TAMSULOSIN HYDROCHLORIDE- tamsulosin hydrochloride capsule

United States - English - NLM (National Library of Medicine)

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Active ingredient:
TAMSULOSIN HYDROCHLORIDE (UNII: 11SV1951MR) (TAMSULOSIN - UNII:G3P28OML5I)
Available from:
Mylan Institutional Inc.
INN (International Name):
TAMSULOSIN HYDROCHLORIDE
Composition:
TAMSULOSIN HYDROCHLORIDE 0.4 mg
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Tamsulosin hydrochloride capsules are indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH) [see Clinical Studies (14)] . Tamsulosin hydrochloride capsules are not indicated for the treatment of hypertension. Tamsulosin hydrochloride capsules are contraindicated in patients known to be hypersensitive to tamsulosin hydrochloride or any component of tamsulosin hydrochloride capsules. Reactions have included skin rash, urticaria, pruritus, angioedema, and respiratory symptoms [see Adverse Reactions (6.2)]. Administration of tamsulosin hydrochloride 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 tamsulosin hydrochloride to pregnant rabbits at dose levels up to 50 mg/kg/day produced no evidence of fetal harm. Tamsulosin hydrochloride capsules are not indicated for use in women. Tamsulosin hydrochloride capsules are not indicated for use in women
Product summary:
Tamsulosin Hydrochloride Capsules, USP are available containing 0.4 mg of tamsulosin hydrochloride, USP. The 0.4 mg capsule is a hard-shell gelatin capsule with a blue opaque cap and a blue opaque body filled with white to off-white beads. The capsule is axially printed with MYLAN over 2500 in black ink on both the cap and the body. They are available as follows: NDC 51079-294-20 – Unit dose blister packages of 100 (10 cards of 10 capsules each). Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from moisture. PHARMACIST: Dispense a Patient Information Leaflet with each prescription.
Authorization status:
Abbreviated New Drug Application
Authorization number:
51079-294-01, 51079-294-20

TAMSULOSIN HYDROCHLORIDE- tamsulosin hydrochloride capsule

Mylan Institutional Inc.

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HIGHLIGHTS OF PRESCRIBING INFORMATION

These highlights do not include all the information needed to use TAMSULOSIN HYDROCHLORIDE

CAPSULES safely and effectively. See full prescribing information for TAMSULOSIN HYDROCHLORIDE

CAPSULES.

TAMSULOSIN HYDROCHLORIDE capsules, for oral use

Initial U.S. Approval: 1997

RECENT MAJOR CHANGES

Dosage and Administration ( 2) 10/2014

Warnings and Precautions

Intraoperative Floppy Iris Syndrome ( 5.5) 07/2014

INDICATIONS AND USAGE

Tamsulosin hydrochloride capsules are an alpha

adrenoceptor antagonist indicated for treatment of the signs and

symptoms of benign prostatic hyperplasia ( 1)

Tamsulosin hydrochloride capsules are not indicated for the treatment of hypertension ( 1)

DOSAGE AND ADMINISTRATION

0.4 mg once daily taken approximately one-half hour following the same meal each day. Tamsulosin hydrochloride

capsules should not be crushed, chewed or opened. ( 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 (

If discontinued or interrupted for several days, therapy should start again with the 0.4 mg once daily dose ( 2)

DOSAGE FORMS AND STRENGTHS

Capsules: 0.4 mg ( 3)

CONTRAINDICATIONS

Contraindicated in patients known to be hypersensitive to tamsulosin hydrochloride or any component of tamsulosin

hydrochloride capsules ( 4, 6.2)

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. ( 5.1)

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 and glaucoma surgery in some patients.

Advise patients considering cataract or glaucoma surgery to tell their ophthalmologist that they have taken 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)

ADVERSE REACTIONS

The most common adverse events (≥ 2% of patients and at a higher incidence than placebo) 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 Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-

4-INFO-RX) or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

DRUG INTERACTIONS

Tamsulosin hydrochloride capsules 0.4 mg should not be used with strong inhibitors of CYP3A4 (e.g., ketoconazole).

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)

USE IN SPECIFIC POPULATIONS

Pediatric Use: Not indicated for use in pediatric populations ( 8.4, 12.3)

Geriatric Use: No overall differences in efficacy or safety vs. younger patients, but greater sensitivity of some older

adults cannot be ruled out ( 8.5, 12.3)

Renal Impairment: Has not been studied in patients with end-stage renal disease ( 8.6, 12.3)

Hepatic Impairment: Has not been studied in patients with severe hepatic impairment ( 8.7, 12.3)

See 17 for PATIENT COUNSELING INFORMATION and FDA-approved patient labeling.

