Veltam-F

Finasteride:

• Indications and usage
• Dosage and administration
• Dosage forms and strengths
• Contraindications
• Warnings and precautions
• Adverse reactions
• Drug interactions
• Use in specific populations
• Overdosage
• Description
• How supplied/storage and handling
• Patient counseling information
• Veltam-F (Finasteride) reviews

1 INDICATIONS AND USAGE

Veltam-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):

• Improve symptoms
• Reduce the risk of acute urinary retention
• Reduce the risk of the need for surgery including transurethral resection of the prostate (TURP) and prostatectomy.

Veltam-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: Veltam-F (Finasteride) is not approved for the prevention of prostate cancer (1.3).

1.1 Monotherapy

Veltam-F (Finasteride)^® is indicated for the treatment of symptomatic benign prostatic hyperplasia (BPH) in men with an enlarged prostate to:

• Improve symptoms
• Reduce the risk of acute urinary retention
• Reduce the risk of the need for surgery including transurethral resection of the prostate (TURP) and prostatectomy.

1.2 Combination with Alpha-Blocker

Veltam-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).

1.3 Limitations of Use

Veltam-F (Finasteride) is not approved for the prevention of prostate cancer.

2 DOSAGE AND ADMINISTRATION

Veltam-F may be administered with or without meals.

Veltam-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).

2.1 Monotherapy

The recommended dose of Veltam-F (Finasteride) is one tablet (5 mg) taken once a day .

2.2 Combination with Alpha-Blocker

The recommended dose of Veltam-F (Finasteride) is one tablet (5 mg) taken once a day in combination with the alpha-blocker doxazosin .

3 DOSAGE FORMS AND STRENGTHS

5-mg blue, modified apple-shaped, film-coated tablets, with the code MSD 72 on one side and Veltam-F (Finasteride) on the other.

5-mg film-coated tablets (3).

4 CONTRAINDICATIONS

Veltam-F (Finasteride) is contraindicated in the following:

• Hypersensitivity to any component of this medication.
• Pregnancy. Veltam-F (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), Veltam-F (Finasteride) may cause abnormalities of the external genitalia of a male fetus of a pregnant woman who receives Veltam-F (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. In female rats, low doses of Veltam-F (Finasteride) administered during pregnancy have produced abnormalities of the external genitalia in male offspring.

Hypersensitivity to any components of this product (4).

Women who are or may potentially be pregnant (4, 5.4, 8.1, 16).

5 WARNINGS AND PRECAUTIONS

• Veltam-F reduces serum prostate specific antigen (PSA) levels by approximately 50%. However, any confirmed increase in PSA while on Veltam-F (Finasteride) 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 (5.1).
• Veltam-F (Finasteride) may increase the risk of high-grade prostate cancer (5.2, 6.1).
• Women should not handle crushed or broken Veltam-F (Finasteride) tablets when they are pregnant or may potentially be pregnant due to potential risk to a male fetus (5.3, 8.1, 16).
• Veltam-F (Finasteride) is not indicated for use in pediatric patients or women (5.4, 8.1, 8.3, 8.4, 12.3).
• Prior to initiating treatment with Veltam-F (Finasteride) for BPH, consideration should be given to other urological conditions that may cause similar symptoms (5.6).

5.1 Effects on Prostate Specific Antigen (PSA) and the Use of PSA in Prostate Cancer Detection

In clinical studies, Veltam-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 Veltam-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 Veltam-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 Veltam-F (Finasteride) therapy may also affect PSA test results. To interpret an isolated PSA value in patients treated with Veltam-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 Veltam-F (Finasteride).

Veltam-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 Veltam-F (Finasteride). If clinicians elect to use percent free PSA as an aid in the detection of prostate cancer in men undergoing Veltam-F (Finasteride) therapy, no adjustment to its value appears necessary.

5.2 Increased Risk of High-Grade Prostate Cancer

Men aged 55 and over with a normal digital rectal examination and PSA ≤3.0 ng/mL at baseline taking Veltam-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.

5.3 Exposure of Women - Risk to Male Fetus

Women should not handle crushed or broken Veltam-F (Finasteride) tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of Veltam-F (Finasteride) and the subsequent potential risk to a male fetus. Veltam-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.

5.4 Pediatric Patients and Women

Veltam-F is not indicated for use in pediatric patients or women .

5.5 Effect on Semen Characteristics

Treatment with Veltam-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.

5.6 Consideration of Other Urological Conditions

Prior to initiating treatment with Veltam-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 Veltam-F (Finasteride) therapy.

6 ADVERSE REACTIONS

The drug-related adverse reactions, reported in ≥1% in patients treated with Veltam-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 .

6.1 Clinical Trials Experience

Veltam-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 Veltam-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 Veltam-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 Veltam-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 4Combined Years 2-4 (%)
	Veltam-F (Finasteride)	Placebo	Veltam-F (Finasteride)	Placebo
N = 1524 and 1516, Veltam-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 Veltam-F (Finasteride) 5 mg/day (n=768), doxazosin 4 or 8 mg/day (n=756), the combination of Veltam-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 Veltam-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 Veltam-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 mgDoxazosin dose was achieved by weekly titration (1 to 2 to 4 to 8 mg). The final tolerated dose (4 mg or 8 mg) was administered at end-Week 4. Only those patients tolerating at least 4 mg were kept on doxazosin. The majority of patients received the 8-mg dose over the duration of the study. (N=756) (%)	Veltam-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

Long-Term Data

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 Veltam-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 Veltam-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 Veltam-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 Veltam-F (Finasteride) but no cases in men not treated with Veltam-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 Veltam-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 Veltam-F (Finasteride), and 1 case of breast cancer in men treated with placebo. The relationship between long-term use of Veltam-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 Veltam-F (Finasteride). New reports of drug-related sexual adverse experiences decreased with duration of therapy.

6.2 Postmarketing Experience

The following additional adverse events have been reported in postmarketing experience with Veltam-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:

• hypersensitivity reactions, such as pruritus, urticaria, and angioedema (including swelling of the lips, tongue, throat, and face)
• testicular pain
• sexual dysfunction that continued after discontinuation of treatment, including erectile dysfunction, decreased libido and ejaculation disorders (e.g. reduced ejaculate volume). These events were reported rarely in men taking Veltam-F (Finasteride) for the treatment of BPH. Most men were older and were taking concomitant medications and/or had co-morbid conditions. The independent role of Veltam-F (Finasteride) in these events is unknown.
• male infertility and/or poor seminal quality were reported rarely in men taking Veltam-F (Finasteride) for the treatment of BPH. Normalization or improvement of poor seminal quality has been reported after discontinuation of Veltam-F (Finasteride). The independent role of Veltam-F (Finasteride) in these events is unknown.
• depression
• male breast cancer.

The following additional adverse event related to sexual dysfunction that continued after discontinuation of treatment has been reported in postmarketing experience with Veltam-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:

• orgasm disorders

7 DRUG INTERACTIONS

7.1 Cytochrome P450-Linked Drug Metabolizing Enzyme System

No drug interactions of clinical importance have been identified. Veltam-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.

