Clinical medicine profile
Finasteride / Tamsulosin
5-alpha Reductase Inhibitor [EPC]
- Route
- See product SmPC
- Schedule
- POM
- ATC
- Not assigned
- PPB status
- registered
Safety essentials
The information most likely to change a prescribing or dispensing decision.
Contraindications
- 4 CONTRAINDICATIONS Finasteride tablets USP are contraindicated in the following: • Pregnancy.
- Finasteride use is contraindicated in women when they are or may potentially be pregnant.
- Because of the ability of Type II 5α-reductase inhibitors to inhibit the conversion of testosterone to 5α-dihydrotestosterone (DHT), finasteride may cause abnormalities of the external genitalia of a male fetus of a pregnant woman who receives finasteride.
- If this drug is used during pregnancy, or if pregnancy occurs while taking this drug, the pregnant woman should be apprised of the potential hazard to the male fetus. [ See Warnings and Precautions (5.1) , Use in Specific Populations (8.1) , How Supplied/Storage and Handling (16) and Patient Counseling Information (17.1) .] In female rats, low doses of finasteride administered during pregnancy have produced abnormalities of the external genitalia in male offspring. • Hypersensitivity to any component of this medication. • Pregnancy ( 4 , 5.1 , 8.1 , 16 ). • Hypersensitivity to any components of this product ( 4 ).
Precautions
- 5 WARNINGS AND PRECAUTIONS Finasteride tablets USP are not indicated for use in women or pediatric patients ( 5.1 , 5.4 ). • Women should not handle crushed or broken finasteride tablets USP when they are pregnant or may potentially be pregnant due to potential risk to a male fetus ( 5.1 , 8.1 , 16 ). • Finasteride tablets USP causes a decrease in serum PSA levels.
- Any confirmed increase in PSA while on finasteride tablets USP may signal the presence of prostate cancer and should be evaluated, even if those values are still within the normal range for men not taking a 5α-reductase inhibitor ( 5.2 ). • 5α-reductase inhibitors may increase the risk of high-grade prostate cancer ( 5.3 , 6.1 ). 5.1 Exposure of Women - Risk to Male Fetus Finasteride tablets USP are not indicated for use in women.
- Women should not handle crushed or broken finasteride tablets USP, when they are pregnant or may potentially be pregnant because of the possibility of absorption of finasteride and the subsequent potential risk to a male fetus.
- Finasteride tablets USP are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed. [S ee Indications and Usage (1) , Contraindications (4) , Use in Specific Populations (8.1) , How Supplied/Storage and Handling (16) and Patient Counseling Information (17.1) . ] 5.2 Effects on Prostate Specific Antigen (PSA) In clinical studies with finasteride tablets USP in men 18 to 41 years of age, the mean value of serum prostate specific antigen (PSA) decreased from 0.7 ng/mL at baseline to 0.5 ng/mL at Month 12.
- Further, in clinical studies with finasteride tablets USP 5 mg when used in older men who have benign prostatic hyperplasia (BPH), PSA levels are decreased by approximately 50%.
- Other studies with finasteride tablets USP 5 mg showed it may also cause decreases in serum PSA in the presence of prostate cancer.
- These findings should be taken into account for proper interpretation of serum PSA when evaluating men treated with finasteride.
- Any confirmed increase from the lowest PSA value while on finasteride tablets USP may signal the presence of prostate cancer and should be evaluated, even if PSA levels are still within the normal range for men not taking a 5α-reductase inhibitor.
- Non-compliance to therapy with finasteride tablets USP may also affect PSA test results. 5.3 Increased Risk of High-Grade Prostate Cancer with 5-Reductase Inhibitors Men aged 55 and over with a normal digital rectal examination and PSA ≤3 ng/mL at baseline taking finasteride 5 mg/day (5 times the dose of finasteride tablets USP 1 mg) in the 7-year Prostate Cancer Prevention Trial (PCPT) had an increased risk of Gleason score 8 to 10 prostate cancer (finasteride 1.8% vs placebo 1.1%). [ See Adverse Reactions (6.1) . ] Similar results were observed in a 4-year placebo-controlled clinical trial with another 5α-reductase inhibitor (dutasteride, AVODART)(1% dutasteride vs 0.5% placebo). 5α-reductase inhibitors may increase the risk of development of high-grade prostate cancer.