Revised: 7/2016

FULL PRESCRIBING INFORMATION: CONTENTS*

1 INDICATIONS AND USAGE

2 DOSAGE AND ADMINISTRATION

3 DOSAGE FORMS AND STRENGTHS

4 CONTRAINDICATIONS

5 WARNINGS AND PRECAUTIONS

5.1 Orthostasis

5.2 Drug Interactions

5.3 Priapism

5.4 Screening for Prostate Cancer

5.5 Intraoperative Floppy Iris Syndrome

5.6 Sulfa Allergy

6 ADVERSE REACTIONS

6.1 Clinical Trials Experience

6.2 Postmarketing Experience

7 DRUG INTERACTIONS

7.1 Cytochrome P450 Inhibition

7.2 Other Alpha Adrenergic Blocking Agents

7.3 PDE5 Inhibitors

7.4 Warfarin

7.5 Nifedipine, Atenolol, Enalapril

7.6 Digoxin and Theophylline

7.7 Furosemide

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

8.3 Nursing Mothers

8.4 Pediatric Use

8.5 Geriatric Use

8.6 Renal Impairment

8.7 Hepatic Impairment

10 OVERDOSAGE

11 DESCRIPTION

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

12.2 Pharmacodynamics

12.3 Pharmacokinetics

13 NONCLINICAL TOXICOLOGY

13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility

14 CLINICAL STUDIES

16 HOW SUPPLIED/STORAGE AND HANDLING

17 PATIENT COUNSELING INFORMATION

FULL PRESCRIBING INFORMATION

1 INDICATIONS AND USAGE

Tamsulosin hydrochloride capsules are indicated for the treatment of the signs and symptoms of benign

prostatic hyperplasia (BPH) [see Clinical Studies (14)] . Tamsulosin hydrochloride capsules are not

indicated for the treatment of hypertension.

2 DOSAGE AND ADMINISTRATION

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. Tamsulosin hydrochloride capsules should not be crushed, chewed or opened.

For those patients who fail to respond to the 0.4 mg dose after 2 to 4 weeks of dosing, the dose of

tamsulosin hydrochloride capsules can be increased to 0.8 mg once daily. Tamsulosin hydrochloride

capsules 0.4 mg should not be used in combination with strong inhibitors of CYP3A4 (e.g.,

ketoconazole) . For those patients who fail to respond to the 0.4 mg dose after 2 to 4 weeks of dosing,

the dose of tamsulosin hydrochloride capsules can be increased to 0.8 mg once daily. 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 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.If

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.

3 DOSAGE FORMS AND STRENGTHS

Capsule: 0.4 mg, hard-shell gelatin capsule with a blue opaque cap and a blue opaque body filled with

white to off-white beads. The capsule is axially printed with MYLAN over 2500 in black ink on both

the cap and the body.

Sections or subsections omitted from the full prescribing information are not listed.

4 CONTRAINDICATIONS

Tamsulosin hydrochloride capsules are contraindicated in patients known to be hypersensitive to

tamsulosin hydrochloride or any component of tamsulosin hydrochloride capsules. Reactions have

included skin rash, urticaria, pruritus, angioedema, and respiratory symptoms [see Adverse Reactions

(6.2)].

5 WARNINGS AND PRECAUTIONS

5.1 Orthostasis

The signs and symptoms of orthostasis (postural hypotension, dizziness, and vertigo) were detected

more frequently in 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 tamsulosin hydrochloride capsules should be cautioned to avoid

situations in which injury could result should syncope occur.

5.2 Drug Interactions

Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6. Tamsulosin hydrochloride

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)] . 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)] .

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)] .

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 tamsulosin hydrochloride capsules

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 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 alpha

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.

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 tamsulosin hydrochloride capsules and at regular intervals

afterwards.

5.5 Intraoperative Floppy Iris Syndrome

Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract and glaucoma surgery in

some patients on or previously treated with alpha1 blockers, including tamsulosin hydrochloride

capsules [see Adverse Reactions (6.2)] .

Most reports were in patients taking the alpha blocker when IFIS occurred, but in some cases, the alpha

blocker had been stopped prior to surgery. In most of these cases, the alpha 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 alpha 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. Most

reports were in patients taking the alpha

blocker when IFIS occurred, but in some cases, the alpha

blocker had been stopped prior to surgery. In most of these cases, the alpha

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 alpha

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

alpha

blocker therapy prior to cataract or glaucoma surgery has not been established. The initiation of

therapy with tamsulosin in patients for whom cataract or glaucoma surgery is scheduled is not

recommended.