7.2 Other Concomitant Therapy

Although specific interaction studies were not performed, Veltam-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.

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Pregnancy Category X.

Veltam-F (Finasteride) is contraindicated for use in women who are or may become pregnant. Veltam-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, Veltam-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 Veltam-F (Finasteride) through contact with crushed or broken Veltam-F (Finasteride) tablets or semen from a male partner taking Veltam-F (Finasteride). With regard to Veltam-F (Finasteride) exposure through the skin, Veltam-F (Finasteride) tablets are coated and will prevent skin contact with Veltam-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 Veltam-F (Finasteride) tablets because of possible exposure of a male fetus. If a pregnant woman comes in contact with crushed or broken Veltam-F (Finasteride) tablets, the contact area should be washed immediately with soap and water. With regard to potential Veltam-F (Finasteride) exposure through semen, two studies have been conducted in men receiving Veltam-F (Finasteride) 5 mg/day that measured Veltam-F (Finasteride) concentrations in semen .

In an embryo-fetal development study, pregnant rats received Veltam-F (Finasteride) during the period of major organogenesis (gestation days 6 to 17). At maternal doses of oral Veltam-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 Veltam-F (Finasteride).

No developmental abnormalities were observed in the offspring of untreated females mated with Veltam-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 Veltam-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 Veltam-F (Finasteride) effects on development of male external genitalia in the rabbit.

The fetal effects of maternal Veltam-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 Veltam-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 Veltam-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 Veltam-F (Finasteride) (2 mg/kg/day or approximately 18,000 times the highest estimated blood levels of Veltam-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.

8.3 Nursing Mothers

Veltam-F (Finasteride) is not indicated for use in women.

It is not known whether Veltam-F (Finasteride) is excreted in human milk.

8.4 Pediatric Use

Veltam-F is not indicated for use in pediatric patients.

Safety and effectiveness in pediatric patients have not been established.

8.5 Geriatric Use

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 .

8.6 Hepatic Impairment

Caution should be exercised in the administration of Veltam-F in those patients with liver function abnormalities, as Veltam-F (Finasteride) is metabolized extensively in the liver .

8.7 Renal Impairment

No dosage adjustment is necessary in patients with renal impairment .

10 OVERDOSAGE

Patients have received single doses of Veltam-F (Finasteride) up to 400 mg and multiple doses of Veltam-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 Veltam-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.

11 DESCRIPTION

Veltam-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).

Veltam-F (Finasteride) is 4-azaandrost-1-ene-17-carboxamide, N-(1,1-dimethylethyl)-3-oxo-,(5α,17ß)-. The empirical formula of Veltam-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 (%)patients with multiple events may be counted more than once for each type of event
Event	Placebo N=1503	Veltam-F (Finasteride) N=1513	Relative RiskHazard ratio based on log rank test	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, Veltam-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 Veltam-F (Finasteride); 51% reduction in risk, 95% CI: (34 to 63%)]. Compared with placebo, Veltam-F (Finasteride) was associated with a significantly lower risk for surgery [10.1% for placebo vs 4.6% for Veltam-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 Veltam-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, Veltam-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 Veltam-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 Veltam-F (Finasteride) who remained on therapy, prostate volume was reduced compared with both baseline and placebo throughout the 4-year study. Veltam-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 Veltam-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.

14.2 Combination with Alpha-Blocker Therapy

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 Veltam-F (Finasteride) 5 mg/day (n=768), doxazosin 4 or 8 mg/day (n=756), the combination of Veltam-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 Veltam-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 Veltam-F (Finasteride) alone (49%; p≤0.001) or doxazosin alone (46%; p≤0.001).

	Treatment Group
	Placebo	Doxazosin	Veltam-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 Veltam-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 Veltam-F (Finasteride) alone (p<0.001) and compared to doxazosin alone (p=0.037).

Treatment with Veltam-F (Finasteride), doxazosin or the combination of Veltam-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	Veltam-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 Veltam-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 Veltam-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 Veltam-F (Finasteride) compared to patients treated with placebo (0.8% for Veltam-F (Finasteride) and 2.4% for placebo). Also, the risk of requiring BPH-related invasive therapy was reduced by 64% in patients treated with Veltam-F (Finasteride) compared to patients treated with placebo (2.0% for Veltam-F (Finasteride) and 5.4% for placebo).

14.3 Summary of Clinical Studies

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 Veltam-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

16 HOW SUPPLIED/STORAGE AND HANDLING

No. 3094 - Veltam-F (Finasteride) tablets 5 mg are blue, modified apple-shaped, film-coated tablets, with the code MSD 72 on one side and Veltam-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 Veltam-F (Finasteride) tablets when they are pregnant or may potentially be pregnant because of the possibility of absorption of Veltam-F (Finasteride) and the subsequent potential risk to a male fetus .

17 PATIENT COUNSELING INFORMATION

17.1 Increased Risk of High-Grade Prostate Cancer

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 Veltam-F (Finasteride), compared to those treated with placebo in studies looking at the use of these drugs to prevent prostate cancer .

17.2 Exposure of Women - Risk to Male Fetus

Physicians should inform patients that women who are pregnant or may potentially be pregnant should not handle crushed or broken Veltam-F tablets because of the possibility of absorption of Veltam-F (Finasteride) and the subsequent potential risk to the male fetus. Veltam-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 Veltam-F (Finasteride) tablets, the contact area should be washed immediately with soap and water .

17.3 Additional Instructions

Physicians should inform patients that the volume of ejaculate may be decreased in some patients during treatment with Veltam-F (Finasteride). This decrease does not appear to interfere with normal sexual function. However, impotence and decreased libido may occur in patients treated with Veltam-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 Veltam-F (Finasteride) and to reread it each time the prescription is renewed so that they are aware of current information for patients regarding Veltam-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

Veltam-F (Finasteride)^® (finasteride) Tablets

Patient Information about

Veltam-F (Finasteride)^® (Prahs-car)

Generic name: Veltam-F (Finasteride)

(fin-AS-tur-eyed)

Veltam-F (Finasteride) is for use by men only.

Please read this leaflet before you start taking Veltam-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 Veltam-F (Finasteride) when you start taking your medication and at regular checkups.

What is Veltam-F (Finasteride)?

Veltam-F (Finasteride) is a medication used to treat symptoms of benign prostatic hyperplasia (BPH) in men with an enlarged prostate. Veltam-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.

Veltam-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 Veltam-F (Finasteride)?

Veltam-F (Finasteride) is for use by MEN only.

Do Not Take Veltam-F (Finasteride) if you are:

• a woman who is pregnant or may potentially be pregnant. Veltam-F (Finasteride) may harm your unborn baby. Do not touch or handle crushed or broken Veltam-F (Finasteride) tablets (see "A warning about Veltam-F (Finasteride) and pregnancy" ).
• allergic to Veltam-F (Finasteride) or any of the ingredients in Veltam-F (Finasteride). See the end of this leaflet for a complete list of ingredients in Veltam-F (Finasteride).

