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DRUGS & SUPPLEMENTS
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Finasteride:
Tampace-F, is a 5α-reductase inhibitor, indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to (1.1):
Tampace-F (Finasteride) administered in combination with the alpha-blocker doxazosin is indicated to reduce the risk of symptomatic progression of BPH (a confirmed ≥4 point increase in American Urological Association (AUA) symptom score) (1.2).
Limitations of Use: Tampace-F (Finasteride) is not approved for the prevention of prostate cancer (1.3).
Tampace-F (Finasteride)® is indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to:
Tampace-F administered in combination with the alpha-blocker doxazosin is indicated to reduce the risk of symptomatic progression of BPH (a confirmed ≥4 point increase in American Urological Association (AUA) symptom score).
Tampace-F (Finasteride) is not approved for the prevention of prostate cancer.
Tampace-F may be administered with or without meals.
Tampace-F (Finasteride) may be administered with or without meals (2).
Monotherapy: One tablet (5 mg) taken once a day (2.1).
Combination with Doxazosin: One tablet (5 mg) taken once a day in combination with the alpha-blocker doxazosin (2.2).
The recommended dose of Tampace-F (Finasteride) is one tablet (5 mg) taken once a day .
The recommended dose of Tampace-F (Finasteride) is one tablet (5 mg) taken once a day in combination with the alpha-blocker doxazosin .
5-mg blue, modified apple-shaped, film-coated tablets, with the code MSD 72 on one side and Tampace-F (Finasteride) on the other.
5-mg film-coated tablets (3).
Tampace-F (Finasteride) is contraindicated in the following:
Hypersensitivity to any components of this product (4).
Women who are or may potentially be pregnant (4, 5.4, 8.1, 16).
In clinical studies, Tampace-F (Finasteride) reduced serum PSA concentration by approximately 50% within six months of treatment. This decrease is predictable over the entire range of PSA values in patients with symptomatic BPH, although it may vary in individuals.
For interpretation of serial PSAs in men taking Tampace-F (Finasteride), a new PSA baseline should be established at least six months after starting treatment and PSA monitored periodically thereafter. Any confirmed increase from the lowest PSA value while on Tampace-F (Finasteride) 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 with Tampace-F (Finasteride) therapy may also affect PSA test results. To interpret an isolated PSA value in patients treated with Tampace-F (Finasteride) for six months or more, PSA values should be doubled for comparison with normal ranges in untreated men. These adjustments preserve the utility of PSA to detect prostate cancer in men treated with Tampace-F (Finasteride).
Tampace-F (Finasteride) may also cause decreases in serum PSA in the presence of prostate cancer.
The ratio of free to total PSA (percent free PSA) remains constant even under the influence of Tampace-F (Finasteride). If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men undergoing Tampace-F (Finasteride) therapy, no adjustment to its value appears necessary.
Men aged 55 and over with a normal digital rectal examination and PSA ≤3.0 ng/mL at baseline taking Tampace-F 5 mg/day in the 7-year Prostate Cancer Prevention Trial (PCPT) had an increased risk of Gleason score 8-10 prostate cancer (finasteride 1.8% vs placebo 1.1%). 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.
Women should not handle crushed or broken Tampace-F (Finasteride) tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of Tampace-F (Finasteride) and the subsequent potential risk to a male fetus. Tampace-F (Finasteride) tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed.
Tampace-F is not indicated for use in pediatric patients or women .
Treatment with Tampace-F (Finasteride) for 24 weeks to evaluate semen parameters in healthy male volunteers revealed no clinically meaningful effects on sperm concentration, mobility, morphology, or pH. A 0.6 mL (22.1%) median decrease in ejaculate volume with a concomitant reduction in total sperm per ejaculate was observed. These parameters remained within the normal range and were reversible upon discontinuation of therapy with an average time to return to baseline of 84 weeks.
Prior to initiating treatment with Tampace-F (Finasteride), consideration should be given to other urological conditions that may cause similar symptoms. In addition, prostate cancer and BPH may coexist.
Patients with large residual urinary volume and/or severely diminished urinary flow should be carefully monitored for obstructive uropathy. These patients may not be candidates for Tampace-F (Finasteride) therapy.
The drug-related adverse reactions, reported in ≥1% in patients treated with Tampace-F and greater than in patients treated with placebo over a 4-year study are: impotence, decreased libido, decreased volume of ejaculate, breast enlargement, breast tenderness and rash (6.1).
To report SUSPECTED ADVERSE REACTIONS, contact Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., at 1-877-888-4231 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
Tampace-F (Finasteride) is generally well tolerated; adverse reactions usually have been mild and transient.
4-Year Placebo-Controlled Study (PLESS)
In PLESS, 1524 patients treated with Tampace-F (Finasteride) and 1516 patients treated with placebo were evaluated for safety over a period of 4 years. The most frequently reported adverse reactions were related to sexual function. 3.7% (57 patients) treated with Tampace-F (Finasteride) 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 1 presents the only clinical adverse reactions considered possibly, probably or definitely drug related by the investigator, for which the incidence on Tampace-F (Finasteride) was ≥1% and greater than placebo over the 4 years of the study. In years 2-4 of the study, there was no significant difference between treatment groups in the incidences of impotence, decreased libido and ejaculation disorder.
Year 1 (%) | Years 2, 3 and 4 (%) | |||
---|---|---|---|---|
Tampace-F (Finasteride) | Placebo | Tampace-F (Finasteride) | Placebo | |
N = 1524 and 1516, Tampace-F (Finasteride) vs placebo, respectively | ||||
Impotence | 8.1 | 3.7 | 5.1 | 5.1 |
Decreased Libido | 6.4 | 3.4 | 2.6 | 2.6 |
Decreased Volume of Ejaculate | 3.7 | 0.8 | 1.5 | 0.5 |
Ejaculation Disorder | 0.8 | 0.1 | 0.2 | 0.1 |
Breast Enlargement | 0.5 | 0.1 | 1.8 | 1.1 |
Breast Tenderness | 0.4 | 0.1 | 0.7 | 0.3 |
Rash | 0.5 | 0.2 | 0.5 | 0.1 |
Phase III Studies and 5-Year Open Extensions
The adverse experience profile in the 1-year, placebo-controlled, Phase III studies, the 5-year open extensions, and PLESS were similar.
Medical Therapy of Prostatic Symptoms (MTOPS) Study
In the MTOPS study, 3047 men with symptomatic BPH were randomized to receive Tampace-F (Finasteride) 5 mg/day (n=768), doxazosin 4 or 8 mg/day (n=756), the combination of Tampace-F (Finasteride) 5 mg/day and doxazosin 4 or 8 mg/day (n=786), or placebo (n=737) for 4 to 6 years.
The incidence rates of drug-related adverse experiences reported by ≥2% of patients in any treatment group in the MTOPS Study are listed in Table 2.
The individual adverse effects which occurred more frequently in the combination group compared to either drug alone were: asthenia, postural hypotension, peripheral edema, dizziness, decreased libido, rhinitis, abnormal ejaculation, impotence and abnormal sexual function. Of these, the incidence of abnormal ejaculation in patients receiving combination therapy was comparable to the sum of the incidences of this adverse experience reported for the two monotherapies.
Combination therapy with Tampace-F (Finasteride) and doxazosin was associated with no new clinical adverse experience.
Four patients in MTOPS reported the adverse experience breast cancer. Three of these patients were on Tampace-F (Finasteride) only and one was on combination therapy.
The MTOPS Study was not specifically designed to make statistical comparisons between groups for reported adverse experiences. In addition, direct comparisons of safety data between the MTOPS study and previous studies of the single agents may not be appropriate based upon differences in patient population, dosage or dose regimen, and other procedural and study design elements.