5.6 Sulfa Allergy

In patients with sulfa allergy, allergic reaction to tamsulosin hydrochloride capsules has been rarely

reported. If a patient reports a serious or life-threatening sulfa allergy, caution is warranted when

administering tamsulosin hydrochloride capsules.

6 ADVERSE REACTIONS

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 tamsulosin

hydrochloride capsules were used. These studies evaluated safety in 1,783 patients treated with

tamsulosin hydrochloride capsules and 798 patients administered placebo. Table 1 summarizes the

treatment-emergent adverse events that occurred in ≥ 2% of patients receiving either 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 1,487 men.

Table 1: Treatment-Emergent

Adverse Events Occurring in ≥ 2% of Tamsulosin

Hydrochloride Capsules or Placebo Patients in Two U.S. Short-Term Placebo-Controlled Clinical

Studies

Body System/

Adverse Event

Tamsulosin Hydrochloride Capsules Groups

Placebo

0.4 mg

0.8 mg

n = 493

*

n = 502

n = 492

Body As Whole

Headache

97 (19.3%)

104 (21.1%)

99 (20.1%)

Infection

45 (9%)

53 (10.8%)

37 (7.5%)

Asthenia

39 (7.8%)

42 (8.5%)

27 (5.5%)

Back Pain

35 (7%)

41 (8.3%)

27 (5.5%)

Chest Pain

20 (4%)

20 (4.1%)

18 (3.7%)

Nervous System

Dizziness

75 (14.9%)

84 (17.1%)

50 (10.1%)

Somnolence

15 (3%)

21 (4.3%)

8 (1.6%)

Insomnia

12 (2.4%)

7 (1.4%)

3 (0.6%)

Libido Decreased

5 (1%)

10 (2%)

6 (1.2%)

Respiratory System

Rhinitis

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%)

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%)

2 (0.4%)

Signs and Symptoms of Orthostasis

In the two U.S. studies, symptomatic postural hypotension 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 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

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.

Coding preferred terms also include cold, common cold, head cold, flu, and flu-like symptoms.

Coding preferred terms also include nasal congestion, stuffy nose, runny nose, sinus congestion, and hay fever.

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 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

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 tamsulosin hydrochloride capsules 0.4 mg once daily

group, 92 of the 491 patients (19%) in the 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 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 tamsulosin

hydrochloride capsules administration and was dose-related in the U.S. studies. Withdrawal from these

clinical studies of 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 tamsulosin hydrochloride capsules are known. Treatment with

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 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 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, erythema multiforme, dermatitis

exfoliative, constipation, vomiting, dry mouth, visual impairment, and epistaxis have been received

during the postmarketing period.

During cataract and glaucoma surgery, a variant of small pupil syndrome known as Intraoperative Floppy

Iris Syndrome (IFIS) has been reported in association with alpha

blocker therapy [see Warnings and

Precautions (5.5)] .

7 DRUG INTERACTIONS

7.1 Cytochrome P450 Inhibition

Strong and Moderate Inhibitors of CYP3A4 or CYP2D6

Strong and Moderate Inhibitors of CYP3A4 or CYP2D6

Tamsulosin is extensively metabolized, mainly by CYP3A4 and CYP2D6.

Concomitant treatment with ketoconazole (a strong inhibitor of CYP3A4) resulted in an increase in the C

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 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

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 tamsulosin

hydrochloride capsules 0.4 mg is co-administered with strong CYP3A4 inhibitors in CYP2D6 PMs,

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 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 tamsulosin

hydrochloride capsules have not been evaluated. However, there is a potential for significant increase

in tamsulosin exposure when tamsulosin hydrochloride capsules 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 tamsulosin

hydrochloride, which resulted in a moderate increase in 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 tamsulosin hydrochloride capsules and

other alpha adrenergic blocking agents have not been determined; however, interactions between

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 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 tamsulosin 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 hydrochloride capsules [see

Warnings and Precautions (5.2) and Clinical Pharmacology (12.3)] .

7.5 Nifedipine, Atenolol, Enalapril

Dosage adjustments are not necessary when 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 tamsulosin hydrochloride capsule is administered

concomitantly with digoxin or theophylline [see Clinical Pharmacology (12.3)] .

7.7 Furosemide

Tamsulosin hydrochloride capsules had no effect on the pharmacodynamics (excretion of electrolytes)

of furosemide. While furosemide produced an 11% to 12% reduction in tamsulosin hydrochloride C

and AUC, these changes are expected to be clinically insignificant and do not require adjustment of

the tamsulosin hydrochloride capsules dosage [see Clinical Pharmacology (12.3)] .