A warning about Veltam-F (Finasteride) and pregnancy:

Women who are or may potentially be pregnant must not use Veltam-F (Finasteride). They should also not handle crushed or broken tablets of Veltam-F (Finasteride). Veltam-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 Veltam-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 Veltam-F (Finasteride), a doctor should be consulted.

How should I take Veltam-F (Finasteride)?

Follow your doctor's instruction.

• Take one tablet by mouth each day. To avoid forgetting to take Veltam-F (Finasteride), you can take it at the same time every day.
• If you forget to take Veltam-F (Finasteride), do not take an extra tablet. Just take the next tablet as usual.
• You may take Veltam-F (Finasteride) with or without food.
• Do not share Veltam-F (Finasteride) with anyone else; it was prescribed only for you.

What are the possible side effects of Veltam-F (Finasteride)?

Veltam-F (Finasteride) may increase the chance of a more serious form of prostate cancer.

The most common side effects of Veltam-F (Finasteride) include:

• trouble getting or keeping an erection (impotence)
• decrease in sex drive
• decreased volume of ejaculate
• ejaculation disorders
• enlarged or painful breast. You should promptly report to your doctor any changes in your breasts such as lumps, pain or nipple discharge.

The following have been reported in general use with Veltam-F (Finasteride) and/or Veltam-F (Finasteride) at lower doses:

• allergic reactions, including rash, itching, hives, and swelling of the lips, tongue, throat, and face
• rarely, some men may have testicular pain
• trouble getting or keeping an erection that continued after stopping the medication
• problems with ejaculation that continued after stopping the medication
• male infertility and/or poor quality of semen. Improvement in the quality of semen has been reported after stopping the medication.
• depression
• decrease in sex drive that continued after stopping the medication
• in rare cases, male breast cancer has been reported.

You should discuss side effects with your doctor before taking Veltam-F (Finasteride) and anytime you think you are having a side effect. These are not all the possible side effects with Veltam-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 Veltam-F (Finasteride):

• You should see your doctor regularly while taking Veltam-F (Finasteride). Follow your doctor's advice about when to have these checkups.
• Checking for prostate cancer. Your doctor has prescribed Veltam-F (Finasteride) for BPH and not for treatment of prostate cancer - but a man can have BPH and prostate cancer at the same time. Your doctor may continue checking for prostate cancer while you take Veltam-F (Finasteride).
• About Prostate-Specific Antigen (PSA). Your doctor may have done a blood test called PSA for the screening of prostate cancer. Because Veltam-F (Finasteride) decreases PSA levels, you should tell your doctor(s) that you are taking Veltam-F (Finasteride). Changes in PSA levels will need to be evaluated by your doctor(s). Any increase in follow-up PSA levels from their lowest point may signal the presence of prostate cancer and should be evaluated, even if the test results are still within the normal range. You should also tell your doctor if you have not been taking Veltam-F (Finasteride) as prescribed because this may affect the PSA test results. For more information, talk to your doctor.

How should I store Veltam-F (Finasteride)?

• Store Veltam-F (Finasteride) tablets in a dry place at room temperature.
• Keep Veltam-F (Finasteride) in the original container and keep the container closed.
  

  Veltam-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 Veltam-F (Finasteride) and all medications out of the reach of children.

Do not give your Veltam-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 Veltam-F (Finasteride)?

Active ingredients: Veltam-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:

• a weak or interrupted urinary stream
• a feeling that you cannot empty your bladder completely
• a feeling of delay or hesitation when you start to urinate
• a need to urinate often, especially at night
• a feeling that you must urinate right away.

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 Veltam-F (Finasteride) does:

Veltam-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. Veltam-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:

• Even though the prostate shrinks, you may NOT notice an improvement in urine flow or symptoms.
• You may need to take Veltam-F (Finasteride) for six (6) months or more to see whether it improves your symptoms.
• Therapy with Veltam-F (Finasteride) may reduce your risk for a sudden inability to pass urine and the need for surgery for an enlarged prostate.

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

Veltam-F (Finasteride)^®

(finasteride) Tablets

5 mg

WARNING: Veltam-F (Finasteride)^® (finasteride) should

not be used by women or children.

Women who are or may potentially be

pregnant must not use Veltam-F (Finasteride). They

should also not handle crushed or broken

tablets of Veltam-F (Finasteride).

Rx only

30 Tablets

Tamsulosin Hydrochloride:

•   indications and usage
•   dosage and administration
•   dosage forms and strengths
•   contraindications
•   warnings and precautions
•   adverse reactions
•   drug interactions
•   use in specific populations
•   overdosage
•   description
•   clinical pharmacology
•   nonclinical toxicology
•   clinical studies
•   how supplied/storage and handling
•   patient counseling information
• Veltam-F (Tamsulosin Hydrochloride) reviews

1  INDICATIONS AND USAGE

Veltam-F (Tamsulosin Hydrochloride)^® (tamsulosin hydrochloride) capsules are indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH) [ see Clinical Studies (14) ]. Veltam-F (Tamsulosin Hydrochloride) capsules are not indicated for the treatment of hypertension.

• Veltam-F (Tamsulosin Hydrochloride) is an alpha₁ adrenoceptor antagonist indicated for treatment of the signs and symptoms of benign prostatic hyperplasia (1)
• Veltam-F (Tamsulosin Hydrochloride) capsules are not indicated for the treatment of hypertension (1)

2  DOSAGE AND ADMINISTRATION

Veltam-F (Tamsulosin Hydrochloride) capsules 0.4 mg once daily is recommended as the dose for the treatment of the signs and symptoms of BPH. It should be administered approximately one-half hour following the same meal each day.

For those patients who fail to respond to the 0.4 mg dose after 2 to 4 weeks of dosing, the dose of Veltam-F (Tamsulosin Hydrochloride) capsules can be increased to 0.8 mg once daily. Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) 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.

• 0.4 mg once daily taken approximately one-half hour following the same meal each day (2)
• Can be increased to 0.8 mg once daily for patients who fail to respond to the 0.4 mg dose after 2 to 4 weeks of dosing (2)
• If discontinued or interrupted for several days, therapy should start again with the 0.4 mg once-daily dose (2)

3  DOSAGE FORMS AND STRENGTHS

Capsule: 0.4 mg, olive green and orange hard gelatin, imprinted on one side with Veltam-F (Tamsulosin Hydrochloride) 0.4 mg and on the other side with BI 58

• Capsules: 0.4 mg (3)

4  CONTRAINDICATIONS

Veltam-F (Tamsulosin Hydrochloride) capsules are contraindicated in patients known to be hypersensitive to Veltam-F (Tamsulosin Hydrochloride) or any component of Veltam-F (Tamsulosin Hydrochloride) capsules. Reactions have included skin rash, urticaria, pruritus, angioedema, and respiratory symptoms [ see Adverse Reactions (6.2) ].