- Whether the effect of 5α-reductase inhibitors to reduce prostate volume, or study-related factors, impacted the results of these studies has not been established. 5.4 Pediatric Patients Finasteride tablets USP are not indicated for use in pediatric patients [ see Use in Specific Populations (8.4) ].
Dosing matrix
Population and organ-function guidance, shown together for faster comparison.
2 DOSAGE & ADMINISTRATION Finasteride tablets USP may be administered with or without meals. The recommended dose of finasteride tablets USP is one tablet (1 mg) taken once daily. In general, daily use for three months or more is necessary before benefit is observed. Continued use is recommended to sustain benefit, which should be re-evaluated periodically. Withdrawal of treatment leads to reversal of effect within 12 months. • Finasteride tablets USP may be administered with or without meals ( 2 ). • One tablet (1 mg) taken once daily ( 2 ). • In general, daily use for three months or more is necessary before benefit is observed ( 2 ).
8.4 Pediatric Use Finasteride tablets USP are not indicated for use in pediatric patients. Safety and effectiveness in pediatric patients have not been established.
Review renal impairment dosing; many agents need CrCl/eGFR adjustment.
- CrCl 0–120: Confirm renal dosing in product SmPC / primary label.
Review hepatic impairment dosing; monitor LFTs if agent is hepatically cleared or hepatotoxic.
Use, effects & interactions
Indications
- 1 INDICATIONS & USAGE Finasteride tablets USP are indicated for the treatment of male pattern hair loss (androgenetic alopecia) in MEN ONLY.
- Efficacy in bitemporal recession has not been established.
- Finasteride tablets USP are not indicated for use in women. • Finasteride tablets USP are 5α-reductase inhibitors indicated for the treatment of male pattern hair loss (androgenetic alopecia) in MEN ONLY ( 1 ). • Finasteride tablets USP are not indicated for use in women ( 1 , 4 , 5.1 ).
Adverse effects
- 6 ADVERSE REACTIONS The most common adverse reactions, reported in ≥1% of patients treated with finasteride tablets USP and greater than in patients treated with placebo are: decreased libido, erectile dysfunction and ejaculation disorder ( 6.1 ).
- To report SUSPECTED ADVERSE REACTIONS, contact Hetero Labs Limited at 866-495-1995 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
- See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice.
- Clinical Studies for Finasteride Tablets USP 1 mg in the Treatment of Male Pattern Hair Loss In three controlled clinical trials for finasteride tablets USP of 12-month duration, 1.4% of patients taking finasteride tablets USP (n=945) were discontinued due to adverse experiences that were considered to be possibly, probably or definitely drug-related (1.6% for placebo
- Clinical adverse experiences that were reported as possibly, probably or definitely drug-related in ≥1% of patients treated with finasteride tablets USP or placebo are presented in Table 1.
- TABLE 1 Drug-Related Adverse Experiences for Finasteride Tablets USP, 1 mg in Year 1 (%) MALE PATTERN HAIR LOSS Finasteride tablets USP N=945 Placebo N=934 Decreased Libido 1.8 1.3 Erectile Dysfunction 1.3 0.7 Ejaculation Disorder (Decreased Volume of Ejaculate) 1.2 (0.8) 0.7 (0.4) Discontinuation due to drug-related sexual adverse experiences 1.2 0.9 Integrated analysis of clinical adverse experiences showed that during treatment with finasteride tablets USP 36 (3.8%) of 945 men had reported one or more of these adverse experiences as compared to 20 (2.1%) of 934 men treated with placebo (p=0.04).
- Resolution occurred in men who discontinued therapy with finasteride tablets USP due to these side effects and in most of those who continued therapy.
- The incidence of each of the above adverse experiences decreased to ≤0.3% by the fifth year of treatment with finasteride tablets USP.
- In a study of finasteride 1 mg daily in healthy men, a median decrease in ejaculate volume of 0.3 mL (-11%) compared with 0.2 mL (-8%) for placebo was observed after 48 weeks of treatment.
- Two other studies showed that finasteride at 5 times the dosage of finasteride tablets USP (5 mg daily) produced significant median decreases of approximately 0.5 mL (-25%) compared to placebo in ejaculate volume, but this was reversible after discontinuation of treatment.
- In the clinical studies with finasteride tablets USP, the incidences for breast tenderness and enlargement, hypersensitivity reactions, and testicular pain in finasteride-treated patients were not different from those in patients treated with placebo.