8 USE IN SPECIFIC POPULATIONS

8.1 Pregnancy

Teratogenic Effects. Pregnancy Category B

Administration of tamsulosin hydrochloride 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 tamsulosin hydrochloride to pregnant rabbits at dose levels up to 50 mg/kg/day

produced no evidence of fetal harm. Tamsulosin hydrochloride capsules are not indicated for use in

women.

8.3 Nursing Mothers

Tamsulosin hydrochloride capsules are not indicated for use in women.

8.4 Pediatric Use

Tamsulosin hydrochloride capsules are not indicated for use in pediatric populations.

Efficacy and positive benefit/risk of tamsulosin hydrochloride was not demonstrated in two studies

conducted in patients 2 years to 16 years of age with elevated detrusor leak point pressure (> 40 cm H

O) associated with known neurological disorder (e.g., spina bifida). Patients in both studies were

treated on a weight-based mg/kg schema (0.025 mg, 0.05 mg, 0.1 mg, 0.2 mg, or 0.4 mg tamsulosin

hydrochloride) for the reduction in detrusor leak point pressure below 40 cm H

O. In a randomized,

double-blind, placebo-controlled, 14-week, pharmacokinetic, safety and efficacy study in 161 patients,

no statistically significant difference in the proportion of responders was observed between groups

receiving tamsulosin hydrochloride and placebo. In an open-label, 12-month safety study, 87 patients

were treated with tamsulosin hydrochloride. The most frequently reported adverse events (≥ 5%) from

the pooled data of both studies were urinary tract infection, vomiting, pyrexia, headache,

nasopharyngitis, cough, pharyngitis, influenza, diarrhea, abdominal pain, and constipation.

8.5 Geriatric Use

Of the total number of subjects (1,783) in clinical studies of tamsulosin, 36% were 65 years of age and

over. No overall differences in safety or effectiveness were observed between these subjects and

younger subjects, and the other reported clinical experience has not identified differences in responses

between the elderly and younger patients, but greater sensitivity of some older individuals cannot be

ruled out [see Clinical Pharmacology (12.3)] .

8.6 Renal Impairment

Patients with renal impairment do not require an adjustment in tamsulosin hydrochloride capsules dosing.

However, patients with end-stage renal disease (CL

< 10 mL/min/1.73 m

) have not been studied [see

Clinical Pharmacology (12.3)] .

8.7 Hepatic Impairment

Patients with moderate hepatic impairment do not require an adjustment in tamsulosin hydrochloride

capsules dosage. Tamsulosin hydrochloride has not been studied in patients with severe hepatic

impairment [see Clinical Pharmacology (12.3)] .

10 OVERDOSAGE

Should overdosage of 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 tamsulosin

hydrochloride is 94% to 99% protein bound; therefore, dialysis is unlikely to be of benefit.

11 DESCRIPTION

Tamsulosin hydrochloride is an antagonist of alpha

adrenoceptors in the prostate.

Tamsulosin hydrochloride is (-)-( R)-5-[2-[[2-( o-Ethoxyphenoxy)ethyl]amino]propyl]-2-

methoxybenzenesulfonamide, monohydrochloride. Tamsulosin hydrochloride, USP is a white to off-

white 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 molecular formula of tamsulosin hydrochloride is C

S HCl. The molecular weight

of tamsulosin hydrochloride is 444.97. Its structural formula is:

Each tamsulosin hydrochloride capsule, USP for oral administration contains tamsulosin hydrochloride

0.4 mg, and the following inactive ingredients: calcium stearate, D&C Red No. 28, FD&C Blue No. 1,

gelatin, methacrylic acid copolymer, microcrystalline cellulose, polysorbate 80, sodium hydroxide,

sodium lauryl sulfate, talc, titanium dioxide and triethyl citrate.

The imprinting ink contains the following: black iron oxide, D&C Yellow No. 10 Aluminum Lake,

FD&C Blue No. 1 Aluminum Lake, FD&C Blue No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum

Lake, propylene glycol and shellac glaze.

Meets USP Dissolution Test 5.

12 CLINICAL PHARMACOLOGY

12.1 Mechanism of Action

The symptoms associated with benign prostatic hyperplasia (BPH) 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 alpha

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 alpha

adrenoceptor blocking agent, exhibits selectivity for alpha

receptors in the

human prostate. At least three discrete alpha

adrenoceptor subtypes have been identified: alpha

alpha

, and alpha

; their distribution differs between human organs and tissue. Approximately 70%

of the alpha

receptors in the human prostate are of the alpha

subtype.

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 tamsulosin hydrochloride 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 tamsulosin hydrochloride from tamsulosin hydrochloride capsules 0.4 mg is essentially

complete (> 90%) following oral administration under fasting conditions. 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 (T

) is reached by 4 to 5 hours under fasting conditions and by 6

to 7 hours when tamsulosin hydrochloride capsules are administered with food. Taking tamsulosin

hydrochloride capsules under fasted conditions results in a 30% increase in bioavailability (AUC) and

40% to 70% increase in peak concentrations (C

) compared to fed conditions (Figure 1).

