The following Structured Product Label (SPL) was submitted to the FDA by Contract Pharmacy Services-pa for the product Bupropion Hydrochloride (NDC 67046-082). This document serves as the official prescribing information, containing essential scientific data and clinical materials required for healthcare providers and patients.
This specific version of the label includes detailed information regarding 1 indications and usage, 2 dosage and administration, 3 dosage forms and strengths, 4 contraindications, 5.1 orthostasis, 5.2 drug interactions, 5.3 priapism, 5.4 screening for prostate cancer, and other regulatory disclosures. Use the navigation below to review specific sections of the FDA submission.
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
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)
[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.
Capsule: 0.4 mg are olive green opaque/orange opaque size ‘0’ hard gelatin capsules imprinted with ‘D’ on cap and ‘53’ on body with black edible ink filled with white to off-white beadlets.
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)].
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.
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 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)].
Rarely (probably less than 1 in 50,000 patients), tamsulosin, like other alpha 1antagonists, 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.
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.
Intraoperative Floppy Iris Syndrome (IFIS) has been observed during cataract and glaucoma surgery in some patients on or previously treated with alpha
1blockers, including tamsulosin hydrochloride capsules
[see
Adverse Reactions (6.2)]
.
Most reports were in patients taking the alpha
1blocker when IFIS occurred, but in some cases, the alpha
1blocker had been stopped prior to surgery. In most of these cases, the alpha
1blocker 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
1blocker 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
1blocker 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.
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.
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 1783 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 1487 men.
| BODY SYSTEM/ADVERSE EVENT | TAMSULOSIN HYDROCHLORIDE CAPSULES GROUPS | PLACEBO | |
|---|---|---|---|
| 0.4 mg
n=502 | 0.8 mg
n=492 | n=493 | |
| 1A 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;
2Coding preferred terms also include cold, common cold, head cold, flu, and flu-like symptoms. 3Coding preferred terms also include nasal congestion, stuffy nose, runny nose, sinus congestion, and hay fever. | |||
| BODY AS WHOLE | |||
| Headache
| 97 (19.3%)
| 104 (21.1%)
| 99 (20.1%)
|
| Infection
2 | 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
3 | 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 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 capsules-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).
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
1blocker therapy
[see
Warnings and Precautions (5.5)]
.
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
maxand 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
maxand 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 0.4 mg is co-administered with strong CYP3A4 inhibitors in CYP2D6 PMs, 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)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 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)]
.
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)] .
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)] .
A definitive drug-drug interaction study between tamsulosin hydrochloride and warfarin was not conducted. Results from limited in vitroand in vivostudies 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)] .
Dosage adjustments are not necessary when tamsulosin hydrochloride capsules are administered concomitantly with nifedipine, atenolol, or enalapril [see Clinical Pharmacology (12.3)] .
Dosage adjustments are not necessary when a tamsulosin hydrochloride capsule is administered concomitantly with digoxin or theophylline [see Clinical Pharmacology (12.3)] .
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 maxand 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)] .
Risk Summary
Tamsulosin hydrochloride is not indicated for use in women. There are no adequate data on the developmental risk associated with the use of tamsulosin hydrochloride in pregnant women. No adverse developmental effects were observed in animal studies in which tamsulosin hydrochloride was administered to rats or rabbits during the period of organogenesis (GD 7 to 17 in the rat and GD 6 to 18 in the rabbit) [
see Data]
.
In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.
Data
Administration of tamsulosin hydrochloride to pregnant female rats during the period of organogenesis at dose levels up to approximately 50 times the human therapeutic AUC exposure (300 mg/kg/day) revealed no evidence of harm to the fetus. Administration of tamsulosin hydrochloride to pregnant rabbits during the period of organogenesis at dose levels up to 50 mg/kg/day produced no evidence of fetal harm.
Tamsulosin hydrochloride is not indicated for use in women. There are no data on the presence of tamsulosin hydrochloride in human milk, the effects of tamsulosin hydrochloride on the breastfed infant, or the effects of tamsulosin hydrochloride on milk production. Tamsulosin hydrochloride is present in the milk of lactating rats [
see Data]
.
Data
Oral administration of radiolabeled tamsulosin hydrochloride to rats demonstrated that tamsulosin hydrochloride and/or its metabolites are excreted into the milk of rats.
Infertility
Males
Abnormal ejaculation including ejaculation failure, ejaculation disorder, retrograde ejaculation, and ejaculation decrease has been associated with tamsulosin hydrochloride [
see
Clinical Trials Experience (6.1)]
.Studies in rats revealed significantly reduced fertility in males considered to be due to impairment of ejaculation, which was reversible [
see
Nonclinical Toxicology (13.1)]
.
Females
Tamsulosin hydrochloride is not indicated for use in women. Female fertility in rats was significantly reduced, considered to be due to impairment of fertilization [
see
Nonclinical Toxicology (13.1)]
.
