Veltam Plus

Each capsule contains Dutasteride (Veltam Plus) 0.5 mg and Tamsulosin (Veltam Plus) HCl 0.4 mg.

It also contains the following excipients: Mono-di-glycerides of caprylic/capric acid, butylhydroxytoluene, gelatin, glycerol, titanium dioxide, purified water, cellulose, microcrystalline, methacrylic acid-ethyl acrylate copolymer, talc, triethyl citrate, carrageenan, potassium chloride, hypromellose, medium chain triglycerides, lecithin, carnauba wax, maize starch, yellow iron oxide, red iron oxide, FD & C yellow 6.

Benign Prostatic Hyperplasia (BPH) Treatment

Veltam Plus® (Dutasteride (Veltam Plus) and Tamsulosin (Veltam Plus) hydrochloride) capsules are indicated for the treatment of symptomatic BPH in men with an enlarged prostate.

Limitations of Use

Dutasteride (Veltam Plus)-containing products, including Veltam Plus, are not approved for the prevention of prostate cancer.

Note: Women of childbearing potential should not use or handle Dutasteride (Veltam Plus) and Tamsulosin (Veltam Plus). Dutasteride (Veltam Plus) can cause birth defects in male fetuses.

Dutasteride (Veltam Plus) and Tamsulosin (Veltam Plus) combination is used to treat men who have symptoms of an enlarged prostate gland, which is also known as benign prostatic hyperplasia (BPH). Benign enlargement of the prostate is a problem that can occur in men as they get older. The prostate gland is located below the bladder. When the prostate gland gets larger, certain muscles in the gland get in the way of the tube that drains urine from the bladder. This can cause problems with urinating, such as a need to urinate often, a weak stream when urinating, or a feeling of not being able to empty the bladder completely.

Dutasteride (Veltam Plus) blocks the action of an enzyme called 5-alpha-reductase. This enzyme changes testosterone to another hormone that causes the prostate gland to grow. Dutasteride (Veltam Plus) will cause the size of the prostate to decrease, but the effect lasts only as long as the medicine is taken. If it is stopped, the prostate begins to grow again.

Tamsulosin (Veltam Plus) helps relax the muscles in the prostate gland and the opening of the bladder. This may help increase the flow of urine or decrease symptoms.

Dutasteride (Veltam Plus) and Tamsulosin (Veltam Plus) is available only with your doctor's prescription.

The recommended dosage of Veltam Plus is 1 capsule (0.5 mg Dutasteride (Veltam Plus) and 0.4 mg Tamsulosin (Veltam Plus) hydrochloride) taken once daily approximately 30 minutes after the same meal each day.

The capsules should be swallowed whole and not chewed or opened. Contact with the contents of the Veltam Plus capsule may result in irritation of the oropharyngeal mucosa.

How supplied

Dosage Forms And Strengths

Veltam Plus capsules, containing 0.5 mg Dutasteride (Veltam Plus) and 0.4 mg Tamsulosin (Veltam Plus) hydrochloride, are oblong, hard-shell capsules with a brown body and an orange cap imprinted with “GS 7CZ” in black ink.

Storage And Handling

Veltam Plus capsules, containing 0.5 mg Dutasteride (Veltam Plus) and 0.4 mg Tamsulosin (Veltam Plus) hydrochloride, are oblong hard-shell capsules with a brown body and an orange cap imprinted with “GS 7CZ” in black ink. They are available in bottles with child-resistant closures as follows:

Bottle of 30 (NDC 0173-0809-13).

Bottle of 90 (NDC 0173-0809-59).

Store at 25°C (77°F); excursions permitted 15° to 30°C (59° to 86°F). Capsules may become deformed and/or discolored if kept at high temperatures.

Dutasteride (Veltam Plus) is absorbed through the skin. Veltam Plus capsules should not be handled by women who are pregnant or who could become pregnant because of the potential for absorption of Dutasteride (Veltam Plus) and the subsequent potential risk to a developing male fetus.

Manufactured for: GlaxoSmithKline, Research Triangle Park, NC 27709. Revised: January 2015

See also:
What is the most important information I should know about Veltam Plus?

Hypersensitivity to Tamsulosin (Veltam Plus), Dutasteride (Veltam Plus), other ingredients of Veltam Plus or to other 5α-reductase inhibitors; history of orthostatic hypotension, severe hepatic impairment.