The effects of food on the pharmacokinetics of tamsulosin hydrochloride are consistent regardless of

whether a tamsulosin hydrochloride capsule is taken with a light breakfast or a high-fat breakfast (Table

Table 2: Mean (± S.D.) Pharmacokinetic Parameters Following Tamsulosin Hydrochloride

Capsules 0.4 mg Once Daily or 0.8 mg Once Daily with a Light Breakfast, High-Fat Breakfast or

Fas ted

Pharmacokinetic

Parameter

0.4 mg QD to healthy

volunteers; n = 23

(age range 18 to 32 years)

0.8 mg QD to healthy volunteers; n = 22

(age range 55 to 75 years)

Light Breakfast

Fas ted

Light

Breakfas t

High-Fat

Breakfas t

Fas ted

(ng/mL)

4 ± 2.6

3.8 ± 2.5

12.3 ± 6.7

13.5 ± 7.6

13.3 ±

13.3

(ng/mL)

10.1 ± 4.8

17.1 ± 17.1

29.8 ± 10.3

29.1 ± 11

41.6 ±

15.6

Ratio

3.1 ± 1

5.3 ± 2.2

2.7 ± 0.7

2.5 ± 0.8

3.6 ± 1.1

(hours)

(hours)

14.9 ± 3.9

AUC (nghr/mL)

151 ± 81.5

199 ± 94.1

440 ± 195

449 ± 217

557 ± 257

= observed minimum concentration

= observed maximum tamsulosin hydrochloride plasma concentration

= median time-to-maximum concentration

= observed half-life

AUC = area under the tamsulosin hydrochloride plasma time curve over the dosing interval

Distribution

The mean steady-state apparent volume of distribution of tamsulosin hydrochloride after intravenous

administration to ten healthy male adults was 16 L, which is suggestive of distribution into extracellular

fluids in the body.

Tamsulosin hydrochloride is extensively bound to human plasma proteins (94% to 99%), primarily

alpha

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 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, tamsulosin hydrochloride had no effect on the extent of binding of these

drugs.

Metabolism

There is no enantiomeric bioconversion from tamsulosin hydrochloride [R(-) isomer] to the S(+) isomer

in humans. 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 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 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 tamsulosin hydrochloride interaction with diclofenac and warfarin were

equivocal.

Excretion

On administration of the radiolabeled dose of tamsulosin hydrochloride to four 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 tamsulosin hydrochloride in plasma ranged from 5 to 7 hours. Because of absorption rate-

controlled pharmacokinetics with tamsulosin hydrochloride capsules, the apparent half-life of

tamsulosin hydrochloride is approximately 9 to 13 hours in healthy volunteers and 14 to 15 hours in the

target population.

Tamsulosin hydrochloride undergoes restrictive clearance in humans, with a relatively low systemic

clearance (2.88 L/h).

Specific Populations

Pediatric Use

Tamsulosin hydrochloride capsules are not indicated for use in pediatric populations [see Use in

Specific Populations (8.4)] .

Geriatric (Age) Use

Cross-study comparison of tamsulosin hydrochloride capsules overall exposure (AUC) and half-life

indicates that the pharmacokinetic disposition of tamsulosin hydrochloride may be slightly prolonged in

geriatric males compared to young, healthy male volunteers. Intrinsic clearance is independent of

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 tamsulosin hydrochloride have been compared in six subjects with mild-

moderate (30 ≤ CL

< 70 mL/min/1.73 m

) or moderate-severe (10 ≤ CL

< 30 mL/min/1.73 m

) renal

impairment and six normal subjects (CL

> 90 mL/min/1.73 m

). While a change in the overall plasma

concentration of tamsulosin hydrochloride was observed as the result of altered binding to AAG, the

unbound (active) concentration of tamsulosin hydrochloride, as well as the intrinsic clearance, remained

relatively constant. Therefore, patients with renal impairment do not require an adjustment in tamsulosin

hydrochloride capsules dosing. However, patients with end-stage renal disease (CL

< 10 mL/min/1.73

) have not been studied [see Use in Specific Populations (8.6)] .

