Date of approval.
Date of revision.
Finasteride Tablets Instructions
Please read the instructions carefully and use under the guidance of a physician
Use with caution in athletes
Drug Name
Generic Name: Finasteride Tablets
Trade name: Aesculus
English Name: Finasteride Tablets
Chinese Pinyin: Feinaxiong’an Pian
The main ingredient of this product is finasteride, whose chemical name is: N-tert-butyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide
The chemical structure formula is
Molecular formula: C23H36N2O2
Molecular weight: 372.55
Characteristic]
This product is a film-coated tablet, which appears white or off-white after removing the coating.
Indications
This product is indicated for the treatment and control of benign prostatic hyperplasia (BPH) and the prevention of urinary events by.
— Reduces the risk of acute urinary retention.
—Reduces the risk of requiring transurethral resection of the prostate (TURP) and prostatectomy.
It may reduce the size of the enlarged prostate, improve urinary flow and improve symptoms associated with prostate enlargement.
This product is indicated for the treatment of patients with an enlarged prostate.
Specification
5mg
Dosage]
The recommended dose is 1 tablet per day, 5 mg per tablet, with or without food.
Dosage for patients with renal insufficiency
No dose adjustment is required for patients with various degrees of renal insufficiency (creatinine clearance as low as 9 mL/min), as pharmacokinetic studies confirm no alteration in the in vivo course of finasteride.
Dosing in the elderly
Although pharmacokinetic studies have shown reduced clearance of finasteride in patients over 70 years of age, no dose adjustment is required.
[Adverse Reactions].
This product is well tolerated.
In the PLESS study, 1524 patients taking 5 mg of this product daily and 1516 patients taking placebo were evaluated for safety over 4 years. 4.9% (74 patients) discontinued treatment due to adverse reactions related to this product, compared to 3.3% (50 patients) in the placebo group. Treatment discontinuation due to adverse reactions related to sexual function was the most reported adverse reaction in 3.7% (57 patients) of patients taking this product and in 2.1% (32 patients) of placebo-treated patients.
Over the 4+ years of the study, the clinical adverse reactions considered by the investigators to be likely, probable and definitively related to the product, with an incidence ³1% and greater than placebo, were primarily impaired sexual function, breast discomfort and rash. In the first year of the study, impotence occurred in 8.1% of patients taking the product compared to 3.7% of patients on placebo; decreased libido was 6.4 versus 3.4% and ejaculatory disturbances were 0.8 versus 0.1%. There was no significant difference in the incidence of these three adverse effects between the two treatment groups during the second to fourth years of the study. Cumulative incidence in years two through four: impotence (5.1% with this product; 5.1% with placebo); decreased libido (2.6%; 2.6%); and ejaculatory dysfunction (0.2%; 0.1%). In the first year, 3.7 and 0.8% of patients had reduced ejaculation with this product and placebo, respectively; in the second to fourth years, the cumulative incidence was 1.5% with this product and 0.5% with placebo. In the first year, breast enlargement was reported as (0.5%; 0.1%), breast tenderness (0.4%; 0.1%), and rash (0.5%; 0.2%) in the Benzedrine and placebo groups. Cumulative incidence in years two to four: breast enlargement (1.8%; 1.1%); breast tenderness (0.7%; 0.3%); and rash (0.5%; 0.1%).
In the one-year, placebo-controlled Phase III clinical study and in the five-year extension (853 patients extended to five to six years of treatment), the profile of adverse reactions was similar to that reported in PLESS at two to four years. No adverse reactions were identified that increased with the extended treatment period of this product. The incidence of new drug-related adverse reactions related to sexual function decreased with longer treatment duration.
Information from other long-term studies
In a 7-year, placebo-controlled clinical study, a total of 18,882 healthy men were enrolled. In the analysis of data from 9,060 of these men who underwent prostate needle aspiration biopsy, the incidence of prostate cancer was observed in 803 (18.4%) of this product; in 1,147 (24.4%) of the placebo group. Prostate cancer with a Gleason score of 7-10 was found in 280 (6.4%) of the patients in the product group and 237 (5.1%) of the patients in the placebo group by prostate needle aspiration biopsy. Further analysis showed that the increase in patients with high-scoring prostate cancer in the Gleason group may be due to a detection bias due to the effect of Gleason on prostate volume. The clinical significance of the Gleason score of 7-10 is not known.