• Contraindicated in patients known to be hypersensitive to Veltam-F (Tamsulosin Hydrochloride) or any component of Veltam-F (Tamsulosin Hydrochloride) capsules (4, 6.2)

5  WARNINGS AND PRECAUTIONS

• Advise patients about the possibility of symptoms related to postural hypotension and to avoid situations where injury could result should syncope occur
• Should not be used in combination with strong inhibitors of CYP3A4. Use with caution in combination with moderate inhibitors of CYP3A4, with strong or moderate inhibitors of CYP2D6, in patients known to be CYP2D6 poor metabolizers, or in combination with other cytochrome P450 inhibitors. (5.2, 7.1, 12.3)
• Should not be used in combination with other alpha adrenergic blocking agents (5.2, 7.2, 12.3)
• Exercise caution with concomitant administration of warfarin (5.2, 7.4, 12.3)
• Advise patients about the possibility and seriousness of priapism (5.3)
• Intraoperative Floppy Iris Syndrome has been observed during cataract surgery in some patients. Advise patients considering cataract surgery to tell their ophthalmologist that they have taken Veltam-F (Tamsulosin Hydrochloride) capsules. (5.5)
• Advise patients to be screened for the presence of prostate cancer prior to treatment and at regular intervals afterwards (5.4)

5.1  Orthostasis

The signs and symptoms of orthostasis (postural hypotension, dizziness, and vertigo) were detected more frequently in Veltam-F (Tamsulosin Hydrochloride) capsule-treated patients than in placebo recipients. As with other alpha adrenergic blocking agents there is a potential risk of syncope [ see Adverse Reactions (6.1) ]. Patients beginning treatment with Veltam-F (Tamsulosin Hydrochloride) capsules should be cautioned to avoid situations in which injury could result should syncope occur [ see Patient Counseling Information (17.1) ].

5.2  Drug Interactions

Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6. Veltam-F capsules 0.4 mg should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole) [ see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ]. Veltam-F (Tamsulosin Hydrochloride) capsules should be used with caution in combination with moderate inhibitors of CYP3A4 (e.g., erythromycin), in combination with strong (e.g., paroxetine) or moderate (e.g., terbinafine) inhibitors of CYP2D6, in patients known to be CYP2D6 poor metabolizers particularly at a dose higher than 0.4 mg (e.g., 0.8 mg) [ see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ].

Veltam-F (Tamsulosin Hydrochloride) 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) ].

Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) capsules [ see Drug Interactions (7.4) and Clinical Pharmacology (12.3) ].

5.3  Priapism

Rarely (probably less than 1 in 50,000 patients), tamsulosin, like other alpha₁ antagonists, has been associated with priapism (persistent painful penile erection unrelated to sexual activity). Because this condition can lead to permanent impotence if not properly treated, patients must be advised about the seriousness of the condition [ see Patient Counseling Information (17.2) ].

5.4  Screening for Prostate Cancer

Prostate cancer and BPH frequently co-exist; therefore, patients should be screened for the presence of prostate cancer prior to treatment with Veltam-F capsules and at regular intervals afterwards [ see Patient Counseling Information (17.3) ].

5.5  Intraoperative Floppy Iris Syndrome

Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract surgery in some patients on or previously treated with alpha₁ blockers, including Veltam-F (Tamsulosin Hydrochloride) capsules [ see Adverse Reactions (6.2) ].

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 tamsulosin in patients for whom cataract surgery is scheduled is not recommended.

5.6  Sulfa Allergy

In patients with sulfa allergy, allergic reaction to Veltam-F (Tamsulosin Hydrochloride) capsules has been rarely reported. If a patient reports a serious or life-threatening sulfa allergy, caution is warranted when administering Veltam-F (Tamsulosin Hydrochloride) capsules.

6  ADVERSE REACTIONS

• The most common adverse events with the 0.4 mg dose or 0.8 mg dose were headache, dizziness, rhinitis, infection, abnormal ejaculation, asthenia, back pain, diarrhea, pharyngitis, chest pain, cough increased, somnolence, nausea, sinusitis, insomnia, libido decreased, tooth disorder, and blurred vision (6.1)

To report SUSPECTED ADVERSE REACTIONS, contact Boehringer Ingelheim Pharmaceuticals, Inc. at (800) 542-6257 or (800) 459-9906 TTY, or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

6.1  Clinical Trials Experience

Because clinical studies are conducted under widely varying conditions, adverse reactions rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

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 Veltam-F (Tamsulosin Hydrochloride) capsules were used. These studies evaluated safety in 1783 patients treated with Veltam-F (Tamsulosin Hydrochloride) capsules and 798 patients administered placebo. Table 1 summarizes the treatment-emergent adverse events that occurred in ≥2% of patients receiving either Veltam-F (Tamsulosin Hydrochloride) 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	Veltam-F (Tamsulosin Hydrochloride) 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: The adverse event occurred for the first time after initial dosing with double-blind study medication. The adverse event was present prior to or at the time of initial dosing with double-blind study medication and subsequently increased in severity during double-blind treatment; or The adverse event was present prior to or at the time of initial dosing with double-blind study medication, disappeared completely, and then reappeared during double-blind treatment.
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%)

Signs and Symptoms of Orthostasis

In the two U.S. studies, symptomatic postural hypotension was reported by 0.2% of patients in the 0.4 mg group, 0.4% of patients (2 of 492) in the 0.8 mg group, and by no patients in the placebo group. Syncope was reported by 0.2% of patients (1 of 502) in the 0.4 mg group, 0.4% of patients (2 of 492) in the 0.8 mg group, and 0.6% of patients (3 of 493) in the placebo group. Dizziness was reported by 15% of patients (75 of 502) in the 0.4 mg group, 17% of patients (84 of 492) in the 0.8 mg group, and 10% of patients (50 of 493) in the placebo group. Vertigo was reported by 0.6% of patients (3 of 502) in the 0.4 mg group, 1% of patients (5 of 492) in the 0.8 mg group, and by 0.6% of patients (3 of 493) in the placebo group.

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 Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) capsules 0.4 mg once-daily group, 92 of the 491 patients (19%) in the Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) capsule-treated patients than in placebo recipients, there is a potential risk of syncope [ see Warnings and Precautions (5.1) ].

Abnormal Ejaculation

Abnormal ejaculation includes ejaculation failure, ejaculation disorder, retrograde ejaculation, and ejaculation decrease. As shown in Table 1, abnormal ejaculation was associated with Veltam-F (Tamsulosin Hydrochloride) capsules administration and was dose-related in the U.S. studies. Withdrawal from these clinical studies of Veltam-F (Tamsulosin Hydrochloride) capsules because of abnormal ejaculation was also dose-dependent, with 8 of 492 patients (1.6%) in the 0.8 mg group and no patients in the 0.4 mg or placebo groups discontinuing treatment due to abnormal ejaculation.

Laboratory Tests

No laboratory test interactions with Veltam-F capsules are known. Treatment with Veltam-F (Tamsulosin Hydrochloride) capsules for up to 12 months had no significant effect on prostate-specific antigen (PSA).