Use in pregnancy: No studies have been conducted with Veltam Plus to investigate the effect on pregnancy. The following statements reflect the information available on the individual components. 5α-reductase inhibitors can inhibit the development of the external genitalia of male foetuses.

As Dutasteride (Veltam Plus) is absorbed through the skin, contact (especially with leaking capsules) should be avoided during pregnancy.

It is not known whether a male foetus may be adversely affected if his mother is exposed to the semen of a patient being treated with Dutasteride (Veltam Plus).

Use in lactation: Veltam Plus is contraindicated in women. No studies have been conducted with Veltam Plus to investigate the effect on lactation. It is not known whether Dutasteride (Veltam Plus) or Tamsulosin (Veltam Plus) are excreted in human breast milk. Use in children: Veltam Plus is not indicated in patients ≤21 years.

Use Dutasteride (Veltam Plus)/Tamsulosin (Veltam Plus) as directed by your doctor. Check the label on the medicine for exact dosing instructions.

• An extra patient leaflet is available with Dutasteride (Veltam Plus)/Tamsulosin (Veltam Plus). Talk to your pharmacist if you have questions about this information.
• Take Dutasteride (Veltam Plus)/Tamsulosin (Veltam Plus) by mouth about 30 minutes after the same meal each day.
• Swallow Dutasteride (Veltam Plus)/Tamsulosin (Veltam Plus) whole. Do not break, crush, chew, or open before swallowing. Do not take capsules that are cracked, deformed, discolored, or leaking. Dutasteride (Veltam Plus)/Tamsulosin (Veltam Plus) can irritate your lips, mouth, and throat.
• Take Dutasteride (Veltam Plus)/Tamsulosin (Veltam Plus) on a regular schedule to get the most benefit from it. Taking Dutasteride (Veltam Plus)/Tamsulosin (Veltam Plus) at the same time each day will help you remember to take it.
• Continue to take Dutasteride (Veltam Plus)/Tamsulosin (Veltam Plus) even if you feel well. Do not miss any doses.
• If you miss a dose of Dutasteride (Veltam Plus)/Tamsulosin (Veltam Plus), you may take the missed dose later that same day, 30 minutes after a meal. If it is almost time for your next dose, skip the missed dose and go back to your regular dosing schedule. Do not take 2 doses at once. If you miss taking Dutasteride (Veltam Plus)/Tamsulosin (Veltam Plus) for several days, contact your doctor for instructions.

Ask your health care provider any questions you may have about how to use Dutasteride (Veltam Plus)/Tamsulosin (Veltam Plus).

This product is used in men to treat the symptoms of an enlarged prostate (benign prostatic hyperplasia-BPH). Dutasteride (Veltam Plus) works by reducing the size of the enlarged prostate. Tamsulosin (Veltam Plus) is known as an alpha-blocker and works by relaxing muscles in the bladder and prostate. This product helps to relieve symptoms of BPH such as difficulty in beginning the flow of urine, weak stream, and the need to urinate frequently or urgently (including during the middle of the night).

Dutasteride (Veltam Plus) is not approved for prevention of prostate cancer. It may slightly increase the risk of developing a very serious form of prostate cancer. Talk to your doctor about the benefits and risks.

This medication should not be used by women or children.

How to use Veltam Plus

Read the Patient Information Leaflet if available from your pharmacist before you start taking this medication and each time you get a refill. If you have any questions, ask your doctor or pharmacist.

Take this medication by mouth as directed by your doctor, usually once daily, 30 minutes after the same meal each day. Swallow this medication whole. Do not crush, chew, or open the capsules.

This medication may cause a sudden drop in your blood pressure, which could lead to dizziness or fainting. This risk is higher when you first start taking this drug or if you restart treatment after you stop taking it. During these times, avoid situations where you may be injured if you faint.

Take this medication regularly in order to get the most benefit from it. To help you remember, take it at the same time each day.

Since this drug can be absorbed through the skin and may harm an unborn baby, women who are pregnant or who may become pregnant should not handle this medication.

It may take up to 4 weeks to notice an improvement in symptoms. Tell your doctor if your symptoms do not improve after 4 weeks or if they worsen.

See also:
What other drugs will affect Veltam Plus?