Breast cancer
In the MTOPS study, which enrolled 3047 men over 4-6 years and was controlled with placebo and controls, there were 4 cases of breast cancer in men treated with finasteride and no cases of breast cancer in men not treated with finasteride. In the 4-year, placebo-controlled PLESS study, which enrolled 3040 men, there were 2 cases of breast cancer in men treated with placebo but no cases in men treated with finasteride. In the 7-year, placebo-controlled Prostate Cancer Prevention Trial (PCPT), which enrolled 18,882 men, there was one case of breast cancer in men treated with finasteride and one case of breast cancer in men treated with placebo. There have been post-marketing reports of breast cancer in men using finasteride. The relationship between long-term use of finasteride and breast tumor formation in men is not known.
Post-marketing experience with the product
The following are post-marketing adverse reactions reported with Finasteride Tablets 5mg and/or low dose Finasteride. Because these adverse reactions were spontaneously reported by populations of uncertain size, it is sometimes not possible to reliably assess their incidence or to determine a causal relationship with drug exposure.
Immune system disorders: hypersensitivity reactions such as pruritus, urticaria and angioedema (including swelling of the lips, tongue, throat and face).
Musculoskeletal and connective tissue disorders: rhabdomyolysis, myopathy, myalgia, muscle weakness, elevated creatine kinase. In some cases, these events are reversible after cessation of finasteride treatment.
Psychiatric disorders: depression, anxiety, decreased libido that continues after discontinuation of treatment.
Cardiac disorders: palpitations.
Hepatobiliary disorders: elevated liver enzymes.
Reproductive and breast disorders: sexual dysfunction (erectile dysfunction and ejaculatory abnormalities), testicular pain, hematospermia, male infertility and/or poor semen quality that persist after discontinuation of treatment. Normalization or improvement in semen quality after discontinuation of finasteride administration has been reported. Breast cancer in men.
Laboratory test results
Decreased PSA levels in patients taking this product (see Precautions) should be taken into account when evaluating laboratory test results.
There were no other differences in standard laboratory parameters in patients taking this product or placebo.
Contraindications]
This product is not intended for use in women and children.
This product is contraindicated in the following conditions.
Hypersensitivity to any of the ingredients of this product.
Pregnancy – Pregnant and potentially pregnant women (see Pregnant and Lactating Women).
[Precautions].
General Precautions
Other urological conditions that may cause similar symptoms should be considered before starting treatment with this product. In addition, prostate cancer and BPH may coexist .
Patients with large amounts of residual urine and/or severely reduced urinary flow should be closely monitored for obstructive urologic disease.
Effect on PSA and prostate cancer screening
So far, no clinical efficacy has been seen in patients with prostate cancer treated with this product. In controlled clinical studies, patients with prostate enlargement and elevated prostate-specific antigen (PSA) were monitored by serial PSAs and prostate biopsies. In these studies of prostate enlargement, this product did not alter the rate of detection of prostate cancer and there was no significant difference in the overall incidence of prostate cancer between patients using this product and those using placebo.
Regular rectal examinations before and after a period of treatment with this product, as well as other tests for prostate cancer, are recommended. Serum PSA is also used to screen for prostate cancer. In general, a baseline PSA>10 ng/mL (Hybritech) suggests further testing and consideration of biopsy; PSA levels between 4 and 10 ng/mL are recommended for further testing. There is some overlap in PSA levels in men with and without prostate cancer. Therefore, a PSA level within the normal reference range in men with prostate enlargement, with or without this product, does not exclude the possibility of prostate cancer. If the baseline PSA<4 ng/mL also does not rule out prostate cancer.