Hepatic Impairment

The pharmacokinetics of tamsulosin hydrochloride have been compared in eight subjects with moderate

hepatic impairment (Child-Pugh’s classification: Grades A and B) and eight normal subjects. While a

change in the overall plasma concentration of tamsulosin hydrochloride was observed as the result of

altered binding to AAG, the unbound (active) concentration of tamsulosin hydrochloride does not

change significantly, with only a modest (32%) change in intrinsic clearance of unbound tamsulosin

hydrochloride. Therefore, patients with moderate hepatic impairment do not require an adjustment in

tamsulosin hydrochloride capsules dosage. Tamsulosin hydrochloride has not been studied in patients

with severe hepatic impairment [see Use in Specific Populations (8.7)] .

Drug Interactions

Cytochrome P450 Inhibition

Strong and Moderate Inhibitors of CYP3A4 or CYP2D6

The effects of ketoconazole (a strong inhibitor of CYP3A4) at 400 mg once daily for 5 days on the

pharmacokinetics of a single 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

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 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 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

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

tamsulosin hydrochloride 0.4 mg capsules is co-administered with strong CYP3A4 inhibitors in

CYP2D6 PMs, 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 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 tamsulosin

hydrochloride capsules have not been evaluated. However, there is a potential for significant increase

in tamsulosin exposure when 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)] .

Cim e tidine

The effects of cimetidine at the highest recommended dose (400 mg every 6 hours for 6 days) on the

pharmacokinetics of a single tamsulosin hydrochloride capsule 0.4 mg dose was investigated in ten

healthy volunteers (age range 21 to 38 years). Treatment with cimetidine resulted in a significant

decrease (26%) in the clearance of tamsulosin hydrochloride, which resulted in a moderate increase in

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 tamsulosin hydrochloride capsules and

other alpha adrenergic blocking agents have not been determined; however, interactions between

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 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 tamsulosin hydrochloride 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 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, tamsulosin

hydrochloride capsules 0.4 mg for 7 days followed by 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

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 (n = 10 per study; age range 19 to 39 years) receiving tamsulosin

hydrochloride capsules 0.4 mg/day for 2 days, followed by 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 tamsulosin hydrochloride capsule is administered concomitantly with digoxin or

theophylline [see Drug Interactions (7.6)] .

Furosemide

The pharmacokinetic and pharmacodynamic interaction between tamsulosin hydrochloride capsules 0.8

mg/day (steady-state) and furosemide 20 mg intravenously (single dose) was evaluated in ten healthy

volunteers (age range 21 to 40 years). Tamsulosin hydrochloride capsules had no effect on the

pharmacodynamics (excretion of electrolytes) of furosemide. While furosemide produced an 11% to

12% reduction in tamsulosin hydrochloride C

and AUC, these changes are expected to be clinically

insignificant and do not require adjustment of the 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 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 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 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.

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 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 tamsulosin hydrochloride (1/5 and 16 times the anticipated human AUC

exposure) did not significantly alter fertility in male rats. Effects of 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 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

2,296 patients (1,003 received tamsulosin hydrochloride capsules 0.4 mg once daily, 491 received

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)], 1,486 men with the signs and symptoms of BPH were enrolled. In both studies,

patients were randomized to either placebo, tamsulosin hydrochloride capsules 0.4 mg once daily, or

tamsulosin hydrochloride capsules 0.8 mg once daily. Patients in tamsulosin hydrochloride capsules

0.8 mg once daily treatment groups received a dose of 0.4 mg once daily for 1 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 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 tamsulosin hydrochloride capsules 0.4 mg

and 0.8 mg once daily groups compared to placebo in Study 1, and for the 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.

Table 3: Mean (± S.D.) Changes from Baseline to Week 13 in Total AUA Symptom Score

and

Peak Urine Flow Rate (mL/sec)

Total AUA Symptom Score

Peak Urine Flow Rate

*

Mean Baseline

Value

Mean

Change

Mean Baseline

Value

Mean

Change

Study 1

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

Tamsulosin Hydrochloride

Capsules

0.4 mg once daily

19.8 ± 5

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

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

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

n = 239

-3.6 ± 5.7

n = 235

9.95 ± 3.12

n = 239

0.93 ± 3.28

n = 235

Week 13: For patients not completing the 13-week study, the last observation was carried forward.

Mean total AUA Symptom Scores for both 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 1 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 1 year.

Total AUA Symptom Scores ranged from 0 to 35.

Peak urine flow rate measured 4 to 8 hours post dose at Week 13.

Statistically significant difference from placebo (p-value ≤ 0.050; Bonferroni-Holm multiple test procedure).

Peak urine flow rate measured 24 to 27 hours post dose at Week 13.

16 HOW SUPPLIED/STORAGE AND HANDLING

Tamsulosin Hydrochloride Capsules, USP are available containing 0.4 mg of tamsulosin

hydrochloride, USP. The 0.4 mg capsule is a hard-shell gelatin capsule with a blue opaque cap and a

blue opaque body filled with white to off-white beads. The capsule is axially printed with MYLAN

over 2500 in black ink on both the cap and the body. They are available as follows:

NDC 51079-294-20 – Unit dose blister packages of 100 (10 cards of 10 capsules each).