- Controlled Clinical Trials and Long-Term Open Extension Studies for finasteride tablets USP, 5 mg and AVODART (dutasteride) in the Treatment of Benign Prostatic Hyperplasia In the finasteride tablets USP, 5 mg Long-Term Efficacy and Safety Study (PLESS), a 4-year controlled clinical study, 3040 patients between the ages of 45 and 78 with symptomatic BPH and an enlarged prostate were evaluated for safety over a period of 4 years (1524 on finasteride tablets USP, 5 mg/day and 1516 on placebo). 3.7% (57 patients) treated with finasteride tablets USP, 5 mg and 2.1% (32 patients) treated with placebo discontinued therapy as a result of adverse reactions related to sexual function, which are the most frequently reported adverse reactions.
- Table 2 presents the only clinical adverse reactions considered possibly, probably or definitely drug related by the investigator, for which the incidence on finasteride tablets USP, 5 mg was ≥1% and greater than placebo over the 4 years of the study.
- In years 2 to 4 of the study, there was no significant difference between treatment groups in the incidences of impotence, decreased libido and ejaculation disorder.
Drug interactions
Open multi-drug checker ↗- Fixed-dose/multi-ingredient product.
- Clinical details partially inherited from component monographs: Finasteride, Tamsulosin.
- Confirm combination SmPC for exact dosing.
Mechanism & disposition
12.
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12.1 Mechanism of Action Finasteride is a competitive and specific inhibitor of Type II 5α-reductase, an intracellular enzyme that converts the androgen testosterone into DHT. Two distinct isozymes are found in mice, rats, monkeys, and humans: Type I and II. Each of these isozymes is differentially expressed in tissues and developmental stages. In humans, Type I 5α-reductase is predominant in the sebaceous glands of most regions of skin, including scalp, and liver. Type I 5α-reductase is responsible for approximately one-third of circulating DHT. The Type II 5α-reductase isozyme is primarily found in prostate, seminal vesicles, epididymides, and hair follicles as well as liver, and is responsible for two-thirds of circulating DHT. In humans, the mechanism of action of finasteride is based on its preferential inhibition of the Type II isozyme. Using native tissues (scalp and prostate), in vitro binding studies examining the potential of finasteride to inhibit either isozyme revealed a 100-fold selectivity for the human Type II 5α-reductase over Type I isozyme (IC 50 =500 and 4.2 nM for Type I and II, respectively). For both isozymes, the inhibition by finasteride is accompanied by reduction of the inhibitor to dihydrofinasteride and adduct formation with NADP+. The turnover for the enzyme complex is slow (t 1/2 approximately 30 days for the Type II enzyme complex and 14 days for the Type I complex). Inhibition of Type II 5α-reductase blocks the peripheral conversion of testosterone to DHT, resulting in significant decreases in serum and tissue DHT concentrations. In men with male pattern hair loss (androgenetic alopecia), the balding scalp contains miniaturized hair follicles and increased amounts of DHT compared with hairy scalp. Administration of finasteride decreases scalp and serum DHT concentrations in these men. The relative contributions of these reductions to the treatment effect of finasteride have not been defined. By this mechanism, finasteride appears to interrupt a key factor in the development of androgenetic alopecia in those patients genetically predisposed.
Product-specific
Product-specific
See product SmPC
In a study in 15 healthy young male subjects, the mean bioavailability of finasteride 1-mg tablets was 65% (range 26 to 170%), based on the ratio of area under the curve (AUC) relative to an intravenous (IV) reference dose. At steady state following dosing with 1 mg/day (n=12), m...
Mean steady-state volume of distribution was 76 liters (range, 44 to 96 liters; n=15). Approximately 90% of circulating finasteride is bound to plasma proteins. There is a slow accumulation phase for finasteride after multiple dosing. Finasteride has been found to cross the blood...
Finasteride is extensively metabolized in the liver, primarily via the cytochrome P450 3A4 enzyme subfamily. Two metabolites, the t-butyl side chain monohydroxylated and monocarboxylic acid metabolites, have been identified that possess no more than 20% of the 5α-reductase inhibi...
Following intravenous infusion in healthy young subjects (n=15), mean plasma clearance of finasteride was 165 mL/min (range, 70 to 279 mL/min). Mean terminal
in plasma was 4.5 hours (range, 3.3 to 13.4 hours; n=12). Following an oral dose of 14 C-finasteride in man (n=6), a mean of 39% (range, 32 to 46%) of the dose was excreted in the urine in the form of metabolites; 57% (range, 51 to 64%) was excreted in the feces. Mean terminal ha...