Adverse Experience | Placebo (N=737) (%) | Doxazosin 4 mg or 8 mg (N=756) (%) | Tampace-F (Finasteride) (N=768) (%) | Combination (N=786) (%) | |
---|---|---|---|---|---|
Body as a whole | |||||
Asthenia | 7.1 | 15.7 | 5.3 | 16.8 | |
Headache | 2.3 | 4.1 | 2.0 | 2.3 | |
Cardiovascular | |||||
Hypotension | 0.7 | 3.4 | 1.2 | 1.5 | |
Postural Hypotension | 8.0 | 16.7 | 9.1 | 17.8 | |
Metabolic and Nutritional | |||||
Peripheral Edema | 0.9 | 2.6 | 1.3 | 3.3 | |
Nervous | |||||
Dizziness | 8.1 | 17.7 | 7.4 | 23.2 | |
Libido Decreased | 5.7 | 7.0 | 10.0 | 11.6 | |
Somnolence | 1.5 | 3.7 | 1.7 | 3.1 | |
Respiratory | |||||
Dyspnea | 0.7 | 2.1 | 0.7 | 1.9 | |
Rhinitis | 0.5 | 1.3 | 1.0 | 2.4 | |
Urogenital | |||||
Abnormal Ejaculation | 2.3 | 4.5 | 7.2 | 14.1 | |
Gynecomastia | 0.7 | 1.1 | 2.2 | 1.5 | |
Impotence | 12.2 | 14.4 | 18.5 | 22.6 | |
Sexual Function Abnormal | 0.9 | 2.0 | 2.5 | 3.1 |
High-Grade Prostate Cancer
The PCPT trial was a 7-year randomized, double-blind, placebo-controlled trial that enrolled 18,882 men ≥55 years of age with a normal digital rectal examination and a PSA ≤3.0 ng/mL. Men received either Tampace-F (Finasteride) (finasteride 5 mg) or placebo daily. Patients were evaluated annually with PSA and digital rectal exams. Biopsies were performed for elevated PSA, an abnormal digital rectal exam, or the end of study. The incidence of Gleason score 8-10 prostate cancer was higher in men treated with Tampace-F (Finasteride) (1.8%) than in those treated with placebo (1.1%) . In a 4-year placebo-controlled clinical trial with another 5α-reductase inhibitor (dutasteride, AVODART), similar results for Gleason score 8-10 prostate cancer were observed (1% dutasteride vs 0.5% placebo).
No clinical benefit has been demonstrated in patients with prostate cancer treated with Tampace-F (Finasteride).
Breast Cancer
During the 4- to 6-year placebo- and comparator-controlled MTOPS study that enrolled 3047 men, there were 4 cases of breast cancer in men treated with Tampace-F (Finasteride) but no cases in men not treated with Tampace-F (Finasteride). During the 4-year, placebo-controlled PLESS study that enrolled 3040 men, there were 2 cases of breast cancer in placebo-treated men but no cases in men treated with Tampace-F (Finasteride). During the 7-year placebo-controlled Prostate Cancer Prevention Trial (PCPT) that enrolled 18,882 men, there was 1 case of breast cancer in men treated with Tampace-F (Finasteride), and 1 case of breast cancer in men treated with placebo. The relationship between long-term use of Tampace-F (Finasteride) and male breast neoplasia is currently unknown.
Sexual Function
There is no evidence of increased sexual adverse experiences with increased duration of treatment with Tampace-F (Finasteride). New reports of drug-related sexual adverse experiences decreased with duration of therapy.
The following additional adverse events have been reported in postmarketing experience with Tampace-F (Finasteride). Because these events are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure:
The following additional adverse event related to sexual dysfunction that continued after discontinuation of treatment has been reported in postmarketing experience with Tampace-F (Finasteride) at lower doses used to treat male pattern baldness. Because the event is reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate its frequency or establish a causal relationship to drug exposure:
No drug interactions of clinical importance have been identified. Tampace-F does not appear to affect the cytochrome P450-linked drug metabolizing enzyme system. Compounds that have been tested in man have included antipyrine, digoxin, propranolol, theophylline, and warfarin and no clinically meaningful interactions were found.
Although specific interaction studies were not performed, Tampace-F (Finasteride) was concomitantly used in clinical studies with acetaminophen, acetylsalicylic acid, α-blockers, angiotensin-converting enzyme (ACE) inhibitors, analgesics, anti-convulsants, beta-adrenergic blocking agents, diuretics, calcium channel blockers, cardiac nitrates, HMG-CoA reductase inhibitors, nonsteroidal anti-inflammatory drugs (NSAIDs), benzodiazepines, H2 antagonists and quinolone anti-infectives without evidence of clinically significant adverse interactions.
Pregnancy Category X.
Tampace-F (Finasteride) is contraindicated for use in women who are or may become pregnant. Tampace-F (Finasteride) is a 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, Tampace-F (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 Tampace-F (Finasteride) through contact with crushed or broken Tampace-F (Finasteride) tablets or semen from a male partner taking Tampace-F (Finasteride). With regard to Tampace-F (Finasteride) exposure through the skin, Tampace-F (Finasteride) tablets are coated and will prevent skin contact with Tampace-F (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 Tampace-F (Finasteride) tablets because of possible exposure of a male fetus. If a pregnant woman comes in contact with crushed or broken Tampace-F (Finasteride) tablets, the contact area should be washed immediately with soap and water. With regard to potential Tampace-F (Finasteride) exposure through semen, two studies have been conducted in men receiving Tampace-F (Finasteride) 5 mg/day that measured Tampace-F (Finasteride) concentrations in semen .
In an embryo-fetal development study, pregnant rats received Tampace-F (Finasteride) during the period of major organogenesis (gestation days 6 to 17). At maternal doses of oral Tampace-F (Finasteride) approximately 0.1 to 86 times the maximum recommended human dose (MRHD) of 5 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 is a critical period in male fetal rats for differentiation of the external genitalia. At oral maternal doses approximately 0.03 times the MRHD (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 0.003 times the MRHD (based on AUC at animal dose of 0.003 mg/kg/day). No abnormalities were observed in female offspring at any maternal dose of Tampace-F (Finasteride).
No developmental abnormalities were observed in the offspring of untreated females mated with Tampace-F (Finasteride) treated male rats that received approximately 61 times the MRHD (based on AUC at animal dose of 80 mg/kg/day). Slightly decreased fertility was observed in male offspring after administration of about 3 times the MRHD (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 Tampace-F (Finasteride) during the period of major organogenesis (gestation days 6-18) at maternal oral 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 Tampace-F (Finasteride) effects on development of male external genitalia in the rabbit.
The fetal effects of maternal Tampace-F (Finasteride) exposure during the period of embryonic and fetal development were evaluated in the rhesus monkey (gestation days 20-100), in a species and development period more predictive of specific effects in humans than the studies in rats and rabbits. Intravenous administration of Tampace-F (Finasteride) to pregnant monkeys at doses as high as 800 ng/day (estimated maximal blood concentration of 1.86 ng/mL or about 143 times the highest estimated exposure of pregnant women to Tampace-F (Finasteride) from semen of men taking 5 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 Tampace-F (Finasteride) (2 mg/kg/day or approximately 18,000 times the highest estimated blood levels of Tampace-F (Finasteride) from semen of men taking 5 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.
Tampace-F (Finasteride) is not indicated for use in women.
It is not known whether Tampace-F (Finasteride) is excreted in human milk.
Tampace-F is not indicated for use in pediatric patients.
Safety and effectiveness in pediatric patients have not been established.
Of the total number of subjects included in PLESS, 1480 and 105 subjects were 65 and over and 75 and over, respectively. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients. No dosage adjustment is necessary in the elderly .
Caution should be exercised in the administration of Tampace-F in those patients with liver function abnormalities, as Tampace-F (Finasteride) is metabolized extensively in the liver .
No dosage adjustment is necessary in patients with renal impairment .
Patients have received single doses of Tampace-F (Finasteride) up to 400 mg and multiple doses of Tampace-F (Finasteride) up to 80 mg/day for three months without adverse effects. Until further experience is obtained, no specific treatment for an overdose with Tampace-F (Finasteride) can be recommended.
Significant lethality was observed in male and female mice at single oral doses of 1500 mg/m2 (500 mg/kg) and in female and male rats at single oral doses of 2360 mg/m2 (400 mg/kg) and 5900 mg/m2 (1000 mg/kg), respectively.
Tampace-F (finasteride), a synthetic 4-azasteroid compound, is a specific inhibitor of steroid Type II 5α-reductase, an intracellular enzyme that converts the androgen testosterone into 5α-dihydrotestosterone (DHT).