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.]

Protect from moisture.

PHARMACIST: Dispense a Patient Information Leaflet with each prescription.

17 PATIENT COUNSELING INFORMATION

Advise the patient to read the FDA-approved patient labeling (Patient Information Leaflet).

Hypotens ion

Advise the patient about the possible occurrence of symptoms related to postural hypotension, such as

dizziness, when taking tamsulosin hydrochloride capsules, and they should be cautioned about driving,

operating machinery, or performing hazardous tasks [see Warnings and Precautions (5.1)] .

Drug Interactions

Advise the patient that tamsulosin hydrochloride capsules should not be used in combination with strong

inhibitors of CYP3A4 [see Warnings and Precautions (5.2) and Drug Interactions (7.1)] .

Priapis m

Advise the patient about the possibility of priapism as a result of treatment with tamsulosin

hydrochloride 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)] .

Screening for Prostate Cancer

Prostate cancer and BPH frequently co-exist; therefore, screen patients for the presence of prostate

cancer prior to treatment with tamsulosin hydrochloride capsules and at regular intervals afterwards

[see Warnings and Precautions (5.4)].

Intraoperative Floppy Iris Syndrome

Advise the patient when considering cataract or glaucoma surgery to tell their ophthalmologist that they

have taken tamsulosin hydrochloride capsules [see Warnings and Precautions (5.5)] .

Adminis tration

Advise the patient that tamsulosin hydrochloride capsules should not be crushed, chewed or opened

[see Dosage and Administration (2)] .

FDA-approved Patient Labeling

Patient labeling is provided as a tear-off leaflet at the end of this prescribing information.

PATIENT INFORMATION LEAFLET

TAMSULOSIN HYDROCHLORIDE CAPSULES, USP

(tam soo' loe sin hye'' droe klor' ide)

0.4 mg

Read the Patient Information that comes with 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 are tamsulosin hydrochloride capsules?

Tamsulosin hydrochloride capsules are 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.

Tamsulosin hydrochloride capsules are not for women.

Tamsulosin hydrochloride capsules are not for children.

Who should not take tamsulosin hydrochloride capsules?

Do not take 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 tamsulosin hydrochloride capsules.

What should I tell my doctor before using tamsulosin hydrochloride capsules?

Before taking 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 or glaucoma 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 tamsulosin hydrochloride capsules work. Especially

tell your doctor if you take a medicine for high blood pressure. You should not take tamsulosin

hydrochloride capsules 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 tamsulosin hydrochloride capsules?

Take tamsulosin hydrochloride capsules exactly as prescribed by your doctor.

Do not crush, chew, or open tamsulosin hydrochloride capsules.

Take tamsulosin hydrochloride capsules one time each day, about 30 minutes after the same meal

each day. For example, you may take tamsulosin hydrochloride capsules 30 minutes after dinner

each day.

If you miss a dose of tamsulosin hydrochloride capsules, 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 tamsulosin hydrochloride capsules for several days, talk with your

doctor before starting again.

If you take more tamsulosin hydrochloride capsules than prescribed, call your doctor right away.

What are the possible side effects of tamsulosin hydrochloride capsules?

Possible side effects of tamsulosin hydrochloride capsules may include:

Decreased blood pressure when changing positions. 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 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 tamsulosin hydrochloride capsules.

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. 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 or glaucoma surgery. During cataract or glaucoma surgery, a

condition called intraoperative floppy iris syndrome (IFIS) can happen if you take or have taken

tamsulosin hydrochloride capsules. If you need to have cataract or glaucoma surgery, be sure to tell

your surgeon if you take or have taken tamsulosin hydrochloride capsules.

Common side effects of tamsulosin hydrochloride capsules may include:

runny nose

dizziness

decreased semen

These are not all the possible side effects with 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 tamsulosin hydrochloride capsules?

Avoid driving, operating machinery, or other dangerous activities, until you know how tamsulosin

hydrochloride capsules affect you. 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 tamsulosin hydrochloride capsules?"

How do I store tamsulosin hydrochloride capsules?

Store tamsulosin hydrochloride capsules at 20° to 25°C (68° to 77°F). Short-term exposure to higher or

lower temperatures [from 59ºF (15ºC) to 86ºF (30ºC)] is acceptable. Ask your doctor or pharmacist if

you have any questions about storing your capsules.

Keep 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 tamsulosin hydrochloride capsules to other people, even if they have the same

symptoms that you have. It may harm them.

