TAMSULOSIN HYDROCHLORIDE- tamsulosin hydrochloride_capsule

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 1 1 1 1 1A 1B 1D 1 1A Urologic pharmacodynamic effects have been evaluated in neurologically impaired pediatric patients and in adults with BPH [see Use in Specific Populations (8. 4) Clinical Studies (14) 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. max max 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 2). Table 2 Mean (+/- S. ) 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 Fasted Pharmacokinetic 0. 4 mg QD to healthy 0. 8 mg QD to healthy volunteers; n=22 Light Fasted Light High-Fat Fasted C min max max 1/2 tau C min 4 +/- 2. 1 +/- 11 41. 6 C max min 3. 1 T max 6 4 7 6. 6 5 T 1/2 - - - - 14. 9 AUC tau 151 +/- 81. 5 199 +/- 94. 1 440 +/- 195 449 +/- 217 557 +/- 257 Distribution 1 in vitro [see Warnings and Precautions (5. 2) Drug Interactions (7. 1) in vitro [see Use in Specific Populations (8. 4) Geriatric (Age) Use [see Use in Specific Populations (8. 5) cr 2 cr 2 cr 2 cr 2 [see Use in Specific Populations (8. 6) [see Use in Specific Populations (8. 7) max [see Warnings and Precautions (5. 2) Clinical Pharmacology (12. 3) [see Warnings and Precautions (5. 1) max [see Warnings and Precautions (5. 1) [see Warnings and Precautions (5. 1) Cimetidine [see Warnings and Precautions (5. 2) [see Warnings and Precautions (5. 3) in vitro in vivo [see Warnings and Precautions (5. 4) [see Drug Interactions (7. 5) Digoxin and Theophylline [see Drug Interactions (7. 6) Furosemide max [see Drug Interactions (7. 7) Figure 1 Mean Plasma Tamsulosin Hydrochloride Concentrations Following Single-Dose Administration of Tamsulosin Hydrochloride Capsules 0. 4 mg Under Fasted and Fed Conditions (n=8).

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

Tamsulosin hydrochloride capsules [see Warnings and Precautions (5. 2) If tamsulosin hydrochloride capsules administration is discontinued or interrupted for several days at either the 0. 8 mg dose, therapy should be started again with the 0. 4 mg once-daily dose. 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 (2) If discontinued or interrupted for several days, therapy should start again with the 0. 4 mg once-daily dose (2).

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 Aurobindo Pharma USA, Inc. at 1-866-850-2876 or FDA at 1-800-FDA-1088 or www. gov/medwatch. 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. Table 1 Treatment-Emergent 1 BODY SYSTEM/ADVERSE EVENT TAMSULOSIN HYDROCHLORIDE CAPSULES GROUPS PLACEBO 0. 8 mg 1 The adverse event was present prior to or at the time of initial dosing with double-blind study medication and subsequently increased in severity during double-blind treatment; or The adverse event was present prior to or at the time of initial dosing with double-blind study medication, disappeared completely, and then reappeared during double-blind treatment. 2 3 BODY AS WHOLE Headache 97 (19. 3%) 104 (21. 1%) Infection 2 45 (9%) 53 (10. 5%) Asthenia 39 (7. 5%) Back pain 35 (7%) 41 (8. 5%) Chest pain 20 (4%) 20 (4. 7%) NERVOUS SYSTEM Dizziness 75 (14. 1%) Somnolence 15 (3%) 21 (4. 6%) Insomnia 12 (2. 6%) Libido decreased 5 (1%) 10 (2%) 6 (1. 2%) RESPIRATORY SYSTEM Rhinitis 3 66 (13. 3%) Pharyngitis 29 (5. 7%) Cough increased 17 (3. 4%) Sinusitis 11 (2. 6%) DIGESTIVE SYSTEM Diarrhea 31 (6. 5%) Nausea 13 (2. 2%) Tooth disorder 6 (1. 2%) 10 (2%) 7 (1. 4%) UROGENITAL SYSTEM Abnormal ejaculation 42 (8. 2%) SPECIAL SENSES Blurred vision 1 (0. 2%) 10 (2%) 2 (0. 4%) Signs and Symptoms of Orthostasis [see Warnings and Precautions (5. 1) Laboratory Tests 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. 1 [see Warnings and Precautions (5.