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
2O) 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
2O. 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.
Of the total number of subjects (1783) in clinical studies of tamsulosin, 36% were 65 years of age and over. No overall differences in safety or effectiveness were observed between these subjects and younger subjects, and the other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out [see Clinical Pharmacology (12.3)] .
Patients with renal impairment do not require an adjustment in tamsulosin hydrochloride capsules dosing. However, patients with end-stage renal disease (CL cr<10 mL/min/1.73 m 2) have not been studied [see Clinical Pharmacology (12.3)] .
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)] .
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.
Tamsulosin hydrochloride is an antagonist of alpha
1Aadrenoceptors in the prostate.
Tamsulosin hydrochloride is (-)-(
R)-5-[2-[[2-(
o-Ethoxyphenoxy) ethyl]amino]propyl]-2-methoxybenzenesulfonamide, monohydrochloride. Tamsulosin hydrochloride USP is a white or almost white crystalline powder that melts with decomposition at approximately 230°C. It is sparingly soluble in water and methanol, slightly soluble in glacial acetic acid and ethanol, and practically insoluble in ether.
The molecular formula of tamsulosin hydrochloride is C
20H
28N
2O
5S • HCl. The molecular weight of tamsulosin hydrochloride is 444.98. Its structural formula is:
Each tamsulosin hydrochloride capsule, USP for oral administration contains tamsulosin hydrochloride USP 0.4 mg, and the following inactive ingredients: calcium stearate, FD&C Blue 2, gelatin, iron oxide red, iron oxide yellow, microcrystalline cellulose, methacrylic acid and ethyl acrylate copolymer dispersion, sodium lauryl sulfate, talc, triacetin, and titanium dioxide. The capsules are printed with SW-9008 Black Ink containing black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, shellac, and strong ammonia solution.
Meets USP dissolution test 10.
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
1adrenoceptors, 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
1adrenoceptor blocking agent, exhibits selectivity for alpha
1receptors in the human prostate. At least three discrete alpha
1adrenoceptor subtypes have been identified: alpha
1A, alpha
1B, and alpha
1D; their distribution differs between human organs and tissue. Approximately 70% of the alpha
1receptors in the human prostate are of the alpha
1Asubtype.
Tamsulosin hydrochloride capsules are not intended for use as an antihypertensive drug.
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)] .
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 vitroin 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 vivosister 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.
Tamsulosin Hydrochloride Capsules USP, 0.4 mgare olive green opaque/orange opaque size ‘0’ hard gelatin capsules imprinted with ‘D’ on cap and ‘53’ on body with black edible ink filled with white to off-white beadlets.
Bottles of 100 NDC 65862-598-01
Bottles of 500 NDC 65862-598-05
3 x 10 Unit-dose Capsules NDC 65862-598-10
Store at20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Preserve in tight container. Avoid excessive moisture.
Keep tamsulosin hydrochloride capsules and all medicines out of reach of children.
Advise the patient to read the FDA-approved patient labeling (Patient Information)
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)] .
Advise the patient that tamsulosin hydrochloride should not be used in combination with strong inhibitors of CYP3A4 [see Warnings and Precautions (5.2)and Drug Interactions (7.1)] .
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)] .
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)].
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)] .
Advise the patient that tamsulosin hydrochloride capsules should not be crushed, chewed or opened
[seeDosage and Administration (2)].
FDA-approved Patient Labeling
Patient labeling is provided at the end of this prescribing information.
Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520
Manufactured by:
Aurobindo Pharma Limited
Hyderabad-500 032, India
Revised: 09/2021
Tamsulosin Hydrochloride Capsules, USP
(tam soo' loe sin hye" droe klor' ide)
Read the Patient Information that comes with tamsulosin hydrochloride capsules before you start taking them 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.
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:
Tell your doctor about all the medicines you take, including:
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?
What are the possible side effects of tamsulosin hydrochloride capsules?
Possible side effects of tamsulosin hydrochloride capsules may include:
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 may include:
Rare and more serious allergic reactions may also occur. Get medical help right away if you have any of the following reactions:
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:
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 room temperature 20° to 25°C (68° to 77°F). Short-term exposure to higher or lower temperatures [from 59°F (15°C) to 86°F (30°C)] is acceptable. Ask your doctor or pharmacist if you have any questions about storing your capsules.
Keep 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. They 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. For more information call Aurobindo Pharma USA, Inc. at 1-866-850-2876.
What are the ingredients in tamsulosin hydrochloride capsules?
Distributed by:
Aurobindo Pharma USA, Inc.
279 Princeton-Hightstown Road
East Windsor, NJ 08520
Manufactured by:
Aurobindo Pharma Limited
Hyderabad-500 032, India
Revised: 09/2021
Label (Tamsul.4mg)
* Please review the disclaimer below.