While taking tamsulosin hydrochloride capsules, 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 tamsulosin hydrochloride capsules

and at regular intervals afterwards.

This patient information leaflet summarizes the most important information about tamsulosin

hydrochloride capsules. If you would like more information, talk with your doctor. You can ask your

pharmacist or doctor for information about tamsulosin hydrochloride capsules that is written for health

professionals. You can also call Mylan Pharmaceuticals Inc. at 1-877-446-3679 (1-877-4-INFO-RX)

for more information.

What are the ingredients in tamsulosin hydrochloride capsules?

Active Ingredient: tamsulosin hydrochloride

Inactive Ingredients: calcium stearate, D&C Red No. 28, FD&C Blue No. 1, gelatin, methacrylic

acid copolymer, microcrystalline cellulose, polysorbate 80, sodium hydroxide, sodium lauryl

sulfate, talc, titanium dioxide and triethyl citrate. The imprinting ink contains the following: black

iron oxide, D&C Yellow No. 10 Aluminum Lake, FD&C Blue No. 1 Aluminum Lake, FD&C Blue

No. 2 Aluminum Lake, FD&C Red No. 40 Aluminum Lake, propylene glycol and shellac glaze.

Manufactured by:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Distributed by:

Mylan Institutional Inc.

Rockford, IL 61103 U.S.A.

S-12079 R3

7/16

PRINCIPAL DISPLAY PANEL - 0.4 mg

NDC 51079-294-20

Tamsulosin HCl

Capsules, USP

0.4 mg

100 Capsules (10 x 10)

Each capsule contains:

Tamsulosin

hydrochloride, USP 0.4 mg

Usual Adult Dosage: See

accompanying prescribing

information and Patient

Information Leaflet.

Store at 20° to 25°C (68° to 77°F).

[See USP Controlled Room Temperature.]

Protect from moisture.

Manufactured by:

Mylan Pharmaceuticals Inc.

Morgantown, WV 26505 U.S.A.

Rx only

S-10707 R3

Packaged and Distributed by:

Mylan Institutional Inc.

Rockford, IL 61103 U.S.A.

This unit dose package is not child resistant.

For institutional use only.

Keep this and all drugs out of the reach of children.

This container provides light-resistance.

See window for lot number and expiration date.

TAMSULOSIN HYDROCHLORIDE

tamsulosin hydrochloride capsule

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:510 79 -29 4(NDC:0 378 -250 0 )

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

TAMSULO SIN HYDRO CHLO RIDE (UNII: 11SV19 51MR) (TAMSULOSIN -

UNII:G3P28 OML5I)

TAMSULOSIN

HYDROCHLORIDE

0 .4 mg

Inactive Ingredients

Ingredient Name

Stre ng th

Mylan Institutional Inc.

CALCIUM STEARATE (UNII: 776 XM70 47L)

D&C RED NO . 2 8 (UNII: 76 7IP0 Y5NH)

FD&C BLUE NO . 1 (UNII: H3R47K3TBD)

GELATIN, UNSPECIFIED (UNII: 2G8 6 QN327L)

MICRO CRYSTALLINE CELLULO SE (UNII: OP1R32D6 1U)

PO LYSO RBATE 8 0 (UNII: 6 OZP39 ZG8 H)

SO DIUM HYDRO XIDE (UNII: 55X0 4QC32I)

SO DIUM LAURYL SULFATE (UNII: 36 8 GB5141J)

TALC (UNII: 7SEV7J4R1U)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

TRIETHYL CITRATE (UNII: 8 Z9 6 QXD6 UM)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

D&C YELLO W NO . 10 (UNII: 35SW5USQ3G)

FD&C BLUE NO . 2 (UNII: L0 6 K8 R7DQK)

FD&C RED NO . 4 0 (UNII: WZB9 127XOA)

PRO PYLENE GLYCO L (UNII: 6 DC9 Q16 7V3)

SHELLAC (UNII: 46 N10 7B71O)

METHACRYLIC ACID - ETHYL ACRYLATE CO PO LYMER ( 1:1) TYPE A (UNII: NX76 LV5T8 J)

Product Characteristics

Color

blue (pro cess blue o paque)

S core

no sco re

S hap e

CAPSULE

S iz e

19 mm

Flavor

Imprint Code

MYLAN;250 0

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:510 79 -29 4-20

10 0 in 1 CARTON

0 5/0 7/20 10

1

NDC:510 79 -29 4-0 1

1 in 1 BLISTER PACK; Type 0 : No t a Co mbinatio n Pro duct

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA0 9 0 40 8

0 5/0 7/20 10

Labeler -

Mylan Institutional Inc. (039615992)

Revised: 12/2018

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