Pregnancy, lactation & diet
8.1 Pregnancy Teratogenic Effects : Pregnancy Category X [ see Contraindications (4) ]. Finasteride tablets USP is contraindicated for use in women who are or may become pregnant. Finasteride tablets USP are Type II 5α-reductase inhibitor that prevents conversion of testosterone to 5α-dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia. In animal studies, finasteride caused abnormal development of external genitalia in male fetuses. If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, the patient should be apprised of the potential hazard to the male fetus. Abnormal male genital development is an expected consequence when conversion of testosterone to 5α-dihydrotestosterone (DHT) is inhibited by 5α-reductase inhibitors. These outcomes are similar to those reported in male infants with genetic 5α-reductase deficiency. Women could be exposed to finasteride through contact with crushed or broken finasteride tablets or semen from a male partner taking finasteride tablets USP. With regard to finasteride exposure through the skin, finasteride tablets USP are coated and will prevent skin contact with finasteride during normal handling if the tablets have not been crushed or broken. Women who are pregnant or may become pregnant should not handle crushed or broken finasteride tablets USP because of possible exposure of a male fetus. If a pregnant woman comes in contact with crushed or broken finasteride tablets , the contact area should be washed immediately with soap and water. With regard to potential finasteride exposure through semen, a study has been conducted in men receiving finasteride tablets USP 1 mg/day that measured finasteride concentrations in semen [ see Clinical Pharmacology (12.3) ]. In an embryo-fetal development study, pregnant rats received finasteride during the period of major organogenesis (gestation days 6 to 17). At maternal doses of oral finasteride approximately 1 to 684 times the recommended human dose ( RHD ) of 1 mg/day (based on AUC at animal doses of 0.1 to 100 mg/kg/day) there was a dose-dependent increase in hypospadias that occurred in 3.6 to 100% of male offspring. Exposure multiples were estimated using data from nonpregnant rats. Days 16 to 17 of gestation are a critical period in male fetal rats for differentiation of the external genitalia. At oral maternal doses approximately 0.2 times the RHD (based on AUC at animal dose of 0.03 mg/kg/day), male offspring had decreased prostatic and seminal vesicular weights, delayed preputial separation and transient nipple development. Decreased anogenital distance occurred in male offspring of pregnant rats that received approximately 0.02 times the RHD (based on AUC at animal dose of 0.003 mg/kg/day). No abnormalities were observed in female offspring exposed to any dose of finasteride in utero . No developmental abnormalities were observed in the offspring of untreated females mated with finasteride-treated male rats that received approximately 488 times the RHD (based on AUC at animal dose of 80 mg/kg/day). Slightly decreased fertility was observed in male offspring after administration of about 20 times the RHD (based on AUC at animal dose of 3 mg/kg/day) to female rats during late gestation and lactation. No effects on fertility were seen in female offspring under these conditions. No evidence of male external genital malformations or other abnormalities were observed in rabbit fetuses exposed to finasteride during the period of major organogenesis (gestation days 6 to 18) at maternal doses up to 100 mg/kg/day (finasteride exposure levels were not measured in rabbits). However, this study may not have included the critical period for finasteride effects on development of male external genitalia in the rabbit. The fetal effects of maternal finasteride exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days 20 to 100), in a species and development period more predictive of specific effects in humans than the studies in rats and rabbits. Intravenous administration of finasteride to pregnant monkeys at doses as high as 800 ng/day (estimated maximal blood concentration of 1.86 ng/mL or about 930 times the highest estimated exposure of pregnant women to finasteride from semen of men taking 1 mg/day) resulted in no abnormalities in male fetuses. In confirmation of the relevance of the rhesus model for human fetal development, oral administration of a dose of finasteride (2 mg/kg/day or approximately 120,000 times the highest estimated blood levels of finasteride from semen of men taking 1 mg/day) to pregnant monkeys resulted in external genital abnormalities in male fetuses. No other abnormalities were observed in male fetuses and no finasteride-related abnormalities were observed in female fetuses at any dose.