There have been no drug interaction trials using Veltam Plus. The following sections reflect information available for the individual components.

Cytochrome P450 3A Inhibitors

Dutasteride (Veltam Plus)

Dutasteride (Veltam Plus) is extensively metabolized in humans by the CYP3A4 and CYP3A5 isoenzymes. The effect of potent CYP3A4 inhibitors on Dutasteride (Veltam Plus) has not been studied. Because of the potential for drug-drug interactions, use caution when prescribing a Dutasteride (Veltam Plus)-containing product, including Veltam Plus, to patients taking potent, chronic CYP3A4 enzyme inhibitors (e.g., ritonavir).

Tamsulosin (Veltam Plus)

Strong and Moderate Inhibitors of CYP3A4 or CYP2D6: Tamsulosin (Veltam Plus) is extensively metabolized, mainly by CYP3A4 or CYP2D6.

Concomitant treatment with ketoconazole (a strong inhibitor of CYP3A4) resulted in increases in the Cmax and area under the concentration-time curve (AUC) of Tamsulosin (Veltam Plus) by factors of 2.2 and 2.8, respectively. Concomitant treatment with paroxetine (a strong inhibitor of CYP2D6) resulted in increases in the Cmax and AUC of Tamsulosin (Veltam Plus) by factors of 1.3 and 1.6, respectively. A similar increase in exposure is expected in poor metabolizers (PM) of CYP2D6 as compared to extensive metabolizers (EM). Since CYP2D6 PMs cannot be readily identified and the potential for significant increase in Tamsulosin (Veltam Plus) exposure exists when Tamsulosin (Veltam Plus) 0.4 mg is coadministered with strong CYP3A4 inhibitors in CYP2D6 PMs, Tamsulosin (Veltam Plus) 0.4 mg capsules should not be used in combination with strong inhibitors of CYP3A4 (e.g., ketoconazole). The effects of coadministration of both a CYP3A4 and a CYP2D6 inhibitor with Tamsulosin (Veltam Plus) have not been evaluated. However, there is a potential for significant increase in Tamsulosin (Veltam Plus) exposure when Tamsulosin (Veltam Plus) 0.4 mg is coadministered with a combination of both CYP3A4 and CYP2D6 inhibitors.

Cimetidine: Treatment with cimetidine resulted in a moderate increase in Tamsulosin (Veltam Plus) hydrochloride AUC (44%).

Warfarin

Dutasteride (Veltam Plus)

Concomitant administration of Dutasteride (Veltam Plus) 0.5 mg/day for 3 weeks with warfarin does not alter the steady-state pharmacokinetics of the S- or R-warfarin isomers or alter the effect of warfarin on prothrombin time.

Tamsulosin (Veltam Plus)

A definitive drug-drug interaction trial between Tamsulosin (Veltam Plus) hydrochloride 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 Tamsulosin (Veltam Plus)-containing products, including Veltam Plus.

Nifedipine, Atenolol, Enalapril

Tamsulosin (Veltam Plus)

Dosage adjustments are not necessary when Tamsulosin (Veltam Plus) is administered concomitantly with nifedipine, atenolol, or enalapril.

Digoxin And Theophylline

Dutasteride (Veltam Plus)

Dutasteride (Veltam Plus) does not alter the steady-state pharmacokinetics of digoxin when administered concomitantly at a dose of 0.5 mg/day for 3 weeks.

Tamsulosin (Veltam Plus)

Dosage adjustments are not necessary when Tamsulosin (Veltam Plus) is administered concomitantly with digoxin or theophylline.

Furosemide

Tamsulosin (Veltam Plus)

Tamsulosin (Veltam Plus) had no effect on the pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to 12% reduction in Tamsulosin (Veltam Plus) hydrochloride Cmax and AUC, these changes are expected to be clinically insignificant and do not require adjustment of the dose of Tamsulosin (Veltam Plus).

Calcium Channel Antagonists

Dutasteride (Veltam Plus)

Coadministration of verapamil or diltiazem decreases Dutasteride (Veltam Plus) clearance and leads to increased exposure to Dutasteride (Veltam Plus). The change in Dutasteride (Veltam Plus) exposure is not considered to be clinically significant. No dosage adjustment of Dutasteride (Veltam Plus) is recommended.