Tampace-F (Finasteride) is 4-azaandrost-1-ene-17-carboxamide, N-(1,1-dimethylethyl)-3-oxo-,(5α,17ß)-. The empirical formula of Tampace-F (Finasteride) is C23H36N2O2 and its molecular weight is 372.55. Its structural formula is:
Results seen in earlier studies were comparable to those seen in PLESS. Although an early improvement in urinary symptoms was seen in some patients, a therapeutic trial of at least 6 months was generally necessary to assess whether a beneficial response in symptom relief had been achieved. The improvement in BPH symptoms was seen during the first year and maintained throughout an additional 5 years of open extension studies.
Effect on Acute Urinary Retention and the Need for Surgery
In PLESS, efficacy was also assessed by evaluating treatment failures. Treatment failure was prospectively defined as BPH-related urological events or clinical deterioration, lack of improvement and/or the need for alternative therapy. BPH-related urological events were defined as urological surgical intervention and acute urinary retention requiring catheterization. Complete event information was available for 92% of the patients. The following table (Table 5) summarizes the results.
| Patients (%) | | | | |
Event | Placebo N=1503 | Tampace-F (Finasteride) N=1513 | Relative Risk | 95% CI | P Value |
All Treatment Failures | 37.1 | 26.2 | 0.68 | (0.57 to 0.79) | <0.001 |
Surgical Interventions for BPH | 10.1 | 4.6 | 0.45 | (0.32 to 0.63) | <0.001 |
Acute Urinary Retention Requiring Catheterization | 6.6 | 2.8 | 0.43 | (0.28 to 0.66) | <0.001 |
Two consecutive symptom scores ≥20 | 9.2 | 6.7 | |||
Bladder Stone | 0.4 | 0.5 | |||
Incontinence | 2.1 | 1.7 | |||
Renal Failure | 0.5 | 0.6 | |||
UTI | 5.7 | 4.9 | |||
Discontinuation due to worsening of BPH, lack of improvement, or to receive other medical treatment | 21.8 | 13.3 |
Compared with placebo, Tampace-F (Finasteride) was associated with a significantly lower risk for acute urinary retention or the need for BPH-related surgery [13.2% for placebo vs 6.6% for Tampace-F (Finasteride); 51% reduction in risk, 95% CI: (34 to 63%)]. Compared with placebo, Tampace-F (Finasteride) was associated with a significantly lower risk for surgery [10.1% for placebo vs 4.6% for Tampace-F (Finasteride); 55% reduction in risk, 95% CI: (37 to 68%)] and with a significantly lower risk of acute urinary retention [6.6% for placebo vs 2.8% for Tampace-F (Finasteride); 57% reduction in risk, 95% CI: (34 to 72%)]; see Figures 2 and 3.
Effect on Maximum Urinary Flow Rate
In the patients in PLESS who remained on therapy for the duration of the study and had evaluable urinary flow data, Tampace-F (Finasteride) increased maximum urinary flow rate by 1.9 mL/sec compared with 0.2 mL/sec in the placebo group.
There was a clear difference between treatment groups in maximum urinary flow rate in favor of Tampace-F (Finasteride) by month 4 (1.0 vs 0.3 mL/sec) which was maintained throughout the study. In the earlier 1-year studies, increase in maximum urinary flow rate was comparable to PLESS and was maintained through the first year and throughout an additional 5 years of open extension studies.
Effect on Prostate Volume
In PLESS, prostate volume was assessed yearly by magnetic resonance imaging (MRI) in a subset of patients. In patients treated with Tampace-F (Finasteride) who remained on therapy, prostate volume was reduced compared with both baseline and placebo throughout the 4-year study. Tampace-F (Finasteride) decreased prostate volume by 17.9% (from 55.9 cc at baseline to 45.8 cc at 4 years) compared with an increase of 14.1% (from 51.3 cc to 58.5 cc) in the placebo group (p<0.001).
Results seen in earlier studies were comparable to those seen in PLESS. Mean prostate volume at baseline ranged between 40-50 cc. The reduction in prostate volume was seen during the first year and maintained throughout an additional five years of open extension studies.
Prostate Volume as a Predictor of Therapeutic Response
A meta-analysis combining 1-year data from seven double-blind, placebo-controlled studies of similar design, including 4491 patients with symptomatic BPH, demonstrated that, in patients treated with Tampace-F (Finasteride), the magnitude of symptom response and degree of improvement in maximum urinary flow rate were greater in patients with an enlarged prostate at baseline.
The Medical Therapy of Prostatic Symptoms (MTOPS) Trial was a double-blind, randomized, placebo-controlled, multicenter, 4- to 6-year study (average 5 years) in 3047 men with symptomatic BPH, who were randomized to receive Tampace-F (Finasteride) 5 mg/day (n=768), doxazosin 4 or 8 mg/day (n=756), the combination of Tampace-F (Finasteride) 5 mg/day and doxazosin 4 or 8 mg/day (n=786), or placebo (n=737). All participants underwent weekly titration of doxazosin (or its placebo) from 1 to 2 to 4 to 8 mg/day. Only those who tolerated the 4 or 8 mg dose level were kept on doxazosin (or its placebo) in the study. The participant's final tolerated dose (either 4 mg or 8 mg) was administered beginning at end-Week 4. The final doxazosin dose was administered once per day, at bedtime.
The mean patient age at randomization was 62.6 years (±7.3 years). Patients were Caucasian (82%), African American (9%), Hispanic (7%), Asian (1%) or Native American (<1%). The mean duration of BPH symptoms was 4.7 years (±4.6 years). Patients had moderate to severe BPH symptoms at baseline with a mean AUA symptom score of approximately 17 out of 35 points. Mean maximum urinary flow rate was 10.5 mL/sec (±2.6 mL/sec). The mean prostate volume as measured by transrectal ultrasound was 36.3 mL (±20.1 mL). Prostate volume was ≤20 mL in 16% of patients, ≥50 mL in 18% of patients and between 21 and 49 mL in 66% of patients.
The primary endpoint was a composite measure of the first occurrence of any of the following five outcomes: a ≥4 point confirmed increase from baseline in symptom score, acute urinary retention, BPH-related renal insufficiency (creatinine rise), recurrent urinary tract infections or urosepsis, or incontinence. Compared to placebo, treatment with Tampace-F (Finasteride), doxazosin, or combination therapy resulted in a reduction in the risk of experiencing one of these five outcome events by 34% (p=0.002), 39% (p<0.001), and 67% (p<0.001), respectively. Combination therapy resulted in a significant reduction in the risk of the primary endpoint compared to treatment with Tampace-F (Finasteride) alone (49%; p≤0.001) or doxazosin alone (46%; p≤0.001).
Treatment Group | |||||
Placebo | Doxazosin | Tampace-F (Finasteride) | Combination | Total | |
N=737 | N=756 | N=768 | N=786 | N=3047 | |
Event | N (%) | N (%) | N (%) | N (%) | N (%) |
AUA 4-point rise | 100 (13.6) | 59 (7.8) | 74 (9.6) | 41 (5.2) | 274 (9.0) |
Acute urinary retention | 18 (2.4) | 13 (1.7) | 6 (0.8) | 4 (0.5) | 41 (1.3) |
Incontinence | 8 (1.1) | 11 (1.5) | 9 (1.2) | 3 (0.4) | 31 (1.0) |
Recurrent UTI/urosepsis | 2 (0.3) | 2 (0.3) | 0 (0.0) | 1 (0.1) | 5 (0.2) |
Creatinine rise | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) | 0 (0.0) |
Total Events | 128 (17.4) | 85 (11.2) | 89 (11.6) | 49 (6.2) | 351 (11.5) |
The majority of the events (274 out of 351; 78%) was a confirmed ≥4 point increase in symptom score, referred to as symptom score progression. The risk of symptom score progression was reduced by 30% (p=0.016), 46% (p<0.001), and 64% (p<0.001) in patients treated with Tampace-F (Finasteride), doxazosin, or the combination, respectively, compared to patients treated with placebo. Combination therapy significantly reduced the risk of symptom score progression compared to the effect of Tampace-F (Finasteride) alone (p<0.001) and compared to doxazosin alone (p=0.037).
Treatment with Tampace-F (Finasteride), doxazosin or the combination of Tampace-F (Finasteride) with doxazosin, reduced the mean symptom score from baseline at year 4. Table 7 provides the mean change from baseline for AUA symptom score by treatment group for patients who remained on therapy for four years.