6.2  Postmarketing Experience

The following adverse reactions have been identified during post-approval use of Veltam-F (Tamsulosin Hydrochloride) capsules. Because these reactions 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. Decisions to include these reactions in labeling are typically based on one or more of the following factors: (1) seriousness of the reaction, (2) frequency of reporting, or (3) strength of causal connection to Veltam-F (Tamsulosin Hydrochloride) capsules.

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) ].

7  DRUG INTERACTIONS

• Veltam-F capsules 0.4 mg should not be used with strong inhibitors of CYP3A4 (e.g., ketoconazole). Veltam-F (Tamsulosin Hydrochloride) capsules should be used with caution in combination with moderate inhibitors of CYP3A4 (e.g., erythromycin), in combination with strong (e.g., paroxetine) or moderate (e.g., terbinafine) inhibitors of CYP2D6, or in patients known to be CYP2D6 poor metabolizers, particularly at a dose higher than 0.4 mg (e.g., 0.8 mg). (5.2, 7.1, 12.3)
• Concomitant use of PDE5 inhibitors with tamsulosin can potentially cause symptomatic hypotension (5.2, 7.3, 12.3)

7.1  Cytochrome P450 Inhibition

Strong and Moderate Inhibitors of CYP3A4 or CYP2D6

Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6.

Concomitant treatment with ketoconazole resulted in an increase in the C_max and AUC of 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 Veltam-F (Tamsulosin Hydrochloride) 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 C_max and AUC of 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 tamsulosin exposure exists when Veltam-F (Tamsulosin Hydrochloride) 0.4 mg is co-administered with strong CYP3A4 inhibitors in CYP2D6 PMs, Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) capsules have not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when Veltam-F (Tamsulosin Hydrochloride) 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) ].

Cimetidine

Treatment with cimetidine resulted in a significant decrease (26%) in the clearance of Veltam-F (Tamsulosin Hydrochloride), which resulted in a moderate increase in Veltam-F (Tamsulosin Hydrochloride) AUC (44%) [ see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ].

7.2  Other Alpha Adrenergic Blocking Agents

The pharmacokinetic and pharmacodynamic interactions between Veltam-F capsules and other alpha adrenergic blocking agents have not been determined; however, interactions between Veltam-F (Tamsulosin Hydrochloride) capsules and other alpha adrenergic blocking agents may be expected [ see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ].

7.3  PDE5 Inhibitors

Caution is advised when alpha adrenergic blocking agents including Veltam-F (Tamsulosin Hydrochloride) 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 Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ].

7.4  Warfarin

A definitive drug-drug interaction study between Veltam-F and warfarin was not conducted. Results from limited in vitro and in vivo studies are inconclusive. Caution should be exercised with concomitant administration of warfarin and Veltam-F (Tamsulosin Hydrochloride) capsules [ see Warnings and Precautions (5.2) and Clinical Pharmacology (12.3) ].

7.5  Nifedipine, Atenolol, Enalapril

Dosage adjustments are not necessary when Veltam-F (Tamsulosin Hydrochloride) capsules are administered concomitantly with nifedipine, atenolol, or enalapril [ see Clinical Pharmacology (12.3) ].

7.6  Digoxin and Theophylline

Dosage adjustments are not necessary when a Veltam-F capsule is administered concomitantly with digoxin or theophylline [ see Clinical Pharmacology (12.3) ].

7.7  Furosemide

Veltam-F (Tamsulosin Hydrochloride) capsules had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to 12% reduction in Veltam-F (Tamsulosin Hydrochloride) C_max and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the Veltam-F (Tamsulosin Hydrochloride) capsules dosage [ see Clinical Pharmacology (12.3) ].

8  USE IN SPECIFIC POPULATIONS

• Pediatric Use: Not indicated for use in pediatric populations
• 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

Teratogenic Effects, Pregnancy Category B.

Administration of Veltam-F to pregnant female rats 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 Veltam-F (Tamsulosin Hydrochloride) to pregnant rabbits at dose levels up to 50 mg/kg/day produced no evidence of fetal harm. Veltam-F (Tamsulosin Hydrochloride) capsules are not indicated for use in women.

8.3  Nursing Mothers

Veltam-F (Tamsulosin Hydrochloride) capsules are not indicated for use in women.

8.4  Pediatric Use

Veltam-F capsules are not indicated for use in pediatric populations.

Efficacy and positive benefit/risk of Veltam-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 Veltam-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 Veltam-F (Tamsulosin Hydrochloride) and placebo. In an open-label, 12-month safety study, 87 patients were treated with Veltam-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.

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 Veltam-F capsules dosing. However, patients with end-stage renal disease (CL_cr <10 mL/min/1.73 m²) have not been studied [ see Clinical Pharmacology (12.3) ].

8.7  Hepatic Impairment

Patients with moderate hepatic impairment do not require an adjustment in Veltam-F (Tamsulosin Hydrochloride) capsules dosage. Veltam-F (Tamsulosin Hydrochloride) has not been studied in patients with severe hepatic impairment [ see Clinical Pharmacology (12.3) ].

10  OVERDOSAGE

Should overdosage of Veltam-F (Tamsulosin Hydrochloride) capsules lead to hypotension [ see Warnings and Precautions (5.1) and Adverse Reactions (6.1) ], support of the cardiovascular system is of first importance. Restoration of blood pressure and normalization of heart rate may be accomplished by keeping the patient in the supine position. If this measure is inadequate, then administration of intravenous fluids should be considered. If necessary, vasopressors should then be used and renal function should be monitored and supported as needed. Laboratory data indicate that Veltam-F (Tamsulosin Hydrochloride) is 94% to 99% protein bound; therefore, dialysis is unlikely to be of benefit.

11  DESCRIPTION

Veltam-F (Tamsulosin Hydrochloride) is an antagonist of alpha_1A adrenoceptors in the prostate.

Veltam-F (Tamsulosin Hydrochloride) is (-)-( R )-5-[2-[[2-( o -Ethoxyphenoxy) ethyl]amino]propyl]-2-methoxybenzenesulfonamide, monohydrochloride. Veltam-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 Veltam-F (Tamsulosin Hydrochloride) is C₂₀H₂₈N₂O₅S - HCl. The molecular weight of Veltam-F (Tamsulosin Hydrochloride) is 444.98. Its structural formula is:

Each Veltam-F (Tamsulosin Hydrochloride) capsule for oral administration contains Veltam-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.

12  CLINICAL PHARMACOLOGY

12.1  Mechanism of Action

The symptoms associated with benign prostatic hyperplasia are related to bladder outlet obstruction, which is comprised of two underlying components: static and dynamic. The static component is related to an increase in prostate size caused, in part, by a proliferation of smooth muscle cells in the prostatic stroma. However, the severity of BPH symptoms and the degree of urethral obstruction do not correlate well with the size of the prostate. The dynamic component is a function of an increase in smooth muscle tone in the prostate and bladder neck leading to constriction of the bladder outlet. Smooth muscle tone is mediated by the sympathetic nervous stimulation of alpha₁ adrenoceptors, which are abundant in the prostate, prostatic capsule, prostatic urethra, and bladder neck. Blockade of these adrenoceptors can cause smooth muscles in the bladder neck and prostate to relax, resulting in an improvement in urine flow rate and a reduction in symptoms of BPH.

