a big role in the treatment of baldness.
What drugs based on dutasteride are used?
Or Avodart is a drug containing 0.5 mg of dutasteride in each tablet. Manufactured by GlaxoSmithKline. Used to treat prostate adenoma. There is no official analogue for the treatment of baldness, as is the case with finasteride (Propecia). But this does not prevent you from using Avodart to stop hair loss. There is also an Indian analogue of Avodart - Duprost, which is manufactured by Cipla. Each capsule contains 0.5 mg of dutasteride.
How is dutasteride taken to treat hair loss?
Take 0.1 mg of dutasteride 3 times a week and 4 times 0.5 mg of finasteride every other day. This scheme allows you to achieve good results and reduce side effects, which we will discuss separately. That is, the Avodart tablet is divided into 5 parts. You can also determine the appropriate dosage based on the graphs of changes in dihydrotestosterone levels, which are presented below.
Dutasteride is best taken on an empty stomach, this ensures an increase in blood concentration by 10-15% (original source Avodart: Highlights of prescribing information, see section 12.3 Pharmacokinetics - Absorption).
How do dihydrotestosterone levels decrease when taking dutasteride and finasteride?
How does dutasteride affect hair thickness?
According to this graph (original source Avodart), 0.1 mg of dutasteride is similar in effectiveness to 5 mg of finasteride and on average provides you with +72 hairs per 2.54 cm (1 inch) round area of scalp. The measurements in this graph were taken 6 months after the start of treatment. A dose of 0.5 mg of dutasteride daily provides +92 hairs per similar area of skin.
After a series of preclinical and clinical trials, the drug was approved in the United States for widespread clinical use in patients with prostatic hyperplasia in 1992, and then, in 1995, it was registered in Russia. Somewhat later than finasteride, a potentially more powerful inhibitor of type I and II 5a-reductase, dutasteride, was developed: the results of the first clinical trials of this drug appeared in the literature in 1998. Unlike finasteride, dutasteride has the ability to inhibit 5a-reductase not only type II, but also type I - thus the drug provides maximum suppression of dihydrotestosterone production. In Western countries, dutasteride under the commercial name "Avodart" was registered and approved for clinical use in 2002, in Russia - in 2005.
It is well known that both before and after official registration, medications are tested not only for their effectiveness, but also for their safety. The effectiveness of the use of 5a-reductase inhibitors in patients with BPH has always received much attention, and this problem is well covered in the medical literature. In this article, we would like to dwell on the results of recently completed large clinical studies that examined the safety and tolerability of Avodart (dutasteride) therapy.
Comprehensive data on the safety and tolerability of Avodart (dutasteride) in patients with BPH were obtained from three large randomized, double-blind, placebo-controlled studies (ARIA 3001, ARIA 3002 and ARIB 3003, ) and one randomized, double-blind study (ARI 40001), in in which patients in the control group received finasteride. The studies ARIA 3001, ARIA 3002 and ARIB 3003 involved 4325 patients with BPH (2167 in the dutasteride group, 2158 in the placebo group), the duration of therapy was 2 years. In a finasteride-controlled study with a treatment duration of 1 year, 1630 patients were randomized: 813 to the dutasteride group and 817 to the finasteride group. Note that the number of patients in the groups and the duration of therapy are more than sufficient to assess the effectiveness and safety of the drug under study.
Analysis of data obtained from the above-mentioned placebo-controlled studies showed that adverse events (AEs) that occurred were usually mild or moderate in severity and most often related to sexual dysfunction (Table 1). Moreover, both in the Avodart group and in the placebo group, the vast majority of patients (89% and 94%, respectively) had no sexual dysfunction.
Interestingly, in terms of the frequency of recorded adverse events associated with taking the drugs, statistically significant differences between the dutasteride and placebo groups were, as a rule, observed only during the first 6 months of therapy. During further treatment, differences between groups in the most common adverse events disappeared. For example, in the first 6 months of treatment, erectile dysfunction (ED) was observed in 4.7% of patients in the dutasteride group and in 1.7% of patients in the placebo group - the differences between the groups were statistically significant. Subsequently, the frequency of ED in the groups did not have significant differences, amounting to 1.4% and 1.5% in the 7-12th month; in the 13-18th month - 1% and 0.5%, and in the 19-24th month - 0.8 and 0.9%, respectively. A similar pattern was found for the slightly less common ejaculation disorders and decreased libido. The only adverse event associated with taking the drug that occurred significantly more often in patients in the dutasteride group, from the 7th month of use until the end of the study, was gynecomastia. The incidence of gynecomastia in the dutasteride group, however, was generally low and did not exceed 1.1% throughout the study. It is also important that among the adverse events, the most common reason for stopping taking the drug was erectile dysfunction: in the dutasteride group there were 24 (1.1%) such patients, and in the placebo group - 15 (0.69%). Based on the presented data, it can be argued that the tolerability of long-term (over 2 years) therapy with dutasteride is good, and only a small percentage of patients may experience clinically significant adverse events during this treatment.