Even in the presence of prostate cancer, this product may reduce serum PSA concentrations by approximately 50% in patients with prostate enlargement. When evaluating PSA data and not excluding the presence of concomitant prostate cancer, it should be considered that this product decreases serum PSA levels in patients with prostatic hyperplasia. Although there are individual differences in patients, the degree of reduction is predictable in the range of PSA values data. Analysis of PSA data from the 4-year, double-blind, placebo-controlled Long-Term Efficacy and Safety Study (PLESS) of this product in more than 3,000 patients demonstrated that a typical patient treated with this product for 6 months or longer should have a doubled PSA value compared to normal PSA values in untreated men. This adjustment not only preserves the sensitivity and specificity of the PSA test, but also maintains its efficacy in detecting prostate cancer.
Persistently elevated PSA levels in patients treated with finasteride should be evaluated with caution, including consideration of noncompliance with this treatment.
This product does not cause a significant decrease in free PSA percentage (free PSA/total PSA) and the free PSA/total PSA value remains constant under the influence of this product. When the free PSA percentage is used to detect prostate cancer, the value does not need to be adjusted.
Increased risk of high-grade prostate cancer
In a 7-year prostate cancer prevention trial (PCPT), men aged 55 years and older with normal rectal exams and baseline PSA values ≤3.0 ng/ml taking finasteride 5 mg/day had an increased risk of prostate cancer with a Gleason score of 8-10 (finasteride 1.8% vs. placebo 1.1%). Similar results were observed in another 4-year controlled clinical trial of a 5α-reductase inhibitor (dutasteride) versus placebo (1% dutasteride vs. 0.5% placebo). 5α-reductase inhibitors may increase the risk of high-grade prostate cancer. It has not been determined whether the effect of 5α-reductase inhibitors in reducing prostate volume or the influence of study-related factors influenced the results of these studies.
Mood changes and depression
Mood changes including depression, depression, and suicidal ideation (less frequently) have been reported in patients treated with finasteride 5 mg. Patients should be monitored for mental status and advised to consult a physician if these symptoms occur.
Effects on semen characteristics
Semen parameters of healthy male volunteers assessed after 24 weeks of finasteride 5 mg administration did not reveal any clinically meaningful effects of finasteride on sperm concentration, motility, morphology, or pH. A reduction of 0.6 ml (22.1%) in median ejaculate volume and a reduction in total sperm volume per ejaculate were observed. These parameters remained within normal limits and were recoverable after discontinuation of the drug, with a mean time to return to baseline of 84 weeks.
Drug/laboratory test interactions
Effect on PSA levels
Serum PSA concentration is related to patient age and prostate volume, which in turn is related to patient age. When evaluating the results of PSA laboratory measurements, the fact that PSA levels are reduced in patients treated with this product should be taken into account. In most patients, PSA decreases rapidly during the first month of treatment, followed by stabilization of PSA levels at a new baseline. The post-treatment baseline value is approximately half of the pre-treatment baseline value. Therefore, the typical patient treated with this product for six months or longer should have a doubled PSA value when compared to the normal PSA value in untreated men. See Precautions – Effects on PSA and Prostate Cancer Screening for clinical interpretation.
Lactose
Tablets contain lactose. This product is contraindicated in patients with any of the following genetic defects: galactose intolerance, total lactase deficiency, or glucose-galactose malabsorption disorder.
For Pregnant and Lactating Women
This product is contraindicated in women who are pregnant or at risk of conception (see [Contraindications]).
Because type II 5a-reductase inhibitors, including finasteride, have the ability to inhibit the conversion of testosterone to dihydrotestosterone, they can cause male fetal external genital abnormalities when administered to pregnant women.
Finasteride exposure – risk to the male fetus
Because of the potential for risk to the male fetus secondary to absorption of finasteride, women should not touch pieces and lobes of this product when they are pregnant or may become pregnant. This product is a coated tablet and contact with its active ingredients can be avoided under normal circumstances. Therefore, the tablets provided should be unbroken.
Nursing women
This product is not indicated for use in women.
It is not known whether finasteride is excreted from human milk.
Pediatric Use
This product is not intended for use in children.
Information on the safety and efficacy of this drug in children has not been established.
Geriatric use
See [Dosage] for specific description.
