Tamsulosin Hydrochloride

TAMSULOSIN HYDROCHLORIDE- tamsulosin hydrochloride capsule
QYK BRANDS LLC

INDICATIONS AND USAGE

Tamsulosin hydrochloride capsules are indicated for the treatment of the signs and symptoms of benign prostatic hyperplasia (BPH). Tamsulosin hydrochloride capsules are not indicated for the treatment of hypertension.

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) [ 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.

Dosage Forms and Strengths

Capsule: 0.4 mg, white opaque cap and white opaque body. printed with “A02” in black ink on the cap and “TS 0.4mg” in black ink on the body.

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)].

Warning 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 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 1 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 alpha 1 blockers, including tamsulosin hydrochloride capsules [ see Adverse Reactions (6.2)].

Most reports were in patients taking the alpha 1 blocker when IFIS occurred, but in some cases, the alpha 1 blocker had been stopped prior to surgery. In most of these cases, the alpha 1 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 1 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 1 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.

Adverse Reactions

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, USP and 798 patients administered placebo. Table 1 summarizes the treatment-emergent adverse events that occurred in ≥ 2% of patients receiving either tamsulosin hydrochloride capsules, USP 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.

Drug Interaction

7.1  Cytochrome P450 Inhibition

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 max 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 max 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 0.4 mg is co-administered with strong CYP3A4 inhibitors in CYP2D6 PMs, tamsulosin hydrochloride 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)].

7.2  Other Alpha Adrenergic Blocking Agents

The pharmacokinetic and pharmacodynamic interactions between tamsulosin hydrochloride and other alpha adrenergic blocking agents have not been determined; however, interactions between tamsulosin hydrochloride 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 [ 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 max 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)].