Cholestyramine

Dutasteride (Veltam Plus)

Administration of a single 5-mg dose of Dutasteride (Veltam Plus) followed 1 hour later by a 12-g dose of cholestyramine does not affect the relative bioavailability of Dutasteride (Veltam Plus).

Use In Specific Population

Pregnancy

Pregnancy Category X. There are no adequate and well-controlled studies in pregnant women with Veltam Plus or its individual components.

Dutasteride (Veltam Plus)

Dutasteride (Veltam Plus) is contraindicated for use in women of childbearing potential and during pregnancy. Dutasteride (Veltam Plus) is a 5-alpha-reductase inhibitor that prevents conversion of testosterone to dihydrotestosterone (DHT), a hormone necessary for normal development of male genitalia. In animal reproduction and developmental toxicity studies, Dutasteride (Veltam Plus) inhibited normal development of external genitalia in male fetuses. Therefore, Dutasteride (Veltam Plus) may cause fetal harm when administered to a pregnant woman. If Dutasteride (Veltam Plus) is used during pregnancy or if the patient becomes pregnant while taking Dutasteride (Veltam Plus), the patient should be apprised of the potential hazard to the fetus.

Abnormalities in the genitalia of male fetuses is an expected physiological consequence of inhibition of the conversion of testosterone to DHT by 5-alpha-reductase inhibitors. These results are similar to observations in male infants with genetic 5-alpha-reductase deficiency. Dutasteride (Veltam Plus) is absorbed through the skin. To avoid potential fetal exposure, women who are pregnant or could become pregnant should not handle Dutasteride (Veltam Plus)-containing capsules, including Veltam Plus capsules. If contact is made with leaking capsules, the contact area should be washed immediately with soap and water. Dutasteride (Veltam Plus) is secreted into semen. The highest measured semen concentration of Dutasteride (Veltam Plus) in treated men was 14 ng/mL. Assuming exposure of a 50-kg woman to 5 mL of semen and 100% absorption, the woman's Dutasteride (Veltam Plus) concentration would be about 0.0175 ng/mL. This concentration is more than 100 times less than concentrations producing abnormalities of male genitalia in animal studies. Dutasteride (Veltam Plus) is highly protein bound in human semen (greater than 96%), which may reduce the amount of Dutasteride (Veltam Plus) available for vaginal absorption.

In an embryo-fetal development study in female rats, oral administration of Dutasteride (Veltam Plus) at doses 10 times less than the maximum recommended human dose (MRHD) of 0.5 mg daily resulted in abnormalities of male genitalia in the fetus (decreased anogenital distance at 0.05 mg/kg/day), nipple development, hypospadias, and distended preputial glands in male offspring (at all doses of 0.05, 2.5, 12.5, and 30 mg/kg/day). An increase in stillborn pups was observed at 111 times the MRHD, and reduced fetal body weight was observed at doses of about 15 times the MRHD (animal dose of 2.5 mg/kg/day). Increased incidences of skeletal variations considered to be delays in ossification associated with reduced body weight were observed at doses at about 56 times the MRHD (animal dose of 12.5 mg/kg/day).

In a rabbit embryo-fetal study, doses 28- to 93-fold the MRHD (animal doses of 30, 100, and 200 mg/kg/day) were administered orally during the period of major organogenesis (gestation days 7 to 29) to encompass the late period of external genitalia development. Histological evaluation of the genital papilla of fetuses revealed evidence of feminization of the male fetus at all doses. A second embryo-fetal study in rabbits at 0.3- to 53-fold the expected clinical exposure (animal doses of 0.05, 0.4, 3.0, and 30 mg/kg/day) also produced evidence of feminization of the genitalia in male fetuses at all doses.

In an oral pre- and post-natal development study in rats, Dutasteride (Veltam Plus) doses of 0.05, 2.5, 12.5, or 30 mg/kg/day were administered. Unequivocal evidence of feminization of the genitalia (i.e., decreased anogenital distance, increased incidence of hypospadias, nipple development) of male offspring occurred at 14- to 90-fold the MRHD (animal doses of 2.5 mg/kg/day or greater). At 0.05-fold the expected clinical exposure (animal dose of 0.05 mg/kg/day), evidence of feminization was limited to a small, but statistically significant, decrease in anogenital distance. Animal doses of 2.5 to 30 mg/kg/day resulted in prolonged gestation in the parental females and a decrease in time to vaginal patency for female offspring and a decrease in prostate and seminal vesicle weights in male offspring. Effects on newborn startle response were noted at doses greater than or equal to 12.5 mg/kg/day. Increased stillbirths were noted at 30 mg/kg/day.

In an embryo-fetal development study, pregnant rhesus monkeys were exposed intravenously to a Dutasteride (Veltam Plus) blood level comparable to the Dutasteride (Veltam Plus) concentration found in human semen. Dutasteride (Veltam Plus) was administered on gestation days 20 to 100 at doses of 400, 780, 1,325, or 2,010 ng/day (12 monkeys/group). The development of male external genitalia of monkey offspring was not adversely affected. Reduction of fetal adrenal weights, reduction in fetal prostate weights, and increases in fetal ovarian and testis weights were observed at the highest dose tested in monkeys. Based on the highest measured semen concentration of Dutasteride (Veltam Plus) in treated men (14 ng/mL), these doses represent 0.8 to 16 times the potential maximum exposure of a 50-kg human female to 5 mL semen daily from a Dutasteride (Veltam Plus)-treated man, assuming 100% absorption. (These calculations are based on blood levels of parent drug which are achieved at 32 to 186 times the daily doses administered to pregnant monkeys on a ng/kg basis). Dutasteride (Veltam Plus) is highly bound to proteins in human semen (greater than 96%), potentially reducing the amount of Dutasteride (Veltam Plus) available for vaginal absorption. It is not known whether rabbits or rhesus monkeys produce any of the major human metabolites.

Estimates of exposure multiples comparing animal studies to the MRHD for Dutasteride (Veltam Plus) are based on clinical serum concentration at steady state.

Tamsulosin (Veltam Plus)

Administration of Tamsulosin (Veltam Plus) to pregnant female rats at dose levels up to approximately 50 times the human therapeutic AUC exposure (animal dose of 300 mg/kg/day) revealed no evidence of harm to the fetus. Administration of Tamsulosin (Veltam Plus) hydrochloride to pregnant rabbits at dose levels up to 50 mg/kg/day produced no evidence of fetal harm. However, because of the effect of Dutasteride (Veltam Plus) on the fetus, Veltam Plus is contraindicated for use in pregnant women. Estimates of exposure multiples comparing animal studies to the MRHD for Tamsulosin (Veltam Plus) are based on AUC.

Nursing Mothers

Veltam Plus is contraindicated for use in women of childbearing potential, including nursing women. It is not known whether Dutasteride (Veltam Plus) or Tamsulosin (Veltam Plus) is excreted in human milk.

Pediatric Use

Veltam Plus is contraindicated for use in pediatric patients. Safety and effectiveness of Veltam Plus in pediatric patients have not been established.

Geriatric Use

Of 1,610 male subjects treated with coadministered Dutasteride (Veltam Plus) and Tamsulosin (Veltam Plus) in the CombAT trial, 58% of enrolled subjects were aged 65 years and older and 13% of enrolled subjects were aged 75 years and older. No overall differences in safety or efficacy were observed between these subjects and younger subjects but greater sensitivity of some older individuals cannot be ruled out.

Renal Impairment

The effect of renal impairment on Dutasteride (Veltam Plus) and Tamsulosin (Veltam Plus) pharmacokinetics has not been studied using Veltam Plus. Because no dosage adjustment is necessary for Dutasteride (Veltam Plus) or Tamsulosin (Veltam Plus) in patients with moderate-to-severe renal impairment (10 ≤ CLcr < 30 mL/min/1.73 m²), no dosage adjustment is necessary for Veltam Plus in patients with moderate-to-severe renal impairment. However, patients with end-stage renal disease (CLcr < 10 mL/min/1.73 m²) have not been studied.

Hepatic Impairment

The effect of hepatic impairment on Dutasteride (Veltam Plus) and Tamsulosin (Veltam Plus) pharmacokinetics has not been studied using Veltam Plus. The following text reflects information available for the individual components.

Dutasteride (Veltam Plus)

The effect of hepatic impairment on Dutasteride (Veltam Plus) pharmacokinetics has not been studied. Because Dutasteride (Veltam Plus) is extensively metabolized, exposure could be higher in hepatically impaired patients. However, in a clinical trial where 60 subjects received 5 mg (10 times the therapeutic dose) daily for 24 weeks, no additional adverse events were observed compared with those observed at the therapeutic dose of 0.5 mg.