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: alpha_1A, alpha_1B, and alpha_1D; their distribution differs between human organs and tissue. Approximately 70% of the alpha₁ receptors in the human prostate are of the alpha_1A subtype.

Veltam-F (Tamsulosin Hydrochloride) capsules are not intended for use as an antihypertensive drug.

12.2  Pharmacodynamics

Urologic pharmacodynamic effects have been evaluated in neurologically impaired pediatric patients and in adults with BPH [ see Use in Specific Populations (8.4) and Clinical Studies (14) ].

12.3  Pharmacokinetics

The pharmacokinetics of Veltam-F have been evaluated in adult healthy volunteers and patients with BPH after single and/or multiple administration with doses ranging from 0.1 mg to 1 mg.

Absorption

Absorption of Veltam-F (Tamsulosin Hydrochloride) from Veltam-F (Tamsulosin Hydrochloride) capsules 0.4 mg is essentially complete (>90%) following oral administration under fasting conditions. Veltam-F (Tamsulosin Hydrochloride) exhibits linear kinetics following single and multiple dosing, with achievement of steady-state concentrations by the fifth day of once-a-day dosing.

Effect of Food

The time to maximum concentration is reached by 4 to 5 hours under fasting conditions and by 6 to 7 hours when Veltam-F (Tamsulosin Hydrochloride) capsules are administered with food. Taking Veltam-F (Tamsulosin Hydrochloride) capsules under fasted conditions results in a 30% increase in bioavailability (AUC) and 40% to 70% increase in peak concentrations (C_max) compared to fed conditions (Figure 1).

Figure 1 Mean Plasma Veltam-F (Tamsulosin Hydrochloride) Concentrations Following Single-Dose Administration of Veltam-F (Tamsulosin Hydrochloride) Capsules 0.4 mg Under Fasted and Fed Conditions (n=8)

The effects of food on the pharmacokinetics of Veltam-F (Tamsulosin Hydrochloride) are consistent regardless of whether a Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) plasma concentration
Tmax = median time-to-maximum concentration
T1/2 = observed half-life
AUCτ = area under the Veltam-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

Distribution

The mean steady-state apparent volume of distribution of Veltam-F (Tamsulosin Hydrochloride) after intravenous administration to 10 healthy male adults was 16 L, which is suggestive of distribution into extracellular fluids in the body.

Veltam-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 Veltam-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, Veltam-F (Tamsulosin Hydrochloride) had no effect on the extent of binding of these drugs.

Metabolism

There is no enantiomeric bioconversion from Veltam-F [R(-) isomer] to the S(+) isomer in humans. Veltam-F (Tamsulosin Hydrochloride) is extensively metabolized by cytochrome P450 enzymes in the liver and less than 10% of the dose is excreted in urine unchanged. However, the pharmacokinetic profile of the metabolites in humans has not been established. Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6 as well as via some minor participation of other CYP isoenzymes. Inhibition of hepatic drug-metabolizing enzymes may lead to increased exposure to tamsulosin [ see Warnings and Precautions (5.2) and Drug Interactions (7.1) ]. The metabolites of Veltam-F (Tamsulosin Hydrochloride) undergo extensive conjugation to glucuronide or sulfate prior to renal excretion.

Incubations with human liver microsomes showed no evidence of clinically significant metabolic interactions between Veltam-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 Veltam-F (Tamsulosin Hydrochloride) interaction with diclofenac and warfarin were equivocal.

Excretion

On administration of the radiolabeled dose of Veltam-F (Tamsulosin Hydrochloride) to 4 healthy volunteers, 97% of the administered radioactivity was recovered, with urine (76%) representing the primary route of excretion compared to feces (21%) over 168 hours.

Following intravenous or oral administration of an immediate-release formulation, the elimination half-life of Veltam-F (Tamsulosin Hydrochloride) in plasma ranged from 5 to 7 hours. Because of absorption rate-controlled pharmacokinetics with Veltam-F (Tamsulosin Hydrochloride) capsules, the apparent half-life of Veltam-F (Tamsulosin Hydrochloride) is approximately 9 to 13 hours in healthy volunteers and 14 to 15 hours in the target population.

Veltam-F (Tamsulosin Hydrochloride) undergoes restrictive clearance in humans, with a relatively low systemic clearance (2.88 L/h).

Specific Populations

Pediatric Use

Veltam-F capsules are not indicated for use in pediatric populations [ see Use in Specific Populations (8.4) ].

Geriatric (Age) Use

Cross-study comparison of Veltam-F (Tamsulosin Hydrochloride) capsules overall exposure (AUC) and half-life indicates that the pharmacokinetic disposition of Veltam-F (Tamsulosin Hydrochloride) may be slightly prolonged in geriatric males compared to young, healthy male volunteers. Intrinsic clearance is independent of Veltam-F (Tamsulosin Hydrochloride) binding to AAG, but diminishes with age, resulting in a 40% overall higher exposure (AUC) in subjects of age 55 to 75 years compared to subjects of age 20 to 32 years [ see Use in Specific Populations (8.5) ].

Renal Impairment

The pharmacokinetics of Veltam-F have been compared in 6 subjects with mild-moderate (30≤ CL_cr <70 mL/min/1.73 m²) or moderate-severe (10≤ CL_cr <30 mL/min/1.73 m²) renal impairment and 6 normal subjects (CL_cr >90 mL/min/1.73 m²). While a change in the overall plasma concentration of Veltam-F (Tamsulosin Hydrochloride) was observed as the result of altered binding to AAG, the unbound (active) concentration of Veltam-F (Tamsulosin Hydrochloride), as well as the intrinsic clearance, remained relatively constant. Therefore, patients with renal impairment do not require an adjustment in Veltam-F (Tamsulosin Hydrochloride) capsules dosing. However, patients with end-stage renal disease (CL_cr <10 mL/min/1.73 m²) have not been studied [ see Use in Specific Populations (8.6) ].

Hepatic Impairment

The pharmacokinetics of Veltam-F (Tamsulosin Hydrochloride) have been compared in 8 subjects with moderate hepatic impairment (Child-Pugh’s classification: Grades A and B) and 8 normal subjects. While a change in the overall plasma concentration of Veltam-F (Tamsulosin Hydrochloride) was observed as the result of altered binding to AAG, the unbound (active) concentration of Veltam-F (Tamsulosin Hydrochloride) does not change significantly, with only a modest (32%) change in intrinsic clearance of unbound Veltam-F (Tamsulosin Hydrochloride). Therefore, patients with moderate hepatic impairment do not require an adjustment in Veltam-F (Tamsulosin Hydrochloride) capsules dosage. Veltam-F (Tamsulosin Hydrochloride) has not been studied in patients with severe hepatic impairment [ see Use in Specific Populations (8.7) ].