Placebo N=534 | Doxazosin N=582 | Tampace-F (Finasteride) N=565 | Combination N=598 | |
Baseline Mean (SD) | 16.8 (6.0) | 17.0 (5.9) | 17.1 (6.0) | 16.8 (5.8) |
Mean Change AUA Symptom Score (SD) | -4.9 (5.8) | -6.6 (6.1) | -5.6 (5.9) | -7.4 (6.3) |
Comparison to Placebo (95% CI) | -1.8 (-2.5, -1.1) | -0.7 (-1.4, 0.0) | -2.5 (-3.2, -1.8) | |
Comparison to Doxazosin alone (95% CI) | -0.7 (-1.4, 0.0) | |||
Comparison to Tampace-F (Finasteride) alone (95% CI) | -1.8 (-2.5, -1.1) |
The results of MTOPS are consistent with the findings of the 4-year, placebo-controlled study PLESS in that treatment with Tampace-F (Finasteride) reduces the risk of acute urinary retention and the need for BPH-related surgery. In MTOPS, the risk of developing acute urinary retention was reduced by 67% in patients treated with Tampace-F (Finasteride) compared to patients treated with placebo (0.8% for Tampace-F (Finasteride) and 2.4% for placebo). Also, the risk of requiring BPH-related invasive therapy was reduced by 64% in patients treated with Tampace-F (Finasteride) compared to patients treated with placebo (2.0% for Tampace-F (Finasteride) and 5.4% for placebo).
The data from these studies, showing improvement in BPH-related symptoms, reduction in treatment failure (BPH-related urological events), increased maximum urinary flow rates, and decreasing prostate volume, suggest that Tampace-F (Finasteride) arrests the disease process of BPH in men with an enlarged prostate.
Image of Figure 1 Image of Figure 2 Image of Figure 3 Image of Figure 4 Image of Figure 5
No. 3094 - Tampace-F (Finasteride) tablets 5 mg are blue, modified apple-shaped, film-coated tablets, with the code MSD 72 on one side and Tampace-F (Finasteride) on the other. They are supplied as follows:
NDC 0006-0072-31 unit of use bottles of 30
NDC 0006-0072-58 unit of use bottles of 100.
Storage and Handling
Store at room temperatures below 30°C (86°F). Protect from light and keep container tightly closed.
Women should not handle crushed or broken Tampace-F (Finasteride) tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of Tampace-F (Finasteride) and the subsequent potential risk to a male fetus .
Patients should be informed that there was an increase in high-grade prostate cancer in men treated with 5α-reductase inhibitors indicated for BPH treatment, including Tampace-F (Finasteride), compared to those treated with placebo in studies looking at the use of these drugs to prevent prostate cancer .
Physicians should inform patients that women who are pregnant or may potentially be pregnant should not handle crushed or broken Tampace-F tablets because of the possibility of absorption of Tampace-F (Finasteride) and the subsequent potential risk to the male fetus. Tampace-F (Finasteride) tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets have not been broken or crushed. If a woman who is pregnant or may potentially be pregnant comes in contact with crushed or broken Tampace-F (Finasteride) tablets, the contact area should be washed immediately with soap and water .
Physicians should inform patients that the volume of ejaculate may be decreased in some patients during treatment with Tampace-F (Finasteride). This decrease does not appear to interfere with normal sexual function. However, impotence and decreased libido may occur in patients treated with Tampace-F (Finasteride) .
Physicians should instruct their patients to promptly report any changes in their breasts such as lumps, pain or nipple discharge. Breast changes including breast enlargement, tenderness and neoplasm have been reported .
Physicians should instruct their patients to read the patient package insert before starting therapy with Tampace-F (Finasteride) and to reread it each time the prescription is renewed so that they are aware of current information for patients regarding Tampace-F (Finasteride).
Dist. by: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA
For patent information: www.merck.com/product/patent/home.html
Copyright © 1992, 1995, 1998, 2011 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.
uspi-mk0906-5t-1309r011
Tampace-F (Finasteride)® (finasteride) Tablets
Patient Information about
Tampace-F (Finasteride)® (Prahs-car)
Generic name: Tampace-F (Finasteride)
(fin-AS-tur-eyed)
Tampace-F (Finasteride) is for use by men only.
Please read this leaflet before you start taking Tampace-F (Finasteride). Also, read it each time you renew your prescription, just in case anything has changed. Remember, this leaflet does not take the place of careful discussions with your doctor. You and your doctor should discuss Tampace-F (Finasteride) when you start taking your medication and at regular checkups.
What is Tampace-F (Finasteride)?
Tampace-F (Finasteride) is a medication used to treat symptoms of benign prostatic hyperplasia (BPH) in men with an enlarged prostate. Tampace-F (Finasteride) may also be used to reduce the risk of a sudden inability to pass urine and the need for surgery related to BPH in men with an enlarged prostate.
Tampace-F (Finasteride) may be prescribed along with another medicine, an alpha-blocker called doxazosin, to help you better manage your BPH symptoms.
Who should NOT take Tampace-F (Finasteride)?
Tampace-F (Finasteride) is for use by MEN only.
Do Not Take Tampace-F (Finasteride) if you are:
A warning about Tampace-F (Finasteride) and pregnancy:
Women who are or may potentially be pregnant must not use Tampace-F (Finasteride). They should also not handle crushed or broken tablets of Tampace-F (Finasteride). Tampace-F (Finasteride) tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets are not broken or crushed.
If a woman who is pregnant with a male baby absorbs the active ingredient in Tampace-F (Finasteride) after oral use or through the skin, it may cause the male baby to be born with abnormalities of the sex organs. If a woman who is pregnant comes into contact with the active ingredient in Tampace-F (Finasteride), a doctor should be consulted.
How should I take Tampace-F (Finasteride)?
Follow your doctor's instruction.
What are the possible side effects of Tampace-F (Finasteride)?
Tampace-F (Finasteride) may increase the chance of a more serious form of prostate cancer.
The most common side effects of Tampace-F (Finasteride) include:
The following have been reported in general use with Tampace-F (Finasteride) and/or Tampace-F (Finasteride) at lower doses:
You should discuss side effects with your doctor before taking Tampace-F (Finasteride) and anytime you think you are having a side effect. These are not all the possible side effects with Tampace-F (Finasteride). For more information, ask your doctor or pharmacist.
Call your doctor for medical advice about side effects. You may report side effects to FDA at: 1-800-FDA-1088.
What you need to know while taking Tampace-F (Finasteride):
How should I store Tampace-F (Finasteride)?
Tampace-F (Finasteride) tablets are coated and will prevent contact with the active ingredient during normal handling, provided that the tablets are not broken or crushed.
Keep Tampace-F (Finasteride) and all medications out of the reach of children.
Do not give your Tampace-F (Finasteride) tablets to anyone else. It has been prescribed only for you.
For more information call 1-800-622-4477.
What are the ingredients in Tampace-F (Finasteride)?
Active ingredients: Tampace-F (Finasteride)
Inactive ingredients: hydrous lactose, microcrystalline cellulose, pregelatinized starch, sodium starch glycolate, hydroxypropyl cellulose LF, hydroxypropyl methylcellulose, titanium dioxide, magnesium stearate, talc, docusate sodium, FD&C Blue 2 aluminum lake and yellow iron oxide.
What is BPH?
BPH is an enlargement of the prostate gland. The prostate is located below the bladder. As the prostate enlarges, it may slowly restrict the flow of urine. This can lead to symptoms such as:
In some men, BPH can lead to serious problems, including urinary tract infections, a sudden inability to pass urine (acute urinary retention), as well as the need for surgery.
What Tampace-F (Finasteride) does:
Tampace-F (Finasteride) lowers levels of a hormone called DHT (dihydrotestosterone), which is a cause of prostate growth. Lowering DHT leads to shrinkage of the enlarged prostate gland in most men. This can lead to gradual improvement in urine flow and symptoms over the next several months. Tampace-F (Finasteride) will help reduce the risk of developing a sudden inability to pass urine and the need for surgery related to an enlarged prostate. However, since each case of BPH is different, you should know that:
Dist. by: Merck Sharp & Dohme Corp., a subsidiary of
MERCK & CO., INC., Whitehouse Station, NJ 08889, USA
For patent information: www.merck.com/product/patent/home.html
Copyright © 1992, 1995, 1998, 2011 Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc.
