Complete SPL Sections#
1 INDICATIONS & USAGE
INDICATIONS & USAGE SECTION
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 & ADMINISTRATION
DOSAGE & ADMINISTRATION SECTION
• 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.
3 DOSAGE FORMS & STRENGTHS
DOSAGE FORMS & STRENGTHS SECTION
Capsule: 0.4 mg, olive green opaque cap imprinted “CL 23” and orange opaque body imprinted "0.4" in black ink.
4 CONTRAINDICATIONS
CONTRAINDICATIONS SECTION
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
WARNINGS AND PRECAUTIONS SECTION
6 ADVERSE REACTIONS
ADVERSE REACTIONS SECTION
7 DRUG INTERACTIONS
DRUG INTERACTIONS SECTION
8 USE IN SPECIFIC POPULATIONS
USE IN SPECIFIC POPULATIONS SECTION
10 OVERDOSAGE
OVERDOSAGE SECTION
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
DESCRIPTION SECTION
Tamsulosin hydrochloride USP is an antagonist of alpha1A adrenoceptors in the prostate. Tamsulosin hydrochloride USP is (-)-(R)-5-[2-[[2-( o -Ethoxyphenoxy) ethyl]amino]propyl]-2-methoxybenzenesulfonamide, monohydrochloride. Tamsulosin hydrochloride USP is a white crystalline powder that melts with decomposition at approximately 230°C. It is sparingly soluble in water and methanol, slightly soluble in glacial acetic acid and ethanol, and practically insoluble in ether. The molecular formula of tamsulosin hydrochloride USP is C 20 H 28 N 2 O 5 S • HCl. The molecular weight of tamsulosin hydrochloride USP 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: polysorbate 80, methacrylic acid copolymer dispersion, triacetin, sodium lauryl sulfate, microcrystalline cellulose and calcium stearate. The capsule shells have the following inactive ingredients: FD & C Blue 2, iron oxide black, iron oxide red, iron oxide yellow, titanium dioxide and gelatin. The black ink has the following inactive ingredients: shellac, propylene glycol, black iron oxide E172 and potassium hydroxide. USP dissolution test pending.
12 CLINICAL PHARMACOLOGY
CLINICAL PHARMACOLOGY SECTION
13 NONCLINICAL TOXICOLOGY
NONCLINICAL TOXICOLOGY SECTION
14 CLINICAL STUDIES
CLINICAL STUDIES SECTION
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.S. and Europe. In the two U.S. placebo-controlled, double-blind, 13-week, multicenter studies [Study 1 (US92-03A) and Study 2 (US93-01)], 1486 men with the signs and symptoms of BPH were enrolled. In both studies, patients were randomized to either placebo, 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 one week before increasing to the 0.8 mg once-daily dose. The primary efficacy assessments included: 1) total American Urological Association (AUA) Symptom Score questionnaire, which evaluated irritative (frequency, urgency, and nocturia), and obstructive (hesitancy, incomplete emptying, intermittency, and weak stream) symptoms, where a decrease in score is consistent with improvement in symptoms; and 2) peak urine flow rate, where an increased peak urine flow rate value over baseline is consistent with decreased urinary obstruction. Mean changes from baseline to Week 13 in total AUA Symptom Score were significantly greater for groups treated with 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 ± 5.0 n=254 -8.3* ± 6.5 n=246 9.46 ± 2.49 n=254 1.75* ± 3.57 n=254 Placebo 19.6 ± 4.9 n=254 -5.5 ± 6.6 n=246 9.75 ± 2.54 n=254 0.52 ± 3.39 n=253 Study 2 ‡ 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 ± 6.0 n=239 -3.6 ± 5.7 n=235 9.95 ± 3.12 n=239 0.93 ± 3.28 n=235 * Statistically significant difference from placebo (p-value ≤0.050; Bonferroni-Holm multiple test procedure). ** Total AUA Symptom Scores ranged from 0 to 35. † Peak urine flow rate measured 4 to 8 hours post dose at Week 13. ‡ Peak urine flow rate measured 24 to 27 hours post dose at Week 13. Week 13: For patients not completing the 13-week study, the last observation was carried forward. 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 one year. Of these, 81% (97 patients) on 0.4 mg, 74% (75 patients) on 0.8 mg, and 56% (57 patients) on placebo had a response ≥25% above baseline in total AUA Symptom Score at one year. Figure 2A Mean Change from Baseline in Total AUA Symptom Score (0-35) Study 1 * indicates significant difference from placebo (p-value ≤0.050). B = Baseline determined approximately one week prior to the initial dose of double-blind medication at Week 0. Subsequent values are observed cases. LOCF = Last observation carried forward for patients not completing the 13-week study. Note: Patients in the 0.8 mg treatment group received 0.4 mg for the first week. Note: Total AUA Symptom Scores range from 0 to 35. Figure 2B Mean Change from Baseline in Total AUA Symptom Score (0-35) Study 2 * indicates significant difference from placebo (p-value ≤0.050). Baseline measurement was taken Week 0. Subsequent values are observed cases. LOCF = Last observation carried forward for patients not completing the 13-week study. Note: Patients in the 0.8 mg treatment group received 0.4 mg for the first week. Note: Total AUA Symptom Scores range from 0 to 35. Figure 3A Mean Increase in Peak Urine Flow Rate (mL/Sec) Study 1 * indicates significant difference from placebo (p-value ≤0.050). B = Baseline determined approximately one week prior to the initial dose of double-blind medication at Week 0. Subsequent values are observed cases. LOCF = Last observation carried forward for patients not completing the 13-week study. Note: The uroflowmetry assessments at Week 0 were recorded 4 to 8 hours after patients received the first dose of double-blind medication. Measurements at each visit were scheduled 4 to 8 hours after dosing (approximate peak plasma tamsulosin concentration). Note: Patients in the 0.8 mg treatment groups received 0.4 mg for the first week. Figure 3B Mean Increase in Peak Urine Flow Rate (mL/Sec) Study 2 * indicates significant difference from placebo (p-value ≤0.050). Baseline measurement was taken Week 0. Subsequent values are observed cases. LOCF = Last observation carried forward for patients not completing the 13-week study. Note: Patients in the 0.8 mg treatment group received 0.4 mg for the first week. Note: Week 1 and Week 2 measurements were scheduled 4 to 8 hours after dosing (approximate peak plasma tamsulosin concentration). All other visits were scheduled 24 to 27 hours after dosing (approximate trough tamsulosin concentration).
16 HOW SUPPLIED/STORAGE AND HANDLING
HOW SUPPLIED SECTION
Tamsulosin hydrochloride capsules, USP are comprising of olive green opaque cap imprinted CL 23, and orange opaque body imprinted 0.4 in black ink. Tamsulosin hydrochloride capsules, USP 0.4 mg are supplied as below: NDC 68071-4872-9 BOTTLES OF 90 Store at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Keep tamsulosin hydrochloride capsules and all medicines out of reach of children.
17 PATIENT COUNSELING INFORMATION
INFORMATION FOR PATIENTS SECTION
Advise the patient to read the FDA-approved patient labeling (Patient Information) • Hypotension 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 should not be used in combination with strong inhibitors of CYP3A4 [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7.1 )] • Priapism 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 )]. • Administration 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. Manufactured for: Macleods Pharma USA, Inc. Plainsboro, NJ 08536 Manufactured by: Macleods Pharmaceuticals Ltd. Macleods Pharmaceuticals Ltd. Baddi, Himachal Pradesh, INDIA Revised: May 2017 PM02364002
SPL PATIENT PACKAGE INSERT
SPL PATIENT PACKAGE INSERT SECTION
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PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL
