Product Overview
[Drug name]
Generic name: Finasteride Tablets
English name: Finasteride Tablets
Chinese Pinyin: Feinaxiong’an Pian
[Ingredients]
The main ingredient of this product is finasteride.
Chemical name: N-tert-butyl-3-oxo-4-aza-5α-androst-1-ene-17β-carboxamide
[Properties]
This product is a film-coated tablet, which is white or off-white after removing the coating.
[Indications] This product is suitable for the treatment of male baldness (androgenic alopecia), which can promote hair growth and prevent further hair loss. This product is not suitable for women and children.
[Specifications] 1mg
[Usage and Dosage]
The recommended dose is once a day, 1 tablet (lmg) per time, with or without food. Generally, the effect of increased hair growth, increased hair number and/or prevention of further hair loss can be observed after continuous use of the drug for three months or more. It is recommended to continue using the drug to achieve the maximum therapeutic effect. The therapeutic effect can be reversed within 12 months after stopping the drug. No dosage adjustment is required for patients with renal insufficiency.
[Adverse Reactions]
This product is generally well tolerated, and adverse reactions are usually mild, and generally do not require discontinuation of treatment.
Clinical trial experience
It is reported that the safety of finasteride in the treatment of alopecia has been evaluated in a series of clinical studies involving more than 3,200 male patients. In three 12-month, placebo-controlled, double-blind studies involving multiple research centers, the safety of finasteride treatment was similar to that of placebo. 1.7% of the 945 male patients treated with finasteride discontinued treatment due to adverse reactions, while 2.1% of the 934 male patients treated with placebo discontinued treatment due to adverse reactions.
In these studies, ≥1% of male patients treated with finasteride experienced the following medication-related adverse reactions: decreased libido (1.8% for this product, 1.3% for placebo) and erectile dysfunction (1.3% for this product, 0.7% for placebo). In addition, 0.8% of male patients treated with finasteride experienced reduced ejaculation volume, compared with 0.4% in the placebo control group. These adverse reactions disappeared after finasteride treatment was discontinued, and many patients also had these adverse reactions disappear on their own during continued medication. In another study, the effect of finasteride on ejaculation volume was tested and found to be no different from placebo.
Comprehensive clinical adverse reaction statistics showed that during the treatment of the finasteride group, 36 of 945 men (3.8%) experienced one or more adverse reactions, while the number in the placebo group (p=0.04) was 20 of 934 (2.1%). Men who stopped using finasteride due to these side effects and most of the men who continued treatment recovered. After five years of finasteride administration, the incidence of each of the above adverse reactions was reduced to ≤0.3%. In a 48-week clinical study of healthy men, the finasteride group was given 1 mg per day, and the median decrease in ejaculation volume was 0.3 ml (-11%), while the placebo group was 0.2 ml (-8%) during the same period. Two other studies showed that when finasteride was administered at a five-fold dose (5 mg daily), the median decrease was close to 0.5 ml (-25%), which was significantly different from the placebo group, but this result could be reversed after discontinuation of the drug.
In clinical studies, there was little difference in adverse reactions of breast pain, enlargement, allergic reactions, and testicular pain between the finasteride group and the placebo group.
Breast cancer
Finasteride has also been reported to be studied in men with prostate disease, but the dose used was five times the recommended dose for the treatment of male pattern baldness. In the 4-6-year placebo-controlled PLESS study of 3,047 men enrolled in the Medical Treatment of Prostate Symptoms (MTOPS) study, there were 4 cases of breast cancer in men treated with 5 mg finasteride, and no cases of breast cancer in men who did not receive 5 mg finasteride. In the 4-year placebo-controlled PLESS study of 3,040 men enrolled in the placebo-controlled study, there were 2 cases of breast cancer in men treated with placebo, but no cases of breast cancer in men treated with 5 mg finasteride. In the 7-year, placebo-controlled Prostate Cancer Prevention Trial (PCPT) of 18,882 men, there was 1 case of breast cancer in men treated with 5 mg finasteride and 1 case of breast cancer in men treated with placebo. There have been post-marketing reports of breast cancer in men using 1 mg and 5 mg of finasteride. The relationship between long-term use of finasteride and male breast tumor formation is unknown.
Prostate cancer
A randomized, double-blind, placebo-controlled Prostate Cancer Prevention Trial (PCPT) of 18,882 healthy men aged 55 years and older (normal rectal examination and PSA ≤ 3.0 ng/ml) was enrolled for 7 years. Patients received daily finasteride 5 mg or placebo, and PSA and rectal examination were evaluated annually. Biopsy was required when PSA was elevated, rectal examination was abnormal, or at the end of the study. When the Gleason score reached 8-10, the incidence of prostate cancer was 1.8% in the finasteride group, which was higher than 1.1% in the placebo group. In a 4-year clinical trial of another 5α-reductase inhibitor (dutasteride, AVODART) versus placebo, the incidence of prostate cancer was similar at Gleason scores of 8 to 10 (dutasteride 1%, placebo 0.5%). The clinical significance of these findings for men taking finasteride 1 mg is unknown.
Finasteride 5 mg has not shown clinical benefit in patients with prostate cancer, and finasteride 5 mg is not approved for reducing the risk of prostate cancer.
Post-Marketing Experience
The following are other adverse reactions reported post-marketing. Because these adverse reactions are reported spontaneously from a population of uncertain size, it is not always possible to reliably estimate their incidence or to establish a causal relationship to drug exposure.
Immune System Disorders: Hypersensitivity reactions such as rash, pruritus, urticaria, and angioedema (including swelling of the lips, tongue, throat, and face).
Musculoskeletal and Connective Tissue Disorders: Rare cases of rhabdomyolysis, myopathy, myalgia, muscle weakness, and elevated CK have been reported. In some cases, these adverse reactions were reversible after discontinuation of finasteride.
Psychiatric Disorders: Depression, anxiety, decreased libido that persisted after discontinuation of treatment.
Reproductive System: Sexual dysfunction that persisted after discontinuation of treatment, including erectile dysfunction, decreased libido, abnormal ejaculation, and orgasmic dysfunction. Hematospermia, male infertility and/or poor semen quality (semen quality has been reported to improve or return to normal after discontinuation of treatment), testicular pain. [See "Adverse Reactions (Clinical Trial Experience)". ]
Hepatobiliary disorders: Increased liver enzymes.
Tumors: Male breast cancer.
Breast disorders: Breast pain and enlargement.
[Contraindications]
This product is contraindicated for:
• Pregnant women or women who may become pregnant (see [Pregnant and lactating women use]).
• People who are allergic to any of the ingredients in this product.
This product is not suitable for women and children.
During use, it should not be taken at the same time as finasteride 5mg for the treatment of benign prostatic hyperplasia or any other 5α-reductase inhibitors.
【Precautions】
1. Direct contact with women - risk to male fetus
This product is not for use by women. Pregnant or potentially pregnant women must not come into contact with broken finasteride tablets to prevent absorption of finasteride and potential harm to the male fetus in the abdomen. Finasteride tablets have an outer film coating to prevent contact with the active ingredients of the drug during normal operation when the tablets are not broken.
2. Effect on PSA (serum prostate-specific antigen)
In a clinical study of men aged 18 to 41, serum prostate-specific antigen (PSA) dropped from a baseline level of 0.7ng/ml to 0.5ng/ml after taking finasteride 1mg for 12 months. In addition, when finasteride 5mg was used to treat elderly male hair loss patients with benign prostatic hyperplasia (BPH), serum prostate-specific antigen levels dropped by nearly 50%. Other studies have shown that finasteride 5mg can also reduce serum prostate-specific antigen in patients with prostate cancer. These findings can be used to explain the serum prostate-specific antigen levels in men treated with finasteride. Any confirmed increase in serum prostate-specific antigen during finasteride 1 mg, even if the value is within a reasonable range for men not taking 5α-reductase inhibitors, requires evaluation because it indicates the possibility of prostate cancer. Failure to comply with the finasteride 1 mg treatment regimen will also affect the results of serum prostate-specific antigen tests.
3. 5α-reductase inhibitors increase the risk of high-grade prostate cancer
In a 7-year prostate cancer prevention trial (PCPT), men over 55 years old who passed routine rectal examinations and had PSA ≤ 3.0 ng/ml were given finasteride 5 mg/day (5 times the dose of finasteride 1 mg tablets). When the Gleason score reached 8-10, the incidence of prostate cancer in the finasteride group was 1.8%, higher than 1.1% in the placebo group. In a 4-year clinical trial of another 5α-reductase inhibitor (dutasteride, AVODART) and placebo, the incidence of prostate cancer was similar, 1% in the dutasteride group and 0.5% in the placebo group. The clinical significance of these findings for men using finasteride 1 mg is unknown. 5α-reductase inhibitors may increase the risk of high-grade prostate cancer. The effect of 5α-reductase inhibitors on reducing prostate volume or whether study-related factors affect these findings has not been determined.
4. Mood changes and depression: Mood changes, including low mood, depression, and uncommon suicidal thoughts, have been reported in patients taking finasteride tablets 1 mg. The patient's mental state should be monitored, and if the above reactions occur, finasteride should be discontinued and a doctor's advice should be sought.
5. There is no data showing that finasteride affects the ability to drive or use machines.
6. During the use of this product, if any adverse events and/or adverse reactions occur, please consult a doctor.
7. Please inform your doctor if you are using other medicines at the same time.
8. Keep out of the reach of children.
9. Use with caution in patients with abnormal liver function.
10. No dose adjustment is required for patients with renal impairment.
[Pregnant and lactating women]
This product is contraindicated for use in pregnant women or women who may become pregnant. Because type II 5α-reductase inhibitors inhibit the conversion of testosterone to dihydrotestosterone in certain tissues, such inhibitors (including finasteride) can cause malformations in the external genitalia of male fetuses if used in pregnant women. Pregnant women or women who may become pregnant should not come into contact with broken finasteride tablets. Because the drug may be absorbed and then cause harm to the male fetus. The intact tablets have an outer coating to prevent contact with the active ingredients of the drug during normal operation. Breastfeeding women This product is not suitable for women. It is not clear whether finasteride is secreted in human milk.
【Pediatric Use】
This product is not suitable for children. Safety and efficacy studies in pediatric patients have not been established.
【Elderly Use】
Clinical studies on the use of this product in the treatment of male pattern baldness in elderly male patients have not been conducted.
【Drug Interactions】
No important drug interactions have been found clinically. Finasteride does not affect the drug metabolizing enzyme system related to cytochrome P450. Drugs that have been studied in men include antipyrine, digoxin, glyburide, propranolol, theophylline and warfarin, and no interactions have been found. Patients taking narrow therapeutic index drugs (such as phenytoin) should be carefully monitored when starting this product.
Although specific interaction studies have not been conducted, in clinical studies, no significant adverse interactions were observed when finasteride was used in doses of 1 mg or more with angiotensin-converting enzyme inhibitors, acetaminophen, alpha blockers, benzodiazepines, beta blockers, calcium channel blockers, nitrates, diuretics, H2 receptor antagonists, beta-hydroxy-beta-methylglutaryl coenzyme A reductase inhibitors, prostaglandin synthetase inhibitors, and quinolones.
[Overdose]
In clinical studies, no adverse reactions occurred when finasteride was used in single doses of 400 mg or multiple doses, with a total daily dose of 80 mg, for three consecutive months.
There is no recommended specific treatment for overdose of this product.
【Pharmacology and Toxicology】
Pharmacology
Mechanism of Action
Finasteride is a synthetic steroid compound that is a specific inhibitor of the intracellular enzyme type II 5α-reductase in the process of metabolizing the androgen testosterone into dihydrotestosterone. Finasteride has no affinity for androgen receptors, and has no androgenic, anti-androgenic, estrogen-like, anti-estrogen-like or progestational effects. Inhibition of this enzyme can hinder the conversion of testosterone to androgen dihydrotestosterone in peripheral tissues, significantly reducing the concentration of dihydrotestosterone in serum and tissues. Compared with placebo, the level of testosterone in the blood circulation can be increased by about 10~15%, but it is still within the physiological range. Finasteride can rapidly reduce the concentration of dihydrotestosterone in serum and significantly reduce it within 24 hours after administration.
Hair follicles contain type II 5α-reductase. In the bald area of the scalp of patients with male pattern baldness, the hair follicles become smaller and dihydrotestosterone increases. Administration of finasteride can reduce the concentration of dihydrotestosterone in the scalp and serum of these patients. Men who are congenitally deficient in type II 5α-reductase do not suffer from male pattern baldness. These data, along with the results of clinical studies, confirm that finasteride can inhibit the shrinkage of scalp hair follicles and reverse the process of hair loss.
Toxicological studies
Carcinogenicity/mutagenicity/impairment of fertility
A 24-month carcinogenicity study in rats showed an increased incidence of thyroid follicular adenomas in male rats receiving 160 mg/kg of finasteride per day (statistically significant trend test). This oral dose in rats is more than 800 times the recommended human dose (based on the area under the 0-24 hour drug-time curve). The effect of finasteride on the rat thyroid gland is caused by an increase in thyroxine clearance, not a direct effect of the drug. These observations in rats are not considered relevant to humans.
In a 19-month mouse carcinogenicity study, mice given 250 mg/kg of finasteride orally daily (estimated to be more than 1700 times the recommended human dose) had a statistically significant increase in the incidence of testicular Leydig cell adenomas; no adenomas were found at 2.5 or 25 mg/kg per day.
Increased incidence of Leydig cell hyperplasia was found in mice given 25 mg/kg per day (approximately 90 times the recommended human dose) and in rats given >40 mg/kg per day (approximately 300 times the recommended human dose).
In both rodent species treated with high doses of finasteride, a correlation has been demonstrated between changes in Leydig cell hyperplasia and increases in serum luteinizing hormone (LH) levels (2-3 times above control). This suggests that changes in Leydig cells are a function of increased serum luteinizing hormone (LH) levels rather than a direct effect of finasteride.
When rats and dogs were given finasteride at 20 mg/kg (about 220 times the recommended human dose) and 45 mg/kg (about 2600 times the recommended human dose) daily for one year, and mice were given 2.5 mg/kg (about 9 times the recommended human dose) daily for 19 months, no drug-related stromal cell changes were found.
No evidence of mutagenicity was found in in vitro bacterial mutagenesis experiments, mammalian cell mutagenesis experiments, and in vitro alkaline elution experiments. In the in vitro chromosome aberration experiment, Chinese rat ovarian cells were treated with high concentrations (450~550μmol) of finasteride, and chromosome aberrations increased slightly. This concentration exceeds the peak plasma concentration of humans at a total dose of 1 mg, which is not achievable by biological systems. In the in vivo chromosome aberration experiment in mice, no treatment-related increase in chromosome aberrations was found when the maximum tolerated dose of finasteride was given.
Male rabbits did not impair fertility when they were given finasteride at 80 mg/kg (about 4000 times the recommended human dose) daily. Male rats treated with oral finasteride 80 mg/kg daily (approximately 440 times the recommended human dose) for 24 to 30 weeks showed a significant decrease in fertility, accompanied by a significant reduction in the weight of the genital vesicles and prostate. These effects were reversible within 6 weeks of discontinuation of treatment.
The decrease in fertility in rats is secondary to the effects of finasteride on the accessory organs, resulting in the inability to form a semen plug, which is necessary for rat fertility but not relevant to humans.
Developmental studies
Pregnant rats given oral finasteride at doses ranging from 100 μg/kg to 100 mg/kg (>5 times the recommended human dose) had hypospadias in 3.6 to 100% of male offspring. In addition, male offspring born to pregnant rats given oral finasteride at 30 μg/kg (>1.5 times the recommended human dose) had decreased prostate and genital vesicle weights, prolonged preputial separation, and transient nipple development, and decreased anogenital interval when given oral finasteride at 3 μg/kg (approximately one-fifth the recommended human dose) daily. The critical period for the production of these effects has been limited to 16 to 17 days of gestation in male rats.
The above changes are believed to be pharmacological effects of type II 5α-reductase inhibitors. Some of the changes in male rats exposed to finasteride in utero, such as hypospadias, are similar to those reported in male rats with congenital type II 5α-reductase deficiency. There were no effects in female rats exposed in utero to any dose of finasteride.
Finasteride administration to rats during late pregnancy and lactation resulted in a slight reduction in fertility in the first generation of male offspring (3 mg/kg per day). No developmental abnormalities were found in the first generation of male and female offspring born from male rats treated with finasteride (80 mg/kg per day) mated with naive females.
There was no evidence of malformations in rabbit fetuses exposed in utero to 100 mg/kg of finasteride per day from gestational days 6 to 18.
An assessment of the effects of in utero exposure to finasteride during embryonic and fetal development in rhesus monkeys (gestational days 20 to 100) suggests that this species is more similar to humans than rats and rabbits. No abnormalities were found in male fetuses given intravenously to pregnant monkeys at a dose of 800 ng of finasteride per day (at least 750 times the maximum estimated amount of finasteride in semen to which pregnant women may be exposed, based on body weight). To confirm the relevance of the rhesus monkey model to human fetal development, oral administration of high doses of finasteride (2 mg/kg per day; 100 times the recommended human dose or based on body weight, approximately 12 million times the maximum estimated amount of finasteride in semen that pregnant women may be exposed to) to pregnant monkeys resulted in abnormalities of the external genitalia of male fetuses. No other abnormalities were found in male fetuses, and no finasteride-related abnormalities were observed in female fetuses at any dose.
[Pharmacokinetics]
Absorption: Compared with intravenous administration, the bioavailability of finasteride after oral administration is about 65%. Oral bioavailability is not affected by food. The concentration of finasteride in plasma reaches its peak about 1 to 2 hours after oral administration, with an average peak concentration of 9.2ng/ml, and the area under the drug-time curve from 0 to 24 hours is 53ng•hr/ml.
Distribution: The plasma protein binding rate is about 90%. The distribution volume of finasteride is about 76 liters. There will be a slow accumulation period after multiple doses of finasteride. Finasteride can pass through the blood-brain barrier. In a 6-week study of semen levels in 35 men who took 1mg of finasteride per day, finasteride was not detected in 60% (21 out of 35) of the samples (less than 0.2ng/ml). The average detection value of finasteride was 0.26ng/ml, and the highest was 1.52ng/ml. Assuming that the semen contains the highest level of finasteride, 5 ml of semen is ejaculated every day and 100% is absorbed, the exposure absorbed from the vagina is 7.6 ng per day, but it is still 650 times lower than the limit (5 μg) of finasteride affecting male dihydrotestosterone levels.
Metabolism: Finasteride is mainly metabolized under the catalysis of the cytochrome P450 3A4 enzyme system. There are two metabolites, tert-butyl side chain monohydroxylation and monocarboxylic acid metabolites, which have the activity of inhibiting 5α-reductase, and their activity does not exceed 20% of the activity of finasteride.
Elimination: After a man takes 14C-labeled finasteride once, 39% of the drug is excreted in the urine in the form of metabolites (in fact, no prototype drug is excreted in the urine), and 57% of the drug is excreted in the feces. The plasma clearance rate is about 165 ml/min. The average elimination half-life in plasma is 4.5 hours. The elimination rate of finasteride decreases with age. In men aged 18 to 60, the average elimination half-life of finasteride is about 5 to 6 hours, and in men over 70 years old, the elimination half-life is 8 hours. This difference is not clinically significant, so the elderly do not need to reduce the dosage.
Patient characteristics: For patients with chronic renal impairment with a creatinine clearance of 9 to 55 ml/min, the distribution of a single dose of 14C-finasteride is similar to that of healthy volunteers. Protein binding is also no different in patients with renal impairment. Some metabolites that are normally excreted by the kidneys are excreted in the feces. As a result, there will be an increase in fecal excretion equivalent to the decrease in renal excretion. Therefore, it is not necessary to adjust the dosage for patients with impaired renal function who are not on dialysis. The pharmacokinetic effects of finasteride administration to patients with liver damage have not been studied. Since finasteride is extensively metabolized in the liver, patients with liver damage need to be careful when taking finasteride 1 mg.
[Storage]
Light-proof, sealed.
[Packaging]
Aluminum-aluminum blister eye packaging, 28 pieces/box.
[Validity period]
24 months
[Approval number]
National Medicine Standard H20100160
[Drug marketing authorization holder]
Name: Beijing Hanmei Pharmaceutical Co., Ltd.