Drug Interactions

Cytochrome P450 Inhibition

Strong and Moderate Inhibitors of CYP3A4 or CYP2D6

The effects of ketoconazole at 400 mg once daily for 5 days on the pharmacokinetics of a single Veltam-F (Tamsulosin Hydrochloride) 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 C_max and AUC of 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 Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) 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 C_max and AUC of 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 tamsulosin exposure exists when Veltam-F (Tamsulosin Hydrochloride) 0.4 mg is co-administered with strong CYP3A4 inhibitors in CYP2D6 PMs, Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) capsules have not been evaluated. However, there is a potential for significant increase in tamsulosin exposure when Veltam-F (Tamsulosin Hydrochloride) 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) ].

Cimetidine

The effects of cimetidine at the highest recommended dose (400 mg every 6 hours for 6 days) on the pharmacokinetics of a single Veltam-F (Tamsulosin Hydrochloride) capsule 0.4 mg dose was investigated in 10 healthy volunteers (age range 21 to 38 years). Treatment with cimetidine resulted in a significant decrease (26%) in the clearance of Veltam-F (Tamsulosin Hydrochloride), which resulted in a moderate increase in Veltam-F (Tamsulosin Hydrochloride) AUC (44%) [ see Warnings and Precautions (5.2) and Drug Interactions (7.1) ].

Other Alpha Adrenergic Blocking Agents

The pharmacokinetic and pharmacodynamic interactions between Veltam-F capsules and other alpha adrenergic blocking agents have not been determined; however, interactions between Veltam-F (Tamsulosin Hydrochloride) capsules and other alpha adrenergic blocking agents may be expected [ see Warnings and Precautions (5.2) and Drug Interactions (7.2) ].

PDE5 Inhibitors

Caution is advised when alpha adrenergic blocking agents, including Veltam-F (Tamsulosin Hydrochloride), 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 Warnings and Precautions (5.2) and Drug Interactions (7.3) ].

Warfarin

A definitive drug-drug interaction study between Veltam-F and warfarin was not conducted. Results from limited in vitro and in vivo studies are inconclusive. Therefore, caution should be exercised with concomitant administration of warfarin and Veltam-F (Tamsulosin Hydrochloride) capsules [ see Warnings and Precautions (5.2) and Drug Interactions (7.4) ].

Nifedipine, Atenolol, Enalapril

In three studies in hypertensive subjects (age range 47 to 79 years) whose blood pressure was controlled with stable doses of nifedipine, atenolol, or enalapril for at least 3 months, Veltam-F (Tamsulosin Hydrochloride) capsules 0.4 mg for 7 days followed by Veltam-F (Tamsulosin Hydrochloride) capsules 0.8 mg for another 7 days (n=8 per study) resulted in no clinically significant effects on blood pressure and pulse rate compared to placebo (n=4 per study). Therefore, dosage adjustments are not necessary when Veltam-F (Tamsulosin Hydrochloride) capsules are administered concomitantly with nifedipine, atenolol, or enalapril [ see Drug Interactions (7.5) ].

Digoxin and Theophylline

In two studies in healthy volunteers receiving Veltam-F (Tamsulosin Hydrochloride) capsules 0.4 mg/day for 2 days, followed by Veltam-F (Tamsulosin Hydrochloride) capsules 0.8 mg/day for 5 to 8 days, single intravenous doses of digoxin 0.5 mg or theophylline 5 mg/kg resulted in no change in the pharmacokinetics of digoxin or theophylline. Therefore, dosage adjustments are not necessary when a Veltam-F (Tamsulosin Hydrochloride) capsule is administered concomitantly with digoxin or theophylline [ see Drug Interactions (7.6) ].

Furosemide

The pharmacokinetic and pharmacodynamic interaction between Veltam-F (Tamsulosin Hydrochloride) capsules 0.8 mg/day (steady-state) and furosemide 20 mg intravenously (single dose) was evaluated in 10 healthy volunteers (age range 21 to 40 years). Veltam-F (Tamsulosin Hydrochloride) capsules had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to 12% reduction in Veltam-F (Tamsulosin Hydrochloride) C_max and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the Veltam-F (Tamsulosin Hydrochloride) capsules dosage [ see Drug Interactions (7.7) ].

13  NONCLINICAL TOXICOLOGY

13.1  Carcinogenesis, Mutagenesis, Impairment of Fertility

Rats administered doses up to 43 mg/kg/day in males and 52 mg/kg/day in females had no increases in tumor incidence, with the exception of a modest increase in the frequency of mammary gland fibroadenomas in female rats receiving doses ≥5.4 mg/kg (P<0.015). The highest doses of Veltam-F (Tamsulosin Hydrochloride) evaluated in the rat carcinogenicity study produced systemic exposures (AUC) in rats 3 times the exposures in men receiving the maximum therapeutic dose of 0.8 mg/day.

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 Veltam-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 tamsulosin hydrochloride-induced hyperprolactinemia. It is not known if Veltam-F (Tamsulosin Hydrochloride) capsules elevate prolactin in humans. The relevance for human risk of the findings of prolactin-mediated endocrine tumors in rodents is not known.

Veltam-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 Veltam-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 Veltam-F (Tamsulosin Hydrochloride) (1/5 and 16 times the anticipated human AUC exposure) did not significantly alter fertility in male rats. Effects of Veltam-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 Veltam-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.

14  CLINICAL STUDIES

Four placebo-controlled clinical studies and one active-controlled clinical study enrolled a total of 2296 patients (1003 received Veltam-F (Tamsulosin Hydrochloride) capsules 0.4 mg once daily, 491 received Veltam-F (Tamsulosin Hydrochloride) capsules 0.8 mg once daily, and 802 were control patients) in the U.S. and Europe.

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, Veltam-F (Tamsulosin Hydrochloride) capsules 0.4 mg once daily, or Veltam-F (Tamsulosin Hydrochloride) capsules 0.8 mg once daily. Patients in Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) capsules 0.4 mg and 0.8 mg once-daily groups compared to placebo in Study 1, and for the Veltam-F (Tamsulosin Hydrochloride) 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.
Study 1 †
Veltam-F (Tamsulosin Hydrochloride) 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
Veltam-F (Tamsulosin Hydrochloride) 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
Study 2 ‡
Veltam-F (Tamsulosin Hydrochloride) 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
Veltam-F (Tamsulosin Hydrochloride) 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

Mean total AUA Symptom Scores for both Veltam-F (Tamsulosin Hydrochloride) capsules 0.4 mg and 0.8 mg once-daily groups showed a rapid decrease starting at 1 week after dosing and remained decreased through 13 weeks in both studies (Figures 2A and 2B).

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 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 tamsulosin concentration).

All other visits were scheduled 24 to 27 hours after dosing (approximate trough tamsulosin concentration).

16  HOW SUPPLIED/STORAGE AND HANDLING

Veltam-F (Tamsulosin Hydrochloride) capsules 0.4 mg are supplied in high density polyethylene bottles containing 100 hard gelatin capsules with olive green opaque cap and orange opaque body. The capsules are imprinted on one side with Veltam-F (Tamsulosin Hydrochloride) 0.4 mg and on the other side with BI 58.

Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) capsules and all medicines out of reach of children.

17  PATIENT COUNSELING INFORMATION

See FDA-Approved Patient Labeling.

17.1  Hypotension

Patients should be told about the possible occurrence of symptoms related to postural hypotension, such as dizziness, when taking Veltam-F (Tamsulosin Hydrochloride) capsules, and they should be cautioned about driving, operating machinery, or performing hazardous tasks [ see Warnings and Precautions (5.1) ].

17.2  Priapism

Patients should be advised about the possibility of priapism as a result of treatment with Veltam-F capsules and other similar medications. Patients should be informed that this reaction is extremely rare, but if not brought to immediate medical attention, can lead to permanent erectile dysfunction (impotence) [ see Warnings and Precautions (5.3) ].

17.3  Screening for Prostate Cancer

Prostate cancer and BPH frequently co-exist; therefore, patients should be screened for the presence of prostate cancer prior to treatment with Veltam-F (Tamsulosin Hydrochloride) capsules and at regular intervals afterwards [ see Warnings and Precautions (5.4) ].

17.4  Intraoperative Floppy Iris Syndrome

Patients considering cataract surgery should be advised to tell their ophthalmologist that they have taken Veltam-F capsules [ see Warnings and Precautions (5.5) ].

17.5  Administration

Patients should be advised not to crush or chew the Veltam-F (Tamsulosin Hydrochloride) capsules.

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

Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride)?

Veltam-F (Tamsulosin Hydrochloride) 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.

• Veltam-F (Tamsulosin Hydrochloride) is not for women.
• Veltam-F (Tamsulosin Hydrochloride) is not for children.

Who should not take Veltam-F (Tamsulosin Hydrochloride)?

Do not take Veltam-F (Tamsulosin Hydrochloride) capsules if you are allergic to any of its ingredients. See the end of this leaflet for a complete list of ingredients in Veltam-F (Tamsulosin Hydrochloride) capsules.

What should I tell my doctor before using Veltam-F (Tamsulosin Hydrochloride)?

Before taking Veltam-F (Tamsulosin Hydrochloride) capsules, tell your doctor about all your medical conditions, including:

• any kidney or liver problems.
• any history of low blood pressure.
• any allergies to sulfa or any other medicines.
• if you are planning to have cataract surgery.

Tell your doctor about all the medicines you take, including:

• any prescription medicines, including blood pressure medicines.
• any non-prescription medicines, including vitamins and herbal supplements.

Some of your other medicines may affect the way Veltam-F (Tamsulosin Hydrochloride) capsules work. Especially tell your doctor if you take a medicine for high blood pressure. You should not take Veltam-F (Tamsulosin Hydrochloride) if you are already taking certain blood pressure medicines.

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 Veltam-F (Tamsulosin Hydrochloride)?

• Take Veltam-F (Tamsulosin Hydrochloride) exactly as prescribed by your doctor.
• Do not crush, chew, or open Veltam-F (Tamsulosin Hydrochloride) capsules.
• Take Veltam-F (Tamsulosin Hydrochloride) one time each day, about 30 minutes after the same meal each day. For example, you may take Veltam-F (Tamsulosin Hydrochloride) 30 minutes after dinner each day.
• If you miss a dose of Veltam-F (Tamsulosin Hydrochloride), take it as soon as you remember. If you miss your dose for the whole day, continue with your next dose on your regular schedule. Do not take two doses at the same time.
• If you stop or forget to take Veltam-F (Tamsulosin Hydrochloride) for several days, talk with your doctor before starting again.
• If you take more Veltam-F (Tamsulosin Hydrochloride) capsules than prescribed, call your doctor right away.

What are the possible side effects of Veltam-F (Tamsulosin Hydrochloride) capsules?

Possible side effects of Veltam-F (Tamsulosin Hydrochloride) may include:

• Decreased blood pressure when changing positions. Veltam-F (Tamsulosin Hydrochloride) capsules may cause a sudden drop in blood pressure upon standing, especially after the first dose or when changing doses.
  

  Symptoms may include:

  • fainting
  • dizziness
  • lightheadedness
  Change positions slowly from lying down to sitting up or from a sitting to a standing position until you learn how you react to Veltam-F (Tamsulosin Hydrochloride) capsules. If you begin to feel dizzy, sit or lie down until you feel better. If the symptoms are severe or do not improve, call your doctor.
  

• Allergic reactions. Make your doctor aware of any allergic reactions you may experience while taking Veltam-F (Tamsulosin Hydrochloride).
  

  Allergic reactions may include:

  • rash
  • itching
  • hives
  Rare and more serious allergic reactions may also occur. Get medical help right away if you have any of the following reactions:
  • swelling of face, tongue, or throat
  • difficulty breathing
  • blistering of the skin
    

• A painful erection that will not go away. Veltam-F (Tamsulosin Hydrochloride) capsules can cause a painful erection (priapism), which cannot be relieved by having sex. If this happens, get medical help right away. If priapism is not treated, you may not be able to get an erection in the future.
  

• Eye problems during cataract surgery. During cataract surgery, a condition called intraoperative floppy iris syndrome (IFIS) can happen if you take or have taken Veltam-F (Tamsulosin Hydrochloride) capsules. If you need to have cataract surgery, be sure to tell your surgeon if you take or have taken Veltam-F (Tamsulosin Hydrochloride) capsules.

Common side effects of Veltam-F (Tamsulosin Hydrochloride) capsules may include:

• runny nose
• dizziness
• decreased semen

These are not all the possible side effects with Veltam-F (Tamsulosin Hydrochloride) capsules. Tell your doctor if you have any side effect that bothers you or that does not go away.

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 Veltam-F (Tamsulosin Hydrochloride) capsules?

Avoid driving, operating machinery, or other dangerous activities, until you know how Veltam-F (Tamsulosin Hydrochloride) affects you. Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) capsules? "

How do I store Veltam-F (Tamsulosin Hydrochloride) capsules?

Store Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) to other people, even if they have the same symptoms that you have. It may harm them.

While taking Veltam-F (Tamsulosin Hydrochloride), 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 Veltam-F (Tamsulosin Hydrochloride) capsules and at regular intervals afterwards.

This patient information leaflet summarizes the most important information about Veltam-F (Tamsulosin Hydrochloride). If you would like more information, talk with your doctor. You can ask your pharmacist or doctor for information about Veltam-F (Tamsulosin Hydrochloride) 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 Veltam-F (Tamsulosin Hydrochloride) capsules?

• Active Ingredient: Veltam-F (Tamsulosin Hydrochloride)
• 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.

Distributed by:

Boehringer Ingelheim Pharmaceuticals, Inc.

Ridgefield, CT 06877 USA

Veltam-F (Tamsulosin Hydrochloride) 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

Veltam-F (Tamsulosin Hydrochloride) Structure Figure 1 Figure 2a Figure 2b Figure 3a Figure 3b