Tamsulosin (Veltam Plus)

Patients with moderate hepatic impairment do not require an adjustment in Tamsulosin (Veltam Plus) dosage. Tamsulosin (Veltam Plus) has not been studied in patients with severe hepatic impairment.

See also:
What are the possible side effects of Veltam Plus?

Clinical Trials Experience

There have been no clinical trials conducted with Veltam Plus; however, the clinical efficacy and safety of coadministered Dutasteride (Veltam Plus) and Tamsulosin (Veltam Plus), which are individual components of Veltam Plus, have been evaluated in a multicenter, randomized, double-blind, parallel group trial (the Combination with Alpha-Blocker Therapy, or CombAT, trial). Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trial of another drug and may not reflect the rates observed in practice.

• The most common adverse reactions reported in subjects receiving coadministered Dutasteride (Veltam Plus) and Tamsulosin (Veltam Plus) were impotence, decreased libido, breast disorders (including breast enlargement and tenderness), ejaculation disorders, and dizziness. Ejaculation disorders occurred significantly more in subjects receiving coadministration therapy (11%) compared with those receiving Dutasteride (Veltam Plus) (2%) or Tamsulosin (Veltam Plus) (4%) as monotherapy.
• Trial withdrawal due to adverse reactions occurred in 6% of subjects receiving coadministered Dutasteride (Veltam Plus) and Tamsulosin (Veltam Plus) and in 4% of subjects receiving Dutasteride (Veltam Plus) or Tamsulosin (Veltam Plus) as monotherapy. The most common adverse reaction in all treatment arms leading to trial withdrawal was erectile dysfunction (1% to 1.5%).

In the CombAT trial, over 4,800 male subjects with BPH were randomly assigned to receive 0.5 mg Dutasteride (Veltam Plus), 0.4 mg Tamsulosin (Veltam Plus) hydrochloride, or coadministration therapy (0.5 mg Dutasteride (Veltam Plus) and 0.4 mg Tamsulosin (Veltam Plus) hydrochloride) administered once daily in a 4-year double-blind trial. Overall, 1,623 subjects received monotherapy with Dutasteride (Veltam Plus); 1,611 subjects received monotherapy with Tamsulosin (Veltam Plus); and 1,610 subjects received coadministration therapy. The population was aged 49 to 88 years (mean age: 66 years) and 88% were white. Table 1 summarizes adverse reactions reported in at least 1% of subjects receiving coadministration therapy and at a higher incidence than subjects receiving either Dutasteride (Veltam Plus) or Tamsulosin (Veltam Plus) as monotherapy.

Table 1: Adverse Reactions Reported over a 48-Month Period in ≥ 1% of Subjects and More Frequently in the Coadministration Therapy Group than the Dutasteride (Veltam Plus) or Tamsulosin (Veltam Plus) Monotherapy Group (CombAT) by Time of Onset

Cardiac Failure

In CombAT, after 4 years of treatment, the incidence of the composite term cardiac failure in the coadministration group (12/1,610; 0.7%) was higher than in either monotherapy group: Dutasteride (Veltam Plus), 2/1,623 (0.1%) and Tamsulosin (Veltam Plus), 9/1,611 (0.6%). Composite cardiac failure was also examined in a separate 4-year placebo-controlled trial evaluating Dutasteride (Veltam Plus) in men at risk for development of prostate cancer. The incidence of cardiac failure in subjects taking Dutasteride (Veltam Plus) was 0.6% (26/4,105) compared with 0.4% (15/4,126) in subjects on placebo. A majority of subjects with cardiac failure in both trials had comorbidities associated with an increased risk of cardiac failure. Therefore, the clinical significance of the numerical imbalances in cardiac failure is unknown. No causal relationship between Dutasteride (Veltam Plus) alone or coadministered with Tamsulosin (Veltam Plus) and cardiac failure has been established. No imbalance was observed in the incidence of overall cardiovascular adverse events in either trial.

Additional information regarding adverse reactions in placebo-controlled trials with Dutasteride (Veltam Plus) or Tamsulosin (Veltam Plus) monotherapy follows.

Dutasteride (Veltam Plus)

Long-term Treatment (Up to 4 Years): High-grade Prostate Cancer: The REDUCE trial was a randomized, double-blind, placebo-controlled trial that enrolled 8,231 men aged 50 to 75 years with a serum PSA of 2.5 ng/mL to 10 ng/mL and a negative prostate biopsy within the previous 6 months. Subjects were randomized to receive placebo (n = 4,126) or 0.5-mg daily doses of Dutasteride (Veltam Plus) (n = 4,105) for up to 4 years. The mean age was 63 years and 91% were white. Subjects underwent protocol-mandated scheduled prostate biopsies at 2 and 4 years of treatment or had “for-cause biopsies” at non-scheduled times if clinically indicated. There was a higher incidence of Gleason score 8 to 10 prostate cancer in men receiving Dutasteride (Veltam Plus) (1.0%) compared with men on placebo (0.5%). In a 7-year placebo-controlled clinical trial with another 5-alpha-reductase inhibitor (finasteride 5 mg, PROSCAR), similar results for Gleason score 8 to 10 prostate cancer were observed (finasteride 1.8% versus placebo 1.1%).

No clinical benefit has been demonstrated in patients with prostate cancer treated with Dutasteride (Veltam Plus).

Reproductive and Breast Disorders

In the 3 pivotal placebo-controlled BPH trials with Dutasteride (Veltam Plus), each 4 years in duration, there was no evidence of increased sexual adverse reactions (impotence, decreased libido, and ejaculation disorder) or breast disorders with increased duration of treatment. Among these 3 trials, there was 1 case of breast cancer in the Dutasteride (Veltam Plus) group and 1 case in the placebo group. No cases of breast cancer were reported in any treatment group in the 4-year CombAT trial or the 4-year REDUCE trial.

The relationship between long-term use of Dutasteride (Veltam Plus) and male breast neoplasia is currently unknown.

Tamsulosin (Veltam Plus)

According to the Tamsulosin (Veltam Plus) prescribing information, in two 13-week treatment trials with Tamsulosin (Veltam Plus) monotherapy, adverse reactions occurring in at least 2% of subjects receiving 0.4 mg Tamsulosin (Veltam Plus) hydrochloride and at an incidence higher than in subjects receiving placebo were: infection, asthenia, back pain, chest pain, somnolence, insomnia, rhinitis, pharyngitis, cough increased, sinusitis, and diarrhea.

Signs and Symptoms of Orthostasis: According to the Tamsulosin (Veltam Plus) prescribing information, in clinical trials with Tamsulosin (Veltam Plus) monotherapy, a positive orthostatic test result was observed in 16% (81/502) of subjects receiving 0.4 mg Tamsulosin (Veltam Plus) hydrochloride versus 11% (54/493) of subjects receiving placebo. Because orthostasis was detected more frequently in the Tamsulosin (Veltam Plus)-treated subjects than in placebo recipients, there is a potential risk of syncope.

Postmarketing Experience

The following adverse reactions have been identified during post-approval use of the individual components of Veltam Plus. 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. These reactions have been chosen for inclusion due to a combination of their seriousness, frequency of reporting, or potential causal connection to drug exposure.

Dutasteride (Veltam Plus)

Immune System Disorders: Hypersensitivity reactions, including rash, pruritus, urticaria, localized edema, serious skin reactions, and angioedema.

Neoplasms: Male breast cancer.

Psychiatric Disorders: Depressed mood.

Reproductive System and Breast Disorders: Testicular pain and testicular swelling.

Tamsulosin (Veltam Plus)

Immune System Disorders: Hypersensitivity reactions, including rash, urticaria, pruritus, angioedema, and respiratory problems have been reported with positive rechallenge in some cases.

Cardiac Disorders: Palpitations, dyspnea, atrial fibrillation, arrhythmia, and tachycardia.

Skin Disorders: Skin desquamation, including Stevens-Johnson syndrome, erythema multiforme, dermatitis exfoliative.

Gastrointestinal Disorders: Constipation, vomiting, dry mouth.

Reproductive System and Breast Disorders: Priapism.

Respiratory: Epistaxis.

Vascular Disorders: Hypotension.

Ophthalmologic Disorders: Blurred vision, visual impairment. During cataract surgery, a variant of small pupil syndrome known as Intraoperative Floppy Iris Syndrome (IFIS) associated with alpha–adrenergic–antagonist therapy.