Drug Interactions
No clinically significant drug interactions have been identified. This product has no significant effect on the cytochrome P450-associated drug metabolizing enzyme system. Propranolol, digoxin, glibenclamide, warfarin, theophylline and antipyrine have been tested in men and no clinically significant interactions with this product have been identified.
Other combination therapy
Although no specific drug interaction studies have been performed, in clinical studies this product was combined with angiotensin-converting enzyme inhibitors, acetaminophen, acetylsalicylic acid, a-blockers, b-blockers, calcium channel blockers, nitrates for cardiac use, diuretics, H2 antagonists, HMG-CoA reductase inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), quinolones, and benzodiazepines No clinically significant adverse interactions were found when used concomitantly.
Drug overdose]
No adverse reactions were observed in patients taking single doses of up to 400 mg of this product and in patients taking multiple doses of 80 mg per day for 3 months.
There is no specific treatment recommended for overdose.
Pharmacology and Toxicology
Pharmacological effects
This product is a 4-azasteroid compound, which is a specific inhibitor of intracellular enzyme-II 5α-reductase in the metabolism of testosterone to the more potent androgen dihydrotestosterone (DHT). While benign prostatic hyperplasia (BPH) or called prostatic hypertrophy depends on the conversion of testosterone to DHT in the prostate. Finasteride has no affinity for the androgen receptor.
Clinical Pharmacology
Benign prostatic hyperplasia (BPH) occurs mainly in men over 50 years of age and its incidence increases with age. Epidemiological studies have shown that those with an enlarged prostate have a 3-fold increased risk of acute urinary retention and the need for prostate surgery. Men with an enlarged prostate are three times more likely to have moderate to severe urinary symptoms and decreased urinary flow rates than men with a smaller prostate.
The development and enlargement of the prostate gland and the subsequent development of benign prostatic hyperplasia (BPH) are dependent on the amount of the active androgen dihydrotestosterone (DHT) in the body. Testosterone is secreted by the testes and adrenal glands and is then rapidly converted to dihydrotestosterone (DHT) by type II 5α-reductase enzymes found primarily in the prostate, liver and skin, and then preferentially bound to the nucleus in these tissues.
Finasteride is a competitive inhibitor of human type II 5α-reductase that slowly forms a stable enzyme complex with type II 5α-reductase. The cycling process of this complex is very slow (t1/2 of 30 days). In vivo and in vitro tests have demonstrated that finasteride is a specific inhibitor of type II 5α-reductase with no affinity for the androgen receptor.
Single dose administration of 5 mg of finasteride resulted in a rapid decrease in serum DHT concentrations, with the maximum effect occurring 8 hours after administration. Plasma finasteride concentrations varied over 24 hours, while serum DHT levels remained unchanged during this period, indicating that plasma drug concentrations did not directly correlate with plasma DHT concentrations.
After 4 years of finasteride administration at a dose of 5 mg/day in patients with BPH, circulating DHT concentrations were reduced by approximately 70% on average and were accompanied by a reduction in prostate volume of approximately 20%. In addition, PSA was reduced by approximately 50% from baseline values, indicating a reduction in prostate epithelial cell growth. suppression of DHT levels, degeneration of the hyperplastic prostate and concomitant reduction in PSA levels were maintained throughout the 4 years of the study. In these studies, circulating blood levels of testosterone increased by approximately 10-20%, but remained within physiological levels.
The administration of this product for 7-10 days in patients undergoing elective prostatectomy caused an approximate 80% reduction in intraprostatic DHT levels. The level of testosterone in the prostate increased to 10 times the pre-treatment level.
In healthy volunteers who discontinued the drug after 14 days of treatment with this product, DHT levels returned to pre-treatment levels within approximately 2 weeks. Patients treated for 3 months had a reduction in prostate volume of approximately 20%, which returned to near baseline values after 3 months of discontinuation.