All rights reserved.
Revised: 09/2013
usppi-mk0906-5t-1309r011
PRINCIPAL DISPLAY PANEL - 5 mg Bottle Label
NDC 0006-0072-31
Tampace-F (Finasteride)®
(finasteride) Tablets
5 mg
WARNING: Tampace-F (Finasteride)® (finasteride) should
not be used by women or children.
Women who are or may potentially be
pregnant must not use Tampace-F (Finasteride). They
should also not handle crushed or broken
tablets of Tampace-F (Finasteride).
Rx only
30 Tablets
Tamsulosin:
For those patients who fail to respond to the 0.4 mg dose after 2 to 4 weeks of dosing, the dose of Tampace-F (Tamsulosin) capsules can be increased to 0.8 mg once daily. Tampace-F (Tamsulosin) capsules 0.4 mg should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [ see Warnings and Precautions (5.2) ].
If Tampace-F (Tamsulosin) capsules administration is discontinued or interrupted for several days at either the 0.4 mg or 0.8 mg dose, therapy should be started again with the 0.4 mg once-daily dose.
Tampace-F (Tamsulosin) capsules should be used with caution in combination with cimetidine, particularly at a dose higher than 0.4 mg (e.g., 0.8 mg) [ see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ].
Tampace-F (Tamsulosin) capsules should not be used in combination with other alpha adrenergic blocking agents [ see Drug Interactions (7.2) and Clinical Pharmacology (12.3) ].
Caution is advised when alpha adrenergic blocking agents including Tampace-F (Tamsulosin) are co-administered with PDE5 inhibitors. Alpha-adrenergic blockers and PDE5 inhibitors are both vasodilators that can lower blood pressure. Concomitant use of these two drug classes can potentially cause symptomatic hypotension [ see Drug Interactions (7.3) and Clinical Pharmacology (12.3) ].
Caution should be exercised with concomitant administration of warfarin and Tampace-F (Tamsulosin) capsules [ see Drug Interactions (7.4) and Clinical Pharmacology (12.3) ].
Most reports were in patients taking the alpha1 blocker when IFIS occurred, but in some cases, the alpha1 blocker had been stopped prior to surgery. In most of these cases, the alpha1 blocker had been stopped recently prior to surgery (2 to 14 days), but in a few cases, IFIS was reported after the patient had been off the alpha1 blocker for a longer period (5 weeks to 9 months). IFIS is a variant of small pupil syndrome and is characterized by the combination of a flaccid iris that billows in response to intraoperative irrigation currents, progressive intraoperative miosis despite preoperative dilation with standard mydriatic drugs and potential prolapse of the iris toward the phacoemulsification incisions. The patient's ophthalmologist should be prepared for possible modifications to their surgical technique, such as the utilization of iris hooks, iris dilator rings, or viscoelastic substances.
IFIS may increase the risk of eye complications during and after the operation. The benefit of stopping alpha1 blocker therapy prior to cataract surgery has not been established. The initiation of therapy with Tampace-F (Tamsulosin) in patients for whom cataract surgery is scheduled is not recommended.
The incidence of treatment-emergent adverse events has been ascertained from six short-term U.S. and European placebo-controlled clinical trials in which daily doses of 0.1 to 0.8 mg Tampace-F (Tamsulosin) capsules were used. These studies evaluated safety in 1783 patients treated with Tampace-F (Tamsulosin) capsules and 798 patients administered placebo. Table 1 summarizes the treatment-emergent adverse events that occurred in ≥2% of patients receiving either Tampace-F (Tamsulosin) capsules 0.4 mg or 0.8 mg and at an incidence numerically higher than that in the placebo group during two 13-week U.S. trials (US92-03A and US93-01) conducted in 1487 men.
BODY SYSTEM/ ADVERSE EVENT | Tampace-F (Tamsulosin) CAPSULES GROUPS | PLACEBO | |
---|---|---|---|
0.4 mg n=502 | 0.8 mg n=492 | n=493 | |
1 A treatment-emergent adverse event was defined as any event satisfying one of the following criteria:
| |||
2 Coding preferred terms also include cold, common cold, head cold, flu, and flu-like symptoms. | |||
3 Coding preferred terms also include nasal congestion, stuffy nose, runny nose, sinus congestion, and hay fever. | |||
BODY AS WHOLE | |||
Headache | 97 (19.3%) | 104 (21.1%) | 99 (20.1%) |
Infection2 | 45 (9.0%) | 53 (10.8%) | 37 (7.5%) |
Asthenia | 39 (7.8%) | 42 (8.5%) | 27 (5.5%) |
Back pain | 35 (7.0%) | 41 (8.3%) | 27 (5.5%) |
Chest pain | 20 (4.0%) | 20 (4.1%) | 18 (3.7%) |
NERVOUS SYSTEM | |||
Dizziness | 75 (14.9%) | 84 (17.1%) | 50 (10.1%) |
Somnolence | 15 (3.0%) | 21 (4.3%) | 8 (1.6%) |
Insomnia | 12 (2.4%) | 7 (1.4%) | 3 (0.6%) |
Libido decreased | 5 (1.0%) | 10 (2.0%) | 6 (1.2%) |
RESPIRATORY SYSTEM | |||
Rhinitis3 | 66 (13.1%) | 88 (17.9%) | 41 (8.3%) |
Pharyngitis | 29 (5.8%) | 25 (5.1%) | 23 (4.7%) |
Cough increased | 17 (3.4%) | 22 (4.5%) | 12 (2.4%) |
Sinusitis | 11 (2.2%) | 18 (3.7%) | 8 (1.6%) |
DIGESTIVE SYSTEM | |||
Diarrhea | 31 (6.2%) | 21 (4.3%) | 22 (4.5%) |
Nausea | 13 (2.6%) | 19 (3.9%) | 16 (3.2%) |
Tooth disorder | 6 (1.2%) | 10 (2.0%) | 7 (1.4%) |
UROGENITAL SYSTEM | |||
Abnormal ejaculation | 42 (8.4%) | 89 (18.1%) | 1 (0.2%) |
SPECIAL SENSES | |||
Blurred vision | 1 (0.2%) | 10 (2.0%) | 2 (0.4%) |
Multiple testing for orthostatic hypotension was conducted in a number of studies. Such a test was considered positive if it met one or more of the following criteria: (1) a decrease in systolic blood pressure of ≥20 mmHg upon standing from the supine position during the orthostatic tests; (2) a decrease in diastolic blood pressure ≥10 mmHg upon standing, with the standing diastolic blood pressure <65 mmHg during the orthostatic test; (3) an increase in pulse rate of ≥20 bpm upon standing with a standing pulse rate ≥100 bpm during the orthostatic test; and (4) the presence of clinical symptoms (faintness, lightheadedness/lightheaded, dizziness, spinning sensation, vertigo, or postural hypotension) upon standing during the orthostatic test.
Following the first dose of double-blind medication in Study 1, a positive orthostatic test result at 4 hours post-dose was observed in 7% of patients (37 of 498) who received Tampace-F (Tamsulosin) capsules 0.4 mg once daily and in 3% of the patients (8 of 253) who received placebo. At 8 hours post-dose, a positive orthostatic test result was observed for 6% of the patients (31 of 498) who received Tampace-F (Tamsulosin) capsules 0.4 mg once daily and 4% (9 of 250) who received placebo (Note: patients in the 0.8 mg group received 0.4 mg once daily for the first week of Study 1).
In Studies 1 and 2, at least one positive orthostatic test result was observed during the course of these studies for 81 of the 502 patients (16%) in the Tampace-F (Tamsulosin) capsules 0.4 mg once-daily group, 92 of the 491 patients (19%) in the Tampace-F (Tamsulosin) capsules 0.8 mg once-daily group, and 54 of the 493 patients (11%) in the placebo group.
Because orthostasis was detected more frequently in Tampace-F (Tamsulosin) capsule-treated patients than in placebo recipients, there is a potential risk of syncope [ see Warnings and Precautions (5.1) ].