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) Contraindicated in patients known to be hypersensitive to tamsulosin hydrochloride or any component of tamsulosin hydrochloride capsules (4 6.

Pediatric Use: Not indicated for use in pediatric populations. 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. 3) Renal Impairment: Has not been studied in patients with end-stage renal disease (8. 3) Hepatic Impairment: Has not been studied in patients with severe hepatic impairment (8. 3) Risk Summary see Data. 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. Infertility see Clinical Trials Experience (6. see Nonclinical Toxicology (13. Tamsulosin hydrochloride capsules are not indicated for use in pediatric populations. 2 2 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 2 [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.

Tamsulosin hydrochloride capsules 0. 4 mg should not be used with strong inhibitors of CYP3A4 (e. , ketoconazole). Tamsulosin hydrochloride capsules should be used with caution in combination with moderate inhibitors of CYP3A4 (e. , erythromycin), in combination with strong (e. , paroxetine) or moderate (e. , terbinafine) inhibitors of CYP2D6, or in patients known to be CYP2D6 poor metabolizers, particularly at a dose higher than 0. 3) Concomitant use of PDE5 inhibitors with tamsulosin can potentially cause symptomatic hypotension. 3) Strong and Moderate Inhibitors of CYP3A4 or CYP2D6 max [see Warnings and Precautions (5. 2) Clinical Pharmacology (12. 3) [see Warnings and Precautions (5. 3) max [see Warnings and Precautions (5. 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. 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. 3) A definitive drug-drug interaction study between tamsulosin hydrochloride and warfarin was not conducted. Results from limited in vitro in vivo [see Warnings and Precautions (5. 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 max [see Clinical Pharmacology (12.

OVERDOSAGE
Should overdosage of tamsulosin hydrochloride capsules lead to hypotension [see Warnings and Precautions (5.1) Adverse Reactions (6.1)
NONCLINICAL TOXICOLOGY
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. in vitro in vivo
CLINICAL STUDIES
Four placebo-controlled clinical studies and one active-controlled clinical study enrolled a total of 2296 patients (1003 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. Table 3 Mean (+/-S. ) 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 Mean Mean Baseline Mean * Statistically significant difference from placebo (p-value <=0. 050; Bonferroni-Holm multiple test procedure). dagger double dagger Study 1 dagger Tamsulosin hydrochloride capsules 19. 35 Tamsulosin hydrochloride capsules 19. 57 Placebo 19. 39 Study 2 double dagger Tamsulosin hydrochloride capsules 18. 36 Tamsulosin hydrochloride capsules 17. 64 Placebo 19. 28 Mean total AUA Symptom Scores for both tamsulosin hydrochloride capsules 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). * indicates significant difference from placebo (p-value <=0. Figure 2A Mean Change from Baseline in Total AUA Symptom Score (0 to 35) Study 1 Figure 2B Mean Change from Baseline in Total AUA Symptom Score (0 to 35) Study 2 Figure 3A Mean Increase in Peak Urine Flow Rate (mL/Sec) Study 1 Figure 3B Mean Increase in Peak Urine Flow Rate (mL/Sec) Study 2.
PATIENT INFORMATION
Tamsulosin Hydrochloride Capsules, USP What are tamsulosin hydrochloride capsules? Tamsulosin hydrochloride capsules are not for women. Tamsulosin hydrochloride capsules are not for children. Who should not take 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. 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 capsule, 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? Decreased blood pressure when changing positions. 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. 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. Eye problems during cataract or glaucoma surgery. 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. What should I avoid while taking tamsulosin hydrochloride capsules? “What are the possible side effects of tamsulosin hydrochloride capsules?” How do I store tamsulosin hydrochloride capsules? Keep tamsulosin hydrochloride capsules and all medicines out of the reach of children. General information What are the ingredients in tamsulosin hydrochloride capsules? Active Ingredient: tamsulosin hydrochloride 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. Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762

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TAMSULOSIN HYDROCHLORIDE- tamsulosin hydrochloride_capsule Product manual source documgent