Finasteride had no effect on circulating levels of cortisol, estradiol, prolactin, thyroid-stimulating hormone, or thyroxine in the blood compared with placebo. There were no clinically meaningful effects on blood lipids (e.g., total cholesterol, LDL, HDL, and triglycerides) or bone mineral density. Luteinizing hormone (LH) increased by approximately 15% and follicle stimulating hormone (FSH) by approximately 9% in patients treated for 12 months; however, these hormone levels remained within the physiological range. The levels of gonadotropin-releasing hormone-stimulated production of LH and FSH were unchanged, indicating that the regulatory control of the pituitary-testicular axis was not affected. Administration of this product to healthy male volunteers for 24 weeks to evaluate semen parameters showed no clinically meaningful effects on sperm concentration, motility, morphology or pH. A mean reduction in ejaculate volume of 0.6 ml was observed in the trial, accompanied by a reduction in the total number of sperm per ejaculate. These parameters remained within normal limits and were reversible upon discontinuation of the drug.
Finasteride inhibits C19 and C21 steroid metabolism and therefore inhibits both hepatic and peripheral type II 5α-reductase. Serum DHT metabolites androstenediol glucosinolates and androstenedione glucosinolates were also significantly reduced. This metabolic pattern is similar to that observed in patients with congenital type II 5α-reductase deficiency, who have significantly lower levels of DHT, smaller prostates, and do not develop BPH. These individuals were born with urogenital defects and biochemical abnormalities, but did not have other clinically important disorders due to type II 5α-reductase deficiency.
Animal Pharmacology
The ability of finasteride to inhibit 5α-reductase and block DHT formation was demonstrated in in vivo tests in male rats and dogs. Tests were performed to confirm a reduction in prostate DHT levels or a reduction in prostate volume. A decrease in prostate DHT concentration occurred in rats after subcutaneous administration of 0.1 mg of finasteride for 4 hours. Dogs given finasteride at 1 mg/kg orally (in 4 doses over 18 hours) showed a decrease in prostatic DHT concentrations 6 hours after the last dose. These studies demonstrate that finasteride prevents DHT formation in vivo.
The reduction in DHT concentration resulted in a decrease in prostate volume. Sexually mature dogs given finasteride orally at 1 mg/kg/day for 6 weeks showed a reduction in prostate volume. Comparison of prostate volume before and after administration showed that finasteride reduced prostate volume by more than 40%. A similar effect was seen in immature male desiccated rats given testosterone. Finasteride at an oral dose of 0.1 mg/day significantly inhibited the growth effect of exogenous testosterone on the accessory gonads due to specific inhibition of 5α-reductase. Finasteride at 2.5 mg/day did not inhibit the pro-growth effect of exogenous DHT on seminal vesicles and prostate gland in experimental animals.
It has no affinity for androgen receptors in rat prostate cytosol and therefore has no direct anti-androgenic activity. Finasteride at concentrations up to 10-4 M did not prevent 3H-DHT binding, while unlabeled DHT inhibited its binding with an IC50 of 2.9 nM.
Standard tests performed in rats, mice or rabbits confirm that finasteride does not inhibit gonadotropin secretion or display any anti-estrogenic, pro-uterine, anti-progestational, androgen-like or progestational-like activity. These data are consistent with finasteride being a specific 5α-reductase inhibitor with no other hormone-like activity.
In a hepatotoxicity test, dogs were given finasteride orally at 40 mg/kg per day for 28 days. Venous blood was taken to determine ALT (SGPT) and AST (SGOT). Both transaminases were not elevated, indicating that finasteride does not cause liver damage.
Several other pharmacological studies have been used to evaluate the effects of finasteride on organ systems and biological parameters. There were no significant changes in renal, gastric or respiratory function in dogs, or in cardiovascular function in dogs and rats.
Toxicological studies
The oral LD50 for finasteride in male and female mice was approximately 500 mg/kg. The oral LD50 for finasteride in female and male rats was 400 and 1000 mg/kg, respectively.
Carcinogenic and mutagenic effects
A 24-month test in rats given finasteride at doses up to 320 mg/kg/day (3200 times the recommended human dose of 5 mg/day) showed no carcinogenic effects.