[Finasteride] Assess infant risk vs benefit of maternal therapy; prefer agents with lactation data. [Tamsulosin] • Pediatric Use: Not indicated for use in pediatric populations ( 8.4 , 12.3 ) • Geriatric Use: No overall differences in efficacy or safety vs. younger patients, but greater sensitivity of some older adults cannot be ruled out ( 8.5 , 12.3 ) • Renal Impairment: Has not been studied in patients with end-stage renal disease ( 8.6 , 12.3 ) • Hepatic Impairment: Has not been studied in patients with severe hepatic impairment ( 8.7 , 12.3 ) 8.1 Pregnancy Risk Summary Tamsulosin hydrochloride is not indicated for use in women. There are no adequate data on the developmental risk associated with the use of tamsulosin hydrochloride in pregnant women. No adverse developmental effects were observed in animal studies in which tamsulosin hydrochloride was administered to rats or rabbits during the period of organogenesis (GD 7 to 17 in the rat and GD 6 to 18 in the rabbit) [see Data]. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2%–4% and 15%–20%, respectively. Data Administration of tamsulosin hydrochloride to pregnant female rats during the period of organogenesis at dose levels up to approximately 50 times the human therapeutic AUC exposure (300 mg/kg/day) revealed no evidence of harm to the fetus. Administration of tamsulosin hydrochloride to pregnant rabbits during the period of organogenesis at dose levels up to 50 mg/kg/day produced no evidence of fetal harm. 8.2 Lactation Tamsulosin hydrochloride is not indicated for use in women. There are no data on the presence of tamsulosin hydrochloride in human milk, the effects of tamsulosin hydrochloride on the breastfed infant, or the effects of tamsulosin hydrochloride on milk production. Tamsulosin hydrochloride is present in the milk of lactating rats [see Data]. Data Oral administration of radiolabeled tamsulosin hydrochloride to rats demonstrated that tamsulosin hydrochloride and/or its metabolites are excreted into the milk of rats. 8.3 Females and Males of Reproductive Potential Infertility Males Abnormal ejaculation including ejaculation failure, ejaculation disorder, retrograde ejaculation, and ejaculation decrease has been associated with tamsulosin hydrochloride [see Clinical Trials Experience (6.1)]. Studies in rats revealed significantly reduced fertility in males considered to be due to impairment of ejaculation, which was reversible [see Nonclinical Toxicology (13.1)]. Females Tamsulosin hydrochloride is not indicated for use in women. Female fertility in rats was significantly reduced, considered to be due to impairment of fertilization [see Nonclinical Toxicology (13.1)]. 8.4 Pediatric Use Tamsulosin hydrochloride capsules are not indicated for use in pediatric populations. Efficacy and positive benefit/risk of tamsulosin hydrochloride was not demonstrated in two studies conducted in patients 2 years to 16 years of age with elevated detrusor leak point pressure (>40 cm H 2 O) associated with known neurological disorder (e.g., spina bifida). Patients in both studies were treated on a weight-based mg/kg schema (0.025 mg, 0.05 mg, 0.1 mg, 0.2 mg, or 0.4 mg tamsulosin hydrochloride) for the reduction in detrusor leak point pressure below 40 cm H 2 O. In a randomized, double-blind, placebo-controlled, 14-week, pharmacokinetic, safety and efficacy study in 161 patients, no statistically significant difference in the proportion of responders was observed between groups receiving tamsulosin hydrochloride and placebo. In an open-label, 12-month safety study, 87 patients were treated with tamsulosin hydrochloride. The most frequently reported adverse events (≥5%) from the pooled data of both studies were urinary tract infection, vomiting, pyrexia, headache, nasopharyngitis, cough, pharyngitis, influenza, diarrhea, abdominal pain, and constipation. 8.5 Geriatric Use Of the total number of subjects (1783) in clinical studies of tamsulosin, 36% were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and the other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3)]. 8.6 Renal Impairment Patients with renal impairment do not require an adjustment in tamsulosin hydrochloride capsules dosing. However, patients with end-stage renal disease (CL cr <10 mL/min/1.73 m 2 ) have not been studied [see Clinical Pharmacology (12.3)]. 8.7 Hepatic Impairment Patients with moderate hepatic impairment do not require an adjustment in tamsulosin hydrochloride capsules dosage. Tamsulosin hydrochloride has not been studied in patients with severe hepatic impairment [see Clinical Pharmacology (12.3)].
Brands & loaded prices
| Brand | Manufacturer | Pack | Observed price |
|---|---|---|---|
| FINOSIN TABS *30`S | Not recorded | — | KES 1,796.97Daima Chemist price-list reference ↗ Source date not recorded · verify current price |
Sources & review state
Decision support only. Confirm patient-specific decisions against the current product SmPC, Kenya STG/EML, and professional judgement.