Allergic-type reactions such as skin rash, urticaria, pruritus, angioedema, and respiratory symptoms have been reported with positive rechallenge in some cases. Priapism has been reported rarely. Infrequent reports of dyspnea, palpitations, hypotension, atrial fibrillation, arrhythmia, tachycardia, skin desquamation including reports of Stevens-Johnson syndrome, constipation, and vomiting have been received during the postmarketing period.
During cataract surgery, a variant of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) has been reported in association with alpha1 blocker therapy [ see Warnings and Precautions (5.5) ].
Concomitant treatment with ketoconazole (a strong inhibitor of CYP3A4) resulted in an increase in the Cmax and AUC of Tampace-F (Tamsulosin) by a factor of 2.2 and 2.8, respectively [ see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ]. The effects of concomitant administration of a moderate CYP3A4 inhibitor (e.g., erythromycin) on the pharmacokinetics of Tampace-F (Tamsulosin) have not been evaluated [ see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ].
Concomitant treatment with paroxetine (a strong inhibitor of CYP2D6) resulted in an increase in the Cmax and AUC of Tampace-F (Tamsulosin) by a factor of 1.3 and 1.6, respectively [ see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ]. A similar increase in exposure is expected in CYP2D6 poor metabolizers (PM) as compared to extensive metabolizers (EM). Since CYP2D6 PMs cannot be readily identified and the potential for significant increase in Tampace-F (Tamsulosin) exposure exists when Tampace-F (Tamsulosin) 0.4 mg is co-administered with strong CYP3A4 inhibitors in CYP2D6 PMs, Tampace-F (Tamsulosin) 0.4 mg capsules should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [ see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ].
The effects of concomitant administration of a moderate CYP2D6 inhibitor (e.g., terbinafine) on the pharmacokinetics of Tampace-F (Tamsulosin) have not been evaluated [ see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ].
The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with Tampace-F (Tamsulosin) capsules have not been evaluated. However, there is a potential for significant increase in Tampace-F (Tamsulosin) exposure when Tampace-F (Tamsulosin) 0.4 mg is co-administered with a combination of both CYP3A4 and CYP2D6 inhibitors [ see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ].
Efficacy and positive benefit/risk of Tampace-F (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 H2O) 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 Tampace-F (Tamsulosin) hydrochloride) for the reduction in detrusor leak point pressure below 40 cm H2O. 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 Tampace-F (Tamsulosin) hydrochloride and placebo. In an open-label, 12-month safety study, 87 patients were treated with Tampace-F (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.
Tampace-F (Tamsulosin) hydrochloride is (-)-( R )-5-[2-[[2-( o -Ethoxyphenoxy) ethyl]amino]propyl]-2-methoxybenzenesulfonamide, monohydrochloride. Tampace-F (Tamsulosin) hydrochloride is a white crystalline powder that melts with decomposition at approximately 230°C. It is sparingly soluble in water and methanol, slightly soluble in glacial acetic acid and ethanol, and practically insoluble in ether.
The empirical formula of Tampace-F (Tamsulosin) hydrochloride is C20H28N2O5S - HCl. The molecular weight of Tampace-F (Tamsulosin) hydrochloride is 444.98. Its structural formula is:
Each Tampace-F (Tamsulosin) capsule for oral administration contains Tampace-F (Tamsulosin) hydrochloride 0.4 mg, and the following inactive ingredients: methacrylic acid copolymer dispersion, NF; microcrystalline cellulose, NF; triacetin, USP; calcium stearate, NF; talc, USP; FD&C blue No. 2; titanium dioxide; ferric oxide; gelatin, and trace amounts of black edible ink.
Tampace-F (Tamsulosin), an alpha1 adrenoceptor blocking agent, exhibits selectivity for alpha1 receptors in the human prostate. At least three discrete alpha1 adrenoceptor subtypes have been identified: alpha1A, alpha1B, and alpha1D; their distribution differs between human organs and tissue. Approximately 70% of the alpha1 receptors in the human prostate are of the alpha1A subtype.
Tampace-F (Tamsulosin) capsules are not intended for use as an antihypertensive drug.
Figure 1 Mean Plasma Tampace-F (Tamsulosin) Hydrochloride Concentrations Following Single-Dose Administration of Tampace-F (Tamsulosin) Capsules 0.4 mg Under Fasted and Fed Conditions (n=8)
The effects of food on the pharmacokinetics of Tampace-F (Tamsulosin) hydrochloride are consistent regardless of whether a Tampace-F (Tamsulosin) capsule is taken with a light breakfast or a high-fat breakfast (Table 2).
Pharmacokinetic Parameter | 0.4 mg QD to healthy volunteers; n=23 (age range 18-32 years) | 0.8 mg QD to healthy volunteers; n=22 (age range 55-75 years) | |||
---|---|---|---|---|---|
Light Breakfast | Fasted | Light Breakfast | High-Fat Breakfast | Fasted | |
Cmin = observed minimum concentration | |||||
Cmax = observed maximum Tampace-F (Tamsulosin) hydrochloride plasma concentration | |||||
Tmax = median time-to-maximum concentration | |||||
T1/2 = observed half-life | |||||
AUCτ = area under the Tampace-F (Tamsulosin) hydrochloride plasma time curve over the dosing interval | |||||
Cmin (ng/mL) | 4.0 ± 2.6 | 3.8 ± 2.5 | 12.3 ± 6.7 | 13.5 ± 7.6 | 13.3 ± 13.3 |
Cmax (ng/mL) | 10.1 ± 4.8 | 17.1 ± 17.1 | 29.8 ± 10.3 | 29.1 ± 11.0 | 41.6 ± 15.6 |
Cmax/Cmin Ratio | 3.1 ± 1.0 | 5.3 ± 2.2 | 2.7 ± 0.7 | 2.5 ± 0.8 | 3.6 ± 1.1 |
Tmax (hours) | 6.0 | 4.0 | 7.0 | 6.6 | 5.0 |
T1/2 (hours) | - | - | - | - | 14.9 ± 3.9 |
AUCτ (ng-hr/mL) | 151 ± 81.5 | 199 ± 94.1 | 440 ± 195 | 449 ± 217 | 557 ± 257 |
Tampace-F (Tamsulosin) hydrochloride is extensively bound to human plasma proteins (94% to 99%), primarily alpha1 acid glycoprotein (AAG), with linear binding over a wide concentration range (20 to 600 ng/mL). The results of two-way in vitro studies indicate that the binding of Tampace-F (Tamsulosin) hydrochloride to human plasma proteins is not affected by amitriptyline, diclofenac, glyburide, simvastatin plus simvastatin-hydroxy acid metabolite, warfarin, diazepam, propranolol, trichlormethiazide, or chlormadinone. Likewise, Tampace-F (Tamsulosin) hydrochloride had no effect on the extent of binding of these drugs.
Incubations with human liver microsomes showed no evidence of clinically significant metabolic interactions between Tampace-F (Tamsulosin) hydrochloride and amitriptyline, albuterol (beta agonist), glyburide (glibenclamide) and finasteride (5alpha-reductase inhibitor for treatment of BPH). However, results of the in vitro testing of the Tampace-F (Tamsulosin) hydrochloride interaction with diclofenac and warfarin were equivocal.
Following intravenous or oral administration of an immediate-release formulation, the elimination half-life of Tampace-F (Tamsulosin) hydrochloride in plasma ranged from 5 to 7 hours. Because of absorption rate-controlled pharmacokinetics with Tampace-F (Tamsulosin) capsules, the apparent half-life of Tampace-F (Tamsulosin) hydrochloride is approximately 9 to 13 hours in healthy volunteers and 14 to 15 hours in the target population.
Tampace-F (Tamsulosin) hydrochloride undergoes restrictive clearance in humans, with a relatively low systemic clearance (2.88 L/h).
The effects of ketoconazole at 400 mg once daily for 5 days on the pharmacokinetics of a single Tampace-F (Tamsulosin) capsule 0.4 mg dose was investigated in 24 healthy volunteers (age range 23 to 47 years). Concomitant treatment with ketoconazole resulted in an increase in the Cmax and AUC of Tampace-F (Tamsulosin) by a factor of 2.2 and 2.8, respectively [ see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ]. The effects of concomitant administration of a moderate CYP3A4 inhibitor (e.g., erythromycin) on the pharmacokinetics of Tampace-F (Tamsulosin) have not been evaluated [ see Warnings and Precautions (5.2) and Drug Interactions (7.1) ].