A similar profile of adverse events was reported in the finasteride-controlled study ARI 40001. Data from this study suggest that dutasteride and finasteride may cause similar adverse events (Table 2), the frequency and severity of the most significant of them are low, and the tolerability of both The drugs are generally good.
It should be noted that in all the above-mentioned studies, dynamic monitoring of a number of hematological (leukocytes, platelets, red blood cells, hemoglobin, etc.) and biochemical (glucose, sodium, potassium, albumin, total protein, creatinine) laboratory parameters, including indicators of liver function - alkaline phosphatase, ALT and total bilirubin. Analysis of the results showed that taking dutasteride does not have a negative effect on any of the laboratory parameters studied. Changes in parameters in the dutasteride group were no different from those in the placebo group and in the finasteride group.
The safety of Avodart (dutasteride) in humans has also been studied in healthy volunteers. Thus, in connection with the theoretical possibility of drugs that modulate testosterone metabolism to influence bone density, a randomized, double-blind, placebo- and finasteride-controlled study (ARIA 1009) was conducted, which assessed the effect of dutasteride on bone density (by X-ray densitometry), indicators bone metabolism (osteocalcin, bone alkaline phosphatase serum and urine n-telopeptide), as well as lipid profile (cholesterol, triglycerides, high and low density lipoproteins serum). The duration of therapy was almost 1 year (52 weeks) with subsequent control examinations for 24 weeks. The results of the study showed no signs of a negative effect of dutasteride on bone metabolism and the lipid profile of humans. The data obtained in the dutasteride group did not differ from those in the placebo and finasteride groups.
Also, drug interactions of dutasteride with drugs most often used in elderly patients have now been well studied. Thus, no pharmacodynamic and pharmacokinetic interactions were identified between dutasteride and tamsulosin (data from the ARIA1011 study), warfarin (data from the ARI10016 study), digoxin (data from the ARI10017 study) and cholestyramine (data from the ARIA1010 study). Subsequent phase 3 studies demonstrated the absence of clinically significant interactions of dutasteride with ACE inhibitors, b-blockers, calcium channel antagonists, diuretics, corticosteroids, antihyperlipidemic agents, non-steroidal anti-inflammatory drugs, fluoroquinolones and phosphodiesterase type 5 inhibitors.
Thus, the results of studies conducted with the participation of several hundred healthy volunteers and more than 6,000 patients with prostate hyperplasia allow us to confidently assert that even with long-term use of the 5a-reductase inhibitor of both types Avodart (dutasteride), the drug is well tolerated, and its use is associated with minimal risk of adverse events.
Literature
1. Gormley GJ, Stoner E, Bruskewitz RC, et al. The effect of finasteride in men with benign prostatic hyperplasia. The Finasteride Study Group. N Engl J Med. 1992;327:1185-1191.
2. Gisleskog PO, Herman D, Hammarlund-Udenaes M, et al. A model of the turnover of dihydrotestosterone in the presence of the irreversible 5(-reductase inhibitors GI198745 and finasteride. Clin Pharmacol Ther. 1998; 64:636-647.
3. Bramson HN, Hermann D, Batchelor KW, et al. Unique preclinical characteristics of GG745, a potent dual inhibitor of 5AR. J Pharmacol Exp Ther. 1997;282:1496-1502.
4. Debruyne F, Barkin J, van Erps P, et al. ARIA3001, ARIA3002, ARIB3001 study investigators. Efficacy and safety of long term treatment with the dual 5-(-reductase inhibitor dutasteride in men with symptomatic benign prostatic hyperplasia. Eur Urol. 2004, 46:488-494.
5. GlaxoSmithKline Document BP2001/00017/00. Data on File. Clinical trial report study ARI 40001.