In a 19-month carcinogenicity test in mice, a statistically significant increase (P≤0.05) in the incidence of testicular Leydig cell adenomas was observed in the 250 mg/kg/day group (2500 times the recommended human dose of 5 mg/day); no adenomas were observed in mice given 2.5 or 25 mg/kg/day (25 and 250 times the recommended human dose, respectively). times the recommended human dose).
An increased incidence of Leydig cell hyperplasia was observed in mice given 25 mg/kg per day and in rats given more than 40 mg/kg per day (250 and 400 times the recommended human dose of 5 mg per day, respectively). A correlation between Leydig cell proliferation alterations and increased serum luteinizing hormone (LH) (2-3 fold higher than control) was confirmed in both rodent studies given high doses of finasteride. It is suggested that the Leydig cell alterations result from an increase in serum LH levels rather than a direct effect of finasteride.
No drug-related Leydig cell alterations were observed in rats or dogs given finasteride at doses of 20 and 45 mg/kg per day (200 and 450 times the recommended human dose of 5 mg per day, respectively) for one year or in mice given finasteride at 2.5 mg/kg per day (25 times the recommended human dose of 5 mg per day) for 19 months.
In vitro bacterial mutagenicity assays, mammalian cell mutagenicity assays, or in vitro alkaline elution assays showed no mutagenic effects. In an in vitro chromosomal aberration assay, Chinese hamster ovary cells administered with high concentrations (450-550 μmol) of finasteride showed a mild increase in chromosomal aberrations. These concentrations were equivalent to 4000-5000 times the peak plasma concentrations produced by the administration of 5 mg of finasteride in humans. In addition, the concentrations of 450-550 μmol used in in vitro assays are not attainable in biological systems. In an in vivo chromosomal aberration assay in mice, no increase in the number of chromosomal aberrations associated with finasteride administration was observed at the maximum tolerable dose (250 mg/kg per day, 2500 times the recommended human dose of 5 mg per day).
Reproductive toxicity test
Sexually mature male rabbits given finasteride at 80 mg/kg per day (800 times the recommended human dose of 5 mg per day) for 12 weeks showed no changes in fertility, sperm count or ejaculate volume.
Sexually mature male rats given the same dose of finasteride for 6 or 12 weeks showed no significant effects on fertility; however, if administration was continued for 24 or 30 weeks, significant reductions in fertility and conception rates were observed, accompanied by significant reductions in seminal vesicle and prostate weights. All of these effects were restored after 6 weeks of discontinuation.
The reduction in fertility in rats treated with finasteride was secondary to its effect on the accessory sex organs, prostate and seminal vesicles, resulting in failure of sperm peg formation. Sperm pegs are required for normal fertility in rats, but are not relevant in humans, as they do not form mating pegs. No alterations in testes or mating behavior related to administration were observed in rats and rabbits.
Developmental toxicity test
Pregnant rats given finasteride at doses of 100 μg/kg/day-100 mg/kg/day (1-1000 times the recommended human dose of 5 mg/day) developed a dose-dependent increase in hypospadias in male offspring, with incidences of 3.6-100%, respectively. In addition, at doses ≥30 μg/kg per day (≥30% of the human recommended dose of 5 mg per day), male offspring from pregnant rats showed reduced prostate and seminal vesicle weights, delayed foreskin separation, and transient papillae development; at doses ≥3 μg/kg per day (≥3% of the human recommended dose of 5 mg per day), shortened urogenital tract spacing occurred. The critical period for these effects in rats was day 16-17 of pregnancy.
The above alterations are the expected pharmacological effects of a type II 5α-reductase inhibitor. Many of the alterations, such as hypospadias, appear in male rats exposed in utero to finasteride, which is similar to those reported in male infants with congenital defects in type II 5α-reductase. There were no abnormal effects in female offspring exposed in utero to any dose of finasteride.
Administration of finasteride during late pregnancy and lactation in rats resulted in a mild reduction in fertility in first-generation male offspring (3 mg/kg per day; 30 times the recommended human dose of 5 mg per day). No developmental abnormalities were observed in the first generation male or female offspring born after mating in male rats given finasteride (80 mg/kg per day; 800 times the recommended human dose of 5 mg per day) and in female rats not given finasteride.
