Tamsulosin Hydrochloride (Page 2 of 6)

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 alpha1 blocker therapy [see Warnings and Precautions (5.5)].

7 DRUG INTERACTIONS

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 Cmax 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 Cmax 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 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)].

CimetidineTreatment 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 Cmax 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

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.

8.2 Lactation

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.

8.3 Females and Males of Reproductive Potential

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) ].

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