The effects of paroxetine (a strong inhibitor of CYP2D6) at 20 mg once daily for 9 days on the pharmacokinetics of a single Tampace-F (Tamsulosin) capsule 0.4 mg dose was investigated in 24 healthy volunteers (age range 23 to 47 years). Concomitant treatment with paroxetine resulted in an increase in the Cmax and AUC of Tampace-F (Tamsulosin) by a factor of 1.3 and 1.6, respectively [ see Warnings and Precautions (5.2) and Drug Interactions (7.1) ]. A similar increase in exposure is expected in CYP2D6 poor metabolizers (PM) as compared to extensive metabolizers (EM). A fraction of the population (about 7% of Caucasians and 2% of African Americans) are CYP2D6 PMs. Since CYP2D6 PMs cannot be readily identified and the potential for significant increase in Tampace-F (Tamsulosin) exposure exists when Tampace-F (Tamsulosin) 0.4 mg is co-administered with strong CYP3A4 inhibitors in CYP2D6 PMs, Tampace-F (Tamsulosin) 0.4 mg capsules should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [ see Warnings and Precautions (5.2) and Drug Interactions (7.1) ].
The effects of concomitant administration of a moderate CYP2D6 inhibitor (e.g., terbinafine) on the pharmacokinetics of Tampace-F (Tamsulosin) have not been evaluated [ see Warnings and Precautions (5.2) and Drug Interactions (7.1) ].
The effects of co-administration of both a CYP3A4 and a CYP2D6 inhibitor with Tampace-F (Tamsulosin) capsules have not been evaluated. However, there is a potential for significant increase in Tampace-F (Tamsulosin) exposure when Tampace-F (Tamsulosin) 0.4 mg is co-administered with a combination of both CYP3A4 and CYP2D6 inhibitors [ see Warnings and Precautions (5.2) and Drug Interactions (7.1) ].
Mice were administered doses up to 127 mg/kg/day in males and 158 mg/kg/day in females. There were no significant tumor findings in male mice. Female mice treated for 2 years with the two highest doses of 45 and 158 mg/kg/day had statistically significant increases in the incidence of mammary gland fibroadenomas (P<0.0001) and adenocarcinomas (P<0.0075). The highest dose levels of Tampace-F (Tamsulosin) hydrochloride evaluated in the mice carcinogenicity study produced systemic exposures (AUC) in mice 8 times the exposures in men receiving the maximum therapeutic dose of 0.8 mg/day.
The increased incidences of mammary gland neoplasms in female rats and mice were considered secondary to Tampace-F (Tamsulosin) hydrochloride-induced hyperprolactinemia. It is not known if Tampace-F (Tamsulosin) capsules elevate prolactin in humans. The relevance for human risk of the findings of prolactin-mediated endocrine tumors in rodents is not known.
Tampace-F (Tamsulosin) hydrochloride produced no evidence of mutagenic potential in vitro in the Ames reverse mutation test, mouse lymphoma thymidine kinase assay, unscheduled DNA repair synthesis assay, and chromosomal aberration assays in Chinese hamster ovary cells or human lymphocytes. There were no mutagenic effects in the in vivo sister chromatid exchange and mouse micronucleus assay.
Studies in rats revealed significantly reduced fertility in males dosed with single or multiple daily doses of 300 mg/kg/day of Tampace-F (Tamsulosin) hydrochloride (AUC exposure in rats about 50 times the human exposure with the maximum therapeutic dose). The mechanism of decreased fertility in male rats is considered to be an effect of the compound on the vaginal plug formation possibly due to changes of semen content or impairment of ejaculation. The effects on fertility were reversible, showing improvement by 3 days after a single dose and 4 weeks after multiple dosing. Effects on fertility in males were completely reversed within nine weeks of discontinuation of multiple dosing. Multiple doses of 10 and 100 mg/kg/day Tampace-F (Tamsulosin) hydrochloride (1/5 and 16 times the anticipated human AUC exposure) did not significantly alter fertility in male rats. Effects of Tampace-F (Tamsulosin) hydrochloride on sperm counts or sperm function have not been evaluated.
Studies in female rats revealed significant reductions in fertility after single or multiple dosing with 300 mg/kg/day of the R-isomer or racemic mixture of Tampace-F (Tamsulosin) hydrochloride, respectively. In female rats, the reductions in fertility after single doses were considered to be associated with impairments in fertilization. Multiple dosing with 10 or 100 mg/kg/day of the racemic mixture did not significantly alter fertility in female rats.
In the two U.S. placebo-controlled, double-blind, 13-week, multicenter studies [Study 1 (US92-03A) and Study 2 (US93-01)], 1486 men with the signs and symptoms of BPH were enrolled. In both studies, patients were randomized to either placebo, Tampace-F (Tamsulosin) capsules 0.4 mg once daily, or Tampace-F (Tamsulosin) capsules 0.8 mg once daily. Patients in Tampace-F (Tamsulosin) capsules 0.8 mg once-daily treatment groups received a dose of 0.4 mg once daily for one week before increasing to the 0.8 mg once-daily dose. The primary efficacy assessments included: 1) total American Urological Association (AUA) Symptom Score questionnaire, which evaluated irritative (frequency, urgency, and nocturia), and obstructive (hesitancy, incomplete emptying, intermittency, and weak stream) symptoms, where a decrease in score is consistent with improvement in symptoms; and 2) peak urine flow rate, where an increased peak urine flow rate value over baseline is consistent with decreased urinary obstruction.
Mean changes from baseline to Week 13 in total AUA Symptom Score were significantly greater for groups treated with Tampace-F (Tamsulosin) capsules 0.4 mg and 0.8 mg once daily compared to placebo in both U.S. studies (Table 3, Figures 2A and 2B). The changes from baseline to Week 13 in peak urine flow rate were also significantly greater for the Tampace-F (Tamsulosin) capsules 0.4 mg and 0.8 mg once-daily groups compared to placebo in Study 1, and for the Tampace-F (Tamsulosin) capsules 0.8 mg once-daily group in Study 2 (Table 3, Figures 3A and 3B). Overall there were no significant differences in improvement observed in total AUA Symptom Scores or peak urine flow rates between the 0.4 mg and the 0.8 mg dose groups with the exception that the 0.8 mg dose in Study 1 had a significantly greater improvement in total AUA Symptom Score compared to the 0.4 mg dose.
Total AUA Symptom Score | Peak Urine Flow Rate | |||||
---|---|---|---|---|---|---|
Mean Baseline Value | Mean Change | Mean Baseline Value | Mean Change | |||
* Statistically significant difference from placebo (p-value ≤0.050; Bonferroni-Holm multiple test procedure). | ||||||
** Total AUA Symptom Scores ranged from 0 to 35. | ||||||
† Peak urine flow rate measured 4 to 8 hours post dose at Week 13. | ||||||
‡ Peak urine flow rate measured 24 to 27 hours post dose at Week 13. | ||||||
Week 13: For patients not completing the 13-week study, the last observation was carried forward. | ||||||
| ||||||
Tampace-F (Tamsulosin) capsules 0.8 mg once daily | 19.9 ± 4.9 n=247 | -9.6* ± 6.7 n=237 | 9.57 ± 2.51 n=247 | 1.78* ± 3.35 n=247 | ||
Tampace-F (Tamsulosin) capsules 0.4 mg once daily | 19.8 ± 5.0 n=254 | -8.3* ± 6.5 n=246 | 9.46 ± 2.49 n=254 | 1.75* ± 3.57 n=254 | ||
Placebo | 19.6 ± 4.9 n=254 | -5.5 ± 6.6 n=246 | 9.75 ± 2.54 n=254 | 0.52 ± 3.39 n=253 | ||
| ||||||
Tampace-F (Tamsulosin) capsules 0.8 mg once daily | 18.2 ± 5.6 n=244 | -5.8* ± 6.4 n=238 | 9.96 ± 3.16 n=244 | 1.79* ± 3.36 n=237 | ||
Tampace-F (Tamsulosin) capsules 0.4 mg once daily | 17.9 ± 5.8 n=248 | -5.1* ± 6.4 n=244 | 9.94 ± 3.14 n=248 | 1.52 ± 3.64 n=244 | ||
Placebo | 19.2 ± 6.0 n=239 | -3.6 ± 5.7 n=235 | 9.95 ± 3.12 n=239 | 0.93 ± 3.28 n=235 |
In Study 1, 400 patients (53% of the originally randomized group) elected to continue in their originally assigned treatment groups in a double-blind, placebo-controlled, 40-week extension trial (138 patients on 0.4 mg, 135 patients on 0.8 mg, and 127 patients on placebo). Three hundred twenty-three patients (43% of the originally randomized group) completed one year. Of these, 81% (97 patients) on 0.4 mg, 74% (75 patients) on 0.8 mg, and 56% (57 patients) on placebo had a response ≥25% above baseline in total AUA Symptom Score at one year.