Rabbits exposed to doses of finasteride up to 1000 mg/kg/day (1000 times the recommended human dose of 5 mg/day) on days 6-18 of pregnancy did not develop malformations in their fetuses.
Trials examining the in utero effects of finasteride exposure on days 20-100 of pregnancy during embryonic and fetal development in rhesus monkeys, which better predict the effects on human development than rats or rabbits. Pregnant monkeys given intravenous doses of up to 800 ng of finasteride per day (at least 60-120 times the estimated maximum exposure of pregnant women due to ingestion of 5 mg of finasteride per day of male semen) did not develop male fetal malformations. To confirm the relevance of the rhesus monkey model to human embryonic development, pregnant monkeys were orally administered very high doses of finasteride (2 mg/kg per day; 20 times the recommended human dose of 5 mg per day or approximately 1 to 2 million times the estimated maximum exposure due to male intake of 5 mg per day of finasteride), resulting in male fetuses with external genital malformations. No other malformations were observed in male fetuses, and no finasteride related abnormalities were observed in female fetuses at any dose.
Pharmacokinetics]
After a single oral dose of 14C-finasteride in males, 39% of the administered dose was excreted in the urine as a metabolite (virtually no prodrug form in the urine) and 57% of the total amount was excreted in the feces. The two metabolites of finasteride identified in this study play only a minor role in the 5α-reductase inhibitory activity of finasteride.
The oral bioavailability of finasteride is approximately 80% relative to the single intravenous dose of interest. This bioavailability is not affected by food. Finasteride reaches maximum plasma concentration about 2 hours after administration and is completely absorbed 6-8 hours after administration. The mean plasma clearance half-life of finasteride is 6 hours. The protein binding rate is approximately 93%. The plasma clearance and volume of distribution of finasteride were approximately 165 mL/min and 76 L, respectively.
Repeated dosing tests confirmed a small slow accumulation of finasteride over time. After daily administration of 5 mg, the steady-state trough of finasteride plasma concentration was 8-10 ng/mL and remained stable for a period of time.
The elimination rate of finasteride is somewhat reduced in elderly patients. The half-life increased with age, with a mean half-life of approximately 6 hours in men aged 18-60 years and 8 hours in men aged 70 years and older. This finding was not clinically significant and therefore no dose reduction was necessary.
The distribution of 14C-finasteride after single-dose administration in patients with concomitant chronic renal dysfunction (creatinine clearance in the range of 9-55 mL/min) did not differ from that of healthy volunteers. Protein binding was also unchanged in patients with renal dysfunction. Some of the metabolites that are normally excreted by the kidneys are excreted in the feces. Thus, an increase in fecal excretion of metabolites and a corresponding decrease in urinary excretion occurred. Non-dialysis patients with renal impairment do not require dose adjustment.
Finasteride is recovered in the cerebrospinal fluid (CSF) of patients after 7-10 days of finasteride administration, but the drug is not predominantly concentrated in the CSF. Finasteride was also recovered in the semen of patients taking 5 mg of this product daily. In adult males, finasteride 5mg had no effect on circulating DHT levels, and the amount of finasteride in semen was 50-100 times less than this dose (see Animal Toxicology, Developmental Toxicity).
Storage】Store under 30℃ under shade and seal.
Package】Polyamide/Aluminium/PVC cold pressed solid pharmaceutical compound hard tablets and pharmaceutical aluminum foil; 7 tablets per plate, 1 plate per box, 2 plates per box; 10 tablets per plate, 1 plate per box, 2 plates per box, 3 plates per box.
【Expiration date】 24 months
【Execution approval
【Approval Number】
State Drug Authentication H20051921
【Manufacturer】
Company Name: Hangzhou Kangenbei Pharmaceutical Co.
Address: No. 568, Binkang Road, Changhe Street, Binjiang District, Hangzhou, China
Postal Code: 310052
Telephone number: 0571-86622535
Fax number: 0571-87774127
Web address: www.hzconba.conbagroup.com