Figure 2A Mean Change from Baseline in Total AUA Symptom Score (0-35) Study 1
* indicates significant difference from placebo (p-value ≤0.050).
B = Baseline determined approximately one week prior to the initial dose of double-blind medication at Week 0.
Subsequent values are observed cases.
LOCF = Last observation carried forward for patients not completing the 13-week study.
Note: Patients in the 0.8 mg treatment group received 0.4 mg for the first week.
Note: Total AUA Symptom Scores range from 0 to 35.
Figure 2B Mean Change from Baseline in Total AUA Symptom Score (0-35) Study 2
* indicates significant difference from placebo (p-value ≤0.050).
Baseline measurement was taken Week 0. Subsequent values are observed cases.
LOCF = Last observation carried forward for patients not completing the 13-week study.
Note: Patients in the 0.8 mg treatment group received 0.4 mg for the first week.
Note: Total AUA Symptom Scores range from 0 to 35.
Figure 3A Mean Increase in Peak Urine Flow Rate (mL/Sec) Study 1
* indicates significant difference from placebo (p-value ≤0.050).
B = Baseline determined approximately one week prior to the initial dose of double-blind medication at Week 0.
Subsequent values are observed cases.
LOCF = Last observation carried forward for patients not completing the 13-week study.
Note: The uroflowmetry assessments at Week 0 were recorded 4 to 8 hours after patients received the first dose of double-blind medication.
Measurements at each visit were scheduled 4 to 8 hours after dosing (approximate peak plasma Tampace-F (Tamsulosin) concentration).
Note: Patients in the 0.8 mg treatment groups received 0.4 mg for the first week.
Figure 3B Mean Increase in Peak Urine Flow Rate (mL/Sec) Study 2
* indicates significant difference from placebo (p-value ≤0.050).
Baseline measurement was taken Week 0. Subsequent values are observed cases.
LOCF = Last observation carried forward for patients not completing the 13-week study.
Note: Patients in the 0.8 mg treatment group received 0.4 mg for the first week.
Note: Week 1 and Week 2 measurements were scheduled 4 to 8 hours after dosing (approximate peak plasma Tampace-F (Tamsulosin) concentration).
All other visits were scheduled 24 to 27 hours after dosing (approximate trough Tampace-F (Tamsulosin) concentration).
Tampace-F (Tamsulosin) capsules 0.4 mg, 100 capsules (NDC 0597-0058-01)
Store at 25°C (77°F); excursions permitted to 15°C–30°C (59°F–86°F).
Keep Tampace-F (Tamsulosin) capsules and all medicines out of reach of children.
Patient labeling is provided as a tear-off leaflet at the end of this prescribing information.
Distributed by:
Boehringer Ingelheim Pharmaceuticals, Inc.
Ridgefield, CT 06877 USA
Tampace-F (Tamsulosin) is a registered trademark of, and licensed from:
Astellas Pharma Inc.
Tokyo 103-8411, JAPAN
Copyright 2012, ALL RIGHTS RESERVED
IT8004TE082012
PRT97
PATIENT INFORMATION
Flomax® (Flō-max)
(tamsulosin hydrochloride)
Capsules, 0.4 mg
Read the Patient Information that comes with Tampace-F (Tamsulosin) capsules before you start taking it and each time you refill your prescription. The information may have changed. This leaflet does not take the place of discussions with your doctor about your medical condition or your treatment.
What is Tampace-F (Tamsulosin)?
Tampace-F (Tamsulosin) is a prescription alpha-blocker medicine used to treat the signs and symptoms of benign prostatic hyperplasia (BPH), a condition your doctor may refer to as an enlarged prostate.
Do not take Tampace-F (Tamsulosin) capsules if you are allergic to any of its ingredients. See the end of this leaflet for a complete list of ingredients in Tampace-F (Tamsulosin) capsules.
What should I tell my doctor before using Tampace-F (Tamsulosin)?
Before taking Tampace-F (Tamsulosin) capsules, tell your doctor about all your medical conditions, including:
Know the medicines you take. Keep a list of them and show it to your doctor and pharmacist when you get a new medicine.
How should I take Tampace-F (Tamsulosin)?
Possible side effects of Tampace-F (Tamsulosin) may include:
Symptoms may include:
Allergic reactions may include:
Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088, or by visiting www.fda.gov/medwatch.
What should I avoid while taking Tampace-F (Tamsulosin) capsules?
Avoid driving, operating machinery, or other dangerous activities, until you know how Tampace-F (Tamsulosin) affects you. Tampace-F (Tamsulosin) capsules may cause a sudden drop in blood pressure upon standing, especially after the first dose or when changing doses. See " What are the possible side effects of Tampace-F (Tamsulosin) capsules? "
How do I store Tampace-F (Tamsulosin) capsules?
Store Tampace-F (Tamsulosin) capsules at Room Temperature [77°F (25°C)]. Short-term exposure to higher or lower temperatures [from 59°F (15°C) to 86°F (30°C)] is acceptable. Ask your doctor or pharmacist if you have any questions about storing your capsules.
Keep Tampace-F (Tamsulosin) capsules and all medicines out of the reach of children.
General information
This medicine was prescribed for you by your doctor for your condition. Do not use it for another condition. Do not give Tampace-F (Tamsulosin) to other people, even if they have the same symptoms that you have. It may harm them.
While taking Tampace-F (Tamsulosin), you must have regular checkups. Follow your doctor's advice about when to have these checkups.
BPH can occur with other more serious conditions, including prostate cancer. Therefore, ask your doctor about screening for prostate cancer prior to treatment with Tampace-F (Tamsulosin) capsules and at regular intervals afterwards.
This patient information leaflet summarizes the most important information about Tampace-F (Tamsulosin). If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Tampace-F (Tamsulosin) that is written for health professionals. For more information call Boehringer Ingelheim Pharmaceuticals, Inc. at 1-800-542-6257, or (TTY) 1-800-459-9906.
What are the ingredients in Tampace-F (Tamsulosin) capsules?
Boehringer Ingelheim Pharmaceuticals, Inc.
Ridgefield, CT 06877 USA
Tampace-F (Tamsulosin) is a registered trademark of, and licensed from:
Astellas Pharma Inc.
Tokyo 103-8411, JAPAN
Copyright 2012, ALL RIGHTS RESERVED
IT8004TE082012
PRT97
Revised: May 2012
Tampace-F (Tamsulosin) Structure Figure 1 Figure 2a Figure 2b Figure 3a Figure 3b
Depending on the reaction of the Tampace-F after taken, if you are feeling dizziness, drowsiness or any weakness as a reaction on your body, Then consider Tampace-F not safe to drive or operate heavy machine after consumption. Meaning that, do not drive or operate heavy duty machines after taking the capsule if the capsule has a strange reaction on your body like dizziness, drowsiness. As prescribed by a pharmacist, it is dangerous to take alcohol while taking medicines as it exposed patients to drowsiness and health risk. Please take note of such effect most especially when taking Primosa capsule. It's advisable to consult your doctor on time for a proper recommendation and medical consultations.
Is Tampace-F addictive or habit forming?Medicines are not designed with the mind of creating an addiction or abuse on the health of the users. Addictive Medicine is categorically called Controlled substances by the government. For instance, Schedule H or X in India and schedule II-V in the US are controlled substances.
Please consult the medicine instruction manual on how to use and ensure it is not a controlled substance.In conclusion, self medication is a killer to your health. Consult your doctor for a proper prescription, recommendation, and guidiance.
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The information was verified by Dr. Rachana Salvi, MD Pharmacology